Australian Biography: Don Metcalf
Professor Donald Metcalf (1929–2014) was internationally renowned for his pioneering medical research on the control of blood cell formation.
This fundamental research has been used in the treatment of millions of cancer patients around the world.
Born in 1929, Donald and his researchers at the Walter and Eliza Hall Institute in Melbourne made their scientific breakthrough in the 1960s when they began the task of isolating, purifying and cloning natural hormones called colony stimulating factors (CSFs) which stimulate the production of white blood cells.
They established that CSFs could be given to cancer patients, enabling them to have stronger treatment and to recover faster.
Interviewer: Robin Hughes
Recorded: November 7, 2006
This is a transcript of the complete original interview conducted for the Australian Biography project.
Don, you were born in 1929 — that was the height of the Great Depression — did that circumstance have any effect on your early life?
I think it probably did ... my father was a schoolteacher in a remote little village outside Mittagong and of course there were no neighbours there, so you never saw any impact of it. I think where I saw it was later, about five, six years later, when we went to a small town called Kingsvale, near Young, and there, the local store used to have a queue of people picking up their dole, so these were people who were unemployed getting paid. Ah, other than that, I think life was very simple, people didn't have possessions, they didn't expect to have possessions, and whether it was the '20s or whether it was the Depression ... the '20s and '30s, I don't know. But compared with now it was a very simple life, simple pleasures, you enter ... entertained yourself, there were no movies to go to, there was ... nobody had a radio and you made your own entertainment. So there are photographs of swimming parties down on the Murray or ... but it was simple you ... you drove there or you took your horse and cart there and ... had the day. That's what ...
... and if you look at the photographs of schoolchildren at that time, a lot of the kids have no shoes or socks, and hand-me-down clothes, now was that what it always was like in the country? I don't know, I think it probably was the Depression.
Did it affect your father's job in any way?
Not really, so in the New South Wales education system you started in [a] little one-man school and then as you get better you get promoted and moved to another village, a bit bigger, two-teacher school, four-teacher school. So that progressed and went on, the kids went to school, that's ... that was it, that's your job. We, at that time, had a house attached to the school so the house existed and we moved and my father moved and everything was arranged so that you put it in packing cases and labelled and off you went to the next school.
What effect did all this moving have on you as a child?
It's hard to know, you ... you can't run this again as a control experiment and say, ‘Well, what would happen if I grew up in the city?’ I suppose it meant you were self-contained and you knew the friends you made for the next couple of years were not going to be your friends in a few years’ time. And you learnt to get by yourself, self-contained, I think, self-reliant. Reliance wasn't a word that they used about me, I was a bit of a ratbag, I think, as a child.
I think I was probably a ratbag.
Ah, what's an example of me being a ratbag in a nice way? I was always wandering off and finding coins or notes instead of walking between the house and school. I'd be wandering up the banks and looking at places. Ah, that sort of thing.
You were finding coins and notes in the bush?
I had ... this was in Goulburn within the rough grass alongside the footpath. Did this mean I was looking at the ground all the time? Probably. I find coins down on the beach now, it's probably a habit.
Maybe a reflection of a poor childhood.
No, no, I don't think so. We had ... no, no, that's one thing you could say, we had no sense that we were living poorly and in all truth I'm sure we weren't, compared with a lot of people. So we never went without a meal, goodness me. We were always clothed, it looks nice in the photographs, that's sort of how I remember. No, we weren't hard done by.
Did you have brothers and sisters?
One elder sister, one younger sister. So I was sandwiched in the middle.
And as the only boy, did you get special privileges?
Not that I remember, no. I don't think so, no. My elder sister was considered to be smarter than me in the sense that she was two years ahead of her class at school, and went to high school when she was nine, and was indeed very smart, so I think she carried the burden of expectations of my family and I just trailed along behind. Perhaps.
Did she go on to fulfil those expectations?
She became a teacher, a Latin teacher, sent of all the places to Tenterfield to teach Latin, which must have been a little bit stressful. Ah, then at the age of 20 she went off to America on a bride ship to marry an American serviceman that she'd met in Sydney, and got married in San Francisco in borrowed clothes, because she'd lost her baggage and the minister lent her some clothes, and my mother had never seen her son-in-law and was not impressed by this. She developed an agonising ache in her arm which she had for months afterwards.
Was that ... so that was the end of your sister's career? But back ...
No, she then became a teacher in Delaware, which was amusing. They considered that the training she'd had in Australia wasn't up to scratch so in Delaware she was retrained as a teacher and taught First Grade kids for 30 years then. So, was that a successful career? No, I think she could have done a lot better than that but that was her choice. She was clever.
What was the general expectation of the family — in other words, we use these days the word values, the word values seems to be around ... but what were the values of the household you grew up in?
Um, I think you were expected to make a serious effort at school. School was their world, they knew what kids should or should not be doing at school ... were you performing up to scratch? If not, I can't recall being punished but it was made known that that was not, you know ... I think one of my reports said, ‘Surely a better effort could be made.’ Well, that was the attitude my parents took. Um, strict, I suppose that's being strict. But then when there's no television, when there's no radio, and you've got some homework to do or what else is there to do? You do it. Um, yes, sort of strict. But nobody said, ‘You have to do better than this, you are supposed to be becoming a medical student, that's not good enough.’ That's ... I can't remember them saying that.
What sort of things did you get into trouble for, apart from schoolwork? What kind of things were punished?
Ah, when I nearly killed my younger sister by pulling her hands through her legs and jerking her up. She was supposed to come up in a circle but hit her head on the floor. That I think must have alarmed my father beyond belief and I got thrashed for that, I can't remember too many thrashings, but occasionally he did.
Hand. That's quite, quite satisfactory on [a] six-year-old or however old I was.
But it didn't happen very often?
At school they got the cane and since I was occasionally in my father's class, if I'd earned the cane, I got it. Out in front. Six on each hand like everyone else. But that was normal. Ah, what did I get that for? Throwing stones across a school ground, you know, the usual sort of anti-social behaviour.
Apart from the times when you bashed their heads inadvertently, did you play with your sisters much?
Not much. My older sister was sort of remote, she was at high school, I'm still at primary school, that sort of thing. Gone to university, I'm still at high school. Younger sister, no, not really very much interaction. There must have been some but it was ... when you're separated, as she was, four years younger, again she's at a different school from me and you don't ... when you're in the country and you're going to a high school 10 miles away it ... it separates you. You don't often interact as a family except at weekends, I guess.
You said that because you moved so much, you were always a little unsure who your friends were going to be, because you'd make friends and ...
Oh you ... you picked friends with all the most likely looking lads in the class. First thing that happened when you went to school was you sat down and said, ‘What religion are you?’ And you looked around the class and you sort of sussed who ... who was the most interesting, listened to what they said as their religion and that's the one you said you were. Because in the end you got put in that class for religious instruction, which you had in those days. So you chose your friends and chose your religion at the same time. I have a wide ...
... a wide experience of religions.
So how did you pick a likely looking lad? What did a likely looking ...
I don't know. Looked like they'd get into trouble, I think. Bright-eyed, bushy-tailed. Um, I think we were a pretty normal sort of lot but looking at the photos, which is all you can do at a distance, you say, my goodness, you know, this fellow looks as though he's going to be in trouble always and it's interesting what you remember is pretty accurately what they were like.
And did ... what sort of things did you ... what sort of games did you play in those days, of no television, etcetera?
Um, at primary school, probably cricket and hockey, I can remember playing men's hockey. Um, then at high school you played whatever was going, at summertime it was cricket, wintertime it was football and tennis, then. We lived beside a golf links at one stage, so I used to play golf. One, one club. Um, and played basketball at high school, running.
And what about in the backyard, what did you play then?
In the backyard, nothing. Who do you play with? When you're in a schoolhouse and school's gone, there are no kids around you. You've got two sisters, one of whom's away at school and one's somewhere else, you play with yourself, play with your toy soldiers or something.
Toy soldiers, not many but enough's enough.
Marbles, you played marbles, yes. I can't remember any other games.
What was your father like as a person?
He was very serious, I mean he ... he'd left Victoria and gone to New South Wales, got married at a very early age, with the disapproval I think of the family, so he was out to ... to succeed and he was a migrant, he'd sort of come from Scotland at the age of about six, I think. So there was a big pressure for him to succeed. And so the pictures of him look solemn and determined and I think he was an excellent teacher, and the proof of that came later when he was made headmaster of a demonstration school where you actually train teachers. He obviously knew about teaching ... but full of good fun and enterprise, wanting to try things, usually it was my mother who said, ‘No, no. I'm not properly dressed’ or ‘I don't want to do this.’ I think he sort of was frustrated, he'd like to have done a lot more things than he actually did.
What kind of things did he feel frustrated about, do you think?
Oh, I think he probably would have liked to have jumped into his car and driven around Australia and explored — this is just guessing, it was wartime by then and there was no petrol so you didn't travel much. But I remember times when I was sure he wanted out ... doing something, going out for the day, and it was not welcomed and he stayed home. This is just guessing, guesswork, you know.
But you felt that there was a curiosity there and an adventurous spirit?
Oh yes, I think so. Yeah.
What sort of a person was your mother?
She is ... I remember her as being solemn all the time. Now she couldn't possibly have been as solemn as I remember but, again, I think this ... this effort to succeed and show that the family back in Shepparton had made a mistake in rubbing her off. And so she was trying to have a successful brood of children and getting by in the Depression and, yeah, I think a stressful time.
Why was the family back in Shepparton wanting to ... ?
I don't know, we never asked. They ... he ... her father was a rich farmer and he had four daughters and they all married well and she married this young penniless schoolteacher and I suspect that this was not well-regarded and off they went. We never enquired because, ah, one didn't. There was a bit of a stress I think.
But she'd fallen ... she'd fallen out with her family?
I'm guessing, I'm guessing.
So you didn't have much to do with that side of the family as you grew up?
Not at all. I didn't realise until the reunion about 10 years ago that I had 400 relatives around Shepparton. I'd never seen a single one of them. That happens, I think, particularly when you move to another state and it just ... different world. So, it's interesting, isn't it, the way families become separate somehow.
So in ... in terms of your relationship with your mother, what was that like?
Well, I think she ... well, she loved me and fed me well and dressed me well and expected me to do well at school, and she was quite disappointed when I didn't become a general practitioner in a country town, I think that was her ambition for me to be a successful GP. And when I started in medical research, she was not very impressed. And never really understood that maybe I was becoming successful at that too. So, she was not one who was given to bursting into laughter and doing maniacal things.
Now, you said that you'd chosen a religion by the look of the boys that were ... were saying that they adhered to a particular faith — if they looked naughty enough, you'd ... you'd go for that religion.
Interesting. Let's say.
What religion were ... were you brought up in?
Um, we fluctuated ourselves, as we moved from one town to another. I suppose if there was a Presbyterian church we went to that. If we went to a Methodist ... because there was a Methodist close by. Usually it was one or the other. So I guess you'd say we're Presbyterian. Being Scottish by origin.
Was the ... at that time, was it fairly standard that you went to church anyway, everybody did?
Ah, if there was a church nearby I think the kids did, they went to Sunday School and Sunday afternoon — that was what you went to, you didn't go to church. Certainly that was true in Goulburn, which had a much broader range of places to choose from. After a time I got sick of it, at about the age of 15 or 16, decided that I knew enough about religion and didn't need to be told it every ... every week so I stopped going. Ah, did people go to church? Yes, I think they did. More often than they do now, or at least people in the country did. Which is all I know about. But I suspect the people in the country go to church more often now than city people do anyway. I suspect.
How many different country towns did you go to as a child?
Oh well, I was born in Mittagong, we moved to Womboota then — was a metropolis down near Moama — it has about 10 houses in still, I think. Then we moved to Kingsvale, which is about 10 miles from Young. Then we hit Goulburn, then we went to Wallerawang. Then to Inverell, then to Tamworth, then to ... that was it for me then. My father went on to Wagga and then he went to Lane Cove which is ... he was moving up the order of progression and from Wagga ... from Tamworth to Wagga to Lane Cove was a sequence of better and better demonstration schools. So he was the number one teacher in the state, pretty much, by the time he went to Lane Cove.
How old were you when you started school?
How was that? Well, we were in Womboota, which had a one-class school and my mother used to teach needlework at the school and would bring the pram in and put me in the back of the room while she did that. And I must have listened to what was going on and by the time I was three I could read and so I think they just said, ‘Okay, you can go into First Grade.’ And that was the beginning of my downfall because I was always two years younger than the rest of the class, which leads to mischievous behaviour. So I had started high school by the age I was nine and in principle would have been ready for university at age of 14, so they had to say, ‘Okay, you'll repeat the intermediate, repeat the leaving and then you'll be 16 and then you can go to medical school.’ Which I did. But I still have nightmares about repeating the leaving or the intermediate and saying, you know, ‘I did this last year, I haven't studied this year, just keep the results from last year.’ So I do not recommend starting kids at an early age. It was innocently done, they weren't pushing it I'm sure. And they eventually had to take the decision in high school to stop it and let me catch up.
And which high school was that, that took that decision?
Oh, I think that ... I don't think the school said, ‘Hang on a bit, this kid's too immature, too small, too young.’ Um, it happened once in Lithgow and once in Tamworth. I wasn't welcome at Tamworth because I came from Inverell and became dux of the school at Tamworth, displacing the kid who'd been dux of the school all the way through and he was not best pleased.
And you were younger than him?
Well, in my second year I was again dux and he should have been the dux. It's interesting, Tamworth High had no great reputation for scholasticism — they were great swimmers, great at cricket — and it's interesting that two of the kids in the same class have both [become] fellows of the [Australian] Academy of Science. This kid and me. He's a mathematician, I'm a biologist.
How old were you when you went to Tamworth?
I'd be 14. At the start of the year. And doing the leaving, that's the fifth year, and repeating it the next year at the age of 15 — that was the year the war ended and then, 16, to go to university.
And did you beat this other boy in both those ... no, you repeated of course, so he came on ... yes of course.
The year that I ... yes it was not ... not well-done but ...
Now tell me, being younger like that, I mean dramatically younger, a couple of years younger, presumably smaller ...
What effect do you think that has?
I think you're out of sight of a teacher and when you had a few kids in a class, and you were sitting in the back row, and the smallest, the most mischievous, you were not paying attention, you were not soaking it in. You were just immature so on paper you could get through the ... the examinations, but were you really taking in what they were telling you? I doubt it. Doubt it.
Socially, this disjunction between your intellectual development and ... and your emotional age, what effect did that have on how you related to the other boys?
I don't think it did much harm. What you did learn was to be more cunning because you were the smallest and therefore you could persuade them to do things that they might not otherwise have thought of doing. So you weren't regarded as the runt of the pack, you were probably a ringleader sometimes. You learnt to get by.
How important was sporting prowess?
Um, it was important in schools at that time, you know, the biggest dunce in the school was the fastest swimmer and he was God in the school. So you had to have some ability or you were poorly regarded but if you had enough ability then you were just one of the pack.
So how did you get on in that respect?
Oh, quite well, I was quite a good tennis player and I could run fast for a time, not long, but for a short time ...
Being younger though, you know, affects your ability at sport — smaller, younger.
Yes, I guess you don't ... you're not prominent when young but when you get older you're slowly catching up and getting to be of the same size, so it evened out.
And was there any ... apart from the time that you beat the boy that should have been dux, did you experience any sort of problem associated with being clever?
I think only in the sense that it made you a smart alec and not pay attention to the lessons and therefore get yourself into trouble. I can remember getting into trouble first day in high school and the chemistry teacher, Miss Adams, who was a very large lady, obviously took exception to what I was up to. And gave me 200 lines. Punishment. I'd never heard of lines, I didn't know what lines were. So I went home, didn't tell my parents this disgrace, and I got the poetry book out and I found a poem that had the shortest line in it. And the kids said, ‘You've got to write the lines out.’ So I wrote Charge of the Light Brigade out. You know, ‘half a league, half a league, half a league. On ...
Came back the next day, 200 lines. She said, ‘You're a smart alec, do it again. I must not behave as a smart alec.’ Um, that sort of thing, occasionally got you into trouble. I'm sure I was an impeccably behaved child really. No troubles. But mischievous.
But you remember yourself as mischievous?
Only under pressure. I think it's very hard to remember childhood really. So extraordinary things like getting told you had 200 lines stand out in your memory.
Are there any other memories like that, that you have of ... of school and your relationship with the teachers or the other students?
I'm sure there were, I'm sure, I mean, it depended where you were. And I remember when we were in Goulburn once and we, as boys, had bicycles and we had a job from the local movie theatre to deliver flyers advertising what was on at the movies at the weekend. And I was given the job of delivering them in the East Goulburn and if you've ever been to East Goulburn, it's a sort of vertical suburb and it was hot and I decided I didn't want to do this. So I just took the bundle and threw them in the rubbish tin. And forever after was certain that I'd been seen doing that and that I'd be caught and were ... you know, was almost afraid to go to the pictures again. That was a ... a plot involving a couple of people who decided they didn't really want to deliver them. How anyone ever figured out they weren't delivered, I don't know. But there were complaints and I was sacked. So, that was a short job.
Was that the wickedest thing you ever did?
... [interruption] ... I doubt it. I think the wickedest thing I ever did was to break all the telephone cups on the main western telephone trunk line during the war, which on reflection was a dastardly thing to do. But when you're waiting in the cold for a bus to take you to school and the bank is loaded with stones of the right size and the telephone cups are sitting up there, it's inevitable you're going to throw one to see if you can break one. And over the weeks you manage to break them all. What that did to communications in 1941, I think, one doesn't know. Maybe we nearly lost the war. The police did come and question me, I denied everything, and I think they knew damn well it had to be me. Only two children waiting out there for the bus. I don't know, I never tried to see whether the communications work when there's no ... you know, the china telephone cups on the poles ...
When the police came, did they come to your home?
No, they came to school because the school was next door and ... but I was going to high school and just happening to wait there for ... so I think they'd been through the school and decided that it wasn't any of the schoolkids and ...
How terrified were you when the police ... ?
Pretty, pretty terrified. I'm sure I was obviously guilty and they knew it and I knew it and that was enough said. There were no more cups broken.
This may get me in jail. You realise that, there's probably a long ... it's not a seven-year, you know, moratorium, you know. Yeah.
Statute of limitations? Right, what ... what ... why ...
I mean, if you had a kid who broke telephone cups now, you'd strangle them, wouldn't you? Ah, no. Look it's bleak and it's cold, if you go to Wallerawang now in the middle of winter and wait on the roadside, with a pile of stones, I think you'll pick one up and throw it.
That sounds to me as if you're trying to excuse yourself, even at this late stage.
I'm explaining my unsocial acts.
Now, you said that this was wartime, what are your memories ... what are your memories, apart from trying to break Australian communications during the war, what are your memories of the war and the outbreak of war?
I can remember the announcement that Menzies made on the radio. We had a radio then, '39. I can remember the year before the ... this was in Goulburn and it must have been the headquarters of a light brigade so the horsemen came in and it was still summer and the parade ground was opposite our house, so that was exciting, to see columns of horsemen riding in and ... so that was the outbreak of war and it pretty much happened, as you know ... in World War II, for a while, and then 1940, we're still living in Goulburn, things had turned nasty. Then we moved to Lithgow and it was totally different. Lithgow is a mining town and was in the middle of a miners' strike. If you can imagine in the middle of the war, having a miners' strike, but all the kids were getting free lunches sent in, by somebody, by the government I suppose. So the miners' kids were getting these great sandwiches and oranges and things and I was making do with whatever I brought home from ... brought to school, so you rapidly became a miner's child and got the free handout. So that was one part of the thing — our Latin teacher rejoiced, by the name of Mr Starling, and he was the local communist candidate up for election that year. So we'd see him on a soapbox on the corner as we left the school. We were transported from Wallerawang, a tough load of ... a busload of toughies that hit this tough Lithgow high school, which was no great shakes, so there were about 80 children jammed on a bus that was legally supposed to have 25 and later it ... had a gas bag on top, a great big canvas bag of town gas as the fuel supply, so it was pretty ordinary climbing over the mountains in this, particularly if you missed the bus and had to walk home — that was that part of the war then things got quiet again.
I remember they used to show Russian movies every so often which were pretty horrifying, these documentaries, but that was in about '44, '45, a Russian offensive, people charging over the snow and getting mown down. Where they came from, goodness knows, how they got to Australia, I don't know.
Maybe Mr Starling had something to do with it?
I'm not sure. Anyway, they were interesting, then the war ended, or the war ended in Europe and the war ended in the Pacific. But because you're in the country you really saw very little of this except when we lived in Lithgow, it was the most desperate time — that was when the Japanese entered the war at the end of '41 — and so Lithgow became an armed camp, there were dumps of fuel in the fields, they built a fake village into a mountainside, a fake railway line at Marangaroo, and stored ammunition in the mountain so all the kids knew what was going on. And Lithgow had the small arms factory so they were manufacturing machine guns and rifles there. So the kids used to collect rifle parts out of waste tins and everyone had their own rifle. So it was said.
I didn't but we all joined the cadet corps and so we had our own rifles. Like the ones used in Zulu. Martini-Henrys, just slid the bullet in the back ... there was that part of it and then at Tamworth they were training pilots in the latter part of the war, so the air was full of Tiger Moths flying round and round as they taught them how to take off and land. That's my memory of the war.
People were in 1941, they were alarmed. Were they scared? There was rationing then too. And so things were short even though it was the countryside, butter was rationed. Sugar, eggs.
They had coupons, you were given little sheet of coupons, and if you wanted a shirt, they'd use 12 coupons, if you wanted something else, I don't know. My parents looked after that.
Ah, sort of. We had a big backyard so we had our own cows and chooks and would sell the eggs to other people in the village. Is that black market? No, it's not. Not really. Was ... and if you were friends of the grocer he managed to have a can of sliced peaches or sugar or something, I know that, because I used to work in the grocer shop at the weekend. People would come in and [he’d] nod and wink and put his hand under the counter and get a tin of goodies. Goodness knows, I mean there was probably black marketing everywhere and you never knew.
While you were a kid at school, did you always have jobs at the weekend?
From about the middle of high school onwards. My earliest job was at the age of six, I became a member of the plumbers' union. Because I ... the school in Kingsvale was about a foot from the ground and they had to put pipes in underneath, so I was small enough to climb in under and thread the pipes through to put water in the classrooms so they made me a member of the plumbers' union, got paid a penny a day. Good money.
For a six-year-old, but not union rates, though.
When you were at school, was there any teacher that particularly inspired you towards science?
No ... there were some good ones, at ... each school had its good teachers and its bad teachers and when you were changing almost once a year it's a bit hard to say, Mr So and So, he was the one. But there was one maths teacher who was pretty electrifying as a Fourth Year student and then he became the headmaster of Tamworth, so he was a teacher in Inverell and a headmaster in Tamworth. He was one I remember, but no, no, there were a lot of good teachers.
Ah, he sort of had the whole class on their toes. The sort of mental arithmetic [for] fourth year students, what's x plus y ... and you had your hand up in the air quickly and snap it out. Ah, he was the dynamic teacher I think, yeah, I think he was a ... he explained things well and so that's good.
Wasn't there a problem with shifting schools that you would be in a different place in the curriculum or ... ?
No, no, curriculum is absolutely the same in the whole of New South Wales, that didn't matter a jot. And it didn't much matter that your teachers were different because normally if you stay in any one school the teachers are going to be different in second year, third year and fourth year. It doesn't make a heck of a lot of difference. You're in with a class of different people but otherwise things are pretty much the same.
And you only ever moved at the beginning of a school year so you had ... [interruption] ...
Not always, but often we did. Often we did.
If there were gaps, did your parents step in to help make it up? Was it a help to have schoolteacher parents?
There was a time when I was having a lot of trouble with algebra, I think, where my father stepped in but I mean, he was a primary school teacher and if you're having trouble with advanced high school stuff it was difficult; that was the only time I can remember, yeah.
Was there anything else in your life that made you particularly drawn to the scientific subjects, rather than to the other ones?
I don't know. I could read at a very early age and you would think that, at least judging from our kids, who became bookworms — all four of them — that I should've been an avid reader and therefore would probably end up being a lawyer or a teacher or something in that line. I can't remember reading books at the age of six or seven or eight. Ah, I don't know why. Perhaps I did, I can't remember. In all events, I wasn't wedded to ... to novels and to literature so that part of it wasn't comfortable with me and I struggled to write a page of an essay, which is a laugh now, when I'm in the middle of writing my 680th scientific paper, which means that once a month for the last 50 years, I've been writing a paper, so that's a bigger output than a novelist. So how come? Well, it happened gradually, but I can remember in high school, just finding it incredibly difficult to do a one-page essay, so I was not ... not good in that. I was okay in mathematics and mathematics is a chancy subject, you can either do very well in it or you can bomb out. According to what sort of question you get asked, and I liked chemistry, they were the ones, chemistry and two mathematics. Did any of that interest me as a ... to become a scientist? No, and I ... late in high school I was interested in astronomy. Which is a weird sort of interest but when you live in the country, the sky's very bright and it's a bit hard to ignore it.
Did you ever get the chance to look through a telescope?
No. Still haven't. That's one of my big ambitions, to look through a telescope, and for somebody who looks through a microscope, six, eight hours a day, never to have seen through a telescope is just beyond belief. One day I'll do it. Um, so I can't remember when it was implanted in my head that I was going to become a medical student if I worked hard enough. And I ... I don't know. I sort of liked the idea but if you think about it and you live in the country, you've never seen ... I'd never been to a doctor as a patient, in my life. I mean, most places we lived, had no doctor. So, you ... you had your diseases and you got over them. Ah, but apart from having my tonsils out, I'd never seen a doctor until I was about 18, so you had no idea of what being a doctor meant. Because you'd never been in a waiting room. And you had no idea of specialties, you know, the idea of becoming a haematologist — what's that? So you didn't know. And so when we had our single visit from student advisors, big, big excitement, whole final year was advised on what to do, he ended up saying, ‘I think you should go into forestry.’ That was it. Now, how did all that turn out into going to medical school? I can't really remember. I think my parents said, ‘I think we'd like you to be a doctor.’ But I can't remember, can't well ... I know they were annoyed when I didn't become a country doctor and practicing doctor.
At that stage did you have any impulse towards the caring side of doctoring?
No, I think even as a young medical student you don't ... well you didn't get to see patients, you went to medical school in the old medical school building and then three years later you went to the new medical school and that's when you began to see patients. And so your contact with patients was minimal until the quite advanced stage. Ours was minimal particularly because there were 650 students in the class and it meant that on ward rounds there were 40 students around one bed. So all the small girls got the inner ring, all the smaller people got the next and you were out three rows back. I never heard a heart murmur, all the time I was a student. And we spent a lot of time talking to the patients in the bed next door, but that was about the extent of the contact. Now, in retrospect, I suspect it's ... it goes a lot better now, I mean, students have contact with patients from quite an early age on.
Before we get you properly to medical school, I want to go back and just finish at your high school education. Do you ... what year did you finish and do the leaving certificate for the second time?
Second time? 1945. So that was ...
Right, so you were quite young going to university anyway?
I was 16 when I enrolled and my birthday's in February so I was quite soon 17. That's ... it was sort of not atypical, there were others, but the particular class I was in had mostly ex-servicemen so ... and a few migrants from Europe who were having to repeat their medical school.
So you weren't sure why you were doing medicine but you decided to do it, and there you were and did you need a scholarship to go?
I needed one and that's why, in part why, I had to repeat the leaving because you had to win a bursary at Sydney University and you had to be in the top hundred in the state to get one. But I did.
What subjects did you do for the leaving?
I did English, French, chemistry, 2 mathematics, honours chemistry, honours mathematics, that made eight.
No physics, no, which was a pity.
So and ... and but it was a very science-oriented course? No history and no ...
Yeah, I suppose, so we'd had history until the leaving. I think we had a much broader education than kids do at present. Kids start specialising now at a very early age. So we'd had European history until the year before.
Now you said that classes at Sydney University at that time were very large, why was that?
There was no quota system. As long as you passed the leaving — you could have five Bs and you could get into medical school. I know because the queue for enrolment had people in it who had five Bs and I thought, ‘Gee, that's not much.’
Their parents could pay the fees?
Or the government was paying them, because they were servicemen. Ex-servicemen.
So what was the situation that made so many ex-servicemen there at the university?
Well, it was the first year after the war and so there were all sorts of people who for some reason or other decided to become medical students. My best friend was a newspaper man before the war. He rejoiced in having an IQ of 80. But he also had a photographic memory so he topped the year in physics because the examiners set the questions from the back of the textbook, which he memorised, just by looking at them; he was a strange guy. So what made him a medic ... become a medical student, goodness knows, he'd just come out of Changi as a prisoner of war for four years, some of them, goodness knows. They were a great collection of strange people. There was one fellow who thought that the only way to learn anything was to hit yourself on the head. And he studied anatomy you know, and, ‘This is the femur,’ whack, whack. ‘This is the attachment of the gluteus maximus’, whack, whack. We had an Empire weightlifting champion. We had thieves and rogues, scallywags used to work Randwick as bookies’ clerks, there were ex-fighter pilots, goodness knows — great collection.
Was there a government scheme for these guys after the war?
