Nobel Prize in Physiology or Medicine

The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin) administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by  Swedish chemist Alfred Nobel, the inventor of dynamite, in his will. Nobel was personally interested in experimental physiology and wanted to establish a prize for progress through scientific discoveries in laboratories. The Nobel prize is presented to the recipient(s) at an annual ceremony on December 10, the anniversary of Nobel's death, along with a diploma and a certificate for the monetary award. The front side of the medal provides the same profile of Alfred Nobel as depicted on the medals for Physics, Chemistry, and Literature; its reverse side is unique to this medal.

As of 2011, 102 Nobel Prizes in Physiology or Medicine have been awarded to 199 men, and 10 women. The first Nobel Prize in Physiology or Medicine was awarded in 1901 to the German physiologist Emil Adolf von Behring, for his work on serum therapy and the development of a vaccine against diphtheria. The first woman to win the Nobel Prize in Physiology or Medicine, Gerty Cori, received it in 1947 for her role in elucidating the metabolism of glucose, important in many aspects of medicine, including treatment of diabetes. In 2011, the prize was awarded to Bruce Beutler of the United States and Jules A. Hoffmann of France "for their discoveries concerning the activation of innate immunity" and to Ralph M. Steinman of Canada "for his discovery of the dendritic cell and its role in adaptive immunity."

Some awards have been controversial. This includes one to António Egas Moniz in 1949 for the prefrontal leucotomy, bestowed despite protests from the medical establishment. Other controversies resulted from disagreements over who was included in the award. The 1952 prize to Selman Waksman was litigated in court, and half the patent rights awarded to his co-discoverer Albert Schatz who was not recognized by the prize. The 1962 prize awarded to James D. Watson, Francis Crick and Maurice Wilkins for their work on DNA structure and properties did not acknowledge the contributing work from others, such as Oswald Avery and Rosalind Franklin who had died by the time of the nomination. Since the Nobel Prize rules forbid nominations of the deceased, longevity is an asset, one prize being awarded as long as 50 years after the discovery. Also forbidden is awarding any one prize to more than three recipients, and since in the last half century there has been an increasing tendency for scientists to work as teams, this rule has resulted in controversial exclusions.

Background


Alfred Nobel was born on October 21, 1833 in Stockholm, Sweden into a family of engineers. He was a chemist, engineer and inventor who amassed a fortune during his lifetime, most of it from his 355 inventions of which dynamite is the most famous. He was interested in experimental physiology and set up his own labs in France and Italy to conduct experiments in blood transfusions. Keeping abreast of scientific findings, he was generous in his donations to Ivan Pavlov's laboratory in Russia, and was optimistic about the progress resulting from scientific discoveries made in laboratories.

In 1888, Nobel was surprised to read his own obituary, titled ‘The merchant of death is dead’, in a French newspaper. As it happened, it was Nobel's brother Ludvig who had died, but Nobel, unhappy with the content of the obituary and concerned that his legacy would reflect poorly on him, was inspired to change his will. In his last will, Nobel requested that his money be used to create a series of prizes for those who confer the "greatest benefit on mankind" in physics, chemistry, peace, physiology or medicine, and literature. Though Nobel wrote several wills during his lifetime, the last was written a little over a year before he died at the age of 63. Because his will was contested, it was not approved by the Storting (Norwegian Parliament)  until April 26, 1897.

After Nobel's death, the Nobel Foundation was set up to manage the assets of the bequest. In 1900, the Nobel Foundation's newly created statutes were promulgated by Swedish King Oscar II. According to Nobel's will, the Karolinska Institutet in Sweden, a medical school and research center, is responsible for the Prize in Physiology or Medicine. Today the prize is commonly referred to as the Nobel Prize in Medicine.

Nomination and selection
It was important to Nobel that the prize be awarded for a "discovery" and that it was of "greatest benefit on mankind".

Per the provisions of the will, only select persons are eligible to nominate individuals for the award. These include members of academies around the world, professors of medicine in Sweden, Denmark, Norway, Iceland and Finland, as well as professors of selected universities and research institutions in other lands. Past Nobel laureates may also nominate. Until 1977, all professors of Karolinska Institutet together decided on the Nobel Prize in Physiology or Medicine. That year, changes in Swedish law forced the Institute to make any documents pertaining to the Nobel Prize public and it was considered necessary to establish a legally independent body for the Prize work. Therefore, the Nobel Assembly was constituted, consisting of 50 professors at Karolinska Institutet. It elects the Nobel Committee with 5 members who evaluate the nominees, the Secretary who is in charge of the organization, and each year 10 adjunct members to assist in the evaluation of candidates. In 1968, a provision was added that no more than three persons may share a Nobel prize. The 2011 winners were announced October 3, 2011.

