Clarkson Magazine

Discovering the "Molecule of the Year"

Dr. George Prell displays the new
molecule he discovered in the brain
using techniques learned as an
undergraduate. "I made educated
guesses about the identity of this
molecule," he says. "We prepared
several candidate compounds and
found which one is present in tissues.
It was like going back in time to
second year, except now we use
better equipment!"

"It's the discovery of a lifetime!" says Dr. George Prell '73 (Cm), a professor of Pharmacology and Biological Chemistry at Mount Sinai Medical Center in New York City. He heads an international research team that just discovered a critical molecule in the brain that regulates blood pressure. Their findings were recently reported in the prestigious Proceedings of the National Academy of Sciences (PNAS), one of the top-three science journals in the world.

Sir James Black, a Nobel Laureate in Physiology or Medicine who had expressed interest in the team's work, sponsored the report in PNAS and helped the team to navigate some of the politics of competitive publication.

The substance they discovered is called imidazole-4-acetic acid-ribotide (IAA-RP). It is abundant in the region at the base of the brain called the medulla, which controls blood pressure, heart rate, and the sympathetic nervous system. "This may be the breakthrough university laboratories and drug companies have sought since the early 1980s," says George. That's when reports began hinting about the existence of an unidentified molecule in the brain that controlled blood vessels and sympathetic activity.

"It's been known for decades that when particular nerves in the medulla are over-stimulated, blood vessels constrict," he explains. "This causes blood pressure to rise and produces hypertension. As part of our study, we showed that blood pressure spiked after we injected IAA-RP that we made in the lab into the medulla. Now we can begin to develop strategies to alter IAA-RP's abnormal activities."

In addition to their blood pressure findings, the team also discovered important implications for type II diabetes. "We found that IAA-RP is one of the most potent stimulants of insulin release ever discovered," says George. "Thus in cases such as type II diabetes, where release of insulin into the bloodstream is insufficient or absent, small amounts of IAA-RP could be therapeutic." However, excessive amounts of IAA-RP block insulin release, so too much IAA-RP may cause diabetes!

"Our working hypothesis is that over-accumulation of IAA-RP may lead to hypertension and diabetes, two chronic disorders that are increasingly seen together in patients," he says. "We've now found that IAA-RP is present in every brain region and is probably involved in nerve-to-nerve communication throughout the brain. Its distribution suggests it may be involved in Parkinson's or Alzheimer's diseases."

"This is every scientist's dream, to make a discovery that will help mankind and start new areas of scientific investigation."

"This is every scientist's dream, to make a discovery that will help mankind and start new areas of scientific investigation," says George enthusiastically. Endocrine Today titled an article about his team's work "New molecular discovery could be the missing link between hypertension and diabetes." The International Society for Cell and Molecular Biology Research named it "Molecule of the Year."

George attributes much of his research success to what he learned as a Clarkson undergraduate. "I considered myself an average student who graduated from one of the top chemistry departments in the country. This gave me the confidence to focus on the chemistry side of pharmacology – the study of drugs and chemicals in biological tissues," he says.

He earned his doctorate from the Faculty of Medicine at the University of Ottawa. Originally from Syracuse, he was used to Potsdam-like weather and he also wanted to stay in touch with his fraternity, ΤΕΦ . "Ottawa seemed to be a good fit," he recalls. "Yet the biology backgrounds of my professors did not mesh well with my interest in drugs as chemicals, so I was left to do research mainly on my own. With a strong foundation in chemistry, my leaps into biochemistry, and then pharmacology and neurochemistry were easy to handle."

The breadth of his self-education paid off. Just a few months into his post-doctoral fellowship at Mount Sinai, he was offered a tenure-track faculty position. Since then, he's continued to use his undergraduate training to synthesize the compounds he's needed, some containing stable and radioactive isotopes. "It's increasingly rare for pharmacologists to do their own organic synthesis," he says, "but I had great teachers."

George is optimistic about his team's findings, but says many hurdles remain. "Our research is in its infancy. The trick will be to custom-design drugs that specifically target IAA-RP's abnormal actions while maintaining more beneficial effects. This may soon be on the horizon if we can develop interest in our newly issued patent." (George can be reached at georgeprell@msn.com or george.prell@mssm.edu.)