A Norwegian-American boyhood
Christian Boehmer Anfinsen Jr. was born on March 26, 1916, in Monessen, Pennsylvania, a steel town on the Monongahela River. His parents, Sophie Rasmussen and Christian Boehmer Anfinsen Sr., a mechanical engineer, were Norwegian immigrants who brought up their children on the Norwegian language and its history and culture. In the 1920s the family moved to Philadelphia.
In 1933 Anfinsen went to Swarthmore College on a scholarship. He played varsity football and earned a bachelor’s degree in chemistry in 1937. Years later, with characteristic modesty, he recalled that everyone at Swarthmore had been a genius except him.
Copenhagen, Harvard and the war
After a master’s degree in organic chemistry at the University of Pennsylvania in 1939, Anfinsen won an American-Scandinavian Foundation fellowship to the Carlsberg Laboratory in Copenhagen, one of Europe’s leading centres for the study of proteins. The outbreak of the Second World War cut his stay short. He returned to the United States and completed a doctorate in biochemistry at Harvard Medical School in 1943, with a dissertation on the chemistry of the retina. During the war he also worked for the federal Office of Scientific Research and Development.
He stayed at Harvard Medical School as an instructor and then assistant professor until 1950, with a year in 1947 and 1948 at the Medical Nobel Institute in Stockholm working with the biochemist Hugo Theorell. His early research at Harvard, with Daniel Steinberg, looked at how radioactive labels were distributed in newly made proteins, a technique that later helped other scientists show that cells build protein chains in sequence from one end to the other. In 1950 he moved to the National Institutes of Health in Bethesda, Maryland, as chief of the Laboratory of Cellular Physiology at the National Heart Institute. It was at NIH, the American government’s medical research agency, that he did the work that made him famous.
A riddle about proteins
Proteins do most of the work in living cells. Each is a long chain of amino acids, strung together in an order dictated by a gene. But a protein is not useful as a floppy string. To work, the chain must fold into one precise three-dimensional shape, the way a key must have the right cuts to open a lock. In the 1950s nobody knew where the instructions for that shape came from. Did the cell need extra machinery or extra genetic information to fold each protein correctly, or was the shape somehow written into the chain itself?
Anfinsen chose an enzyme called ribonuclease to find out, partly for practical reasons: the Armour meat-packing company in Chicago could supply his laboratory with a steady stream of raw material from cattle pancreas. Ribonuclease is a fairly small protein held in shape by four chemical cross-links, called disulfide bonds, between pairs of the amino acid cysteine.
Unfolding and refolding
In a series of experiments in the late 1950s and early 1960s, Anfinsen and his colleagues, including the postdoctoral scientists Michael Sela and Fred White, used harsh chemicals to break ribonuclease’s cross-links and unravel the chain completely, destroying its activity. Then they gently removed the chemicals and let the protein sit in a neutral solution exposed to air.
The result was striking. The chain folded itself back up, re-formed its cross-links in the right places and regained its enzyme activity. With eight cysteines there are 105 possible ways to pair them, and only one gives a working enzyme, yet the protein found that one arrangement on its own. Anfinsen concluded that the information needed to fold a protein into its working shape lies entirely in its sequence of amino acids, and that the native shape is simply the most stable one under the conditions inside a cell. He called this the thermodynamic hypothesis. Others came to call it Anfinsen’s dogma.
The path there was not smooth, and Anfinsen was honest about it. A paper he published in 1955 after a year back at the Carlsberg Laboratory reached a conclusion that he later decided was wrong, and he spent, in his words, about fifteen years disproving it. His laboratory also discovered an enzyme in cells that speeds up the shuffling of disulfide bonds, helping explain how proteins fold quickly enough in living tissue.
From a test tube to AlphaFold
Anfinsen’s finding opened two enormous fields. The first is experimental protein folding. Because proteins can fold by themselves in a test tube, scientists could study how they do it, and the biotechnology industry could learn to refold proteins made in bacteria or yeast into their active forms. That matters for the manufacture of many protein medicines.
