The campaigner

Following a 30-year stint heading up the Walter and Eliza Hall Institute, Sir Gustav Nossal is now a top level advisor helping to advance the cause of global health. Here he reflects on his long and fruitful career.

Australian Life Scientist: How did you get your start in medical science?

Sir Gus Nossal: I wanted to be a doctor for as long as I can remember. Certainly at least from about the age of seven. It probably relates to a kind of hero worship that my parents had of their own paediatrician. I was quite a sickly little boy: I had diphtheria, I had whooping cough and my parents didn’t believe in immunisation at that stage, this being the 1930s. It was the healing hand of the doctor to the forehead that helped me - there was not much else they could do in those days. I think that’s where it came from.

So off I trotted to become a doctor in 1948. This was still at a time when the ex-service men and women were streaming into universities as part of their resettlement. There was no quota, so anyone who matriculated and had the money for the modest fees could get into medicine. We were the first year of 600.

The universities were woefully underfunded. The staff/student ratios were execrable. I essentially wasted the first two years at this university; I didn’t learn a thing, besides from some horrible anatomy. So we started asking what were we going to do about execrable teaching?

In the third year, about a dozen or so of us so-called ‘clever kids’ decided to teach one another. We would take a subject in physiology or biology, chemistry, neuroanatomy, etc. We would study in the library, not from primary resources, but from reviews, and then give each other seminars. This worked extraordinarily well. We taught each other a lot. That got me blooded in research. That thrill, particularly in biochemistry, of being there at the cutting edge.

At the end of my third year, I went to see the Dean, Sir Harold Dew - who, by the way, was a first-assistant at WEHI. I said I would like to do what was then a completely new course, only two years old: a bachelor of science medical. That meant taking a year off and becoming a research apprentice in a laboratory, and at the end of the year you were a bachelor of science medical. It was a way of getting, on the cheap, a bit of a blooding in research.

The Dean said: “No, you don’t want to do a year in biochemistry, there are plenty of PhDs to do that. I want you to do something of a more clinical nature. In fact, I want you to do a year of virology, with a senior lecturer with a biochemistry bent: Patrick de Burgh.”

Pat de Burgh was not a famous man, but he had very fine scientific tastes. Would you believe, Don Metcalf, Jacques Miller and I all got our start with Pat de Burgh?

So Pat took me and one other student down to Melbourne to spend a week there to see what ‘real research’ was like. Of course I was utterly hooked. I was 21, completely naive, and the thought of being in a lab that did research at international levels, published in Nature, it was unbelievable. That, in a sense, was the sealing of my destiny.

So off I trot to Melbourne in 1957. I walk in and Macfarlane Burnet says: “It’s great to have you; however, I have one thing to tell you: we are no longer studying viruses. We’re studying the immune system defence against viruses.”

And, of course, the bottom fell out of my world. The way we’d be taught, immunology was about the most boring subject there was. But unbeknownst to me, Burnet had identified a wave before it crested. And, of course, I became an immunologist.

ALS: In your area of immunology, a great deal has changed over the span of your career. We now have new avenues to produce vaccines, such as the DNA vaccines Ian Frazer is working on, yet a malaria vaccine remains elusive. Why is that?

GN: I’m tempted to say that the alluvial gold has gone. We’ve had a wonderful decade with the so-called conjugate vaccines for the encapsulated bacteria pneumococcus, meningococcus, even Haemophilus influenzae B - great vaccines that have virtually made meningitis a thing of the past.

In a manner of speaking, these are straightforward vaccines. What that leaves us with is the tough problems. By these I mean disease whereby nature itself does not produce robust immunity. Have you ever pondered the fact that a person can harbour HIV for 20 years and still not become immune? Or, for that matter, tubercle bacillus, where we sometimes pacify it, but when we age or we’re under stress, out it pops.

Malaria is perhaps the doyen of these, having co-evolved with humanity for all human history. This wily foe has learned the Joseph’s Coat of Many Colours. It has learned to change itself to dodge away from immune response. Whereas people living in endemic areas develop a modest non-sterilising immunity; therefore they probably will not die of the disease, they’re never really fully immune.

What I’m saying is, in these more complex diseases, and malaria is the paradigm, we have to be smarter than nature. My old boss, Mac Burnet, used to say: “Gus, a malaria vaccine will never work because nature hasn’t meant there to be immunity.” I replied that there are lots of things like flying where we’re doing better than nature. But he was right in that we have to figure out a way to engender an immune response which the disease itself does not do.

ALS: After 30 years heading up the Walter and Eliza Hall, how did you come to make the transition from research to advocacy, working with the World Health Organization and the Bill and Melinda Gates Foundation?

GN: The decision to leave research was not an easy one. I still have a very bittersweet recurrent dream of being back in the lab doing something fiendishly difficult - I always loved technical challenges in the lab. And the dream is both happy and sad: I’m happy being in the lab, but I’m sad to know in my dreaming state that it’s not really true. I miss research frightfully. Now comes the “but” ...

When I retired as director of the Walter and Eliza Hall Institute after a 30-year period, I had a fairly fundamental decision to make. I said to myself, I can do what I’m doing on large scale, but only on a small scale. Or I could do something different.

That was where happenchance played a big role, because I always had a side interest in the World Health Organization. In fact, I’d been on committees since 1964, and with the march of time, the chairman of some important ones. I had been chairman for a dreadfully long period of the committee felicitously named SAGE - Strategic Advisory Group of Experts - on everything to do with vaccines and biologicals. Someone stuck my name in front of Gates Foundation and I was made the founding chairman of the strategic advisory council of the Bill and Melinda Gates Children’s Vaccine Program back in 1997, even before the Foundation was fully established. I held that post until 2003.

