Month: November 2018

Stephen L. DeFelice, M.D.

(Over the years I’ve tried by intensive educational efforts, without success, to bring about general change that would speed up the discovery of new medical therapies for the treatment of disease, disabilities and other conditions that ail us by establishing a “health cure” policy. In this article I thought that by presenting FIM’s arguments in a make-believe Congressional hearing on “cure care” would be readily understandable. Regarding health issues, I’ve been following the White House and Congress since the early sixties. The overwhelming majority of hearings and policies have dealt with “health care” such as Medicare, Medicaid, availability of pharmaceuticals at reduced or no costs and the recent Obamacare. None, unbelievable as it may seem, has dealt with “health cure”).

A Senate Health Committee decided to hold a hearing on the current status of research on Alzheimer’s disease. A number of guests were invited including John Salute, M.D., the President of the Alzheimer Association of Concerned Citizens. The veteran Chairman of the Committee, Senator Bruce Byron, commenced the hearing by first calling on Dr. Salute.
“Thank you, Mr. Chairman, for inviting me to this important gathering. As you know our association is very much concerned about the slow pace regarding new effective therapies for Alzheimer’s disease. We’ve spoken to other organizations that deal with a number of diseases and disabilities and they all share the same concern regarding their constituents. I, therefore, feel an obligation to talk not only about Alzheimer’s but also about other diseases that afflict us.

“We believe there’s something radically wrong with our general medical discovery system. For example, with all of our current exquisite technology that can take us to the moon as well as create a living cell why can’t we cure the common cold? Just before this hearing began I spoke to my one of my colleagues from a lung cancer foundation, and he wondered why little progress has been made against this disease over the past 30 years. It’s about time that Congress looks into this matter and finds out the answers.

“Now I mean no disrespect but the federal government, the Congress and the current and past administrations, has almost exclusively dealt with health care and ignored what the people really want. If you were to ask a patient or a healthy person who will inevitably become a patient the question, ‘What do you want?’ “Well, the patient would logically answer, ‘Get rid of my cursed disease’ and the healthy person likewise would say, ‘Prevent me from getting my cursed disease’. Both would emphatically add, ‘We don’t want health care and free hospitalization. We never want to see the inside of a hospital! We want a health cure system along with a health care one.’

“Mr. Chairman, the only way to do this is by speeding up the discovery of new medical therapies. To repeat, Congress has never had a hearing on how to accelerate medical discovery, and we believe that one is urgently needed.”

Senator Byron, clearly surprised and somewhat puzzled by Dr. Salute’s unexpected opening remarks points out, “But Dr. Salute, I’m sure you’re aware that Congress has passed tons of legislation to sponsor medical discovery research projects. Just look at the National Institutes of Health where the annual budget is over $30 billion. Do you and your colleagues believe we’re not spending enough? Is that your point?”

“Unfortunately not, Mr. Chairman. I wish it were so for then the solution would be a simple one by just spending more money. It, instead, has to do with our entire medical system. It’s profoundly counter productive, and what I’m about to say is more than a bit controversial but, in my opinion, the truth. We indeed do generously spend money to fund scientific and medical research to conquer disease but at the same time we paradoxically create barriers to bring these potential new therapies to the people. It’s, in real sense, a medical perversion.”

Senator Byron, not knowing whether to be insulted or curious about these comments chose the latter. He began, “Dr. Salute I mean no disrespect but what you have just said, if true, is one of the greatest national scandals in the history of our country. We always enact health legislation with the best interests of the American people. Though the vast majority of us in Congress are lawyers and not scientists or physicians we do heavily rely on the advice of medical experts when dealing with medical scientific legislation. Not one has ever mentioned what you have just said which, frankly speaking, makes me extremely curious how you have come to this conclusion.

“You are well aware that my mother has Alzheimer’s disease and is losing her battle to hold on to her mind. And let me add that your organization has been the leader in the quest to conquer this awful disease. And you are also aware that the government has heavily funded it to find new effective therapies. Yet what you are saying is that we do it in the wrong way, and, I, as well as my colleagues on this senatorial committee, would surely like to know what you know that we, and everybody else, don’t know.”

There was an uncomfortable pause in the hearing room because of this unexpected and dramatic turn of events. All came prepared to address the issue of Alzheimer’s disease and not the so-called perverse medical discovery system. Dr. Salute, a veteran of Washington politics, was well aware of this and thought about how to get the senator off the hook and yet make his point. He concluded that the best way was to tell the truth.

He began, “Mr. Chairman, I fully appreciate what you have said and it would be impossible to thoroughly cover the issue at this very important Alzheimer’s hearing with the limited time available for my comments. First of all, our great country which, though blessed by untold scores of well meaning charitable people and organizations for reasons only known to God, has a cultural blind spot regarding general nuts and bolts ways to generally increase the discovery of new medical therapies for all diseases. We concentrate, instead, on funding research for specific diseases such as AIDS, breast cancer and, yes, Alzheimer’s. By the very fact that Congress or past administrations have not shown interest or had a hearing on this issue confirms the existence of this pervasive cultural blind spot.

“Let me give you one specific example of a proposal to rapidly speed up medical discovery that’s very clear and difficult to dispute but, unfortunately, only so for a handful of folks. There’s a nonprofit foundation, FIM, the Foundation for Innovation in Medicine that was founded in 1976 by the physician and Chairman, Stephen L. DeFelice.

“His position is simple and easy to implement and, paradoxically, that may be the reason it has been not been understood and ignored. Also, it’s because he’s an individual and not a prestigious blue ribbon expert panel whose recommendations are generally made known to the public and discussed by the experts. He states what should be obvious but is not. The way new therapies are discovered is by testing them in people in a clinical research study not in test tubes or animals. The overwhelming majority of drugs that are effective in laboratory studies do not work in humans. We would have never known whether penicillin cures bacterial pneumonia unless it was given to patients with this disease. And, yes, we don’t know whether a promising new drug in animal studies for Alzheimer’s will be effective until it is tested in these patients. And, to repeat, the probability of success is very low for practically all diseases.

“Now before I go on, Mr. Chairman, I would like to hear from you and the members of this panel whether this message is clear and whether you agree.”
“That’s a very fair and appropriate question, Dr. Salute. It makes sense to me. How about you, gentlemen?” All senators, without delay, nodded in agreement. “Please continue, Dr. Salute.”

