What are the best Nobel Prizes in biochemistry & molecular biology since 1945?

The 2022 Nobel Prize in Physiology or Medicne went to Svante Pääbo “for his discoveries concerning the genomes of extinct hominins and human evolution”. It's one of a long list of Nobel Prizes awarded for technological achievement. It most cases, the new techniques led to a better understanding of science and medicine.

Since World War II, there have been significant advances in our understanding of biology but most of these have come about by the slow and steady accumulation of knowledge and not by paradigm-shifting breakthroughs. These advances don't often get recognized by the Nobel Prize committees because it's difficult to single out any one individual or any single experiment that merits a Nobel Prize. In some cases the Nobel Prize committees have tried to recognize major advances by picking out leaders that have made important contributions over a number of years but their choices don't always satisfy others in the field. One of the notable successes is the awarding of Nobel Prizes to Max Delbrück, Alfred D. Hershey and Salvador E. Luria “for their discoveries concerning the replication mechanism and the genetic structure of viruses” (Nobel Prize in Physiology or Medicine 1969). Another is Edward B. Lewis, Christiane Nüsslein-Volhard and Eric F. Wieschaus “for their discoveries concerning the genetic control of early embryonic development” (Nobel Prize in Physiology or Medicine 1995)

There's no doubt that the scientific approach of the phage group (founded by Delbrück and Luria) made enormous contributions to molecular biology and I'm glad that the Nobel Prize Committee recognized this even if they had to "cheat" a little bit to come up with a significant experiment that was worthy of the prize. Similarly, EVO-DEVO is an important advance but it's a concept, not a single experiment. The idea is that small changes in regulation can give rise to significant changes in phenotype but you can't point to just a small set of experiments that changes everyone's mind. (Indeed, there are still many biologists (cough, ENCODE, cough) who don't understand this point.)

François Jacob, André Lwoff and Jacques Monod were awarded the 1965 Nobel Prize for “for their discoveries concerning genetic control of enzyme and virus synthesis.” This is for work on the regulation of the lac operon and the discovery of messenger RNA. This was a fundamental contribution to understanding genes and their expression.

People forget that our understanding of metabolic pathways only came about in the 20th century. There have been several Noble Prizes that recognize this fundamental part of biochemistry, notably Carl Ferdinand Cori and Gerty Theresa Cory (née Radnitz) “for their discovery of the course of the catalytic conversion of glycogen” (Nobel Prize in Physiology or Medicine 1947). The United States even made a stamp honoring Gerty Cori. Can you spot the error in the structure of glucose-1-phosphate? [Gerty Cori Biochemist on USA Stamp]

Hans Adolf Krebs won “for his discovery of the citric acid cycle” (Nobel Prize in Physiology or Medicine 1953). This may not seem important today, especially to those of you who were forced to memorize the reactions, but it was an important part of the revolution in our understanding of cell metabolism.

Hermann Joseph Muller won the 1946 Nobel Prize in Physiology or Medicine “for the discovery of the production of mutations by means of X-ray irradiation.” This is a recognition of the role of mutation in evolution but today Muller is one of the least well-known Nobel laureates. He went on to publish several important papers on mutation load (genetic load) and the idea that only a small percentage of our genome could be functional. The first of these papers was in 1950 and it marked the beginning of junk DNA debate.

I don't think anyone is going to deny the importance of the 1958 Nobel Prize in Physiology or Medicine to George Wells Beadle and Edward Lawrie Tatum “for their discovery that genes act by regulating definite chemical events.” Beadle and Tatum showed that each gene controls a specific enzyme in a metabolic pathway and they called this the "one gene - one enzyme" hypothesis. It marked a turning point in our understanding of molecular biology. They shared the prize with Joshua Lederberg "for his discoveries concerning genetic recombination and the organization of the genetic material of bacteria." Lederberg clearly belongs on this list.

Most people know Frederick "Fred" Sanger for developing the Sanger DNA sequencing technique but long before that he was working on sequencing proteins. He got the 1958 Nobel Prize in Chemistry “for his work on the structure of proteins, especially that of insulin.” It took him almost a decade to sequence insulin working quietly in the background while people like Perutz, Kendrew, Watson, and Crick got all the glory at Cambridge. Now there's an entire institute named after him: Wellcome Sanger Institute.

