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The Kenneth Blum, PhD Life Story: A man seeking truth while reaching for the Stars.
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I have been involved in scientific, pharmaceutical and nutraceutical exploration for over a half of a century. I was born in Brooklyn and grew up in an orthodox Jewish home with loving parents, my mother being strong willed and my sister Barbara caring. One night ready for bed, when I was eleven years old, lying down looking up onto the white ceiling I asked myself a question" Why am I here... what is my purpose in life" I remember thinking: Win an Oscar; win a Pulitzer prize, receive the Noble prize in Medicine. Later, my mother had refused to let me attend the New York School of performing arts in spite of applying and getting accepted without my parent's permission -"I want my son to be a doctor not a waiter... (actor) Harry slap him!"
The first step to that end came when I was accepted to the class of 1961 at Columbia University College of Pharmacy. This is when and where I had my first interaction with the world of drugs where I developed a strong interest in research. I began to carry out research in the department of pharmacology on a project involving mucopolysaccharides and stress in rodents. My interest in research was recognized very early on and I was awarded upon graduation the prestigious Bigelow Fellowship, given to the student most likely to succeed in research pursuit. However for me it was much more exciting that I was the only Gringo who ever won The New York Palladium Mambo contest 8 weeks in a row and Joe Cuba at that time pronounced me as the Mambo Jew".
After graduating from college, I married Arlene. She gave me 37 years of a happy marriage and two wonderful children, both boys, Jeff and Seth.
Using the stipend from the Bigelow Fellowship, I entered New Jersey College of Medicine. Being distraught because of the death of my father (Harry), I left the college after receiving a master's degree in Medical Science. My thesis involved the role of dopamine in neuromuscular skeletal junction. It was a study which provided the world with an early view of the role of dopamine in peripheral motor control and tremor production due to central deficiency. When the paper was published in 1969 in Archives of International Pharmacodynamie Therapeutics1 to my surprise, I received thousands of requests for the paper. This, my first published article became the cornerstone of the dopamine research that followed.
Following a small stint at U.S. Vitamin Pharmaceutical Corporation in Yonkers New York, where I served as chief neurophramcologist, I entered New York College of Medicine to receive a PhD in neurophramacology. This brought great joy especially to my mother (Lena). I studied under the tutelage of Joseph Seifter, a student of Oswald Schmiedeberg, the author of the first textbook in pharmacology in 1878. In later years, Joseph Seifter became the director of all research for Wyeth Laboratories, the company that developed the first use of tranquilizers in America.
I did my Ph.D. thesis on a substance that has become quite popular, Carnitine (vitamin BT). My thesis was signed off by Carl Pfeifer, a world class scientist in the field of nutrition medicine. Unbeknownst to me at the time, I would eventually publish a book with Carl Pfeifer and Eric Braverman called "The Healing Within". In our published paper, we discovered that this substance, when acetylated (acetyl-carnitine), mimics the action of acetylcholine, a chemical in the brain2. My interest had turned toward psychopharmacology. A former professor of mine, Irving Geller, and my mentor Joseph Seifter, pressured me to continue in research. Professor Geller actually bought Arlene and me a round trip ticket to Texas. He also made a phone call to his brother Eli, chairman of Medical School admissions of Einstein, cancelling my acceptance to Einstein College of Medicine in New York City where I was set to pursue an MD degree. Reluctantly, I found myself in San Antonio at Southwest Foundation for Biological Science working as a senior research scientist in the division of behavioral sciences for $11,000 per annum. In 1968, the foundation was famous for their research on baboons. I had screaming sweaty awakening nightmares about working with Baboons. They say dreams come true. It must be so as one day I found myself running down the highway being chased by a big baboon. This was my TV debut in Texas; but that is another story.
That same year a new institute, the National Institute of Alcoholism and Alcohol Abuse (NIAAA) arrived on the scene. At that time, I had no interest in the pharmacology of alcohol or clinical alcoholism. However, Irving Geller and I requested a grant from NIAAA to show the effects of stress, (something that I knew about) on alcohol intake and related brain chemistry in animals.
As many people believe, "there are no accidents!" Fatefully, the individual who reviewed the grant and visited our laboratory was Ernest P. Noble. He is a man of vision who not only approved the grant, but became a colleague of mine. In later years, our collaboration resulted in the discovery of the first gene association with severe alcoholism. We have been friends for over forty-two years. The grant he approved initiated my research into the neuropsychopharmacology and genetics of alcoholism.
My humble entrance into the field of alcoholism , being a young man seeking scientific truth, has always been tempered by my childhood dream of exploring the universe and finding the extraordinary in spite of the challenges before me. In terms of research aspirations, I wanted to reach for the stars. My scientific journey has been filled with drama, intrigue, controversy and excitement not that different from the likes of an Agatha Christie Murder Mystery novel where my character mimics that of Miss Jane Marple, an unfailing sleuth.
To begin with, Geller and I found that rodents exposed to stress drank large amounts of alcohol only on weekends when there was no stress; a surprising development. It was as if we were looking at a human binge drinker, and we had no explanation for this phenomenon. One explanation for this surprising result was that during the weekend when the lights were turned off, darkness and the natural substance melatonin, generated from the pineal gland, had something to do with aberrant drinking behavior. Following a quick trip to Atlantic City where Geller and I listened to Nobel Prize -winner Julius Axelrod discuss circadian rhythm, Geller placed rats in a dark closet and found copious drinking in rats that hated alcohol3. As a young scientist I agonized over the fact that my associate Irving Geller published the seminal work in Science ( the most respected journal in the field) intentionally leaving my name off the publication. But once again, things happen for the best and in this case quitting the Foundation became a very positive step toward my future research explorations.
