Nobel Prize in Chemistry – Expert reaction

The Nobel Medal for Physics and Chemistry. Registered trademark of the Nobel Foundation. © ® The Nobel FoundationThe 2015 Nobel Prize in Chemistry has been awarded to Prof Tomas Lindahl of the Francis Crick Institute, jointly with Prof Paul Modrich of Duke University School of Medicine, and Prof Aziz Sancar of the University of North Carolina School of Medicine.

The prize was awarded to the trio “for mechanistic studies of DNA repair”.

 Our colleagues at the UK SMC collected the following expert commentary.

Prof Mike Stratton, Director of the Wellcome Trust Sanger Institute, comments:

“I am absolutely delighted that Tomas Lindahl has been honoured by the Nobel committee for his fundamental research into DNA repair. The extraordinary challenge of faithfully replicating millions of letters of DNA code in millions of cells daily coupled with the remorseless assault on DNA from agents that damage it, makes mutations and their consequences, including cancer, a major risk for living organisms. In his absolutely pioneering work Tomas Lindahl provided profound insights into the extent of this problem and led us to understanding of how cells reduce its impact by repairing DNA damage. This is fundamental research into a profound conundrum at the centre of our existence and the award is thoroughly deserved.

Sir Paul Nurse, Director of The Francis Crick Institute, comments:

“I offer congratulations from everyone at the Francis Crick Institute and myself to Tomas Lindahl, Paul Modrich and Aziz Sancar for sharing the Nobel Prize in Chemistry. I am absolutely delighted that Tomas, an Emeritus Professor at the Crick Institute’s Clare Hall Laboratory, has been recognised for his outstanding work on DNA. As director of the Clare Hall Laboratory of the Imperial Cancer Research Fund and then Cancer Research UK from 1986 to 2005, Tomas has been an inspiration to his colleagues and peers for decades. This honour is most richly deserved.”

Prof Tom Brown, Professor of Nucleic Acid Chemistry, University of Oxford, comments:

“DNA repair is one of the most fundamentally important processes in all life forms. It protects our genomes from damaging agents such as UV light and chemical carcinogens.

“Today’s Nobel laureates are the pioneers; their seminal work has contributed hugely to the field. Yet despite these achievements, there is still much to learn about DNA repair.

“Importantly, the field is ripe for exploitation in the therapeutic context (drug development) and in the final analysis it is all chemistry.”

Philip Driver, Senior Science Programme Manager, Royal Society of Chemistry, comments:

“We congratulate Tomas Lindahl, Paul Modrich, and Aziz Sancar on the award of the 2015 Nobel Prize for Chemistry in recognition for their contributions in the field of DNA repair. Without repair our genetic code would rapidly become corrupted due to the accumulated effects of environmental damage and replication errors.

“The pioneering discoveries of Lindahl, Modrich, and Sancar have opened the door to understanding mechanisms of DNA repair and will allow future development in applications such as treating disease. This award underscores the value of chemistry to advancing our understanding of genetics, physiology and life itself.”

Dr Qian An, Senior Research Fellow, University of Portsmouth, comments:

“I am really thrilled by the wonderful news. Tomas was my boss when I did my first post-doc at CRUK and the experience was extremely beneficial for me. His pioneering work in the DNA repair field has significantly enhanced our understanding of the mechanisms, which in turn has made a fundamental impact on biomedical research. My heartfelt congratulations on this well-deserved prize.”

Dr Chris Lord, Team Leader in Gene Function at The Institute of Cancer Research, London, comments:

“This is great news for the field and recognises the importance of DNA repair, both as a normal process but also as a process that is often dysfunctional in diseases such as cancer. Some of the seminal work that the recipients carried out has informed our understanding not only of cancer biology but also how we treat the disease.”

Prof Sir Colin Blakemore, Director of the Centre for the Study of the Senses, University of London, comments:

“Another Nobel Prize for the UK – and a wonderful start for the Francis Crick Institute. But let’s not forget that Tomas Lindahl is Swedish. He came to this country more than 30 years ago because Britain welcomed talented people from overseas and because it valued science and scientists. Britain is rightly proud of its extraordinary harvest of Nobel Prizes, but a quarter of them were won by people born elsewhere. If we want to maintain our prestige as a leading scientific nation we must give the science budget the priority it deserves, and we must continue to welcome scientists from abroad.”

Prof Shirley Hodgson, Professor of Cancer Genetics at St George’s, University of London (SGUL), comments:

“I was delighted to hear that Tomas Lindahl was one of three scientists awarded the Nobel prize for chemistry today. The work that these scientists have done is crucial to our understanding of the mechanisms of DNA breakage and repair in the organism. This knowledge has been fundamental to the development of knowledge in the field of DNA repair, which we now know can be faulty in certain individuals, leading to an increased susceptibility to certain cancers, and it has also contributed to our understanding of the environmental causes of DNA breaks which can cause cancer initiation and development.

“Thomas is a friend and colleague -with rather a retiring manner – so it is wonderful to hear he has received such an accolade.”

