Rosalind Franklin and the Structure of DNA
X-Ray Crystallography, Photo 51, and a Disputed Credit
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Franklin's work extended beyond DNA to coal and virus research, including important studies of tobacco mosaic virus. She was one of the few women in physics during her time. Linus Pauling had also been working on DNA structure but his approach differed from Franklin's.
The Nobel Prize in Physiology or Medicine went to Watson, Crick, and Maurice Wilkins in 1962, excluding Franklin entirely. This book explores why she received no recognition for her crucial contribution to understanding life's most fundamental molecule.
Anyone interested in scientific discovery and the role of women in science will find this story both compelling and necessary.
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Overview
Rosalind Franklin was an English chemist and X-ray crystallographer whose work helped reveal the structures of DNA, RNA, viruses, coal, and graphite. She earned a PhD from Cambridge in 1945 after researching coal with the British Coal Utilisation Research Association. In 1947, she moved to Paris as a postdoctoral researcher under Jacques Mering. Franklin joined King's College London in 1951, where she took X-ray images of DNA, including Photo 51, which contributed to the discovery of the double helix. After a disagreement with her colleagues Maurice Wilkins and John Randall, she moved to Birkbeck College in 1953. She died of ovarian cancer at age 37 in 1958, just before revealing the structure of the tobacco mosaic virus. Her colleague Aaron Klug continued her research and won the Nobel Prize in Chemistry in 1982.
Family
Rosalind Franklin was born into a family deeply committed to social justice and intellectual rigor. Her father, Ellis Arthur Franklin, was a liberal merchant banker who taught at London's Working Men's College, covering topics like electricity, magnetism, and the history of the Great War. Her mother, Muriel Frances Waley, was the daughter of a prominent Jewish family; her paternal great-uncle, Sir Herbert Samuel, served as Home Secretary in 1916 and was the first practising Jew to join the British Cabinet. Rosalind's aunt, Helen Caroline Franklin—known as Mamie—was married to Norman Bentwich, the Attorney General in the British Mandate of Palestine, and was active in trade union work and women's suffrage. Her uncle Hugh Franklin also played a role in the suffrage movement, though his actions brought embarrassment to the family. Rosalind's middle name, "Elsie," honored Hugh's first wife, who died during the 1918 flu pandemic. The Franklins were involved in helping Jewish refugees escape Nazi persecution, including taking in two children from the Kindertransport, one of whom, Evi Eisenstädter, lived with Jenifer, Rosalind's younger sister.
Education
Rosalind Franklin showed remarkable intelligence as a child, doing arithmetic for pleasure by age six according to her aunt Mamie. She attended Norland Place School with brother Roland, then Lindores School for Young Ladies in Sussex, a seaside boarding school meant to support her health. At eleven, she began at St Paul's Girls' School in Hammersmith, one of the few girls' schools offering physics and chemistry. There, she excelled in science, Latin, sports, and languages, becoming fluent in French while learning German. She topped her classes and won annual awards, although her music skills were weak—her school's composer Gustav Holst once asked her mother if there might be hearing problems or tonsillitis. In 1938, she passed her matriculation with six distinctions, earning the School Leaving Exhibition of £30 a year for three years, plus £5 from her grandfather. Her father asked her to give the money to a refugee student instead.
Cambridge and World War II
Rosalind Franklin went to Newnham College, Cambridge, in 1938, where she studied chemistry as part of the Natural Sciences Tripos. There, she met Bill Price, who worked with her as a lab demonstrator and later became one of her senior colleagues at King's College London. In 1941, she earned second-class honours, which was accepted as a bachelor's degree for employment purposes. During her final year, she met Adrienne Weill, a former student of Marie Curie, who influenced her life and helped improve her French. Franklin was awarded a research fellowship at Newnham, joining the physical chemistry lab under Ronald Norrish, who later won the Nobel Prize in Chemistry. She found his leadership difficult and eventually left his lab. In 1942, she fulfilled National Service by working at the British Coal Utilisation Research Association in Kingston upon Thames. There, she studied coal porosity using helium to determine density and discovered how substances were expelled based on molecular size as temperature rose. This work formed the basis of her PhD thesis, awarded by Cambridge in 1945.