“Dr. DeFelice then argues that, if there are powerful obstacles to clinical research or testing new therapies in patients, and then this, by necessity, will slow down the discovery of new therapies. Once more, Mr. Chairman, I’d like to know whether this point is clear to you and your colleagues and whether you agree.”

There was a brief pause, and then the Chairman answered, “You know I have to say it makes a hell of a lot of sense to me.” He turned to the other senators and asked, “How about you?” One senator answered, “It’s tough to argue against what seems obvious.” The others on the panel once more nodded in agreement.

Dr. Salute was both surprised and happy with the agreement among the senators but he knew that things would now change. He continued, “Now here’s the disturbing news. Dr. DeFelice argues that years ago powerful barriers to clinical testing began and are getting stronger every day. He logically concludes that as a result the discovery and availability of new medical therapies have actually been dramatically blocked and the American people have clearly suffered needlessly and died before they should have. He has other things to say but I’m sure you and the distinguished members of this panel have some questions and comments at this point.”

Senator Byron’s facial body language spoke of puzzlement coupled with a tinge of impatience. “Dr. Salute, I think your doctor friend has now gone too far. If this were the case we here in Congress would have known about it and taken action to correct it. I …”

Dr. Salute decided it was appropriate to interrupt the senator before he continued and said, “Mr. Chairman, what I’m about to say you and your distinguished colleagues would not like to hear but it’s important that you do before we go on or else I wouldn’t bring it up. Dr. DeFelice believes that, bottom line, it is the Congress that is the institution most responsible for powerful barriers to clinical testing by tremendously raising the costs and risks to conduct clinical studies. He believes, as I said before, such actions are perverted. Congress funds scientific studies in order to discover new therapies and then it, paradoxically, creates enormous barriers to test them in patients. There’s one more piece to his thinking that I’d like to talk about but I’m sure you and other members of the panel would like to make some comments at this point.”

Bordering on the verge of anger, Senator Byron, his vocal decibel level now elevated responds, “Who does he think he is by accusing us of perverted actions against the sick? Besides, no one has informed us that there are these barriers to clinical research that are robbing patients of new cures or at least helpful ones. Dr. Salute, if it wasn’t for my respect for you, I’d immediately shut down this discussion about this rogue doctor.”
An elderly, well respected white-haired committee senator who recently lost his wife to brain cancer interjected, “Mr. Chairman, suppose this analysis by this DeFelice guy is correct- and, in my mind, there is this possibility because I believe Dr. Salute may think so because he brought it up, and that’s good enough for me- it’s our duty to carefully hear what more he has to say.”

Senator Byron, respected the wisdom of his longtime colleague and replied, “I agree. Dr. Salute, please hold no punches and go ahead with the DeFelice Theory.” “Mr. Chairman, no one may have informed you personally but since FIM was formed Dr. DeFelice has futilely spent substantial amounts of money including the use of multiple public relations firms trying to educate just about everyone that’s important from the media to the Congress not only about the problem but also his proposed specific solutions which I’ll talk about in a minute.

“There are solid unequivocal data that clearly prove that the barriers to clinical research studies have and continue to dangerously increase. I can assure you that this reality would become very obvious during a Senate hearing.

“He had high hopes and counted on the health oriented media to spearhead a national educational effort but they had and continue to have zero interest. Mr. Chairman, we’re talking about a personal intense and expensive effort of over thirty-five years without arousing any significant level of interest in any sector. Regarding Congress, let me tell you he has exerted an enormous effort to arouse interest both in the House and the Senate without success.”
Senator Byron, caught somewhat off guard, said, “If he did all of that why the hell haven’t I heard about it?”

“Mr. Chairman you hit the basic point right on the nose. This is why Dr. DeFelice says we have a cultural blind spot to understanding the critical importance of clinical testing. He opened the door with a few Congressmen and their staffers but then, because of a lack of understanding and interest, the doors quickly closed. There was one hopeful exception which I’ll mention in a moment.

Senator Byron, took a deep breath and then in a voice that expressed a bit of bona fide bewilderment said, “Dr. Salute, that’s hard to believe, very hard to believe. Anyway, please go on.”

“Mr. Chairman, making the assumption that what he proposes is true, he’s come up with a couple of relatively simple solutions. The first deals with a simple specific one regarding the FDA and the second, much more important general one, deals with the Congress.

“To repeat, his main objective is to remove the unnecessary barriers to clinical testing and speed up the creative testing of potential new, promising therapies in patients. Regarding FDA, for example, though it’s recently been a little bit more flexible in certain limited cases, a long time ago it established an anti-patient policy that virtually eliminated the testing of combination drugs in clinical studies. If for example, the combination of three drugs holds promise to be effective for the treatment of Alzheimer’s, it would not be sufficient just to study the three drugs together or, let’s say, against only a placebo but to compare it to each drug individually and every possible combination of them. It’s like evaluating the role of every ingredient in a meal to prove that eating keeps you alive. The cost and risks would be out of sight and this is why combinations are not studied and patients, of course, pay the price. Dr. DeFelice claims that all that FDA has to do is to rescind that policy which would take about five minutes to do which will allow more rapid discovery of new therapies. It is a simple administrative step.

“Before I forget he writes in more detail about this on FIM’s website, www.fimdefelice.org, under the DeFelice Commentary in the article, “Medical Versus Scientific Clinical Research – Time for an Immediate Change!“

Senator Byron, feeling somewhat left out and uncomfortable because of his ignorance of the subject matter, now had something of substance to contribute the discussion. “Dr. Salute, perhaps Dr. DeFelice is not up to date with current FDA policies. It now permits clinical studies in certain diseases with cocktails or combinations.”

“This is certainly encouraging but only applies to a few disease states such as AIDS. Dr. DeFelice believes this policy is also a perversion and should apply to all disease and disability conditions and that there should be no ‘privileged’ patient groups when dealing with suffering and premature death.”

Senator Byron commented, “These are pretty strong words but I wasn’t aware of these privileged groups, and I certainly will look into it. Now Dr. Salute, I am and I can assure so are my colleagues, extremely anxious to hear what Dr. DeFelice thinks Congress can do to speed up the discovery of medical breakthroughs. Please proceed.”

“Well, Mr. Chairman, like that of the combination recommendation, it’s relatively simple. As a young physician, Dr. DeFelice saw that the barriers to conducting clinical testing were not only blocking medical discovery then but would increase dramatically over time. And history has certainly proven his vision correct.