True to its mandate, the Committee has selected researchers working in the basic sciences over those who have made applied contributions. Harvey Cushing, a pioneering American neurosurgeon who identified Cushing's syndrome never was awarded the prize, nor was Sigmund Freud, as his psychoanalysis lacks hypotheses that can be tested experimentally. The public expected Jonas Salk or Albert Sabin to win the prize for their development of the polio vaccines, but instead the award went to John Enders, Thomas Weller, and Frederick Robbins whose basic discovery that the polio virus could reproduce in monkey cells in laboratory preparations was a fundamental finding that led to the elimination of the disease of polio.

Through the 1930s, there were frequent prize winners in classical Physiology, but after that the field began dissolving into specialties. The last classical physiology winners were John Eccles, Alan Hodgkin and Andrew Huxley in 1963 for their findings regarding "unitary electrical events in the central and peripheral nervous system."

Prizes
A Medicine or Physiology Nobel Prize laureate, earns a gold medal, a diploma bearing a citation, and a sum of money. These are awarded at the Nobel Banquet.

Medals
The Nobel Prize medals, minted by Myntverket in Sweden are registered trademarks of the Nobel Foundation. Each medal features an image of Alfred Nobel in left profile on the obverse (front side of the medal). The Nobel Prize medals for Physics, Chemistry, Physiology or Medicine, and Literature have identical obverses, showing the image of Alfred Nobel and the years of his birth and death (1833–1896). Before 1980, the medals were made of 23K gold; since then the medals are of 18K green gold, plated with 23K gold.

The medal awarded by the Karolinska  Institute displays an image of  "the Genius of Medicine holding an open  book in her lap, collecting the water pouring out from a rock in  order to quench a sick girl's thirst." The medal is inscribed with words taken from Virgil's Aeneid and reads: Inventas vitam juvat excoluisse per artes, which translates to "inventions enhance life which is beautified  through art."

Diplomas
Nobel laureates receive a Diploma directly from the King of Sweden. Each Diploma is uniquely designed by the prize-awarding institutions for the laureate that receives it. In the case of the Nobel Prize in Physiology or Medicine, that is the Nobel Assembly  at Karolinska Institute. Well known artists and calligraphers from Sweden are commissioned to create it. The Diploma contains a picture and text which states the name of the laureate and a citation as to why they received the prize.

Award money
The amount of prize money fluctuates depending on how much money the Nobel Foundation can award that year, and is awarded in Swedish kronor (SEK). The first award in 1901 was for 150,782 kronor (7,872,648 kronor in 2009 value). In 2009, the prize money totaled 10,000,000 kronor. If there are two winners in a particular category, the award grant is divided equally between the recipients. If there are three, the awarding committee has the option of dividing the grant equally, or awarding one-half to one recipient and one-quarter to each of the others.

Ceremony and banquet
The awards are bestowed at a gala ceremony followed by a banquet. The Nobel Banquet is a extravagant affair with the menu, planned months ahead of time, kept secret until the day of the event. The Nobel Foundation chooses the menu after tasting and testing selections submitted by  selected chefs of international repute. Currently it is a three course dinner, although it was originally six courses when it began in 1901. Every Nobel Prize winner is allowed to bring up to 16 guests, and Sweden's royal family is always there. Typically the Prime Minister and other members of the government attend as well as representatives of the  Nobel family.

Laureates


The first Nobel Prize in Physiology or Medicine was awarded in 1901 to the German physiologist Emil Adolf von Behring. Behring's discovery of serum therapy in the development of the diphtheria and tetanus vaccines put "in the hands of the physician a victorious weapon against illness and deaths". In 1902, the award went to Ronald Ross for his work on malaria, "by which he has shown how it enters the organism and thereby has laid the foundation for successful research on this disease and methods of combating it". He identified the mosquito as the transmitter of malaria, and worked tirelessly on measures to prevent malaria worldwide. The 1903 prize was awarded to Niels Ryberg Finsen, the first Danish winner, "in recognition of his contribution to the treatment of diseases, especially lupus vulgaris, with concentrated light radiation, whereby he has opened a new avenue for medical science". He died within a year after receiving the prize at the age of 43. Pavlov, whose work Nobel admired and supported, won the prize in 1904 for his work on the physiology of digestion.

