Greg Winter won the Nobel Prize for Chemistry last year in recognition of his work on antibodies. He realised they all have the same basic structure, with only small changes making them specific for one target. This discovery led to antibody therapies for cancer and diseases such as rheumatoid arthritis and multiple sclerosis, which have changed the lives of patients across the world. Here we hear from four people who worked with and benefitted from Greg’s discoveries.
‘Greg had a vision to drive things forward – he encouraged people to think, take risks – there was a clamour to be part of his team.”
Peter Jones had known Greg Winter throughout his academic career but a visit to a famous book shop proved to be the start of something special.
“It was summer of 1984 and I’d been living and working in Germany. I came back to visit friends and family and popped up to Cambridge to stock up on English books in Heffers.
“I called into the lab at the MRC Laboratory of Molecular Biology (MRC LMB) to catch up with Greg and I was fascinated to learn of his work.
“Soon after, he badly injured his arm in a road accident and he asked if I was interested in joining his small group at the MRC LMB working on something new. I was back then, literally, his right-arm man.
“Greg had realised that antibodies would play a pivotal role in medicine and had been developing new techniques to create them.
“Back in the early 1980s, the work in this area had focused on creating rodent-based antibodies which were proving extremely powerful diagnostic tools for both research and medicine but limited in use in humans by rejection as foreign proteins.
“Greg thought we could do better and that we should be able to create antibodies which were completely humanised. This is what science is about – gradually doing more and more to push the boundaries. Greg was creating a team to drive forward what was possible – how could I turn down such an opportunity?
“Over the months, we developed new techniques which were successful but cumbersome and time-consuming but gave rise to humanised and clinically relevant antibodies which would be of use to our friends and neighbours in Addenbrooke’s.
“We felt there was a better way and so we looked at how the human body develops antibodies which, to cut a long story short, ultimately led to the discovery of the phage display.
“To put it simply, it provided a way to identify target-binding antibodies from libraries of billions of different human antibodies without the need to screen each molecule separately.
“The discovery meant we could speed up the process of developing and creating fully human antibodies capable of specifically targeting certain diseases.
“Greg has had vision to drive us forward – to be the bridge between technologies. He is fiercely intelligent, a fast learner and someone who inspired all of us to do more. He was a natural leader who respects your ability and encourages you do your thing. This is incredibly powerful.
“I came back from Germany to work with Greg because I trusted his judgment and that his ideas looked like – and have proved to be – the future.
“If he felt it was the right way to go then I believed him because he viewed things with such clarity and could see a way through. I am glad to have been proved right in so many ways and proud to have worked with Greg until I retired.
“His work not only changed careers, it has changed lives.”
Why should Greg Winter’s breakthroughs and the focus on antibodies be seen as such a success story?
The discovery of antibodies encouraged scientists to develop animal and human blood serums to treat viral and bacterial infections.
However, developing antibodies to treat cancer and autoimmune disease has major problems. Scientists have to identify and isolate the disease target – they can be a tiny part in a complex mixture of human proteins (think of it as a needle in a haystack) but they also needed to get the body’s immune system to response positively and not reject the treatment.
By pioneering a technique to ‘humanise’ mouse monoclonal antibodies and then developing methods for making fully human antibodies, Greg found a way to develop treatments which were less likely to provoke an immune response in patients.
Today, monoclonal antibodies account for a third of all new treatments. These include products for breast cancer, leukaemia, asthma, arthritis, psoriasis and transplant rejection, and dozens more that are in late-stage clinical trials.
‘It was like a magic wand …it put my life back in the fast lane’
Theresa Langford went back to motorcycle sidecar racingTheresa Langford worked at the MRC Laboratory of Molecular Biology (MRC LMB) for 29 years, working her way up to become the Head of Biological Services Group.
During her time, while aware of Greg Winter’s work, she couldn’t have foreseen the impact it would have on her life after she was diagnosed with Sjogren’s Syndrome at 32.
“I have Sjogren’s Syndrome which the experts think goes back to when I had a glandular fever-like virus when I was 25. Sjogren’s is an autoimmune disorder where the body’s immune system attacks glands that produce fluid, such as the tear and saliva glands. I kept going down with a succession of odd medical issues and felt utterly, utterly exhausted – all classic signs of the syndrome as basically my thyroid gland had packed up.
“The fatigue was more than just being very tired – it was life-drainingly exhausting.
“To do anything was bloody hard work – even getting up was incredibly demanding, and all together, it was depressing. But I had to get up to go to work to pay the mortgage – I am a tenacious person but all my available energy went into my job, I didn’t have the energy for much of a social life. I had a simple choice: work or anything else.
“This went on year after year as I coped with all the ramifications of a succession of illness, until I was finally diagnosed when I was 32 by Ken Smith (who is now professor of medicine and head of the Department of Medicine at the University of Cambridge). He recognised what was happening to me. However, the seven non-biological treatments available at the time which I tried over a number of years were a mixture – some were OK to take but ineffective while others had awful side-effects and my white blood cell level crashed and/or I felt terrible.
“As well as the tiredness and my tear glands practically not working, I developed rheumatoid arthritis which for someone in their 30s was awful.
“I was always aware of Greg Winter’s work from being in the same building as him and had avidly followed any papers which spoke of a breakthrough in this area.
“It was a fairly short succession from starting CAT that Humira was identified as a potential medicine,
and I was accepted onto a clinical trial which involved a drug called etanercept – part of the family of drugs called ‘the biologicals’. This was in February 2005.
“On clinical trials you don’t get told what you are taking (it’s called double-blinded) but the first morning I woke after starting my course I knew I was on the real stuff. It was like a magic wand – there was no other way of describing it. The swelling from the arthritis and the fatigue just melted away.
“My life began to get back to some sort of relative normality especially after several operations to block my tear ducts. I could ride motorbikes and horses again, go camping – I was keen to do everything as my world was opened back up. I could also go back to sidecar racing with my husband and I am still doing it, we recently competed in four European race meetings.
“I stopped taking etanercept in 2014 as after tests it seemed the rheumatoid arthritis had gone. We aren’t quite sure why but I can only express my huge gratitude to Greg, the people who developed ‘the biologicals’ and the systems we have in place in the UK to allow for such research to take place, from the government grants to the animal research.
“I should also mention the various support groups too – especially the Cambridge branch of the British Sjogrens Syndrome Association, without them I would have been in a very different place.
“I sometimes wonder what would have happened if etnaercept hadn’t been invented. I had worked my way through all the other treatments – there was nothing else left which was either effective or not toxic. I suppose I would have gone back to the least bad and just plodded on.
“I would have had a different career path or not been able to do all the things I wanted to and everything which went with it – and it would have been painful and bloody miserable.
“So I count myself as exceptionally lucky it worked.” Why should Greg Winter’s breakthroughs and the focus on antibodies be seen as such a success story?