Paris
After the war ended in 1945, Rosalind Franklin asked Adrienne Weill for help finding work as a physical chemist with knowledge of coal's porous structure. At a conference in the autumn of 1946, Weill introduced her to Marcel Mathieu, who worked with the Centre national de la recherche scientifique. That connection led to Franklin joining Jacques Mering's team in Paris. She started on 14 February 1947 among fifteen researchers. Mering studied amorphous substances like rayon using X-ray crystallography, a method different from the study of regular crystals. He taught her how to apply this technique to such materials, which posed new experimental and interpretive challenges. Franklin used it to explore how atoms arrange themselves when carbon turns into graphite. She published several papers on the topic and coined the terms graphitising and non-graphitising carbon. Her coal research later appeared in a 1993 monograph and the textbook Chemistry and Physics of Carbon. Mering kept studying carbon using X-ray diffraction and other methods.
King's College London
In 1950, Rosalind Franklin began working at King's College London on a Turner & Newall Fellowship, initially assigned to study proteins and lipids but soon redirected to DNA research by John Randall, who had been influenced by Maurice Wilkins's early work. Franklin was the only experienced diffraction researcher at King's, and Raymond Gosling was reassigned to assist her. Using a new X-ray tube and a camera chamber she improved with humidity control, Franklin produced high-quality images, discovering that DNA existed in two forms—"A" and "B"—at different humidity levels. She concluded the DNA structure was helical, with phosphate groups on the outside, though she couldn't determine how many chains were present. Her lecture in November 1951 noted that the structure likely contained two, three, or four co-axial nucleic acid chains per helical unit. By July 1952, Franklin and Gosling jokingly announced the "death" of the helical A-DNA form, a prank aimed at Wilkins, who believed both forms were helical. Throughout 1952, they applied the Patterson function to their data, and by January 1953, Franklin concluded both DNA forms had two helices.
Discovery of DNA structure
In November 1951, James Watson and Francis Crick at Cambridge began building a molecular model of B-DNA using data from King's College, where Rosalind Franklin was working. Based on Franklin's lecture that DNA was helical with two or three strands, they built a triple-helix model, which was quickly proven wrong. Franklin had pointed out that phosphate groups were likely on the outside and that the bases were probably inside. Her caution against premature modeling contrasted with their approach. After Pauling's flawed triple-helix paper reached Cambridge in January 1953, Bragg encouraged Watson and Crick to resume work. They were spurred on by information from Max Perutz about Franklin's crystallographic findings, which confirmed a 34 Angstrom repeat and C2 symmetry. By early March, they had built their model, finishing just one day before learning that Franklin was leaving King's. Franklin had already concluded B-DNA was double-helical by February 1953, though she wasn't sure of the strand arrangement. Her final manuscript, "A Note on Molecular Configuration of Sodium Thymonucleate," written March 17, showed her data aligned with the Watson-Crick model, even if she didn't fully grasp its implications at the time.
Birkbeck College
Franklin left King's College London in March 1953 for Birkbeck College, describing the move as "from a palace to the slums ... but pleasanter all the same." She was recruited by John Desmond Bernal, who promoted female crystallographers and had been planning the move. Her labs were in 21 Torrington Square, a cramped Georgian house with dilapidated facilities; she often criticized other staff for carelessness, like when workers in the Pharmacy department flooded her first-floor lab. Though Bernal advised her to stop working on nucleic acids, she helped Gosling finish his thesis and they published evidence of a double helix in the A form of DNA in Nature in July 1953. At year's end, Bernal secured funding for her from the Agricultural Research Council, allowing her to supervise her own research group. John Finch joined her in 1954, followed by Kenneth Holmes in July 1955. Despite the funding, Franklin wrote to Bernal that the facilities were still poorly suited for research, saying her desk and lab were on the fourth floor while her X-ray tube was in the basement, and she supervised four people spread across different floors.
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Overview
In 1952, a young scientist named Raymond Gosling, working in Sir John Randall’s group at King's College London, took a photograph using X-ray crystallography. The image was of DNA fiber, captured on a paracrystalline gel. Gosling labeled it “photo 51” because it was the 51st diffraction photograph he had taken. That same year, Maurice Wilkins shared the image with James Watson without permission. This photo became crucial in understanding the structure of DNA.
Use in discovering structure of DNA
Photo 51 was taken on 2 May 1952 by Raymond Gosling under Rosalind Franklin’s supervision. Though it showed a clear diffraction pattern of DNA's "B" form, Franklin focused on the "A" form and set the image aside. After Franklin left King's College, Gosling, now working for Maurice Wilkins, showed the photo to Watson. Watson recognized the helical pattern from prior work by Francis Crick, and together with Wilkins, used features from Photo 51 along with other data to build their DNA model. Their findings, published in 1953 in the same issue of Nature, were based on contributions from Gosling, Franklin, and Wilkins. In 1962, Watson, Crick, and Wilkins received the Nobel Prize; Franklin and Gosling were not included. Watson later admitted his misrepresentation of Franklin in The Double Helix.
