A boy from Ridgewood, Queens
Harvey James Alter was born on September 12, 1935, in New York City, and spent his first seventeen years on one street of apartment houses in Ridgewood, Queens. His parents were first-generation Americans whose own parents had come from western Russia and Poland; a genetic test late in life, he joked, showed him to be 99.5 percent Ashkenazi Jew. His father, one of nine children from Manhattan’s Lower East Side, was college educated, flamboyant and fond of opera; his mother, raised by a grandmother who earned her living with a pushcart in the Bronx, was cautious and kept a kosher home. He had an older sister, Jackie.
He grew up during the Second World War in a mostly German neighbourhood, playing street games with pink Spalding balls. He later wrote that the United States had not entered the war in time to prevent the murder of six million Jews, and that he only understood the horror when he saw films of the camps. When President Roosevelt died, his mother wept, while some neighbours cheered because they saw Roosevelt as anti-German and a friend of the Jews; the latent antisemitism of the neighbourhood, he recalled, rarely showed itself openly. Within a few blocks were a German delicatessen, a kosher delicatessen, a synagogue and the rabbi, who lived next door.
Rochester and a medical detective story
Alter skipped a year of elementary school, entered high school at 13 as the smallest boy in his class, and later chose the University of Rochester, partly for its medical school. After a shaky start he graduated in 1956, then earned his medical degree there in 1960, in a programme that stressed understanding the patient as a person as well as a disease. He trained as an intern and resident at Rochester’s Strong Memorial Hospital.
As an intern he solved his first medical mystery: a truck driver with unexplained kidney failure. Tipped off by another patient’s magazine article, Alter found the man’s truck, climbed into the sleeping cab, and discovered an empty carbon tetrachloride fire extinguisher mounted right above the bed. The patient recovered fully. It was, he later wrote, his first epidemiological investigation.
Drafted into the NIH
In 1961 Alter received a draft notice ordering him to report for army service. Learning that the Public Health Service could take precedence over the draft, he secured a position at the National Institutes of Health and reported for duty on November 27, 1961, three days before he was due at Fort Dix. He was assigned to the blood bank of the NIH Clinical Center, then a small department of about ten people.
There, as a young fellow, he began looking for antibodies in the blood of patients who had received many transfusions. A colleague told him about a geneticist, Baruch Blumberg, who was doing similar experiments, and the two began working together. One day Alter noticed an unusual line in one of their gel tests. The substance it revealed became known as the Australia antigen, which Blumberg later showed was part of the hepatitis B virus, work for which Blumberg won the 1976 Nobel Prize. It was Alter’s introduction to viral hepatitis. After further training in Seattle and at Georgetown University, where he worked as a haematologist from 1965 to 1969, he returned to the NIH in 1969 to study hepatitis after transfusion.
Alter has spent almost his entire working life in the NIH Clinical Center’s blood bank, which grew under three successive chiefs, Paul Schmidt, Paul Holland and Harvey Klein, into the Department of Transfusion Medicine, with a staff of about 150 and a reputation as one of the most innovative in the world. Klein later summed up Alter’s career by saying that co-discovering the Australia antigen, a key to detecting hepatitis B, would have been the highlight for most investigators, but for Alter it was only an auspicious beginning.
The mystery of transfusion hepatitis
In the late 1960s and early 1970s, receiving a blood transfusion carried a serious risk of hepatitis, an inflammation of the liver that can become chronic and lead, often silently over decades, to cirrhosis and liver cancer. Once tests for hepatitis B were introduced, many cases were prevented, but Alter and his colleagues showed that large numbers remained. Tests for hepatitis A, developed around the same time, showed that it was not the cause either.
Alter’s method was patient, careful and prospective. His team followed people who had received transfusions, and kept blood samples from both the donors and the recipients in a carefully catalogued store. In a series of papers from 1972 onward, he and colleagues including Paul Holland, Robert Purcell and Stephen Feinstone showed that most hepatitis after transfusion was caused by neither hepatitis A nor hepatitis B. In 1978 they showed that blood from these patients could transmit the disease to chimpanzees, and that the agent behaved like a virus. The new disease became known as non-A, non-B hepatitis.
