04 Oct 2016
20 years on, what impact has the Nobel Prize for medicine had on our immune systems?
This article was written by Professor Sharon Lewin for The Conversation.
This time of year, Australians obsess over an annual spectacle that celebrates the achievements of our most gifted citizens – though usually, they’re fixating on their respective football codes.
But an even bigger prize is up for grabs tonight – the Nobel Prize in Physiology or Medicine. It’s the first of a big week celebrating the international heroes who receive Nobel Prizes for a range of disciplines, from physics, to economics, to literature.
Twenty years ago, the Nobel Prize in Physiology or Medicine was awarded jointly to Peter Doherty and Rolf Zinkernagel “for their discoveries concerning the specificity of the cell mediated immune defence”.
What did they find?
Doherty and Zinkernagel made their Nobel-winning discovery while working at Canberra’s Australian National University (ANU) in the early 1970s. Doherty, a veterinarian from Queensland, had only just returned to Canberra to set up a laboratory as an independent scientist. Zinkernagel had come to the ANU from Switzerland in 1973 to do his PhD.
The pair happened to share a lab and started talking. A year later, they co-authored two landmark papers in Nature, the Rolls-Royce journal for scientists in all disciplines globally.
Doherty and Zinkernagel had discovered how one critical part of the immune system, the T-cell, recognised and killed virus-infected cells. These killer T-cells patrol our bodies looking for foreign enemies – such as infections or cancer cells – and then move in to attack.
What Doherty and Zinkernagel discovered was the exquisite elegance with which the killer T-cells recognise the enemy.
They proved a radical new idea of how T-cells worked by recognising an “altered self”: the enemy (for example, a virus) could only be recognised when it was presented in combination with the body’s own machinery.
The body’s protein alone or the virus alone didn’t generate the molecular target for the killer T-cell to recognise.
Sounds simple, but the concept was revolutionary.
At the time, Doherty and Zinkernagel were studying mice infected with a virus called lymphocytic choriomeningitis virus (LCMV). But they and others went on to demonstrate that exactly the same process is used to tackle diseases as diverse as influenza, HIV and cancer. The implications of their findings have been spectacular and far-reaching.
In Doherty’s Nobel speech, given in 1996 in Stockholm, he credited for his success the local intellectual environment in Canberra, the excellence in immunology across Australia and that there was “time to discuss and think things through” in the pre-fax, pre-email days. I suspect there was a bit more to it!
What does it mean for patients?
Doherty and Zinkernagel’s insights into how killer T-cells recognise the enemy proved crucial for understanding how viral infections are controlled. More practically, this understanding now shapes modern treatment strategies for cancer and the design of vaccines.
To recover from the common flu, for example, we need T-cells and antibodies, another arm of the immune system. And recent findings by Katherine Kedzierska, a former trainee with Doherty, have shown how T-cell “memory” protects us against the flu.
Following HIV infection, as in flu, people also generate loads of antibodies and killer T-cells. Neither get rid of HIV completely in anyone. But in some people with the right genetic make-up and the right virus, they manage to keep the virus under control.
The explanation? These so-called “elite controllers” make stunningly potent killer T-cells that are able to recognise part of the HIV virus together with part of the body’s immune system.
This finding in HIV-infected elite controllers has revamped our approach to searching for a successful HIV vaccine. We don’t have one yet, but most think that generating effective killer T-cells will be critical.
Great strides have been made in the last few years about how to harness killer T-cells for cancer therapy. These drugs have literally just hit the clinic – only 12 months ago in Australia – with some spectacular results.
In cancer (and in chronic infections such as HIV and indeed LCMV), killer T-cells can become exhausted. They are massively outnumbered by the enemy and they surrender.
New drugs can now revitalise these exhausted T-cells, returning them to their fighting-fit selves. These drugs have transformed the outlook for some cancers, such as melanoma and lung cancer, but only in some people. There are still many puzzles to be solved in this new era of immunotherapy.
What’s next?
After 14 years in the United States working at St Jude Children’s Research Hospital in Memphis, Doherty returned to Australia and the University of Melbourne in 2002. He continued to train and mentor generations of scientists, many of whom still work on killer T-cells and how they tackle viruses like influenza.
The tools of modern immunology have changed. But the principles of good science – intense curiosity to solve a problem, asking the right question and planning the right experiments – are the same now as in 1973.
In 2014, the Doherty Institute was opened. As patron and namesake, Peter still loves to talk science and to interact with young researchers. A joint venture between the University of Melbourne and Royal Melbourne Hospital, the institute has more than 700 staff, all working on infection and immunity.
From basic discovery research, through to clinical and translational research and public health, the institute has the vision to improve health globally through discovery research and the prevention, treatment and cure of infectious diseases. To achieve this ambitious goal, we will use the same principles of great science, “time to talk and think things through” and the humanitarian values of its namesake to continue Peter’s legacy.
Tonight when we hear the next inspiring stories from the winner of the 2016 Nobel Prize in Medicine or Physiology, we should be immensely proud of what Peter Doherty and our own scientists have achieved – and what’s yet to come.
Thanks to Professor Andrew Brooks and Associate Professor Katherine Kedzierska for helpful discussions and input.