EP01 – Forging the Path

World Leading Immunologist Sir Gustav Nossal

We sit down with Sir Gustav Nossal to learn about his early career decisions and hear his advice to students interested in pursuing a career in science and research.

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Interview

You’ve had all these amazing opportunities and all these different potentials for career pathways. How did you decide the direction of your career since you graduated?

Funnily enough I’ve wanted to do medicine and become a doctor as long as I can remember, from probably about the age of seven. Would you believe I was all of 16 years old when I did medical school in 1948. I can tell you because of that I really wasted the first two years and didn’t kind of wake up until third inning… If there’s a pretty good Curriculum Vitae, it’s mainly because I’ve been very lucky in life.

And so you started at a very early age (16) to do medicine but you ended up not as a clinical professional but rather as a research professional.

At the beginning, you know, I thought I would do medicine… and end up as a cardiologist, or neurologist – I was never going to be a surgeon, I was going to be a physician specializing in some interesting fields.

Two things happened in third year that made the difference.

First of all we had enormous classes… 600 in first year! Quite a few failed… we had very bad staff-to-student ratios… and to be absolutely frank we were pretty badly taught. So in my third year a few of us so-called clever kids got together and said, look we’re going to teach one another. We would study up a particular branch of physiology, a particular branch of biochemistry. [We would] then give little seminars to one another, sort of self-help teaching… That got me into the research literature which I found absolutely fascinating.

[Secondly], my elder brother Peter turned to academia. He became a biochemist and a senior lecturer in biochemistry at the University of Adelaide. I think a little bit of hero worship for my brother also helped.

You mentioned that your brother was a mentor and someone who you looked up to, did you also have any other role models and mentors?

Ah, well that’s a very wonderful question that has a very direct answer! I’m unbelievably lucky to have had two quite outstanding mentors.

The first one was Sir McFarlane Burnett. He was the director of the Walter and Eliza Hall Institute, arguably Australia’s greatest biologist ever. It was because of wanting to work under him that I moved from Sydney to Melbourne. I’d been a resident at Prince Alfred hospital and very happy there… but moved to Melbourne in 1957 as a 26 year old young man particularly to work with Burnett, and he was a fantastic mentor.

The second one was my mentor for the postdoctoral period in the United States at Stanford University for one and a half years from… ’59 to ’61, and his name was Josh Lederberg… he also was a Noble laureate.

The two were very different: Burnett was quite contemplative, stern, aloof. He was not much good in a robust discussion, he had to take the problem away studied in a quiet room at night. [He would] come back two or three days later with suggestions and an answer, but wise and deep.

The second chap, Josh Lederberg was a real slow coach, he actually took until age 33 to win the Nobel Prize! The second youngest Nobel Prize winner in medicine ever… So Josh was lightning fast, he loved a robust debate… You could try and expand some kind of scientific idea and he would say, “Yes, yes go on, I’ve got that point, make your next point.”

I worked in his department of Genetics at Stanford University. He was also very interested in what he called Exo-biology (a field which he started) which was about searching for life in outer space. He devised instrumentation that went to the moon to try and gather particles and bring them back and see if they had life.

His other great passion… was computers in medicine. He was really the first one to decide there’s got to be immense potential here. He wrote some of the early programs; for example searching for drugs via images in the computer.

Both of those people took me under their wing sequentially. I had the hugest respect for each of them and they were so different.

How did they affect your career pathway as mentors?

Well each of them… promoted my career. Burnett facilitated my move to Lederberg’s Laboratory. Lederberg… made me an assistant professor after he said “look it’s going to look better on your curriculum vitae than just postdoctoral fellow.” After my planned time there had expired he said, “I’d like you to stay at least another five years and become an associate professor,” which was the next rung up in the career lever. I said “look I’ve really got my heart set on going back to Australia for family reasons.” I could also see Burnett’s retirement not so far off, and maybe I’d even get a tilt at being director of Walter and Eliza Hall myself.

So each of them furthered my career in their own way.

“Try harder to learn than to shine”

Would you be able to speak about some of the failures that you’ve had in your life since [your early career], and what did you learn from that?

Where I have failed, I think, is I’m not a very creative person. I’m very good at analysis, I’ve got tonnes of drive – stick with this go follow your goal to the absolute end. But, of course, to be a great scientist you’ve also got to have a ton of imagination, and to be frank I haven’t got that.

So if you could give one piece of advice to your younger self what would it be would be?

The advice that I would give my younger self is – try harder to learn than to shine.

It was always my insane ambition to be brilliant, to excel. Now if I’d quietened down a bit – I’ve got this opportunity now that to learn… I’m going to learn. I’m gonna put “to shine” to one side. There’s a difference.

Based on everything that we’ve spoken about, how would someone know if they’re on right pathway?

Well of course one simplistic and obvious answer… is if you’re on the right pathway your grades and your achievements in exams and so forth will show it.

I think more important than that is whether you are being true to yourself in terms of the goal setting and the pathway forward. You set out to do something and you say to yourself “I want to do this – I want to become a surgeon, and to do that I’ve got to do medicine, and afterwards I’ve got to do a residency, and after that I’ve got to be a surgical assistant,” and so forth.

Are you in fact being true to the path that you set yourself? If you’ve set yourself a path to be a good carpenter or to be a plumber or whatever it is [ask yourself] “am I in fact on that track, or have I allowed myself to be diverted?”

Would you say that’s one of the most important thing that people can get out of studies and work, or are there other key factors that people should be trying to?