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Overview
DNA is a double helix made of two polynucleotide chains wrapped around each other, carrying genetic instructions for all known organisms and many viruses. Each chain is built from nucleotides, which consist of one of four nitrogen-containing bases — adenine, guanine, cytosine, or thymine — a sugar called deoxyribose, and a phosphate group. The bases pair up in a specific way, with adenine matching thymine and cytosine matching guanine, held together by hydrogen bonds. These chains run in opposite directions, making them antiparallel, and the sequence of bases encodes genetic information. RNA is created using DNA as a template during transcription, with uracil replacing thymine. In eukaryotic cells, DNA is organized into chromosomes inside the nucleus, while prokaryotes store their DNA in the cytoplasm. DNA replication duplicates chromosomes before cell division, ensuring each new cell gets a full set of genetic material.
Properties
DNA is a long molecule made of repeating units called nucleotides, and it usually exists as two strands twisted together into a double helix. Each strand has a backbone of alternating phosphate and sugar groups, with the sugar being 2-deoxyribose. The strands are held together by hydrogen bonds between matching pairs of bases: adenine with thymine, and guanine with cytosine. These two strands run in opposite directions, meaning one end, the 5′ end, has a phosphate group, while the other end, the 3′ end, has a hydroxyl group. The helix wraps around the same axis, with each full twist measuring 34 ångströms, and the overall structure is stabilized by both hydrogen bonds and interactions between the base pairs.
Nucleobase classification
The building blocks of DNA and RNA are called nucleobases, and they fall into two main groups. There are purines, which include adenine and guanine, and these are made of fused five- and six-membered rings. Then there are pyrimidines—cytosine and thymine—which are six-membered rings. A fifth pyrimidine, uracil, appears in RNA instead of thymine, differing from thymine by lacking a methyl group. These nucleobases are key players in how genetic information is stored and copied, forming the essential structure of both natural and artificial nucleic acid systems used today.
Grooves
The DNA molecule is made of two helical strands that wind around each other, forming a double helix. Between these strands are spaces called grooves, which are not the same size. One groove is wider, about 22 angstroms across, and the other is narrower, at 12 angstroms. Because the strands aren’t evenly spaced, this difference in width means that the edges of the DNA bases are more exposed in the wider groove. Proteins that bind to DNA, like transcription factors, usually interact with these base edges in the major groove. This arrangement holds true even when DNA changes shape inside cells, but the names “major” and “minor” groove are always used to describe this size difference as if the DNA were back in its standard B form.
ssDNA vs. dsDNA
Most DNA molecules consist of two complementary strands twisted into a helix held by weak bonds between base pairs; this double-stranded form is stable mainly due to interactions between bases, especially guanine and cytosine. The strands can separate—called melting—at high temperatures, low salt, or high pH. Stability depends on GC content, sequence, and length. Scientists measure this with melting temperature, or Tm, showing the point at which half the molecules become single-stranded. Longer helices with more GC pairs are harder to separate, while shorter ones rich in A and T are easier to pull apart. In biology, regions that need to open easily—like some DNA promoter areas—often have high AT content to make separation simpler. When all base pairs melt, the two strands exist independently in solution, each able to adopt different shapes, though some conformations are more stable than others.
Amount
In human cells, the total DNA in the nucleus stretches to about 6.37 billion base pairs per female cell and 6.27 billion for males, forming a length of roughly 208 centimeters and weighing around 6.5 picograms. Some DNA molecules, like those on chromosome 1, are extremely long—about 85 millimeters when straightened—and contain hundreds of millions of nucleotides. Beyond nuclear DNA, cells also house mitochondrial DNA, which is much smaller and arranged in circular molecules, each about 16,569 base pairs long. Each mitochondrion holds around five of these mtDNA copies, and since a typical cell contains about 100 mitochondria, that means roughly 500 mtDNA molecules per cell. But this number varies greatly by cell type; an egg cell, for instance, may contain up to 100,000 mitochondria, leading to as many as 1.5 million copies of the mitochondrial genome—making up as much as 90% of the DNA in that cell.
