People / Science & Medicine / Arthur Kornberg
Photo: 1959, public domain, via U.S. National Library of Medicine and Wikimedia Commons.
Biochemistry
Field
1918–2007
Lifespan
American
Nationality
20th century
Era
Nobel Prize in Physiology or Medicine 1959, with Severo Ochoa
Honour
Discovered DNA polymerase (1956) and made infectious viral DNA in a test tube (1967)
Discovery
“
No matter how counterintuitive it may seem, basic research has proven over and over to be the lifeline of practical advances in medicine.
Arthur Kornberg · 1918–2007
Arthur Kornberg, Basic Research, the Lifeline of Medicine (1977), quoted by Stanford School of Medicine, 2007

A hardware store in Brooklyn

Arthur Kornberg was born in Brooklyn, New York, on March 3, 1918, the youngest of the three children of Joseph and Lena (née Katz) Kornberg. His parents were Jewish immigrants from Austrian Galicia, in what is now Poland, who had come to New York separately in 1900 and married in 1904. The family name itself was a survival story: his paternal grandfather had exchanged the name Queller for Kornberg by taking on the identity of a man who had already done his military service, to avoid the draft.

Joseph Kornberg had no formal education but spoke at least six languages. For almost thirty years he worked as a sewing-machine operator in the sweatshops of the Lower East Side, and when his health failed he opened a small hardware store in Brooklyn. By the age of nine Arthur was helping customers behind the counter. He was an eager and able student who skipped several grades, finished Abraham Lincoln High School at fifteen, and entered the tuition-free City College of New York in 1933.

From medicine to enzymes

Kornberg did well in chemistry but, in the Depression years, medicine looked like a safer career than research. He graduated from City College in 1937 and earned his medical degree from the University of Rochester in 1941, expecting to become an internist. In medical school he had noticed that he had a mild, harmless jaundice, now known as Gilbert’s syndrome, and surveyed his classmates to see how common it was. The results became his first scientific paper, published in 1942.

That small paper changed his life. Kornberg was serving as a ship’s doctor on a U.S. Coast Guard vessel in the Caribbean when the director of the National Institutes of Health, Rolla Dyer, who was urgently seeking expertise on jaundice, read it and had him reassigned to NIH. There Kornberg studied vitamins in rats, grew fascinated by the enzymes that vitamins help, and in 1946 and 1947 trained in enzyme chemistry with Severo Ochoa at New York University and with Carl and Gerty Cori at Washington University in St. Louis. He called the rest of his career a “love affair with enzymes.”

Finding the enzyme that copies DNA

Back at NIH, and from 1953 as head of microbiology at Washington University, Kornberg became a master at purifying enzymes. When James Watson and Francis Crick described the double helix in 1953, they suggested how DNA might be copied, but nobody knew the chemistry by which a cell actually builds a new strand. Kornberg believed that to understand a biological process you had to find the enzymes that carry it out: “you have to know the actors in order to understand the plot.”

First he had to be able to make the building blocks. Through the early 1950s he and his colleagues worked out how cells synthesise the nucleotides, the units of DNA and RNA, discovering along the way a key intermediate known as PRPP, and by 1954 they had found the enzymes needed to make all four building blocks of RNA. When he learned in 1955 that Severo Ochoa’s group in New York had apparently made an RNA-like chain in the test tube, Kornberg decided to concentrate on DNA.

Working with extracts of the bacterium E. coli and radioactive tracers, he and his colleagues found in 1956 the enzyme that links DNA’s building blocks into a chain, following the sequence of an existing strand as a template. He named it DNA polymerase. Full reports appeared in 1958, and in 1959 Kornberg shared the Nobel Prize in Physiology or Medicine with his former mentor Severo Ochoa “for their discovery of the mechanisms in the biological synthesis” of the nucleic acids. Later work in his laboratory showed that the enzyme also proofreads its work and repairs damaged DNA.

Life in a test tube

In 1959 Kornberg moved to Stanford University to build a new Department of Biochemistry, bringing much of his Washington University team with him. He designed it as a close-knit family: laboratory space and even research grants were shared, students from different groups worked side by side, and the original faculty stayed together for decades. The department became one of the world’s leading centres of DNA research and, through colleagues such as Paul Berg, a birthplace of recombinant DNA.

Kornberg’s next goal was to make DNA in the laboratory that was not just chemically correct but biologically alive. In 1967, using his polymerase together with the newly discovered sealing enzyme DNA ligase, and with help from Robert Sinsheimer at Caltech, Kornberg and Mehran Goulian copied the DNA of a small virus, phi X174, and showed that the synthetic DNA could infect bacteria just like the natural virus. Kornberg asked reporters not to call it “life in a test tube.” That same day President Lyndon Johnson, speaking at the Smithsonian Institution, put down his prepared text and announced that “some geniuses at Stanford University have created life in the test tube,” to Kornberg’s dismay.

