July 4, 2002
Stephen L. DeFelice, M.D.
New Gene Therapy Cure for Alzheimer’s
New Drugs Slow Down Aging
Stem Cell Research Yields Cure for Parkinson’s Disease
Protein Found to Cure Skin Cancer
Unfortunately, it is unlikely that you will see these or similar headlines any time soon. Instead, in the Wall Street Journal, The New York Times, USA Today and the rest, you will read:
– an effective new gene therapy for Alzheimer’s has been found
but it will take years of testing. “new drugs fight aging in animals but such developments for humans are years away.
– new drugs effective for Parkinsonism are expected
to take years of further testing.
– a new protein to treat skin cancer has been tested successfully and
may be ready for humans someday.
Why does it take so long for promising scientific research to be translated into effective medical treatments? Moreover, why doesn’t anyone ask the question, “Why?” Well, I have, and it all began with the carnitine-adriamycin story.
Adriamycin is a powerful anti-cancer drug. The problem is its dose must be limited because it is also cardiotoxic which significantly hampers its tumor kill capacity. If the cardiotoxicity could be eliminated or reduced, more adriamycin could be given that would kill more cancer cells. The result? More lives would be saved or prolonged.
In 1968, at the Walter Reed Institute of Research (WRAIR), James Vick and I conducted a number of laboratory studies in which carnitine, a naturally occurring substance found in the heart, was found to block adriamycin’s cardiotoxicity. This discovery has been independently confirmed and published by other researchers. Yet, over thirty years later, this potentially major breakthrough in cancer treatment remains in limbo.
As a young physician filled with the optimism of youth, I turned to the pharmaceutical industry to sponsor the clinical trials needed to confirm our animal observations. Much to my surprise, I ran into a stone wall. None had interest.
Why? Carnitine, as with almost all natural substances, lacks sufficient patent protection to justify both the investment needed and associated risks to obtain FDA approval. And to make matters worse, since then, costs and risks have dramatically escalated discouraging investment on even strongly patented potential new medical therapies. This situation, not the HMOs or patients rights, is the number one national issue that should be addressed by the Congress .It is a hidden national tragedy. There is no doubt that, at this very moment, our current medical technology ranging from stem cells to tissue transplantation, if properly applied, can eliminate or decrease the impact of many of the current diseases that ail us.
Before I propose a solution, it’s important to understand how medical discoveries are made. Potential medical breakthroughs become real ones only when they are proven to work in clinical studies. Penicillin, aspirin and coronary artery bypass were only shown to have real value after they were tested in people. And this is where the major problem is. Costs and risks to conduct clinical research have placed most of our creative clinical researchers on the sidelines. Joel Goldstein and Michael Brown, Nobel Prize winners in medicine, share the same concern warning that patient oriented research is in serious jeopardy. To add to this national medical tragedy, there is an ongoing alarming decline of U.S. clinical investigators.
How do we solve this medical tragedy? The obvious solution is to reduce the costs and risks of conducting clinical research. Current barriers frustrate even the most patient of physician researchers. Those that look to the FDA for a solution will be disappointed. The FDA is risk-adverse particularly when dealing with volunteers for clinical research. This mentality is harmonious with that of our cultural. We are highly suspicious and fearful of clinical research. The latter is often referred to as human experimentation which bespeaks of this suspicion and fear. Yet astronauts that volunteer to risk and sometimes lose their lives for space exploration are admired. There was no national outcry against space exploration following the death of seven astronauts. They were revered. More recently, pilots volunteered to risk their lives under brutal weather conditions, to rescue a woman with aggressive breast cancer stranded in the South Pole. They were applauded by the mass media. If they had died in their attempt, they would have been revered as national heroes. Witness, however, the national media coverage and uproar as a result of a single death of a volunteer at the University of Pennsylvania undergoing the clinical testing of a promising type of gene therapy. The FDA shut down or temporarily halted other gene studies. The physicians conducting the study were treated like Nazi experimenters. New FDA rules were then issued which increased the already formidable costs and risks to clinical discovery.
After the University of Pennsylvania came Johns Hopkins. Because of a single death the FDA halted all clinical studies at this great institution. The result? More costs and risks. This trend continues unabated and who would you guess pays the price? All of us!.
During the sixties, I observed our nation’s reaction to the thalidomide tragedy. The photos of the deformed children were everywhere to be seen. But another unnoticed but far greater tragedy followed shortly. Fueled by the mentality of fear instead of the need of medical discovery, the federal government, failing to think things through, passed new laws and regulations that dramatically raised the costs and risks of conducting clinical research. And guess what? Drug discovery declined precipitously immediately thereafter.