Based on his experience with the natural substance, carnitine, he wrote his first book, Drug Discovery the Pending Crisis published in 1972, a long time ago before, may I say, many of your senate staffers were born, where he came up with the solution. He proposed that physician patients or even healthy ones should be permitted to volunteer for clinical studies to physician clinical researchers much more easily than non-physician volunteers- that means much less FDA control- and also waive the right to sue. They would be able to take greater risks because they, as physicians, understand such risks and weigh them against the potential benefits.

“Later on he called these physicians Doctornauts and proposed the Doctornaut Act. One high level senator met with Dr. DeFelice and was convinced of the merit of the theory. He had a draft of the Doctornaut Act written and circulated. There was little support but, to be fair, it was a confusing draft and before corrections could be made the overwhelming health care issues took over the senator’s agenda. For your information one can find out more about Doctornauts on the FIM website.

I’m not sure but there are about 700,000 doctors in our country which is a huge potential reservoir for volunteers. Many years ago FIM conducted a survey on whether doctors would volunteer for clinical research on natural substances without FDA supervision. Over 50% agreed. Even if a small percentage of the new breed of modern day physicians agree to volunteer for clinical studies there would be thousands of them to tests hundreds and many more innovative new therapies. He believes that, because of our cultural blind spot and fear of pharmaceuticals, there is no other acceptable way to do this. After all, doctors know what’s involved more than others and if they want to volunteer for a clinical study they are, in a real sense, helping to deliver what patients really want and need. It certainly would beautifully strengthen the patient-doctor relationship that our health system is endangering.

“Senator Byron, before we close this discussion we haven’t made it clear enough what Dr. DeFelice means by our perverted general medical discovery system. For the record he has written extensively on this.

“He claims that our country has been and continues to be too heavily indoctrinated against the safety of pharmaceuticals and, largely because of this, a pervasive national fear exist. He, of course, has no unique vision about this for it has been self evident to most of us for a long, long time. He principally blames the media for both creating and perpetuating this national fear. He claims that the media including medical outlets who should know better have virtually completely ignored the issue of the acceleration of medical discovery which is infinitely more important than safety. He says if we cured diabetes we wouldn’t have to worry about drug toxicity because patients would be drug free.

“Now because of our country’s media generated fear of drug safety, The FDA, under constant political pressure to keep us all safe from the bad effects of drugs, has created a policy almost exclusively based on increasing safety of clinical studies by creating all kinds of barriers from permitting them to happen.

“Let me give you one of his examples that describe his concept of perversion. Not too long ago there was a study where gene therapy was given to patients at one of America’s most prestigious medical institutions. One patient died. The media, based on this single death, created a national feeding frenzy of fear of participating in clinical studies which placed the FDA in a bad light and under relentless pressure. And what did the Congress do? It put additional pressure on the FDA for permitting such a “dangerous” study. And what did the FDA understandably do but increase the rules or barriers to conduct clinical research which further slows down the discovery of new therapies while the media, Congress and just about everyone else ignored other cold facts such as there were thousands of people murdered in our major cities last year that went virtually unnoticed.”

There then followed a pause which seemed to signal the end of the discussion of the Doctornaut Act but Senator Byron, being a veteran of the Washington scene and a proud man, wanted to close the discussion with some semblance of being in charge of at least some of the facts. Smilingly, he asked, “Dr. Salute, we in Congress, in both chambers, have been repeatedly told that there is no doubt that new therapies will be increasingly costly as now evident in the bioengineering field. It appears to me that Dr. DeFelice’s proposal will create more of such expensive therapies significantly increasing health care costs when, in fact, we are trying to reduce them. For completion’s sake, he should have factored this in the Doctornaut Act.”

Dr. Salute also smiling answered, “Senator you hit it right on the nose and may I apologize for not addressing it. I asked Dr. DeFelice precisely this question and believe it or not, I have in my briefcase his response. It’s a brief letter. May I read it?”

Senator Byron, without hesitation, nodded his head in affirmation and Dr. Salute read:

“Dear Dr. Salute,

There is no doubt that the Doctornaut Act will lead to more expensive medical therapies but before jumping to conclusions, it will, in time, lead to a substantial reduction in health care costs. Let me address two points:

To my knowledge, future health care costs are projected on the growth of patient populations using the approximate incidence and prevalence figures of disease that we have today not factoring in substantial cure projections. For example, the cost of end stage renal disease, ESRD, is about $40 billion the major part involving renal dialysis treatment. There are currently in the year 2010 over 500,000 ESRD patients. With the aging population this number will steadily increase. But, if we could cure by a prevention or treatment therapy this condition, then the cost reduction would be enormous. In conclusion and generally speaking,, in the short term the costs would be elevated but in the long term particularly in patients with chronic disease such as cancer, rheumatoid arthritis, heart disease, Alzheimer’s and many others, they would be dramatically reduced.

The Doctornaut Act will permit, at a very low cost, the clinical testing of both low and high cost therapies and they will compete with each other in the medical marketplace. Though it is tough to predict there is little doubt that there will be an abundance of low cost breakthrough medical therapies. We must not forget that natural substances are the best potential therapies that we have but because of the difficulty of obtaining patents, very few are tested. The Doctornaut Act will permit such testing .In our great country, patent or no patent, if a major medical discovery is made it will be developed and made available to those in need.

In conclusion Dr. Salute, if the Doctornaut Act is enacted both current and future patients will have much to gain and health care costs would be significantly reduced and millions of Americans would lead happier lives.

Senator Byron turned to his colleagues on the panel and remarked, “Dr. Salute has effectively presented a point of view that deserves further consideration for a future date but let us know turn to the subject of Alzheimer’s.”

At the end of the day Senator Byron met with his staffers in his office and reviewed the day’s discussions on the status of Alzheimer research. Before they left for the day, he, in a wondering mode, asked his staffers, “What do you guys think about Dr. Salute’s presentation? It was a novel one but on the surface it kind of made some sense. Maybe we ought to hear from this DeFelice guy in person.” His veteran and politically wise chief of staff replied, “Senator, I don’t see any gain in pursuing this because there’s no support out there and perhaps you’ll take a big negative hit because our country views clinical research studies, as Dr. Salute said, as a necessary evil, and you will be labeled as an Auschwitz perverted nut case. I would strongly recommend that we stay away from this guy and the issue.”