I became an assistant professor with tenure in the department of Pharmacology, University of Texas in 1972, until my retirement as full professor in 1995. Russell Reiter the famous Pineal Gland researcher at the University of Texas Health Science Center in San Antonio, Texas and I published seminal articles involving the role of the pineal gland in alcohol seeking behavior in Syrian Golden hamsters and rodents.4-6 During my early tenure at the medical school, I was working with my friend and Chairman of the department of Pharmacology Arthur A. Briggs, who had hired me on the spot, telling me " I don't want you to attend any pharmacology staff meetings... just close yourself up in your lab and get the Noble Prize". Together, we conducted a number of experiments relating to what factors increased or attenuated alcohol craving in rats. This research provided the impetus to the idea that craving for alcohol is related to specific brain chemicals, primarily neurotransmitters. One late night, while working in my lab at the Foundation, taking a brief power nap, I began to see ethanol molecules smashing onto the shores of the blue ocean. Then it hit me...there must be ethanol receptors in the brain. Consumed with intense curiosity as to what they were. I immediately began to write a paper called "brain ethanol receptors." This paper finally got published two years later in 1972 in the European Journal Pharmacology (a different title) one year ahead of the famous Pert and Snyder paper in Science on finding the opiate receptor in brain tissue.
In 1970, while I was still at the Southwest Foundation, Virginia Davis and Michael Walsh7 published the first paper suggesting that when an animal drinks alcohol, it produces a substance called tetrahydropapaveroline (THP). The interesting thing about the substance is that it is also found in the poppy plant, from which morphine is synthesized. Davis and Walsh suggested that the neurochemistry, of the brain of an alcoholic and a heroin addict, are similar. Following this exciting finding, Jerry Cohen and Michael Collins8 at my Alma Mata, Columbia, found another type of isoquinoline salsolinol (TIQ) in animals drinking alcohol, further indicating that there is a reaction in the brain when alcohol is consumed that is similar to the reaction to opiates, such as morphine and heroin. I first heard about all of this work at the second annual meeting of the Society of Neuroscience in Houston, Texas. Following nomination by Sol Snyder, recipient of the Lasker Award (American equivalent to the Noble Prize,) and Floyd Bloom, who later became the editor-in-chief of the Science journal, I too joined the society. Approximately 100 neuroscientists attended that second meeting compared to 33,000 people who now attend annually.
After reading the articles associated with this work, my laboratory began to explore the alcohol/opiate connection. We were the first laboratory to show that a narcotic antagonist, naloxone, blocked alcohol-induced sleep in mice. Naloxone, later naltrexone (variant compound) was produced by Dupont as Revia and is now known as Subloxin. We also showed that this narcotic antagonist blocked alcohol-induced dependence as well as attenuating alcohol intake in rats10-11. These initial experiments met with great controversy. Following my presentation of a paper in Washington DC at the National Academy of Science, supporting the concept of common mechanisms between alcohol and opiates, I was confronted for the first time in my scientific career by Avram Goldstein, a giant in the field. He had published a paper that same year in Science arguing against the link between opiates and alcohol. Harold Isbell, the chairman, stopped the meeting and because of the importance of the topic asked Goldstein to comment on our controversial findings. I sat quietly listened for his rebuttal when to my great surprise Goldstein praised the work and stated that he was wrong and I was right. The room exploded into wild applause and I received my first standing ovation. This work also served as the cornerstone for my first edited book "Alcohol and Opiates: Common Neurochemical and Behavioral Mechanisms.9
Another highlight in my early days was the development of the First National Conference on Drug Abuse. There, I first met David Smith, Andrew Weil, Joel Fort, Gerry Jaffe, Robert Dupont, Harold Isbel, and many other giants in the field. I became Chairperson of the week-long conference held at the University of Texas Health Science Center.
As our work continued, we found the first evidence that the brain chemical dopamine can block withdrawal from alcohol in rodents.12 We also found that morphine, similar to dopamine, could also block alcohol withdrawal.13 For over ten years our laboratory was devoted to understanding how TIQ (which is a condensate of dopamine and dopamine aldehyde being synthesized in the brain following alcohol drinking) could act as an alcohol-like substance as well as an opiate-like substance. Indeed we found that TIQ could enhance alcohol-induced sleep in mice,14 induce withdrawal convulsions in mice blocked by naloxone,15 and potentiate morphine-induced analgesic response.16 Excitement began to build, but most recognized scientists were un-impressed by not only our work but the extensive research of Robert Myers (later to become the Editor-in-Chief of Alcohol, one of the most prestigious journals in the alcohol field) and others showing that TIQ induced alcohol drinking behavior in animals.17 There were two major disbeliefs that clouded the potential importance of the TIQ's in alcoholism. The first had to do with the notion that the TIQ's acted like an opiate and the second had to with an inability to find large enough detectable amounts of TIQ's following alcohol drinking in rodents. On the heels of this heated debate and uncontrolled emotionality in many subsequent meetings, following the discovery and isolation of an opiate receptor first described by Candice Pert and Sol Snyder and confirmed by others, 18 we boldly forwarded a sample of TIQ to the laboratory of Avram Goldstein at Stanford University Medical School. He called me with both excitement and disbelief, the TIQ specifically bound to the opiate receptor. I actually begged Avram to publish the work but he refused. However, this original work was confirmed here in the United States and Italy.19 During the few short years that followed this discovery, the opiate field was buzzing with the identification of a natural ligand for the opiate receptors. The first coming from Kosterlitz and Hughes of Aberdeen, Scotland and others in the United States and abroad.20 In fact at an early House Gordon Research Conference that I attended in Maine, Eric Simon from New York Medical School coined the term "endorphins" derived from endogenous morphine. The world from that... continue reading
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