Sense and antisense
A DNA sequence is called "sense" if it matches the messenger RNA that gets translated into protein. The opposite strand is known as "antisense." Both kinds can exist on different parts of the same DNA strand. In prokaryotes and eukaryotes, antisense RNAs are produced, though their exact role isn’t fully understood. One idea is that they help control gene expression by pairing with other RNAs. Some DNA sequences in bacteria and viruses, especially those in plasmids, have overlapping genes. These sequences can encode different proteins depending on which strand is read. In bacteria, this overlap may affect how genes are turned on or off, while in viruses, it allows more information to fit into a small genome.
Supercoiling
DNA can be twisted like a rope, a process called supercoiling. When DNA is in its relaxed state, the strands wrap around the double helix axis about once every 10.4 base pairs. If the DNA is twisted in the same direction as the helix, it’s positive supercoiling, which holds the bases more tightly together. Twisting in the opposite direction creates negative supercoiling, making the bases easier to separate. Most DNA in nature has a slight negative supercoiling introduced by enzymes called topoisomerases. These same enzymes are also essential for relieving twisting stress during transcription and DNA replication.
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Overview
James Dewey Watson was an American molecular biologist who, in 1953, co-authored a paper with Francis Crick about the double helix structure of DNA, published in Nature. That same year, Watson, Crick, and Maurice Wilkins were awarded the Nobel Prize in Physiology or Medicine for their discoveries concerning the molecular structure of nucleic acids. Watson earned his doctorate from Indiana University in 1950 and worked at the University of Cambridge's Cavendish Laboratory, where he met Francis Crick. He later directed the Cold Spring Harbor Laboratory, expanding its research and shifting focus to cancer studies. Watson also wrote the bestselling book The Double Helix and made controversial remarks about Rosalind Franklin, who had contributed crucial data for the DNA discovery. Between 1988 and 1992, he helped lead the Human Genome Project, which was completed in 2003.
Early life and education
Born in Chicago on April 6, 1928, James Dewey Watson was the only child of Jean and James D. Watson, whose family traced its roots mostly to colonial English settlers. His maternal grandfather came from Glasgow, Scotland, and his grandmother from County Tipperary, Ireland. Raised as a Catholic, Watson later said he saw himself as "an escapee from the Catholic religion," adding, "The luckiest thing that ever happened to me was that my father didn't believe in God." He grew up on Chicago's South Side, attending Horace Mann Elementary and South Shore High School, where his interest in bird watching, a shared hobby with his father, took root. At 15, he entered the University of Chicago on a tuition scholarship, studying under Louis Leon Thurstone and reading Erwin Schrödinger's What Is Life? in 1946, which redirected his ambitions from ornithology to genetics. He earned his Bachelor of Science in zoology the following year and then moved to Indiana University as a graduate student, attracted by Nobel Prize winner Hermann Joseph Muller. Watson completed his PhD in 1950, with Salvador Luria as his advisor.
Luria, Delbrück, and the Phage Group
James Watson first encountered molecular biology through Salvador Luria, who later won a Nobel Prize for the Luria–Delbrück experiment on genetic mutations. Luria was part of the Phage Group, which studied viruses that infect bacteria. In 1948, Watson began his PhD in Luria's lab at Indiana University and met Max Delbrück that summer at Cold Spring Harbor. The Phage Group believed they were close to discovering the physical nature of genes. Watson took a course with Felix Haurowitz, where he learned that DNA was seen as a "stupid tetranucleotide," not the genetic material. He worked on using X-rays to inactivate phages. In 1950, Watson went to Copenhagen for postdoctoral research, first working with Herman Kalckar, then with Ole Maaløe, a Phage Group member. At a Cold Spring Harbor conference, Watson learned about experiments using radioactive phosphate to trace components of phages. Later, in 1951, Linus Pauling and others published their model of the alpha helix, inspiring Watson to learn X-ray diffraction techniques so he could study DNA. That year, Luria arranged for Watson to work in England, and he visited the Stazione Zoologica Anton Dohrn in Naples.
Identifying the double helix
In mid-March 1953, James Watson and Francis Crick figured out the double helix shape of DNA, relying heavily on data from King's College London—mostly gathered by Rosalind Franklin—and never giving her proper credit. Their paper, titled "Molecular Structure of Nucleic Acids," appeared in Nature on April 25. Sir Lawrence Bragg announced their findings at a scientific meeting in Belgium on April 8, though the press ignored it. A group including Sydney Brenner, Jack Dunitz, Dorothy Hodgkin, Leslie Orgel, and Beryl M. Oughton were among the first to see the model at Oxford University in April. The Cambridge student newspaper Varsity reported the discovery on May 30. Watson later presented his work at the Cold Spring Harbor Symposium in early June, where many hadn't heard yet. In 1962, Watson, Crick, and Maurice Wilkins won the Nobel Prize for their work; Rosalind Franklin had already died in 1958 and was not eligible. Her contribution remained largely unrecognized.