Subsequently, those selecting the recipients have exercised wide latitude in determining what falls under the umbrella of Physiology or Medicine. The awarding of the prize in 1973 to Nikolaas Tinbergen, Konrad Lorenz and Karl von Frisch for their observations of animal behavioral patterns could be considered a prize in the behavioral sciences rather than medicine or physiology. Tinbergen expressed surprise in his Nobel Prize acceptance speech at "the unconventional decision of the Nobel Foundation to award this year’s prize ‘for Physiology or Medicine’ to three men who had until recently been regarded as ‘mere animal watchers’".

Laureates have won the Nobel Prize in a wide range of fields that relate to physiology or medicine. , eight Prizes have been awarded for contributions in the field of signal transduction through G proteins and second messengers. 13 have been awarded for contributions in the field of neurobiology and 13 have been awarded for contributions in Intermediary metabolism. The 100 Nobel Prizes in Physiology or Medicine have been awarded to 195 individuals through 2009. Ten women have won the prize: Gerty Cori (1947), Rosalyn Yalow (1977), Barbara McClintock (1983), Rita Levi-Montalcini (1986), Gertrude B. Elion (1988), Christiane Nüsslein-Volhard (1995), Linda B. Buck (2004), Françoise Barré-Sinoussi (2008), Elizabeth H. Blackburn (2009) and Carol W. Greider (2009). Only one woman, Barbara McClintock, has won an unshared prize in this category, for the discovery of genetic transposition. Mario Capecchi, Martin Evans and Oliver Smithies won the prize in 2007 for the discovery of a gene targeting procedure (a type of genetic recombination) for introducing homologous recombination in mice, employing  embryonic stem cells through the development  of the knockout mouse. There have been 37 times when the Nobel Prize in Physiology or Medicine was awarded to a single individual, 31 times when it was shared by two, and 33 times there were three winners (the maximum allowed).

In 2009, the Nobel Prize was awarded to Elizabeth Blackburn, Carol W. Greider and Jack W. Szostak of the United States for discovering the process by which chromosomes are protected by telomeres (regions of repetitive DNA at the ends of chromosomes) and the enzyme telomerase; they shared the prize of 10,000,000 SEK (slightly more than €1 million, or US$1.4 million). Rita Levi-Montalcini, an Italian neurologist, who together with colleague Stanley Cohen, received the 1986 Nobel Prize in Physiology or Medicine for their discovery of Nerve growth factor (NGF), is the oldest living Nobel Laureate, being over 100.



Time factor and death
Because of the length of time that may pass before the significance of a discovery becomes apparent, some prizes are awarded many years after the initial discovery. Barbara McClintock made her discoveries in 1944, before the structure of the DNA molecule was known; she was not awarded the prize until 1983. Similarly, in 1916 Peyton Rous discovered the role of tumor viruses in chickens, but was not awarded the prize until 50 years later, in 1966.

Nobel laurate Carol Greider's research leading to the prize was conducted over 20 years before. She noted that the passage of time is an advantage in the medical sciences, as it may take many years for the significance of a discovery to become apparent. The 2009 award in medicine was the first in the Nobel Prize's history that more than one woman has been the recipient of the Nobel Prize in a single year. It is also the first time two women have be awarded the Physiology or Medicine prize.

Controversial inclusions and exclusions
Some of the awards have been controversial. Who was deserving of the 1923 prize for the discovery of insulin as a  central hormone for controlling diabetes (awarded only a year after its discovery)  has been heatedly debated. It was shared between Frederick Banting and John Macleod; this infuriated Banting who regarded Macleod's involvement as minimal. Macleod was the department head at the University of Toronto but otherwise was not directly involved in the findings. Banting thought his laboratory partner Charles Best, who had shared in the laboratory work of discovery, should have  shared the prize with him as well. In fairness, he decided to give half of his prize money to Best. Macleod on his part  felt the biochemist James Collip,  who joined the laboratory team later, deserved to be included in the award and shared his prize money with him. Moreover, Nicolae Paulescu, a Romanian professor of physiology at the University of Medicine and Pharmacy in Bucharest, was the first to isolate insulin, in 1916, which he called at that time, pancrein. By the time Banting also isolated insulin after reading and citing Paulescu's published work ("Research on the Role of the Pancreas in Food Assimilation", ) in the paper that brought him the Nobel, Paulescu already held a patent for his discovery (April 10, 1922, patent no. 6254 (8322) "Pancreina şi procedeul fabricaţiei ei"/"Pancrein and the process of making it", from the Romanian Ministry of Industry and Trade). The Nobel Committee did not acknowledged Paulescu as the true discoverer of insulin in 1969.