Ah, yes, I forget what it was called but essentially any ex-servicemen could go to university, there were ... there were no limits, so we had a class of 650 and for some lectures there were 650 in the class, they had to build a special lecture theatre for them. Ah, and for a lot of ones it got split up, so you only ever knew the Ms and Ns and Os in the class because you were split alphabetically. So all my friends have names starting with M or K, something. Ah, and that went right through and it was sudden death; if you failed one subject at any one year, you were out. So there was no quota to get in, but then it was take no prisoners. So 30 percent failed every year. So you could be there for five years and fail in one subject of about 20 in the final exam and you were just chucked out. No repeats, no nothing. It was scary stuff if ... when I have nightmares, that's another one of the nightmares. Doing final year medicine exams. Um, and as a consequence everything was crowded. The teaching was really minimal. No bones, so in anatomy you couldn't ... they had a set of bones chained to a post so you had to sit round in the ring, around the posts, and take a femur or a radius and learn the textbooks ... latest were about late 1930s, no textbooks had been printed during the war. And the teachers were tired, the classes were big.
Did you get to carve up bodies?
We did, it was big excitement. If you know the old medical school in Sydney University, it's a stone building and it has a spiral staircase down to the basement and in the basement are these big tanks of formalin in which there were bodies wrapped up like mummies in cloth. And at the start of every year you would carry a body up the spiral stairs to the dissecting room. So it was a crowd scene out of a B movie, passing the bodies up over your head to the dissecting room. Once you got there, then there were 40 people descending on one body. So there ... there were eight on one leg and eight on the other leg, eight on one arm, eight on the other arm, eight on the head and neck. So you got to know those 40 people pretty closely. We had 40 ex-servicewomen on the left arm, they were a tough lot and so it went. A whole room, full, it was a crowd scene, could have made a great movie.
Which bit did you get to cut up?
Oh, in sequence, the next body would be moved to the abdomen, or the chest. You eventually over three years cut up a whole body. I gather they don't teach anatomy much any more, but it was three years of hell trying to remember this because I have a very bad memory for details.
And so how did you do it? How did you remember it? You weren't hitting your head, what ... what did you do?
Oh, just reading it over and over and over and trying to keep it in your head long enough to get through the exam. Exams were pretty stressful.
So as you were going through this time, where were you living?
I was boarding, I boarded at a private house in Neutral Bay, one in Croydon, I was acting as a housemaster of Sydney Grammar School in Clovelly. I was houseminding a house at the back of Randwick Racecourse. I think that was my place as a student. A varied lot.
But you were a boarder? What, you were given a room and ... ?
Boarding, yeah. Had a room. We were fed ... best place was in Croydon because the people there had two dogs and they were fed at the table before we were — the boarders. The dogs got chops and the boarders got sausages. Turns out that I'm allergic to every animal in the animal kingdom with one exception and that's dogs. I say I'm not allergic to dogs because at night, for retaliation, we used to dropkick these two little dogs off the back landing, but we always had our shoes on, so that was no contact. That was boarding, boarding was pretty ... pretty ordinary.
And what were you thinking that you'd do at the end of the degree, what was in your head at that time?
It's hard to know whether you make up stories when you get asked about what made you do this or that. I think, I think for some reason I was always interested in research. But I think also that I was getting a bit dissatisfied with the number of times I was told, ‘We don't understand this disease, we don't have a cure for it. We just don't know.’ And I thought, ‘Well, if we don't know, it's about time somebody found out.’ So when the university introduced a new degree, which was a research degree, Bachelor of Medical Science, where you could break off from being a medical student and do a year in a research laboratory, I thought, that's for me. So I was the first one to do it in senior medical school. And I thought this was great. So I'd had some experience of research and I quite liked being a doctor and quite liked being a resident, probably would've become quite good at it, but I was never in any doubt as to what I wanted to do and when I got a chance to be a research worker, I took it.
That year that you spent in research, did ... was that significant in terms of the people that took that year, and did you have any particular experiences in that year that shaped you later?
It was an interesting department and ... and the medical school was on hard times so it was badly equipped, there was no research equipment, the professor, Pat de Burgh, was eccentric and collected odd bits of equipment and rubbish and the whole room was full of junk. The lab. We had to clear the junk before we could do an experiment. And mice were kept in boxes in the corridor ... was up to us to think of an experiment with them. There were just two of ... two of us. This fellow who had the IQ of 80 and was a ... had a photographic memory and I were the two students. But both the professors would sit and talk to us as adults and discuss what was latest in the journals they'd read and that was quite novel — once you'd grown up in a class of 600 — to actually be spoken to by a professor. And the professors, the two of them were ... had both been at Harvard University so one was the predecessor of the other. And they were both students of the most famous American bacteriologist, Hans Zinsser, who wrote a book called Rats, Lice and History you might have seen. So there was a sort of genealogy of research and ...
Hugh Ward. Hugh Ward was also eccentric. He'd been in the Balkans War in 1912 and a prisoner of war, so he could never stand to be in a room with a closed door. So all his lectures he walked across the front of the students, out the door into the corridor, back again. So you got the first part of the sentence, then pshht, second part of the sentence. And he's ... he had a capacity to sort of make a précis of every subject, so by the end of your hour, you knew everything there was to know about diphtheria or whooping cough or measles or whatever it was. So an excellent teacher but a very eccentric sort of charming, old world, no nonsense, as you could imagine with a background like that. But he'd been Zinsser's student at Harvard with [John] Enders who developed the polio vaccine so the two of them were Zinsser's students. De Burgh was his student, I was de Burgh’s student.
So how did you ... in a room that was full of junk, what kind of junk?
Well, bits of old equipment, he never threw anything away, found bits of dynamos, bits of junk.
You could say it was useless.
And so in this place, without any equipment, trying to learn about how to be experimental scientists and a few mice in the corridor ...
It's not a problem ... no problem.
Well what did ... what made this such an important year for you? What was the essence?
Because you could design an experiment. We were working with a virus that strikes absolute terror into every research institute in the world — it's mouse smallpox virus, ectromelia, because [if] it gets loose in an institute you lose all your mice, but we were studying it and of course liver disease and the liver was ... is a great organ to work with. And we were asking some pretty simple questions about why patches of the liver were losing their glycogen and doing this or that, so it was a bit of biochemistry, bit of biology and a bit of virology. And nobody knew the answers and we were breaking new territory and it was great fun. We had a thesis to write at the end of it, we didn't publish any papers about it but you could see how the day would go when you were actually doing it for a living. And a lot of people would just retreat from that ... it's like there's no way ... ‘I need to be with patients, I need the excitement, the buzz, the interaction.’ But that appealed to me too, but this was ... this was fun. So it was important that we had done that year.
How would you describe what that buzz was, what was that thing that you really knew that you wanted to do in research?
What is it that drives you every day? Still drives me every day? Um, it's sort of selfish in a way, it's the thought that today I'm going to discover something that nobody in the whole world has ever known before. So it's sort of like being a ... an explorer, like Columbus. And tomorrow he's going to see China. Whatever China was, well if he didn't see China, it'd be ... but it was something that no ... he thought nobody had ever seen before. So there's that part of it ... having seen it, and thinking this is something new, then the practicalities cut in and say, ‘Can I find it again tomorrow when I do exactly the same experiment?’ That's the first big worry — a long way down the track is what does it all mean? Am I going to be able to put this to any practical use? So, it's a bit of a mixture, things tend to often start by accident. Something just happens and you notice it and you think, that's strange. And you do it again and whoops, it happened again. And that's pointing you off — now is that curiosity? Is it just being awake to odd things that happen? A bit of everything I think. Now I'm sure when I was young, I went into research thinking I'm going to cure cancer and save the world. I'm sure I did, I can't remember actually thinking that, but I'm sure all young research workers do. And then slowly you get those silly ideas beaten out of you by hard facts of life, which is that it's pretty tricky and your chances of discovering anything are minimal and discovering anything important are even more minimal. And you tailor your ambitions to what it looks like you're going to be able to achieve, so starting out ... why do you start out? Yeah, altruistically but a ... there's a bit of competitiveness there, saying, I want to discover something first. I think that ... we're talking 50 years ago and you can't really remember what motivated you.
Do you remember what it was in the approach that Professor de Burgh and Ward took that was particularly useful in setting the fire going?
They asked your opinion. When was the last time a university lecturer asked your opinion? Well that was pretty novel. And they would consider it, say, ‘Well, it's not bad, but ...’ But, but, but. And you would argue and I think that's all it is. All it takes. Now having known that, do I treat my students the same way? No. No, I don't. I don't like talking to the students and I would rather teach them by example. You want to be like me, copy me. Get out there at the bench and start working. Ah, so it's interesting, isn't it? You realise that what you had as a student, that fired you up, isn't what you're able to give your students to fire them up. Now they mightn't agree with what I'm saying, but I get the feeling that I'm not behaving as well to them as people behaved to me. It's a very powerful thing when you're young, for somebody to take notice of you and say, ‘What do you think?’ It's an interesting question. I never ask my kids that too often.
So they were remarkable listeners, these guys that taught you?
I think they were. They each had a ratty old leather armchair, they had a gas fire, they sat in an empty room and read their journals, because they had no ... no equipment to work with and, I suspect, no great desire to do any work and were ready and available at any time, you could sit in on the circle and say, ‘Well, what do you think about this?’ And off you'd go. It's ...
A remarkable number of the Hall Institute [Walter and Eliza Hall Institute of Medical Research] luminaries went through that system.
They did. They did and it makes you wonder about the need to have high-tech, highly equipped universities. If I think in our ... in that department, you're right, there are three fellows of the Royal Society. Yeah.
Who were they? Who were your colleagues at the Hall Institute then?
Well, years later there was [Jacques] Miller and [Gustav] Nossal, they were a couple of years younger, they were the three I had in mind. It's extraordinary that any one small department would generate three fellows of the Royal Society. All US academicians too. Good record, can't be equalled by high-tech places. So one wonders whether you need all the equipment to train students. Whether you don't need some smart old cookies.
It's possible that you're better off with both.
Um, no, I think you'd be dissatisfied with listening to this old faggot and want to go back to your new toy and generate some more data. I don't think the young like to spend all that much time talking to old folk.
Does it suggest that, in fact, real science is a matter of the mind and not of the equipment, and that what this did was focus you at a young age on the fact that the mind was what mattered?
Did I say that? Did I say the mind mattered? If you talk to the young, they're besotted by high-tech machines and equipment that generate bucketloads of data. Often almost on a random basis, out of which they will pull out patterns and make discoveries. That's the way it's going at the moment, it's just sort of, what I call, shotgun science. And then you say, well, is that all they're thinking about? And ah, then you ... to get further into their minds you've got to sit and talk about it with them and some will have obviously lateral thinking, put things together, and others will be just giant technicians who are slicker, I mean, there aren't many people you meet who you really are quite astonished with their inner intelligence or perception or it's not a ... not a common thing.
Now after you finished this year and you went back to finish off your full clinical medical degree, the practice then was to go and do some clinical practice. Where did you go?
Oh, you had to by law. To be registered as a doctor, you had to do a minimum of one year and it was at Royal Prince Alfred Hospital. As a ... as a resident. Perfectly conventional year. Five terms, one of orthopaedics medicine, one of surgery, one of gynaecology and emergency. I used to like the emergency ward best of all.
Why did you like the emergency ward?
Oh, things happened. I mean, you can imagine Prince Alfred Hospital, I'm sure it hasn't changed, and Saturday night, Sunday night, you get the world traipsing through. It's great fun. Ah, I don't think we handed out too much effective medicine but you certainly see life in the raw.
Is there any particular memory you have of a night?
Yeah, I remember one night, sleeping through the most dramatic night we had. Big black car pulled up at the front door of Prince Alfred, body got shoved out, staggered up the stairs to the front desk, said, ‘Put a bandaid on it.’ And promptly collapsed on the floor. Ah, taken down to casualty, my fellow night surgeon was on duty, I was asleep in one of the examination couches, slept through the whole thing. He'd been shot in the chest and dumped by his gangster friends and he opened the shirt to look at the wound and the bullet dropped out so in the papers next morning, there was a dramatic operation and a bullet was removed from the chest of this guy. He was a nice bloke, they had him in hospital for one day, I think, and then they sent him home. But he always used to come in to casualty and have his dressing checked and he would always leave money in the poor box. Yeah, he was a character. God knows what ... what he was professionally but he was shot and they patched him up and I missed the whole thing, they wrote it in the paper: ‘Drama at Prince Alfred. Gangster shot. Emergency operation, bullet removed.’
Was there anything less dramatic that you did take place ... part in?
Oh, we ... one of the other fun things was that was the year that ... Bobby Lulham, football star, had carried on with his mother-in-law and somebody slipped Bobby Lulham a dose of thallium (thallium was rat poison), a rat poison doesn't taste at all, but ... and it used to be used by dermatologists to get rid of your hair, so that you could get rid of scabies and things out of your scalp. So thallium, Bobby Lulham had a dose of thallium, and he was in the ward that I was resident of. And my wife, who was the nurse in an adjacent ward had, in sequence, Bobby Ludlum's mother-in-law, Bobby Ludlum's wife as I recall and numerous others. We had the collection together of the world's only cases of thallium poisoning. Now, that got spread in the newspapers, and everyone started to come in with what they thought might have been thallium poisoning. So by the time I was a ... down in the emergency ward, every night you had a line-up of people who thought they might have had thallium poisoning, been given rat poison. And the two main symptoms of rat poison are, first of all, that your hair comes out in handfuls and, second, that you have severe gastroenteritis. So we'd stand them up, go along the row, pulling their hair. If it came out, you were in, you were another case, if it stayed you'd go home. They were the days. I'm sure there are the same things happening.
You said that your wife was in the next ward. Were you married at that time?
No, no. No she was a ... I think she was a third or fourth year nurse at Prince Alfred.
In the ward, when I became a ... I think the two wards shared their residents at times, anyway, she was working with me as a nurse. And I rather fancied the look of her. So that ... that's what happened ... [interruption] ...
And had you just ... just now as we're on this subject, when you were a boy at high school and so on and growing up as an adolescent, what part did girls play in your life?
Not much. Not much, actually, although you thought about them an awful lot. You had your fancies. I can't remember now, but I'm sure there were some good-looking women medical students. We were in with the physiotherapy students too ... were a much better looking lot than the medical students.
But we didn't have steady girlfriends, one didn't then, I mean, I can't think of anyone who had a steady live-in girlfriend as happens now. That just didn't happen.
What did you do when you wanted to take a girl out, where did you go?
Well, you went to the pictures or there were dances often or sometimes you'd go to concerts, down at the Town Hall in Sydney, or ... yeah, mainly in the Town Hall, remember the Youth Series concerts, they ... they were on then. What else did you go to? You might visit friends' houses if you knew somebody who lived in Sydney. Went to the beach, went for rides on the Manly ferry. There was no end of things. All pretty simple.
And so what was it about your wife that made you decide that she was special?
Um, I liked the look of her, I liked her bright eyes and her wit and liveliness and ... we seemed to be on the same wavelength. We differ in almost every aspect, that became apparent with the passing years, but we managed to survive nonetheless. We don't agree on any subject, virtually. But the ... there you go. We appeal to each other.
Do you have different politics?
Yes, we don't discuss politics, because she's rabid and I'm not rabid but, no, there are lots of things you don't discuss, we have different religions and we don't discuss that either and we don't agree on many things. But we agree on a few things.
And what do you think made her decide that she wanted to marry you?
Goodness knows. Same sort of thing, I suspect. It's interesting, I lived in an institute full of 600 people, most of whom are under the age of 30, so they're about of an age that we're talking about. And you can go along and look at eyes and say, you know, you're a bright spark, no, you're dull, da-da-da-da. Now they're all formally quite intelligent people but a few of them immediately strike your attention and I think that's what you look for in people. Now, fortunately, everyone has a different idea of who looks interesting or else we'd all be trying to marry the same person. It's ... it's a bit of magic, isn't it?
So it wasn't long after you met her that you got married?
Um, it was ... it was about a year later, about a year later. She wasn't finished and she wanted to spend some time with her widowed mother in the country and so we were engaged and then got married about nine months later.
And what was happening with your career, you were doing a ... you were a clinical residency but you still had this hankering after research, so what did you do?
Well, about half, not, about two-thirds of the way through my first year I didn't know what I was going to be doing the next year and thought maybe I would do haematology. There was a special type of resident who looked after the haematology in the hospital and of all the different disciplines, now that I was beginning to see them, that was the one that had the most interest, blood disease. Right. So I thought, if the worst comes to the worst, I will try and get taken on, appointed as a ... as the haematology resident. But an advertisement had come to my attention for a cancer fellowship in Melbourne, didn't sound right. Sounded, they were looking — and in fact they were — for a professor to start a cancer research unit in Melbourne for the Anti-Cancer Council of Victoria. Now, being a small world as it was then, the head of the Anti-Cancer Council was an old wartime friend of Professor Ward, so he went to him and said, ‘Do you have any young people around Sydney who you think might be fitted for this job?’ And he said, ‘Well, go and see Metcalf or bring him down to Melbourne, look at him and decide.’ Which they did. So I twigged to the fact that they were really after somebody a lot more experienced and important than me and I said I'd ... I'd take the fellowship if it was offered to me but I'd take it at half-salary. Now, I can't remember being equally stupid again. But that appealed to them I think. So I was brought down to Melbourne and examined by a bunch of luminaries here and what I didn't know is that they'd been searching for this fellow, Carden Fellow, for some years and just approaching ex-patriot Australians and saying, ‘Will you come back to Melbourne and run this cancer research group?’ And they weren't interested, that it's a small hick town and they didn't want their career to suffer by going to Melbourne, and they didn't want it. So it came to me. I'm still the same fellow 50 years later because the terms of the fellowship did not have a termination clause in it, so they don't have any way to fire me. And as long as I keep producing scientific papers, they're stuck with me.
Are you still on half-salary, Don?
No, no — am I on half-salary? I took a voluntary cut after I stopped being assistant director and just an ordinary professor's salary. But my current boss thinks I only work half-time and only gives me a half-aliquot of research funds, which I think's a bit stiff since I start work at seven every morning. However we don't go into that. We don't talk about the war.
So way back, starting out, how old were you when you became Carden Fellow for the first time? And did they only give you half-pay by the way?
I don't know. I think they started me off on a lower salary. Um, how old was I? I was 26, I was 26. 26. 26. Yeah, 26.
And so you were quite young and you went down ...
Quite young, quite unexperienced and I knew that the Hall Institute was the best medical research place in the country and I'd been to visit it when I was doing my Bachelor of Medical Science studentship, that was the carrot you got. If you worked hard, you could have one week in Melbourne visiting. So I was headed for Melbourne, and the Anti-Cancer Council with some difficulty had persuaded the director, [Frank Macfarlane] Burnet, to accept me as a fellow, you didn't have to pay my salary or my working expenses. What he didn't like was the notion of anyone in his institute doing cancer research because ... and he told me this at our first interview, he said, ‘Come in, Metcalf, sit down. You want to do cancer research? I have to tell you, cancer is an inevitable disease, people get it, there's no way to prevent it and there's no treatment. And as far as I'm concerned, anyone who wants to do cancer research is either a fool or a rogue. Now, if you're serious, go out there into the lab and for the first two years, work on virology.’ So for the first two years I worked on vaccinia virus. As a virologist. And then I started to get a bit toey and say, ‘I really am hired to work on cancer research and I want to work on leukaemia because it's cancer of blood cells.’ And so I used to go down to Werribee where there was a state farm and collect all the chooks that had leukaemia. Now you can tell a chook's got leukaemia because it has paralysed wings and paralysed legs, so you walked around and if there was a chook walking around with paralysed wings, it had leukaemia and leukaemia in chickens is caused by a virus. It's infectious. So I was still being a virologist but I was now working on leukaemia so I brought ... used to drive a little car down and come back with a carload of sick leukemic chooks and starting to work on them. That's how I got back into leukaemia research. But Burnet was never very fussed with what I was doing because he didn't ... he honestly believed that cancer research was a waste of time.
Now, Sir Macfarlane Burnet believed that cancer research was a waste of time and yet you were housed there but paid by the Anti-Cancer ... what did the Anti-Cancer Council think of you not working on it?
Oh, they were tolerant. They were very tolerant and that was the good fortune I had right through my professional career, that they tolerated me and what I was doing, so for 15 years when I was trying to purify colony-stimulating factors and so year after year I'm still trying, I'm still trying, they ... they put up with me. Whereas the rest of the scientists around the country every three years have to justify what they've done or they get sacked. No more money. So, that first period they understood that there was trouble with Burnet and that I was going to be working on viruses for two years.
So, knowing that Sir Macfarlane Burnet felt this way about cancer research, why had they particularly wanted you to be housed there?
It was ... it was both. The choice was the Peter McCallum Clinic or the university, they didn't want me, and so Burnet grudgingly took me on as a research worker. So I had no training, no formal training in cancer research until I went to work in Harvard Medical School in Boston.
It came about because I was interested in the thymus gland. Why was I interested in the thymus? Well, a Hungarian working in Boston had discovered that mice develop leukaemia very commonly but he discovered that if you take out the thymus gland in the chest they don't get leukaemia. Alright. Now, I had been working not on viruses that caused leukaemia but on the possibility that the reason why you get leukaemia is because the white blood cells in the body are being overstimulated by the hormones that control their growth. And this same man, Jacob Furth, the same Hungarian, had discovered that you could get cancer of organs like the thyroid or the pituitary or the ovary by overstimulating them. So if you had too much prolactin and you overstimulated the breast, you developed a breast cancer. If you were a mouse. And so there was this whole body of knowledge that said, look, you can get cancers by having out of balance the things that are controlling the growth of different tissues and I thought, okay, well, that could be what leukaemia's all about. At that time, in the early 1950s, nobody knew leukaemia was a cancer. Nobody knew. Nobody knew until a few years later.
Could have been like pernicious anaemia, because the bone marrow looks exactly the same and that's just a vitamin deficiency. So there were people, admittedly out in left field, who believed that leukaemia might be a deficiency disease. But I thought, no, okay, it's a cancer. But everyone believed that leukaemia is caused by viruses, because there are viruses that caused leukaemia in chickens, in mice they'd just been discovered, in cattle. And so why not humans? Now, years later, billions of dollars later, they find that one sort of human leukaemia is caused by a virus but that was later. But I thought, no, no, no.
No, well, it is if you live in Japan because it's quite common in the southern islands of Japan. But I liked this other story better, that the over ... imbalance of growth factors controlling things ... so that was the tack I wanted to take. So I had to discover what controlled white blood cells and I had to have a model to work with so ... chickens had leukaemia so I started to ask ... what controls chicken white blood cells? I was in lots of bother there. But it was at that time that this Jacob Furth wrote his papers saying, okay, this virus disease in mice that causes leukaemia, actually you can prevent it by taking the thymus gland out. So my first research was to find out what the thymus gland did. And I was the one who discovered that if you take out the thymus you influence all the other lymphoid tissues in the body. So I was working on the thymus. So I got the chance to go and work in Boston and I went to work with him because he was Mr Thymus and besides he was the originator of this whole piece of cancer biology that said you can get cancers by imbalance of growth factors. So it was there I learnt my trade. He was an experimental pathologist, I sort of learnt what diseases were in the mouse and all about tumour viruses, leukaemia-causing viruses and did my own stuff on the thymus. While I was there, I pretty much wasted my time but I had to be trained ... I got to meet all the people ... there were probably 50 people in the world that worked on leukaemia research then. And I knew them all because I'd met them all at meetings and so it was good from that point of view and I came back to Melbourne with some expert knowledge. And then you learnt on the hoof then, by mistakes.
What was your own stuff on the thymus? What were you doing with it?
I was ... I was taking it out and showing that, when you took it out, the other organs that have lymphoid cells in them were smaller and less active. Possibly that was the reason why taking out the thymus stopped leukaemia development. I thought this was great and I found that maybe the thymus was making something that controlled these blood cells, which it is, but that took another 40, 50 years for other people to come up with. So you start with a notion that's a bit off-centre that you try to follow and you go to the person who has done work on an organ that nobody in the world had ever worked on before. Because it shrivels up in adults, the thymus, just a little shred. So people said, ‘Oh, it shrivels up, it's got no function.’ And it doesn't. I could take your thymus out and nothing bad would happen to you. But if I took it out from you when you were a baby you ... your immune defence system would be shot, would be no good and you'd have no protection against infections. That came later. But it was one of those organs that nobody knew what it did because it didn't seem to matter whether you had it or not. Couldn't say the same about the pancreas, if you took the pancreas out you'd get diabetes. So that's what the pancreas did. Take the thymus out, nothing seemed to happen, so it had no function; that was wrong.
How is it that an organ that's so crucial when you're young, ceases to be relevant when you get older?
Well, if you believe the immunologists they will tell you the following story. The thymus makes one sort of white cell called the T lymphocyte, T for thymus. And T lymphocytes protect you against viruses and foreign tissue grafts and possibly against some sorts of cancer. Now, most of the cells that get made in the thymus die there, within a couple of days. Why do they die? Because they are attacking their own tissues and so they have to be assassinated ... The few that are not, the few that are really interested in looking at strange things like viruses, get out into the body but once they're out there they become long lived memory cells and they live for the lifespan of the person. So you don't have to keep making new ones, after a certain age, so you and I at our age probably don't need to make any brand new T cells because we are running on the memory ones we had as children. And so it didn't matter if you took the thymus out, when you're old. No, that's not my work, but I did some of the early work in that field. So I spent the first 10 years working on the thymus and that sort of leukaemia, lymphoid leukaemia, and it wasn't until we accidentally found how to grow white blood cells in culture, and they were a different sort of white blood cell, that I had to switch to one of the other families of blood cells and learn all about them. So I'm no longer a thymus person but years ago I used to be known as Mr Thymus; that was a very long time ago.
Now, back there in Harvard, did you take your ... did you take your new wife with you?
I took my new wife and I had one daughter and we had two new daughters in Boston, we had two true-blue Boston children ... and in a famous obstetrics hospital there called the Boston Lying-In Hospital, which years later got sold to a drug company that actually mass produced the hormone that I discovered later on. So, I like to say, probably incorrectly, in the same room that my child was born, the first recombinant GM-CSF was produced. It's probably not true but in the same building.
And how did you take your fatherhood?
It was fine. I was a good, good father until the children were about 10 and then I was not a very good father, I was strict and uncompromising. But it ... I was a good father for young kids.
How many children have you got?
Four. Four daughters.
So you were a strict father to teenage daughters?
No, I was just a terrified father sitting at home waiting for them to come back, while they were waiting on the corner until it got late enough to be respectable to come back. You know, 2 am. The joys of parenthood. I ended up with four daughters and none of them are doctors or scientists, they're two lawyers, one artist, one teacher. They said they didn't want to compete with me and they are best-suited doing what they're doing I think.
When you came back to Melbourne, after this stint in one of the great centres of the world, did your stocks with Mac Burnet rise at all?
Well, he was one of the world's great virologists working with viruses when I left to go to Boston. And he'd had a seachange in the two years I was away and he became interested in white cells and immunology. That's the biology of the cells that I'd been working with before I left. So I came back still being an expert on T cells and ... but not as an immunologist, so I wasn't interested in what the T cells were doing protecting a body against infections, I was interested in the cells and how they came to be leukemic when they did. So you can work on the same organ but from a different point of view. I'm still saying, ‘Why are you getting leukaemia?’ And he's now prepared to discuss, ‘Why are you initiating an immune response?’ So we could talk now. We didn't talk often and I was banned to the animal house for seven years so I had to go down, tunnel under the hospital and work in the animal house in some small laboratories there and that's where I did my cancer research, on the thymus. While all of the people in the main institute were now immunologists. And some of them were now working on the thymus but we're still different. I'm still working on cancer of the thymus, all the others are working on other aspects. So I was never on the staff at the institute. if you look at the old annual reports, I'm listed as visiting and attached. And I was visiting and attached for eight years.
Don, why did he put you in the animal house?
Because that had spare labs that were empty, they'd been occupied by Frank Fenner who'd moved to Canberra and ...
He was a virologist so they were virus labs, they ... that's where myxomatosis was developed, in these labs and the insectary there, still had the mosquitos that they were using to infect the rabbits and give them myxomatosis. So I took over those labs, nobody wanted them so I slowly got an assistant and a couple of post-docs and so on and we got up to a team of about 10 there. But we were outsiders, I mean, the tunnel from the hospital is pretty noisesome and you go under it and you go through the laundry, where there were 5,000 Greek women doing the laundry for all the city hospitals, and then you went past the rubbish dump and then you came to the animal house. Now, I'm allergic to animals so I had hayfever every one of those eight years. Just a running nose, sneezing all the time. But it was home, that was our little ...
Now the administration knew you were allergic to, what, mainly mice then?
Oh, look, yeah, if you're allergic that's too bad, a third of the staff are allergic to animals. And that's one of the joys of being a research worker yet you ... that's one of the dangers. You get allergic to animals.
Does it just make you sneeze or ... ?
It does except I get a bit wheezy after a while, but I'm allergic to everything, pollens, there are no flowers in this room because I would be coughing and wheezing.
But you can touch them alright, it doesn't create problems?
If I've got gloves on. Animals ... I wouldn't touch flowers, I mean, you get pollen and you're allergic, the pollen is what makes you allergic. So you can't get downwind of a flower or you'll start sneezing. That's alright.
So, you're down in the animal house sneezing away and how did your work progress?
Ah, it ... what I was trying to do, probably couldn't be done. A whole animal is too difficult to work with, you ... you can ask the questions what ... what makes your white cells this level but how do you go about it? Do you take organs out and see what difference that makes, da, da, da, and you can get a certain amount of information, but you're not really getting the truth of the matter, getting to the bones of it. So, those 10 years, although I discovered a lot of things about the thymus that are still true today, it was ... it was a dead end. I was very glad when the chance came to switch fields because I'd taken it as far as it could go and it hasn't actually been taken any further in some respects. Until the last year or two, was a tough problem that couldn't be solved. How the thymus works. But the ...
