A Brighton Beach childhood
David Jay Julius was born on November 4, 1955, in Brighton Beach, Brooklyn, the seaside neighbourhood that Neil Simon made famous in Brighton Beach Memoirs. In his Nobel autobiography he describes it as a landing pad for Eastern European immigrants like his grandparents, who fled Czarist Russia and antisemitism in search of a better life. His parents were first-generation Americans who grew up in the same enclave, went to public schools and earned their degrees at tuition-free Brooklyn College, something Julius has called an example of the American promise of opportunity for all.
His father was an electrical engineer who designed and maintained emergency power systems for the telephone company; his mother taught in New York City elementary schools. David grew up with two brothers, Martin and Arthur, in the bottom flat of a small semi-attached house, with his maternal grandmother, an aunt, an uncle and two cousins living upstairs and his paternal grandparents a few blocks away. Money was modest, he recalled, but the family was close and spent what it had on opportunities for the children: museums, concerts and Broadway shows were still affordable for a middle-class boy, and the beach was at the end of the street.
A reluctant student finds science
Julius describes himself as a reluctant student who often handed in work late, until around the fifth grade, when he decided to put in more effort and be less afraid of failure. His father pushed him to sit the entrance exam for Stuyvesant, Manhattan’s elite science high school, and he got in, but a three-hour daily round trip on packed subway lines left him miserable. At the start of his second year he walked into the principal’s office and withdrew himself, transferring to his local school, Abraham Lincoln High, which his mother had attended. He never regretted it. Lincoln had already produced three Nobel laureates, Arthur Kornberg, Paul Berg and Jerome Karle; Julius would become the fourth.
There he found time for basketball, folk and jazz clubs in Greenwich Village, theatre, and part-time jobs waiting tables at local weddings and bar mitzvahs. A physics teacher, Herb Isaacson, who challenged students with ideas rather than facts, made him consider science as a career. A classmate suggested he apply to the Massachusetts Institute of Technology, which he had barely heard of. He was accepted, and his parents stretched to pay the fees. At MIT he did undergraduate research in the laboratory of Alexander Rich, and he graduated in 1977. He went on to a doctorate in biochemistry at the University of California, Berkeley, completed in 1984 under Jeremy Thorner and Randy Schekman, where he identified the enzyme Kex2 as the founding member of a family of proteins that activate hormones by cutting them out of larger precursors.
From psychedelics to receptors
As a young scientist Julius became fascinated by how natural substances, from hallucinogens such as LSD and psilocybin to opiates, act on the brain. That curiosity, he later wrote, was the thread that ran through his whole career: nature had already made molecules that fit our receptors like keys, and those keys could be used to find the locks. He took it to Columbia University in New York, where from 1984 he worked as a postdoctoral fellow with Richard Axel, a future Nobel laureate himself. After years of false starts, he devised a function-based cloning method and isolated the gene for a serotonin receptor, the 5-HT1c subtype.
In 1989 he joined the faculty of the University of California, San Francisco, where he has worked ever since. His early laboratory cloned the 5-HT3 serotonin receptor, the target of the anti-nausea drug ondansetron, and receptors for the cell-signalling molecule ATP. His group also cloned P2Y12, the platelet receptor blocked by clopidogrel and related drugs that millions of people take to lower their risk of heart attack and stroke. These ion channels and receptors were abundant in sensory nerve cells, and they drew him toward a question that was poorly understood at the molecular level: how does the body sense temperature and pain?
The heat in a chili pepper
Scientists had known for decades that capsaicin, the compound that makes chili peppers burn, excites a particular set of pain-sensing nerve cells. Finding the receptor it acted on had become a Holy Grail in pain research, and several laboratories had failed. Julius and his postdoctoral fellow Michael Caterina tried an unbiased approach. They built a library of millions of DNA fragments copied from the genes active in sensory neurons, introduced them into cultured cells that normally ignore capsaicin, and searched for the one fragment that made cells respond to it. After a laborious hunt, a single gene did.
The gene encoded a new ion channel, a pore in the nerve cell’s membrane that opens to let charged particles flow in and fire a signal. In a 1997 paper in Nature, the team showed that the same channel, now called TRPV1, also opens in response to heat at temperatures that people experience as painful. It was a molecular explanation for something everyone knows: chili peppers feel hot because they switch on the very sensor that detects scalding heat. In 2000 the group showed that mice lacking TRPV1 lost much of their sensitivity to capsaicin and to painful heat, and that the channel helps make inflamed tissue more sensitive to pain.