Max Perutz and John Kendrew deserved their 1962 Nobel Prize in Chemistry “for their studies of the structures of globular proteins.” They got it in the same year that Jim Watson, Francis Crick and Maurice Wilkins got the Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material." They are pictured below with another Nobel laureate named John Steinbeck—he wrote a travel book. That was also the year that Linus Pauling won his second Nobel Prize. This time it was "for his fight against the nuclear arms race between East and West."

The Nobel Prize in Chemistry 1972 went to Christian B. Anfinsen “for his work on ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation” and Stanford Moore and William H. Stein “for their contribution to the understanding of the connection between chemical structure and catalytic activity of the active centre of the ribonuclease molecule.” These men aren't as well known as some other Nobel laureates but their contributions were important because they led to an understanding of how enzymes catalyze reactions. This is pretty important in biochemistry.

One of the most complicated enzymes is ATP synthase and Paul D. Boyer and John E. Walker were awarded the 1997 Nobel Prize in Chemistry ”for their elucidation of the enzymatic mechanism underlying the synthesis of adenosine triphosphate (ATP).” We're now teaching the third generation of biochemstry students how the protonmotive force drives the spinning of the F₀ component and the phosphorylation of ADP. You can't get much more exciting than that!

ATP synthase is important but animals get most of their energy from plants that fix carbon, powered by the sun. Johann Deisenhofer, Robert Huber and Hartmut Michel won the 1988 Nobel Prize in Chemisrty ”for the determination of the three-dimensional structure of a photosynthetic reaction centre” [A Simple Version of Photosynthesis]. I suspect that most of you have never heard of those scientists and most of you have no idea how a photosynthetic reaction center works. That's because photosynthesis isn't taught in most biochemistry courses. That needs to change. (Deisenhofer (left), Huber (middle), Michel (right))

The 2009 Nobel Prize in Chemistry was controversial. It went to Venkatraman Ramakrishnan, Thomas A. Steitz, and Ada E. Yonath “for studies of the structure and function of the ribosome.” Nobody questions the importance of ribosomes and nobody doubts that those three scientists were deserving Nobel laureates. The problem is that there were others who made substantial contributions. Many of us think that Harry Noller also deserved recognition.

Other noteworthy prize winners are Roger Kornberg ”for his studies of the molecular basis of eukaryotic transcription” (Nobel Prize in Chemistry 2006). Also Sidney Altman and Thomas R. Cech ”for their discovery of catalytic properties of RNA” (Nobel Prize in Chemstry 1989.

I saved the best for the last. There is one scientist who, in my opinion, stands head and shoulders above the rest in terms of his singular contribution to a fundamental concept in biochemistry. That scientist is Peter Mitchell who was recognized “for his contribution to the understanding of biological energy transfer through the formulation of the chemiosmotic theory” (Nobel Prize in Chemistry 1978). There aren't many examples of paradigm shifts in the field of biochemistry and molecular biology but the shift in our understanding of enzyme reactions is one. Before Mitchell, we all thought that most biochemical reactions were similar to simple chemical reactions but Peter Mitchell showed us that creating a proton gradient across a membrane could power the synthesis of ATP. [Ode to Peter Mitchell]

Several Nobel Prizes have been awarded for technological achievements like cloning, sequencing DNA, site-directed mutagenesis, CRISPR/Cas9, and PCR. However, Uli Laemmli never got a Nobel Prize for SDS polyacrylamide gels. (It would have been shared with Bill Studier who developed slab gels.) Also, there was no Noble Prize for C₀t analysis or reassociation kinetics in spite of the fact that it made major contributions to our understanding of genomes. Roy Britten is the obvious choice.

Leonor Michaelis and Maud Menten never got a Nobel Prize for their work on enzyme kinetics (the Michaelis-Menten equation) even though they made a major contributions to our understanding of catalysis and enzyme function.

None of the scientists who are responsible for our understanding of evolution, Ronald Fisher, J.B.S. Haldane, Sewell Wright, Motoo Kimura, and Tomoko Ohta, among others, were ever recognized by the Nobel committees. This is because evolutionary theory doesn't fit into any of the categories defined by Alfred Nobel in his will. But Nobel didn't recognize economics as a legitimate Nobel Prize category so there's an opportunity for someone to set up a seventh Nobel Prize to cover biology.¹

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1. I suppose geology and astronomy would want one too!