Australian Biography

Donald Metcalf - full interview transcript

Tape of 11

Tape 1 2 3 4 5 6 7 8 9 10 11

... [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 ...

Not to do your work?

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.

Do you ever lose count?

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 ...

But it's more bench work.

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.

You said that ...

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] ...

What was it called?

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 ...

In all forms?

If they did, whoever was involved became a saint because you'd done one of ... one of the three miracles. So ...

Was that for all forms?

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.

Why not?

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.

[end of tape]

Proceed to Tape 6