Interactions with Rosalind Franklin and Raymond Gosling
Watson and Crick used unpublished X-ray diffraction data from Rosalind Franklin and her student Raymond Gosling without her knowledge or consent, in building their DNA double helix model. Franklin’s work provided key insights, like the backbones being on the outside and strands being antiparallel. Watson later admitted that “Rosy, of course, did not directly give us her data,” though he acknowledged her results were essential. In The Double Helix, Watson portrayed Franklin negatively, suggesting she was Wilkins’ assistant and unable to interpret her own findings. Critics have called this treatment misogynist. Franklin and Watson later corresponded professionally, consulting on RNA research. All contributors published their work in the same 1953 issue of Nature, with titles including “A Structure for Deoxyribose Nucleic Acid” and “Molecular Configuration in Sodium Thymonucleate.”
Harvard University
In 1956, Watson began teaching at Harvard University’s biology department in Cambridge, Massachusetts, where he studied RNA and its role in transferring genetic information. He remained at Harvard until 1976, even after becoming director of Cold Spring Harbor Laboratory in 1968. During this time, he joined a protest against the Vietnam War, leading a group of twelve biologists and biochemists calling for U.S. troops to leave Vietnam. On the thirtieth anniversary of the Hiroshima bombing in 1975, Watson was among over 2,000 scientists and engineers who urged President Gerald Ford to oppose nuclear proliferation. They warned that radioactive waste could not be safely disposed of and that nuclear plants threatened security by risking plutonium theft. Watson also authored several textbooks, including The Molecular Biology of the Gene, Molecular Biology of the Cell, and Recombinant DNA.
Publishing The Double Helix
In 1968, James Watson published The Double Helix, a book that told the story of how DNA’s structure was discovered, mixing science with personal drama and conflict. The Modern Library later listed it as one of the 100 best nonfiction books of the twentieth century. Watson had originally planned to call it Honest Jim, but controversy followed its release. Francis Crick and Maurice Wilkins objected to the book's publication, and when Harvard University Press refused to publish it, Watson’s own university dropped the project too. The book was eventually published commercially. In a 1975 interview, Francis Crick called Watson’s book a “contemptible pack of damned nonsense.”
Cold Spring Harbor Laboratory
In 1968, James Watson became director of Cold Spring Harbor Laboratory, where he and his wife, Elizabeth, raised two sons between 1970 and 1972. By 1974, the family had settled permanently in Cold Spring Harbor. Watson led the laboratory for about thirty-five years, serving as director, president, and later chancellor. Under his leadership, CSHL grew into a major center for molecular biology and genetics research, especially in understanding cancer and other diseases. Bruce Stillman, who later led the lab, praised Watson’s creation of an unmatched scientific environment. In 2007, Watson said, “I turned against the left wing because they don't like genetics, because genetics implies that sometimes in life we fail because we have bad genes. They want all failure in life to be due to the evil system.”
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Nobel laureates
Five women have won the Nobel Prize in Physics since it was first awarded in 1901 by the Royal Swedish Academy of Sciences. Marie Curie was the first, in 1903, sharing the prize with her husband Pierre and Henri Becquerel for their work on radiation. She later won a second Nobel, in Chemistry, in 1911. Maria Goeppert Mayer won in 1963 for nuclear shell structure, shared with J. Hans D. Jensen and Eugene Wigner. Donna Strickland shared the 2018 prize with Gérard Mourou and Arthur Ashkin for chirped pulse amplification. Andrea Ghez won in 2020 with Reinhard Genzel and Roger Penrose for discovering a supermassive object at the center of our galaxy. In 2023, Anne L'Huillier became the first woman to receive one-third of the monetary award, sharing the prize with Pierre Agostini and Ferenc Krausz for attosecond physics.
