Jonathan Uhr, immunologist who advanced cancer treatment, dies at 96

Jonathan W. Uhr, a medical researcher who expanded the field of immunology with studies that helped explain how antibodies work, led to a therapy that effectively eradicated a blood disorder that could be fatal for newborns, and opened promising new avenues in the treatment of cancer, died Feb. 15 at a hospice center in Dallas. He was 96.

He had prostate cancer, said his wife, Ginger Uhr.

Dr. Uhr entered immunology in the 1950s, when relatively little was known about the functioning of the immune system, a complex shield that protects the body from germs and other outside invaders.

Since the late 1700s, doctors had fought smallpox – to cite one example of such an invader – by exposing patients to cowpox, a similar but less virulent virus. That process, an early form of vaccination, was known to provoke an immune response. But precisely how the response worked was unclear until Uhr embarked on his work.

Early in his career, as a researcher at New York University’s medical school, he made several signal discoveries, according to Ellen Vitetta, who collaborated with Uhr for roughly half a century, first at NYU and later at the University of Texas Southwestern medical school in Dallas, where he chaired the department of microbiology.

Uhr’s work centered on antibodies, which are proteins produced by the immune system to fight foreign substances in the body. At the time, Vitetta said, “nobody really knew where they came from or how they were made or what they actually did.”

In studies conducted on guinea pigs, Uhr revealed that immunization with a virus first produced large antibodies, immunoglobulins known as IgM, and then smaller antibodies, immunoglobulins called IgG.

The latter category creates immunological memory, allowing the body to remember a virus or other invader, recognize it and better ward it off in cases of reinfection. Uhr’s findings help explain why vaccination works and why vaccine boosters are sometimes needed.

In further research, he helped make sense of how antibody production is turned on and off. That work was applied most prominently to the study of Rh disease, which stems from an incompatibility in blood types between a pregnant woman and fetus.

If a pregnant woman is Rh negative and the fetus is Rh positive, that fetus and, even more, fetuses in future pregnancies are at risk for developing Rh disease, in which antibodies produced by the mother’s immune system attack the fetus’s red blood cells. In the most severe cases, the disease may result in miscarriage or stillbirth.

Building on Uhr’s studies, other researchers in the 1960s developed RhoGAM, an injection that is administered to pregnant women whose fetuses are at risk for Rh disease. In countries where the therapy is available, Rh disease has essentially been eliminated.

Uhr’s immunological research eventually led him into oncology. He and colleagues experimented with attaching toxins such as ricin to antibodies, which bond with and then kill cancer cells. Their findings helped broaden cancer care beyond surgery, radiation and chemotherapy to include targeted therapies attacking specific cells.

In another advance in oncology, in the late 1990s, Uhr identified circulating tumor cells, or CTCs, which are found in the blood and, if detected, allow treatment before a relapse or metastasis advances.

“He was the first one who showed we can isolate and identify cancer cells among the millions of other cells we have in the blood,” said Massimo Cristofanilli, chief of breast medical oncology at Weill Cornell Medicine in New York City.

Uhr’s discoveries were first applied to breast, prostate and colorectal cancers but, along with subsequent laboratory discoveries, hold promise for the treatment of other forms of the disease.

“It will change the way we diagnose cancers,” Vitetta said. “We won’t have to wait until they’re big lumps and bumps.”

Jonathan William Uhr, an only child and the grandson of Jewish immigrants from Hungary and Russia, was born in Manhattan on Sept. 8, 1927.

His mother was a lawyer, and his father was a pediatrician who had studied microbiology. Both parents lived to see their son become a doctor before their deaths from cancer, losses that inspired Uhr’s work in oncology.

Uhr grew up in New Brunswick, N.J., and was 16 when he enrolled at Cornell University in Ithaca, N.Y. He was 17 when, with his parents’ permission, he paused his studies to join the Navy and serve stateside during World War II. He graduated from Cornell in 1948.

At the time, a quota system strictly limited the number of Jewish students admitted to medical schools in the United States. Despite his stellar record, he was accepted at no medical school until his father interceded with an acquaintance who was chair of the pathology department at NYU, Uhr later recounted. He was admitted to NYU and received a medical degree in 1952.

There was also an “unwritten rule” at most institutions, Uhr said, that Jews could serve as chief residents in specialties such as pediatrics or psychiatry but not in what were considered the “major” fields of medicine or surgery.

That exclusion did not exist, however, at Mount Sinai Hospital in New York, which had been established in the 19th century for the care of indigent Jews, and where Uhr chose to pursue a residency.

“I could become chief resident in medicine there,” he told the American Association of Immunologists in an oral history, “and I did.”

Uhr had hoped to become “a hands-on clinician,” he said. But during a fellowship with A.M. Pappenheimer Jr., a noted immunologist then at NYU, the excitement surrounding their research shifted his interest to laboratory work.

He also held a fellowship in Australia with Frank Macfarlane Burnet, an immunologist who shared the 1960 Nobel Prize in physiology or medicine.

Uhr joined NYU medical school as a professor in 1962 and spent a decade there before moving to UT Southwestern. In 1997, he became a professor at the university’s cancer immunobiology center. He took emeritus status in 2010. He was a member of the National Academy of Sciences.

Uhr’s marriages to Roberta Klibanoff and Linda Cobb ended in divorce.

Survivors include his wife of 25 years, the former Ginger Lanclos of Dallas; two daughters from his first marriage, Sarita Uhr of La Jolla, Calif., and Jacqueline Guise of Oahu, Hawaii; six grandchildren; and four great-grandchildren.

Beyond his scientific achievements, Uhr was remembered as a mentor to younger scientists entering the field, ever eager to share his knowledge and help them succeed.

Emilian Racila, a professor of pathology at the University of Minnesota, came to the United States from his native Romania in 1992 with $300 in his pocket to work as a postdoctoral fellow in Uhr’s lab at UT Southwestern. Until he began drawing a salary, Racila said, Uhr paid his rent.

Another scientist Uhr encouraged was a young Anthony S. Fauci, who became a major researcher in the field of HIV/AIDS treatment and, as director of the National Institute of Allergy and Infectious Diseases, one of the nation’s top medical officials during the coronavirus pandemic.

Uhr was “clearly one of the most outstanding immunologists in the world,” Fauci said in an interview. “The thing about him I’ll never forget is how when I was starting out and no one knew who I was, he befriended me and treated me like I was a colleague, like I was a peer.”