So, do people who work on it now, come to see you to ask you about what you did?
Not often, sometimes, if they're old enough. No, no. What I ... what I discovered is now sort of given knowledge in textbooks and that's that, you don't ask who discovered that. Listen, if you discover something more than two years ago, it's not recorded anywhere, you're not credited with it. The young don't read anything that's older than two years. So unless you keep working on the same subject, you have no currency whatsoever. If I stop working today, two years’ time, ‘Who's he?’ He's gone. It's a hard life, it's very competitive, medical research. And the young are quite unrelenting in their passion for newness and it's got to be done in the last two years or it's probably wrong and stupid, old-fashioned.
Is that why you won't stop working?
Probably. Probably, too scared. But it's an interesting phenomenon, you ... you actually can be very offended if you are no longer quoted, if you don't realise this phenomenon that unless you're actually still producing information on that subject, you drop out of ... out of recognition ... you're no longer quoted. Now, if you put my name into a computer, you would get the information, it is there, but it's not used by today's workers. So all the marvellous things that got discovered, 30, 40 years ago and some of them were marvellous, are sort of lost.
Lost or just in consolidated revenue?
I would say lost. I found that if you put, for example, a thymus as a graft under the skin, so a mouse had two thymuses — it had its own thymus, had a thymus under its skin which was exactly the same ... exactly the same. And then if the mouse got pregnant, you with me? Mouse is pregnant now, it's got two thymuses. During pregnancy, the mouse's own thymus gets very, very small, withers away. This one, doesn't change. Now, I wrote that up, I described it in Nature, top science journal in the world, has anyone ever quoted that? No. It's true. But it's not relevant, is it? You're not running around being pregnant and with two thymuses. So what's the point of it? Well, the point is we don't understand why that thymus graft didn't change the same way as your own thymus.
In a normal pregnancy with one thymus, does the thymus shrivel up?
I presume it does, in women. It certainly does in a mouse and I assume that women are the same.
And then it'll regrow again once you've delivered. It ... it's not permanently shrivelled as it would be in middle age or old age.
Was the thymus under the skin acting in the body in the same way as the ... ?
As far as you could see it was making its T cells exactly the same way. Smelled the same, looked the same. Did the same things.
Did it have any noticeable affect on the mouse?
No, the thymus is one organ that the body has no knowledge how big it is. The body knows how big the liver should be and if you cut out half your liver, it will grow again in about 48 hours to the same size as a liver. But the body has no idea how big the thymus should be so there's no cut off ... so I put as many as 50 thymuses into a mouse and the mouse was just walking around solid thymus tissue but the body can't tell that. It's one of the curious things about thymus. It's a strange organ.
So if some bright young spark wanted to get some good ideas for research ... ?
They read an old paper and say, ‘Gee, let's put 50 thymuses into a mouse.’ And the thing is that the editor and the referees wouldn't realise that they were repeating something that had been done. Can be done. Can be done.
Plagiarism is alright if it's from ... from someone old?
Can ... can be done. It can be done. Oh it's done all the time.
So, going back to the fact that you were working on a whole animal and you began to realise that this wasn't getting you where you wanted to go, what did you do?
I didn't sort of think that way, I was still working and writing papers and trying to make discoveries, making discoveries, but by accident a colleague of mine in a university had been trying to grow bone marrow cells. Now he'd been trying to grow leukaemia cells from a mouse and I had the mice that got leukaemia so I used to supply him with the leukemic cells. So we were sort of collaborating on this study and he couldn't get the leukemic cells to grow anyway. And he tried a trick that an American had discovered in working in Denver, that if you had an underlayer of cells as a feeder layer then you could make cells grow. So he tried that. And the feeder layer that he used was bone marrow cells. So now he's got a culture dish with two layers. He's got bone marrow cells in the bottom, and he's got the leukemic cells on top. And whoops, colonies of cells grew but they weren't in the layer that had the leukemic cells. He wasn't growing colonies of leukemic cells, he was growing colonies from bone marrow. Nobody in the world had ever been able to grow bone marrow before, ever. There were books written saying it couldn't be done. And so what had happened was that the leukemic cells were making something that was making the bone marrow cells make colonies. So he turned the system upside-down and he had the leukemic cells as a feeder layer and the bone marrow cells as colonies. I thought, that's great. That's the system I'm going to use. Because you had to add things to the cultures before they would grow. And the colonies were colonies of white cells. So I had ... we had a way of growing white blood cells but we had to add something to them, to make them grow. Maybe that was the hormone that normally controls the way those white cells grow. Let's purify it, let's find out what it is. So 20 years later, we'd done just that. We didn't know it was going to be a 20-year job but we had the technique. Now it's by accident. And things in science often — not always — happen by accidents like that, so here was a complete accident and it happened at the same time in Israel in the Weizmann Institute in Rehovot, and they were also trying to grow leukemic cells and they saw this happen. So two groups didn't know each other, no contact, same year discovered the same phenomenon. Now the Israelis always said we stole their technique but we knew we didn't steal it. We'd tell them to get lost. Ah, but things happen by chance and they often happen simultaneously and that often leads to a lot of bad blood in science. It's ... I suspect this happened to a degree with HIV, the AIDS virus. People are working with the same sort of technology, whoops, they discover the same thing at the same time. And then there's bad blood. You stole ours. No, we stole yours.
Now you ... it was Ray Bradley who was ...
He was working in the University of Melbourne.
Yes, and so when you went into his laboratory or you saw this ...
He brought the cultures over to us in the animal house. And it was raining as I remember, him carrying them in, out of the rain. Look at these. It was great.
And did you see the significance straight away?
Yeah, I thought, this is marvellous. God, these things are like galaxies looking at them under the microscope, just star clouds coming at you, like a spaceship. I thought, I'm going to work with that. It's too bad I know nothing about granulocytes or macrophages, the two white cells, I'll just have to start. And it's interesting when you start working in this field, even though you've got a brand new technique that's obviously going to wipe the existing world out, you're not regarded as anyone of consequence because you haven't worked on that field before. They will accept anything I say about the thymus because I've been working in it for 10 years, but about granulocytes? ‘No, he's not a granulocyte man.’ So for about five years, you are nobody, didn't matter what meeting you went to and what results you talked about, ‘He's a novice.’ It happens. So you don't, you shouldn't change your field too often or you ... you're a novice all your life. Anyway, so that's how it happened, by accident.
So you did the right thing in deciding to spend the next 20 years looking at this?
I've ... it's the next 40 years now.
So are you the kind ... [interruption] ...
Ray Bradley had found these ... this way of culturing bone marrow cells, which had suggested ideas to you about what you could do. How does that work? You were talking about the competition with the Israelis — when you have a colleague like that who makes such a fundamental change to the way you're working, how do acknowledgements and credit and all of that, how does that work out in that case?
It can be very awkward. For the first couple of years we worked as a team, doing one part of the technique in his laboratory over the road from us and one part in ours and we were quite careful not to develop the whole technique ourselves. Now it wouldn't happen these days but in the '60s I was quite careful that we wouldn't be seen to be treading on his heels or taking his discovery. Ah, so we waited two years before solo experiments of ours were done and we learnt the technique and an American post-doc came and together we did it. Then by natural instinct the waves parted because he was more interested in the nature of the cells that were growing and I was more interested in what was stimulating those cells to grow. So all of my efforts went down that track, I didn't care whether my cultures were the world's best or biggest as long as they could read out the concentration of what I was putting in. Because the number of colonies you got equals the number ... the concentration. So with time, the two pathways diverged quite a lot and so he has a stream of publications about the nature of those cells and I have a stream of publications on colony-stimulating factors. Um, where it gets awkward is in later life when people start to give you prizes and they're just given to one person. And you have to say, ‘Well this is a very nice prize to win and I'm grateful for that but it was a joint discovery’ and da-da-da-da-da. And you have to say all this. Or when you're writing about it, you're certainly careful to say exactly how it happened. Now a lot of people wouldn't do that but it seemed right to me. What does Ray Bradley think about it all? I don't know, we've never discussed it. But in different institutions with groups that are about the same size and being fairly careful not to work on the same area, [it’s] about all you can do.
And the work that you then went on to do, based on that initial finding, was off on a different path?
And what path was that? What was the next thing?
Well, in principle it was quite simple: bone marrow cells will not grow and make colonies unless you add things to them. What were those things that you added? Well, they were extracts of tissue, so you could grind up lung tissue and add the juice from that to the culture, maybe that would make colonies grow, maybe it wouldn't. So you went around testing all the different tissues in the body to see which ones had activity. Turned out they all did, because these hormones are made all over the body. And then a period of about two or three years elapsed during which we had to get indirect evidence that the whole idea was correct. Now, if we were really detecting what controlled white cells, then the level, the concentration of that thing which we called CSF, should change if you had an infection because you suddenly need a lot of white cells and you need them to work hard so let's go fellas, let's have a high concentration. Did that happen? So we went and studied thousands of patients, some of whom had infections — and were the levels higher of CSF as we could detect in their serum or in their urine? And the answer was yes. So that sort of indirect evidence said, ‘Yep, you're on the right track,’ what you're picking up, what you're calling colony-stimulating factors, does seem to make sense as a regulator of those protective white cells. So then you take a decision: I wonder what the nature of this CSF is. And the chances were quite good that it might have been a virus. Now, you might think it's very easy to tell the difference or not, how to tell the difference between a virus and a protein molecule but in fact, it's quite hard. And some of the most nasty viruses are in fact called prions, that are protein molecules, so you can't tell the difference. Anyway, we finally said, no, this is a protein, let's try and purify it and find out exactly what it is. Well, that was a straightforward question to ask, we put a PhD student to work doing that, Richard Stanley, and he tried to purify it. Well, none of us realised that in 1968 it was absolutely impossible to purify that sort of protein because only one molecule in a million was CSF, and the techniques for separating all the other proteins based on their size or their electrical charge or stickiness just didn't exist. They hadn't been invented yet. So it took a decade for biochemical colleagues around the world to invent the techniques that you needed to do the job of separating CSFs from other proteins. So, we didn't know that at the time. So we had to look around for what's a good source of CSF? What's the cheapest source? Didn't have much money. Turned out that you could detect it in urine, so great. Ah, let's purify CSF from human urine.
So buckets were put in our toilets, women's toilets and men's toilets, everyone on the staff had to use the bucket and not drop cigarette butts in it, and then we had to as the first step ... put this urine into a big sausage bag ... skins and dialyse it against water, and so our lab had an enormous stainless steel tank with evil smelling urine in it and ... being purified for the first step, getting rid of all the things that were soluble and rubbish. And we spent, I suppose we spent, about five years purifying CSF from human urine. And at that stage, Richard Stanley left and went to Toronto to work as a post-doc and that project sort of stopped because CSF in urine is pretty lousy stuff, actually. A much better looking, in terms of what it could do, was CSF out of mouse lung tissue. And that seemed to be a rich source so we started to make mouse lung CSF. Which means injecting a mouse with a bacterial extract and that increases the amount of CSF in the lung and then three hours later, taking the lungs out of a mouse and putting them in a test tube and culturing them for 48 hours and then harvesting the fluid from that little culture. And we had to do that for a quarter of a million mice and that gave us enough CSF to purify. So when it's one molecule in a million it's tough going. And so what with the delays in technology allowing this, it took 15 years to actually end up with a little tube of purified CSF. Which was too small an amount to put into a mouse so you could never prove that it would actually work if you injected it into a mouse. So now we're up to the mid 1980s and we're smart because first of all we found that there wasn't one CSF but there were four of them, four different ones. We'd purified all of them, we were the only people in the world who had pure CSFs, but the amounts we had were too small to do anything but use it carefully in cultures.
So we knew the properties of these molecules but we couldn't actually prove that we hadn't wasted the last 15 years. That's where it becomes important that the Anti-Cancer Council is tolerant and is still happy to support this project, based on no proof of anything other than that you have been busy but maybe wasting your time. So, how to get round this logistical bottleneck? How to mass produce CSF. The molecules are too big and complicated to synthesise, it's impossible. You can't get enough by extracting the richest source, so that's out, and the only way is to find the gene in the body that codes for the production of that CSF and get it out. Now that's easy to say now, it's the sort of job you'd get a student to do. But in 1983, there were only about six genes that had ever been isolated out of the body. So this was very early days and tough going finding these genes, but in a period of three years, genes for all of the four CSFs were isolated, some by us, some by Americans, Japanese. And the other job was to find out: now you've got the gene, how do you mass produce protein from it? The product — well that's dead easy now too. You call up your supplier and they give you a bacterium that you can put the gene in and it will mass produce it. They didn't exist then so it was a tough job for a Swiss company to figure out how to mass produce CSF from our gene in bacteria. It probably cost them about two million dollars to make us a little bit in a bottle. But it was enough then to inject into mice and say, ‘Well does it work? Does it elevate the levels of white blood cells?’ And the answer is, it did. That was a big relief. And a year's work, 15 of purification, not good. But it worked and what was scary was how quickly the corresponding genes in humans were isolated in this same three-year period. Sort of a golden period. And so you suddenly had mass produced human CSF and why not test it in patients? See how it worked. So the tests in patients were actually being done within two years of the tests in mice.
And that ... I never expected that to happen, I just ... it was scary, I thought you'd be testing this stuff in monkeys for a decade before it was safe to test in humans but, no, it was tested and the Royal Melbourne Hospital was one of the hospitals testing it and it worked fine, it wasn't toxic. And you know, within a couple of years the FDA [US Food and Drug Administration] had said, ‘Yep, it works, it's safe, go for it, it's licensed.’ And that was one of the fastest drugs ever licensed by the FDA. And after that, about five million plus patients have had CSF. So it's a funny sort of progression from an accidental discovery, a couple of people working on it, tackling a job that's impossible technically. Getting more and more people to help, of course — by the end of the whole set of experiments there were 300 plus people who'd done various bits of that study, in our labs. And you have to drag in more and more experts, biochemists, the molecular biologists and the clinicians and the nurses and so on and the little ... the whole job was finished. Now, that sort of project is pretty typical of the way medical science goes ... you don't sit down with a blank sheet of paper and say, ‘I am going to discover this and this is the way we will do it this is what we'll need. Give us the money.’ It doesn't happen that way. By accident.
It's much more chaotic in that sense.
You hope it's ordered chaos but it's ... the progress is zigzag. I mean, it used to be infuriating to have students doing their PhD on that project, getting to a certain level of expertise and then, whoops, they've gone. Gone for a post-doc overseas. And you start all over again with another raw student and you're almost back where you started and then you go a bit further and rip, it's like the teeth of a saw, you’re just going up. I feel ... I was a bit on a treadmill at times.
During that very long period that you were trying unsuccessfully to purify it and ...
We were doing lots of other things as well ...
... fortunately, because remember our job was to find out what caused leukaemia and one of the interesting things about these CSFs is that some of them on some leukaemias will turn the leukemic cells back into normal cells. So the whole idea that started this ... is that an imbalance between these great factors, is in fact correct. And for a long time we thought, well, we're really working on a cure for leukaemia, by using these things to make the cells behave. That hasn't worked out that way at all. It ... the CSFs when they're used in the clinic are used for patients with any sort of cancer. They're just used to stimulate blood cell formation. But of necessity we were making all sorts of discoveries about the nature of these white cells and their ancestors and how leukemic cells behaved, and looked at hundreds of patients who had leukaemia and studied their cells, using this culture technique. So there were hundreds of papers being written that are all, in their way, important papers about the biology of blood cells and leukemic cells. But the mainline project was pretty tortuous and it did not bear fruit until 15 years later.
Who thought of the name, colony-stimulating factor, for it and why?
It's a descriptive name, it's the fact that you drop it in the dish to make colonies develop so why not, colony-stimulating factor? Did I think of it, or did Bill Robinson, the American? I don't know, it's in the first paper we wrote together and that's where it came from.
It's unfortunate because it's also the abbreviation of cerebrospinal fluid and a few people get confused and of course nowadays, a little faceless bureaucrat in Washington decides, ‘No, that's not the correct biochemical name, I will rename this molecule, filgrastim.’ Which you can't pronounce and then the company says, ‘Sorry, we have a product that we're selling as Neupogen. And so all the patients ever see is, Neupogen, but if they look at the fine print on the bottle they'll find it's G-CSF [granulocyte colony-stimulating factor]. What's in a name?
The four different kinds of CSFs that you've found, do they have different functions? Do they ...
I'm sure they do. They ... in a sense they all work on the same ancestral population. It's a dopey system where multiple regulators are controlling the same cells and each cell has ... can be spoken to by each one of these regulators but one of them concentrates on one sort of white cell, the granulocyte [while] one concentrates on another, the macrophages, and each one does different jobs, and you realise this when you build mice that have that gene missing and you can do that. It's another two million dollar project but you can build a mouse that looks normal except it has no gene that codes for one of the CSFs and you say, ‘Okay, what's wrong with you?’ And, that'll be wrong and that'll be wrong and that'll be wrong. And you take another mouse and knock out one of the other CSFs and say, ‘What's wrong?’ Nothing, nothing. Oh they've got lung tissue with ... with terrible lesions in it. So it turns out, when you do the knockout studies, you prove that each one, in part, does the same job and in part is separate so none of them are redundant, they're not just duplicating each other for no reason.
So when you come to use it, in an actual clinical form, to give to patients to regenerate bone marrow which one do you use?
The one that is most aggressively sold by the pharmaceutical company. And that is Neupogen, which is an agent that stimulates granulocytes so it's good for infections but not all infections. But you would think that out there in the marketplace there would be pharmaceutical companies desperate to sell any one of these, they're all good agents. But no, the one that has the patent for another one, is pretty lackadaisical and they're not pushing their product. And the patients don't like it, it actually makes them feel a bit achy and so on. The fact that it does them good and saves their life is different; if you don't feel good when they've given it to you, it's no good. And if this company is saying, ‘My stuff's fantastic.’ And advertising it in the New York Times, ‘demand from your doctor that he treats you with Neupogen.’ Ah, that's what you use.
So all four of them would be appropriate for use, you're saying?
On certain occasions, and if you ask how many patients in the world have ever had two of these CSFs together, it's about five. Five patients in the whole world. Why? Because the companies don't talk to each other.
Right, but they would be better off if they ... ?
Well, I believe so, because they're designed to work as collaborators and enhance each other. So you know the biology. And you know what makes sense. But the difference between that and arranging for a patient to have what's sensible is just an impossible hurdle at the moment.
So different companies have got patents on each of the four?
One company has two and the company that has one of them has never set foot in the clinic and so it's ... it's one-and-a-half companies if you like.
Because it sounds like a cocktail of them all would do more good than anything?
Would probably work. What you have to realise ...
Ah, no, because the Federal Drug Administration, the FDA, rules the world in a way that the president of the US can't possibly. And what the FDA says, goes. And the FDA was set up in the late '20s or the '30s to eliminate the problem of kidney disease from taking APC tablets, remember APC tablets? Aspirin phenacetin codeine [caffeine]. They damage your kidney. And so this government agency was set up to stop the sale of medicines that were mixtures of things. So you have to prove that one drug alone will work. Never mind coming along and saying ... but two are better. Don't ... you can't test like that. So that's how companies end up with the patent for one, because it costs a hundred million dollars to test and get approval for any one drug. And nobody's rich enough to try all the different combinations. Truth of the matter is, we're being over simple, if we're talking about these two white blood cells, we now know that there are about, well, let's say 10 to 20 different regulators that can control them to a degree, so you're really saying, ‘Why don't you try all 20 together?’ Now there are a million ways of trying a combination of 20 drugs, literally a million, and it's impossible. So out there somewhere is the perfect cure for Mrs Smith — will Mrs Smith ever get it? No. It's hard bridging the gap between the laboratory, where you can test not a million mice, but a thousand mice, and going to the clinic and testing one patient — now the gap may only be 50 yards down the corridor but it's a big gap.
Do you remember the day that you actually got enough of these cloned to be able to inject into a mouse and seeing that it worked? Do you remember the day that ... ?
I do. I do very well because the end of a glass pipette broke off and dropped into my shoe and stuck into the end of my toe just as we were harvesting the fluid and I was too anxious to stop and pull this bit of glass embedded in my toe out. I do remember it, can take you to the exact room, I think. It was an important day when it came out milky with extra white cells, I thought, ‘Good, we haven't wasted 20 years.’
So apart from the fact that you had a very severe pain in your toe ... ?
It wasn't painful. I was too happy.
But how ... what does that sort of moment actually ... I know it's impossible to describe feelings, but could you have a go for us?
Yeah, I thought ... I felt great. That I hadn't wasted my time. Did I shout Eureka? No, I don't think so. But I certainly breathed a sigh of relief, I thought, bloody hell that's good. There's somebody somewhere who's going to get that stuff.
And that was what it was really about for you?
It wasn't beating the people in the laboratory across the world?
Oh, that too. That ... that's normal everyday interchange, competition. But I can ... after years of thinking about it in terms of leukaemia, and what could it do for a leukemic population, suddenly — and you might think we were a bit stupid and naive ... not to think of this possible use earlier — I could ... if you can change the number of white cells, there's got to be a patient somewhere with some disease where that matters. And if it works in a mouse it's going to work with a human. That's what should happen. Now if you got a splitting headache because you had that drug, that hormone, you couldn't use it. And a lot of perfectly good reagents can't be used because they are toxic. People discovered a similar sort of agent that would control these famous T cells that we were talking about coming from the thymus. But they can't use that stuff because it is ... gives fearful side reactions. So we were lucky in a sense.
Does this give any ... does this give us any ... ?
Oh, it gives a few and now people have the luxury of saying, ‘Hey, I wonder whether there are some patients, like with rheumatoid arthritis, whose condition is made worse by this particular CSF. What would happen if we developed antibodies to the CSF? Could we try them in patients with rheumatoid arthritis?’ And that ... those tests are about to start next year. So that's another turn of the wheel, you knock yourself out for a quarter of a century getting something to work to be used and now you're busy saying, ‘Ooh, I think there are patients I could stop this working in.’
So what was the first major group of patients for whom this was seen to be pretty suitable, and therefore the first that you trialled it all on?
The easiest ones for everyone to try it on ... was pretty much the same in Boston and certainly in Melbourne, were patients who were having bone marrow transplants, because if you've got leukaemia or you've got a bad cancer and you're getting massive doses of chemotherapy, you totally destroy the bone marrow in the patient ... you've killed the patient. The only way you can resuscitate that patient is to give them an injection of bone marrow cells. And they've got to learn to settle down in the bone marrow and grow again because without that you'll have no blood cells. So there are a captive set of patients, that they have had a serious sequence of treatments and it was known that you're going to be in hospital for weeks afterwards while this transplant grew, carefully being nursed; very expensive, difficult technique. Let's try it on those patients and they were the first patients being tried on. That's why José Carreras was one of the first patients ever to get treated with CSF because he had leukaemia, had a marrow transplant, it wouldn't grow, and in Seattle he was one of the first patients. So, the answer to the question is, cancer patients were the most convenient group to try this treatment on. Because they have a common problem that they've had their bone marrow destroyed and they're trying to regrow their cells. It's not touching the cancer at all but it's sort of like a blood transfusion helping the patient. And then there are patients who actually have diseases because they have no ... not enough of these white cells. Curious diseases like cyclic neutropenia. Every 18 days, your white cell levels fall to nothing, every 18 days you get an infection. Might just be a cold, might be a middle-ear infection, might be pneumonia. Every 18 days of your life, you get an infection? These kids' life is a misery, the family can never go on holidays, they can't go to school. There are not very many of these around the world.
This kid in Geelong I met, now has everyday shots of CSF, like you give yourself insulin, and perfectly normal, big strapping kid. So there are uncommon patients who this is the perfect sort of treatment for and then there are the millions who ... whose treatment is helped by it. But it actually isn't anything to do with the treatment. So it's a mixed bag and all those CSFs have been in use clinically for about 15 years, it's still early days. I mean, people are realising, oh my god, one of the things they should be doing: every patient who is badly burnt, you know they're going to get infections, you should start treating them straightaway with CSFs, before they ever get their infections. Does anyone ever do that? Never. You know, people, you just want to knock their heads together and say, ‘For god's sake, use your common sense.’
So if ... sometimes when people are being exposed to infection they're given gamma globulin and so on, that was very common at one stage, did you find?
Would it be possible with ... if CSF was very freely and readily available, to prevent infections with it?
Yeah, I think so. I think so. I mean, let's face it, CSFs aren't all that expensive, I think I'm right, they're only about 100 dollars a day, the treatment, and all I know is if I was badly burnt, I'd want to have a CSF treatment right now, thanks very much. If I had to have an abdominal operation, tomorrow, let's start the CSF treatment because the chances are your wound is going to get infected and da-da-da. And antibiotics are only good so far and they need help from the body's defences. Um, that's me nagging on and somebody I find to give it to me but the average patient doesn't know that and they're not getting it. And doctors are conservative and because, you know, if something goes wrong people will sue and so they're ... there's a real reason for caution. It's just that time goes by, you get a bit impatient.
You're a scientist, stuck away in a laboratory, do you ever get to meet the patients who've benefited from your work?
Not often but sometimes I do. Sometimes you meet them in the supermarket. Um, they did collect together a whole lot of patients at Government House a couple of years ago, just for a big get-together, that was sort of fun.
It was fun. It was a stinking hot day, actually. No, it was fun, it was nice.
And you mentioned José Carreras, the opera singer, one of the great tenors of the world. Your association with him was fruitful in other ways for research, wasn't it? How did that work out?
Um, not really. He now has a leukaemia research foundation of his own and a lot of his royalties he pays into the foundation and it supports young people, training and doing research. We've never taken money from it, but it does exist. And we've met him a few times here, when he's been in Australia. He's a nice, nice man.
The association with him gave a lot of publicity to the work, do you find that slightly ironic?
I found it slightly distasteful I think you shouldn't pick on people and use them as a fundraising manoeuvre, I think I'd be quite cranky if I was that patient.
You participated though in one of those fundraisers and were sung Happy Birthday.
I did. But I wasn't fearfully happy about it, I just felt that, yeah, that's being opportunistic, a little bit — anyway, it was for a good cause.
You made the point at that, that he was a patient, was part of what you considered to be the research team. What did you mean by that?
Well look, if I come along to you with a bottle of new juice and say, ‘I don't know whether this is poisonous or not, are you prepared to volunteer to have it?’ That makes you part of the team. And if you can say, ‘Well this is okay but I'm sorry but I'm getting a ringing in my ear.’ Then nobody else can tell me that, you really are part of this ... this person ... of this, the study ... in figuring out what's going on. So I regard the patients as part of the team, yeah, for sure. Ah, would I volunteer myself? Don't know. If I trusted the scientist, maybe. No, I think, well, if you're in desperate straits and there's nothing else, why not try ... a lot of these things are pretty double-edged. Progress isn't always upwards, progress is a little bit snaggletooth.
Not everybody would be as ambivalent about having José Carreras sing them Happy Birthday, either.
Um, I don't ... I think it's a bit naive to think that it's me that did all this discovering and all this creativity, it really was several hundred people. And so I didn't isolate the genes, I didn't mass produce them, I didn't make that bottle of stuff that he was given, so why parade around saying, ‘It was me. It wasn't hard, it was me.’ You work at every step of the way but, you know, it was a team.
So, I think if the whole 300 were there, we ... Yeah, yeah! Go. But the Americans believe truly that they discovered it. So if you read an account of CSFs now, it starts with the work done in Amgen in Los ... in Los Angeles, yeah. Sorry about that. It started in 1983. And you think, well, that's not quite true. Yeah, but that's ... that's the way history gets revised.
And there is a sort of what they call ‘hero version’ of history, which really requires a single individual hero, and in relation to CSFs in Australia at any rate, you're the hero, but you seem quite uncomfortable with that. Is that a concept ... ?
No, no, I'm comfortable but I'm just a realist and said, ‘Listen, I didn't do that alone.’ Anyone who claims that's a nitwit. And readily demonstrable as just being a blow-hard. Ah, would it have all happened if I'd never set foot on the earth? Yeah, probably, probably. Things tend to happen as the discovery of how the culture cells happened. Yeah, somebody would have twigged to it, somebody would have persisted, somebody would have done it, I suspect. Ah, you're the one that did it, so you can say, you're identified with that and that's what you did.
In respect of this, with all these different people coming in, and increasing numbers of both different disciplines, and increasing numbers of people coming to work on the team, what is the role of the team leader?
Well, it's quite complicated, everything from raising enough money to support them — and remember each research worker costs about half a million dollars a year, not in salary but in costs. Somebody's got to organise that money to be gouged out of somebody. Ah, somebody's got to recruit bright young students, young post-docs, somebody's got to have a game plan and says, ‘This is what we'll do — what we'll try and do.’ And if they're like me, somebody who is prepared to go out there and do it too, because I like to do everything myself as well as everyone else, so we're all working together. Much more fun. And then someone who's put it all together and go and do it all over again, so a team leader is many things. Father, confessor sometimes. Ah, an exemplar, hopefully. A bully sometimes, a ... you know, many parts. What makes a good leader? There ... it's funny if you look around our building, it's got 600 scientists in and say, ‘Who are the good leaders?’ I would pick four or five. And it's interesting, everyone else would pick the same four or five. They're all totally different in characteristics, one's aggressive, one's a flamboyant excessive, one's scholarly, you know, but each in their own way is a good leader. What's interesting is if you say: where'd you grow up? And nearly always 80 percent of the time it's in the country. Where'd you go to school? State school or one of the ...
