A space-age childhood in the Bay Area
Gary Bruce Ruvkun was born in Berkeley, California, on March 26, 1952, into a Jewish family, the son of Samuel and Dora (née Gurevich) Ruvkun. He grew up in nearby Oakland and Piedmont. His father was a civil engineer. His mother was a homemaker who worked her way slowly through college while raising the family, earning her degree in psychology the same year Gary graduated from high school.
He was a child of the space race, and his parents fed his fascination with science, buying him a telescope and a microscope when he was very young. He was drawn to astronomy and radio communication, an interest in the cosmos that would resurface decades later in his scientific career. He has said that the space race of the 1960s was what first sparked his interest in science.
Tree planter, traveller, scientist
Ruvkun entered the University of California, Berkeley, planning to study electrical engineering, switched to physics and graduated in 1973 with a degree in biophysics. Rejected by about ten medical schools, he set off north in a used Dodge van his parents had given him for graduation and joined the Hoedads, a famous tree-planting cooperative in Oregon, spending a cold, wet winter replanting forests. He later called it the hardest work he had ever done and one of the best times of his life; because he had the van, while most planters slept in tents, he joked that he lived like a prince.
In the roughly two years after college he also travelled widely, including some six months in South America. In Bolivia he came across a stack of Scientific American magazines, and reading them rekindled his wish to do science. After a year as a nuclear medicine technician at the University of California, San Francisco, he went to Harvard, where he earned a PhD in biophysics in 1982 in the laboratory of Frederick Ausubel, studying the genes that let bacteria fix nitrogen for plants.
At Harvard, Ausubel’s laboratory studied Rhizobium, soil bacteria that live in the root nodules of legumes such as alfalfa and turn nitrogen from the air into fertiliser for the plant. Ruvkun worked on finding and mapping the bacterial genes involved, an early lesson in how to locate and clone the genes behind a biological process. He also won a junior fellowship in Harvard’s Society of Fellows, which gave him freedom to pursue his own projects. In the 2020s he flew across the country for the Hoedads’ fiftieth-anniversary reunion, and when he won the Nobel Prize he sent his old fellow tree planters his love.
Two worm genes and a tiny RNA
As a postdoctoral fellow, Ruvkun worked with Walter Gilbert at Harvard and with H. Robert Horvitz at MIT, where he studied the genes that control the timing of development in the millimetre-long worm C. elegans. There he and a fellow postdoc, Victor Ambros, became fascinated by two mutant worms, lin-4 and lin-14, in which cells switched developmental programmes at the wrong time. Ambros had shown that lin-4 somehow turned lin-14 off. Ruvkun then opened his own laboratory at Massachusetts General Hospital and Harvard Medical School, while Ambros set up his at Harvard.
Ambros discovered that lin-4 did not make a protein at all, only an unusually short piece of RNA about 22 letters long. Ruvkun, who had cloned lin-14, showed that lin-4 did not stop lin-14’s messenger RNA from being made but blocked the production of protein from it, and that a particular stretch at the end of the lin-14 message was needed for this. When the two compared notes, the short lin-4 RNA matched that stretch. A tiny RNA was switching off a gene by pairing with its message. They published back-to-back papers in the journal Cell in 1993. The response, the Nobel committee later wrote, was almost deafening silence: most scientists assumed it was an oddity of worms.
From worm curiosity to universal rule
That changed in 2000. Ruvkun’s group discovered a second such RNA, encoded by a gene called let-7, which regulates another worm gene in the same way. Later that year his laboratory showed that let-7 exists, with the same sequence, across the animal kingdom, from flies and sea urchins to zebrafish and humans. Suddenly the worm curiosity looked like a general law of biology. Researchers around the world began to find these molecules, now called microRNAs, everywhere. The human genome contains more than a thousand microRNA genes, and a single microRNA can fine-tune hundreds of genes at once. Looking back, Ruvkun has said that at the time he and Ambros were just thinking it was a really interesting finding.
Ruvkun’s laboratory, working with Craig Mello’s, showed that microRNAs share key cellular machinery, including the enzyme Dicer and PIWI-family proteins, with RNA interference, the gene-silencing system that brought Andrew Fire and Mello a Nobel Prize in 2006. The two fields merged into one, the biology of small RNAs. In 2003 his laboratory identified many more microRNAs, including ones made in mammalian nerve cells, and in 2007 it discovered many new protein partners that microRNAs need to work.
