Sunday, January 17, 2010
Big Pharma & many others wants this kept secret.
Drug tests revealed biological principle, says retired scientist
EL JOBEAN -- As a young research scientist at the University of Pittsburgh early in his career, El Jobean retiree Semour Antelman made a ground-breaking discovery.
He found that anti-depressant drugs administered in a single dose given to lab rats only on the first day of a 22-day test had virtually the same effect as giving the rats several doses every day for several weeks.
Even with just one dose, the anti-depressant boosted the electrical activity of dopamine receptors in the rats' midbrain by some 60 percent, the same level as the rats that received daily doses.
That research, conducted in the late 1970s, led to the discovery of what Antelman's research team dubbed "Time-Dependent Sensitization."
The term refers to a phenomenon in which the effect of drugs, and even non-drug stressors such as electro-convulsive shock, strengthens within the body for weeks and, in some cases, months after just a single dose.
The implications of the discovery remain enormous, Antelman said, as he looked back on his career during an interview at his El Jobean home.
Doctors one day could prescribe patients just one pill every three weeks instead of three pills a day.
That would save patients, insurance companies and government programs billions of dollars, he said.
Third World countries, which are plagued with illnesses and can't afford prescription drugs, would reap even bigger benefits, he said.
And the knowledge that both drugs and non-drug stresses have a delayed reaction could be applied to better understand such disorders as drug addiction and post-traumatic stress disorder.
"This holds the key to understanding the development of disease," Antelman says. "That's no small thing."
A turn of events
During his career, Antelman directed the university's psychiatry department, served on two elite research foundations, published 10 papers in peer-reviewed science magazines, lectured at Columbia and Harvard and, at least at first, won an extraordinary number of research grants.
In 1988, however, after journalists from the BBC to the New York Times publicized his discovery around the world, the grant funding began to dry up, he said.
"In science, you have to rely on grants," Antelman said. "I was on the ropes."
Antelman and his wife, Violeta, who summer in Pennsylvania, purchased a winter house here overlooking the Myakka River in 2001.
Antelman said he chose the nondescript house because it was big and would give him a chance to express his creativity.
Since then, he and his wife have remade the house into a unique castle-like abode. Walls have been paneled in stone, rooftops converted into parapets.
The interior is decorated with life-size statues and folk art from China, Thailand, Tibet, India, Africa, Japan and Mexico.
"I like big," Antelman explains.
But he remains frustrated that the world has yet to benefit from his medical discovery.
"It's one of the greatest disappointments of my life," Antelman says. "I mean, to make a discovery like this, that has such enormous implications. We're talking about something that would do no less than reform prescriptive medicine forever worldwide."
Proving it
From the beginning, he knew his discovery would be considered "heresy" to the accepted principles of pharmacology, Antelman acknowledges.
But over the next 20 years, he and other scientists tested the theory, primarily on rats, in studies involving dozens drugs and dozens of bodily "end points."
Some researchers focused on testing anti-depressant and anti-psychotic compounds, others the cancer treatments interleukin-1 and interleukin-2.
Still others tested narcotics, ranging from cocaine to morphine.
The rats' reactions to non-drug stressors, from loud bell ringing to tail pinching, also were studied.
In all cases, the researchers found the effects of the drugs or stressors grew stronger over time to a single dose, and even stronger after a second dose given after a hiatus. That's according to paper summing up the research that Antelman and two other researchers published in 2000 in Molecular Psychiatry.
"The evidence for this is overwhelming," Antelman contends. "I studied this for 22 years. It was done in every way imaginable. It worked with everything."
Why it works remains a mystery.
Antelman theorizes that organisms developed TDS much like they developed immune systems. In both cases, the body reacts to a single exposure to a foreign substance in a defensive reaction that carries on for a long time afterward.
"We're talking about something that is so broad, it reflects a basic principle of biological function," he said.
Colleagues' views
Dr. Robert M. Post of Chevy Chase, Md., who retired in 2006 after 36 years as chief of biological psychiatry at the National Institute of Mental Health, said Antelman's TDS discovery "has been very widely replicated in the literature."
Post cited one tangent of Antelman's research that he considered particularly interesting. It was a study that found the the same quirky behaviors observed in rats treated with amphetamine and cocaine could later be triggered by non-drug stresses, such as a tail pinch, long after the rats were "clean."
That finding is important to clinicians who treat patients affected by both bipolar disorder and substance abuse, Post said. It shows how a drug addict's relapse could "cross over" to trigger a bipolar episode, and vice versa, he said.
More research needs to be done before doctors should prescribe drugs based on a TDS regimen, Post said.
"But the other findings are very important, and (Antelman) should be credited with these discoveries," he said.
"I think he's a respectable scientist and he's done some innovative work," added Dr. John M. Davis, a research professor at the Illinois Psychiatric Institute in Chicago.
Davis said he became so intrigued with Antelman's theories, he considered testing TDS on human subjects. But he and his colleagues never resolved logistical challenges and the research was never initiated, he said.
TDS likely won't be put into practice until the National Institute of Health sponsors large-scale studies on human subjects, Antelman said.
Last March, he wrote President Barack Obama to suggest TDS be pursued as a priority to cut health care costs.
Four months letter, Obama's office sent a reply via a form letter, thanking him for his interest.
Antelman blames human nature.