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Overview
Linus Carl Pauling, an American chemist and peace activist, lived from February 28, 1901, to August 19, 1994. He published over 1,200 papers and books, with about 850 focused on science. Scientific American recognized him as one of the 20 greatest scientists of all time. His scientific achievements earned him the Nobel Prize in Chemistry in 1954, and his activism led to the Nobel Peace Prize in 1962. He is among only five people to win more than one Nobel Prize, and uniquely, he received two unshared prizes, with one in a different field from the other—Marie Curie being the only other such person. Pauling helped found quantum chemistry and molecular biology. His theories on chemical bonds included orbital hybridization and the first accurate electronegativity scale. He studied biological molecules, highlighting the roles of alpha helices and beta sheets in protein structure. His methods used X-ray crystallography, molecular modeling, and quantum chemistry. His work influenced James Watson, Francis Crick, Rosalind Franklin, and Maurice Wilkins in their DNA research, which enabled geneticists to decode DNA. Later in life, he promoted nuclear disarmament and orthomolecular medicine, especially megavitamin therapy using supplements like Vitamin C. None of his medical theories about high-dose vitamins gained broad scientific acceptance. He was married to the human rights activist Ava Helen Pauling.
Early life and education
Linus Carl Pauling entered the world on February 28, 1901, in Portland, Oregon, to Herman Henry William Pauling and Lucy Isabelle "Belle" Darling. His name honored his maternal grandfather, Linus, and his paternal grandfather, Carl, reflecting German and English-Scottish roots. The family relocated often, eventually settling in Condon, Oregon, after Herman died from a perforated ulcer in 1910. Pauling’s fascination with chemistry began during childhood, sparked by experiments conducted with a friend, Lloyd A. Jeffress. By fifteen, he had set up a lab with another friend, Lloyd Simon, using scavenged materials. He attended Oregon State University in September 1917, having left high school without a diploma and worked as a machinist and in photography to fund his education.
Higher education
Linus Pauling entered college in 1919 with a full schedule: two chemistry courses, two in math, mechanical drawing, mining and explosives, modern English prose, gymnastics, and military drill. His roommate was his childhood friend Lloyd Jeffress. He joined the Delta Upsilon fraternity and stayed active on campus. After his second year, he took a job in Portland teaching quantitative analysis at the college where he'd just finished the course, working forty hours a week and earning US$100 a month, or about US$1,600 in today's money. In his final years, Pauling became interested in the work of Gilbert N. Lewis and Irving Langmuir, focusing on how atomic structure relates to chemical properties, helping to found quantum chemistry. He served as teaching assistant to engineering professor Samuel Graf and taught a chemistry course for home economics majors during his senior year—where he met his future wife, Ava Helen Miller. Pauling graduated in 1922 with a degree in chemical engineering and went on to Caltech, where he studied under Roscoe Dickinson and Richard Tolman. There, he used X-ray diffraction to study crystal structures, publishing seven papers on mineral crystals before earning his PhD summa cum laude in 1925.
Career
In 1926, Linus Pauling received a Guggenheim Fellowship taking him to Munich, Copenhagen, and Zürich, where he studied under Arnold Sommerfeld, Niels Bohr, and Erwin Schrödinger, all experts in quantum mechanics. There, he became interested in applying quantum theory to the structure of atoms and molecules. In Zürich, he was introduced to early quantum mechanical work on the hydrogen molecule by Walter Heitler and Fritz London, which he made central to his future research. By 1927, he had taken a position as an assistant professor at Caltech, where he published about fifty papers in five years and developed what are now called Pauling's rules. In 1931, he received the Langmuir Prize from the American Chemical Society for his work. That same year, he also published his influential paper on hybridization of atomic orbitals and the tetravalency of carbon. He later introduced the concept of electronegativity in 1932, creating a numerical scale to predict bond types. In 1936, Pauling became chairman of the division of chemistry and chemical engineering at Caltech, holding both positions until 1958.
Nature of the chemical bond
In the late 1920s, Linus Pauling began publishing papers on the nature of the chemical bond. By 1937, he was a George Fischer Baker Non-Resident Lecturer in Chemistry at Cornell University, where he delivered nineteen lectures and completed his influential textbook The Nature of the Chemical Bond. That work, based largely on his research in this area, earned him the Nobel Prize in Chemistry in 1954. His book became known as chemistry's most important text of the century, cited more than sixteen thousand times in the thirty years after its first edition in 1939. Pauling introduced concepts like orbital hybridization, showing how atomic orbitals mix to form new shapes suited for bonding. He also explored how ionic and covalent bonding are extremes, with most bonds being a blend of both, using electronegativity to predict the degree of ionicity. Additionally, he reexamined benzene's structure, moving beyond Kekulé's idea of rapid interconversion to describe it instead as a resonance structure—an intermediate form blending multiple arrangements.