That night while dining with his wife of many years the senator told her about Doctornauts. She surprisingly said that she thought it was a wonderful idea. Maybe it would bring a cure to her crippling arthritis during her lifetime. She asked him what he planned to do. He paused, looked into outer space and replied, “I don’t know, my love, I just don’t know.”

Stephen L. DeFelice, M.D.

Senator Tom Harkin (D-IA) has been instrumental in helping to shape the direction of the Translational Science efforts in Congress. Pictured with Stephen L. Defelice, M.D.

Awhile back I met with Gordon Bernard, a physician clinical innovator in septic shock research and currently the Associate Vice Chancellor for Clinical and Translational Research at Vanderbilt University School of Medicine. He patiently listened as I pointed out the urgent need for the Doctornaut Act in order to reduce counter-productive barriers to clinical research. After I delivered my piece, he educated me regarding the general Translational Scientific movement and the establishment of Clinical and Translational Science Awards (CTSA) and its patient-oriented goal to also reduce these barriers.

(For the record, Dr. Bernard conducted a clinical study in septic shock patients on a discovery I made in the past. Unfortunately, the results were not encouraging but, despite it all, we remain friends)!

The National Center for Research Resources (3/15/2011) describes the CTSA program as: “A national consortium of medical research institutions, funded through Clinical and Translational Science Awards (CTSA), is working together to improve the way biomedical research is conducted nationwide. Consortium members share a common vision to reduce the time it takes for laboratory discoveries to become treatments for patients, to engage communities in clinical research efforts and to train clinical and translational researchers. The momentum behind the CTSA program continues to build as new connections are emerging within, across and beyond the consortium. Launched in 2006, it now includes 55 medical researchers in 28 states and the District of Columbia. When the program is fully implemented, it will support approximately 60 CTSAs across the nation.”

The broader Translational Science movement continues to gather steam. The prestigious American Society for the Advancement of Science started the new journal, Science Translational Medicine.The highly respected Francis Collins, the Director of the NIH, is energetically pushing for ways to conduct more clinical trials on potential promising new therapies and has recently proposed a separate NIH unit for this purpose. It’s good news, indeed, for patients that a highly visible, distinguished physician and scientist has stepped forward and taken the lead in this very sensitive arena.

NOW HERE’S THE BAD NEWS: THE TRANSLATIONAL RESEARCH MOVEMENT NEEDS HELP: Unfortunately, our current regulatory ground rules, coupled with our pervasive, obdurate cultural suspicion of the risks in clinical research further coupled with our excessive general, cultural preoccupation with risk, remain unbudgeable and will continue to both retard and block clinical studies .If anything is impossible, it would be to convince Congress, let alone the FDA, to significantly lower the barriers for patient volunteers. There is little doubt that the CTSA will spur on innovative clinical research and medical discovery, not the least by reducing logistical logjams, but the principle barriers of the “system” will remain. In addition, the CTSA effort is limited in scope.

Though Thomas Aquinas believed that the argument from authority is the weakest of all, I remember what my father used to periodically emphasize. “Son, there’s an exception to every rule.” I’m speaking from extensive, personal experiences, which are tough to quantify, in the world of clinical research and drug development of new drugs starting from my initial clinical study with carnitine in 1965 up to the present dealing with FDA, Clinical Research Organizations (CROs), IRBs, the Orphan Drug Act, the CME, ethicists- moralists, corporations, academicians, lawyers and international regulators. Whom have I left out? Yes, the powerless patient!

There are huge barriers to clinical research studies. A recent study conducted by Ken Getz at the Tufts Center for the Study of Drug Development found that the median number of procedures per clinical study increased by 49% between 2000-03 and 2004-07, while the total effort required to complete those procedures grew by 54%. He states that, “More complex and burdensome protocols are extending study cycle times, increasing costs and challenging patient recruitment and retention.” He adds that enrollment criteria are discouraging patient enrollments dissuading volunteers from staying in the study until completion.

(As a reminder, may I interject here that the barriers to clinical studies were huge and growing and increasingly stifling a long time before 2003! This pattern should make us all very much disturbed about the inexorable continuum increasing of obstacles to clinical studies).

An eye-opening example of the pervasive multiple obstacles to entering Phase III clinical studies is given by, J. Evan Sadler, the President of the American Society of Hematology, who writes:

“Recent studies in basic and translational research have set the stage for tremendous progress in clinical hematology, but trials to pursue these opportunities can run afoul of many obstacles. For example, David Dilts, Director of Clinical Research of the Knight Cancer Center Institute, reported last year that opening a phase III cooperative group trial requires an average of 2.5 years to accommodate 118 decision points, complete more than 769 process steps, and receive approval up to 36 separate groups and individuals. Whether many of these steps improve trial quality or patient safety is doubtful. Many approved trials never enroll a single patient and barely half are ever completed, which is a total waste of human and financial capital. Small wonder that Garret Fitzgerald, M.D., Director of the Institute of Translational Medicine and Therapeutics at the University of Pennsylvania, has described our current system as “Spreading dysfunction that undermines progress for the sake of managing risks.”

NOW HERE’S THE GOOD NEWS: IT’S THE DOCTORNAUT ACT. The Doctornaut Act, which would permit physicians to volunteer for clinical studies with substantially fewer restraints than non- physicians, would quickly accelerate the number of potential therapies tested in clinical trials and, pari passu, accelerate medical discovery. It would, in my opinion, act synergistically with the general Translational Science movement particularly in Phase I and Phase II studies.

Frankly speaking, a number of my colleagues most of whom, might I add, are highly competent clinical research veterans, have their doubts whether doctornauts would make a significant contribution to translational discovery research. Generally, their initial reactions were those of apprehension rather than optimistic enthusiasm which, in large part, understandably reflect our imbedded cultural fear of risk. Senator Bill Frist, who had a Discussion Draft of the Doctornaut Act circulated for comments, and I discussed this legitimate concern. We agreed that guidelines for doctornauts participation in clinical studies should balance this concern without unreasonably compromising the necessary risk involved of doctornaut participation in clinical studies.

