John S. O’Brien; Discovered Genetic Cause of Tay-Sachs
Dr. John S. O’Brien, the UC San Diego researcher who discovered the genetic cause of Tay-Sachs disease and developed the first tests to identify the neurological disorder affecting mostly children of Eastern European Jewish background, has died. He was 66.
O’Brien died at his La Jolla home Feb. 1, the university announced. The cause of death was not released.
At the time of his death, O’Brien was a neuroscience professor at the UC San Diego School of Medicine, which recruited him in 1968 after he spent six years on the USC faculty. He headed the department from 1970 to 1978.
As a scientist, O’Brien focused on identifying the causes of genetic diseases, but he was equally committed to reducing the incidence of such disorders, and became an advocate for genetic screening and education.
“He was brilliant, a real Renaissance man,” said Dr. Doris Trauner, vice chairman of the neurosciences department at the UC San Diego School of Medicine. “He was not just a world-class researcher; he had a very, very creative mind.
“He was able to take a problem and come up with novel ways of approaching it. He was always so supportive of everyone around him: his trainees, just about anybody who came to him for advice.”
Despite a stroke about two years ago, and the effects of post-polio syndrome, he remained energetic, Trauner said.
O’Brien’s best-known work was in Tay-Sachs. The blood test used to screen for the defective Tay-Sachs gene enabled widespread screening to see if prospective parents are carriers, and prenatal screening of the fetus in the mother’s womb. As a result, the incidence of Tay-Sachs has been reduced by about 90%.
About one in every 27 people of Ashkenazi, or Eastern European Jewish, descent carries the gene, which has a similar incidence among Louisiana’s Cajun community and French Canadians from eastern Quebec. It is also carried by about one in 50 people of Irish ancestry. Because the gene is recessive, both parents must be carriers for a child to develop Tay-Sachs.
O’Brien’s research specialty was studying fatty molecules in the human brain. With Tay-Sachs, affected children lack an enzyme called hexosaminidase A that is needed to break down a fatty substance in brain cells.
They develop mental retardation and blindness, and die either in infancy or early childhood. He studied many so-called storage diseases, in which the body builds up toxic levels of substances that should be broken down. Besides Tay-Sachs, others include Gaucher’s disease.
Although he trained originally in pathology, O’Brien’s interests spanned many disciplines including pediatric neurology, biochemistry, neuroscience and metabolic disease, Trauner said. “He was very passionate about his work and was not content to just sit on his laurels.”
O’Brien’s laboratory also discovered and isolated a group of proteins called saposins, determined their structures and functions, and thus opened up a new area of biochemistry. O’Brien made a major discovery when he identified the precursor to these proteins, called prosaposin, and found that it can stimulate the regeneration and survival of brain cells.
Clinical trials recently began on one of the saposin molecules for relief of a painful diabetic condition called sensory neuropathy; others are potentially promising in neurological diseases such as Alzheimer’s disease and post-polio syndrome, about which he was excited because he suffered from post-polio complications, Trauner said.
A scientist who successfully forged ties with the business world to bring his findings to the marketplace, he also was a founder of Myelos Neurosciences Corp., which commercialized technology developed at the San Diego university.
O’Brien was born July 14, 1934, in Rochester, N.Y., and attended Loyola University in Los Angeles before earning his master’s and medical degrees from Creighton University in Omaha.
He was an accomplished jazz pianist with his own quartet during college and medical school, and his earnings from music helped him pay for his education. He also was an internationally exhibited watercolorist and ceramic artist.
Among his awards were the 1995 Supelco Award from the American Oil Chemists’ Society for outstanding original research on fats, oils, lipid chemistry or biochemistry and the Jacob Javits Neurosciences Investigator Award from the National Institutes of Health.
He is survived by his wife, Susan; his mother, Esther; his sister; six children; and 20 grandchildren.
Private services are planned, and the family has asked that donations be made to the UC San Diego Foundation to support the UC San Diego graduate program in neurosciences.