How it changed medicine and biotechnology

DNA polymerase and the other DNA enzymes found by Kornberg and his students became basic tools of the new biology. They made it possible to copy, cut, join and rebuild genes in the test tube, the toolkit behind recombinant DNA and genetic engineering. Stanford’s medical school noted at his death that these basic studies paved the road to genetic engineering and provided the basis for many drugs used today to treat cancer and viral infections.

Every polymerase chain reaction, or PCR, test, the “molecular photocopying” used to diagnose infections, match forensic samples and study genes, depends on a DNA polymerase to build new strands of DNA, cycle after cycle. Methods of reading DNA also rely on polymerases to copy the strand being sequenced. When a doctor orders a genetic test, or a laboratory sequences a virus, it is using the class of enzyme that Kornberg first purified from bacteria in the 1950s.

A family of scientists

On November 21, 1943, Kornberg married Sylvy Ruth Levy, a biochemist he had met at Rochester. Apart from the years when their sons were small, she worked full-time in his laboratory and contributed significantly to the discovery of DNA polymerase; the family joke, their son Thomas later said, was that when the Nobel Prize was announced she declared, “I was robbed!” They had three sons. Roger, who at twelve watched his father receive the Nobel Prize in Stockholm, became a Stanford structural biologist and won the 2006 Nobel Prize in Chemistry. Thomas, a gifted cellist who turned to science after a hand injury, discovered two further DNA polymerases in the early 1970s. Kenneth became an architect who designs research laboratories.

Sylvy Kornberg died in 1986. Arthur later married Charlene Walsh Levering, who died in 1995, and in 1998 Carolyn Frey Dixon. His mother’s death in 1939 from gas gangrene, caused by a spore-forming bacterium after a routine gall bladder operation, gave him a lifelong interest in bacterial spores, which he studied for years.

Jewish roots

Kornberg’s story is a classic tale of the Jewish immigrant Lower East Side and Brooklyn: parents from Galicia, a father in the garment sweatshops who spoke many languages but had no schooling, a family store, and a son carried into science by New York’s free public schools and City College. His own Abraham Lincoln High School in Brooklyn produced other Nobel laureates, among them Paul Berg and Jerome Karle.

He did not write much about religion, but his Jewish background is recorded in standard biographical sources, and Yeshiva University gave him an honorary doctorate in 1962. His sons grew up in the tightly knit world of the family laboratory, often spending time there outside school hours.

A champion of basic research

Kornberg argued all his life that governments should fund science for curiosity’s sake. Practical payoffs, he said, come as a natural extension of discovery, and without basic research “medicine regresses and reverts to witchcraft.” At the same time he helped connect academic science with the young biotechnology industry: he was a founder of the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto in 1980 and served on the scientific boards of companies including Regeneron. He wrote major monographs on DNA replication, a memoir, For the Love of Enzymes (1989), and The Golden Helix (1995), an insider’s account of biotechnology.

His influence also lives on through people. The “Kornberg school” of his students and their students includes I. Robert Lehman, Charles Richardson, Randy Schekman and James Rothman, the last two themselves Nobel laureates.

Later years and legacy

In 1991, in his seventies, Kornberg switched fields again, returning to an early interest in inorganic polyphosphate, a chain of phosphates found in every cell and long dismissed as a molecular fossil. He showed that it helps bacteria survive stress and cause disease, and suggested that the enzymes making it might one day be targets for a new kind of antibiotic. He kept working in his laboratory until days before his death, of respiratory failure, at Stanford Hospital on October 26, 2007, aged 89. His last book, Germ Stories, a collection of tales about bacteria that he had told his children and grandchildren, appeared a few weeks later.

Arthur Kornberg began as a hardware-store boy and became the scientist who showed how life copies its genetic instructions. The enzyme he found is now in every molecular biology laboratory and every PCR machine on Earth, and the medicine and biotechnology built on it touch the lives of almost everyone.

Sources & further reading

Arthur Kornberg, Biographical, NobelPrize.org · Nobel laureate Arthur Kornberg dies at 89, Stanford Medicine News · The Arthur Kornberg Papers: Biographical Overview and Creating Life in the Test Tube, National Library of Medicine Profiles in Science · Polymerase Chain Reaction (PCR) Fact Sheet, National Human Genome Research Institute · Arthur Kornberg, Jewish Virtual Library · Arthur Kornberg, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.

A life 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.

Did you know?

1 fact about Arthur Kornberg

Related profiles

Other lives in Science & Medicine.

On kindness & the treatment of others
“Honor your father and your mother.”
Exodus 20:12