Let’s now talk about the role CTSAs and doctornauts could play: There are two types of clinical research: pioneering and applied. A pioneering clinical study leads to an important medical discovery such as the H. pylori study by the doctornaut, Dr. Barry Marshall. This type of discovery occurs outside the “system” and comes out of the blue. After the discovery phase then applied clinical research follows in a larger population to better characterize the efficacy and safety of the discovery. With respect to the clinical investigator, I do not consider the first clinical study of a pharmaceutical company discovered molecule, even if it is a medical breakthrough, as pioneering. It is applied. I also do not consider a large clinical trial to determine whether statins or beta- blockers reduce the incidence of myocardial infarction or stroke as pioneering. It is applied. In fact, the vast majority of clinical studies are not pioneering from the point of view of the clinical researcher. The idea isn’t his or hers but put on the clinical research plate by a third party. Our system does not encourage clinical initiative; on the contrary, it powerfully discourages clinical researchers from even daring to think about their own innovative ideas. It’s just too hard to get the job done. The mere existence of the Translational Science movement confirms this reality. This state of affairs must be remedied by our leaders who are concerned about “Cure” as well as “Care”.

What I’m not clear on is the breadth of the mission statement of the CTSA endeavor. Is it primarily to reduce the barriers to clinical studies for promising drugs or devices discovered by third parties, which is a very welcomed step forward in applied research in itself, or, does it also encourage clinical researchers to come up with their own pioneering ideas or by brainstorming with their colleagues?

FIM’s principal objective is to reduce the barriers to Phase I-II studies, the medical discovery step, for both pioneering and applied research and also to encourage and expand the former’s innovative potential which, given today’s expanding technology, is breathtaking. But there is little recognition of this marvelous reservoir from any quarter including the medical research community.

Let’s take some theoretical case scenarios of pioneering clinical studies which hopefully will get the Translational Science leaders thinking more toward how CTSAs can bring into the research fold our potential medical innovators. What can they do to pursue their creative ideas?

1. The blood brain barrier exists for a reason but, because of unknown risks, one must be very careful in any attempt to “open” it. Selective types of small molecules, fortunately, can pass across the barrier, opening the door to expand the pool of potential therapies for CNS diseases and disabilities. In certain instances, however, the oral administration of small molecules may need help to achieve sufficient CNS efficacious tissue levels. For quite a while it has been known that both mannitol and cerebral ischemia do temporarily open the barrier, but clinical studies to better define this phenomenon are lacking. Let’s say that a young curious clinical investigator believes that properly opening the barrier can lead to major medical breakthroughs. He then collaborates with his scientific colleague to design laboratory experiments with a medical device and come up with a way of combining both experimental procedures to effectively open the barriers for a brief, controlled period where small molecules can be administered intravenously to increase tissue levels. Oral administration can then follow maintaining such levels.

2. A cardiovascular physician, while reducing a patient’s body temperature to 91 degrees after cardiac arrest in order to preserve his brain function during a clinical study, is reminded by his nurse that the patient also has early stage pancreatic cancer. An idea spontaneously jumps to mind. Can the patient’s hypothermic state make his tumor or even other tumors more sensitive to chemotherapeutic agents than at normal body temperatures? He then wants to know what the next step should be to test his hypothesis. He discusses the next step with his scientific oncologist colleague experts, and they conduct several animal studies at the physician’s own expense. Creative minds despise barriers, and he didn’t want to wait for the long period of time it takes to obtain a grant, particularly when it is highly probable, because of its out-of-the box approach, that the grant request would be denied. DaVinci simply walked to his canvas with brush in hand with only air as the barrier to create the Mona Lisa and, similarly, Einstein to the black board with chalk in hand to divine his Theory of Relativity. And all Marshall had to do was swig down his H. pylori soup.

3. A busy practicing rheumatologist makes the diagnosis that his mother has crossed the Rubicon and is on her way to crippling rheumatoid arthritis. He simply refuses to accept her rendezvous with pain and loss of mobility which is not a recipe for happiness. He decides to find an answer and surrenders his practice to another physician. He then contacts two expert research scientists in the field, and they work together to come up with a novel treatment approach with FDA approved drugs. They decide to achieve greater efficacy reaching certain blood levels by periodic intravenous infusion of two drugs followed by oral administration of three drugs between the intervals hoping to temporarily halt the process. This regimen is to be repeated when there are signs of the process acting up. (At this point I’d like to raise the point of FDA’s policy on combination drugs which IRBs tend to honor for study approval. This issue is addressed on my Commentary entitled, Medical Versus Scientific Clinical Research: Time for an Immediate Change!

4. A fellow in neurology, while on weekend call and with some free time in his small quarters, reads in a lay journal that in Mongolia there is a virtual absence of Alzheimer’s disease. The author of the article observed that Mongolians eat about a pound a day of the cruciferous vegetable, turnips, usually divided into two meals. He visits the internet searching for the ingredients of this type of turnip but, alas, the answer was not to be found in cyberspace. He contacts his nutritionist friend who, somehow, is able to come up with the list. He is excited about conducting a nutraceutical clinical study. But the Mongolian turnips are not available in the U.S. which presents a problem.

Some ways in which doctornauts could increase the productivity of Translational Research clinical investigators for early clinical discovery studies, which is the principle objective of the Doctornaut Act, are as follows:

1. Broad expansion of IND exemptions which can apply to multiple clinical situations: There already exist IND exemption regulations but they are narrowly restrictive.

2. Significant increase in off- labeling studies.

3. More testing of multiple combinations for diseases and disabilities which FDA NDA policy, with few exceptions, effectively discourages.

4. Third parties, such as pharmaceutical and medical device companies, instead of sponsoring studies with one of their potential discoveries, can sponsor two or more.

5. More studies on the combination of medical devices and pharmaceuticals.

6. Create more entrepreneurial and charitable organizations to clinically evaluate both low and high cost potential therapies.

7. Internationally approved therapies not yet approved in the U.S. will be tested either alone or in combination with FDA approved ones.

8. Increase clinical studies on potential orphan drugs and “orphaned” phases of general disease such as late stage, drug resistant ovarian cancer.

9. Expand nutraceutical-pharmaceutical combinations.

10. Bring into the medical discovery potential the huge creative potential thinking of scientists-physicians to test their ideas. This is a critical element to maximize discovery productivity and must be effectively encouraged.

