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Joseph Knoll

Shattering the Barriers of Maximum Life Span:
An Interview with Dr. Joseph Knoll

By David Jay Brown
Joseph Knoll, M.D., is a Hungarian nuerochemist and pharmacologist. He is probably best known for developing the drug deprenyl (also known as Selegiline), the first selective MAO-B inhibitor, and he has researched the properties of deprenyl for over half a century. 

Dr. Knoll is also the author of the recently published book The Brain and Its Self: A Neurochemical Concept of Innate and Acquired Drives (Springer, 2005), which summarizes his life’s research and his fascinating speculations about the relationship between brain activity and culture. In this book Dr. Knoll describes how his experience as a Nazi concentration camp survivor helped to inspire and motivate much of his scientific research. Although his parents were sent to the gas chamber when he was a teenager, Dr. Knoll survived because he spoke fluent German and was chosen to serve as the personal servant to the Chief of the SS guards. After the war, in 1945 Dr. Knoll returned to his native city of Budapest. He earned his M.D. from the University of Budapest in 1951, and later became a professor and the head of the Department of Pharmacology at the Semmelweiss University of Medicine in Budapest.

In the early 1950s, Dr. Knoll helped to pioneer research into the physiological basis of innate and acquired drives in animals. Trying to make sense of his experience in the Nazi concentration camp, Dr. Knoll became interested in how animals acquire new drives. The research that resulted from Dr. Knoll’s interest in this subject centered around studying the brain changes in rats that had been trained to have an acquired drive for an unnatural object–a glass cylinder. This acquired drive–which urged the animals to search for, and jump to, the rim of a thirty centimeter-high glass-cylinder, and then crawl inside–would often override the animals’ instinctive drives for food and sex.

Dr. Knoll first synthesized deprenyl in his Budapest laboratory in 1961. He showed that deprenyl improves the availability of dopamine, and slows its age-related decline by acting as a selective MAO-B inhibitor. Even more importantly, according to Dr. Knoll, it has an enhancer effect, and it helps maintain healthy brain cells, particularly in the dopamine-producing area of the brain known as the substantia nigra–the area of the brain that degenerates with Parkinson’s Disease. For this reason deprenyl has been used as an effective treatment for Parkinson’s Disease. It has also been shown to be an effective treatment for Alzhiemer’s Disease and other brain disorders that result in cognitive decline.

Deprenyl has been shown to have many uses as a cognitive enhancer. It is a moderate-level stimulant and antidepressant that has been shown to improve memory, protect the brain against cell damage, alleviate depression, extend the life span of laboratory animals, and heighten sexual desire in both men and women. This impressive substance is available by prescription in the U.S., and although it is primarily prescribed to help people with Parkinson’s disease, memory disorder problems, and sometimes depression, a lot of healthy people also use deprenyl to improve their mental performance. In fact, Dr. Knoll himself takes deprenyl every day, and recommends that every sexually mature person should be doing the same. 

I’ve personally been using deprenyl as antidepressant and cognitive enhancer for over ten years, and I can attest to its powerful brain-boosting effects. It improves my mental performance so dramtically that I’ve used it before every public talk that I’ve given since 1995. Along with other cognitive enhancers, such as hydergine and piracetam, I think that deprenyl has incredible potential for enhancing memory, accelerating intelligence, and improving concentration. There is a good deal of scientific evidence to support these claims. For an excellent summary of the scientific studies in this area see John Morgenthaler and Ward Dean’s book Smart Drugs and Nutrients II.

Many people report that deprenyl and other “smart drugs” have sexually-enhancing “side-effects”, although deprenyl appears to have the leading reputation in this area. According to Dr. Dean–the coauthor of Smart Drugs and Nutrients–“anything that improves brain function is probably going to improve sexual functioning.” This is probably because sexuality and health go hand-in-hand, and sexual vitality is a pretty good indicator of overall health. 

