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Crossing the boundaries Pitt's Dr. Michael Gorin understands the research and treatment sides of the genetic equation Sunday, July 09, 2000 By Byron Spice, Science Editor, Post-Gazette
Someday, Dr. Michael Gorin will tell wide-eyed, disbelieving medical students about a time when virtually the only physicians who understood or cared about genes were called geneticists.
They will be shocked to learn that it was once considered odd that Gorin, an ophthalmologist, headed the University of Pittsburgh's Department of Human Genetics. Why shouldn't an eye doctor be concerned about genes, they'll mutter to each other?
No reason that Gorin can imagine. That's why he believes most medical specialties eventually will embrace genetics.
"It used to be that people thought of genetics as this separate entity," he explained. "If you were interested in genes, you went off and you became a geneticist." In his own case, "I really like eyes," so he became an eye specialist. Yet when he sought the causes of the diseases affecting his patients, his queries often led him to consider genetics.
In the clinic, genetic testing will become increasingly important, even for common, benign conditions such as near-sightedness, he predicted.
In fact, one of the latest passions the bespectacled Gorin has is to search for the genes responsible for myopia. Near-sightedness usually develops between ages 8 and 20, he noted. He hopes that people with a genetic susceptibility to myopia might be protected during these critical years by a drug or other intervention.
One thing that makes Gorin a model for the next generation of genetically savvy doctors is that he is not boxed into his own specialty.
"The guy's got a very incisive mind," said Jonathan Jarvik, a molecular biologist at Carnegie Mellon University, who got to know Gorin when they took a business school mini-course. "He's got a sort of wide-eyed, anything's possible manner. ... So many academicians are jaded. They talk about critical thinking, but too often it becomes critical thinking in the parochial sense. He's a boundary crosser."
Born in Baltimore but raised in the San Francisco area, Gorin, 46, is the son of an eye, ear, nose and throat specialist.
"I probably decided to go into medicine in the fourth grade," he recalled. After majoring in biochemistry and zoology at tiny Pomona College, he opted for the University of Pennsylvania's intensive M.D./Ph.D. program. That grueling double doctorate takes a minimum of six years and is designed for aspiring medical researchers.
Charting the progress
That was when Gorin got his first exposure to genetics research. He can chart how far genetics has come in the past quarter century by recounting those early laboratory experiences.
During his days at Penn, Gorin spent 1 1/2 years working with a Temple University biologist to identify the gene for alpha-fetoprotein, an important biological marker used to detect spina bifida in prenatal tests and cancer in adults. Today, a student given the same assignment would be able to download the sequence of that gene on a computer by going to the Human Genome Project's Web site.
After he completed ophthalmology residencies at UCLA and in London in 1987, Gorin landed his own lab at the National Eye Institute, a coup for someone in his early 30s.
"Basically, that's where I learned modern molecular genetics," he said. In the clinic, he saw families plagued by age-related macular degeneration, a disease afflicting 13 million Americans and the most common cause of vision loss in people over age 60.
Macular degeneration damages the center of the eye's retina, causing a growing blind spot in the middle of a person's field of vision. It can end someone's ability to read, drive, recognize faces and see details.
"It's a complex condition and there're all these theories about what causes it," Gorin said. "We know there's a strong family influence." It clearly is caused by multiple genes, he added, though it's impossible yet to say how many.
From those observations began an ongoing study of the genetics of age-related macular degeneration, which has grown to include hundreds of families from all over the nation.
"He's shown incredible perseverance," said Daniel Weeks, a statistical geneticist at Pitt's Graduate School of Public Health, who is collaborating with Gorin. Success in such a study often relies on obtaining consistent diagnoses -- no easy task with so many different patients and doctors. So Gorin personally verifies each diagnosis, reviewing each patient's records and studying photos of their eyes.
"That's unusual, particularly with a study with hundreds of families," said Weeks, who lends his statistical know-how to many research projects. "Almost every weekend, he spends hours looking through boxes of records."