... [question repeated] ... I wonder what you think are the qualities of a good team leader?
Who do I regard as a good team leader? Well, I think it's somebody who you accept as being smart and intelligent, on top of their field, full of good ideas, good creativity record, has a team that look happy, is productive, he's been with [the organisation] a long time, is capable of raising a lot of money for them, is well-equipped, is on a project that's really going somewhere and everyone's trying to copy them. That's the leader. Now, can you find them? What do they look like? Well, no two of them look the same. In our place it's got about 600 smart handpicked scientists from all ‘round Australia, I'd say ... five good team leaders, really outstanding. None of them are the same looking, don't have the same temperaments, they don't have the same way of working and ... but they've got it. So that's sort of what you're looking for and you see the new students coming in and saying to themselves, ‘Which department will I go and work in?’ What they're really saying is, ‘Who's impressing me as being a good leader?’ Now, sometimes it's the most handsome looking man and so on, well that's life. But they're the things they should be looking for. Now, the fun thing is and I've done it a couple of times, to get up and say, to the whole assembled crowd, ‘Hands up everyone who went ... who grew up in the country?’ About 80 percent of the hands go up. So that's the wrong proportion, I mean, most Australians live in the city. So how come most of the people in this building grew up in the country? First interesting point. Second interesting point, how many of you ... I don't ask, ‘How many went to private school?’ But, ‘How many went to a state school and/or in a crummy suburb?’ And again about 80 percent of them will put their hand up. And what's that saying? It's saying, I think, that people who are good in science are determined, persevering, who are able to get over difficulties and get where they're going to get because they're the same qualities that you need tackling any research project. Nothing ever just falls in your lap, it's always, you go round here, correct this, do that. And it's ... it's an interesting ... people don't believe me and I've done it deliberately a couple of times in public, just to prove my point that ... just be careful when you're picking the next lot of students, don't just go for their academic record, just check where they grew up, where they went to school, and if the answer's are bad, bad, bad, country, they're probably going to be winners. That's my bias. That I grew up in the country has nothing to do with that.
So you seem to be saying that doing it tough, is important training for science. That having difficulties, hurdles, not anything served to you on a plate, so to speak, is an important quality?
Um, it doesn't seem to ... that's a good question and you have a double answer. I have seen people who have had the misfortune to become students in a poor department on rotten lousy projects, have never managed to succeed in science as a consequence, it's very hard to dig yourself out of that hole. Now, if you say, go back a bit and let's have a really tough schooling and difficulties there, if you get through that, is that a plus or a minus? That tends to be a good thing. So you can be ... you can have a career absolutely ruined by bad fortune at the beginning. That's why I consider myself very lucky having had two eccentric bosses who ... who happened to know the head of a foundation who happened to have a job, that allowed me to get the best place, and even though it wasn't all that satisfactory, it ... things worked and then you have good fortune, good fortune. There's a lot of luck in it and I sometimes stand on the road outside Sydney University and think, ‘What would've happened if I was still here?’ I'd be working away in one ... chances are — and this is badmouthing Sydney University, which one must never do — that I might be working by myself, without a team, in a room getting nowhere. But trying just as hard. So you can be lucky. I think you can. So it's good to have it tough, but not at the wrong time.
You must have needed quite a bit of that ability to hang in there when things weren't going very well, during that period that, although you were distracted while you were doing the things, and you were doing useful and interesting things, nevertheless it was a long time that you had to hammer away at something that was frustratingly not just falling out the way you might have hoped. Is that a real ... really important characteristic required by anybody working in science, not just leaders, to have that ability to persist?
I think so. I think so. And if you don't have it, you really won't get anywhere, because you're depending on good fortune and things dropping into your lap. And that doesn't happen very often. Ah, if you use the right techniques you shouldn't get yourself into a fix quite like that, you should always have at least two projects going on. One of which is a pretty straightforward thing, a humdrum if you like, thing, that you know will give positive answers that you can use. They're not going to make you the most famous scientist in the world but you'll be productive and you'll get paid and you'll get grant money. And the other one is more dubious one which has the prospect, if it works, of really being something big. So you have two things going, at least two things going at once, that's what I teach everyone. So at any one time, yeah, things might be just going crazy and badly in what you're hoping one day will be a big project, it may turn out to be a fizz. But you ... you've got a steady product here that's building up your reputation. And perhaps not as demonstrably but it is growing in another direction. So you ... it's like the people in finance say, you know, diversify your investments. Diversify your projects to a degree.
How do you know when you're not ... that you're not persisting foolishly?
You never know, you may end up a tired old man of 77 and think, ‘God, I've wasted the whole 50 years, the whole lot's gone.’ Even though things aren't getting to the end and you're not seeing a way to use something, you usually know that you're not completely wasting your time. At the very least you're getting new information and new knowledge. Um, if you're not doing that then, yes, you should change what you're doing. Somebody should change ...
If you're not making some ... if you're not making some progress, you need to be having signs that you might be on the right track?
Yeah, look, the way you do science these days, particularly, is in the apprenticeship scheme. You never start off in a room by yourself, saying, ‘I'm going to be a great scientist. This is what I'm going to do.’ What you do is join somebody's team and it's the team leader's job to sense whether that particular project's going nowhere and will I change it for the person? Ah, and that person might be in the middle of doing a PhD and you say, ‘Look this project is hopeless, we're going to change it and we'll do this.’ And it happens. And several times a year I'll have to stop doing something, it's just getting nowhere, it's probably wrong or it's probably a mistake in the beginning and it's not repeatable and what's it mean? Nobody will believe, da-da-da. I drop it. It happens. Every day, something new happens.
Was the fear of ending up an old man of 77 who'd wasted his life on projects that led nowhere an important motivator for you?
What can you do about it? You can't stop getting old. You ... can you guarantee that the project will work? No, you just grit your teeth and get in there and try and be smart. I never took much notice of what other people said and thought. I hardly ever read the literature and I sometimes get caught because somebody actually has done something that's quite important. I'm not arrogant and think that nobody in the rest of the world can possibly do anything smart, I just am not interested, I've got too many things I'm doing myself. So you can occasionally get caught. So you're not really ... I'm never influenced by what the rest of the world thinks. The rest of the world says, ‘That's a stupid idea,’ I don't believe it for a word. If anything, I'll just work harder at it. Now the ... I sense that there are a lot of people who go the opposite way, they're sort of bandwagon jumpers, if they ... this is a popular subject, I've got to be in it. And I just think that's pointless, I mean, there are already 50 people in it, do you want to be number 51? Forget it. Go and do something else. So if people say it's stupid, I will try to think of an experiment that will prove them wrong and me right. And that's the way you go.
You talked about people growing up in the country, being a large part of the scientific population. In your observation, there's that famous idea that Australians and especially Australians in the country are great ... have to be great improvisers. Do you think that sort of idea of finding your own way through something and not necessarily taking the obvious route was important in your work?
I think so. If you just think in terms of having ideas about what might cause leukaemia, yep, I was taking a completely different tack to the rest of the world. If you think, did I invent a new gadget? Did I, you know, screw two things together and say, hey, this can do that? I'm not good at that, that's where I need to have smart young people with me, who have technological expertise and things and then we can get them all together and work, but I tend to be doing the same things over and over again in a rather routine way. So it's a bit of both. Now, why are the country people good? It's a bit of everything I think. But the thing that I find is that if you've been in a country school, it's pretty ordinary, you don't of necessity find superduper teachers who are shoving the information in with a silver spoon and saying, ‘Here, this is the way you'll get through this exam.’ You've got to figure it out yourself, you've got to push, push, push. And it's that hurdle that, to me, separates the people who are ... have it, the potential there to do it, from the ones, well, you just don't know, they never had to try. Now, the kids in posh private school might be equally smart, but have never had to do it. I don't think humans are different, I mean, the ones that live in the country aren't genetically different from the ones in the city, they have the same number of fingers, usually. Um, but it's the way you grow up and whether you've had pressures put on you that you get certain skills or bring out differences between people.
You've described a variety of different characteristics that are part of good leadership and you say that it's obvious who are the good leaders. In your own case, what would you say would be the distinctive characteristics that have made you successful as a team leader?
My sweet nature. Um, if we go back to the characteristics of being a good leader, I've been fortunate to have people who are very smart and able to work with each other, and that's a big if ... and are creative and if you can hold them together into a project, where they can all do their bit and be seen to be the one who did that bit ... there's nothing worse than being in a team which only has one visible person and no matter how smart you are, there's no credit coming. So I've been lucky in needing to have people in the team who are obviously different. They're a biochemist and I know nothing about biochemistry so they can't possibly say, ‘Eeh, it was all your work.’ No, it's not. So everyone's happy and as long as it's happy, you can keep them happy and you can keep them enthusiastic and pushing, you know, I think success in a retrospective judgement says, yeah, you must have been a good leader.
You also described, earlier, how you like to be a person who does his own work, who's actually at the bench. Who works. A lot of people prefer to give to junior people some of the sort of detailed work at the microscope but you've never done that, why?
That ... it worries the hell out of me, to see this happening. If you go round our institute at the moment you'll find that the oldest person working in the lab is about, let's say, 40. And I find that frightening. Because as a biologist it takes about 10 to 15 years to stop making mistakes. So if you start off, 20, 25, you are 40 by the time you've learnt your trade. Now you're an expert, now you're stopping? And filling in grant applications? Now you're stopping and talking to students? Come on. Who's doing the work? The untrained, young PhD students. So this is a bizarre setup. The most expert people in the building are too tired or too lazy, or claim that they're swept up in committee working too much to actually be doing it. The fun is doing it. I go into work tomorrow morning ...
You raise the ... you raise the age of people sitting at the microscope?
I think it worries the hell out of them that I'm still around, but ...
So what do you do ... [interruption] ...
I can't wait to get to work. I can't wait to get to work and you say, ‘What do you do? You've got the same sort of tray out, you look at the same sort of cultures, are you out of your skull? That's not boring?’ But every one you're looking at is different and you may be thinking, ‘Oh, wonder if ...’ And it's all like opening up a new book. And I wouldn't ... I couldn't change that for anything. So to an outsider looking at me, ‘There's this poor old guy who's been sitting there, man and boy for decade after decade, apparently doing the same thing. Isn't it sad?’ And here I am getting booked for speeding, getting to work at a quarter to six in the morning. Come on, it's exciting. Now, are we discovering marvellous new things? I hope so. Are they going to be applied to any patients? I'm a realist enough to know that the odds are dead against it, we'll certainly try.
Have you ever delegated that, well, apparently boring bench work?
No, I don't trust other people, I mean, listen, if you're going to put your name on a scientific paper and you said you saw that, I want to make sure I did see it. That I ... I didn't want Joe Blow coming in and saying, I saw that. Yeah, yeah. To a degree all papers involve that, you've got to trust your colleagues that they did the actual bit that they said they did. And this is what they actually found. But if it's something of a technique that I can do, then I want to be the one that actually did it so that I know it was there. Now goodness knows that there are many times in the day you don't quite know what you're doing. And you're guessing, that's bad enough, but to have somebody else doing the guessing is not good. But I'm regarded as very strange, very strange person. They leave me alone. In case it's catching.
Is there, in theory, a person that you would ever trust? Or is there nobody?
Oh, I trust everyone in the group. I just ...
I just ... I just don't trust them counting my colonies. I trust them for everything else, that's fair. You've got to have some standards. No, um, when you're a team you have to trust people, you mustn't have it so that ... it's not that you each check on each other, but that you, you know, that it's been done so many times and there are so many other reasons why something is ... is as said, as believed that that is probably right. Probably right. You're never, never, a thousand percent sure that everything you do is right, you try but you can't.
Now you said you wouldn't trust anybody else to count your colonies, what do you mean, counting your colonies?
I mean putting the plate under the microscope and counting, one, two, three, four, five, six, seven. I count in my head, every one. I count. A million, million, million times a day, up and down, up and down. Um, now I wrote somewhere in a book that I wouldn't trust, I think I said, wouldn't trust a technician to do the job. And the reason is their career is not hanging on the answer, that if you make a mistake, they're not going to lose their job, making the next discovery doesn't hinge on what you see down there. You say, ‘What is that?’ Or, ‘I wonder whether that's something I hadn't thought of, I better do that.’ So even the best technician in the world, and I have two of the best technicians in the world, do other parts of the same experiment. They set up the cultures and, you know, they're better at doing that than I am. But I want to see the outcome because I know that this is where you get your next idea from. Well, anyway, some Indian guy read this book and he wrote an infuriated letter saying that I have insulted all medical technicians and I retract this immediately in public. He was pretty angry. Because I said that I wouldn't trust a technician to do it, I may have said, trust, I wouldn't allow or do or something. But the reason is that, it is ... it's like saying to Columbus, ‘Hey, let the, cook sail the next hundred kilometres because the cook's pretty good.’ And you're just about to see the land over there and ... No.
So you're doing more than counting, aren't you, then?
I am worried the hell out of whether the cultures have behaved themselves today, whether the answers are the same as the last two weeks, whether it's really supporting what I believe is going on here and do I see signs that maybe the whole idea is wrong here? Or is this? There are a hundred things that are going through your head as you're counting. So half of my head somehow is in counting mode, it's just going, click, click, click, click, click, click. And one half is wandering round and saying, ‘I wonder what all this means’ and ... you know, da, da, da, da. What's happening? I think brains are capable of that.
All the time. When I get tired and I nod off and it's quiet on a microscope and it's dark and it's ... you've got the light turned down a bit and it's easy to nod off and you just start again. Or if somebody comes in the door you have to start again because I count four different sorts of colony in my head at once, so I sing it to myself as a little song. One, two, three, four. One, three, two, four. One, three, five, four. And then every so often I write it down, otherwise you've got to put your glasses on and write it down and it's hopeless.
And you can do that? You can sing your little song and think on another track? And I'm thinking that the truth is that it's not that you don't trust someone else to do it, it's just that you're having more fun than ...
That's probably true, probably true. Um, it is ... it's like Christmas, isn't it? Opening the incubator door every morning and getting out tray loads of cultures and saying, ‘Well, what's happened? What ... I wonder what's happened?’ Now if it's not ... hasn't worked again, well, another day, it's tomorrow, we'll try again.
So quite a lot can happen in those little cultures overnight?
No, it takes one week of culturing but you don't look at them in-between otherwise you get them contaminated and the gods are nasty, you just ... there are certain pieces of magic that you don't do. And one of them is you don't have ... sneak looks at cultures to see how they're going. Because that's the disaster, never works. That's one of the rules in the place. Ah, things ... but things can happen overnight, yes, if the incubator's running hot, they'll be baked tomorrow, like baked bits of steak.
So you do have these ... these cultures to count but you have other things to do ...
Oh, I have to do all sorts of things.
... that are associated with the work and all those things that you mentioned like applying for money and hiring staff and ...
No, no, no, I mean ... I mean work ... never mind that other rubbish. I do all the pathology, which means that all the sections, all the biopsy material from all the mice with different diseases, are all coming to me for diagnosis and, you know, recordkeeping of what diseases they had, etcetera, etcetera. That stuff, I am getting to hate that a little bit because it really is hard work. But ...
It is working at the bench.
So you're basically at the bench most of the day?
I try to be.
Is that hard physically to sit there all day?
I just write very quickly. It's physically very hard.
I know, it sounds easy doesn't it though ...
It's hard when you've got back disease and you can't sit without backaches and it's quite hard or you get a stiff neck, some people get blinding headaches. I don't get headaches but I get a stiff neck sometimes. You get stiff, you get frozen, it's often cold in there, holding on a lump of metal, it's freezing. But that's alright.
It doesn't sound like a very medically wise profession?
It's not. It's called microscopist’s back and microscopist’s neck and people don't like it, people hate it. Most people hate it, they would pay money not to look down a microscope, they would pay large sums of money. And it's quite interesting the ... most people are hopeless, you give them a plate that has 20 colonies on to count and you say, ‘What was the count?’ They say, ‘150.’ I say, ‘No, it's not 150, go back and count it again.’ ‘There's three.’ And they just can't concentrate enough to ... it's quite curious, the people you run into.
So given that it's physically, you know, at times painful and most people don't like it very much, why do you think you ... it suits you?
It suits me. I think the other people like being biochemists or like being molecular biologists or like writing papers or sitting there looking put upon and sitting in their office. Ah, different people like different things. It's ... microscopic examination of tissues and things are just amazing. Amazing piece of visual art, if you like. They're just magic.
And you get paid for it.
You said that as a little boy you wanted to look in this telescope, do you think you would have seen anything more interesting than you see down the microscope?
I might have, I might have become an astronomer and that's the end of it. When I saw my first nebula, be on... but visual things have always had an impact on me. We had as children the Arthur Mee's Children's Encyclopaedia, a lot of families did. And if you've looked through that, it's the most appalling Victorian, right-wing text but it has full-page drawings and they're the things that I remember. I could go to Arthur Mee's encyclopaedia now and go through drawing after drawing, don't know who did them, they were sort of pre-Raphaelite drawings, you know, Horatius on the bridge, God knows who the Etruscans were, they were some baddies coming in to Rome. Now the fact that you've been to Etruria and you know the Etruscans were twice as smart as the Romans and ... is in one half of your head but the other half is Arthur Mee's picture of Horatius with the Etruscans. And that's all I remember of reading this thing, so visual things do have an impact and the number of people around who are able to look at things and see things is desperately few in number. So, when I leave the institute, there is nobody who can do the job that I'm doing. And you can't interest anyone in learning it ... it's 10, 20 years of learning but at least start. So ... and it's the same all the way around the world, they are desperately short of cell biologists and pathologists, desperately short, it's clear that not everyone has that ... that combination of things they like doing and perhaps it's something to do with visual imagery, I don't know. It's not a popular pastime, I've never succeeded in any student in telling them, ‘Hey listen, come and do what I'm doing.’ Oh no, they end up doing biochemistry or molecular biology. Two years later they come back and say, ‘Would you help me with this? I think I made a mistake. Think I should have done some cell biology.’ And you say, ‘Oh well, give it to me.’ It's a vanishing, vanishing breed of people and it ... you know, they've been trying for at least 20 years to make a machine that will count colonies, so you'd think somebody would design a sensor that could go and handle how to identify spots of different shapes and sizes and count them all as one or subcount them as different ones; they haven't succeeded. Or at least it takes 12 hours to scan one plate instead of 30 seconds. So I'm still in job.
Could they make a machine that could count and think at the same time, like you do?
I'm sure they could, I'm sure there's smart enough people out there.
Can I take you back and pick up on something that you said that you were interested originally, in the fact that you though that it was possible that the leukemic cells might able to be changed, become normal, using CSFs. Is that a line of enquiry that you've pursued at all?
I haven't but the field is actually making good progress. And there's one type of leukaemia that you can literally do that. You give them a drug called Gleevec and the leukemic cells are just turned into normal cells, more or less while you're looking at them, and the patients are going on, happily, this used to be the most vicious form of leukaemia, where you bled to death in days, you were ... you were ... [interruption] ...
This is promyelocytic leukaemia and it ... it's now, or rather, there are two sorts of leukaemia: there's one, chronic myeloid leukaemia, which really wouldn't kill people faster than about four years, but it did for sure ... for whom this new treatment is the perfect answer, and there's another set with this vicious form of leukaemia where the Chinese came up with a treatment and nobody believed them, treat them with arsenic, god, pull my leg. And it's turns out to be a perfect cure. Probably a cure. I mean, the patients have been going on for years and ... so it is possible, it is possible, but in half of your head you know that a leukemic cell has about 50 things wrong with it inside, and how could you possibly in every cell in the body get in there and fix each one of the 50 things that's wrong, in each of the billions of cells in your body? Can't be done. And so you say, this is a stupid way to approach it and it'll never work. It does work, it can be ... work. And so people have taken heart again and it's tough going but ... and there's sometimes not much science to it but it's making progress. It was ... it was more the original idea that we had that this had something to do with why you became leukemic and it turns out now that the reason why cells become cancerous, leukemic, is that two things have happened in the cell: one is that they've learnt how to stimulate their own growth, so they don't need any colony-stimulating factors to make them grow, and the other thing is that they've made a mistake in how they make daughter cells, that they're making like themselves, instead of making two daughters that sort of mature and grow up and die, the two daughters or more than half of the daughters are like the parent. So it's ... it's a mistake in how the cells mature. Now if you do those ... if those two things go wrong, you have got leukaemia.
Now, how those two things can go wrong are in 20 different ways, but in principle there's just two things have happened, so in principle, you could try to cure a leukaemia by hitting one or other of those two things, and one of them involves this making cells mature and that's sort of making the daughters behave as grownups, and the other way is to stop the cells making themselves divide, to cut the motor out of the cell, and that's what this other drug Gleevec does so they're beginning to find agents that are not toxic, don't kill the rest of the bone marrow, aren't horribly nasty but actually will do a job. So it's a great time to be in leukaemia research even though we realise we don't understand more than one percent of what we have to learn, things can be done. So when I started, anyone who had leukaemia, you might as well shoot them, because they were going to be dead for sure, nobody ever survived, or if they did ...
If they did, whoever was involved became a saint because you'd done one of ... one of the three miracles. So ...
For all forms. But some it took a couple of years to kill, some it took a couple of weeks, but everyone died. And now, if you can't cure children with leukaemia, something odd has gone wrong. If you can't cure a young adult with leukaemia, you're a bit unlucky, if you can't cure old trouts like me, there's nothing. If I get leukaemia, it's bye-bye. Because none of the treatments can be used on people of my age.
My body won't stand the punishment of these chemotherapy drugs, which are vicious. Now if somebody gets a smart agent perhaps they can use it on me.
Even with CSFs to replace your destroyed bone marrow when they ... ?
I wouldn't survive. I couldn't. So, what happens when you have a big dose of radiation, or you have a high dose of these chemotherapy agents, is lots of damage is done to lots of things. One of the most obvious is bone marrow, but other things are knocked out ... out of kilter. And a 20-year-old can take it, a kid can take it laughing, and a 50-year-old is battling and a 70-year-old is down the tube. Now, what's the difference between a kid and me? I can find very little difference in the questions I ask, the cells look exactly the same, behave the same way, but there's some difference and one day somebody will figure out, what's the difference? Until that day, best I not get leukaemia.
So the role, is there any chance, I mean, you were thinking that CSFs might have some role in changing the cells when you started out, and you said that there's been development of other things which have done it. What about the CSFs?
CSFs have had a reasonable trial and they aren't able to do it, even though there are some leukemic cell lines that everyone uses in the laboratory where they do work. But it turns out, if you go into the clinic and you just walk up and down the row of patients and say, ‘Are your cells able to respond the same way?’ The answer is, no. So it is not the typical way that typical leukaemias behave. So they do have an action but we don't know the trick of making it happen for all the other patients. So there's a lot more to learn. It's in there is one of the components but there's something ... some other things that are missing, one day it might turn out to be right.
How did you get out of the animal house?
I got away from the animal house when a new director was appointed to the institute, Gus Nossal. And his first act was to ask me to be the assistant director and to come into the main building, and we had a sixth floor there that was not complete so we purpose completed it as a set of labs and we had marvellous new expanded quarters that were purpose built, it was great. So that was 1966, I think. '66. Yeah.
How did that make your work different, being in the new environment?
Didn't make a lot of difference except that you could look out and see the city below you. It was a great view, better labs and so you could put equipment in and increase the number of people in the group. And the mice were in proper animal rooms so I wasn't sneezing all the time, so it was great. And you were with other people so you could collaborate with them, because it's very hard with a colleague who's 50 yards away or a hundred yards away to do an experiment together, whereas, if they're on the floor below you it's quite easy. So more of the experiments were done using additional people with the skills from other groups. So it really surged ahead because if you're given extra space, more people, more opportunities to do the job a different way, it helps.
What was the connection between the move from the animal house and the opera Fidelio that you ... ?
Opera, Fidelio, now that's a good question. The opera ... in the Fidelio all the prisoners come out from the underground prison, isn't it? By pushing open the grates in some productions. Maybe that's what it was. It felt like escaping out of prison. And joining the rest of the world. Were we rescued by a faithful wife? No, I don't think so. A new director.
What other things did the new director mean for you? Was there any other element that changed for you as a result of Gus coming in to replace Mac Burnet?
Well, he was 100 percent for the program we were doing, he wanted to work on leukaemia, he wanted to work on regulators of cell growth, so it was precisely the area that he wanted in his institute and it made it complete for him because he had people working on autoimmune disease, people working on infections and then he had people working on cancer of the same blood cells. So it was a nice match. I think we added some intellectual power but it made the ... it made his grouping balanced and you could see that.
Now, in describing the way in which things developed you've taken us already through the various stages, from the first idea to what inspired, and you're eventually getting clinical trials that worked on human patients, but what happens once you prove that something can be done to make it actually happen in a way that will get it out to a lot of people?
Well, first of all, you need people like Tony Burgess, who was originally my first assistant and while this was going on became director of the Ludwig Institute next door, to go round knocking on company doors and saying, ‘Look these are interesting molecules, they probably have some clinical use, take an interest.’ And eventually slowly, very slowly, companies agree, yes, maybe it is. So he had to line up companies that would possibly have an interest. Once you've done that and, of course, what you must remember at exactly this time, biotechnology companies were starting in California so quite independent of all the academics like us, they were saying, let's develop these agents to make money. Which they did. So Amgen, the most successful one, said, ‘Let's find the gene for CSFs.’ Which they did. And let's make a billion dollars a year. Which they do. And from their little group there are now 16,000 people in a small town all based on the money they earn from CSF and from Erythropoietin, the two similar drugs. So, they're doing it the commercial route with a view to applying it and so they have built up a set of people out advertising, getting clinical trials done and going to doctors, saying, this is the stuff to use. And we're doing the science and, you know, this is what it can do and this is how they should be used. And so on. So, we had to do a lot of sort of leg work trying to interest companies and actually the existing companies never played a part in the development of those agents.
The ... their mental thinking is surprisingly inflexible, enormous companies like Merck Sharp and Dohme or Bayer, have programs that are set in concrete years ahead and even if they wanted to, even if you convinced them, ‘This is the new agent, you should be in it,’ they can't do it. So we learnt that bitterly over the years. They were not the people you approached and in fact the people who successfully introduced things into clinics were these new companies that had no background, weren't in the pharmaceutical industry, and had to develop everything from nothing: their sales people, their medical reps. But in general, through one route or another, mainly through this commercial route, more and more clinical trials are done, all the data ... rooms fulls of data are sent to Washington to be gone through. Yes, it's done all these tests. You've done this, you've done that and then they agree that it can be used. For certain purposes. And they never license anything for any use, so you're allowed to use one CSF for one particular use and nothing else. And it doesn't make sense to me but that's the way it works.
You've talked earlier about the FDA and their incredible power in getting these things to happen. How ... I mean, what actually has to happen with the FDA and a development like this? Do you deal with them or does the biotech or pharmaceutical company deal with them?
Yeah. We deal with them once removed so the company, let's say Amgen, comes to Melbourne, collects all the doctors in the Royal Melbourne together and said, ‘We're prepared to fund a clinical trial. Are you prepared to do it? This is what you have to do. This is all the paperwork you've got to do. You need extra nurses, you need stacks and stacks of clerical people.’ And you produce this room full of data from studies on maybe 30 patients and that's collected and similar sets of data from maybe three or four other hospitals are then all sent to Washington, and they sit in judgement on it and say, well, you know, ‘Does it fulfil the rules? Is it efficacious? Is it safe? Is it da-da-da? And will it be less costly to patients than existing treatment?’ And if the answer to that is yes, then slowly they will approve it for certain uses. If the answer's no, it's back to the starting blocks. Now, why that should cost ... I think it's a thousand million dollars Australian, now, I do not know. There are hundreds of people involved. So we don't have anything to do with it. We've passed our baton on to a patent holding company in America and they've dealt with the company. So it's the company that then comes to us as academics and says, ‘Test the thing and we'll make use of the data, have it licensed and you guys get nothing out of it except that money that supported the trial and the fame and honour of having made money for us. No, the fame of having introduced a new treatment.’ It's a funny business so scientists never are the ones that deal with the government, to get something licensed, so if for example one day stem cell products are used clinically, it won't be the group at Monash who worked with the stem cells and maybe not the group that showed the application, but it'll be by proxy some company that's developed to, you know, expand the subject, get the material all certified, clean and usable.
To create it into a commercial product?
Yeah, it's a very ... there should be a cheaper way of getting new drugs tested because there are a lot of young people out there discovering new things that could be used on somebody, that will never be used. Because the process of doing it ethically and legally is too expensive. So an enormous German company like Bayer can only develop one product a year. Can't afford any more. So if you're a young guy and you've just discovered the hormone that controls, da, da, da, too bad. The company can't afford to test it and develop it.
The reason they can't afford to test and develop it has to do with the whole weight of government and regulatory conservatism ... ?