So I said, gosh, why not make my night job my day job? Why not have a change of life and a complete change of scene and go into advocacy, peer group reviewing, promotion, guidance of third world health etc. And that’s what I chose to do. It was an on-balance decision and I freely admit that in my darker moments I wonder if Don Metcalf made a better choice to stay at the laboratory bench. I can’t answer that. In any case, it has been a very great success and I have developed a second career through it.

ALS: And what are some of the wins you feel you have achieved in the advocacy role?

GN: The biggest single success was something we called GAVI, or the Global Alliance for Vaccines and Immunisation, which is now called the GAVI Alliance. In January 2000 we launched GAVI with a magnificent initial gift of $750 million, which has since doubled and has been buttressed by various governments around the world.

The end result is that immunisation rates in the 72 poorest countries in the world have gone up to 82%, which is still not absolutely fantastic, but is very good. Newer vaccines have been added as they’ve become available. And it’s now, I think, one of the most successful public health programs in the world. That would have to be my number one achievement that I look back on.

Number two is closer to research. The Gates Foundation decided to launch what they call the Grand Challenges Program, which eventually morphed into Grand Challenges Explorations. This includes both very large grants and very adventurous small grants where, for the sake of a two-page application, you could get your first $100,000. That’s been a very exciting program, and at that level they can give out a lot of them. In terms of Grant Challenges, I’ve been very intimately involved from the beginning, and am still heavily involved in peer group reviewing and chairing and so forth.

As that program has matured, and is now run by a very well oiled bureaucracy, I was asked to become the chairman of a small group, the Discovery Experts Group. Roughly, of the $3.5 billion that the Gates Foundation spends annually, only about a quarter goes to blue sky discovery-style research, a half goes to development and a quarter goes to program implementation. For that first quarter - which, of course, has really been my life, namely discovery science - I’m guiding them on strategies and long-range perspectives. That is still a work in progress - I’m in my third year as chairman - but it’s extraordinarily enjoyable and very challenging.

ALS: What are some of the areas where progress hasn’t happened as fast as you would have liked?

GN: Progress for vaccines against the big three: HIV/AIDS, malaria, tuberculosis. Not even the most optimistic person in the world could say they’re anything other than disappointed in this area. That doesn’t mean we’ve given up, but there’s obviously a long way to go before we can develop a vaccine that can face up to broad-scale use.

Second is how far we are from the Millennium Development goals as far as deaths in childbirth are concerned. Would you believe that deaths through pregnancy or childbirth are 400 times more common in the worst country in the world versus the best. Four hundred times! The three main causes - obstructive labour, haemorrhaging and sepsis - are all eminently treatable even with fairly basic health systems. But the health systems are not advanced enough in many of these countries. That’s been very disappointing.

The third, which is gaining momentum and needs to be strongly supported, is genetically modified foods and GM staple crops to add protein, vitamin and mineral content. There’s not so much calorie malnutrition in the world, but there’s plenty of protein malnutrition, and certainly micronutrient deficiency. The big ones are vitamin A, iron, iodine and zinc. If we can get more of that into the staple foods of the developing countries, we can save a lot of lives.

ALS: You’ve long been an advocate for vaccinations. Yet it seems today that there are many societal and cultural pressures emerging that are against vaccines. What happened? And how do we turn this trend around?

GN: It’s a very paradoxical thing. In fact, vaccines have become the prisoners of their own success. The very fact that vaccines have been so successful means that mums and dads no longer have any first-hand evidence of what the epidemics of the past were like. They don’t see a hundred beds in an infectious disease hospital with kids with infantile paralysis in iron lungs. They don’t see the complications that arise from measles, which is a disease that everybody got when it wasn’t immunised. Until quite recently, they didn’t see whooping babies on their television sets. They certainly don’t see the devastation of meningitis today because it’s all but gone because of vaccines.

So this absence of first-hand evidence of a real rip-roaring epidemic has bred, on the one hand, complacency, and on the other, an obsession with adverse events. That hasn’t been helped by some totally spurious claims like that the MMR vaccine causes autism.

The funny thing is, as we have one of the highest vaccination rates in the world - around 92-93% - the parents of the unimmunised kids can afford the luxury of their conscientious objection because of herd immunity.

That’s the story. The adverse events, and we never deny they do occur, are vanishingly rare. And the risk/benefit equation is vastly in favour of having the vaccine rather than having the disease.

The only way to combat this is sweet reason. I’ve said to people: look at what’s happening in developing countries. Look at the amazing fall in mortality as immunisation takes hold. And then look at the stats in our own country. We have very good graphs in the new Australian Academy of Science brochure on vaccines. It has the incidence of deaths per year for something like measles or diphtheria, and a red arrow showing when the vaccine was introduced. And you see deaths falling to nothing. Fortunately, thank God, we haven’t had a measles death for quite a few years, whereas they would be numbered in hundreds in years before the vaccine. People find that persuasive.

Then you take the adverse events one by one and go through them. You show them the studies that show that the link between autism and the MMR is nonsense. If you have the time, many can be persuaded.

On the other hand, there are some people with minds made up - people who’s mind you’ll never change - and to those you give their democratic right to believe what they want believe. And if that’s only 2-3% we can probably put up with that.

But sweet reason goes a long way.