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The Nobel Laureates of AAI

by Charles Richter and John S. Emrich
December 2022

The story of the Nobel Prizes begins in 1850 in the Paris laboratory of the Italian chemist Ascanio Sobrero, where a young Alfred Nobel first encountered nitroglycerine. Sobrero had discovered the unstable and highly explosive chemical three years earlier and Nobel, against Sobrero’s advice, sought to find commercial uses for it. Eventually, after causing an accidental explosion that killed his younger brother, Nobel developed a stable, solid compound of nitroglycerine that he called dynamite. His invention transformed mining and engineering, allowing for feats of construction that would have been impossible without such explosive power.

Of course, dynamite also had military applications. Nobel had somewhat naively believed that dynamite was so frighteningly powerful that it would make war obsolete. According to his biographer, the truth was driven home in 1888 when Nobel opened a newspaper and read his own obituary, which called him a “merchant of death.” The newspaper writer had confused Alfred Nobel with his brother Ludvig, who had in fact died. Not wanting to be remembered as a war profiteer, he decided to use his wealth for good and thus established the Nobel Prizes to recognize “those who have conferred the greatest benefit to humankind.” Unfortunately, no copy of the alleged obituary has ever been located. Nobel never spoke publicly about the actual inspiration behind the prizes.

After a long career of invention and engineering, Nobel stipulated in his will that 94 percent of his estate would be invested, with the interest funding the prizes. The initial five categories of achievement were physics, chemistry, physiology or medicine, literature, and peace, and were to be awarded with “no consideration…given to nationality.” The arrangement angered his family members, who expected to inherit the sizable fortune, as well as many of his fellow Scandinavians, who were incensed that awardees from other countries would be considered.

Immunology Recognized

Alfred Nobel died in 1896, and the first Nobel Prizes were awarded in 1901. The very first prize in Physiology or Medicine was awarded to Emil von Behring for his work on serum therapy, which had laid the foundation for the early field of immunology. Future prizes would confirm the centrality of immunological research to the larger biomedical field and to public health in the world at large.

Since 1901, Nobel Prizes have been awarded to 27 AAI members for their innovation and achievements in immunology and related disciplines. They range from early 20th century discoveries elucidating fundamental properties of blood to more recent breakthroughs that have led to better understanding and successful clinical treatments of both ancient scourges like cancer and novel diseases such as COVID-19. Four laureates spanning nearly 80 years of the association have served as AAI Presidents: Karl Landsteiner (AAI 1922, president 1927–28), John F. Enders (AAI 1936, president 1952–53), Baruj Benacerraf (1957, president 1973–74), and James P. Allison (AAI 1978, president 2001–02). Immunologists continue to make important scientific advances and discoveries with broad reaching possibilities, offering the potential every year for another AAI member to be given this honor. No more than 15 years have ever elapsed between instances of the prize being bestowed on an immunologist, and on two occasions AAI members have been honored in successive years.

Here we present brief profiles of some of the AAI Nobel laureates, representing a selection of the immunological developments to be recognized since 1919. In a previous article, the work of Enders, Thomas Weller (AAI 1943), and Frederick Robbins (AAI 1952) on culturing the poliovirus was featured. Full profiles of all laureates are available on the AAI website at www.aai.org/Nobel.

Bordet (1919)

Jules Bordet (AAI 1960) was the first AAI member to be awarded the Nobel Prize in Physiology or Medicine “for his discoveries relating to immunity.” His peers had previously nominated Bordet in 1902 along with Emile Roux (who never won the prize himself), and Bordet had received additional nominations each year since 1908. Although he won the 1919 prize, an obscure rule in Nobel’s will meant that he would not receive it until the next year. Bordet did not even know he had won until 1920, when the announcement was made while he was traveling in the United States. In the award ceremony, the Nobel committee recognized the critical importance of immunology as a field as well as Bordet’s specific contributions, particularly his discovery of complement and his development of complement fixation tests that led to a wide range of further discoveries and diagnostics.