Cold, wasabi and spider venom
Julius then turned the logic around. If a hot chemical revealed a heat sensor, perhaps a cooling chemical would reveal a cold one. In 2002 his fellows David McKemy and Werner Neuhausser used menthol, the cooling compound in mint, to identify TRPM8, a related channel that responds to cool temperatures. Ardem Patapoutian’s group at Scripps Research found the same receptor independently. Together these discoveries showed that a family of TRP channels, each tuned to a different range of temperatures, gives the nervous system its sense of hot and cold. The Julius laboratory later showed that another family member, TRPA1, is the receptor for the pungent chemicals in mustard oil and wasabi.
His group kept using nature’s chemistry as a tool. In 2006 it reported that the venom of a tarantula causes pain by activating TRPV1, and it has studied toxins from snakes and other animals that target pain pathways. From 2013, working with his UCSF colleague Yifan Cheng, the laboratory used the new technique of electron cryo-microscopy to determine the structure of TRPV1 at near-atomic resolution, and later of TRPA1, showing how these channels open and close and how drugs and toxins bind to them.
Why it matters for pain
Pain protects us, but chronic pain is one of the most common and least well treated medical problems in the world. For decades the strongest painkillers have been opioids, which act in the brain and carry the risk of addiction that has fuelled the opioid epidemic in the United States. Julius’s discoveries identified, for the first time, specific molecules at the very start of the pain pathway, in the nerve endings of the skin and organs. That gave researchers concrete targets for medicines that could dampen pain where it begins, without acting on the brain’s reward system.
The path from discovery to drug has proved harder than hoped, and Julius has been candid about it. Several pharmaceutical companies developed drugs that block TRPV1, but in clinical trials some of them raised patients’ body temperature, revealing that the channel also helps regulate body heat; work continues on compounds that avoid that effect. At the same time, the discovery explained why an old remedy works: high-strength capsaicin, applied to the skin, overstimulates TRPV1 nerve endings until they stop signalling. A prescription capsaicin patch was approved in the United States in 2009 for nerve pain after shingles. Beyond medicine, the TRP channels he found have become a basic part of how biologists understand sensation, inflammation and itch, and laboratories around the world use them in their research.
Nobel Prize
On October 4, 2021, the Nobel Assembly at the Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine jointly to David Julius and Ardem Patapoutian for their discoveries of receptors for temperature and touch. The committee said that his use of capsaicin to find TRPV1 was the breakthrough that allowed scientists to understand how differences in temperature are turned into electrical signals in the nervous system, and that the knowledge was being used to develop treatments for conditions including chronic pain.
The news reached him in a roundabout way. The Nobel Committee could not reach him directly, so in the middle of the night a relative in California texted to say that a man from Stockholm was trying to reach him; Julius at first suspected a prank. By then he had already received many of science’s highest honours, among them the Shaw Prize in 2010, the Canada Gairdner International Award in 2017, and in 2020 both the Breakthrough Prize in Life Sciences and the Kavli Prize in Neuroscience, the latter also shared with Patapoutian. In his Nobel autobiography he used the moment to thank the American public for funding curiosity-driven research through the National Institutes of Health, which he called the engine of biomedical research.
Jewish roots
Julius comes from an Ashkenazi Jewish family whose roots lie in the Russian Empire. His grandparents were part of the great wave of Jewish emigration from Eastern Europe, and he has written plainly that they left to escape antisemitism. Brighton Beach, where three generations of his family lived within a few blocks of each other, was one of New York’s classic Jewish immigrant neighbourhoods, and the institutions that lifted his parents, the city’s free public schools and Brooklyn College, were the same ones that carried so many children of Jewish immigrants into the professions.
He has not written publicly about religious practice, and his own account of his Jewish background is a story of family and neighbourhood rather than faith: an extended family under one roof, weekend jobs serving at bar mitzvahs, and parents who devoted scarce resources to their children’s education. He is counted among the Jewish Nobel laureates in medicine by the Jewish Virtual Library.
The man and his legacy
Julius has lived in Northern California for more than half his life but, as he puts it, remains a native New Yorker in temperament and humour. He has spent his whole independent career at UCSF, where he is professor and chair of the Department of Physiology, and he served for many years as editor of the Annual Review of Physiology. He is married to Holly Ingraham, also a UCSF professor of physiology, whom he calls the other great collaboration of his life; they have a son, Philip. He plays the trumpet, and his family, he jokes, tolerates it. He keeps his laboratory small, usually about eight people, and is proud that many of its alumni now lead their own research groups.
His legacy is a map of how the body feels the world. Before his work, no one knew which molecules let a nerve ending tell warm from scalding, or cool from freezing. Today TRPV1 and TRPM8 are in biology textbooks, and the search for safer, non-addictive painkillers aimed at the pain pathway’s first step owes much to the receptors he found by following the burn of a chili pepper.
Sources & further reading
David Julius, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 2021, NobelPrize.org · Biography of David Julius, UC San Francisco · UCSF Celebrates Its Newest Nobel Laureate David Julius, UC San Francisco · David Julius, Jewish Virtual Library · David Julius, 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.