Gorin's team has narrowed its search to several regions of the genome. Unfortunately, those regions are among the many gaps in the Human Genome Project's rough draft sequence of the genome, so it will take awhile to find and test the candidate genes within those regions.
The search demonstrates the complexity of multiple-gene diseases. For instance, Gorin has found evidence that the gene for apolipoprotein E4 may help protect people from macular degeneration. But the same APOE4 gene is known to increase the risk of Alzheimer's disease and hardening of the arteries.
"That's not unexpected in genetics," he added. "What's bad in one situation is good in another."
Jam-packed office
His triangular, glass-walled office next to his lab at the Eye & Ear Institute in Oakland bespeaks a busy man. The room is neat, but every inch of desk space is packed with piles of journals, files, computers, lightboxes for studying slides and water bottles to quench his thirst.
At home in O'Hara, his wife Jane and their two teen-age sons have installed a pool table to help him unwind. "I was a fanatic when I was a kid," Gorin explained. "I used to spend all my money down at the pool hall."
The demands on his time have only grown in the two years since he assumed the duties of interim chairman of human genetics, a department that straddles both the medical and public health schools, and was first headed by Dr. John Mulvihill, who recruited Gorin in 1990.
Just as he had been an unusually young medical officer at the National Eye Institute, Gorin worries that he might be considered a bit green to be a department chair. But Robert Ferrell, a geneticist at the public health school and another of Gorin's collaborators, maintains Gorin "has done a very good job."
While most members of the department are either laboratory researchers or doctors who work with patients, Gorin is both.
"Mike was one of the first people -- and maybe the only person in Pittsburgh -- who covered both sides well," Ferrell said. He thus may have a broader view of what it takes to achieve the department's goal of translating genetic research into treatments.
Gorin is not a confrontational person, but hasn't flinched from making the hard decisions necessitated by limited resources. "He hasn't been a sugar daddy to everyone," Ferrell added.
One clinical initiative particularly close to Gorin's heart is a Center for Rare and Genetic Disorders, an attempt to catalog all of the UPMC doctors who have expertise in treating any of 900 rare diseases. This database will be used to refer patients to specialists.
Though any single one of these diseases is indeed rare, affecting less than one out of every 20,000 people, collectively they strike one out of every eight people, Gorin said.
"That means there are a lot of people with conditions that most physicians don't know much about," he continued. And that means it may take years for the person to be properly diagnosed and that the job of coordinating specialized care may be beyond the abilities of most medical specialists.
Discovering tumors
Gorin became sensitized to this issue at the National Eye Institute, where for two years he almost exclusively saw patients with von Hippel Lindau Disorder, a genetic condition that can cause the growth of tumors in several areas of the body, including the eyes. Even ophthalmologists who know they should be checking the eyes of these patients, finding and removing the tumors before blindness sets in, may not always recognize what they're looking for, he noted.
Recently a girl with von Hippel Lindau was referred to Gorin. "Her own ophthalmologist one month before had checked her eye and said it was OK. But when I looked, there was a tumor right there." She narrowly avoided losing sight in her right eye, he said, shaking his head.
Often, Gorin finds himself writing to other doctors who are seeing his eye patients who have genetic conditions, suggesting tests and procedures they should be doing for non-eye-related complications. "He's tenacious about following up," said Constance Mulligan, one of Gorin's von Hippel Lindau patients, who lives north of Gettysburg. "Other doctors don't know much about it."
For Michael Gorin, his followups are part of his belief that the doctor of the future will not only need to understand genetics, but will have to maintain good, detailed diagnostic skills.
Gorin recalls treating a pair of brothers, 9 and 10, who had suffered retinal deterioration. During one visit, he noticed one boy's face looked rounded, as if he might have Bardet-Biedl syndrome, a genetic condition that affects many parts of the body, including the retina. People with the syndrome typically are born with extra toes or fingers.
"I asked the parents if his hands or feet had ever been X-rayed and they said, yes, when the boy's extra toes were cut off!" Gorin recalled. He referred the boy to an endocrinologist to help manage other aspects of the syndrome.
"That's successful genetics," he said.
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