And the possibility that Mrs Jones may have bravely volunteered to test this but whoops it killed her, or whoops she became desperately ill, as happened in a clinical trial in England a few months ago. And so there are lawsuits, but that's part of it, now what fraction of the cost is covering that, I don't know but, you know, there are multiple issues at stake and sometimes ... sometimes it takes years to prove that what you're doing is actually better than the existing way. For example, we discovered when we were testing CSFs in the first lot of patients, because we were carefully monitoring everything, that all the stem cells in the bone marrow were coming out into the blood. So the clinician said, ‘Hey, why don't we use blood for a transplant instead of bone marrow?’ Because to take bone marrow, you need an anaesthetic, you need a team of doctors sucking ... trying to suck one litre of bone marrow out of all your bones, everywhere they can find one, it's not a pleasant job. And it's not very efficient. This way, you give a patient an injection of CSF and then just collect their blood, so you're giving a blood transfusion, read a book, watch a television movie, it's over, finished. And it's better, it ... it works faster, you don't have to spend weeks in hospital, and it's less dangerous, right? But proving all that, the step between us finding the stem cells, the clinicians trying the first test and saying, ‘Hey this is working well,’ to having all the clinicians in the country and every other country saying, ‘No more bone marrow transplants, it's all peripheral blood stem cells,’ takes a decade.
So, hardly anyone now uses bone marrow for transplants and yet the original observation was made in 1988. So it takes time. And it's nobody dragging their feet, it's just ... just takes time to accumulate the clinical practice and results.
Ah, I suspect for that one, not a lot of money, because you didn't have to change the setup of a hospital. I mean, it is true now that you can have a transplant almost as an outpatient, so you don't need an elaborate ward with barrier nursing and germ-free containment, that's gone because you don't need it. But that's simplifying a hospital, that's saying, ‘Okay we can do it in the ward instead of having a special ward.’ So that wasn't an expense but that might have happened. So the fact that you can come back now and say, ‘Listen, it only costs a third of the money to do a transplant this way than the old way,’ is part of the story but you also didn't have to build a special hospital to do it. So it all adds up and it ... sometimes new developments do require new capital works, so it's not just that the technique's better, it's ... I've got to change the building and do something else. Train new people.
Now in this whole chain of development of a new drug, when you as the scientists really basically pass on to a commercial enterprise to develop and exploit it, where does the intellectual property go?
Good question. I don't think we made a penny out of that observation. Could be wrong, I don't think so. It happened ... it happened by accident, right, the discovery that stem cells go into the blood was an accident, it wasn't figured on in the original protocol and ... but it was happening, it happened while the company was still applying to the FDA, so it could add that use into the application for licensing. So it didn't need any separate patents, it didn't need any separate official approval, so it's all one packet. It's not that Amgen pays any royalties to us, but if it had been the other way around, I think it would have all been included in the one packet.
Now, in relation to the CSFs, you know, what ... how does that work from the point of view of returns in royalties for the intellectual property in that?
Well, we don't have the intellectual property for the most commonly used CSF, G-CSF, we discovered it, we purified it first, but we didn't clone the gene first. And patents are issued on processes, so if you discover a new method for growing wheat, that's a patent, but if you discover a new form of wheat, that's not a process, that's just discovering what's out there in nature. So CSFs exist in our body, so if we discover them, and say, ‘Hey there's such a thing as CSFs, we've purified it, here it is in a bottle,’ that's not an invention. The invention is to discover a way of making that by getting the gene in this case and making that. So that's what you can patent. Now, we do have the patent for one of the CSFs and it's not used very often because the company is not as aggressive as the other company. But I think it's a more versatile product and it ought to be used more often. Now, turns out that it is being tested now in bowel disease, in Crohn's Disease, and it seems to be working. So, I was discussing earlier this week, what happens now to the patents that we hold if we say, ‘Oh and by the way, you can use it in Crohn's Disease,’ if that turns out to work. And the answer is, that you can't really change the original patent, you have to ... but you can take out a patent called a user patent, which says, I am now describing an invention for making CSF for Crohn's Disease. And maybe you get that, maybe you don't.
So it's funny, to an outsider it must seem ridiculous and cumbersome and it is. I think it is. But it's bureaucracy and that's the way it goes. There ought to be a way of testing drugs more cheaply. I come to you and I say, ‘Look, I've discovered something, I think it's good for you, I think it's going to work, are you willing to have me try it?’ And you say, ‘Ah, yes, and I'm willing not to sue you if it goes wrong.’ And the government says, ‘You get 10 people like that and I think you've made a fair case and we'll license it somehow.’ That shouldn't take a thousand million dollars. There ought to be a simpler way but nobody's found one yet.
So [with] the Walter and Eliza Hall Institute, as an institute, you personally as a scientist have not benefited financially from the work you did on CSFs, which are now used all over the world?
No, that's not quite true. We get royalties from one CSF and in a good year it's about a million dollars a year. Maybe more, maybe two, three million, and I think the patents are beginning to run out in Europe but they are still alive in America, where most of the money comes from. And there's a complex formula that's been developed by the Board at the institute where the institute gets most of the money and the inventors, the people named in the original patent, get portion of the rest. So I, myself, do get some royalties and the institute gets some royalties, they're not mega bucks, they're millions not billions. Um, different institutes do it different ways but it usually works out something like that. It's ... the government and various granting agencies are trying to do something to ... which to them sounds logical but will be a disaster, and they're saying the following, ‘I gave you the money for that research, I want a percent of the royalties.’ And he says, ‘I gave you some of the money for that research.’ Because usually the research money comes from several places. Each one wants a cut of the action. And if it adds up to 100 percent then the institute and the scientists get nothing, because all the research is paid for by somebody else. Right? So unless we do something, unless the rest of the country does something, we're at risk of having everyone who ever contributed any money saying, ‘I want a portion of that royalty.’ Whatever it is, now it's not often much, but sometimes it is.
So the principle is that money can earn money but labour, however skilled, can't.
I'm not ... I'm not sure how it'll end up, we are complaining bitterly to Canberra and anyone who'll listen, but they all say, ‘I'm sorry but it's my money, I gave it and I deserve a piece of the action.’ Now I have to pay money to the Anti-Cancer Council so they get royalties from CSFs and that's the only one but if the federal governments, through NHMRC [National Health and Medical Research Council], said, ‘hey, but we gave (as they did) five million dollars this year’ I think to our group, ‘we want five million dollars worth of the action.’ We're cooked. As an institute, we get nothing. There has to be a way around that one, that's a new twist this year, but it's happening around the world simultaneously, every agency. It started in America with NIH [National Institutes of Health] in Washington — some of our money comes from America — saying, ‘We want part of the royalties.’ And the Anti-Cancer Council saying, ‘We want part of the royalties.’ Canberra saying, ‘We want part.’ Where does it stop? Then 100 percent is reached and we get zip. And we're saying, ‘What is the point of us doing anything if there's no reward at the end?’ Not that you do it to make money but it's sort of nice if you get a bit of credit for what you do. How would you solve it? It's not easy.
Yes, well I was ... I was just thinking it is part of a trend that labour, however skilled, isn't valued the way capital is.
It may ... may be that it's happening, it's ... yes. It's essentially that, it's the money and it's quotes, my money, it's the taxpayer's money usually. There it goes. We have an interesting way to spread our royalty in our institute; everyone on the staff gets a cut. So they each get a cheque about this time of the year, and it's the same sum for everyone: wash-up ladies, animal girls, scientists, director, everyone gets the same percent. And it’s a couple of thousand but it's nice.
That sounds almost socialist, Don.
It does, doesn't it? I try to treat everyone equally and it's quite interesting, in the days when I was assistant director, when you had to sign pay cheques, when there were such things as pay cheques, literally cheques that you signed, to notice that there really wasn't much difference in the pay cheque of an animal technician versus a unit head, a professor. By the time the taxation difference is taken into account that, yeah, it's within spitting distance. So, the fact that you were always just called by first name, never Doctor Metcalf, never Professor Metcalf, just Don, is something you live with and you ... everyone treats everyone else with respect, but as equal. It is a bit socialistic. But then we're all in the same boat. I mean, if an animal technician makes a mistake with the mice, you are screwed, you are in complete disaster, you'll get the wrong answer, you won't know what's happened, it's chaos. So the lowest person in the team can torpedo the whole thing by accident, just as much as the ... one of the leaders goes astray.
What sort of a mistake would he make with the mice?
Oh, some mice, there are more than one sort of mouse that's white-coloured. Mix them up in the breeding boxes, I mean, they're dealing with a quarter of a ... half a million mice a year. They're all inbred mice with maybe 30, 50 different types and if you make a mistake, and it's happened, it's very hard to detect but you get completely different answers. Um, ... you just can't afford it. I mean, if you were to go into our animal house, which is a great performance because it's all automated, each mouse box has its own air supply, you've got to go through air showers and everything's on computer. Our ... every mouse doesn't have a computer chip on its ear but it's getting to that point. It's a lot of high-tech stuff and you can make a mistake entering up mice and mix them up, yes, you can. It's scary. So you have to make sure they know exactly what the project is, what's at issue, what ... why things have to be this way. So there's a lot of ... you don't issue orders any way, this ... like you used to in the old days, now it's ‘sit down, we discuss this. Everyone clear what's happening? Why it has to happen? You know your job, we'll check this when it ...’ So it ends up everyone perhaps being worth much the same sum of money. Anyway, we digress.
Now the whole institute has this relationship with Melbourne University, how does that work? What is the relationship?
It is a fairly loose relationship. We're a university department, which allows us to have postgraduate students, masters and PhD students. So they're students in the university. Each student by law is supposed to be, or the institution that has a student is supposed to get, I don't know, let's say, $15,000 a student from federal government. I think we get about a few hundred so we are chiselled by the university and they don't regard us as part of the university until the day comes they have to describe their research work, then of course we're part of the university. We don't sit on any of the committees and we don't ... we're not allowed to teach any of their undergraduates, they don't like us teaching undergraduates because we might steal them. The brightest, we ... we might well. But ... so it's a ...
Maybe they find their way to you, anyway, Don?
Oh they do. We take our ... the best from all over the whole country but it's not a close relationship you ... you might have a close working relationship with a particular person in a particular department, and there are some departments that are more closely related to us than others, but by and large it's just a place across the road. I shouldn't say that because we're all professors in the university but I don't think the university can have it both ways. They don't really treat us properly and we are a jewel in their crown but they don't wear that crown too often.
Would you like to be teaching undergraduates?
No, I would hate it. I have stood in, taught medical students and that is a frightening experience, to have them sitting there reading the newspaper or eating their lunch, or throwing things at each other. Oh, I would hate that.
Do you think you're a good teacher of the undergraduates or the postgraduates?
Probably. As a formal teacher, yeah, I think probably. I write good books that I intend to be teaching books. Ah, and I'm a good undergraduate lecturer, I just wouldn't like to do it because I find that to give one lecture in a day absolutely wipes you out for the rest of the day, emotionally you just don't feel like working. I really feel sorry for university people who try to do research and teach, it's hopeless.
So, but it's useful to the institute to have postgraduate students?
Absolutely. We have about 90, I think 90 PhD students, at any one time, that's a lot.
So what specifically would you like from the university that you don't get?
Nothing. I'm ... I'm happy, I'm happy. Um, what would we like from the university we don't get? No, I ... no I ... the interaction's fine, really. It ... there are a number ... particularly Melbourne University has a number of institutes that are physically around it, like the [Howard] Florey Institute, like the ones down Royal Parade, and you couldn't really conceive of a university embracing the lot. It's ... it's very like Cambridge and Oxford, there are research institutes there that are often considered part of the university of Oxford or Cambridge but really have little to do with it. I worked in one in Cambridge. Ah, and that's probably how it should be. The needs are different, the way you do things are very different.
You were talking earlier about royalties and intellectual property. You've done quite a lot of collaboration in your own work with the Ludwig Institute, how does it work out when something emerges from that work that has commercial potential?
Well, we share the patents, as we do with GM-CSF, so Ludwig and the institute have half each. And in fact, we passed our rights over completely to the Ludwig, and they worked through their head office in Zurich to interact with the company, so it's a very indirect thing. That's the way you have to do it, you have to ... practicalities, so you need one research institute to handle ... to interact with the next level of development. Or it's chaos, you couldn't expect the drug company to interact simultaneously with some places, it's silly. That's my understanding anyway.
So the CSF on which you have the patent is called a GM?
Yeah, that's because it stimulates granulocytes and macrophages, the two main families of white cells that handle bacteria and fungi.
And you have that patent because you actually cloned the ...
The gene first.
I'm not a molecular biologist.
But therefore you're probably better positioned to explain it than if you were?
How we did it was to painfully purify the protein and you chop the protein up into its building blocks, they're called amino acids, and you work out the sequence of those amino acids along the length of the protein. And once you've got a stretch of about 30 in the right order, you can work out by a formula what gene would have coded for that. So you can artificially make that gene and you make it radioactive by putting radioactive parts in it and you can then use that as a fishing hook to go and say, ‘Where is the gene in this cell that codes for that?’ Now, there's one property, the fishing hook you've made will only bind strongly to the real gene. So you've got 30,000 genes and you've got a little radioactive fishing hook that's part of one of those 30,000. So you just put all the genes like a big stew at random, one into each bacteria, and you grow bacterial colonies. So you've got this plate with bacterial colonies all over it and you put blotting paper on it very carefully and you pull it off very carefully and it takes away part of each one of those bacterial colonies. Then you pour on this radioactive little gene fishing hook and then you develop the x-ray and there's one little black spot and, you say, that's the CSF gene. It's all done in one day, the way I describe it. It actually takes a few months and there it is. It might not be a complete gene and you might have to go back and do it all over again to find another part of the gene, but that's how you do it. That's called ‘cloning the gene’. Because each gene is in a colony or a clone and you've got to find the one that you want. And that's all based on the property that ... the little artificial gene you made and he really sticks hard to the same gene.
You're doing this with your hands in space?
All that happens in the lab is just pouring, people pouring ... pouring what looks like clear water onto clear water and going away and saying, ‘It's there, it's there.’ See. It's boring, molecular biology.
What strikes me when you look ... when you look at that, when you do that, and when you talk about what you're doing with your colonies and so on, and you're explaining what you're looking at like this, it ... the concept of how ...
Visual, the things are there, I'm trying to describe the plate and there it is. There, right there, one spot, you see that one black boy, that's the day that was, that's winning the Melbourne Cup. There! That's it!
The thing is, how small is this?
These colonies, you can see them with your naked eye, they're pin-size. Millions of bacteria but all with the same little gene bit in them, growing in a big plate of nutrient jelly. It's pretty macro, it's a mystery. Mystery is putting that in a machine and saying, ‘That's the sequence.’ And that's what machines do nowadays so that's ... it's stuff I don't understand. That's hard stuff.
But what you're talking about is only pinhead size and without the microscope?
Yes. But you can see a black spot on an x-ray film. It's an x-ray film you put on top of this and you develop it and there's one little black spot and ... and you fit that back onto your original plate, which has all the colonies on, you say, ‘That's the one there that made the black spot.’ And you pick that off and you can grow it. You can grow a big vat of it, you can make a million gallons of that bacteria. And you do. And you make a billion dollars with it. Now, as I say, the techniques for doing that are much, much simpler these days and you really could take a smart student, third-year science student, and say, ‘Please clone the gene for this, this is part of the sequence and bring it back in by February.’ They could do it. If they couldn't do it, you'd wonder how smart they were. Things change.
You said you're quite careful in picking the bright-eyed and bushy-tailed ones to be the people who work with you because you ... you like ... you think, you know, it's good to get the best and the brightest into your lab..
No, I wouldn't take the brightest, no way.
Ah, I distrust anyone who tops the year. Why? Because they've got a photographic memory and they will believe anything they read and can regurgitate it; that's why they topped the year. Now what you read in a text book is 90 percent wrong, everyone realises that. So they're learning complete rubbish. And they're not saying, ‘Hang on a minute, I don't believe that. That, I'm disbelieving.’ So what you're looking for, are people that are smart enough, but not this sort of person. So what I look for are the people in the top third, alright? They're usually troublesome rebel rousers but they know enough and then if they've got bright eyes, I'll pick them. But I've learnt that the ... now people will strangle me, who happen to have topped the year in something, but I can think of some doozies — who I wouldn't trust to treat my cat — who topped the year. It's a difference in [that] people who are very, very good at passing exams usually have a very retentive memory and to me, by definition, that means that they don't doubt or question things. They haven't got time, they ... they're trying to actually soak up the written knowledge and the written knowledge isn't reliable; even my written knowledge is not reliable. Nobody's is. Come on.
Well, it's an interesting prejudice to encounter, Don. The idea that the very best ...
It's not prejudice, it's ... the best in the land, or I'm sure they're good for something.
Yes, well. Probably it wasn't a good year.
So I'm just wondering, among your students that you've had come and work with you, are there any — and I know that it's like picking a favourite child — but are there any that have gone on to do things that really amazed you and ... [interruption] ...
You described how, when you were a little boy, you used to watch the military parades and the planes going over in wartime. Did that affect you later?
It affected me during the war because as a high school boy, just like Hitler Youth, you envisaged the possibility that if we got invaded, you could be in the army fighting. So I learnt how to shoot, how to blow down trees with dynamite and [it] was very much on my mind, much more than schoolwork, so I could identify all the planes that people used, all the tanks and weapons and ... and so I think that carried on. Then as I got older and the war finished, the first flood of books were about World War 2, and then slowly you evolve into military history per se, like the Napoleonic wars or the, you know, the battles at sea. I've always had that part of my mind that was interested in it. Now you shouldn't, as a doctor, you shouldn't be fascinated by killing and fighting but ... but you do. So my favourite wars are the Punic Wars, between the Carthaginians and the Romans.
As an adolescent boy you were interested in this. Were you looking forward to the possibility that you could join in the battle or were you ... ?
Not really, I was determined to do whatever I could but it was not a good time, it was a patriotic time, it was pretty desperate, 1941. So, that was a phase and later on it was just interest. And they're still interesting. I sort of have two things I read — detective stories of an unusual type and military history — and the book I'm reading at the moment combines both of them, oddly, Thieves of Baghdad, which is a story of a US marine, who's a lawyer, tracking down who stole all the artefacts out of the Baghdad Museum. It's a good book so far.
Is the detective story interest part of the investigative mind that brings ... that you bring to the bench?
I don't know, I don't worry about who did it. What I enjoy is reading writing that is elegant and says everything in ... in a line or two. So authors like Nicholas Freeling, who wrote the Van Der Valk series, or the Henri Castang series, just had a way of describing people in Holland ... or in France is it? And elegant writing. Who did what? It doesn't worry me. Now the thing about me is I have a very poor memory and I can re-read one of those books a couple of weeks later and not realise that I have read it, so I can enjoy it again, I know the author's good, I know I will enjoy it and I read it again, still don't know who did it. So it's not that sort of detective story.
You've mentioned your poor memory a few times. Seeing as you mentioned it again, can I ask you, if you have a poor memory, how do you deal with the fact — does that come into play — when you're looking down the microscope and wondering if things are different than what you've seen before?
It does and I think I've had four episodes now where I have noticed something strange, a new phenomenon, I've deliberately set up experiments to repeat it and been able to repeat it, so big excitement, new discovery, worked my way through the whole thing, got to the point of being able to write the scientific paper and then realised I'd done all that before. And had no memory of it, there was the paper written, maybe five years ago. Now, I can only imagine that all of us think in a circular manner and so I wonder whether ... everyone else has this ability to say, ‘Hang on a minute, I've done that. Stop.’ And I can't do that. So I think, ‘Oh great idea. Let's do it and yes I can repeat it, yes it's true.’ So that's a bit disconcerting that, that poor memory.
Most people's memories get worse as they get older, maybe yours will get better?
Um, couldn't ... couldn't get much worse. No, in general you can remember things that matter. Arguments you've had with fellow scientists. Disasters you've had with papers that got rejected. Things that turned out to be wrong. And you remember all those things.
Can I ask you, at the ... what you were doing when the war ended?
I'd just finished high school. The war ended in the Pacific in August, September, '45, and that was, you know, November I'd finished high school for the second time. So I was getting ready to be a medical student.
You told us how you remembered the start of the war with the Menzies announcement on the radio. What do you remember about the end of the war?
I remember the celebrations, we were in Tamworth, so the main street in Tamworth, which I think is Peel Street, was just full of people, driving up and down. Ah, yeah, same everywhere. Do I remember the next day? Yeah, all of those things are going on, you remember troop trains full of people with yellow faces because they'd had Atebrin tablets for malaria and so on, but that was daily life. It did have an impact in country towns. Either people you knew were in the army or troop trains were going through, convoys were going through, or in Tamworth there was a base where you got trained to fly, so you couldn't avoid it.
Your father didn't go to the war?
No, he was in a protected occupation, being a teacher. My grandfather was a professional soldier, he was at Gallipoli and in France and he was then, even during peacetime, in the army.
You also described to us the effect that it had, having parents who were so interested in education, and that that meant that they were very concerned about whether you were focusing on your schoolwork. Did it spill over into everyday life at home? Did you ... were there ways in which they took care of your education around the place?
There were occasions where I was struggling with a particular subject and they would round up somebody to help me with it. Um, or if they could do it, they would help. I don't remember being set rigorous times, ‘You will now do your homework between 4 o'clock and 6 o'clock.’ These were simple times, you know, we had a radio, by then. And there were programs on the radio, I suppose, that I listened to at about 5 or 6 but I don't remember a set time where I had to do homework, it wasn't rigidly laid down like we did with our kids.
What about your father's education himself? You said he was always educating himself. Did that spill over into the way that he communicated with you?
Ah, sort of. He was doing a Bachelor of Arts through Melbourne University and to do that you had to go to Canberra each year to do your exams because Canberra was a branch of the Melbourne University then. So he used to memorise things by having them printed on cards in the cow bail, as he was milking the cows. Ah, he'd be reeling off quotations that he was planning to use in his essays in the exams.
Did you have chores around the place? Were you there in the cow house with him?
Oh yes. Yes, all kids had chores in the country, I had to collect the cows, when we lived in Wallerawang, our cows were let loose in the golf links, I had to round them up each night from the golf links, we had a couple of hundred chooks that we had to feed and, yeah, there were jobs, wood to collect, we collected our coal for our fires from the railway line that ran out the back of us from the collieries, all sorts of jobs. And then ... then, you know, later on, jobs as a shop assistant at weekends and Christmas time at the local shop, and working in the local factories, I made all the dehydrated potatoes for Europe, for UNRA [United Nations Refugee Agency], at a factory in Tamworth. It was a great boring job, soldering the lids onto the cans of dehydrated potato. Every summertime there was a job of some sort or other.
When was the first time you looked down a microscope?
In ... probably in first year university. Probably at a specimen of plant leaves in botany.
No. There were no microscopes at high school. No. There's nothing, Bunsen burners, retorts, remember.
Looking down the microscope, at that botany specimen, did you have any idea how many hours of the rest of your life ... ?
No. No, I didn't. But the specimens were great. I think they were onion leaves or something. Plant cells are marvellously regular, solid walls and line up in rows, looked great. I like patterns.
So from that moment you thought looking down a microscope was a good idea?
Don't remember that. I was too intent on trying to pass botany and get the hell out of it.
Leaping ahead, to when you decided to try for the Carden Fellowship, at that time that you applied for that, were there other applicants?
I don't ... I don't know, to be quite honest, I think ... rather think not, I think I'd been rounded up as a possible candidate, they were getting desperate to find somebody and I was it or they were going back to the drawing board I think. So I was doing a surgical residency then with the worst surgeon at Prince Alfred. And they chose residents with enough mental toughness to be able to put up with his terror tactics. He would electrocute you when you were doing the operation because the gloves were thin and he'd put the diathermy on you if you were a bit slow and he'd — thoo! Your hand would flick back. So it was in the middle of a chest operation when a nurse came in with a telegram saying that I'd been offered that fellowship. So that was dramatic. I told him to get stuffed, actually. The surgeon. Everyone backed back in the operating theatre. I thought, if this is cancer research, it's good.
I'd just had enough of him bullying me. The odd thing was he didn't behave as a bully in private hospitals, it was just at Prince Alfred, just unspeakable. He's dead now, I hope. Won't mention his name.
How did he react to your telling him?
Quietly. I think it was the first time anyone had fought back with him. But I just said, ‘I have another job and I don't give a damn what you do or say. Good afternoon.’ The specialists now are totally different but surgeons in those days were God. You know, you could have a patient opened up and the wrong instruments were out so they'd just walk off, have a cup of tea. Leaving the patient wide open, I don't think that happens any more, there are no prima donnas. Maybe there are. Life was tough then.
During this period that you were doing your clinical work and you were dealing with patients yourself, how did you get on with that? How did you like that interaction?
I thought ... I quite liked it. I think we were so badly trained that by the time we were residents we were pretty incompetent and dangerous. And depended on the senior resident, the one that was a year ahead, to sort of hold your hand and keep you out of trouble. But that aside, patients were fine. They were interesting people.
I've no idea. Quite good I think.
I'm interested in whether or not you found the idea of interacting with patients less appealing than the idea of interacting with a microscope?
No, I quite liked patients and I ... because of working in all sorts of strange jobs during a studentship I, you know, was familiar with most people, and having a class of people who ranged in age from 60 to under 20, all sorts of different backgrounds, interacting with all sorts of people didn't worry me at all. I enjoyed that. And that's a bit unusual, because I keep asking all my medical graduates who are starting off in research, ‘Is this what you really want to do or would you rather work with patients?’ And almost all of them will say, ‘I want to work with patients, I can't stand this.’ So it's unusual to find somebody who's quite happy to be doing both. Now, you know, being a doctor for patients isn't all beer and skittles, there's some pretty horrible jobs you have to do, but no, I used to quite like it. What I didn't look forward to is spending my life doing, say, gastroenterology or doing gynaecology, I thought this ... this was ... would be terrible to be doing this day after day, taking out appendices, taking out appendices, next day, next day, next day. So that's why I thought, if I'm going to stay in clinical work, I actually want to go into the haematology department, the blood disease department. Because it was more interesting. I don't think it was running away from patients, it was just that I couldn't brook the idea of taking out appendices, day after day. This was terrible, I thought. Ah, was I right? I don't know. But I sense that this does happen and that's why a lot of surgeons stop working in the late 40s, 50s, they ... it's repetitive and it's a bit boring. Or else they made a lot of money.
When you went down to start work at the Hall Institute, and you were sort of contracted as the Carden Fellow, what ... what were you ... what did you ... what was on the contract, what did you agree to do as a Carden Fellow?
I've never looked but it's cancer research, that's the name of the fellowship, Carden Fellow in Cancer Research.
Let me just remind you, you did say in one other interview that you signed on to something to find a cure for cancer?
I think they asked me.
Okay, I'll ask you that again.
They asked me, I'm sure during the interview, they asked me what particular sort of cancer research did I want to do, and I certainly wanted to work on leukaemia. Why? Because it was a blood disease and interesting. Why? Because nobody ever survived with leukaemia. It's a good job to try and tackle. Um, now all young people start research with an idea of curing something and I was no different so I most certainly would have said, I want to cure cancer. Ah, but everyone I interview now when pressed will say the same thing. It's only a year or two later, you see ... begin to realise, this is ... it's a little bit tougher than this. Um, a lot of people in our institute aren't medical by training and they don't have this attitude at all. They really do it, they say, because of curiosity, they want to understand how the body works, how the cells work and this is worrying to us because it means they don't really think about patients with diseases and there's a new term now, translational research, which is supposed to take laboratory research to the clinic. And that sort of person is supposed to work and think all the time, ‘What about Mrs Jones? Is this, what I'm doing, going to help her in that disease?’ And my view is that everything ... everybody in the building should be thinking the same way, there shouldn't be any such thing as translational research. It's what everyone should be doing, you're not there for your own entertainment and you're not there to figure out how butterflies work, that's going on somewhere else, you're there to figure out disease and to fix it, prevent it if possible. I'm almost sure I would have said that right at the beginning. It's not such a strange thing to say. I wouldn't hire anyone who said, ‘I want to do cancer research because I'm interested in the way a cancer cell works.’ I say, ‘Good for you but go and do it somewhere else.’
So in finding ... do you think there ever will be a cure for cancer?
There are cures right now. For you've got to remember cancer is a hundred different diseases, they all have different causes and some, like skin cancer, you could be sued if you can't cure it, some, like cancer of the pancreas, where there's no cure, and so you've got a whole range and in the middle are things like, let's say cancer of the uterus, where yes, you ... if medicine's good and surveillance is good, you can cure most of them. So, the answer becomes complicated, and in the case of leukaemia, some sorts of leukaemia, you could just about say are curable, period. If you can't do it you haven't done your job properly and in other cases, you say, well, we haven't got a cure for that. So will it get better? Yes it will. Which one will improve? I can't tell you that. But some will and it's creep, creep, creep up.
What about the causes, how close ... how much closer are we to finding out about what causes cancers?
Yeah, that worries me. It worries me because the molecular biologists for more and more cancers are saying, ‘These cells are cancerous because they've got this mutation and that gene is wrong and that gene's wrong.’ And, you know, you couldn't possibly fix that cell, you can't get in there with your little fingers and fix that gene and that gene and that gene. So you say, ‘How did this happen?’ And they say, ‘Well, the body makes mistakes every time a cell divides, it's got to duplicate every one of those 30,000 genes and they just make spelling mistakes.’ Now there are mechanisms that go up and down the gene that say, ‘Whoops, you've got an A there and you should have a T, correct it.’ And it does that. But no mechanism's perfect. So it's quite common, one in a thousand cells will be ... have some wrong spelling in the genes. Is that a cancer cell? Well, sometimes it is. Now you say, ‘Well, if it's just inevitable you make mistakes, the cells make mistakes, cancer's inevitable.’ That's what Burnet said, that's correct. And if that's true we can't prevent cancer. And that's what, as doctors, we are supposed to be trying to do, prevent people getting cancer. And that's a very gloomy way to argue and the conclusion says, it's ... life's not going to change. Every day, new patients will come into hospital with cancer, can't we do anything about it? Then you've got the people who say, ‘Listen, all those cancers due to cigarette smoking, you can stop cigarette smoking, you can stop getting lung cancer.’ That's true. All of the cancers of the bowel are basically because we're eating cooked food and when we cook the food we make these chemicals that cause cancer. Let's not eat any cooked food any more. Well, there are some people who can do that, most of us can't. So that's a half-and-half one. What about the melanoma and the skin cancers? Do we have to go out and get brown in the sun? Well, we don't, we like to but we don't have to, so you could prevent that. But then you've got a whole bunch of other cancers where we haven't got the faintest idea why the cancer comes, and no notion of whether you can do anything to stop it. And so the answer's a mixed one, the answer in one line of arguing says, ‘Look it's inevitable, cells have to divide, they're going to make mistakes, the surveillance mechanisms aren't perfect.’ You're in trouble. And the older you are, the more mistakes you get so cancer's commoner when you get older.
