Nature & Medicine at Odds
by Stephen L. DeFelice, M.D.
Citadel Press, 1986 $14.95
To purchase this book, please visit The FIM Store here on-line.
Also see La Revolution Nutraceutique. This book is a French translation of From Oysters to Insulin with an international analysis by Professor Andre Rougereau, President L’Lnstitut de Nutrition.
Do you believe that natural substances are important in the prevention and treatment of disease?
Do you believe that natural substances can be useful in such conditions as maintaining physical fitness and slowing down the aging process?
Do you believe that there is significant natural substance research going on to identify their medical value?
The good news: The answers to the first two questions are correct if you said yes; the bad news: sadly incorrect if you said yes to the third.
To those who believe that all is well with natural substance research, citing as examples calcium, fiber, penicillin and interferon Dr. DeFelice replies that “substances such as these merely represent the tip of the tip of the iceberg of nature’s medical promise.” He boldly states that even if water were effective in the treatment of cancer, it would be difficult to prove it in our present system.
From Oysters to Insulin in: Nature and Medicine At Odds raises questions most of us have never thought about. It tells us of problems- and proposes solutions – we didn’t know we had. And yet, ironically, these are questions that will profoundly affect each and every one of us and all of the people we care about.
Stephen L. DeFelice, M.D., begins by telling us of his own entry into the maze: his work for more than twenty years with a natural substance known as carnitine. It was the carnitine saga that introduced him to the incredible series of stone walls our society has erected, walls which virtually guarantee that meaningful research, development and marketing of natural substances cannot take place in America.
Included in the proposed solutions is a call to arms to the public to change the system which prevents us from receiving the proven benefits of nature’s medicines.
Stephen L. DeFelice, M.D., is an internationally recognized authority on clinical research and development of both drugs and natural substances. A graduate of Jefferson Medical College, Dr. DeFelice’s professional experiences encompass the academic, pharmaceutical and government communities. He served as chief of Clinical Pharmacology, Division of Medicinal Chemistry at the Walter Reed Army Institute of Research. He is founder and chairman of the Foundation for Innovation in Medicine, a non-profit educational organization dedicated to monitoring the state of innovation in medicine, particularly in the area of natural substances, and encouraging clinical research.
All proceeds from the sale of this book will be donated to the Foundation.
1. Carnitine Drug, Natural Substance or Food?
2. Food, Nutrient or Drug? No Such Thing
3. The Medical Innovative System
4. Pasta, Wine, Fish and the Health Food Business
5. The Board Meeting
6. A Proposed Natural Substance Classification
7. A Proposed Solution
8. The Supreme Court of Natural Substances and the Law of Acceptable Exceptions
9. Religion, Morals, Ethics and Clinical Research
10. To the Patient: A Call to Action
“A broad mind tackles a difficult medical problem. Essential reading for my media colleagues.” – NATHAN W. GOLDSTEIN, former special assistant to the Publisher of The New York Times
“A brilliant and readable analysis of the forces which hinder the delivery of nature’s medical promise.” – JOSEPH R. DiPALMA, M.D., Vice President and Dean Emeritus, Professor of Pharmacology and Medicine, Hahnemann University School of Medicine
“Provocative treatment of an important but neglected area of medicine.” – LOUIS LASAGNA, M.D., Dean of the Sackler School of Graduate Biomedical Science, Tufts University
“This stimulating and provocative book is a tour de force exposure of the problems in the current regulatory programs of the United States in the food and drug areas. I recommend the book as required reading for regulators, physicians and patients.” – WILLIAM J. CURRAN. J.D., LL.M., S.M.Hyg., Frances Glessner Lee Professor of Legal Medicine, Harvard Medical School
“Dr. DeFelice has focused on the lack of incentives to spend research dollars on natural substances. His personal experiences with our regulatory and economic system are most instructive-and make fascinating reading.” – STEPHEN H. McNAMARA, Esq. of the Washington, D.C. law firm of Hyman, Phelps & McNamara, former Associate Chief Counsel for the United States Food and Drug Administration
Nutrient or Drug?
Review by Irene Alleger
From The Townsend Letter For Doctors, April, 1987
Dr. DeFelice is a recognized authority on clinical research and development of both drugs and natural substances His initial awakening to the promise of natural substances began more than 20 years ago when he took on the job of evaluating the clinical data on carnitine. His findings started him on a long and frustrating journey which he chronicles here, through the bureaucratic maze of NDA’s, FDA approval, and the enormous costs involved in developing and marketing new drugs
Today, carnitine is still not approved by the Food and Drug Administration for medical uses, but is available in health food stores This is a classic example of how we have walled ourselves in with legislation intended to protect the public from tragedies such as thalidomide. Although the intent of the legislation was to prevent future drug tragedies from happening. Little did anyone realize that one result would be the virtual total control of clinical research-the key to medical innovation-by the federal government.