11. Other unforeseen situations that will eventually unfold as the system evolves.

Who will sponsor these clinical studies? A healthy Translational Science movement together with an approved Doctornaut Act will bring about a rapid and substantial increase as well a transformation of research and development players ranging from start-ups, charitable institutions such as foundations, traditional pharmaceutical and device companies and the government. The discovery field will be highly competitive with substantial funding for clinical studies. As previously mentioned, a broad variety of unique types of emerging therapies will not fit into regulatory categories. It is important to note that in our country, once breakthrough therapies are discovered, it is difficult to suppress them, and the regulations will necessarily bend. As Santayana noted about a century ago, America is unique by its preponderance of good will. This coupled with the forces of the marketplace will form a formidable anti-Luddite duo.

A justifiable concern is whether present day physicians, influenced by modern values, would volunteer as doctornauts. FIM’s top priority is an interest in the medical potential of natural substances that are not clinically exploited largely because of patent problems.

Some years ago, FIM funded a physician survey regarding their willingness to be doctornauts for natural substances. The following is a summary:

“A total of 3,100 inquiries were mailed to a cross section of 2,100 male M.D.’s, 500 female M.D.’s and 500 Doctors of Osteopathy. Age was considered. In addition, a telephone survey of seven academic institutions was conducted. A total of 10.3 percent of physicians responded. A simple “Yes” or “No” was required to the following question. ‘Would you as a physician patient want the privilege to volunteer for clinical research of natural substances under the supervision of a physician- clinical researcher without FDA, institutional or other restraints?’

 

 

PHYSICIAN RESPONSE

	Yes %	No %
Male M.D.’s Total	52.5	47.5
Male M.D.’s Under Age 50	56.6	4.4
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

But what is surprising today is that, with few exceptions, almost all of my current physician colleagues doubt whether modern physicians would volunteer to be doctornauts, even for non-risky clinical studies, without FDA supervision. They may be right but if a survey were conducted asking questions such as, “If you are still rational on your way to inevitable mind -destroying Alzheimer’s, or in the late stages of cardiomyopathy with a few years to live, or your cancer is out of control resistant to chemotherapy and you have a certain rendezvous with death within in a year, or two or if your arthritis is becoming so crippling that you can’t even embrace your beloved wife, would you volunteer to be a doctornaut?” Speaking to a number of physicians who have or may in the future have serious diseases I have found that, with few exceptions, they agreed to have the “right” to be a doctornaut. But this is only an impression and not solid survey data so let’s look at it another way: There are about 700,000 physicians in our country. If only 10%, an extremely conservative figure, of our current physician population agrees to be doctornauts, then there will be 70,000 doctornauts, an impressive healthy number, to test many applied and pioneering early clinical discovery studies.

In conclusion, my hat is off to those who conceived of and got the ball rolling on the essential importance of clinical research but let there be no doubt that the obstinate barrier “system” is still intact and even growing which will effectively frustrate the potential of the Translational Research movement. And, as is frequently the case, the patient pays the price.

The Doctornaut Act is a natural partner to the movement. To those of you in doubt consider Pascal’s Wager regarding the need to believe in the existence of God. “There is little to lose and much to gain.”

December 20, 1999

by Stephen L. DeFelice, M.D.

There is currently a great deal of confusion regarding the nature and dynamics of the nutraceutical market mainly due to its newness and because it is different than the traditional pharmaceutical, OTC and health food markets. In fact, to date, there is no bona fide U.S. nutraceutical company. In order to diminish the confusion, and establish a foundation for company participation in this enormous health sector, it is essential to understand its basic dynamics.

The unique dynamics of the nutraceutical health sector first dawned on me in 1983. The NIH convened a consensus group of medical experts to assess the potential role of calcium for the prevention of osteoporosis. After extensive deliberation, the consensus group concluded that calcium was indicated for the prevention of post-menopausal osteoporosis. At that time, little did I realize that this single event marked the beginning of the Nutraceutical Revolution.

About three months after the NIH consensus group issued its recommendations, I was sitting at home during cocktail time reading various lay publications. All contained articles on calcium and osteoporosis, long after the NIH consensus group report was made public. It suddenly occurred to me that, because of the continuing mass media coverage beginning after the consensus group report, the majority of people in the United States were very well aware of the calcium-osteoporosis connection.

This was indeed a unique event, and I wondered about the reasons why. Not even the largest pharmaceutical or food company spending multi-millions of advertising dollars could have achieved this high level of national awareness of a single product.

I then decided to evaluate the dynamics of this unique phenomenon. Its principle characteristics were the following:

1. Published clinical data on the calcium-osteoporosis connection were evaluated by medical experts.

2. Based on such clinical data, medical experts recommended the use of calcium for the prevention of post-menopausal osteoporosis.

3. The mass media communicated with and enthusiastically embraced the recommendations of the medical experts.

4. The mass media then, almost instantaneously, communicated this medical-expert message to the general public including practicing physicians, their patients and relatives.

5. Physicians and patients then began to communicate with each other about this message.

6. Following the mass media educational effort, sales of calcium began to rise and are continuing to do so – over 15 years later.

I then wondered whether this was simply an oddball phenomenon or a reliable sign of the beginning of a new health sector where the mass media, based on the results of clinical data supported by medical experts, would become the major national promotional organ for nutraceuticals. Then the fiber and fish oil nutraceutical phenomena occurred. The dynamics were similar to that of the calcium phenomenon and continued with other nutraceuticals such as folic acid and vitamin E. To be sure, other products such as St. John’s Wort and Echinacea, where sufficient clinical support their efficacy and safety were not published, also captured media attention. But, increasingly, products supported by the results of clinical research which dominate the headlines are being accepted by physicians and the public.

Shortly after the calcium phenomenon, I wondered whether it would be possible to connect the brand name and trademark of a product to the mass media educational phenomenon. “Could it be,” I said to myself, “that it is now possible, based on clinical studies, to launch a product and quickly establish its brand name trademark for very little cost by using the mass media, and not advertising, as the primary vehicle for promotion?”

My experience in the pharmaceutical sector taught me that medical journals use the scientific or generic pharmaceutical name of a product in their publications rather than the commercial brand name. This policy, in part, is due to the fact that penicillin is penicillin regardless of the companies that sell it. The trademark is irrelevant from a medical point-of-view. It primarily serves as a marketing function to establish specific product recognition. But nutraceuticals are quite different than pharmaceuticals. One company’s soup or cereal may be similar to another’s, but they are not exactly the same. If, for example, a study was done with a specific cereal or botanical nutraceutical, with a more or less similar but not exactly the same products on the market, the medical journals must logically mention the trademark of the clinically evaluated product in order to distinguish it from the other products that are not exactly the same and have not been clinically evaluated. A company with a potential competitive product must perform clinical research on its product and establish comparable efficacy, if a medical journal is both to publish the study as well as mention its brand name.