The second is prediction. If the sequence alone determines the shape, then in principle a protein’s structure can be calculated from its sequence, which is far cheaper to read than a structure is to measure. That became the great challenge of biochemistry for half a century. When the Nobel Prize in Chemistry 2024 was awarded for the artificial-intelligence system AlphaFold and for computational protein design, the Swedish Academy’s own explanation began with Anfinsen: his conclusion that a protein’s structure is governed by its amino acid sequence was what made the prediction problem thinkable. AlphaFold has since predicted structures for almost all of the roughly 200 million known proteins, a resource used by researchers developing medicines, vaccines and enzymes worldwide.
The idea also sharpened the study of disease. Illnesses such as Alzheimer’s, Parkinson’s and prion diseases involve proteins that fold wrongly or clump together, and understanding why folding sometimes fails begins with Anfinsen’s picture of how it normally succeeds.
Conversion to Judaism
Anfinsen was not born Jewish. He grew up in a Norwegian Lutheran immigrant family and described himself for most of his life as an agnostic. His connection with Israel began through science: he spent 1958 and 1959 at the Weizmann Institute of Science in Rehovot on a Guggenheim fellowship and from 1962 served on the institute’s board of governors, later chairing its scientific advisory committee.
In 1978 his first marriage, to Florence Kenenger, with whom he had three children, ended in divorce. In 1979 he married Libby Esther Shulman Ely, and that year he converted to Orthodox Judaism, a commitment he kept for the rest of his life. He remained frank about his intellectual temperament. In 1985 he wrote that his feelings about religion still strongly reflected a fifty-year period of what he called orthodox agnosticism, and he described Judaism as an extremely interesting philosophical package. In 1981 he and Libby moved to Israel for a planned post at a new biotechnology company linked to the Weizmann Institute, but its American financial backer pulled out within weeks of their arrival.
Johns Hopkins, hot springs and human rights
Before that, through the 1960s and 1970s, Anfinsen had been one of the leaders of American protein science. He was elected to the National Academy of Sciences in 1963, served as president of the American Society of Biological Chemists in 1971 and 1972, and edited the series Advances in Protein Chemistry. His laboratory spent years on a bacterial enzyme, the extracellular nuclease of Staphylococcus aureus, determining the sequence of its 149 amino acids and, with a crystallography group at MIT led by F. A. Cotton, its three-dimensional structure. That partnership of chemistry and structure was exactly the combination his folding work had called for. After the Israeli setback Anfinsen joined Johns Hopkins University in 1982 as professor of biology. From 1983 until his death his main research was on hyperthermophiles, microorganisms that thrive at temperatures near boiling, whose unusually tough proteins offered new clues about stability and folding and hinted at industrial uses for heat-resistant enzymes. Earlier, from the 1960s to 1981, he had led the Laboratory of Chemical Biology at what is now the National Institute of Diabetes and Digestive and Kidney Diseases, and he wrote The Molecular Basis of Evolution (1959), an early attempt to connect protein chemistry with genetics.
Outside the laboratory he campaigned for nuclear disarmament, against environmental damage and for scientists in other countries whose human rights were abused, and in 1990 he took part in a Nobel conference in Oslo on the anatomy of hate. He played the viola and the piano and was a keen sailor on Chesapeake Bay.
Death and legacy
Christian Anfinsen died of a heart attack on May 14, 1995, in Randallstown, Maryland, less than a year before his eightieth birthday. A year later the Protein Society created the Christian B. Anfinsen Award to honour technical achievements in protein science.
His 1972 Nobel Prize in Chemistry was shared with Stanford Moore and William H. Stein, who studied the same enzyme from a different angle. Anfinsen’s half was for showing the connection between a protein’s amino acid sequence and its biologically active shape. That connection is now one of the foundations of molecular biology. Every time a researcher designs a new enzyme, predicts the structure of a virus protein or studies a disease of misfolded proteins, they are building on the patient experiments of a scientist who simply let a protein fold itself back together and watched what happened. He had found, in one small enzyme from cattle, a rule that holds across the living world.
Sources & further reading
Christian B. Anfinsen, Biographical Overview, Profiles in Science, U.S. National Library of Medicine · Protein Folding and the Thermodynamic Hypothesis, 1950–1962, Profiles in Science, NLM · Christian Anfinsen, Biographical, NobelPrize.org · Popular information: Nobel Prize in Chemistry 2024, NobelPrize.org · Christian Anfinsen, Jewish Virtual Library · Christian B. Anfinsen, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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