What microRNA means for medicine
Cells and tissues cannot develop normally without microRNAs, and when this layer of control goes wrong, people get sick. According to the Nobel committee, abnormal microRNA regulation can contribute to cancer, mutations in microRNA genes cause conditions including congenital hearing loss and eye and skeletal disorders, and mutations in DICER1, a protein needed to make microRNAs, cause a rare syndrome that leads to cancers in many organs. Because microRNA patterns differ between healthy and diseased tissue and can be measured in blood, they are being developed as markers to detect and classify cancers and other diseases, and as targets for drugs that block or replace particular microRNAs.
The discovery that microRNAs and RNA interference use the same machinery has also helped make gene-silencing medicines a reality: since 2018, drugs that switch off disease-causing genes using small RNAs have been approved for rare inherited diseases and for lowering cholesterol.
Insulin, ageing and life beyond Earth
Ruvkun’s laboratory made a second major contribution. Other researchers had found that mutations in certain worm genes made the animals live much longer. Ruvkun’s group showed that one of them, daf-2, encodes a receptor resembling the human insulin receptor, and that it works through a chain of signals to a gene regulator, DAF-16, whose human relatives, the FOXO proteins, are also controlled by insulin. The finding linked metabolism to ageing and revealed pathways relevant to insulin resistance, type 2 diabetes and age-related disease. His laboratory went on to screen the whole worm genome for genes that affect ageing and fat storage, and in 2012 described a way animals detect infection by monitoring their own core cell functions. Many of the genes it found are shared across the animal kingdom and could be targets for diabetes drugs.
Returning to his childhood love of space, Ruvkun co-leads a project called the Search for Extraterrestrial Genomes with scientists at MIT and elsewhere, developing a small DNA-sequencing instrument that could fly to Mars and look for life related to life on Earth.
In 2019 Ruvkun and his collaborators argued that because sophisticated microbial life appeared on Earth soon after the planet cooled, and because planets in other systems have been found to migrate violently, it is plausible that DNA-based life could have spread between worlds. Finding related life on Mars, he has suggested, would be one way to test that idea. The project reflects the curiosity of the boy with a telescope, applied with the tools of a geneticist.
Jewish roots and family
Ruvkun was born into a Jewish family in Berkeley, as the Jewish Virtual Library records; he has not written publicly about religious practice. He lives in the Boston area with his wife, Natasha Staller, an art historian at Amherst College, and they have a daughter, Victoria, who was in high school when he won the Gruber Prize in 2014. In 2011 he shared Tel Aviv University’s Dan David Prize with Cynthia Kenyon for their research on the genetics of ageing.
Legacy
Over about forty years, some hundred doctoral students, postdoctoral fellows and graduate students have trained in Ruvkun’s laboratory. He has received the Lasker Award, the Gairdner Award, the Wolf Prize and the Breakthrough Prize, and in 2024 he and Victor Ambros shared the Nobel Prize in Physiology or Medicine for the discovery of microRNA and its role in gene regulation.
Recognition came well before Stockholm. In 2008 alone he shared the Lasker Award for Basic Medical Research and the Benjamin Franklin Medal with Victor Ambros and David Baulcombe, received the Gairdner International Award with Ambros, and was elected to the US National Academy of Sciences. He shared the Louisa Gross Horwitz Prize in 2009, the Gruber Genetics Prize and the Wolf Prize in Medicine in 2014, and the Breakthrough Prize in Life Sciences in 2015.
A field that began with two puzzled postdocs comparing notes on a worm has grown to well over a hundred thousand scientific studies. It showed that the genome contains a whole hidden layer of tiny regulators, and it is giving medicine new ways to read, and one day to correct, the signals that go wrong in cancer and inherited disease.
Sources & further reading
Press release: The Nobel Prize in Physiology or Medicine 2024, NobelPrize.org · Gary Ruvkun, Gruber Genetics Prize 2014, Gruber Foundation, Yale University · Gary Ruvkun, 2024 Nobel Prize recipient, Mass General Brigham · Hoedad Nobel Prize Winner, Eugene Weekly, 2024 · Gary Ruvkun, Jewish Virtual Library · Gary Ruvkun, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
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