There are three recent case histories which clearly demonstrate the media’s pattern of promoting a specific nutraceutical product’s brand name based on the results of clinical studies. They are Ocean Spray Cranberry Juice, Benecol and Intelligent Quisine. All three products were clinically evaluated and the results published. All partook in the nutraceutical dynamics scenario and all achieved some degree of national recognition without much, if any, advertising. (It is interesting to note, by the way, that both Bencol and Intelligent Quisine were not in distribution when the media trumpeted their messages. It is self-evident that it is best to have one’s product in distribution before trademark promotion.)

In conclusion, it is quite clear that the trademarks of nutraceuticals can achieve national recognition without much advertising and at little cost. It is not clear, however, why company management has not caught on. The most likely reason is that certain characteristics of the nutraceutical OTC market are different than the ethical OTC and health food markets. The former is not advertising or unsubstantiated claims driven. It is media driven based on clinical studies of specific products. And, I can tell you from personal experience, companies are not secure in dealing with media. It is much easier to control advertising than media. On the other hand, the media has been consistent and friendly to nutraceutical products, be they generic or brand, which are supported by clinical data and published in reputable medical journals.

To repeat, we continue to await the birth of the first truly nutraceutical company. It’s exact nature has yet to be determined but you can be sure that it will rely on mass media to establish its brand name and trademarks.

The U.S. craze for the medical miracles of nutraceuticals (dietary supplements, foods and medical foods) continues. The forces that drive this craze are not clear and difficult to quantify. What is clear is that the Nutraceutical Revolution has its own momentum, is international in scope and is unstoppable. The result is a mixed one. Though a multitude of potentially beneficial products is presently available, very few of these have been clinically tested to properly assess their medical-health benefits and risks.

The first time that I entered a health food store was in Greenwich Village during the late 60’s. It was a well organized and consumer-friendly store. I vividly remember being impressed, both with the number of products freely available for purchase, the variety of ingredients contained therein, and the abundance of medical-health claims made on such products. After having observed this fascinating establishment, I remember saying to myself, “All of these products are purportedly natural substances. That means some of them, when taken for the right conditions, can help people with medical-health problems, but we just don’t know which ones work. Also, there is little doubt that some of these products are harmful. But we just don’t know which ones are. It’s a dilemma.”

That was my opinion in the late 60’s, and it remains so.

Yet people continue to embrace dietary supplements and dietary products at an unprecedented pace in a search to prevent or eliminate their diseases or other conditions that ail them. Even physicians have begun to join the bandwagon, albeit it on a more limited and rational basis.

People purchase products that make medical-health claims despite the fact that such claims often unsubstantiated or more often, false. They do not demand “the proof”. This phenomenon is characterized by ignorance and unfounded credibility regarding the purchase and consumption of such products.

Those few products or ingredients that may have medical-health
merit such as calcium, fiber, and low fat diets, are old news; and even these have significant limitations. The calcium message regarding its beneficial impact on osteoporosis is at best limited and oftentimes misleading. Calcium itself is clearly overrated for this use — but few say so. Though embraced until recently, the fiber anti-cancer data are now questionable. The fiber-prevention-of heart attacks clinical data continue to be promising. But, with respect to fiber and the heart, just try asking people how much daily fiber should they take and what specific fiber products will deliver the cardiac promise. This may be a case where the promise is real but the available delivery systems inadequate.

We have all been bombarded, saturation style, with messages regarding the importance of low-fat and low-cholesterol diets on cardiovascular health. What is the truth about these entities? The answer is that there are little convincing clinical data which demonstrate that recommended diets and specific dietary products have had a beneficial impact on cardiac health. There is, in fact, an alarming possibility that the marketing effort behind the messages has played a large role in the current U.S.-obesity and heart disease epidemics. Obesity, we should not forget, is a leading cause of cardiovascular disease and death in the United States.

There have been all too few products (a handful, perhaps!) such as Ocean Spray Cranberry Juice often taken for the prevention of recurrent urinary tract infections in women, where clinical studies support the claims of the specific products sold.

There is little doubt that there is indeed a substantial amount of adverse effects and toxicity currently going on. Large numbers of nutraceutical enthusiasts are, in some way, suffering from the consumption of these products. The problem is, unlike pharmaceuticals, there is no organized system to detect these bad effects. They are largely undetected. When a patient with hepatic or liver failure visits a doctor, the doctor does not think to ask whether the patient is taking a dietary supplement. The physician, instead, usually thinks of viruses or drug toxicity as potential causes of the liver disease.

In addition to obvious detrimental effects, there can be adverse effects that are not considered serious or ìtoxicî problems in themselves but can have a constant and pervasive negative impact which are frequently more damaging on the quality of life than temporary liver damage. Take, for example, calcium. A powerful marketing machine, based on reasonable clinical data, has convinced millions of women to take calcium to help prevent post-menopausal osteoporosis. This same marketing machine, among others, has failed to tell women that constipation commonly occurs with calcium supplementation. (Medical literature, by the way, is strangely silent on this issue.) It is common knowledge that bowel regularity is something that many individuals are keenly conscious of and the interruption of which can lead to mild or significant emotional distress. There is little doubt that a constipatory product will not only impact negatively on the well-being and happiness of the person taking the calcium supplement but, as with infectious diseases such as the common cold and tuberculosis, spread this negativity to those that are near such as family, friends and colleagues at work.

I object, however, to those who hold that the dietary supplement and diet craze have had little impact on U.S. health. It is not unreasonable to assume, for example, that vitamin E, folic acid, and the ingestion of vegetables can be helpful; and let’s not forget the underestimated and powerful placebo effect.

The placebo effect is an extremely powerful one. In carefully controlled pharmaceutical clinical studies where placebo is compared to the drug that is being tested, placebo responses, as measured by clinical improvement, generally range from 30 to 60%. We know that many of those that seek relief from dietary supplements often are pleased with the results. This is, however, oftentimes not due to the clinical effectiveness of the dietary supplement itself but to a placebo effect. “The National Nutraceutical Placebo Effect” is not fully appreciated and embraced. It helps people with their problems and, by the way, significantly reduces health care costs.