It's logical and it's correct and the other people who say, ‘Well no, there are all these outside causes that make that more ... happen more often and more quickly, let's stop those causes.’ And they're true too. So the answer maybe is if we're very smart, we could prevent all cancer until the age of 150. But then they'll happen. Now if we live to 150, we've done our job, perfect prevention of cancer, no more of us will ever get cancer. Now that's possible. So it's a complex answer, isn't it? You ... you have to keep trying to figure out what are the things that make mistakes more often? Happen more often? Are there such things and the answer probably is, yes. And can we eliminate them and still live a normal life? Some of them anyway and if we live to be 150, tough luck, we'll probably get a mistake and get a cancer. That's my view of it.
Do you think we'll ever be able to live to 150?
Do I feel that? I don't know. Maybe we can. Maybe we can.
That's one of life's tough questions, isn't it? I always feel that the Almighty was a bit unfair to us by giving us awareness of our mortality and giving us mortality too. So you sort of ... you have a desire to live for an infinite time and you have to accept the fact that you're not going to and that ... that's a tough set of asks. So if somebody says, ‘Well I can't stand the stress of that, I'm going to smoke to ease the stress.’ I can't say, no that's ... that's stupid. It is a bad scenario that humans have consciousness and mortality. We're getting rather gloomy.
Well, I suppose we can't ever really talk about a life without talking attitudes to mortality. I wonder what you ... what you think about that. You said, the Almighty made a mistake, do you think that? Do you have any conviction that there might be a life after this one?
I'd like to think so but I'm not ... not overly convinced by the evidence. None of us are. What you can ask yourself from time to time, if you ever stop working and start thinking about what you're doing or what you think you're doing, is why bother? Why bother to cure Mrs Smith's cancer of the breast? She's 75, she's going to die anyway, why not just die of that? That is an argument. If you ... if you have a finite lifespan does it much matter? Now, there are some ways of dying that are pretty nasty and you'd want to avoid that if you could, but if you died of a sudden heart attack, that's probably a nice way to go. So would you do cardiological research and the answer usually you come up with is, well, if you're 85 or 90 there isn't much point in trying to find out the nature of that disease. But if the same disease happens in a 35-year-old or a 25-year-old, that's a reason for trying to figure it out and prevent it. So I think that's the way medical research workers sort of convince themselves that, yes, it is worthwhile to attack diseases, try to find what their cause is, prevent them, even though we're all going to die. So the argument is, let's think about the children, let's think about the young adults, let's think about the middle-aged adults and solve their problems, and when you get to be 95 and you've got problems, you say, ‘Well I've had a good innings.’ Because inevitably you ... we're not magicians and we can't actually make people live to 150 yet, maybe we can one day.
What are your own thoughts about your own death?
I don't have any. I don't have any. It's going to happen. My colleagues say I will be found dead working at the microscope and they're going to embalm me and just have me there as a permanent ... permanent warning, I think. No, it doesn't do to dwell on such matters, I think. Basically it's an insufferable position to have to have consciousness and mortality. That's my view. But we put up with it.
You said you were brought up Presbyterian, and that your wife's of a different religion. Do you practice any religion at all, yourself?
No. No. I find that religion's a little bit curious. I think that children should be taught religion. I find it curious that you are expected to have the same religion as your parents, because it's not a genetic trait. There's no reason on earth if your parent is a Catholic, why you should be a Catholic. That's not biological sense. But that's the way it goes, so you're brought up in a family ... with a particular religion and my figuring is, well, okay, you've got to learn about the basic facts and basic ways to behave and the moral standards expected of humans, but once you've learnt them why do you have to be told that once a week for life? Once you've got it straight? That's it, you don't get taught to ride a bike every week for life; once you've learnt to ride the bike, that's it. So, I am afraid that I regard the religious establishments as being sort of self-sustaining things that are really concerned about their own survival and progress. So, why take part? Now, if I knew nothing about it, I would sit down and start reading and figuring it out, I think, and reaching my own conclusion about it. So, you could say, well, you're not anti-religion, you just figure that once you've learnt it and heard all the arguments, ah, just that's it.
Some scientists believe in God and others say it's completely irrational and there's no evidence. Where do you sit in that debate?
I don't get into that debate, I haven't ... that's one of those things that if it amuses you to argue about that, that's fine. There are lots of things you can argue about and speculate about if you have a mind to it. What would happen if the Prussians hadn't arrived at Waterloo in time? Same thing.
And one you find more interesting?
One I know a little bit about because it happened.
You've lived through quite a long period of history and seen a lot of changes in that time. Can I ask you about the changes that occurred in the way research in medical science is conducted since you began in the '50s?
I think if you walked into a lab in the '50s, and walked into one now, the most obvious thing you'd see is a great increase in technology. You'd be surrounded by complicated looking electronic pieces of equipment, you'd see people looking at television monitors and 50 years ago you would have seen people working with a pipette and a test tube and Bunsen burner and perhaps a fertilised egg. So they're the obvious things. Now, what's not so obvious is that 50 years ago, you would do your experiments, probably by yourself. According to your training, that's the sort of experiment you'd be doing. Nowadays you work in teams and there might be 10 people in a team for this project or 30 people and all the little pieces of the jigsaw are being collected by them and it fits together into a more substantial story. So the jobs being tackled are a lot more complicated and they need a lot more manpower and they need a lot more technology. But are they the same sort of questions? Well, in general they are, it's not that you're asking different questions, it's now you've got a power to answer some of them and if you're sensible you realise that you're getting yourself in deeper and deeper water that you don't understand and there's plenty left to discover but ... so that's ... it's more complicated. Interestingly, things change that you wouldn't expect. When I first started to go to medical meetings, if you disagreed with somebody, you stood up and said, you know, ‘What you said's wrong.’ If you were a bit more aggressive, you'd say, ‘You're a liar, I don't believe that.’ And an enormous fight would start in the audience. I've seen people drop dead during these confrontations and just be dragged out by the feet and it goes on. There was real passion in science. You go to a meeting now and nobody will get up and say boo. So I was at ... in San Diego giving a lecture to 9,500 people, 9,500 people in one room. And did anyone stand up and say, ‘I don't believe the second slide you showed us. That's not right.’ Well, why doesn't this happen? Well it ... at my figuring is that it doesn't happen because you can't destroy somebody publicly, because there are too many people in that group whose livelihoods depend on the reputation of that person and their ability to get funds. So you're destroying the lives of 10 or 20 people by destroying them. I think that's why it's happening but that's something you'll notice. If you go to a medical meeting now, there is no nastiness, nobody gets up and says, ‘I don't believe that, that is the greatest bunch of rubbish I've ever heard.’ But you did 50 years ago.
Is there value lost in losing that?
The excitement's lost. There used to be some pretty ... I mean, 50 years ago, in my field there were maybe 50 or at most 100 people working and you knew them all, you knew he was a wild man from Poland and don't cross him or he'll ... he'll do his block or you know he's ... he's a smoothy from England. Um, and now, you probably know as many people but you have to realise there are 10,000 people in that field or could be regarded as being in that field. So you don't know them all. And you have your immediate colleagues, you have your friends amongst them and the others are unknowns. So it's become a little more remote, it's not possible ... it's no longer a family affair. And that, I regret that a little bit. I don't mind it, I don't much care what other people are doing or saying. So, the meetings go on and, ah, I go on.
You've described some of the changes that have occurred in medical research in your lifetime. What about changes to the funding models? How have they changed?
Um, they have changed, of course, because research has become much more expensive, each scientist costs on average about the cost of a suburban house. And as the cost of suburban houses have gone up over the last 50 years, so the cost of each scientist has gone up. Um, where does that money come from? Well, when things were very cheap it was possible, just possible, for some private donor to give enough money to support a little bit of research, as was understood in those days. But even then, the government always paid a sizable fraction of the costs. And it's very interesting, over the 50 years I've been at the Hall Institute, the percent of money of our annual budget that the federal government pays hasn't changed, it's between 30 and 40 percent. So, our place costs 30 million dollars a year to run, let's say the government has given us 15 million, so every year when you wake up, January 1st, you've got to find the other 15 million. And that's a big headache, it means that all of us have to spend weeks, even months, writing grant applications so now we get some of our money from the United States, some will come from other special organisations, like World Health Organization or malaria funds, or in our case we get money from the local cancer society. Some of it you get from little old ladies in their wills. It's not the habit in Australia to leave sums of money for research as it is in the US. So there are no big donors, very rich people who will give you 20 million, 100 million, that's quite common in the US, not here. And despite that, about 10 percent of our money comes from invested gifts, so we invest all our gifts and use the income from them. So it's a little bit of everything. Now that hasn't changed all that much over 50 years, it's just more and more a desperation effort to find the money. It's ... it's tough, it's the one profession where you are paid a salary and then expected to go out and find the money to let you work for that salary. Imagine paying a lawyer a salary and then saying, ‘Well, you go and find some money to build a courthouse and to ...,’ you know, it's a very strange arrangement.
And your situation in having had tenure, for the whole of your life, wasn't uncommon, wasn't so uncommon back then. But is that the situation now for young people?
It was never common. To my knowledge, I'm the only person in the world that's ever had tenure for life as a research worker. You had tenure for your professional life as a professor, which is also not really true any more, but most research workers live on a cycle that might be annual or every three years or every five years. Nobody has a longer appointment ... even the director of our institute only has an appointment for five years. Now it can be renewed, but you don't know that for sure, and it's very tough if you are the second person in the world to discover something, that's bad luck. If you keep on being the second person in the world to discover things you will lose your grant money very quickly and equally quickly you'll lose your salary. It's a real gambler's life you lead. You're gambling that in the next few years I'm going to discover something that will make people say, ‘Okay that was good. We'll give you your salary again, here's some more money.’ That doesn't happen in academic life ... it used not to happen, it is tending to happen now, people are on contracts and presumably if they don't perform they can be not renewed.
And what are the advantages and disadvantages of those two systems, the tenured system and the contract system, in your opinion?
It's a matter of luck, isn't it? If you get somebody who's very good you are extremely happy to support them for life. Now, you could say, how often does that happen? Well it does happen. And if you get somebody who runs out of energy at the age of 35, but has a lifetime appointment, you're stuck. You're cooked, you've got a room full of dead people, dead wood. So you ... you're torn between both systems, saying, well there is some common sense in having a short-term appointment but it's no way to raise a family and have a living. And the other way is, it's great but are you sure you picked the right person? Now, there isn't any simple answer to that.
If you'd been in a situation where you had three-year reviews, say, would you have always been renewed, do you think?
I think I would have been in big trouble some cycles ‘round. There were some times you could get through very easily but others you'd be scratching and saying, ‘Well, we really did try hard and we discovered this and that.’ There was always something you discovered, but basically you weren't succeeding in what you were really trying to do. Now that's exaggerating a bit. If you went and visited our lab any time in the last 50 years there'd be things going on that were working and would be written up as papers. After all, I think I've written 650 plus scientific papers in 50 years. And if you work that out quickly in your head, that's about 13 papers a year. Which means you're writing one a month. Now you've got to do the work before you can write the paper. So, something must have been discovered — I mean you weren't publishing nothing. But you could then say, ‘Hey, hang on a minute, you claim that you're going to purify these, what's the answer, haven't you done it yet?’ So some things were dragging on and if it was a tough committee, as they are very tough nowadays, you would've ... could well've been given the boot. So my employers were pretty tolerant and it's a very unusual thing to do and it's a bit of a dangerous thing to do, if you're thinking now from the point of view of being an employer, you'd say, ‘Well, hang on a minute, we've only got one fellowship to give and this fellow's useless and I'm stuck with him.’ So, it's a gamble they run.
You said that you write lots of papers. How many books have you written in the course of your life?
Nine, I think. Nine.
And is there an art to grant application writing?
Oh yes. It ... it's not an art, it's a skill and our institute is very expert at writing grants, so the ones who write successful grants have to teach the others how to set it out, what things to say. I mean, you can make silly mistakes like have 20 good ideas and put them down and immediately the committee will say, ‘This guy is all over the place, he hasn't got the time to do all these 20.’ Out. Whereas if he'd been better advised to spend it on describing one that's obviously do-able and it's going to get an answer, he'll probably be successful. So there is a real skill in writing the papers and they're written in a different way for different organisations. And we have an organisation, if you like, within the institute that teaches and checks on how each one of those is written so our track record in winning grants is good and others in the university will say, ‘That's not fair, these people are ... not cheating but they are getting an unfair advantage.’ But it's a matter of getting yourself organised. It shouldn't happen, it's just a waste, an enormous waste of mental energy and everyone's time, wasting time sitting on the committee in judgement on your fellows, you're wasting more time writing the things and, one way or another, you seem to end up getting money to work with, it's just how much time you've wasted getting it.
In giving you tenure, they did take a risk but they got someone who just hasn't stopped working ever since and has kept motivated, and it seems to me that that motivation to keep going is the key to your ultimate success with the things you were pursuing. What keeps you motivated?
Persistence, isn't that the word you're after? Um, it's a bit of everything, it's ... it's an absolute determination to figure some things out, to find out how they work and this stems, if you like, from having such a bad memory as a medical student and if I could figure out how the system was working, how the heart worked and what regulated the heartrate, I didn't have to memorise it. So I always would prefer to figure something out, I think that's basically behind it. So you're presented with a problem, even today, we know so little about the systems that we're working with that there's no time to spare not hopping in with the techniques you've got and trying to answer it. What do you call that? Is it curiosity? Is it sort of greed that you want to discover yet more things? A bit of both I suppose and, as the cream on the cake, the thought that you can eventually use this one day, that's what keeps you going. Daily, tomorrow morning when I go to work, what will keep me going is that I hope that what I see tomorrow is exactly the same as I saw yesterday, meaning: that it's repeatable, that's the thing you live in terror of, that the things you find just can't be repeated. Um, everything keeps you going, your colleagues keep you going. It's great working in a group because somebody is always running hot and doing something successful when most of us are just having an ordinary day and repeating something or getting it wrong and can't figure out what's gone wrong. But as long as somebody is ... has got success, everyone's happy. That's the way it goes.
What about the glittering prizes? Because there have been a few of those, haven't there? Do they keep going, and what ones haven't you won?
Um, a lot. Um, does it keep you going? The answer is, I don't think you set out at the beginning of a year saying, I'm going to win a prize this year. No, you don't say that. When you do win a prize, you're embarrassed because you know that what's being honoured is a project and the project is the work of all the people, so they have to pick per chance one person. So that's slightly embarrassing. Um, is it fun winning it? Does the self-esteem go up? Not usually because it's a nervous-making occasion when you're being given it by Hilary Clinton or somebody so you are a little tense in New York getting it. It's a mixture of everything. So, would you be peeved if you never had won a prize, ever? I suppose you would be. Are you looking forward to the next one? I suppose you are, you'd be lying if you didn't, and yet common sense says, ‘No you can't, there's nothing more that you're likely to win, just forget it, just get on with your work.’
Why has the Nobel got so much prestige, do you think?
It's ... it's interesting, isn't it? It's not ... well, I don't think it is the most valuable, it ... it was for a long while, a most valuable prize, so that was part of it, then there's the glitterati associated with going to Stockholm and having the king give it to you in palatial surroundings. All of that. Um, but certain prizes get a ... get a reputation that isn't really deserved from the monetary side of it. The top American prize, the Lasker Prize, only I think gives you 25,000 dollars, now that by today's standards is nothing. General Motors prizes are 300,000 dollars but the Lasker Prize will be announced on the front page of the New York Times and the General Motors one, to their fury, will receive no mention in any US newspaper and they say, ‘How can this be?’ They scratch their heads. I've been on the selection committee and I know that it drives them crazy. We want some publicity for this prize. How does it happen? It's probably an accident of timing; when Lasker first started, there weren't any other prizes around. It was easy and it happened. Lasker, I think, was a newspaper man and probably had an end to getting publicity for his prize. But then it's sort of competition between scientists, ‘Oh he got the Lasker Prize.’ So you're making the story up yourself, in creating the ... the special aura of it. It's ... there's a lot of that in science, in that creating — why do people write articles for Nature or Science? They themselves have said, ‘We're going to regard Nature as the best scientific journal. And we will die trying to get our paper published there.’ Now that's self-inflicted torture, you ... you could publish it anywhere. Publish it in the daily newspaper would be just as effective but so, scientists build things that they then strive to ... to achieve.
Of the prizes that you've received, which one do you value most?
The ones that I value are some odd ones where they're chosen by committees that were quite formidable in their composition. There's a prize from Columbia University where they're extremely serious in how they went through all the possible candidates and people were assigned to read every one of their publications and critically examine them and then committees would get together and out of that, to be picked, you know you've gone through a lot of hoops by serious fellow scientists. So you think, that's good. Ah, there's a similar prize from the US National Academy of Sciences, which you know, if you win that, that's pretty substantial. Or a similar prize from the Royal Society. And none of those are particularly valuable in terms of prize money, mightn't have any prize money, but it's because your peers have ... serious peers who are successful in their professions, have picked you. I think they're the ones that give you the most satisfaction.
So the value that your peers place on you is important to you?
Oh yeah. That's true in science. If you lose your reputation amongst your peers, that's the end of you. You've got to be regarded as telling the truth, of being interesting, coming up with novel ideas, and producing stuff that's correct and repeatable and that's it. You discovered it, it's probably right. Within the limits of what you're doing, so the outside public has no notion of whether you're an idiot or a great scientist, they have to believe what's told to them; people who practice medicine have no idea whether you're particularly good or not. The only people who know whether you're good or not are your colleagues and competitors. And only in the field that they're talking about, so I know nothing about who's a good physicist or a mathematician or a ... who works on the kidney, I know absolutely nothing about them. But if you want to talk about blood diseases, I can tell you who are the people who did what and are the best at their job. So it's very hard when ... to get back to your question about the Nobel Prize, I would hate to be on that committee, sitting down trying to pick a prize that covers the whole of medicine and physiology. Right? It's worse than picking the Melbourne Cup winner and, you know, there are people who are superb but I suspect that they try to rotate around the different fields, so that they're all covered every 10 years or so. And if you're not in the right field at the right time, you ... they have no choice but to just pass you over, I think. I don't know.
You said that your competitors are often on the ... on the review, on the panels that are making these decisions ...
You hope, you hope they are, because at least they know what they're talking about.
And does that ever come in the way of their judgement — do they ever think, this guy's got a different view from me, I'll knock him out?
You would think on principle it would, or more commonly, does one of your competitors go through your manuscript for publication and decide it's no good? And there are people you could ask that question to and are convinced they know it's happened, and they know who it was that torpedoed them. And they will forever after hold that as a grudge and probably wrongly. Um, I haven't seen much sign of it, inevitably people will tend to favour choosing people for positions or prizes or whatever in a field that they know something about. And it's a sort of snowballing effect, there are an awful lot of immunologists who are successful, why? Because there are an awful lot of immunologists. The chances are there are immunologists on every selection committee and it goes on. Is that malignant? No, it just happens that’s all you know about. And ...
How much time is taken up with peer reviewing, I mean, is this a big responsibility?
It ... it is and it takes somewhere between one and two months every year out of a year's work. Now if you take out a month for holidays, if you have holidays, a third of the ... a quarter of the year is gone on what's useless work. Now, you could say, it's not useless to peer review, it is forcing you to think what you're doing and be careful appraising it and presenting it and planning it. And that's lifting up the level of research, so it's not wasted; it's waste for you, but it's not waste for science in general. It's tough but it's getting worse and worse and the bureaucrats are demanding more and more accountability and it's just getting out of control.
Do you think scientists and academics are paid enough?
No. Not when you see what the heads of banks are paid who you know, from meeting, are no brighter than you are, probably less bright and getting paid 10 times as much. Or the head of Telstra. Come on.
A lot more than 10 times in some instances.
Ah, so that's just ridiculous. Are scientists paid enough compared to general practitioners or specialists in medicine? Much more direct comparison. The answer is, probably not quite enough but not disastrously less. And remember that they've got probably superannuation which a surgeon doesn't have and ... I don't notice much difference. I'm sure the most popular plastic surgeon in Sydney or Melbourne earns a lot more than the best scientist, but then it's not something that's very important.
What's your view of the big changes that have occurred in tertiary education in the period that you've been working?
My view is I know nothing about it. I have an unpopular attitude to training PhD students. A lot of people sign on and do PhD degrees in order to get on in their profession. So if you're a medical graduate and you do a PhD it's because you want to get into an academic medical department and rumour has it that you can't get appointed unless you've got a PhD. They don't care tuppence about science and making discoveries and applying it. They want to get their PhD and get the hell out of it. Now, I get furious when I find that we've taken in people with that attitude. Because to me, that's training milkcart horses and we're supposed to be training racehorses. And it's the job of the university to teach that sort of PhD student. It's part of their professional training. So, has that changed in the last 50 years? A little bit, I mean, this is sort of embedded in the ... in the mystique of rising in your profession, that you've got to have a PhD. And some people believe that. Other than that, what's happening in the university is a closed book to me, I mean, I'm astonished that medical classes are so small now. That wasn't the way I grew up. I think they must be spoilt rotten. Are they any better doctors than we turned out? I suspect not. But they ... life was pretty tough in the university, lots of departments are vanishing that should still be there. I mean, you try and find a history department or an English department, French, German, they're all going. And if you're in a medical school and you're trying to do research and teach it is dreadfully hard. Dreadfully. So, in one sense life hasn't changed, in another it's ... it's getting a lot tougher, for everyone.
You were assistant director at the institute, under Gus Nossal, did you ever want to be director?
I think the director's job is like the CEO of an industry, it's ... it's a public relations position, you've got to be familiar to and chat up politicians, incessantly. Visiting firemen who have absolutely no interest in research. And you're not out on the frontline doing the research, you're not at the pitface. And even when you're running your own unit, and there might be 30 or 40 people in it, I won't stop working at the pitface because that's where the action and the excitement is. So the thought of taking over a whole institute, listening to all their squabbles and problems and solving all sorts of ridiculous things, has no appeal. So I suppose I'm saying that power doesn't have much interest. I think power must be a big carrot for somebody who takes that job on. They mightn't agree but that's what I suspect. It's not the sort of job ... the best job is the next one down. Because you have much more freedom and, with luck, not too much chores and you can get on with what you want to do. And still have a certain amount of clout. It's like me not choosing the first in the year as a student but choosing the second or third or somewhere down. It's a ... a warped bit of my personality.
Ah, a successful experiment, a new discovery. We're in the middle of discovering a new gene that causes leukaemia, that's great, that's success for this year. Um, next year, probably, it better be something else, you won't get paid to do the same discovery again. So it's ... it's finding things and proving that you've found it and putting another block in here. That's the everyday success.
And in order to be able to keep up the work that you're doing you need to have a certain amount of confidence in yourself. Where do you think your own confidence, your own ability to believe in what you're doing, comes from?
I think it's whether something works and you discover things. There's an inbuilt mechanism that says, ‘Yes, you've still got ... you're still discovering things. Keep going.’ Um, there are plenty of people who would say, still, ‘This is a boring part of the subject to be working in, it's going to get nowhere.’ And I can say, ‘Well, you're wrong there, because you know we discovered things that people use in the clinic.’ So they can't say that any longer, they used to say that. You have to believe in yourself but you've got things that you can use as yardsticks that say, well, yes, everyone's agreeing that you are making progress. Whether it be getting something published in a top journal, whether having editorials written about, saying, ‘Oh gee, look at that, they discovered that.’ Or winning prizes that say the same thing, Yes, he's a good fella. So what keeps you going tomorrow, instead of thinking, ‘Gee I think I'm wasting my time in doing that.’ Nothing. You have to decide that every morning when you get up. Do I do this experiment again, or should I stop? It's quite hard, quite hard to stop doing things.
Have you had any problems in your work with animal liberationists, with the animal rights groups?
Um, we haven't really, we're very careful the way our mice ... and mostly we just used mice and you could say, look, the average Australian doesn't care about mice. There are mouse plagues, you kill a mouse in the kitchen if you see one, why should you worry about doing experiments? And then there's the other half of the population that says, yeah, but mice are people and you shouldn't do this and you shouldn't do that. And you shouldn't give them cancer. So, we have committees of medical ethics that are quite tough and everything you do has to be submitted to them and they argue about it and say, no, you can't do that or, yes, you can do that bit and do that. Everyone is on their best behaviour. The animal technicians who handle the mouse are a terrific lot of women who have been in this for years and they won't ... they'll interfere if they see something wrong going on. They just will stop it. Um, so we know that our rooms are superbly airconditioned and everything's fine. You would love to have a bed in there and sleep. So when you get inspected by outside organisations, like RSPCA or the animal libbers, they're sort of speechless when they see it. This is superbly kept and administered. As a safeguard, all our doors are electronically shut-able in an instant in case somebody silly has arrived and wants to break in and release all the animals. So, so far in Australia, I think everyone's very careful and people are reasonably sensible and there isn't trouble. I think if you're doing experiments with dogs or monkeys or something like that then there'd be trouble. But in other countries, like the UK, it is an enormous problem and there are constant riots, there are death threats, there are people being killed by animal liberation people, and I've seen some of their demonstrations in London and they are scary, scary. Ah, thank goodness we don't seem to have them here. Because there isn't an answer, I mean, I've heard parliamentarians get up in Trafalgar Square and speak passionately against animal experiments and I've just felt a real criminal. In the long speech there'll be one sentence that actually is wrong and you say, ‘Look you are mistaken. You're not as claimed.’ You've got that lot, you've got the people wielding chains who are out for a fight anyway, the skinheads. And then you've got the people with walking ... pet animals, that's the crowd that makes up the ... the whole front. And they just become violent, they have a tradition of violence in the UK. And not so much in the US, but in Europe it's a bit of a problem.
So what's your own justification for giving a mouse cancer?
Um, my justification is that if I can figure out using that mouse what is happening with that cancer, and figure out a treatment for cancer that can be applied to humans, then I'll do it. So I suppose I'm saying, a mouse is not equivalent to a human. But I have the greatest of respect for mice, and it's tough, you can't have it both ways, you have to say, ‘I'm sorry but I'm going to use you in an attempt to do something.’ I mean, there are certain strains of mice that if you just let them get born, will get cancer. Ninety percent of them will get leukaemia. Now I don't know how the ethicists handle that one, do they say, ‘You're morally wrong to breed those mice, knowing they're going to get leukaemia’? Or you haven't done anything to them except breed them, let them grow up. What's the answer? I don't know. I've never heard anyone address that. Lots of people tell you, ‘You can't inject that chemical into them and cause cancer,’ da, da, da. But to breed a mouse that has cancer? It's like saying to humans, ‘You can't breed, some of you are going to get cancer. It's not right to allow you to breed. Should stop having babies.’
In the broader area of research, at the forefront of where science is taking us these days, there are some ethical questions arising about biotechnology and so on, for example, we've recently been through in this country a big argument about stem cell research, well all over the world. How do you approach these ethical questions?
Look, there are so many hoops and committees you have to go through for anything you do, that all those arguments get argued about over your head and in a sense you don't worry about them. Basically all the arguments to date are so silly in terms of biology and science that it's sort of hard to keep a straight face often. I mean, notions that you might one day grow a human in a bottle, are just so far beyond what's technically possible that in a hundred, in a thousand years, you couldn't even contemplate doing it. So there's that sort of response that, get real, you ... there's no-one could actually do that. Let's stop arguing about it. Um, to questions like the ... I think are more difficult, they're not really research but it is technically possible and it's done to check on a developing baby and say, ‘Look, you're getting ... you will get Huntington's Chorea when you are born and grow up, I'm going to terminate that pregnancy.’ Now that's done every day. Or you are a Down Syndrome and out. Is that ethical? And people I don't think have a common view on that, some would say, look, that's common sense, let's not do it. And others will say, no, it's a human life, we all have an institution that looks after a person that has Down Syndrome. I'm glad that I'm not involved in medical practice, that they're much tougher questions than in the research field. Now you could say well, ‘You didn't treat that mouse too kindly, giving it cancer.’ But then does the average housewife treat a mouse kindly if she finds it running through the kitchen? No, she'll stamp on it, hit it with a broom or catch it in a trap. Kill it. Ah, it's quick I suppose ...
Or jump on the kitchen table ...
Or jump on the kitchen table.
Do you think that the position of scientists and the prestige of scientists has changed in your lifetime, and do you think that it's at a level that is appropriate for their contribution to society?
