Peter Doherty, 20 years after the Nobel Prize

Monday, Sep 12, 2016, 05:52 AM | Source: Pursuit

Peter Doherty AC

The phone call comes on the first Monday in October, as unswerving Swedish protocol dictates. Unaware of this, Penny Doherty answered with the trepidation a 4.20am call inevitably invites. “This is Nils Ringertz, from the Nobel Foundation.” So this would be good news. She passed the phone to her husband.

Peter Doherty learned that morning, October 7, 1996, that he would share the Nobel Prize for Medicine with his Swiss friend and colleague Rolf Zinkernagel, recognition for a discovery the pair had made in a laboratory in Canberra in the mid-‘70s. He was then only the fifth Australian scientist to gain the honour in the years since three more have joined the club. (Australia has 16 Nobel Laureates across all disciplines.) He had a 10-minute window to dial out to share the news, Ringertz advised, after which things would get rather busy. And so it began.

20 years ago Peter Doherty and his research partner Rolf Zinkernagel were awarded their Nobel Prizes.

Today, the buzz and burnish of that Nobel Prize is undiminished. When we meet in his office high in the gleaming Peter Doherty Institute for Infection and Immunity – a joint venture between the University of Melbourne and the Royal Melbourne Hospital of which he is the namesake and Patron – the 16th International Congress of Immunology is in town. The professor, nudging 76, runs the gauntlet of star-struck young scientists wanting to get a picture with him. As a rule he’s an out-and-proud curmudgeon when it comes to celebrity culture and selfies, but this he cheerfully endures in the name of science.

“It’s been a great meeting – a lot of young people speaking, a lot of dynamism in the field. If you had looked at immunology 10 years ago there were almost no immunological products being used in treatment, now there are masses of them.”

A storied career

The 20th anniversary of his Nobel Prize inspires reflection on the other milestones of his long career. It’s almost 60 years since 16-year-old Doherty abandoned a yearning to become a journalist, for which we can all be thankful to the anonymous “scatty, sexy, chain-smoking” young woman in a white coat “and not much else” he encountered at a University of Queensland open day.

He credits her with inspiring the notion that biology could be quite interesting. University also promised a ticket out of the hardscrabble west Brisbane suburb where he grew up, “and getting out of Oxley was a major driver”. (For the record, the next big thing to come out of that neighbourhood was Pauline Hanson.)

Professor Doherty in his offices at the Doherty Institute. Picture: Paul Burston

It’s 50 years since he published his first scientific paper and, having moved from veterinary science to basic immunology, more than 40 years since the discoveries that secured his place in medical history. This latest immunology congress is the 14th of these triennial gatherings he has attended, and he’s quietly thrilled to recognise a little of his legacy in the presentations.

Much of the super-charged energy is around the potential of immunotherapy to treat and beat various cancers, including some that have been until now almost inevitably fatal. The insights being enlisted in the laboratory to achieve these breakthroughs “have some early beginnings in the work we did, you can see the lineage,” Professor Doherty says. “And that is very gratifying.”

Working together at the John Curtin School of Medical Research in Canberra from 1973 to 1975, Doherty and Zinkernagal discovered how the immune system recognises virus-infected cells, laying the foundation for understanding how the cellular immune system scans for both foreign microorganisms and molecules from the self. This knowledge underwrites the continuing, epic campaign by scientists worldwide to enlist the body’s own defences to fight disease.

Professor Doherty at St Jude Children’s Research Hospital, Memphis, in the early 90s.

The pair focused their attention on killer T cells – “the serial killers who bump off cells that have gone wrong – virus infected cells,” explains Professor Doherty. “But what we’ve known for a long time is that these cells are also sitting around in a lot of forms of cancer, but they are not doing anything.

“Over the years a lot of people have tried to wake them up. Back in 1995, a guy called (Professor) Jim Allison came to the conclusion that T cells are actually being turned off, and he could turn them on again. And he pursued that with really basic experiments on mice for decades. Then he moved from the University of California, Berkeley, to work with cancer doctors (at Memorial Sloan Kettering Cancer Center in New York) who were interested in the possibility that blocking these checkpoint inhibitors in patients would turn the killers back on.”

Jim Allison was the headline act at the recent Melbourne congress, and Doherty has him on short odds for a future Nobel Prize. Due to Allison’s efforts the dream of recruiting the body’s own immune system to fight cancer is becoming a reality, with more and more stories of seemingly unbeatable cancers shrinking and even vanishing thanks to drugs like Keytruda. In the US it’s become known as the Jimmy Carter drug, after the former President’s miraculous recovery from aggressive cancers. In Melbourne, it’s worked its way into public consciousness as the one that saved former lord mayor and business leader Ron Walker.

The Doherty Institute in Parkville, part of Melbourne’s world-renowned bio-medical precinct.

“In many of these cancers, like melanoma, oncologists knew at a certain stage that the patient was going to die. But now in 20 per cent of such cases, by blocking these checkpoint inhibitors, it’s possible to bring them back,” says Professor Doherty.

“Even so, while it’s possible to turn these serial killers back on and wipe out tumours, the big question now is how to get the success rate way up above 20 per cent. Perhaps we can improve the situation by combining the checkpoint inhibitors with, say, a vaccine, but that will take a lot more research.”