Dr KJ Patel, Group Leader at the MRC Laboratory of Molecular Biology, comments:

“The award of the Nobel Prize to Tomas Lindhal , Paul Modrich and Aziz Sancar finally rewards pioneers in the field of DNA repair. Soon after the structure of DNA was realised it also became known that exposure to X rays caused the molecule to be damaged and this damage was the basis of radiation sickness and the causes of mutations in DNA that have many consequences to organisms. However it took a long time to realise that our cells invest considerable efforts to reverse the damage caused to DNA.

“This year’s Chemistry Nobel Prize goes to three pioneers whose work uncovered the fundamental mechanisms that repair damaged DNA. Tomas Lindahl in the 1970s made the remarkable discovery that DNA when placed in a solution akin to that present in the cell spontaneously decomposed. It is indeed a much more fragile molecule than what had been appreciated before, but such fragility would seriously damage the ability of the cell to function. Building on this, Lindhal discovered how the decay of the base constituents of DNA are repaired using enzymes that cut out the bad base and replace it with the correct one. This DNA repair pathway which exists in all living organisms on Earth is called base excision repair.

“Moderich uncovered that when DNA is copied, for instance when a cell multiplies, then occasionally the copying process introduces an error, and a repair pathway removes such errors and restores the correct genetic information. This pathway is known as DNA miss match repair, and when it does not work in humans then it causes colon cancer. Finally, Sancar discovered how the cell fixes DNA damage that is commonly caused by exposure to sunlight: again the damaged DNA is seen by the cell and removed by a pathway called nucleotide excision repair.

“The work of these three individuals has transformed our understanding of how organisms ensure that our blue print of life remains intact. When these pathways are overwhelmed ( by excessive exposure to factors that damage DNA – cigarette smoking, alcohol consumption and sunbathing) or if they are inactive, then dangerous changes occur in the blue print of life causing cells to malfunction, age and turn cancerous.”

Dr Jeremy Farrar, Director of the Wellcome Trust, comments:

“Tomas Lindahl is a brilliant scientist whose work has been hugely important to our understanding of how cells work. Him winning the Nobel Prize shows the great impact of sustained support for excellent science and importance of international collaboration.  It’s fantastic news for the Francis Crick Institute, for Cancer Research UK and yet again demonstrates the strength of UK science. Congratulations to Tomas, and to Paul Modrich and Aziz Sancar.”

Prof Dame Kay Davies, University of Oxford & Deputy Chair of the Wellcome Trust, comments:

“It’s wonderful to see basic science recognised by today’s announcement. Tomas Lindahl’s work into DNA repair, which is such a fundamental process, has had a major impact on many diseases. I’m thrilled that this has been honoured!”

Dr Mark Downs, Chief Executive of the Royal Society of Biology, comments:

“The structure of DNA and its function in the inheritance of almost all living organisms remains one of the critical discoveries in science. Almost everyone has heard of DNA. But the way it functions in every cell and how it interacts with other molecules is still being actively researched and continues to reveal how amazing and complex the start, and continuance of life, is. The important work of Lindahl, Modrich and Sancar has provided an answer to one part of this puzzle – how DNA repairs itself when damaged, every day, through processes within each cell. Without these mechanisms we would probably not exist and would certainly all die young. The Royal Society of Biology is delighted to be able to congratulate this year’s recipients of the Nobel prize for Chemistry.”

Prof Gordon McVie, Clinical Research Advisor at the Institute for Molecular Oncology (IFOM) and former CEO at CRUK, comments:

“Super news. The mildest, most modest of men, generous to a fault. Exceptional brain, ground-breaking science and compassionate mentor. Great supporter when we merged CRC and ICRF to form CRUK. Now key leader at the institute of molecular oncology (IFOM) in Milan where our paths have crossed, happily, again.”

Sir Tim Hunt, Nobel Laureate, comments:

“This is wonderful news! Tomas was my boss for almost 20 years, a real scientists’ scientist. Pioneer in the study of DNA decay and its repair. Richly deserved prize.”

Prof Daniela Rhodes, Director of NTU Institute of Structural Biology, comments:

“Tomas was a pioneer in this area of research and is totally deserving of this year’s Chemistry Nobel Prize. His work is of immense fundamental importance for understanding how the genome is maintained to prevent cancer occurrence and other human diseases.”

Prof Malcolm Alison, Professor of Stem Cell Biology, Barts Cancer Institute, Queen Mary University of London, comments:

“The fidelity of the human genome is maintained by DNA repair enzymes that can remove and repair potentially cancer-causing mutations. Tomas Lindahl has been a pioneer in this incredibly important area since all our genomes are continually subjected to millions of DNA-damaging mutations, yet cancer is relatively rare because of these repair (surveillance) mechanisms. DNA repair enzymes are analogous to proof readers of a text, continually searching for errors in the DNA alphabet of four letters (A, T, G and C), and probably succeeding in 99% of cases. “