Alarmed by this phenomenon, I wrote the book “Drug Discovery, The Pending Crisis” which was published in 1972. In the book I call for the establishment of physician volunteers or doctornauts recommending that physicians have the right to volunteer for clinical studies without the standard regulatory constraints as well as waive the right to sue without the standard regulatory. This simple act would dramatically decrease the costs and risks of conducting clinical research, significantly increase the clinical testing of promising therapies and rapidly accelerate medical discovery. To assess doctor’s willingness to take such risks for their patients on natural substances, FIM, the Foundation for Innovation in Medicine, conducted a physician survey. Over fifty per cent responded in the affirmative!
Congress has an obligation to expeditiously respond to the needs of patients and enact a new law that will make physician doctornauts a reality. As with astronauts, soldiers, policemen, firemen and many others, it is time to grant the right to physicians to take risks, even life threatening, to rid us of unnecessary suffering and premature death. If physicians are willing, what, may I ask are the objections?
Christopher Reeve, after hearing about new exciting laboratory technology that could be used to repair severe nerve damage, commented that he wished he were a rat. The implication, of course, is that it will take a long time to clinically test these new potential therapies. If doctornauts existed, they could be tested today. Yes, the same holds true with adriamycin and cancer. Need I say more!
Readers Comments and Questions
Health Care Cost Reduction: A number of readers have called to my attention that I failed to mention that the discovery of new effective therapies will not only help patients but also reduce health care costs.
Unfortunately, this is not necessarily true. For example, the dialysis machine, a medical device, was a great step forward in medical innovation. Its use, however, has enormously increased the costs to treat patients with end stage kidney disease. Before this device became available, such patients would not survive and the costs of therapy would be infinitesimal compared to today’s patients who, because of this device, can live for years at total annual costs of billions of dollars.
Let’s look at another example regarding the pharmaceutical, medical device and surgical approaches to heart attacks and strokes. Medical innovations in these areas have dramatically reduced the mortality associated with these conditions resulting in impressive long-term survival rates. Many of these surviving patients then, however, suffer with chronic problems ranging from heart failure to mental and emotional dysfunction which dramatically raises their health care costs.
Must we then assume that increased medical innovation will lead to increased costs? Of course not!
A large percentage of patients undergoing renal dialysis are diabetics. A significant percentage of patients that have heart attacks and strokes are also diabetic. A well thought out pharmaceutical-nutraceutical combination alone that could even partially prevent the blockage of large and small arteries would significantly reduce the need for dialysis as well as the number of heart attacks and strokes.
In the final analysis, our society has already accepted the credo that medical innovation is good coupled, however, with the need to limit costs. By increasing the clinical testing of potential new therapies, we will then discover both high and low cost modalities and make our decisions on which ones to use accordingly.
Physicians Willingness to Become Doctornauts: A distinguished scholar and physician called me and questioned whether his medical colleagues would be willing to volunteer for clinical studies at increased personal risk. He asked if FIM had conducted a survey on physician attitudes.
About twenty years ago FIM was interested in determining whether physicians would want the privilege of being a doctornaut for clinical studies on natural substances.
A total of 3,100 inquires were mailed to 2,100 male M.D.’s, 500 female M.D.’s and 500 D.O.’s. A total of 10.3 per cent of the physicians responded. In addition, a telephone survey of seven medical institutions was conducted.
A simple ” Yes” or “No” response was asked of the following question, “Would you as a physician-patient want the privilege to volunteer for clinical research of natural substance under the supervision of a physician-clinical researcher without FDA, institutional or other restraints.
The response was as follows:
Physician Response Yes % No % Male M.D.'s Total 52.5 47.5 Male M.D.'s Under Age 50 56.6 44.4 Male M.D.'s Over Age 50 50.0 50.0 Male D.O.'s 60.0 40.0 Female M.D.'s 56.3 43.7 Academic Institutions 57.7 42.3
My distinguished physician colleague commented that the survey dealt with natural substances only and was two decades old. He wondered whether modern physician attitudes have changed and whether they would be inclined to be doctornauts for all potential therapies be they nutraceuticals, pharmaceuticals, medical devices, etc.
I told him that, apart from our survey, physicians have a history of volunteering for clinical research at great risk. Even if only 20 percent of America’s 700,000 physicians would volunteer to be doctornauts, that would immediately make available 140,000 doctornauts for clinical research.
Can doctornauts help children? A mother of a child stricken by a severe disability commented that doctornauts are adults and whether they can help children. The answer is, “Yes!” For example, positive studies on ways to transplant central nervous system tissues in adults can rapidly be applied to children with cerebral palsy or other central nervous system diseases. Also, one major factor in delivering effective gene therapy is the difficulty in finding carriers to deliver genetic materials into the cells. Once they are tested and discovered in doctornaut clinical studies, the gene carriers can then be used for the treatment of children.
And let’s not forget the adriamycin-carnitine combination! (See DeFelice Commentary: Adriamycin & Carnitine). If it destroys cancel cells and protects the heart in doctornauts, it will most likely do the same in children.