The cost for a pharmaceutical company to have one new prescription drug approved by the FDA is around $100 million. In order to justify this investment, the company must be assured that it will have no competition over a period of years in order to recoup its investment. This can only be done with a product patent. If pharmaceutical companies must invest millions of dollars in mass-producing a new drug. it is not surprising that they prefer to “invent” new- drugs through technology, which they can then patent, guaranteeing profitability.
Given the amount of money it takes now to do the controlled studies needed for FDA approval of a new drug these companies are not about to invest millions in research and development of natural substances which cannot be protected by patent. Natural substances are sometimes granted a “use” patent, or limited exclusivity, but this is not sufficient incentive for the massive investment needed.
Even though there is a mountain of data showing the benefits of these natural substances and even though consumers are now buying these products in health food stores and using them across the nation, there is no way at this time for pharmaceutical companies to produce FDA-approved natural substances for use by physicians
Bureaucratic red tape and enormous costs are not the only problems involved either. One major problem that confronts companies interested in natural substances is the extreme difficulty of isolation and production. This involves the FDA policy toward mixtures Many natural molecules are large and complex and cannot, even if chemically characterized, be produced in a large quarterly. Secondly, many natural substances, such as vitamins, act together to produce an effect. Current regulatory policies force researchers to break apart the plant chemically to isolate and synthesize different entities Only a handful of reputable companies worldwide have made serious efforts to develop major research and development on extraction technology; the risk is too great. Dr. DeFelice says “There is little doubt that animal-organ or plant-extract technology could produce more mayor medical advances than most experts realize.”
Government efforts to protect the public from risks has created these seemingly unresolvable dilemmas There is also the problem of drug “lag” with the development time for new drugs now about ]4 years. The government, not content with decreasing our U.S. medical creativity, also strained the resources of the pharmaceutical industry by directing its energy away from innovative into defensive clinical research. DeFelice reports “The FDA, utilizing the National Academy of Sciences (NAS) and the National Research Council (NRC), convened representatives of the academic community to review all drugs marketed from 1938 to 1962. The NAS/NRC reviewed approximately 4,000 drugs encompassing about 16,000 indications These panels rated drugs as: 1) effective, 2) probably effective, 3) possibly effective, or 4) ineffective, according to how much data was available on them. If drugs rated less than effective were to remain on the market, more clinical research was required. The sponsors of these drugs moreover, were required to produce data that conformed with the legal definition of a controlled study. usually requiring the utilization of the double-blind technique. Assuming that each indication required 3 controlled studies to evaluate its efficacy, the tote] number of studies would be 78,00(). a figure many times the number of studies that capable investigators could perform. The NAS/NRC rated approximately 80% of all indications as less than effective.”
No small part of this tangled web is the definition of “drug” Some natural substances such as insulin, antibiotics and interferon are called drugs Even vitamin A, a natural substance, if taken in excessive amounts, is considered “drug toxicity.” Dr. DeFelice reasons that until clear definitions of nutrients, food and drugs are made, there will be little done to change the situation.
These complex problems affect all of us and Dr. DeFelice has written a detailed and interesting background to these contemporary medical issues He also offers some provocative solutions
1. Physician volunteers for clinical research.
2. Deregulation of early clinical research on natural substances in medical schools.
3. Create a new specialty – the clinical developer
4.. Establish natural substance clinical research centers supported by no-strings government grants
This book covers a lot of ground explaining the convolutions of government control and elucidates the many factors involved in the pharmaceutical drug/natural substance debate. I doubt that changes in the present system will be easy, but Dr. DeFelice’s message is clear: the time has come to harness the vast medical potential of natural substances and put them to immediate use.
From time-to-time we glean quotations & illustrations from:
The Earth. Speaks Ed. by Steve Van Matre & Bill Weiler
Blockprints by Gwen Frostie.
Institute for Earth Education,
P.O.B. 288, Warrenville, IL 60555
The Promise of Natural Substances
Review by Louis Lasagna, M.D.
Dean, Sackler School of Graduate Sciences Tufts University. Boston, Mass.