"There is such a bias toward things continuing to be done the way they have always been done," he said. "It's just: Let's remain in ignorance."
EL JOBEAN -- As a young research scientist at the University of Pittsburgh early in his career, El Jobean retiree Semour Antelman made a ground-breaking discovery.
He found that anti-depressant drugs administered in a single dose given to lab rats only on the first day of a 22-day test had virtually the same effect as giving the rats several doses every day for several weeks.
Even with just one dose, the anti-depressant boosted the electrical activity of dopamine receptors in the rats' midbrain by some 60 percent, the same level as the rats that received daily doses.
That research, conducted in the late 1970s, led to the discovery of what Antelman's research team dubbed "Time-Dependent Sensitization."
The term refers to a phenomenon in which the effect of drugs, and even non-drug stressors such as electro-convulsive shock, strengthens within the body for weeks and, in some cases, months after just a single dose.
The implications of the discovery remain enormous, Antelman said, as he looked back on his career during an interview at his El Jobean home.
Doctors one day could prescribe patients just one pill every three weeks instead of three pills a day.
That would save patients, insurance companies and government programs billions of dollars, he said.
Third World countries, which are plagued with illnesses and can't afford prescription drugs, would reap even bigger benefits, he said.
And the knowledge that both drugs and non-drug stresses have a delayed reaction could be applied to better understand such disorders as drug addiction and post-traumatic stress disorder.
"This holds the key to understanding the development of disease," Antelman says. "That's no small thing."
A turn of events
During his career, Antelman directed the university's psychiatry department, served on two elite research foundations, published 10 papers in peer-reviewed science magazines, lectured at Columbia and Harvard and, at least at first, won an extraordinary number of research grants.
In 1988, however, after journalists from the BBC to the New York Times publicized his discovery around the world, the grant funding began to dry up, he said.
"In science, you have to rely on grants," Antelman said. "I was on the ropes."
Antelman and his wife, Violeta, who summer in Pennsylvania, purchased a winter house here overlooking the Myakka River in 2001.
Antelman said he chose the nondescript house because it was big and would give him a chance to express his creativity.
Since then, he and his wife have remade the house into a unique castle-like abode. Walls have been paneled in stone, rooftops converted into parapets.
The interior is decorated with life-size statues and folk art from China, Thailand, Tibet, India, Africa, Japan and Mexico.
"I like big," Antelman explains.
But he remains frustrated that the world has yet to benefit from his medical discovery.
"It's one of the greatest disappointments of my life," Antelman says. "I mean, to make a discovery like this, that has such enormous implications. We're talking about something that would do no less than reform prescriptive medicine forever worldwide."
Proving it
From the beginning, he knew his discovery would be considered "heresy" to the accepted principles of pharmacology, Antelman acknowledges.
But over the next 20 years, he and other scientists tested the theory, primarily on rats, in studies involving dozens drugs and dozens of bodily "end points."
Some researchers focused on testing anti-depressant and anti-psychotic compounds, others the cancer treatments interleukin-1 and interleukin-2.
Still others tested narcotics, ranging from cocaine to morphine.
The rats' reactions to non-drug stressors, from loud bell ringing to tail pinching, also were studied.
In all cases, the researchers found the effects of the drugs or stressors grew stronger over time to a single dose, and even stronger after a second dose given after a hiatus. That's according to paper summing up the research that Antelman and two other researchers published in 2000 in Molecular Psychiatry.
"The evidence for this is overwhelming," Antelman contends. "I studied this for 22 years. It was done in every way imaginable. It worked with everything."
Why it works remains a mystery.
Antelman theorizes that organisms developed TDS much like they developed immune systems. In both cases, the body reacts to a single exposure to a foreign substance in a defensive reaction that carries on for a long time afterward.
"We're talking about something that is so broad, it reflects a basic principle of biological function," he said.
Colleagues' views
Dr. Robert M. Post of Chevy Chase, Md., who retired in 2006 after 36 years as chief of biological psychiatry at the National Institute of Mental Health, said Antelman's TDS discovery "has been very widely replicated in the literature."
Post cited one tangent of Antelman's research that he considered particularly interesting. It was a study that found the the same quirky behaviors observed in rats treated with amphetamine and cocaine could later be triggered by non-drug stresses, such as a tail pinch, long after the rats were "clean."
That finding is important to clinicians who treat patients affected by both bipolar disorder and substance abuse, Post said. It shows how a drug addict's relapse could "cross over" to trigger a bipolar episode, and vice versa, he said.
More research needs to be done before doctors should prescribe drugs based on a TDS regimen, Post said.
"But the other findings are very important, and (Antelman) should be credited with these discoveries," he said.
"I think he's a respectable scientist and he's done some innovative work," added Dr. John M. Davis, a research professor at the Illinois Psychiatric Institute in Chicago.
Davis said he became so intrigued with Antelman's theories, he considered testing TDS on human subjects. But he and his colleagues never resolved logistical challenges and the research was never initiated, he said.
TDS likely won't be put into practice until the National Institute of Health sponsors large-scale studies on human subjects, Antelman said.
Last March, he wrote President Barack Obama to suggest TDS be pursued as a priority to cut health care costs.
Four months letter, Obama's office sent a reply via a form letter, thanking him for his interest.
Antelman blames human nature.
"There is such a bias toward things continuing to be done the way they have always been done," he said. "It's just: Let's remain in ignorance."
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