Christian Anfinsen was an American biochemist who advanced molecular biology and protein research. His work illuminated how proteins achieve their three-dimensional structures, a process fundamental to life. A Nobel laureate, he was recognized for his impact on the scientific community.
Christian Anfinsen’s Early Life and Scientific Path
Christian Boehmer Anfinsen Jr. was born on March 26, 1916, in Monessen, Pennsylvania, to Norwegian immigrant parents. His family moved to Philadelphia in the 1920s, where he began his academic journey. Anfinsen attended Swarthmore College on a scholarship, earning a Bachelor of Science degree in chemistry in 1937.
He continued his studies at the University of Pennsylvania, receiving a Master of Science degree in organic chemistry in 1939. A 1939 fellowship from the American-Scandinavian Foundation allowed him to study enzyme structure at the Carlsberg Laboratory in Copenhagen, Denmark, mentored by Kaj Ulrik Linderstrøm-Lang, a scientist known for defining protein structures. World War II prompted his return to the United States in 1940. He pursued doctoral studies at Harvard Medical School, earning his Ph.D. in biochemistry in 1943. Anfinsen remained at Harvard as an instructor and assistant professor until 1950, researching malaria, proteolytic enzymes, and radioactive labeling.
Unraveling Protein Folding The Anfinsen Dogma
Anfinsen addressed a central mystery in biochemistry: how a linear chain of amino acids, known as a polypeptide, folds into a specific, functional three-dimensional structure. He hypothesized that the amino acid sequence itself contained all the necessary information for a protein to spontaneously achieve its correct folded shape.
To test this idea, Anfinsen conducted experiments using bovine pancreatic ribonuclease A (RNase A), an enzyme composed of 124 amino acids and containing four disulfide bonds. He denatured, or unfolded, the enzyme using a combination of urea and beta-mercaptoethanol. Urea disrupted the non-covalent interactions that maintain the protein’s secondary and tertiary structures, while beta-mercaptoethanol broke the disulfide bonds.
After denaturing RNase A, Anfinsen removed both denaturing agents. He observed that the protein spontaneously refolded into its original, biologically active conformation, regaining its enzymatic function. This demonstrated that the protein’s primary amino acid sequence alone was sufficient to dictate its specific three-dimensional structure and function.
This concept became known as the “Anfinsen Dogma” or the thermodynamic hypothesis of protein folding. It posits that the native, functional structure of a protein is the most thermodynamically stable state under a given set of environmental conditions. This means the protein naturally seeks out the lowest energy conformation dictated by its amino acid sequence. Further experiments by Anfinsen reinforced this, showing that if disulfide bonds formed incorrectly, the protein would be scrambled and inactive, but could refold correctly when trace amounts of beta-mercaptoethanol were added, allowing disulfide bonds to rearrange into the most stable configuration.
The Significance of Anfinsen’s Discoveries and the Nobel Prize
The Anfinsen Dogma established a foundational principle of protein structure in biochemistry and molecular biology. This understanding helps comprehend how proteins function and how their misfolding can lead to diseases like Alzheimer’s and Parkinson’s. The ability of proteins to spontaneously fold based on their sequence opened new avenues for research into protein engineering and drug design.
Anfinsen’s work received international recognition. In 1972, he was awarded the Nobel Prize in Chemistry. He shared the prize with Stanford Moore and William H. Stein of Rockefeller University. Their collective contributions focused on ribonuclease, with Anfinsen recognized for his work on the connection between the amino acid sequence and the biologically active conformation.
Moore and Stein were honored for their contributions to understanding ribonuclease’s chemical structure and catalytic activity. While Anfinsen elucidated protein folding, Moore and Stein detailed the enzyme’s amino acid sequence and identified specific amino acids involved in its catalytic function. Together, their research provided a comprehensive picture of ribonuclease, from its linear sequence to its functional three-dimensional form.
Beyond Protein Folding Anfinsen’s Wider Scientific Contributions
Beyond his Nobel-recognized research, Christian Anfinsen held significant leadership roles. In 1950, he joined the National Institutes of Health (NIH) in Bethesda, Maryland, becoming Chief of the Laboratory of Cellular Physiology and Metabolism. He later headed the Laboratory of Chemical Biology at the National Institute of Arthritis, Metabolism, and Digestive Diseases from 1963 to 1982.
Anfinsen also authored the book, “The Molecular Basis of Evolution,” published in 1959. This work explored the relationship between protein chemistry, genetics, and evolutionary theory, highlighting how macromolecular structure information could be used in evolutionary analysis.
His intellectual breadth extended to humanitarian efforts, as he actively promoted human rights for scientists globally.