Dr. Knoll and colleagues first reported indications for deprenyl’s potential as a sexuality enhancer in 1983, with reports that old male rats had increased their “”mounting frequency” and “intromission” when they were treated with deprenyl. This contrasted dramatically with the untreated control animals. Many anecdotal reports, from both men and women, have confirmed that these aphrodisiac-like effects apply to humans as well. Because Deprenyl inhibits MAO–the dopamine-destroying enzyme–levels of the excitatory neurotransmitter dopamine rise in the brain, which generally causes people to feel more pleasure and become more physiologically aroused. 

Interestingly, unlike most other MAO inhibitor drugs (such as the antidepressant Nardil), there are usually no dietary restrictions necessary when one takes deprenyl. When taken at moderate levels (under 10 mg.), deprenyl only inhibits the action of  a specific type of MAO–MAO B–which doesn’t interfere with the body’s ability to metabolize the amino acid tyrosine, like a broad-spectrum MAO inhibitor does. This is why most other MAO-inhibiting drugs carry the serious danger of triggering a hypertensive reaction if one eats tyrosine-rich foods, like cheese or wine. Deprenyl has been described by researchers as working with great precision in this regard, and the physicians that I spoke with agreed that it was unusually safe.

In fact, deprenyl is better than safe. This truly remarkable drug has also been shown to increase the maximum lifespan of laboratory animals by close to forty percent. This is the equivalent of a human being living to be around a hundred and fifty years of age. Giving deprenyl to animals is the only experimental treatment–besides caloric restriction–that has been shown to increase maximum life span. [Extending maximum life span–as opposed to extending average life span–means extending the maximum number of years that the longest-lived members of a particular species has been known to attain.]

To fully appreciate how significant deprenyl’s life extension potential is, one has to understand the difference between maximum life span and average life span. Many factors can affect the average lifespan (or the “normal life expectancy”) that an animal lives–genetics, diet, exercise, nutritional supplements, mental attitude, ect. However, even under the very best of conditions, there is an upper limit at which the longest-lived animals of a particular species can survive, and that is the animal’s maximum life span. 

The average life span of a human being is approximately seventy to eighty years. However, the maximum life span of a human being is around a hundred and twenty years. The laboratory animals in the deprenyl studies showed a forty percent increase in maximum life span, the human equivalent of living a hundred and fifty years. Since deprenyl’s primary effects work the same in all mammalian brains, it stands to reason that deprenyl’s life extension effects are likely to carry over to humans, just as the mental benefits do. Many people have certainly verified that the increase in sex drive occurs in both humans and laboratory animals.

To follow are some excerpts from the interview that I conducted with Dr. Knoll in September of 2005. Born in 1925, Dr. Knoll was eighty at the time of this interview. We spoke about how his experience with the holocaust influenced his decision to become a research scientist, how people can utilize deprenyl for its cognitive enhancing and antiaging benefits, and what type of antiaging treatments might be available in the future.

David: How did your experience with the holocaust when you were young influence your decision to become a research scientist, and what inspired your interest in neurochemistry?

Dr. Knoll: It is a horrifying fact that in Germany millions of single-minded little-men, who had previously lived a honest simple life and never belonged to extremist groups, dramatically changed within a few years after 1933 and, imbued with the Nazi ideology, became unbelievably cool-headed murders of innocent civilians during the Second World War. This phenomenon has been documented from many angles in dozens of novels, films, and so on. However, we are still waiting for an adequate elucidation of the brain mechanism responsible for this dramatic and rapid change in the behavior of millions.

As a survivor of Auschwitz, and one of the 1300 survivors of the “Dachau death train,” I had the opportunity to directly experience a few typical representatives of this type of manipulated human beings, and had more than enough time and direct experience to reflect upon the essential changes in the physiological manipulability of the human brain. It was therefore not just by mere chance that, when in the early 1950s I finally had the opportunity to approach this problem experimentally, I decided to develop a rat model to follow the changes in the brain in the course of the

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