Nobel Prize 2018, in Physiology or Medicine

Nobel Prize 2018, in Physiology or Medicine

Dr. A P Jayaraman, (https://www.drapjayaraman.com/science) senior retired BARC nuclear scientist who worked with the likes of Dr R Chidambaram and Dr Anil Kakodkar, whose initials match with the legendary APJ Kalam, very kindly asked me if he could use my FB posts on the Nobel Prizes. It was an honour for me to honour his request. Dr. Jayaraman, post his retirement has been very actively engaged in science communication and is a great friend and philosopher of our science centre. He has received global acclaim for his inimitable style of science story telling and he is also a prolific writer on science and literature. Unfortunately I had missed out FB posting on the Nobel Prize in Medicine and had only posted write ups on Chemistry and Physics Prizes. I am making amends and am posting this write up on the Nobel Prize 2018, in Physiology or Medicine. Though very late some friends may still like to read it.

This year’s coveted Nobel prize in physiology or medicine has been awarded to the two immunologists, Dr. James P Allison, from the University of Texas, MD Anderson Cancer Centre, USA and to Dr. Tasuku Honjo, Professor at Kyoto University in Japan, for their path breaking discoveries of harnessing the power of the immune system to combat cancer.

There are moments in history of scientific achievements that herald the beginning of a new era. The significance of such achievements - the inflexion points - are sometimes very apparent like the General Relativity, which eclipsed the Newtonian classical physics to herald a new era of Quantum mechanics, or Neil Armstrong’s first step onto the surface of the moon, in 1969, which marked a new phase of space exploration. There are however several other advances in science which take many years for their significance to manifest, and this year’s Nobel winning works in medicine is one such example. Our immune system is nature equipped with the best of molecular mechanism to combat diseases. Over the past several years’ scientists, including this year’s Nobel laureates, have been researching to harness the power of our immune system to fight cancer. The very word Cancer, the lexicon of which in itself manifests a terror in the minds of the people, has plagued human society for several centuries and attempts to rid people of cancer dates back to the period since when the disease was first recognised sometime in 1500 BC. However, the idea of using cancer patient’s own immune system to combat cancer is more recent.

The first scientist to postulate that the immune system might control tumours was Paul Ehrlich, the Nobel prize winning German physician and scientist who worked in the fields of haematology, immunology, and antimicrobial chemotherapy. He shared the 1908 Nobel Prize in Medicine with Ilya Ilyich Mechnikov for their work on immunity. Ever since, researchers have tried to harvest the power of the immune system to wipe out cancers. This year’s Nobel Prize winning scientist in Physiology or Medicine, Dr. James P. Allison and Dr. Tasuku Honjo, have succeeded in discovering methods to inhibit negative immune regulation, thus providing a paradigm shift in the way cancer can be treated by stimulating the inherent ability of the human immune response to unleash an attack on cancerous tumour cells. Their research findings have led to new medicines that activate the immune system to fight cancers.

Dr. Allison’s research of over two decades has resulted in the discovery of a protein in the immune system - the T cell protein CTLA-4 - that functions as a brake on the immune response. Dr Allison looked at this protein from a completely different perspective to the one which most others followed of treating it as a target in the treatment of autoimmune disease. He developed an antibody that could bind to this protein and block its function. In the process, Dr Allison and his team found that the CTLA-4, protein blockade could disengage the T-cell brake and unleash the immune system to attack cancer cells, which they observed, could cure cancer while experimenting on the mice. Dr Allison worked on his research to develop a strategy called the immunotherapy for humans, which showed outstanding healing effects in patients with advanced melanoma. His clinical trials on humans showed remarkable results and in several of his patients signs of cancer almost disappeared completely. Allison’s work followed its logical conclusion eventually leading to the development of the drug Yervoy (ipilimumab), which is now used to treat melanoma skin cancer and some other cancers.

Working in parallel, Dr. Tasuku Honjo discovered that another protein PD-1, which is found on the surface of immune cells (T cells) also work as a check point protein. This protein, similar to Dr Allisons’s CTLA-4 protein, functions as a T-cell brake, but with a different mechanism. When this protein was attached to another protein, called the PD-L1 on cancer cells, it could prevent the T cells from recognising the cancer cells, as a result the immune system will not be in a position to destroy the cancer cells. The findings of Dr Honjo meant that blocking the PD-L1 protein on cancer cells, or the corresponding PD-1 protein on immune cells, will allow the immune system to recognise the cancer cells as foreign and attack them. Therapies, which were based on the discovery of Dr Honjo have proved to be strikingly effective in the fight against cancer.

These pioneering works of the two scientists, on the CTLA4 and PD1 immune checkpoints, have revealed that these pathways act as so-called ‘brakes’ on the immune system, and showed that inhibition of these checkpoint pathways allows T cells to more effectively eradicate cancer cells. This research has laid the foundation for the clinical development of immune checkpoint inhibitors, which have dramatically improved outcomes for many people with cancer. These revolutionary findings have established a landmark in the human fight against cancer. Over the past several years, tackling the body’s own immune system to fight cancer has been one of the main focuses of researchers and drugmakers alike. While conferring the two scientists with the award the Nobel committee, said “the immune checkpoint therapy has revolutionised cancer treatment, which has led to the development of several drugs which act as “checkpoint inhibitors”. These drugs when infused into patients, block molecules that put the brakes on T cells. By releasing these brakes, the body’s own immune system is able to fight cancer.

Dr. Allison and Honjo’s works have been pathbreaking that have revolutionised the human understanding of how the immune system recognizes tumor cells. Their works have led to a paradigm shift in clinical oncology, which is likely to alter how we treat cancer in the foreseeable future. Until now the best known tools in the arsenal of oncology doctors for the treatment of cancer have been surgery, radiation therapy and chemotherapy. Sooner than later the new found cancer immunotherapy is likely to equal, or rival, the impact of radiation and chemotherapy for patients diagnosed with cancer. Hopefully, in the decades to come and with more research, the prediction of the then US President, Bill Clinton, that Cancer “will be known to our grandchildren only as a constellation of stars”, may turn out to be truly prophetic.