I ... looking back at the written accounts of people like Pasteur and Koch and so on in the late 19th century, they're portrayed as giants now. You are left with the impression that maybe everything they did was written about on the front page of the daily newspaper; whether that's true or not, I've got no way of knowing. But you're left with the impression the public was aware. Now, there were dramatic things they were achieving. They were preventing diphtheria or you know, the plague. So if there are world shattering events that you've succeeded in solving you are a well-known, popular figure. If you came up with a cure for AIDS, a proper cure, I'm sure your face would be on Time magazine and you'd be a well-known person. Ah, that doesn't happen too often. So, the average scientist is anonymous. Now, is the average scientist being interviewed as often as the average footballer? Well, you know the answer is, no you're not. You can listen to an hour’s interview with a footballer's bad knee and think, well, how about an hour’s interview with a scientist, who might one day save your life? Um, so there is that argument that says you're not exposed enough. The argument then becomes, well, does the general public know enough in the broad sense about the science? Or is it impossibly difficult to explain? Now for a physicist, I think it is probably impossibly difficult. For me, as a biologist, I can talk to the general public and, I think, explain to them what I'm doing and they can associate with it, because Aunty Jo has just had this or something. So you could say, there should be more programs like Norman Swan or that Robyn Williams should actually talk to more scientists than he does, never mind the archaeology and the fossils, talk to the working scientists.
Whatever the reason, the scientists are not immediately visible. Now, if I think back over 50 years, where I'm a little more sure of what happened, the situation in Australia has always been that there are one or two people who are consulted on any question. Right? Now, I'd say there are about 10 or 20 people whose opinions are sought by the newspapers or the radio on any particular subject. So is Burnet the same as Gus Nossal? The answer is, yes he is. Because I'm sure Burnet was asked his opinion on all manner of things, as Gus Nossal is asked about ... so that the media have a sort of a limitation in their range of awareness of people you could ask to talk to. And so, passively, any public attention is focused through a few figureheads. And that of course doesn't happen with sport. You are possibly talking to all 18 football players. Maybe you talk more often to two or three. But for whatever reason, scientists are not popular figures and if you say to a newspaper man, ‘Why aren't you writing more about science? Why isn't there a bit on every page? Why aren't they rock star type personalities?’ They will say the public doesn't understand and yet, you know, the surveys say the public is most interested in news items that are about medicine, that's what they're really interested in. So who's at fault? Ah, it's blamed on the scientists who can't communicate, they flagellate themselves and go away and learn how to communicate and nothing much changes. So the answer is: it hasn't changed all that much, I think, in 50 years. But I speculate idly that maybe ... maybe in 1890 it was different, but maybe it wasn't. Maybe they were rock stars in 1890.
For the scientists, what are the practical effects of not having a level of prestige that they might have in a ... even in a different society from Australia?
I haven't been in a country where scientists actually are publicly known figures, it's not true in the UK, not true in Europe, Germany, not true in Italy, Lord help us, and not true in the US for that matter. Um, just for a brief period, the atomic bomb scientists were public figures but with those exceptions maybe Jonas Salk, somebody like that, polio vaccine, one or two but by and large, no. And what do scientists think about this? They grizzle about it if asked. And they say, ‘Wouldn't it be nice if ...’ And if it did happen, they would very soon get sick of it, have the telephone ringing and have somebody ask their opinion about this and that. That's what directors get asked and that's why I don't like being a director and that's true of most people. So they ... they'd rather be anonymous I think but if you put the question, ‘Wouldn't you like to be more publicly famous?’ They'd say, ‘Oh, yes please.’
How important have sabbaticals and periods away working in other institutes been to the progress of your work?
Um, they were important and it's a vanishing phenomenon now, there are very few people go on sabbatical leaves so, in the sense that you work six years, you had one year where you went away to some other country. Ah, that's the system I grew up with but it essentially has stopped. Why? Because meetings are more common, people fly away to meetings, it's a pseudo-sabbatical. Ah, was it important? I think you could say in one sense they were very important, you ... you met other colleagues, you met ... got exposed to different ways of doing things, different cultures, etcetera. So it was a plus. On the other hand, there were times when being away on sabbatical leave meant that a project limped along and the ... we lost the race because of it. So it was a double-edged sword. The time we spent in Holland and in the UK was the year we could've been in the first to purify and patent G-CSF and made ourselves millionaires. But ... was great living in Holland, it was great living in Cambridge, so was it better to have done the move? Yes, I think on balance. So it's something that used to be good and is now past history a bit. People now are terrified of getting lost on the ladder, if you go away you ... you're out of circulation for a year, you're a less productive ... da da and less likely to get your grant and so people don't do it. It's tougher, tougher life.
You mentioned the race, is there a race? How does the race work? Have you ever lost a race?
There are all sorts of races: there's a race to be the first to achieve something, to discover something, and you sort of know that there are four other groups working on this subject and what progress they're at. So that's a direct race. Have you got it first? Did you get it published first? It all depends on the publication date, that's a race. Um, is there a race ... race is perhaps not quite the right word. There is intense competition, starting with being a very young scientist to get tenure, tenure meaning to get made a research fellow, which is a three-year appointment. It's not tenure, it's a ... but at least you've got your first foot on the ladder and next foot up, that is a higher grade fellow and so you would work up to a senior research fellow or a principal research fellow. That's a level of a professor. Now that depends on your productivity, so were you the first to discover something? Were you in the best journals? Are you the most cited scientist, etcetera, etcetera? All of those things will determine whether or not you make that next jump. So that's a ... it becomes, in a sense, the same race, it was the same race to get that piece of science published and finished first that will make you the most likely to get made the ... the next step up on the ladder. Now you have to go up the ladder, it's up or out. That's the rule. You can't stay being a research fellow for 20 years, you get thrown out. That's ... the rules say, no, you've got to ... you've got to keep going. It's not a good life.
What about the race to patent things?
That happens very rarely but it is a real race and we have lost patent races by half a day. Half a day, so you work on a project for several years and in half a day, somebody has filed essentially the same patent in Europe or US. It happens.
Oh, it's happened to us twice. We've lost a patent by hours.
Tell us about the day. What happened, why ... you were going to file it?
That's it. Well it's ... you know, you work on a project for three years, when it’s the day you decide you've got enough and the lawyers have gone through it and it's correct and it's filed. And it's that minute of filing that determines the priority.
So you were in a position where you were ready to file?
Well, because we were going to do it this afternoon and somebody else did it this morning. Ah, that happens. It's a competitive life. It's like saying, ‘Why didn't you run faster in the Melbourne Cup, you could've got your head ... head, that half-head, should've started bit more quickly.’ World's full of should haves.
And sometimes we've beaten people. Beaten big US companies who are furious that they picked up a journal and there was our publication. Some ... some you win, some you lose.
How did you realise that you'd been pipped at the post?
Oh, you ... it's all on file, you can check, see whose patent applications are in and what the ... it's all accessible on the web, oh yes. Now we have an office that does that but you can do it yourself.
Now when you first went to the Hall Institute, the famous Macfarlane Burnet was the director. What was he like?
He was a strange mixture of being ... an introverted person. He was quite unable to give a lecture, couldn't stand up at a podium and speak, he always read his lecture. Now the last time I've seen anyone read a written lecture is 30, 40 years ago. And people, in fact, it's a very difficult thing to be able to read a lecture, newsreaders I admire, I mean, it's a skill. Okay, so there was that aspect to him. He liked to work by himself in the lab. He'd work in the morning and in the afternoons he'd go to his office and do his writing. Um, was he approachable? Sort of, yes, you could go to him with a body of evidence and say, ‘Look, I'll run this by you, what do you think?’ Um, he was very shy in public. And yet, he sought the admiration and adulation, and people are mixtures. So you could say he was egotistical in part, on the other hand you could say, well, he's an introvert. So he was not a hail fellow, well met, back-slapping, gregarious sort. No, he'd be in ... over in the corner of the room with people avoiding him because it was hard to think of anything to attract his attention.
You were already at the institute when he got his Nobel Prize?
Was that a great time of celebration there?
We went to Jimmy Watson's [wine bar and restaurant] for a barbecue lunch. Jimmy Watson's, it's a good place to have a celebration, lots of wine to drink. He wasn't a great drinker but I'm sure he had a couple. That's a pretty modest sort of celebration but then people were modest in 1962. It was a big deal to walk over to Jimmy Watson's and have a barbecue.
And although he had a certain sort of, how shall we say, scepticism about what you were doing, and the work that you were doing in cancer research, how did he actually treat you, one to one?
Ah well, I was prone to make outrageous statements, I was probably an adult ratbag often and on those occasions he would treat me with disdain. Um, no, as a junior colleague there was nothing ... nothing strange about the way he behaved, still you couldn't get him particularly interested in talking about, for example, cancer. But with time the two fields moved together some and he became quite interested in immunology and how it might have an impact on cancer so on those, you know, late in life, it was quite easy to talk about subjects that had some interest to him. But that's the same with everyone, if somebody came and talked to me about lung disease or heart disease I'd ... that's not my field, I've got nothing to say much.
When you had a change of director and Gus Nossal came in as director, what ... how would you describe Gus?
Well, he was the extroverted, back-slapping type, wasn't he? He was an Austrian, exuberant, enthusiastic. He taught me one important thing, which was if you want to criticise somebody, compliment them. If they're being recalcitrant and a pain in the neck, congratulate them on something. Slap their back and say, ‘You've done a fantastic job.’ And with my Scottish upbringing I thought this was crazy, I would haul them over the coals and rabbit on. So I decided to try this. Compliment, and it's a very powerful system for bringing people to heel, to say, ‘You have done a fantastic job. Now how about ...’ So, he had this sort of instinctive ability to deal with people and manipulate them. It wasn't that there weren't fights amongst staff that he found very difficult to cope with but, in general, it was perpetual enthusiasm, everything was on a roll and it was go, go, go. And so people did sort of behave the same way, that's being a leader in the positive, enthusiastic sense. Treated the same with politicians and so the money rolled in and you could do what you wanted to do. Um, was he able to discuss science with a junior colleague and provide some insights that might help the project along? Yeah, probably. In his field, but it wasn't ... our fields weren't completely overlapping so it didn't happen very often.
As the second in charge, did you find yourself doing more of that kind of close work with the ... with the scientific work while he did the more public face?
That's the way he did it, that was the nice thing about him, he sort of did all the PR administrative chores and it was only when he was away on sabbatical leave that I had to do it. So I was left pretty free. Which doesn't always happen. Assistant directors, some get dumped with all the dirty work.
You have really contrasted personalities.
We do. Strange that, isn't it? But we never really had any fights. We were totally different personalities and probably disagreed on most things but we got on pretty well. Didn't have any fights. That I recall.
What about his scientific work, was he able to continue it at all after he took on that job? You avoided the job, were afraid of that.
Um, he tried and he did, and managed to keep the pot boiling to a certain level but it's an impossible job, there are demands on your time and you just have to stop — once you stop in the middle of something you ... it's cooked. So if he was in a team and he was doing one particular job and time permitted, well he could keep going but it wasn't the same as working 24 hours a day on it. So he would say, he was a failure as a scientist, he wasn't able to keep going, was one of the regrets he had that he could no longer be a scientist and I would agree. You can't do it.
There was a lot of publicity, some time back, more than 10 years ago, when you were supposed to have retired. What happened?
I came to work the next morning. Um, it actually became illegal to sack anyone on the basis of age that year, I think. But I just turned up the next morning, 7 o'clock, started working again. The terms of my fellowship had no termination age, the new director sort of agreed to let me keep working and actually, by law now, if you can keep earning your research grants, you're allowed to keep working, it doesn't matter how old you are. It's the same in the US, same in England. So there are 80-year-olds who are dragging in their research grants and working. Not working at the bench but leading teams that are successful.
In February of that year, when you turned 65, what actually were you required to retire from?
It happened in two stages: Gus asked me to stay on as assistant director until he retired and he's two years younger than me, so we were really talking about when Gus became 65 and I was now 67. And the only overt sign of it, apart from the fact that you were no longer director and assistant director, was that you were no longer a professor in the university because they still had the retiring age of 65. But then if you were well-behaved you became an emeritus professor, so ... which we both did eventually. But otherwise you ... you're no longer head of your unit or your team or your division or whatever it was called. So I was still the head of my laboratory and I still am, but I have a boss over me. I have two bosses, a director and a ... the head of the division, who used to be under me. So it was changing, changing stools.
I feel fine with it. Whether he feels that there's a grey ghost that's difficult to dislodge, I don't know. But if I produce the goods for him, he should be satisfied, I keep out of his hair.
Nick ... Nick Nicola.
And how do you get on with him?
He's fine. Fine. But you tend to be marginalised as you get older and I wrote a paper about relevance. You are no longer relevant, you're no longer in a power structure so you're not relevant in the sense that you used to be assistant director, therefore you are a pretty high-powered semi-god. Um, you're no longer leading your unit, so the work that you might be doing is no longer visible as some powerful group in the world. And what you're doing suddenly becomes irrelevant. And you say, ‘Well who ... who invented relevance? What is relevance?’ So I wrote this essay about relevance and being relevant. And it's fashions. So you have an important person in a field who says, ‘I'm going to work on the thymus.’ And that's it. The thymus is it. And you have a whole bunch of other people that say, ‘Gee let's work on the thymus, that's where the action is.’ And the grants might go to the people working on the thymus. So if you're working on the big toe and doing fantastic work, nobody wants to know about it, you can't stop them in the street and say, ‘Look what I've done for the big toe, it's fantastic.’ So that's what you tend to find happening, so your colleagues are no longer coming to you with their data, as they used to when you were the boss, and you perhaps are not getting invited to international meetings to be a speaker. Because you're not part of the current visible view. And you become a sort of non-person and that's when you really have to hang on hard to your self-belief and say, ‘What I'm doing is actually important and I don't care that people aren't paying attention. I will still do it.’ It's an interesting cycle you go through.
I don't find that hard now, because I actually collaborate with at least 12 other groups of younger people and they are desperate to get me to do their part of the work for them, so I'm in demand. But am I regarded internationally as being one of the top dogs? I don't think so. No, because you're not the one that's leading that particular study. So I'm part of the action which is great. But I'm not creating the action, which I don't mind.
One reason that there was a retirement age was that, otherwise, how do you get rid of people who are no longer useful? How will you know when it's time to go, when you're not being effective any more?
I get examined for my senility twice every two years, formally. A little committee meets to consider whether I should still be employed and still be the fellow and I front up to them and basically they are producing a report that says, ‘Look, 12 publications, come on? Who else in the place has got 12 publications in the last year? Show me somebody who's got a better performance?’ It's ... there's no argument to that.
So, is it making your work even harder at 77, Don?
Oh yes. Yeah, I would hate to be senile and not realise it. So I am hoping that people do say, ‘Sorry, listen, you've done enough, stop.’ Somebody has to say that at some stage. I don't ... you never change, you may have noticed this, that you stay a little young person staring out of your eyes and you haven't changed since you were 15. And it's very hard to realise that outside you are getting old and tired and slow-looking and maybe are not competent, so it's sort of sad when you come across people who are over the hill to say, ‘Look, stop.’ Most often they've stopped anyway but for people like me it's going to fall on somebody one day to say, ‘Look, you're just ... you've got to stop.’
And when that happens, and you're not getting up and going every day to the lab, what will you do?
Yes, there's going to be real trouble, I will become a menace in the household, probably. I will start reading more books, I will start listening to more records and, don't know, cause trouble. What I ... what I ...
Do you dread the day, do you dread it?
Ah, I don't envisage the day, I really do think I'll be found dead at the microscope, I hope that's what happens. Why stop? Why stop if you're competent enough to be doing something? There is absolutely no point, there's an infinity of stuff to discover and if you can keep discovering things, why stop?
And what is it now that you're working on?
What am I working on now? I'm working on some mouse disease models, that are detecting a new gene, and so I'm asking questions. How does that gene work? Why is it that if you have too much of its product, you're getting leukaemia? What's it done to the cells? What's it made them do that's changed? A whole series of techniques for analysing what's changed in their behaviour. That's one of my projects, I like doing that one, it's a good one. But there are other mutant mice that have various diseases and I'm trying to figure out what it is that is responsible for the fact that they've got low white cell levels or low platelet levels or whatever. So it's experimental pathology, trying to figure out the causes and mechanisms that have gone wrong. It ... I've got an enormous backlog of stuff to do. It's harder working now than it was 10 years ago, 20 years ago.
Because there's a shortage of people with my skills so we've got an institute full of molecular biologists, generating these fabulous models, and nobody able to take them to pieces and say, ‘What's happened? What's gone wrong?’ It's a very strange time. A golden age for biologists. Because you would have killed to have disease models like this 20, 30 years ago. And they're everywhere, take your pick. Marvellous.
Why aren't there more people with your skills, given all the people who've passed through your hands and worked with you and learnt from you? What's happened to them?
It's a worry, isn't it? They ... they've become administrators or famous professors of pathology or bacteriology or something. Have I trained successes? Yes, I've trained successes, one is the head of the Ludwig Institute, one is my boss, the obvious ones. But they're not, they don't have my skill base, they have different skills: one's a biochemist, both are biochemists, so they're not, in a sense, replacing me and it's curious that I can't persuade anyone to do exactly the same sorts of techniques that I do. And it should be a worry to the whole institute, they can't start developing a replacement, so it's going to be in real trouble, the day I stop.
Is it because what you're doing is too hard?
Oh, absolutely. It requires brilliance, perception and it requires years of slog, slog, learning what's what and making mistakes and getting experience. And people don't like working at microscopes, they find it physically exhausting. Um, I can't believe they find it boring, it's not a boring subject. Um, and they find it demanding in that there are no easy fixes and you've got to learn your trade and it takes decades of experience. So it's unappealing to the young, they want to get rich and famous, fast. Not rich, but successful.
With this range of things that you're working on at the moment, are any of them promising you something like the CSFs, something like that, that will really make a difference? You've spoken about how important it is to you to do things that have relevance.
Yeah. The answer is, yes, but it's getting indirect and it's a bit out of our hands but, for example, this new gene that my colleagues and I are working on, it's ... whose function we've just discovered and we know when it's overactive, causes leukaemia. So you could say, okay the protein that that gene codes for, must be nasty news inside a white cell. Bad for it. And you make an artificial molecule that will block its action. Or destroy it and the answer is, in principle, yes you can. But you need then to go to other people, like medicinal chemists, like structural biologists, who can figure out the exact shape of the molecule and figure out how you can put something in here that would block its action. Now that's another department so you have to persuade them this is a tech ... this is a question that's going to be great. So that's going on. There are lots of molecules we've discovered and they're being worked on by structural biologists and maybe antagonists will come out of it. And then you'll be testing them in the clinic and seeing if they work. Things take a long time. CSF story took 30 years, so will these stories, even today. So the molecules that are a family, called the Socs molecules, are being developed — will they ever be used clinically? Come back in 20 years’ time and we can perhaps tell you, but it's ... it's a complex process in finding and synthesising the little key that will block this lock. But it can be done, there are successful examples, so it is the right track to follow, it's just finding enough bodies to do it and spending the years trial and error.
You're just going to have to go on working until you're 100.
Yes, it's a worry, isn't it?
You've described the commercial advantages of some of the ... the commercial exploitation of some of the things that have been discovered in a laboratory. Is the commercial environment in which science now operates helpful or not in relation to the development of new ideas, do you think?
It depends who you ask. There are some people who really detest this whole thing, they say, ‘I'm a pure scientist, I don't want to be bothered by such crass matters.’ Um, the rest of us know one important thing: if you make a discovery and you want it to be used in the clinic, you must have a patent on it. Why? Because the people who are going to develop your discovery, the drug companies, are not going to touch that discovery unless they have the protection of a patent because they're going to spend up to a thousand million dollars developing your discovery. So they have to have the protection. So as a scientist, you learn that everything that is possibly able to be used commercially must be covered by a patent. And so, we have a ... actually a little department that handles patent work because now our colleagues might look on us and say, ‘You're very commercial, you are doing this to make money.’ And we say, ‘No, we're being practical because we would like our discovery to be used.’ Now, does it change the sort of experiments that I do, or anyone else does? And the answer is, no. Not at all. Nobody has ever set out to do an experiment thinking, hey, this could be used as a drug and make millions. I've never met anyone who had that as their aim.
You might say somebody like Ian Fraser, who developed the vaccine against the papilloma virus, for cancer of the uterus, didn't he have in mind that one day this would make millions? I don't think so, I think what he had in mind was getting a vaccine that would prevent cancer of the cervix, number one. And maybe way down the line, number 10, and yes, it can be exploited. No, I don't think scientists think that way, they don't ... they don't sit down ... now if you're in an industry, employed as a scientist, maybe you would sit down and think, ‘What are the big needs, what's missing in medicine that could be developed? Is there a tablet that would cure the symptoms of influenza? Let's do it, let's make it.’ But not in academic life.
But sometimes in academic life funding is coming from drug companies and so on for specific research, I mean, if we were in a situation where the ratio of funding moved so that there wasn't any public funding and everything was done ...
Yeah, that would be a real problem. Ah, at the moment, the way it works is that, yes, some of our money comes from industry, let's say at most ... a third, let's say it was a third. What's happened is, we've made discoveries and then gone to industry and say, ‘Listen, this could be of interest to you, will you help us develop it more quickly by giving us some extra money?’ And the answer is, yes, they'll do it. They'll fast track it. But it's a discovery that was made by us, by accident or other ... for other reasons. So yes, you can look at a place like ours and say that there's a lot of industry money coming into this thing, aren't you just employees of industry? And we would do anything to avoid that. We would never do any research for a fee. Then we're just employees and we don't want that.
So you wouldn't like to see a day in which a government moved out of research funding altogether, which could improve the situation?
No, it loses the buffer you have between the freedom to do what you want to do and being an employee. If you were an employee you might as well join the drug company, you'd get a higher salary and a more secure job. That's for sure, because people try to headhunt us and give us bigger salaries working for industry. But it's better to be free and poor, sometimes poor or always feeling tense — where is the money coming from? Nobody's ever discovered anything that I can recall by design. Nobody sat down with a piece of paper and said, ‘We will now figure out a way to cure measles.’ It ... it's done in this sort of haphazardly way by accident, sometimes hopefully by design, but you can't write prescriptions for discovering things.
If your goal is altruistic, that is, wanting to find something to cure people, why does it matter whether you register the patent before somebody else or not, given that the result will be the same for the world at large?
That's a good question. Um, often it's more complicated than that. I mean, somebody else may have made the same discovery but their background is different, and the discovery patented may need to be amplified and extended and you may have the ability to do that, and the other group doesn't. So, a drug company faced with the choice — which one do you go for? — would go for the one that has the will and the ability to do the necessary work in-between development. And that's what happened with the CSFs, that CSFs required a lot of spadework and testing in the development stage rather than the discovery stage, and we were fitted to do that because we'd done the discovery bit. But it was a sort of applied research almost, that all the tests on the patients was, you could say, routine testing, no it wasn't because it made new discoveries, but we were about the only place that was set up to be able to do that. So if somebody in Sydney had made the same discovery, it's possible that they couldn't have helped in the development so there is a difference. It's still nice to be the one that has the patent first. And you're right, in principle it wouldn't matter how the other person might be able to tie up with somebody who developed it. So are you saying that I'm not really altruistic, I'm competitive? Yes, I'm competitive, absolutely.
It's funny, the people, the Japanese group that beat us to cloning G-CSF and therefore had the patent for G-CSF, wrote ... what you have to do is still write a scientific paper about it and they submitted their paper to Nature, and it was sent to me to referee. Their head competitor had just scooped me by this paper. Now my reaction was, great, I don't mind losing. I mind a bit but I don't really mind losing and I spent the night changing the English of it so that it was acceptable as a publication. But I'm a bit unusual. But that ... that happened twice, happened twice with the same group. One of the smartest scientists in our field is Nagato, who's Japanese, and he just keeps discovering things, he's amazing.
Oh yes. He's a nice bloke.
No, probably not, I'm sure he doesn't, no, you work on different ends of the earth and how do you know you don't learn from people? I suppose you learn by seeing their success stories and thinking, not consciously but unconsciously, maybe you do. Um, I'm sure that you do learn from others, I don't think anyone knows how to do everything.
You described how sitting at a bench, working long hours every day, is actually physically very demanding. It doesn't look physically demanding so how is it demanding? What strains does it put on you?
Have you tried sitting in a church stall for two hours, or three hours? That's demanding. Um, what happens is that you get back aches and neck aches and stiff and physically it's very tiring. I mean, at the end of a day you are dog-tired, physically. Now you mightn't have moved or done much in the way of running up and down stairs but that's tiring, sitting, holding your muscles absolutely bone still.
Well, I've had a lot of back disease and a lot of back operations. Um, was it caused by what I was doing? I suspect not. I suspect I had the genetic make-up that made for bad discs and they popped out and that's what happened. It's just that when you work at a microscope it doesn't pay to have back problems because you get terrible backaches, stiff backs, you ... I used to spend at least a week in every year with stiff backs, for 20 years, and that probably wouldn't have happened if I'd had some other occupation. I would hate to have been a surgeon because I think I would've been in bed most of the year but, you know, it is physically demanding.
But not even chronic back aches could keep you away from the microscope?
Um, you have to earn your living. And that's the way I earned my living. Oh, no, you have to persist, if you're persistent those things can be lived through.
Now we've talked about the changes that you've seen in your lifetime. One of the major changes that you've lived through are the changes for the position of women in society. And, of course, in science. What have you observed in the time that you've been in science about the changes in ... for women? Were there many about when you started?
Well, there were a fair number of women at work in the institute that I joined 50 years ago. They weren't in positions of power, they weren't heads of units and they weren't the director ... what did happen was when they got married, they had to leave, that was routine, I think that's true. Certainly if they became pregnant they had to leave. And now of course that's changed. So now, there's a bigger percentage of women in the institute and maybe 70 percent, we have a woman director, we have a woman manager, so top positions are women. And if the women get pregnant, they're on maternity leave and they have the expectation of being able to come back to precisely the job they had when they left. Which can be quite disruptive but there it is. So that's changed, I think if you asked a woman what's changed, they'd say, nothing much. Where are the women that are running departments and deciding on research projects and changing the face of science through their discoveries? And there, the numbers are smaller and the reason for that is a bit hard to figure out, because they start with what seemed to be the same advantages as the men but, of course, that's not true, if they're married, they've got to go home at night, they've got their children to look after, they're distracted; it isn't the same for a man. So it isn't a fair competition but having said that, I think there is a sex difference, in ... call it what you like, aggressiveness or determination to have your way even though people disagree, that might make a difference, just speculation. There are plenty of successful women scientists around but in terms of the numbers that start off with equal academic records and are put through what seems to be the same set of hurdles, the differences do come out. That's a very sexist attitude perhaps but I'm just observing a passing scene.
In your teams have you found much difference in people working under you and with your general leadership between the men and the women?
I think you see the same differences. One or two of my people have been extremely aggressive in the nicest possible way of trying new things and rounding up people to help them exploit things. And they're one day going to be the leaders of the pack. Um, did we have any women who were that way inclined? Maybe I chose the wrong sort of people to start with but ... not exhibiting these same qualities of aggression and dominant leadership, I think it's random chance and I ... I just can't think of anyone in our particular staff who would be in that degree of a ... a real up and comer, stop nowhere, scientist. Which you sort of need to succeed.
Yes, why do you need that style of leadership? Could you conceive of other styles of leadership that might result in ... similar success or do you think that you can only have an aggressive style?
I think if you were a mathematician or a physicist, you could afford to be introverted, preferring solo work, thinking with your head and then the chances are they have to be equal, that a woman and a man would be equally likely to be smart and hit on this idea and be successful. But the sort of biology we do does need teamwork and it is a lot of hard yakka and a lot of it boringly repetitious. In other words it requires that determination and the aggression, if you like, to push it through and that's where I think you end up needing different qualities. I can't think of somebody ... I keep thinking of our staff, as an example, 600 people, who should be a fair sample. Is there anyone in that building who single-handedly thought of something that was so outstandingly good that it created a new field and made a new discovery? And the answer is, no. There are ... there are groups that have done this but not just a single person doing it. It's interesting because you look back in the 19th century and you say, ‘What about Pasteur, he must have just been a single person thinking of this?’ Well, we're not sure whether he had a whole lot of people working with him and he was just ruling the roost or whether, in those days, that was good enough, one good person, one set of ideas. Doesn't seem to work that way now, it's too complicated.
At a personal level you've spent your life surrounded by women. You were the only boy with two sisters, and then when you married you had four daughters. What part have women played in your life, as a person?
Surrounded by women, I'm dominated by women. I have women bosses, my goodness. Um, our children were always, what would now be called, women's libbers. They were always ... I think the school taught them to be free thinking and stand up for themselves. So, there was never any question of dominating them and saying, do this or do that. Choose this career, choose that. They decided what they wanted to do. Um, I think you learn, I hope you learn, to be more tolerant of the differences between men and women and ... and there are lots of differences. Lots of strengths that women have that men don't have. And networking ability in times of trouble, I think women are much better equipped for that than men. Um, and you are protective of women in the sense that you don't like to see them exposed to footballing hoboes and ... I think you do. For all I know, parents of boys are equally protective and don't like to see them being led astray, I have no experience.
Were you disappointed that you didn't have a son?
Sort of, after about the third one, I gave up. And thought I must not have a Y chromosome, there's no point. No, they're all very different children. Some are ... some have natural aggression, some have high spirits and high wits, and some are stable, and none of them particularly normal.
Did you ever feel any kind of conflict between the amount of work you did and the demands of home?