Ionic crystal structures
In 1929, Linus Pauling introduced five rules that help explain the crystal structures of ionic compounds. These rules look at things like the size ratio between cations and anions, how strong electrostatic bonds are, and how polyhedra share corners, edges, and faces. They also consider what happens when crystals contain different types of cations and follow a principle of simplicity known as the rule of parsimony.
Biological molecules
In the 1930s, Linus Pauling turned his attention to biological molecules, influenced by the Rockefeller Foundation's funding priorities and interactions with biologists like Thomas Hunt Morgan and Alfred Sturtevant. He studied hemoglobin with student Charles Coryell, discovering how it changed structure when binding oxygen, which led him to explore protein structure more deeply. Using X-ray diffraction, he revisited earlier work by William Astbury but couldn't explain his results until 1948, when he realized Astbury's samples were tilted. Pauling proposed the alpha helix and beta sheet as key structural motifs in proteins, introducing an unconventional idea that one turn of the helix could contain a non-integer number of amino acids. In 1951, he suggested DNA was a triple helix, though his model had flaws, including incorrect phosphate charges. At the Cavendish Laboratory, James Watson and Francis Crick were allowed to build a DNA model using data from Maurice Wilkins and Rosalind Franklin, who had produced the best X-ray images of DNA at King's College. Pauling later said this was "the biggest disappointment in his life," though he had seen some of Franklin's work through his assistant Robert Corey, who attended a 1952 protein conference in England while Pauling was blocked by a withheld passport due to political suspicion. Despite having the chance to see Franklin's data, Pauling did not visit her lab and instead moved on, grateful for his earlier discoveries. He also studied enzyme reactions and proposed that enzymes stabilize transition states, and with Max Delbrück, suggested DNA replication relies on structural complementarity rather than similarity.
Molecular genetics
In November 1949, Linus Pauling and colleagues Harvey Itano, S. J. Singer, and Ibert Wells published "Sickle Cell Anemia, a Molecular Disease" in Science, proving the first human disease stemmed from an abnormal protein. Using electrophoresis, they showed people with sickle cell anemia had modified hemoglobin while those with the trait carried both normal and abnormal versions. This was the first time a specific protein defect was causally linked to a disease, demonstrating how Mendelian inheritance determines protein properties. Pauling later speculated that other illnesses, including schizophrenia, might also stem from genetic flaws. As chairman of the Division of Chemistry and Chemical Engineering at Caltech, he pushed for a chemical-biomedical approach to mental illness. In 1951, he gave a lecture titled "Molecular Medicine," and in the late 1950s studied enzymes in brain function, believing mental illness could be partly due to enzyme dysfunction. In the 1960s, working with student Emile Zuckerkandl, he proposed the molecular evolutionary clock—the idea that mutations in DNA and proteins accumulate at a steady rate over time.
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Overview
The Nobel Prize in Physiology or Medicine is awarded annually by the Nobel Assembly at Karolinska Institutet to scientists who have made exceptional contributions to health and medicine. Created according to Alfred Nobel's 1895 will, the prize recognizes discoveries that have brought the greatest benefit to humankind. Since its first award in 1901, 116 prizes have been given to 232 individuals—218 men and 14 women. The first woman to win was Gerty Cori in 1947, for her work on glucose metabolism. The most recent prize, announced in 2025, went to three scientists: Mary E. Brunkow and Fred Ramsdell from the United States, and Shimon Sakaguchi from Japan, for their research on immune tolerance. Each winner receives a medal, diploma, and monetary award, presented annually on December 10, the anniversary of Nobel's death. Some awards have been controversial, such as António Egas Moniz's 1949 prize for prefrontal lobotomy, which drew criticism from the medical community. Another dispute involved Selman Waksman's 1952 award, which led to a court case over patent rights. The Nobel Prize cannot be awarded posthumously and is limited to no more than three recipients per year.
Background
Alfred Nobel, a chemist and inventor who made his fortune from 355 inventions—dynamite being most well known—was born in Stockholm, Sweden, into a family of engineers. He developed interest in experimental physiology and established laboratories in France and Italy where he studied blood transfusions. In 1888, shocked to read his own obituary titled "The Merchant of Death Is Dead" in a French newspaper, not realizing it referred to his brother Ludvig, he rewrote his will specifying wealth be used to award prizes in physics, chemistry, peace, physiology or medicine, and literature. His final will was drawn up just over a year before he passed away in 1896 at age sixty-three, not approved by Norwegian Parliament until 1897. After his death, the Nobel Foundation was formed to manage his estate. In 1900, Swedish King Oscar II issued the foundation's statutes. According to Nobel's wishes, the Karolinska Institute in Sweden awards the Prize in Physiology or Medicine, now commonly called the Nobel Prize in Medicine.
