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Thursday, February 16, 2023

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

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


Patricia Romans said...

Barbara McClintock was omitted from your list. She won the 1983 prize in Physiology or Medicine for her discovery of mobile genetic elements. She should also have won for her much earlier work that proved the chromosome theory of inheritance, Creighton and McClintock, 1931.

If there had been a Nobel Prize in Geosciences away back when, any or all of Alfred Wegener, Bruce Heezen (and Marie Tharp), Vic Vaquier, Edward Bullard and John Tuzo Wilson, would have won for their contributions to continental drift/plate tectonics.

Larry Moran said...


I met Barbara McClintock. I’m sure others will have their own list. I probably should have included Dorothy Hodgkin.

Robert Byers said...

I notice something is wrong with these awards.what does it mean? What if that year you had nine worthy to win and the next year none? The award would not tell the tale of accomplishment. From your long list it would include thousands in just one subject. either they really are not such a big deal or all of them are. I think the concept of judging accomplishment in science subjects has no meaning. Something could be more complicated and so a greater conquest but a less complicated thing might save many people in some health issue. is the the smart curve or the useful curve that deserves a award? is science about smart thinking/results or excellent results including smart thinking?
In primitive days when nothing was known it was easy for a single person to figure out a notable thing but today the easy stuff has been done and its harder to figure stuff out and they really don't do much. There is no winners today because so many are doing something and nobody is doing anything notable.
Also of coarse evolution and plate teutonics are speculative and not facts. it all started with the first awrd called the copley award.
i only heard , before closer attention to science history, ever of nobel awards as going to Einstein, Watson and cRick, and the three who invented the transistor. Nothing else was noted by regular folks.

Matt G said...
This comment has been removed by the author.
Snake said...

I'm glad Larry mentioned Dorothy Hodgkin in the comments, as I was about to argue for her inclusion. She was famously honoured in the UK national press with the headline "Oxford wife wins Nobel prize"

Joe Felsenstein said...

The photo of Josh Lederberg does not show him with Beadle and Tatum. The guy in the center is James F. Crow, a longtime colleague of Lederberg when Lederberg was at the University of Wisconsin. The guy on the right is, I think, the University's President Fred Harrington.

Joe Felsenstein said...

Should also note that, although Hermann J. Muller may be less well-known now than are important molecular biologists, he was fairly clearly the leading classical geneticist. (Classical genetics was the field of genetics from 1900 to 1950. I keep hearing people say that genetics began with Watson and Crick, but not so.) He showed that irradiation could induce mutations by constructing extremely clever chromosome rearrangement genotypes and making crosses using them. He was President of the Genetics Society of America in 1947, his immediate predecessors being George Beadle (1946) and Barbara McClintock (1945).

Larry Moran said...


Now I'm confused. The photo I posted is from the University of Wisconsin - Madison and the caption says, "Joshua Lederberg, who founded the department of medical genetics at the University of Wisconsin - Madison, poses with George Beadle and Edward L. Tatum, with whom he shared the Nobel Prize. Joshua Lederberg won the 1958 Nobel Prize in medicine for his work discovering sharing of genes in bacteria."

I looked closely at the photo and thought I saw a resemblance between the men in this photo and other pictures of Beadle and Tatum although I was puzzled by the glasses on all three.

Now that you've brought it to my attention, it's clear that the man in the middle is, indeed, James Crow.

I've removed the photo. You should probably contact Wisconsin.

Larry Moran said...


I agree that Muller doesn't get enough credit. I discussed his ideas about mutation load with the student who wrote a history of junk DNA.

I tried to convince her that it was Muller and J.B.S. Haldane (and others) who raised the issue of genomes being too large. She rejected that idea because, according to her, the idea of junk DNA began when scientists realized that not all DNA was coding DNA in 1957-59. That's when they starting calling noncoding DNA "junk."

I wish I could have met Muller - he died in 1967. He sounds like a very smart man judging by his papers, which should be more widely read.

Joe Felsenstein said...

I looked closely at the photo and thought I saw a resemblance between the men in this photo and other pictures of Beadle and Tatum although I was puzzled by the glasses on all.
Having known Jim Crow for 51 years, I instantly recognized him. You can compare the guy on the right with Fred Harvey Harrington, of whom there are good photos on the web.

SPARC said...

I would appreciate if Marilyn Kozak would be nominated. I wonder if aligning sequences and calculating a consensus was common knowledge in 1984.

Joe Felsenstein said...

I wonder if aligning sequences and calculating a consensus was common knowledge in 1984.
Short answer: yes. Aligning sequences was necessary in the study of protein sequences. It could often be done by hand with protein sequences; the Smith-Waterman algorithm was published in 1981. Phylogenies made with protein sequences, in the 1960s, all started with alignments of those sequences.

Larry Moran said...


Here's a brief summary of the trees constructed in the 1960s by aligning the amino acid sequences of cytochrome c. I included a copy of a table from Margoliash (1963).

Jonathan Badger said...

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

There is already a prestigious prize for those fields, which is analogous to the Nobel and, like the Nobel, it is even presented by the King of Sweden. It's called the Crafoord prize. Evolutionary biologists like Tomoko Ohta, E.O. Wilson, Richard Lewontin and Carl Woese have won it, as have astronomers like Martin Rees, Andrea Ghez (before she won the Nobel, which astronomers and evolutionary biologists can win, if rarely) and Roy Kerr.

Wade said...

Regards Sanger, in talks I used to reuse a 'joke' that Sanger spent years working out the sequence of insulin and the result was that he decided to invent DNA sequencing so he didn't have to do that anymore.

Bayesian Bouffant, FCD said...

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

Is this some kind of trick question? There are no Nobel Prizes in Biochemistry & Molecular Biology. There are prizes in Chemistry and in Medicine & Physiology.

Anonymous said...

You obviously know this but omitted mentioning that Fred Sanger won not one but TWO Nobel Prizes. In a 2010 (or so) interview he said he would never be able to survive academically in the current system and that his contributions were possible because no one bothered him with "productivity" or "impact factor" and the like. And of course he was entirely nonchalant and dismissive of his awards, like a truly wise person should be. He was smart enough to realize that he would soon be forgotten and that science students would eventually think "Sanger" sequencing stands for "the name of the company that invented sequencing". (This is a true story).