Landsteiner (1930)

Karl Landsteiner was the first Nobel Laureate to be an active AAI member at the time of the award, which was given in 1930 “for his discovery of human blood groups.” Although Landsteiner had made his initial findings in 1900, the importance of blood groups was not widely realized until 1910. When The Journal of Immunology was founded in 1916, Landsteiner’s impact was obvious in the many studies on blood groupings that were published in the early volumes. The Nobel committee also acknowledged the legal and forensic doorways that blood typing opened, as now blood samples could be used to rule out crime suspects or potential fathers in a paternity dispute.

Stanley (1946)

Wendell Stanley (AAI 1957) holds the distinction of being the only member of AAI to receive the Nobel Prize in Chemistry, which he shared with John Howard Northrop in 1946 “for their preparation of enzymes and virus proteins in a pure form.” Prior to Stanley’s research, the physical nature of viruses was unknown. In the 1930s, he managed to crystalize the tobacco mosaic virus, ending the debate and demonstrating that viruses were particles too small to be filtered or seen by the equipment of the day. Further experimentation showed that viruses were composed of proteins and RNA, which explained how they are replicated. Stanley’s work transformed the field of virology and was a key step in understanding how to produce immunity to viruses. Later in his career, Stanley turned his attention to cancer, and announced to a skeptical audience at the 1956 National Cancer Conference: “I believe the time has come when we should assume that viruses are responsible for most, if not all, kinds of cancer.”

Edelman and Porter (1972)

Gerald Edelman (AAI 1970) and Rodney Porter (AAI 1973) shared the 1972 Nobel Prize in Physiology or Medicine “for their discoveries concerning the chemical structure of antibodies.” Working independently in 1959, both scientists had broken antibody molecules into fragments to see how their properties would be altered. Porter split an antibody with the enzyme papain, and found that it divided into three fragments, two of which retained the ability to combine with its antigen. Edelman separated the antibody into several chains with no such capability. The well-known Y-shaped model of the antibody comes from Porter’s explanation that the chains Edelman found were arranged into branches, and it is the specific arrangement of elements that enables reactivity to antigens.

The Nobel Committee’s press release for the award contained a rather back-handed compliment to the field: when Edelman and Porter “provided a clear picture of the structure and mode of action of a group of biologically particularly important substances… they laid a firm foundation for truly rational research, something that was previously largely lacking in immunology.”

Baltimore (1975)

David Baltimore (AAI 1984) received the 1975 Nobel Prize for Physiology or Medicine, sharing it with Renato Dulbecco and Howard Temin “for their discoveries concerning the interaction of tumor viruses and the genetic material of the cell.” In 1970, following Dulbecco’s discovery that genetic material from DNA tumor viruses actually remains in and is replicated by host cells, Baltimore and Tenin both found an enzyme in RNA tumor viruses that could form DNA from an RNA template. This enzyme became known as reverse transcriptase.

The discovery of reverse transcriptase allowed for the development of several new microbiological advances and technologies, including enrichment of cellular mRNA, molecular cloning, and the discovery of oncogenes.

Benacerraf, Dausset, and Snell (1980)

Baruj Benacerraf, Jean Dausset (AAI 1975), and George Snell were awarded the 1980 Nobel Prize in Physiology or Medicine “for their discoveries concerning genetically determined structures on the cell surface that regulate immunological reactions.” Independently, the three scientists made key contributions that built on one another: Snell discovered the role of the histocompatibility gene H-2 in transplant rejection; Dausset showed the existence of H-2 in humans; and Benacerraf discovered the immune response (Ir) genes. Together, these findings elucidated the major histocompatibility complex (MHC), which is a component of the immune system of all vertebrates.

Jerne, Kohler, and Milstein (1984)

Niels Jerne (AAI 1965) won the 1984 Nobel Prize in Physiology or Medicine “for theories concerning the specificity in development and control of the immune system,” sharing the prize with Georges Köhler (AAI 1985) and César Milstein (AAI 1979), who were honored for “the discovery of the principle for production of monoclonal antibodies.” Jerne “outlined the development of modern immunology” in three crucial theories: (1) that specific antibody response is predetermined in the womb; (2) that lymphocytes “learn” to distinguish self from non-self in the thymus where they are exposed to histocompatibility antigens; and (3) that antibodies can stimulate the production of anti-antibodies in a cascading manner that finds equilibrium under normal conditions. The third of these, known as the “Network Theory,” provided the foundation for numerous translational applications ranging from allergy and infectious disease treatment to transplantation and autoimmune disorder management.