Nomination and selection
The Nobel Prize in Physiology or Medicine rewards discoveries benefiting mankind, with nominations from Karolinska Institute professors, global academy members, and past laureates. Until 1977, Karolinska's professors selected winners directly, but Swedish law changes created the independent Nobel Assembly with fifty members forming a five-member Nobel Committee, Secretary, and ten adjunct members to evaluate nominees. In 1968, it was ruled no more than three people can share a prize. The committee has always favored basic science over applied work—Jonas Salk and Albert Sabin were not awarded for polio vaccines, though John Enders, Thomas Weller, and Frederick Robbins were for discovering how the virus reproduced in lab settings. Classical physiology laureates were last in 1963, when John Eccles, Alan Hodgkin, and Andrew Huxley were honored for their work on electrical events in the nervous system.
Medals
The Nobel Prize in Physiology or Medicine medal features Alfred Nobel's left-profile portrait on the front, designed by Erik Lindberg. The reverse shows the Genius of Medicine holding an open book, collecting water from a rock to quench a sick girl’s thirst. It includes the Latin inscription "Inventas vitam iuvat excoluisse per artes," an adaptation of a line from Virgil’s Aeneid. Below the figures, the recipient’s name is engraved, along with "REG. UNIVERSITAS MED. CHIR. CAROL." denoting the Karolinska Institute. From 1902 to 2010, these medals were produced by Myntverket in Eskilstuna. In 2011, the task moved to Det Norske Myntverket in Kongsberg, and since 2012, Svenska Medalj has taken over production in Eskilstuna.
Diplomas
The Nobel Prize in Physiology or Medicine is awarded by the Nobel Assembly at Karolinska Institute, and each laureate receives a diploma directly from the King of Sweden. These diplomas are individually crafted, with well-known Swedish artists and calligraphers responsible for their creation. Every diploma features both an image and text that formally recognize the winner’s name and the reason for their honor.
Award money
At the awards ceremony, the laureate receives a document showing the amount of the cash prize. The sum varies from year to year depending on funding from the Nobel Foundation. In 2009, the total was 10 million SEK, which equals about US$1.4 million. By 2012, it had dropped to 8 million Swedish Krona, or roughly US$1.1 million. When there are two winners in a category, the award is split equally between them. If there are three, the committee can choose to divide it evenly or give half to one person and a quarter to each of the others.
Ceremony and banquet
The awards are given at a grand ceremony and then followed by a banquet. The Nobel Banquet is a fancy event where the menu is chosen months ahead and kept secret until the day itself. A team from the Nobel Foundation selects it after tasting dishes from top chefs around the world. Right now, it's a three-course meal, though it used to have six courses back in 1901. Each Nobel Prize winner can bring up to sixteen guests. The Swedish royal family usually shows up, along with the Prime Minister and other government officials, as well as members of the Nobel family.
Laureates
The Nobel Prize in Physiology or Medicine began in 1901 when Emil Adolf von Behring was honored for serum therapy. Ronald Ross received the 1902 award for identifying mosquitoes as malaria carriers. The following year, Niels Ryberg Finsen was recognized for using light radiation to treat diseases like lupus vulgaris. Ivan Pavlov earned the 1904 prize for digestion studies. Over time, the scope expanded to include signal transduction and neurobiology. In 1973, Nikolaas Tinbergen, Konrad Lorenz, and Karl von Frisch shared the award for animal behavior observations. As of 2025, 116 prizes have been given to 232 individuals, with thirteen women winners including Rosalyn Yalow in 1977 and Barbara McClintock in 1983. In 2007, Mario Capecchi, Martin Evans, and Oliver Smithies were recognized for gene targeting in mice. The following year, Elizabeth Blackburn, Carol W. Greider, and Jack W. Szostak shared the prize for discovering how chromosomes are protected by telomeres and the enzyme telomerase. Rita Levi-Montalcini, who lived to 100, was the first Nobel laureate to reach that age. Through 2025, the prize had been awarded to one person 40 times, to two laureates 35 times, and to three people 41 times.
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