Armen Tashjian

Toxic comes from the latin word for poison, and toxicology is often described as the study of chemical injury. Over the past two decades, Professor Armen Tashjian, Jr., has deftly steered the School’s toxicology program toward research that analyzes "chemical injury" at the most basic level–at the cell membrane, in the cytoplasm, and along the spiral staircase of DNA. His insistence that toxicology needed to peer into the black boxes of the most fundamental molecular and cellular processes has required a good deal of persistence. Skeptics, some of them holding important purse strings, would ask "but is that really toxicology?" Tashjian’s research agenda also has meant his program is something of a David among the Goliaths that roam the biomedical research world of cell and molecular biology. "You just have to be a little bit smarter and work a little bit harder," says Tashjian with a smile.

Tashjian was born in Cleveland in 1932 and named for his father, an Armenian immigrant who swam across the Bosporus Strait to escape Turkish authorities and went on to establish a successful engineering and architectural business. A scholarship to Philips Exeter Academy put Tashjian on the road to a blue-ribbon education: after Exeter, he attended Yale College for three years and then went to Harvard Medical School. Tashjian had thoughts of a research career early on, but he really caught the research bug while on a postdoctoral fellowship at Harvard Medical School. On the surface, a researcher’s work might seem to be a rather peaceful, if somewhat solitary, endeavor: it’s just you, the lab, and your cells or molecules. But Tashjian points out that research is actually a high-wire act, full of excitement but also anxiety. "Here you are, a young person, entering a world of discovery. And you know the chances of success are 10- or 100-to-one against you." The key, he said, is to find both a mentor who can help and a problem that can be solved.

"If you begin to work on a problem, and it begins to be solved, you get an extraordinary sense of elation that comes with discovery: nobody has ever seen this before, I thought of this, I did it! There is a shiver of excitement. It is almost an orgasmic experience to go through that," he says.

Tashjian says he had several mentors, but the key person was Paul Munson, an expert on calcium meta-bolism on the faculty of Harvard’s School of Dental Medicine. Calcium metabolism is heavily inþuenced by hormones, and the whole field of hormone research and endocrinology was booming in the early 1960s as technological advances in protein chemistry and immunology started to make it much easier to measure and characterize hormones in blood. Munson, Ernest Knobil, Roy Greep (who would go on to hold the John Rock Professorship of Population Sciences from 1967-1972), and other investigators had turned the dental school into a "mecca of endocrinology," notes Tashjian.

Early in his career, Tashjian’s niche was the parathyroid hormone. Produced by four small glands in the neck, the parathyroid hormone plays a key role in regulating calcium levels in the blood. Tashjian quickly became one of the world’s leading authorities on parathyroid hormones as his research yielded novel assays for the hormone and shed new light on its mechanism of action.

Lawrence Levine, a biochemistry professor at Brandeis who has collaborated with Tashjian for over 30 years, remembers when Tashjian first approached him about learning some immunology: "He was so damn bright. In five years, he knew more immunology than I did!" says Levine.

Tashjian took over Munson’s lab in 1965 when he left Harvard. Tashjian’s interest soon extended to calcitonin, another calcium-regulating hormone produced by the thyroid gland. And like many others in his field, he was also intrigued by findings that hinted that cancer cells disrupted normal calcium metabolism. In 1971, Tashjian led a research team that discovered in 1971 that calcitonin levels could be used to identify a pre-cancerous condition in families at risk of getting a rare, inherited form of thyroid cancer. (The prostate-specific antigen (PSA) test for prostate cancer is based on the same general concept.) People with the pre-cancerous condition could have their thyroid glands removed, avoid cancer, and lead normal lives. Though the calcitonin test has now been supplanted by genetic tests, it probably saved several thousand lives while it was still in use.

Tashjian’s transfer to the School of Public Health came about when he agreed to help his friend and colleague, hsph Dean Howard Hiatt, build up the School’s basic biology research. As a member of the search committee to select someone to lead a new Laboratory of Toxicology, Tashjian had argued persuasively that the person chosen shouldn’t be a traditional toxicologist, but someone prepared to take advantage of the exciting new developments in molecular and cellular biology. Hiatt, a molecular biologist, agreed wholeheartedly. During his absence from one of the committee meetings, Tashjian’s name was added to the list of candidates for the job, and the rest is history.

Tashjian describes his first years as head of the School’s toxicology lab diplomatically "as an interesting challenge for me." The program had to be built up from scratch, he says. What’s more, he says he wanted to build it in an unconventional way, attracting people who were top-shelf molecular and cellular biologists and "not necessarily toxicologists by any formal identification." Government funding agencies looked askance at his approach, however and for a couple of years Tashjian’s applications for training grants–the lifeblood of many research labs–were rejected. "The reviewers said, ‘None of your people are toxicologists. How can you expect to be training toxicologists?’ " says Tashjian. Eventually, Tashjian was rewarded not only with training grants but also with kudos for setting the pace in modern toxicology by emphasizing detailed study of cellular and molecular mechanisms of injury.

Under Tashian’s direction, the Laboratory of Toxicology evolved into the Department of Molecular and Cellular Toxicology, with a research staff of 55 and an annual sponsored research budget of almost $1 million. Professors Leona Samson and Bruce Demple, experts on DNA damage and repair, are leaders in the field of genetic toxicology. Associate Professor Robert Schiestl has developed the del assay, a new genetic test for determining whether a chemical might cause cancer. In September 1997, this department merged with the Laboratory of Radiobiology to create a new, larger Department of Cancer Cell Biology under the direction of Professor Jack Little. Tashjian is once again free to focus on his own research, which is still centered around calcium regulation, but now at the intracellular level. He also sits on a Food and Drug Administration advisory committee in hopes of making new molecular tests the norm in toxicity testing, which still depends on giving high doses to lab animals.

Tashjian, a veteran of uphill fights, acknowledges that it is sometimes difficult to compete in the world of high-powered, genome-sequencing basic research. But he says an abiding concern with practical applications and opportunities to work with other public health disciplines creates some special advantages for public health-oriented toxicology. A few years ago, he recalls, a chance lunchtime discussion in the School’s cafeteria between a member of his department and a member of the epidemiologic team investigating elevated bladder cancer rates among rubber workers in Akron, Ohio’s, tire factories led to the identification of a new mutagen.

"I don’t think that happens too often elsewhere," Tashjian says with a smile.

- Peter Wehrwein