I'm sure there was — did I feel the conflict? I'm sure the conflict existed, I'm sure that nobody can work long hours, six days a week and not be accused of ignoring their families. Um, I used to feed all the children breakfast, I'd take them to school when they were small children and later on those sort of chores fell to my wife completely, so that their love of literature probably came through her, and it's very hard to avoid parents having an influence on children in a passive sort of way. Um, no, we always went on holidays together and I don't ... how do you ... how do you know whether you're ignoring your family? You need to ask the family.
As the family.
Have you ever had complaints from them?
No. No, I don't think so. I don't think so, I think doctors are in a different kettle of category aren't they? I don't ... I can't believe that children of doctors complain and say, ‘My father's never home, he's always busy’. Whereas they might if you were a banker or somebody. Hope they would.
Do you have much to do with your grandchildren?
Ah, not much. They all live in Melbourne and I see them. I figure that I spent a lot of man-hours raising my children, it's somebody else's job to raise the next lot. It is said that grandchildren and grandparents are natural allies but, no, we don't see much of them.
You've said that you and Jo have a lot of differences in your outlook on the world, that you've had a good marriage. Has Jo been interested in your work?
Um, in as much as she was a nurse and therefore and her father was doctor and therefore was a sort of medical background, yes. But in the day to day work she doesn't understand what's at issue and doesn't enquire soulfully every night, ‘How did it go today?’ No, no.
I think it's a reasonable way to go on. She has her priorities, she would much rather be figuring out what the grandchildren were doing than ... than worrying about whether I've got the right formula.
You've been married for a good many years, what's the secret of a long marriage like that, do you think?
Habit, I think, isn't it? Ah, look, if you can't figure out how to live together after 50 years, you might as well give up. What's the secret? I think tolerance is the secret and everyone's different and we're all bound to have lots of differences from your spouse and you just recognise it and figure out a way to get around it. Develop it, share it, change your ways. I'm sure she's changed her ways.
And so, in looking back, you know, over the sweep of your life, what part has the family played in that, in your life, and what significance has it had for you?
It's been ever present, hasn't it? We had our first child within a year of getting married so we had no ... as is common now, a married life in the absence of children for long periods, so we didn't have that, so they've always been there. So how do I know whether it had an influence? You ... one doesn't know. Ah, I suppose, having families is a stimulus for work and making sure they get fed but did they change the way I did an experiment? No. Did they stop me from doing an experiment? No. No, we managed to do everything that needed to be done.
Would you describe yourself as a workaholic?
Probably. Others would. Is it a workaholic if you're having fun doing it? I don't know. I suppose you're a workaholic.
Now, turning away from work a little to your interests, you've talked about your interest in military matters, stemming from your childhood, you were a cadet at school. Did you do anything more with the army after you left school?
No. I joined the navy when I was a resident for a short-term appointment, which somehow lasted five years before I could figure out how to get out of it ...
How do you join the navy as a resident? How did that work?
They went recruiting, they were desperate. It was towards the end of the Korean War and they were desperately short of doctors and they went to Prince Alfred and said, ‘Does anyone want to volunteer to join the navy as a doctor on a short-term appointment?’ So I put my hand up and ...
Why? Because I wanted to be near my beloved, who was a nurse at Prince Alfred. It's a strange reason to join the navy, isn't it? It was true because I was working at the naval hospital at Balmoral and knew I'd be there so it was a way to stay in Sydney and get paid and there it was. And so it was an aberration. What I thought you were going to ask me, what ... what reading I was up to and do I spend a lot of ...
No, I wanted to ask, did you ever find yourself doing naval ... naval-related work?
In later life? Not really. No. I ... when I was in Boston I was sent down to Washington for a little while, representing the Australian Navy, but it was for medical work ... it was pretty much.
Relax. I can't do any sport now because of all my back operations, I just can't do a sausage, so I've been essentially crippled for 40 years. So what do I do? I read books. I read other detective stories or war history, military history. Strange combination. And I listen to music, I can't play music, there's no tradition of music in the family, but for whatever reason I like classical music mostly and I have it on most times of the day when I'm home, never have it at work, it ... some people have headphones on at work and I just dismiss this, they're not paying attention to what they're doing. But at home, when I'm writing and there's a lot of writing to do, I'll have music on all the time. And then you discover they're very interesting differences between composers. You can have Mozart on in your background and it doesn't interfere with your thought processes and what you're writing. You can have Haydn on. You can't have Beethoven. Beethoven's very demanding. If you listen, the volume of the music goes up and down, you've got to pay attention all the time, you find yourself just stopping and listening to it. So you have favourites you can ... you can get by with Vivaldi quite nicely. Um, so that goes on as the constant ... go to concerts, we go to opera, we've been going for 40 years but so ... passive musicians, not ... my wife plays the piano but I don't. So I can't play and I can't tell you, I can't read the music and I can tell you when they're playing the wrong notes and whether I don't like it or not but it's as an amateur music listener. Can I tell a good book when I'm reading it? I'm a little more skilled at writing and, yes, there are some authors who have a superlative way of writing a sentence and a half that says everything — beautiful. And you sort of look at them, you dribble, and you say, I wish I could write like that.
And the visual arts? You're a very visual person, you said.
Um, yeah, we go through all the museums when we're travelling and we had a competition whether we could see every painting that Vermeer had ever painted, I think there are only 28, and living in Holland we saw about six of them and we ... we slowly got up to 27, I think, but there's one the Queen has that she doesn't often show to people, we ... we've never seen that one. Does that make us an art lover? No, we ... we have our likes and the Dutch painting school is one of our likes.
Talking of the Queen, in the course of your life, you've met quite a lot of famous people through your work ...
Haven't met the Queen.
Is there anybody, you know, you've met various prime ministers and ... and so on, is there any of the people that have been there when you've got prizes or have been there to congratulate you that really stand out in your memory?
As exceptional? Ah, I have to say that Hillary Clinton is a very impressive woman. We had lunch with her when I was getting the Lasker Prize in New York. She was impressive. Some of them impress you with their stupidity and their arrogance, and they shall remain nameless. We all can imagine who they might be.
Oh yes, you can. Um, it ... it's interesting when an institute like ours becomes famous, it gets on the VIP shortlist for visitors that get sent ... President of Indonesia will drop in. Well, what he knew about medical research you could put on the back of a stamp. But he seemed to be enthusiastic and ... and so it went. So you have a lot of strange visitors come but Margaret Thatcher would be there, Duke of Edinburgh would come. And simply because it's somewhere to send them that will fill in a half-day for them, we think. Um, so you see a few and it's interesting to see them in real life and talk a little bit with them and see the ... a glimpse of the real person behind the publicity but most of them are pretty much as you would have expected from their public visage. Occasionally you meet, there was a German woman, Minister of Health, who seemed particularly smart and with it, I can remember. No, it ... they're a mixed bag, like the rest of us.
What was it that impressed you about Hillary Clinton?
Her intelligence, she is one very bright, perceptive person. It was very interesting. Mary Lasker — and the Lasker Prize is about the two Laskers — was about 80 at the time and she was frail and she was seated in a low armchair in the room with her relatives and hangers-on waiting for Hillary Clinton to arrive so that the luncheon could begin. And I can remember them all saying, ‘How will we arrange this? How will we arrange ... how do you bring in the First Lady and greet the grand lady?’ As it were. She came in the door, just plonked down on her knees and said, ‘Hi, I'm Hillary.’ So there was that side to her and then there was the smart side, picking up on snippets of conversation and welding them into a talk that she thought ... developed on top of her head to an audience of a thousand top New Yorkers, and that — that's being smart, I think. Seemed a sensible woman. I think she might become the next president.
Yeah, it'd be great.
Do you think she's got the aggression that's needed, for doing it?
I think she does. Yeah. I think she's a tough lady, probably.
Now, there are a couple of things that I ... I need to pick up on that Rod's pointed out, for example, one of the things that I asked you about this morning we sort of spoke over each other a bit. And so we didn't sort of get the story quite clean, and that was the story of your receiving the news that you'd got the Carden Fellowship when you were in the surgeon's theatre. So I'm going to ask you a question about that because we ... that's such a good story, we want it.
I tend to exaggerate, that story, who knows what actually happened.
A bit of licence is okay, just a little.
The characters are all dead so I can say what I like, can't I?
You can say what you like, yeah. So I'll just ask you ... I'll just ask you about that again.
How did I find out about the Carden Fellowship? My memory, and it could be wrong, is that it ... that the telegram inviting me to come ... no the telegram telling me that I had been awarded the fellowship came when I was in the operating theatre and it, being a Thursday afternoon, it was chest operation day and that was a horrendous day physically because keeping your ribs separated, apart on a patient and working down a hole and being terrorised by the surgeon was ... was never pleasant and not when it went on hour after hour. And she came in the middle of that and said, ‘You've been awarded this fellowship.’ And I said, ‘Great. And you can get stuffed too.’ To my boss. Or words to that effect, I can't remember whether I actually said that but I said, ‘I'm free of you lot.’ Everyone backed back in horror and the operation went on but that was great. Because I really did think, standing there, this is a way out, this is what I want to do, this is the escape from this sort of hellish occupation here, being mistreated and there's got to be something in cancer research.
Why did you dislike this surgeon so much?
He was incredibly demanding and when you're working as an assistant you are holding forceps that are tying off blood vessels and if you use a diathermy, you touch the forceps with what's a live electrical wire and it just sst! ... burns the vessel and burns it together. But if you were slow at releasing the artery forceps, he would just jab the diathermy needle into your hand. Now, he was wearing thick rubber gloves — the residents have ones that have been used 20 times over and very thin — and the electric current would just go into your arm and it would go out of control, was like having an electrocution. Well, you didn't have to do that. You could tell your assistant to get a move on or do something. But surgeons in those days were inclined to be very arbitrary and bullying and he was the worst one in the hospital. So much so that they had to pick particular residents who they thought could stand this sort of mistreatment and not break down and go off sick. So it was not a happy time. What I find very hard to believe is that same surgeon, working in a private hospital in Sydney, Lewisham, was sweetness and light, they used to love him. But he for some reason in Prince Alfred just chose to be a bully. Was he a good surgeon? Yeah, I think he was a good surgeon. Did it matter that he burnt my hands to hurry it along? Possibly it made the operation a bit better but one doesn't know.
And how did he react when you told him to get stuffed?
He looked a bit surprised, I think. Because it's the first time anyone had actually, I think, told him that he wasn't up to speed.
Did this piece of larrikinism make you popular among your fellow ... ?
I think I was a hero for the night. Hero. Heroes last a very short time as residents; by the next morning you're dead. But I was happy I had a fellowship.
The other lovely story that I'd like you to tell us sort of clean is picked up from when you described Gus Nossal, that you walked out of the animal house and you were emerging like Fidelio.
What happened for you personally when Gus Nossal took over the Hall Institute?
The first thing I remember him doing, was saying, ‘Look, would you be the assistant director?’ And I said, ‘Sure that's great.’ ‘And would you move your lab back into the main building onto the sixth floor?’ Which hadn't actually been completed and was ... could be fitted out and used. And I said, ‘Yes, please.’ And so my little group, which had about 10 people in it, sort of emerged out of the animal house and it literally did have bars on the lower windows, like the prisoners out of Fidelio did when they flung the grates open. Um, and so we emerged into the sunlight and joined the population. It was great. The people that were there, and the former manager is one of the ones, she still remembers that as being like straight out of Fidelio. Yep. That was ... that was a very dramatic time for us, dramatic change in fortunes for us. From being still visiting and attached ... to belonging ... to running the place, damn it, in the best, newest lab in the whole place.
Okay, a less salubrious tale was ... concerns ... you asked about Burnet and what his mannerisms and manner were and he was modest. But he, when he won the Nobel Prize, he felt rightly that people round the world should acknowledge that he was number one and issue him invitations. So when the Japan Microbiological Association was having their annual meeting, goodness knows who'd want to go to that. Ah, he wrote to the organisers and said, ‘I really think you should invite me there.’ And so this obviously put the Japanese in ... into a fit of terror because it's 1962, they'd had few foreigners there. I happen to have a Japanese post-doc working with me, he was the first or the second in Australia. So, he'd forgotten that he'd told us at morning tea that he'd written to Japan essentially demanding an invitation. So then he came in a few weeks later, shy, and said, ‘Look what the Japanese have offered me.’ And it was a letter of invitation. Furthermore it was to meet the Emperor and to receive an award. And isn't that nice of them? And he'd sort of forgotten that he'd ... he'd spilt the beans by saying he'd written this letter demanding to be ... to be so honoured. Anyway, he went to Japan, duly met the Emperor, came back with this beautifully lacquered box in which was this enormous Japanese decoration that had only, I think, for the first time been awarded to a foreigner — I think it was the Order of the Chrysanthemum, Second Class, or the Rising Sun, Second Class. Anyway, beautiful lacquered box with the traditional Japanese writing on the lid. Which he couldn't read. And so he gave it to my Japanese post-doc who was a high-born, from a famous family, saying, ‘Can you read this inscription on the box?’ And he picked it up and was fumbling and the Japanese don't like to admit they can't do anything. Ah, was fumbling and oohing and aaahhing, and for some reason I said, ‘Give it to me, I think I can read it. Think I can read it. It says, Made in Japan.’ And the sort of stony silence round the dining room and I was dead for the next six months. Because in those days, just like the headline on the newspaper this morning, Made in Japan used to be a ... something that you said for something that's cheap and nasty but what made me say things like that? And cause my slow progress in science? I do not know. But every so often one would pop out and did not help my career at all. And that story is told all around the world, I've heard that story told in Russia. Accurately. How does ... how does it spread, that sort of story? I don't know.
Maybe it's not just Australians but the whole world who love irreverence?
Ah, or else there's not much to laugh about in science. I don't know. I wish I had a smaller mouth sometimes. I mean, that's ... that's insulting, isn't it? Would I have liked somebody to say that to me? I wouldn't have minded. But ...
I don't, I have no idea. It may have said, Made in Japan. I really don't know, it ... no, it's a nice medal, I have to say that. And nowadays, Made in Japan, is a pretty good advertisement if it's a watch ... [General discussion about questions that may have been missed and conjecture about who took the photograph that went on the postage stamp that Don was on] ...
I think that sounds ... yeah. And he was hired by Australia Post to come and take the photographs of the people on the stamp. I thought they were going to do drawings but they had used photographs, and he came into the Australia Post headquarters downtown and they were obviously frightened out of their wits by him. He sort of swung in as a prima donna, dropped his bag on the end of the table, sort of lay back at the end of this table talking to me down the other end, with his camera on the table just going, t-t-t-t-t. And then left. And they bowed and scraped their way out and I didn't really know who he was or that he was Mr Big. Ah, and the photograph they chose, I don't think's particularly good, but yeah, that's the one. Ah, that's ... that was a fun occasion. They're actually having a 10th anniversary of a series next Australia Day, when all the distinguished people will reunite in all their glory. That was Australia Post. It's good fun. They gave us a tremendous pile of free stamps and, of course, they used to be 45 cents, now they're 50, so you have to stick another five cent stamp on, but I still use them. Any nasty, overdue bills, I use Gus Nossal's face on them and put them on, any nice letters I'll put mine on. Oh dear. Small things in life ... [interruption] ...
... And you ... you're at a disadvantage because technically you're not a musician so you can't say the right technical expressions, never the less, you have ... there are all sorts of fascinating things about music, for example. What fascinates me is that music written by kids of seven, eight, 10, 12 ... so who have we got? Beethoven, Mozart. We've got the Rossini String Quartets written by a 16-year-old? Over a weekend, larking around with his friends. You've got Mendelssohn — that whole swag of them. That's mind-blowing to me because I was a highly intelligent child and I could no more have done any of that than fly, so I'm sort of just fascinated by that. I have collected all the pieces that are written by young people and they're just astonishing, so there are odd quirky things about it and ... and you find odd records. There's Frederick the Great, was a flautist of note, and he had composers hired to write music for him, his flute concertos are great. Now Frederick the Great, whoever talks about him being a great flautist? Nobody. He built Prussia up but ... so there are all sorts of oddball things about music that aren't talked about too much so it strikes the fancy. Got nothing to do with science in a way. At all.
That's reminded me of something I really would like to ask you. Everybody knows that you have to be intelligent to be a scientist, and that intelligence is very important. What about creativity? What about that thing that allows people to think differently?
Well, that's how you earn your bread and butter, isn't it? If you ... if everyone in this room can think of the same experiments to do, nobody would get paid to do it, I mean, it's an obvious thing to do. Now you're getting paid a salary and given grant money to do something, often it's quite unexpected, it's lateral thinking, it's ... it's a jump, it might be a little jump, but it's a jump. And that's creativity. If you can actually strike out in a new patch and make a new discovery and develop a field that's creativity. Ah, can you express it in some way? Well, no, not ... not naked creativity. Can you make a graph that shows the data in a way that nobody else has ever shown it? Can you make it an artistic presentation? No, that's not the sort of creativity that's welcome. Can you write the prose in a way, in your scientific paper, that's elegant and a joy to read? Yes, you can do that. And some have that capacity. I take a lot of care in the way my figures are drawn because that's to me an important part of it, and the photographs look great and they're saying what they're supposed to say, and that's artistic and creative to me. Um, so that's creativity, discovery.
You've got a daughter who's a visual artist, and you're a very visual person. Do you ever see any connection between practicing the arts and undertaking the sort of things that you do?
It's hard to see an obvious connection because I can't paint and therefore I've ... she's painted portraits of me and I've seen her at work and her tongue out and her concentration and, you know, that's a skill that you just have no ability to feel what's going on in her head. But on the other hand sometimes she'll paint a picture that just has a few traffic barriers and this and that and to ... oh, that looks good. And sometimes you recognise that sort of thing just travelling around somewhere, maybe there is something in common between me being able to see a pattern that's rather nice and funny and she seeing that and making a painting of it. Ah, otherwise it's a bit hard to see connections. I mean, there are artists who painted exact replicas of real-life things, like in the Banks Florilegium, where there's absolutely accuracy in the shape of the leaves and the seeds and the roots and so on. And that you could say is a scientific drawing, it is a scientific experiment, you're accurately representing what's there. Um, so there’s that sort of connection. I thought, I thought you might say, Well, there ... aren't there a lot of doctors who are composers? And there are, and what's the connection there? And I don't know, I think that's just chance probably.
Some people say that there's a big connection between mathematical ability and musical ability but there are a lot of exceptions to that as well.
I imagine that Bach must have been a fabulous mathematician. Never put to the test to see what he could actually do because there was no formal, I think, algebra then. But to be able to write his style of music, with its complexities and interwoven variations and so on, that has to be mathematical. And that was just instinctive, I mean, that was impossibly complex. I've heard it explained and analysed and that ... that's real smart ... smart creativity, isn't it?
Would you say you loved your work?
Yes. I trust that everyone loves their work. I mean, it's really ... it's horrible to think of doing something that you don't really enjoy. Now what's the difference between enjoying and loving? I don't think there is a difference, it's just words. Are you passionate enough to fight for the right to keep doing what you're doing? It's ... that's something else again. It's not love, that's passion, isn't it? No. I ... yeah, I love what I'm doing, what the hell. That's what I do, if you didn't love it, it's going to be a hard day's work. I like the sort of people I work with, I like the ... the whole bit that we've been talking about — competition, discovery, excitement, disappointments, major disappointment — the whole bit.
Would you describe for us what a typical day at the office is like for you?
Well, it looks, it could well look very boring, I mean, what has happened in the last 30 years for me is that there are techniques that you start that last one week. So if you start an experiment today, being Wednesday, you know next Wednesday you're going to have those cultures and you have to analyse them, count them, do something with them. So most days, you've set up something a week before so it's waiting for you to do. And it's a bad day if you haven't got something to do because I like to get started at 7am and, before too many people are around, get stuck into the physical part of actually analysing what's happened, what was started a week before. Um, that might go on until morning tea, stop for 10 minutes, morning tea, then you start again and go through to lunchtime, you have a seminar often, might be giving a seminar, more likely listening to one, or if you're not then you have a 10-minute break for a sandwich, and then you start again and you work through. Now in the interim, there might be half a dozen people have come into your room, your office where you're working, discussing projects that we have got going in common. What should we do next? What's happened here? What's ... what do we have to do? Um, somebody might come in with a grizzle and saying, ‘Look we've run out of mice, have you got any to give me’ or ‘the machine's broken and I don't know how to fix it, who should we call?’ Ah, the airconditioning may have broken down, might have people clambering over your head, fixing something. Um, a high-tech institute always has things breaking down, that's why they have a big engineering department. Um, there probably are a few visitors in the place from overseas that you may or may not get to meet. And then you might decide it's time you start to collate all the data that you got last week that's sitting around in bundles before you forget what you did. And spend the time number crunching and drawing up tables, planning figures. Going down to the art department, grovelling and trying to get them to draw them for you, and you spend a lot of time grovelling, getting people to agree to do something. Then it's time to go home. You go home with a bag full of work that you hope you're going to do, which would be papers to read, things to referee, papers to write yourself. And if you don't sit listening to music and you're wafting off into dreamland, you might actually do some of it before bedtime. Before bed you will start reading whatever book it is you're reading. Ah, that's an average day. Terribly exciting.
So even the god professor has to grovel?
Oh yes, there's a lot of grovelling in life. Grovelling means being extremely polite to colleagues who have special skills that you need.
What happens if they come in while you're counting?
They know to stand in the doorway looking forlorn and lost until I lift my head up because I can sort of see them out the corner of my eye but I will not stop in the middle of counting, not when you're up to 183. There's just no way I'm going to stop and most of them are pretty savvy about that.
Is there any mistake that you remember making that can still make you jump with horror to think about it?
That was absolutely wrong? That took years to unravel and get straight? Ah, not really, nothing, nothing major, I mean most things you do end up having a different twist to what you think of, so the discussions of scientific papers do not make pleasant reading years later, because they're just witless and silly. I mean, silly things that aren't your fault. Like, until 1970 ... oh let's say 1980, people did not know that on the surface of a cell there were special molecules called receptors that allowed things like CSFs to lock onto the cell and tell the cell what to do. So all the discussion of what CSFs were doing before then, reads like stone age stuff, because you had no way, you had no idea maybe the ... these molecules got inside the cell somehow and went somewhere and did something. So discussions and ideas change very markedly over a decade. So — is that wrong? No, it's not wrong, as long as the observations are correct and the context is the same, you'll make the same observation in a hundred years time. Ah, that's okay. So in that sense, there haven't been any complete disasters but most often things happen for a reason that you don't understand and that later events, more information, will say why it was happening. So if you're smart enough and observant enough, you describe what happened and that's right. So do the same set of experiments in 20 years’ time, exactly the same thing will happen, but now you know the reason why it's happening, it's different.
Um, there aren't ... I can't think of many bad mistakes in science where absolutely wrong ideas, completely ... there probably are examples, there might be examples. In the years before we got started, some German got a Nobel Prize for claiming that he'd discovered a worm in the stomach that caused stomach cancer. He got a Nobel Prize, almost, just for saying that. It was a bit political in the mid '30s, that was totally wrong. Totally wrong. That sort of big, big mistake, there are the occasional, once every five years, major fakers that are caught out and are just telling lies and manufacturing all their data. Ah, they're spectacular and make great reading in Nature but pretty rare.
Is there ... at the time that you decided that you would take up the Carden Fellowship, there were people who said that coming to Melbourne would destroy their international careers ...
Their careers, yes.
Now you had the potential and I'm sure you would have been offered opportunities to work in places other than Melbourne. Is that a decision you've ever regretted?
I don't think so, look, as a first-year resident you are the lowest of the low. You are so low you're invisible. And you are untrained, non-entity. To be offered something, a paid research job, was a rarity and that ... that didn't happen. Now, could I have ended up working in Sydney University? I suppose so. Eventually or ...
Later in life, for example, you know, you went to Boston and you've had stints ...
Oh you ... you got invited to positions in Boston and I got invited ... I got begged to take a job as a professor in North Carolina when in Buffalo, they're the ones I remember. And I'm thoroughly glad I didn't do it, because I would have hated to have had a family grow up in the US but I haven't made a career decision that I regretted, no. Which mostly meant doing nothing: not accepting the blandishments of some promises.
You didn't think you could do better anywhere else?
Ah, I knew that I had what I needed and one way or another we'd succeed in what we were trying to do. I didn't want to be running 500 people and getting half a million a year, I mean, gee, no.
Not a ... not a great deal. I mean, you need a certain amount of money to live but not in a grand style. I mean, you don't have enough time if you're working five and a half days a week, when are you getting the time to spend all this money? Do you want an enormous house that's too big to manage? Do you need luxurious furniture? You don't. Um, do you have enough money to buy the books you want, if you're a bookaholic? Yes, now that's important. You go down to JB Records which has got cut price CDs and you take your luck down there. And, what else do you need money for? Look it's ... the answer is, when you're working you don't need to get dressed up in finery, you don’t ...
It also sounds as if ... when you made a decision not to accept offers of jobs in the States, you were putting your family before work.
Ah, I think, no. Well I figured ... I would never have been afraid to work alone or to build up a little group to work independently. I value being independent and being able to do what I want to do and I knew I could do that in Australia. When you've worked in the States, and I've worked there for two places, you realise that life's a bit of a delusion. Yes, you've got these grand titles, you've got the large salary and you've got an awful lot of people interacting, telling you what to do and pressuring you this way and that. And it's not a great life. It's not. And the quality of life isn't a patch on the quality of life in Australia. It's not a patch. I sometimes wish we'd lived in Europe because you've got access to all the ... the splendours of Europe but then you say, well, which country would you like to live in? And you can think of 50 reasons why you didn't want to live in places. You couldn't speak the language and that the UK was for one reason or another not very satisfactory, so stay home.
What does it mean to you to be Australian?
All of the things we've just mentioned. To have the tolerant society, to have freedom to do what you want, to have ... to still have people that are not all that fussed about earning large sums of money, I think. Certain simplicity in life. They're some of the things, there are a million things.
If push had come to shove and you'd had a choice between things that would help your scientific work and issues about your family, and this is a very hypothetical situation, because it never happened to you, but how would you choose?
I'd choose what almost everyone else does, family. There are very few people who would, for example, choose to go and work in America for the sake of a very plush job. One or two. They have often come back after a few years. And glad to get back I think. And never heard of anyone retiring ... the answer's different. If you spoke to a Greek of my age, he might well say, ‘Look, I would like to retire now and go back home to Greece.’ Which is quite common. Go back home to Italy. Less common to go back home to the UK. But if you're born in Australia, home is here.
When you talked about counting, you mentioned counting four things at once and you had a sing-song thing, could you do that aloud for about 30 seconds or does it happen in your head?
There are three types of colony that are the most common, so if you're counting one, two three. One, three, four, one, five, four, it’s automatically counting the number of each of those three categories. Now there are two that are more rare so that gives you five and I can't ... I can't always cope with five. So the problem I have is the problem most people have, they've got to put their glasses on to write it down and be able to read it, so it's a ... you end up with a hybrid system where you're counting four things and then quickly jotting down with your hand the fifth and sixth. Okay, so counting colonies you do in your head, now, other people use mechanical counters but I count in my head. So and you will lose count unless you somehow emphasise the different colonies so there are three common types of colony. And you count them as you come to them, you're moving up and down in a fixed pattern, up and down, up and down. Up and down. So let's say you go, one, zero, zero, one, zero, one, one, two, one, three, four, one, and you find that if you sing that in your head, it's easier to remember, because you've got a rhythm, because it's quite easy to forget which was the one. Was it the first type or the second type. So you need a rhythm and then you can add one extra, whatever that is in music, one extra instrument for the last colonies and, whoops, there's an eosinophil colony, got to write it down and megakaryocyte colony, that's worth writing down too. So you've got, you've got six categories.
Is the rhythm Bach or ... what ?
Is the rhythm Bach? It is not in a waltz, I wish it was a waltz and it depends, sometimes the going is pretty fast because there aren't many to go, and you can rip along and they're easy to count and it's well-stained and it goes quickly. Sometimes it's a real swine and you're sitting there having to make decisions — are these two overlapping? Are they — what, what, what? Are they sitting on top of one another? And it helps then to have a semi-musical rhythm in your head. I think other people do this by having a keyboard that they have a different key for each different type of colony. But the problem is, that you've got to focus up and down with one hand and move the stage backwards and forwards with the other, so it's a two-handed job at the microscope. And you don't have a hand to play the key. So you're taking your hand off the focusing knob, to play the keyboard. Now I do that if I'm working with blood films or smears of cells where you have to count eight or nine types, you really do need to be able to play the piano. But, for counting colonies, it's a head job. Which is why when the telephone rings and it's not good, when somebody comes in the door and you have to stop, you've got to do the whole damn thing over again. Or if you see them coming you can put the last down count and an arrow to tell you which direction you're going. Because microscopes are so good they won't slip out of place if you stand up and walk away, and you can keep going down the same track. But the trick is not to let it slip over so you're double counting ones. It's good fun. Three dimensional and you've got to go up and down, up and down, up and down, counting, one, two, three, one, two, three.
I'm afraid that I'm running out of neurones because the way I figure it, the way you remember is that you've got one nerve cell remembering, one. And another nerve cell remembering, two. And if you use them up, you've got none left, which is why I have no memory because I'm ... don't remember names, I'm saving neurones that way, I don't remember places, I don't remember where I left my car. What I read last week. Now I think that's all rubbish, I think every time you go to bed and go to sleep you wipe the slate clean but if we don't, I'm about to run out of neurones because I think at last count I had counted something like three million cultures and each one had about a hundred on, so that's three hundred million counted and I think that's about as many neurones as I've got left so I'm getting a little bit worried.
Well, Count Don, that's all I've got to ask.