Reprinted from Medical Tribune Wednesday, June 25, 1986
Steve DeFelice is a romantic at heart, despite his scientific acumen and scholarly attributes. His mission is simple in concept but difficult to achieve: “to harness the vast medical potential of natural substances and put them to immediate use.” He describes, in this book, a promise that is “breathtaking . . . the natural substances presently available for medical use represent only the ‘tip of the tip’ of the iceberg. ”
The major barriers to achievement of Dr. DeFelice’s goal are, in his view, the bureaucrats in industry, government, and academia who lack vision and discourage innovation in this arena.
Appropriately enough, the first chapter deals with the author’s remarkable persistence in bringing carnitine to the world market as a therapeutic substance. L-carnitine is found naturally in the body, but its role in the body’s economy is still obscure after years of research and hundreds of published papers. But clearly carnitine has interesting biological activity.
Dr. DeFelice, on the basis of clinical observations begun over twenty years ago, and basic laboratory work supported to a considerable extent by his own money, postulated that carnitine “had medical promise in a wide variety of diseases, ranging from angina pectoris . . . to a natural aging.”
Because of the precarious patent position of carnitine, Dr. DeFelice suffered disappointment after disappointment in his attempts to interest pharmaceutical firms (22 American and 11 international companies). Finally, a savior appeared in the form of Dr. Claudio Cavassa; the no-nonsense owner and president of Sigma Tau has marketed carnitine in Europe where it has sold very well indeed, although the book does not explain clearly for what medical indications the substance is promoted abroad.
Since carnitine facilitates the transport and metabolism of fatty acids, it helps produce energy within cells. It appears that in addition to the rare congenital carnitine deficiency, the material may have utility in the treatment of muscle diseases, of patients undergoing renal dialysis, in hyperlipidemia, cardiac diseases, and intravenous feeding.
Just as carnitine was being positioned for approval in the United States as a prescription drug, Dr. DeFelice received another blow-the ready availability (without prescription) of carnitine made by other manufactures in health food stores. Dr. DeFelice sought legal help, and the FDA has decided to block the importation of DL-carnitine, but not L-carnitine, for health food use, perhaps because Dcarnitine is an unnatural substance and not a food. (Sigma Tau tried to develop a method for production of L-carnitine, since the unnatural D-moiety might prove toxic on chronic administration.)
Dr. DeFelice has some amusing and interesting things to say about the health food industry and specific examples of conflict between government, industry, and the public, such as the flap about All-Bran and its possible deterrent effect on the development of colon cancer. One of the most provocative sections of the book has to do with Dr. DeFelice’s suggestion about “physician volunteers for clinical research.” He proposes that any physician, healthy or sick, be permitted to freely volunteer to be a subject for a physician-therapist if the latter wishes to evaluate a natural substance, and that this relationship should be immune from all legal and established restraints and that the physician-therapist be free from all liability. His Foundation for Innovation in Medicine conducted a survey of physicians to find out how willing they would be to engage in such a program, and found that over half of those surveyed indicated that they would want the privilege to volunteer.
He has three other specific suggestions that are also provocative. He believes that society should encourage the creation of a new specialty-the Clinical Developer, who is to be “a generalist who has a reasonable mastery of pharmacology, toxicology, statistics, medicine, economics. the current morality of the day, and the complex regulatory requirements.”
He also wants society to establish natural substance clinical research centers supported by no-strings government grants.
Finally, he believes that there should be created a “Supreme Court of Natural Substances and the Law of Acceptable Exceptions.” This court should have power to adjudicate cases of liability, truth in labeling, and other pivotal issues.
One suspects that Dr. DeFelice. on the basis of this book, will shortly be appearing on many talk shows. His concern with natural substances and with nutritional problems is close to the heart of many laymen and laywomen. Indeed, it is paradoxical that at a time when the American public has never been more interested in nutntional matters, academia by and large has taken a condescending attitude towards nutrition and looks upon it almost as a pseudoscience. It is a case of the public leading (or trying to lead) science and the university world instead of the other way around. Dr. DeFelice deserves credit for bringing these problems to the attention of the lay and professional public.
From the Tip of the Tip of the Iceberg To ‘Nature’s Vast Medical Potential’
We believe that we can count on one thing, to wit, in the years ahead our patients will benefit from the “breath-taking [promise that] natural substances presently available for medical use represent only the ‘tip of the tip’ of the iceberg of nature’s vast medical potential.” The opening of this potential will require the breakdown of stereotype thinking, of prejudiced orientations, and of bureaucratic constriction, be they in government, industry or academia.
Enough of this! The reader would do well to turn to Professor Lasagna’s review of the book Oysters to Insulin by Steve DeFelice on page 55.
A. M. S.