- Person
- Christian Anfinsen
- Lived
- 1916–1995
- Field
- Biochemistry
- From
- American
The story
Proteins do most of the work in living cells, and each one is a chain of amino acids whose order is set by a gene. To work, the chain must fold into one precise three-dimensional shape. In the 1950s nobody knew where the instructions for that shape came from: did cells need extra machinery or genetic information, or was the shape written into the chain itself?
Christian Anfinsen, a biochemist at the U.S. National Institutes of Health who was born to Norwegian immigrants in 1916 and converted to Judaism in 1979, studied the question with the enzyme ribonuclease, supplied by a Chicago meat-packing company. With colleagues including Michael Sela and Fred White, he used chemicals to break the enzyme’s four internal cross-links and unravel its chain completely, destroying its activity. When the chemicals were removed and the protein was left in a mild solution, it refolded on its own, re-formed its cross-links correctly and became active again. Of the 105 possible ways its eight cysteine amino acids could pair up, it found the single correct one by itself.
Anfinsen concluded that all the information a protein needs to fold is contained in its amino acid sequence, and that its working shape is simply its most stable one under the conditions in a cell. He called this the thermodynamic hypothesis; it is often called Anfinsen’s dogma. He shared the 1972 Nobel Prize in Chemistry for this work.
The idea opened two great fields. Because proteins can fold by themselves in a test tube, scientists could study folding experimentally, and biotechnology could learn to refold proteins made in microbes into active forms. And because sequence determines structure, it should be possible to predict a protein’s shape from its sequence. When the 2024 Nobel Prize in Chemistry was awarded for the AI system AlphaFold and for computational protein design, the Swedish Academy’s explanation began with Anfinsen’s 1961 conclusion as the insight that set up this half-century challenge. AlphaFold has now predicted structures for almost all of the roughly 200 million known proteins, a resource used worldwide in research on medicines, vaccines and enzymes.
Why it matters
Anfinsen’s principle that sequence determines shape is the foundation of protein folding research and of AI tools like AlphaFold used to design medicines.
About Christian Anfinsen
NIH biochemist who showed that a protein’s amino-acid sequence alone sets its 3D shape, the idea behind modern protein design and AI structure prediction. Converted to Judaism in 1979. Nobel 1972.
Sources
- Protein Folding and the Thermodynamic Hypothesis, 1950–1962 Profiles in Science, U.S. National Library of Medicine
- Press release: The Nobel Prize in Chemistry 1972 NobelPrize.org
- Popular information: The Nobel Prize in Chemistry 2024 NobelPrize.org
- Christian B. Anfinsen, Biographical Overview Profiles in Science, U.S. National Library of Medicine
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.