Jonathan Uhr, 96; his work advanced cancer therapies
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.
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 Dr. 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 Dr. 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.
Dr. 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, Dr. 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. Dr. Uhr’s findings help explain why vaccination works and why vaccine boosters are sometimes needed.
He later 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 Dr. 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.
Dr. 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, Dr. 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.
Dr. Uhr’s discoveries were first applied to breast, prostate, and colorectal cancers but, along with subsequent discoveries, hold promise for the treatment of other forms of the disease.
“It will change the way we diagnose cancers,” Vitetta said.
Dr. 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. Both parents lived to see their son become a doctor before their deaths from cancer, losses that inspired his work in oncology.
He grew up in New Brunswick, N.J., and was 16 when he enrolled at Cornell University in Ithaca, N.Y. He paused his studies to join the Navy and serve stateside in 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, Dr. Uhr later recounted. He received a medical degree from NYU in 1952.
There was also an “unwritten rule” at most institutions, Dr. 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. That exclusion did not exist at Mount Sinai Hospital in New York, which was established for the care of indigent Jews and where Dr. Uhr pursued a residency.