In 1949, despite protests from the medical establishment, the Portuguese neurologist António Egas Moniz received the Physiology or Medicine Prize for his development of the prefrontal leucotomy, which he promoted by declaring the procedure's success just 10 days postoperative. Due largely to the publicity surrounding the award, it was prescribed without regard for modern medical ethics. Favorable results were reported by such publications as The New York Times. It is estimated that around 5,000 lobotomies were performed between 1949 and 1952 in the United States, until the procedure's popularity faded. Joseph Kennedy, the father of John Kennedy, subjected his daughter, Rosemary, to the procedure which incapacitated her to the degree that she needed to be institutionalized for the rest of her life.

The 1952 prize, awarded solely to Selman Waksman for his discovery of streptomycin, omitted the recognition some felt due to his co-discoverer Albert Schatz. There was litigation brought by Schatz against Waksman over the details and credit of the streptomycin discovery;  Schatz was awarded a substantial settlement, and, together with Waksman, Schatz was to be officially recognized as a co-discoverer of streptomycin as far as patent rights. However, he is not recognized as a Nobel Prize winner.

The 1962 Prize awarded to James D. Watson, Francis Crick and Maurice Wilkins—for their work on DNA structure and properties—did not recognize contributing work from others, such as Alec Stokes and Herbert Wilson. In addition, Erwin Chargaff, Oswald Avery and Rosalind Franklin (whose key DNA x-ray crystallography work was the most detailed yet least acknowledged among the three) contributed directly to the ability of Watson and Crick to solve the structure of the DNA molecule—but Avery died in 1955, and Franklin in 1958 and posthumous nominations for the Nobel Prize are not permitted. However, recently unsealed files of the Nobel Prize nominations reveal that no one ever nominated Franklin for the prize when she was alive. Wilkins' only contribution was to show Rosa Franklin's key x-ray photos to Watson. As a result of Watson's misrepresentations of Franklin and her role in the discovery of the double helix in his controversial book The Double Helix, Franklin has come to be portrayed as a classic victim of sexism in science. Chargaff, for his part, was not quiet about his exclusion from the prize, bitterly writing to other scientists about his disillusionment regarding the field of molecular biology.

The 2008 award went to Harald zur Hausen in recognition of his discovery of the human papillomavirus (HPV) causing cervical cancer, and to Françoise Barré-Sinoussi and Luc Montagnier for discovering the Human immunodeficiency virus (HIV). Whether Robert Gallo or Luc Montagnier deserved more credit for the discovery of the virus that causes AIDS has been a matter of considerable controversy. As it was, Gallo was left out and not awarded a prize. Additionally, there was scandal when it was learned that Harald zur Hausen  was being investigated for having a financial interest in vaccines for the cervical  cancer HPV can cause. AstraZeneca, which has a stake in two lucrative HPV vaccines therefore can gain financially from the prize, had agreed to sponsor Nobel Media and Nobel Web. According to Times Online, two senior figures in the selection process that chose zur Hausen also had strong links with AstraZeneca.

Limits on number of awardees
The provision that restricts the maximum number of nominees to three for any one prize, introduced in 1968, has caused considerable controversy. From the 1950s onward, there has been an increasing trend to award the Nobel Prize in Physiology or Medicine to more than one person. There were 59   people who received the prize in the first 50 years of the last century, while 113 individuals received it  between 1951 and    2000. This increase could be attributed to the rise of the international scientific community after World   War II, resulting in more persons being responsible for the discovery, and nominated for, a particular prize. Also, current   biomedical research is more often carried out by teams rather than by scientists    working alone, making it unlikely that any one scientist, or even a few, is primarily responsible for a discovery; this has meant that a  prize nomination  that would have to  include more than three contributors is automatically excluded from consideration. Also, deserving contributors may not be nominated at all because the restriction results in a cut off point of three nominees per prize, leading to controversial exclusions.

Years without awards
There have been nine years in which the Nobel Prize in Physiology or Medicine was not awarded (1915–1918, 1921, 1925, 1940–1942). Most of these occurred during either World War I (1914–1918) or World War II (1939–1945). In 1939, Adolf Hitler's Third Reich forbade Gerhard Domagk from accepting his prize. He was later able to receive the diploma and medal but not the money.