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May 25

Would you like to win a Nobel Prize?

Interveiw with Nobel Prize Winner Peter Doherty.

by Dick Ahlstrom

Top tip: If you want to win a Nobel Prize don’t study veterinary science, this advice courtesy of a Nobel laureate who happens to be a veterinarian.

Peter Doherty won the Nobel in physiology or medicine in 1996 with Rolf Zinkernagel for the discovery of how our immune systems recognise virus-infected cells. Yet he is full of interesting stories about other things, field work as a vet, teaching science, and his predilection for non-conformism, something that should help make his plenary lecture at next July’s Euroscience Open Forum meeting in Dublin a must attend event.

You would want to hear him speak if only because he is named an “Australian Living Treasure” by that country’s National Trust. But it could all have been very different had he followed his original inclinations. “I was kind of interested in language and literature,” he says of his early schooling. He thought he might pursue that when he turned towards university, but thought again. “I decided I wanted to do something practical so I decided to do veterinary science.”

He acknowledges the arbitrariness of his choice given the gravity of such a choice. “I was 17 and no 17 year old boy is remotely sure about making that kind of decision,” he admits. And yet the humanities’ loss later became with world’s gain as Doherty came to make his profoundly important discovery about the operation of our immune systems.

He was born in the sub-tropical city of Brisbane, Queensland, doing his secondary school studies at Indooroopilly State High School. He admits to being deeply influenced by his two grandmothers, one a devout Methodist and the other a lapsed Quaker, a Brit from the old country. Back along the family tree there were also ties to Co Louth dating to the 1840s, undoubtedly a connection that left him with very fair skin and the conviction that he was totally unsuited for life in a city that he says is described as the melanoma capital of the world.

You would wonder then how he decided to choose the outdoor life as it were, field work as a big animal vet. He signed on at the University of Queensland’s vet school and found himself spending long holidays working on sheep and cattle farms and working with rural veterinarians.

While there he studied a range of relevant sciences and worked with leading lights in ecology, population genetics, infectious disease and parasitology. Having won a scholarship to study at Queensland, he also was left with the later payback as a “bonded” scholar, working for several years in the Queensland Department of Agriculture and Stock. “I expressed enthusiasm for laboratory-based research, so the Department immediately sent me to the country as a rural veterinary officer,” as he later described in writings published as part of the Nobel Prize Lectures.

He soon got even though. Dutifully driving great distances between farms reporting dead livestock in order to conduct post mortems, he soon come up with a diagnosis of Trichomoniasis, a venereal disease, in an area where the authorities believed total eradication had been achieved.

Realising that he now represented a danger to the Department’s regulatory efforts, he was whisked back to the state veterinary laboratory, the Animal Research Institute at Yeerongpilly. Here he studied animal disease, particularly Leptospira Pomona which can infect animals as well as humans.

 He can thank the Lab at Yeerongpilly for encouraging his interest in virology, but also for helping him find a wife. He married microbiology graduate at the lab Penny Stephens in 1965.

From this point on Doherty followed his scientific nose, looking for more training and experience in virology. He signed on for a PhD at the Moredun Research Institute in Edinburgh that had an affiliation with the University of Edinburgh. The Moredun was running a large programme looking at sheep scrapie and he signed up but then moved from scrapie to the study of a tickborne flavivirus. Importantly he also signed on as a graduate student at Edinburgh’s medical school.

 While the young couple nearly remained in Edinburgh, Doherty was tempted back to Australia, taking a position at the John Curtain School of Medical Research at Canberra in 1971. He immersed himself in immunological analysis using a number of models.

 It was while at the John Curtain School that his path crossed that of Rolf Zinkernagel when the latter arrived there in 1973. As luck would have it Zinkernagel was moved for space reasons into the lab were Doherty was based. The two also lived in the same university housing complex and used to share rides to and from the lab.

 The two began to collaborate and the rest is history. Doherty describes studying everything from sheep to mice, studying killer t cells and the immune system. “We were looking at another question and we got this unexpected result and it seemed intriguing. Sometimes you get really lucky.”

 Together they discovered the “major histocompatibility complex” a mouthful that actually opened up our understanding of how killer T cells recognise and attack virus-infected cells. T cells are part of our acquired immune system, the part that learns each time it recognises and destroys an invading pathogen. It retains a “memory” of the pathogen, ready to pounce and kill if it appears again. Vaccines create this type of immunity against common diseases.

Viruses invade host cells, taking over the cell’s protein factories in order to replicate itself. Killer T cells are able to recognise an infected cell and destroys them so the virus cannot duplicate itself. The two researchers discovered how killer T cells were able to recognise infected cells, identifying a marker or antigen belonging to the virus but also a marker for the major histocompatibility complex. Once both signals are there the killer T cell knows it should attack.

 Both researchers travelled between conferences, giving talks about their discovery. Their ideas contradicted the accepted North American model for immune response genes, something that made those listening to the talks sceptical, Doherty says.

 And despite their research success there was no reward in the form of a long-term appointment at the John Curtain School. Zinkernagel moved on to a faculty position at the Scripps Institute at La Jolla, California and Doherty was offered an associate professorship at the Wistar Institute in Philadelphia, Pennsylvania.

 In more recent years Doherty shares his time between the University of Melbourne and the University of Tennessee. “I am still interested about looking at immunity,” he says, working in Melbourne and conducting further studies of killer T cells. When in the US he is more likely to be working on systems biology.

 Things are much different in the lab today because scientists have powerful new tools that allow you to look much more closely at what is happening within cells, he says. “Now we can really see what is going on.”

 He also finds time to write including his highly entertaining semi-autobiography, The Beginners Guide to Winning the Nobel Prize, published in 2005. It is here were he provided valuable information about how to capture a prize. “I am the first veterinarian to get a Nobel prize,” he says. “People didn’t go to veterinary school looking to win the Nobel prize.”

He is also interested in the challenge of encouraging more students to do science, engineering and maths. These subjects have inbuilt disincentives hwoever. “Part of the problem is [science] is difficult and hard and the job prospects are not good.” Despite his accomplishments at the John Curtain School, he lost his perch because there was no permanent position available for him.

Another deep seated problem about encouraging kids into science is it is often taught by presenting a lot of facts and figures and things that don’t interest young people. The detail seems remote and detached from common experience. It doesn’t have to be taught in this way and while chemistry and physics may unavoidably be more structured, this is not “what biology is fundamentally about. You have to approach it as chaotic”, he says.

 Then there is the issue that when you train in science students only about 10 in 100 will do science. The other 90 will end up doing something else, he says. And yet this is not a bad thing. “Science training is actually good training for looking at data and evidence and assessing evidence,” he believes. It also helps you think clearly. “Lawyers think pretty clearly but in a different way than scientists.”

 At the end of the day however young students need to be told about the excitement inherent in science. “What i tell kids is what really makes you interested is you are discovering something that has never been discovered in the history of the planet.” And that is just what he did.  

 

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