The stored samples became one of the most valuable resources in hepatitis research. Because each recipient had been followed over time, and blood from every donor had been kept, Alter could later go back and test the samples whenever a new test or a new candidate virus appeared. The approach also showed how common and how serious the disease was: many of those infected developed chronic hepatitis, sometimes without symptoms, and some went on to cirrhosis years later. The NIH project was also part of the effort that changed blood collection itself, including the move away from paid donors, whose blood carried a higher risk of hepatitis.
Naming hepatitis C
For more than a decade the virus defied every standard method of identification. Finally Michael Houghton and his colleagues at the company Chiron, working with blood from an infected chimpanzee, isolated a fragment of the virus’s genetic material using antibodies from patients’ blood, and named it hepatitis C virus; the discovery was published in Science in April 1989. Alter’s group confirmed the finding by testing their stored panel of samples, showing that the new virus accounted for the great majority of non-A, non-B hepatitis cases. Charles Rice later provided the final proof that the virus alone could cause the disease.
The discovery made possible sensitive blood tests for hepatitis C, and screening of donated blood began soon afterwards. Combined with the earlier exclusion of paid donors and testing for hepatitis B, the risk of hepatitis after transfusion in the United States fell from about 30 percent in 1970 to nearly zero. In 2000 Alter and Houghton shared the Lasker Award for Clinical Medical Research for this work, which the award recognised as having essentially eliminated transfusion-associated hepatitis in the United States.
From detection to cure
Identifying the virus also opened the way to treatment. Researchers were able to study its genes and proteins and develop antiviral drugs aimed directly at them. The Nobel Assembly noted that, for the first time in history, hepatitis C can now be cured, raising hopes of eliminating the virus from the world population, provided blood testing and antiviral drugs can be made available across the globe.
Blood-borne hepatitis causes more than a million deaths a year worldwide, according to the Nobel Assembly, a burden comparable to HIV and tuberculosis. Thanks in large part to the work that began with Alter’s stored blood samples, a transfusion in most of the world no longer carries the risk it once did, and people already infected can be diagnosed and cured before their livers are destroyed.
The Nobel Prize
On October 5, 2020, the Nobel Assembly at the Karolinska Institutet awarded the Nobel Prize in Physiology or Medicine jointly to Harvey Alter, Michael Houghton and Charles Rice for the discovery of hepatitis C virus. Because of the Covid-19 pandemic, Alter received the prize remotely rather than in Stockholm. He was 85.
He responded, characteristically, with humour, writing a poem for his Nobel autobiography under the title I Never Had No Nobel Dreams, and paying tribute to the NIH, where he has spent most of his career as chief of the infectious disease section and associate director for research in the Department of Transfusion Medicine at the Clinical Center. He has also received the Distinguished Service Medal, the highest award given to civilians in the United States public health service, and has been elected to the National Academy of Sciences and the Institute of Medicine.
Family and faith
Alter grew up in a Jewish home and has written frankly about the expectation, which he called powerful, that he should marry within his faith, an expectation he later broke through. He met his first wife, Barbara, at the NIH; they had two children, Mark, a physician, and Stacey, a teacher, before divorcing after twelve years. In 1995 he married Diane Dowling, a psychotherapist, whom he credits with making him a better husband, parent and person; she brought two daughters, Lydia and Erinn, whom he considers his own, and the family has nine grandchildren.
Writing in his eighties, he described the losses of old age, the parents, sister, cousins and friends now gone, with the same mix of candour and wit that runs through his scientific memoir. He has said he owes everything he achieved to the NIH, a public institution where a young doctor drafted for national service could spend decades methodically following patients and saving their blood, until the samples revealed the virus that had been hiding in the world’s blood supply.
Sources & further reading
Harvey J. Alter, Biographical, NobelPrize.org · Press release: The Nobel Prize in Physiology or Medicine 2020, NobelPrize.org · Harvey J. Alter, 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.