Köhler and Milstein developed the hybridoma technique for producing monoclonal antibodies by fusing antigen-immunized cells to immortalized myeloma cells, effectively creating a factory for antigen-specific antibodies. Without their innovation, we would not have had one of the most important treatments for immunocompromised and immunosuppressed people during the COVID-19 pandemic.

Doherty and Zinkernagel (1996)

The 1996 Nobel Prize in Physiology or Medicine went to Peter Doherty (AAI 1976) and Rolf Zinkernagel (AAI 1976, DFAAI 2019) “for their discoveries concerning the specificity of the cell mediated immune defense.” Their research showed that when a cell has been infected by a virus, a lymphocyte must recognize two factors in that cell before killing it: MHC antigens and the virus. This simultaneous recognition of and distinction between both self and non-self factors is one of the checks that limits the cellular immune system from activating inappropriately. Understanding that the strongest T cell responses are elicited by “altered self” targets led to advances in transplantation, vaccine development, and treatment of autoimmune and infectious diseases.

Prusiner (1997)

Stanley Prusiner (AAI 1981) received the 1997 Nobel Prize in Physiology or Medicine “for his discovery of Prions—a new biological principle of infection.” When one of his patients died of Creutzfeldt-Jakob Disease (CJD), Prusiner decided to identify the mysterious infectious agent that was neither bacterium nor virus. Knowing that the CJD and similar diseases such as kuru and scrapie were transmitted via brain tissue, he eventually produced from hamster brains a preparation containing the agent: a single protein he named a proteinaceous infectious particle, or “prion” for short. Prusiner’s 1982 discovery came just in time to help inform the management of the “mad cow disease” epidemic of bovine spongiform encephalitis (BSE) in the United Kingdom.

Allison and Honjo (2018)

The most recent Nobel laureates in AAI are James Allison and Tasuku Honjo (AAI 1988), who won the 2018 Nobel Prize in Physiology or Medicine “for their discovery of cancer therapy by inhibition of negative immune regulation.” Curing cancer has always been one of the most sought-after goals in medical science, and the immunotherapy that Allison and Honjo made possible is one of the most promising developments in history. Working with the T cell protein CTLA-4, understood to act as a “brake” on the immune system, Allison discovered a way of “releasing the brake” and letting the T cells attack tumor cells when they otherwise would not. Honjo identified a second brake protein that worked differently but also proved effective in attacking cancer.

Allison and Honjo certainly will not be the last AAI members to be recognized by the Nobel Committee, as the field continues to produce important research with wide applications in both basic and translational realms.

Other Nominations

Although the Nobel nominations are sealed for 50 years, the available records show that many other AAI members have been recommended for the award, some several times. Among the presidents of AAI, John Kolmer (AAI 1913, president 1917–18), Hans Zinsser (AAI 1917, president 1919–20), Rufus Cole (AAI 1917, president 1920–21), Frederick Novy (AAI 1920, president 1924–25), Ludvig Hektoen (AAI 1919, president 1926–27), Karl F. Meyer (AAI 1922, president 1940–41), Thomas Francis Jr. (AAI 1930, president 1949–50), and Colin MacLeod (AAI 1937, president 1951–52) were all nominated once. Thomas Rivers (AAI 1921, president 1933–34) received nominations in two years, and Alphonse Dochez (AAI 1920, president 1931–32) in three. The two past presidents with the most frequent nominations are Michael Heidelberger (AAI 1935, president 1946–47, 1948–49), nominated 18 times between 1937 and 1962, and Oswald T. Avery (AAI 1920, president 1929–30), with 18 between 1932 and 1957.

Nearly all of these nominations were in Physiology or Medicine, but occasionally a member has been nominated for the Chemistry prize as well. Understandably, the Nobel Committee issues the prizes to scientists in a wide range of fields, but hardly a year has gone by that an immunologist has not been considered for the highest honor in science.

For more in-depth profiles of every one of the 27 AAI Nobel laureates, including their background, research, and influences, visit the AAI History site at www.aai.org/Nobel.

 

References

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