The Nobel dilemma: to reward scientific discovery or benefit to mankind?

Introduction

Alfred Nobel was born in Stockholm, invented and patented Dynamite and was a rich man when he died in 1896. His will stipulated that his fortune should fund annual awards for the most important discoveries in chemistry, physics, physiology or medicine, literature, peace and, subsequently, economics. The prize in physiology or medicine is the best known, the winner or winners being chosen by the Nobel Assembly of the Karolinska Institute in Stockholm.

The selection process

Alfred Nobel’s will stipulated that prizes should be awarded ‘to those who, during the preceding year, shall have conferred the greatest benefit to mankind.’¹ It also specified that one of the prizes should go to ‘the person who shall have made the most important discovery within the domain of physiology or medicine’. The selection process for the prize in physiology or medicine is extremely rigorous but not perfect.² For example, its award in 1949 to Egas Moniz for inventing leucotomy to treat psychotic disorders has been heavily criticized because of the operation’s disastrous side effects. In contrast, Oswald Avery’s discovery in 1944 of DNA as the carrier of heredity was a major achievement, yet despite being nominated 46 times, he died without being awarded the Nobel prize.² The latter cannot be awarded posthumously.

Assessing Nobel prize worthiness

Some of the scientists and physicians awarded the Nobel prize in physiology or medicine were depicted in Nobel Prizes That Changed Medicine.³ The sequel, Pioneers of Medicine Without a Nobel Prize,⁴ described an equally remarkable group of individuals who have not received it. The latter should not be written off as second rate—there are simply not enough Nobel prizes to reward all those who have made major discoveries in biomedical science. The prize in physiology or medicine is limited to three laureates annually and an embarrass de richesses of outstanding candidates means that hard and difficult choices must be made every year in Stockholm. Recently, there has been a distinct bias towards rewarding basic scientific discoveries at the expense of clinically related ones, as illustrated in Table 1.

Table 1.

Nobel prizes in physiology or medicine, 2000–2014

Year	Laureates	Topic	Nationalities
2000	Carlsson, Greengard, Kandel	CNS signalling	Sweden, USA, USA
2001	Hartwell, Hunt, Nurse	Control of cell cycling	USA, UK, UK
2002	Brenner, Horwitz, Sulston	Genetic regulation of organs/cells	UK, USA, UK
2003	Lauterbur, Mansfield	Magnetic resonance imaging	USA, UK
2004	Axel, Buck	Olfactory receptors	USA, USA
2005	Marshall, Warren	Helicobacter Pylori	Australia, Australia
2006	Fire, Mello	RNA interference	USA, USA
2007	Capecchi, Evans, Smithies	Gene targetting	USA, UK, UK
2008	zur Hausen, Barre-Sinoussi, Montagnier	HPV and HIV	Germany, France, France
2009	Blackburn, Greider, Szostak	Telomeres and telomerase	USA, USA, USA
2010	Edwards	In vitro fertilisation	UK
2011	Beutler, Hoffmann, Steinman	Adaptive and innate immunity	USA, Luxembourg, Canada
2012	Gurdon, Yamanaka	Reprogramming mature cells into stem cells	UK, Japan
2013	Rothman, Schekman, Sudhof	Regulating vesicle traffic in cells	USA, USA, Germany
2014	O'Keefe, Moser, Moser	Positioning system in the brain	USA, Norway, Norway

CNS, central nervous system; HPV, human papilloma virus; HIV, human immunodeficiency virus; RNA, ribonucleic acid.

Some current non-winners of the Nobel prize

Many believe that Boyer and Cohen's development of the cloning of recombinant DNA in the 1970s⁴ deserves a Nobel prize. This discovery resulted in an explosion of knowledge and understanding of human genetics that benefitted all aspects of clinical medicine. One factor that may have influenced the failure of their work to be recognized as Nobel prize-worthy was Boyer’s co-founding in 1976 of Genentech, a company set up to pursue research into the medical uses of recombinant DNA. This innovation was regarded with suspicion by the scientific establishment, who considered commercial gain incompatible with true research.

It is ironic that the spread of the hepatitis C virus was unwittingly facilitated by the development of the hypodermic needle and use of blood transfusions. These advances saved countless lives but have also been responsible for transmitting disease to millions of people. Working at the National Institutes of Health and the Chiron Corporation, respectively, Harvey Alter and Michael Houghton⁴ discovered the hepatitis C virus and developed assays that eliminated the risk of transmitting all forms of viral hepatitis by blood transfusions. These achievements were the basis for their Lasker Award in 2000 and some argue that they also deserve a Nobel prize.

Mark Twain stressed the importance of primacy in any discovery and Akira Endo’s discovery of the cholesterol-lowering properties of Penicillium citrinium, while working for Sankyo⁴ was as much a first as was Alexander Fleming’s discovery of the antibiotic properties of penicillin. Fleming was awarded the Nobel prize in 1945 but Endo, ‘whose discovery of statins changed the world’,⁵ lacks such recognition. The scientific importance of his discovery is undeniable as is its benefit to mankind in reducing morbidity and mortality from atherosclerotic cardiovascular disease.

Each of these discoveries has one thing in common, namely a link between one of the scientists involved and commerce. However, because of the Nobel Committee’s secrecy rule, whether this is the reason they have been ignored will not be revealed until 50 years after their nominations were first considered.

Trends in medical research

A recent development is the use of Mendelian randomization and genome-wide association studies (GWAS), which provide invaluable information on whether correlations between biomarkers and disease are causal. This raises the question of whether future advances arising from GWAS might be eligible for consideration by the Nobel Assembly. Another development has been the emergence of translational research, which aims to facilitate the conversion of basic science discoveries into clinically relevant advances in investigation and treatment. A classic example, which occurred long before the term was coined, was Fleming’s serendipitous but crucial observation of the contaminated culture plate, which would have remained of purely academic interest if Florey and Chain had not subsequently devised a means of producing penicillin in sufficient quantity and purity for clinical use. The current enthusiasm for translational research is not shared by the Nobel laureates Goldstein and Brown who consider that ‘Individual curiosity driven science has been replaced by large consortia dedicated to the proposition that gathering vast amounts of correlative data will somehow provide the answer to life’s fundamental questions.’⁶

The challenge facing the Nobel Foundation is how to cope with these changes, especially when there are scores of authors of a crucial publication. In this situation, it may be virtually impossible to decide which three of the individuals involved were responsible for a potential Nobel prize-winning discovery.

The future

It is questionable whether Nobel’s wishes have always been carried out in the spirit he intended; in particular is too much emphasis placed on the scientific quality of a discovery and not enough on the benefit it confers on mankind? One way of resolving this issue would be to treat the physiology and medicine components of the prize as separate entities. Thus the prize in physiology would be awarded for basic scientific research whereas the prize in medicine would be reserved for advances in diagnosis, therapeutics and the clinical applications of translational research. This would double the number of potential recipients and help redress the perceived bias against clinically related discoveries. Considering that the first prize in physiology or medicine was awarded in 1901, it is remarkable that the selection process has survived virtually unchanged. But if change does come, it must not compromise the Nobel prize’s unrivalled reputation for rewarding excellence.

Conflict of interest: None declared.