Well of course out of studies and work, the first and most important thing is to develop a skill set… To be a surgeon you gotta be dexterous you’ve gotta know where to cut, you’ve gotta know when to cut and so forth. So it is very important to develop a skill set, but also it’s very important to dream a little bit… They say a person’s reach should exceed their grasp – dream a little bit more, dream a little bit further. Try to be the very best person that you can in your chosen field.

Would there be any other tips that you can offer specifically the students who are trying to start their journey in the world of research or science?

Yes there’d be two things that I’d say to the young person who is contemplating a career in research.

The first is think big! Choose some goal that is meaningful, don’t bother about being the one to cross the T’s or dot the I’s, or fill in some tiny little detail about Multiple Sclerosis… and so forth. Think big! Espouse big and ambitious goals. You won’t reach them, but if you don’t aim high, you certainly will not get to a high point in your research… Try and extend that concept in as many directions as you can.

The second thing is – and it’s very interesting how little students think about this – be very careful about the choice of a mentor!

If you just listen to the person who’s your lecturer in physiology [and say] “oh that lecture on hematology sounded pretty interested, I’m gonna do my Bachelor of medical science with that woman…”

Now, if you haven’t done your research you might pick up absolute lemon, who just happens to be an intriguing lecturer that’s got a bit of flair for an acting. By doing your research, I mean particularly look into the question of whether that person has got some achievements in research. They might not be very charismatic, but they might have that kind of depth and reality of expertise that you’re looking for.

I’m often amazed at how little effort people put into the choice of their mentor; how that’s an almost accidental thing as they breeze through their course.

You mentioned that you should look into their research or their achievements… Are there any specifics… that people should look for?

Again this is not so obvious, I wouldn’t look so much for numbers of publications. I’d look for the quality of the journals in which the person publishes. You know it’s pretty easy to get a paper published… Everybody knows that for the short articles it’s Nature in the UK or Science in the US. For the more deliberate of articles it might be the Journal of Experimental Medicine or Cell. It’s not likely to be the Pakistani Journal of Wellness. And that’s quite an important trick.

A second thing that you can do… don’t just look for the number of publications, look for the number of citations!

How often has a scientist published something that another scientist will want to quote in her paper? That’s now much easier to be done than it used to be in my day. You can actually find out how often a particular article has been cited.

On the future of science and research

You oversee cutting-edge research in immunology and clinical science. What do you think the future holds for individuals working in these fields or for the field?

It’s a marvellous time to be young in medical science. There are so many openings and that is because the technologies that we have today are so powerful.  We have learned so much in the past as a platform on which to gaze into the future. I think the future in medical science is going to be quite remarkable.

Now if you are talking specifics, they would be three things that I would mention:

1. Instrumentation – The synchrotron at Monash University is just one example of a really sophisticated instrument that allows you to do so many things.
2. Gene sequencing – trying to figure out the details of the DNA of particular cells of particular individuals, giving you a depth of insight.
3. Bioinformatics – you can now extract wisdom and depth and interest from masses of data that, at first, appear to be particularly interesting. If we have other data cross-interrogated smartly enough, then you can learn very interesting new things.

What do you think of impact of technologies like Artificial Intelligence in expanding these fields?

Well I don’t know a great deal about artificial intelligence but I can tell you one thing: The last Nobel Prize in medicine was very smartly awarded.

[The prize] went to two guys – James Alison… and Tasuku Honjo… They discovered something… incredibly simple; they discovered that you can activate something by inhibiting the inhibitor. Now let me say that a little bit more simply… Think of the immune response – [it] depends on dividing cells. Those first cells keep dividing, dividing, dividing – they take over your whole body and you’ll become a mass of white blood cells and nothing else.

There’s got be something that holds those back and that’s what we call T-regs, or… suppressor cells. The suppressor cells are always there to put a limit on the degree to which an immune response rolls forward. And it turns out that in the cancer cell field, your own lymphocytes are trying to beat that cancer. And they do! It’s been shown quite conclusively that immunodeficient people have a much higher incidence of cancer. The immune system does prevent cancers from developing, but there’s somewhere it fails. And in those situations if you destroy or inhibit those suppressor cells you unleashed the bodies’ cells to fight the cancer better.

That was first shown for melanoma. It’s now also true for lung cancer and breast cancer. Goodness knows where that field will go. I think that there’s a tremendous field to follow.

Well I wanted to thank you very much for your time. I think you’ve really helped give insight to people who are interested in careers in research and science. I’m sure you will continue to inspire people to pursue careers in research and in science.

And for the young people I would say – continue with your dream.

I’ll tell you this: most people in research don’t make much money but boy do they have an exciting life, they have a wonderful life. Pitting yourself against the unknown, breasting these particular challenges. Young people, give it a go, you’ll enjoy it!

About the Guest

Sir Gustav Nossal is a distinguished Australian biology research, specialising in antibody formation and immunology. He attended The University of Sydney, graduating with First Class Honours.

While working at the Walter and Eliza Hall Institute of medicine he received his PhD. The main focus of this was on Immunology and antibody formation.

Sir Nossal has since gone on to be recognised with almost every honour and award scientists can be recognised with. This includes the Albert Einstein world award of science and Australian of the Year.

Sir Nossal was knighted by the Queen for his ground-breaking research. He has headed the world-leading Walter and Eliza Hall research institute since the age of 35. He has worked with some incredible people and organisations like the Bill and Melinda Gates Foundation.

Sir Nossal has received numerous lifetime achievement awards for his contribution to medicine and biology.