Meanwhile, the stumbling block is that these new drugs are still impossibly expensive. Keytruda can cost $120,000 a year unsubsidised. “But it really is an incredible time in biomedical science.” And it is, Professor Doherty says, another potent reminder of the need for government and society to invest in audacious, long-haul, exploratory science. “The point is that if you want to do this stuff, if you want to have impact, you’ve got to do the basic science.”

Too often the thinking that comes out of Canberra is to just jump into the glamorous end-stage of medical research. But “if you don’t have the intellectual property, you’re not going to be doing it. And you don’t have a scientific culture if you just do end stage trials”.

as an author

Professor Doherty has been spruiking this message loudly, spurred by cuts to the Australian Research Council, which funds a lot of very basic research, and to the CSIRO. “No strategy was made to protect what people talk about as ‘public good’ science, but which I think of as long-term economic good science: climate science, tide science, soil science, water science, all absolutely essential to our future.”

It’s the latest shameless deployment of his Nobel status to explain, promote and defend science. He’s written five books that tackle these themes in various ways, from the autobiographical The Beginner’s Guide to Winning the Nobel Prize (The Miegunyah Press 2005) to The Knowledge Wars (MUP 2015).

He’s become an emphatic, often infuriated Tweeter (@ProfPCDoherty), particularly on research, policy and politics around climate change, advocating forcefully for urgent and dramatic action to try to haul down emissions.

“Many probably think I’m a mad leftie. But then I’m pro-GM and think we should think seriously about using nuclear power.” He’s unapologetic – indeed reassured – if a carefully considered position puts him on the nose with all sides.

“People can listen to me or not. Do they take notice because of the Nobel Prize?” He shrugs. But as he explained laying out his motives in his first book, he has no qualms about enlisting the Nobel gravitas to be heard in politics and society as much as in science. He sees the prize as a device for focusing the attention of society on values that “relate to rational, evidence-based enquiry, truth and peace, the basic building blocks of prosperity and of participatory democracy”. Call it Nobel oblige.

Professor Doherty with a researcher.

That said, the beauty of bench research in the laboratory is that in the end you know precisely what you have proven, or disproven, and with what plus or minus degree of confidence. In science communication, “you can never know how effective or ineffective the message is. It is very hard to cut through, very hard to get across what science is and how it works. Journalists won’t read it, politicians won’t read it. It’s sad, actually. It’s not hard”.

In The Knowledge Wars he walks non-scientists through how to check out the credentials of a person claiming scientific expertise; how to read a paper; and how to judge the merits of a particular journal and the process of peer review.

All this is shared to try to overcome the disillusionment and disinformation that mires modern science, despite its astonishing success. In the medical realm he observes that his father died of cardiovascular disease aged 48, and that without taking statins he would likely not have lived long enough to claim his Nobel Prize.

challenges for science

“Part of that is to do with modern media, where there is all sorts of information out there, but no curating of the information.” He’s maddened by the false-balance equation that plays out in so much “journalism”, which will give a tiny minority of quasi-scientists, celebrities and commentators equal time with an overwhelming majority of credentialed and published opinion. “It’s so depressing, and it is very hard to debate with these people.

“We’re living in a very strange time, a transitional time, and the challenges for science are just enormous.”

Professor Doherty opines with passion, frustration, anger, wit and earthy humility. He will let rip at tin-foil-headed denialist politicians, corporate bullies, and preening commentators, yet pull himself up mid-rant to declare “but I’m an old guy, and the best thing is to do everything possible to see they retire to private life”. Despite all his anxiety about the state of the planet, he still manages to sound notes of optimism, most of them founded on the capability, possibility and energy within the next generation of scientists and, indeed, in all motivated young people who reject cant and hypocrisy.

Peter and Penny Doherty after he had received his Nobel Prize for Medicine.

This is because for all the rarefied aura of “the Swedish effect”, there’s nothing quite like the magic (for want of a more scientific term) that happens in a research laboratory. Peter Doherty cherishes the excitement of those intense, late-night, heart-stopping months of discovery culminating in the moment when a few “spare” mice that an obliging colleague in another program “alienated” for the pair to work on “blew the story wide open”. And the rest was history.

Rolf Zinkernagel is still a close friend – the Dohertys stayed with him in Switzerland last year. Intriguingly, he still has a bit to do with (non-laboratory) mice, at least conceptually. He collects mouse traps, acquiring some 750 of them.

“He has mouse traps that crush mice, traps that drown mice, and a little German mousetrap that actually shoots mice,” Professor Doherty explains with the same tone of bewildered delight he uses to elaborate on the behaviour of T cells. In his retirement Rolf Zinkernagel is working to catalogue the collection, and treks up and down mountains.

Meanwhile Peter Doherty collects Twitter followers (though he despairs that such engagement rarely penetrates beyond the “echo chamber”), is in hot demand as a speaker in scientific and general forums, and shuttles between his work in the University of Melbourne’s Department of Microbiology and Immunology at the Doherty Institute and the St Jude Children’s Research Hospital in Memphis, Tennessee, where he has worked for several months of every year since 1997. He is now easing out of his US faculty obligations, and is working on his sixth book, this one something of a diversion on his previous publications (stay tuned).

“I always intended to retire at 65 and write books. Probably if I hadn’t won the Nobel Prize, nobody would have published them.”

Banner Image: Artwork: Sarah Fisher

University of Melbourne Researchers