And now, let’s talk about the very good news. The current clinically demonstrated medical-health value of dietary supplements, foods and medical foods coupled with the benefits of the national placebo effect are paltry and miniscule in scope compared to the true medical-health promise of nutraceuticals. Let’s look at three examples of such promise in the areas of cancer, heart disease and diabetes.

1. Adriamycin-carnitine and cancer: Adriamycin is an extremely effective chemotherapeutic agent against certain types of cancer cells. The problem with this drug is that, in addition to killing cancer cells, it kills heart cells too. This cardiotoxicity problem limits the dose of adriamycin that can be given to a patient with cancer thereby severely limiting its capacity to kill tumor cells. As a result, the patient is robbed of the true medical potential of this drug.

Carnitine, a naturally occurring substance that is present in high concentrations in everyone’s heart, keeps your heart pumping by driving fatty acids into the mitochondria (the furnaces of your cells) where they are metabolized to produce energy. Animal studies report that carnitine can dramatically block the cardiotoxicity of adriamycin. There are some preliminary clinical studies that also support this possibility but the definitive study has not yet been done.

What does this mean? There is the possibility that a cancer patient can take carnitine supplementation to protect his heart while the dose of adriamycin is increased to much higher levels than normal resulting in the death of more cancer cells. If this be true, then many patients with cancer could be either cured or at least survive for significantly longer periods of time.

2. Alcohol-folic acid, women and coronary artery disease: A study was published in JAMA which reported that women who take moderate amounts of alcohol plus folic acid have a reduction of cardiovascular events such as heart attacks by approximately 80 percent. The effect of this combination substantially exceeds the positive effects of other nutraceuticals and even highly touted cardioprotective pharmaceuticals. The data on men have not yet been published. What does this mean? If these clinical findings are real then we can dramatically reduce heart attacks to levels never seen before.

Also, one can wonder whether the addition of vitamin E along with other cardiovascular nutraceuticals as well as pharmaceuticals could drive this figure closer to — shall I say, “zero”?

3. Magnesium-complications of diabetes: Over 50 percent of diabetics have magnesium deficiency. When this happens many pathologic biologic processes can happen such as increased blood clotting, constriction of small arteries and insulin resistance. All of these events can lead to decreased delivery of oxygen to body tissue which plays a major role in diabetic complications such as heart attack, loss of limbs, blindness, kidney failure, etc. There is reasonable clinical evidence that magnesium supplementation can reverse these processes. Also, large clinical studies have shown that magnesium deficiency is associated with an increased incidence of diabetes.

What does this mean? There is the possibility that magnesium supplementation can help reduce the incidence and severity of diabetes including its complications. Also, there is the possibility that other cardiovascular nutraceuticals such as alcohol-folic acid, vitamin E and carnitine can further help ameliorate the diabetic condition.

There are many, many other nutraceutical opportunities. For example, statins are important pharmaceuticals that lower cholesterol and reduce heart attacks. They also, however, deplete the heart of CoQ-10, an important substance for cardiac health. Perhaps supplementation with CoQ-10 can increase the clinical effectiveness of the statins.

And now the bad news: Current federal laws and regulations profoundly discourage financial investment in nutraceutical clinical research which is unnecessary to demonstrate the clinical efficacy or effectiveness and safety of specific nutraceutical products. Penicillin in a test tube is undiscovered until it is clinically tested and proven to be of value. To correct this situation, FIM has proposed the NREA (The Nutraceutical Research & Education Act) which is based on the principles of the successful Orphan Drug Act. The NREA grants a ten year exclusivity period for the medical-health claim to the sponsor based on the results of clinical studies conducted on the specific product evaluated. Congressman Frank Pallone, Jr. (D-NJ) has recently introduced the NREA in Congress which, if enacted, will encourage substantial investment in clinical research and rapidly lead to new nutraceutical discovery, If not enacted, we will continue to live with the status quo which is highly detrimental to the health of the vast majority of Americans.

What is urgently needed is more clinical research to prove the benefit of all nutraceutical possibilities.

Nuclear transplantation, embryonic blastocyst stem cells, fetal cells, be they embryonic or adult stem cells, and adult stem cells from adults: All offer enormous promise to rid us of diseases that rob us of the joy of life and even life, itself. Which type of cell offers the greatest promise? No one knows at this point in our early research phases, and it will take time to find out. Because, however, of the magnitude of the medical promise, it is morally imperative that we press forward with our research efforts without undue delay.

It is postulated, with solid reasoning to support it, that the blastocyst embryonic cells are the most promising ones because they are still young enough to be totipotent having the miraculous capacity to create all the biologic systems required for the creation of a newborn baby.

The other cell types are thought to be more differentiated or pluripotent making them less capable of generating the natural therapies needed to attack disease. There is a reason to believe, however, that some fetal cells may also be totipotent.

Since embryonic and fetal cells offer great promise in the battle against disease, it is mandatory to address the moral objections against such use.

Objections to using embryonic stem and fetal cells for research purposes have to do with murder, not necessarily with killing. But the definition of murder is dependent on the particular circumstance. For example, killing another person in self-defense is not murder.

There is, I believe, a specific circumstance in which the use of such embryonic stem and fetal cells for research is not murder.

Women with serious medical problems undergo hysterectomies. Not uncommonly, they are in various phases of pregnancy at the time of their hysterectomies. Embryonic and fetal cells are present in these cases.

Women also undergo abortion in early pregnancy with the same embryonic stem and fetal cells available. There is, however, a clear and distinct moral difference between the two situations regarding the use of such cells for research purposes.

The uterus is the life-support system of the embryo and fetus. Once removed via hysterectomy, the uterus is no longer capable of supplying nature’s life-sustaining substances to the embryo and fetus. Neither, therefore, is viable any longer.

An analogy to a non-viable embryo or fetus is the brain-dead patient in irreversible coma whose life is totally dependent on a medically delivered life-support system. It is generally morally acceptable to remove the life-support system because the patient, like the hysterectomized embryo or fetus, is no longer a “viable person”. The act of removing life support is not, therefore, considered murder. Even Pope Paul II, a fervent supporter of the sanctity of life, in his encyclical letter, Evangelium Vitae, writes that life support systems can morally be terminated in certain conditions, “When death is imminent and inevitable.”

When an abortion is performed, the uterus or life-support system remains intact. This is comparable to the removal of a life-support system from a patient who still has the mental and physical ability to function as a person.

I propose that medical centers that specialize in the isolation and maintenance of embryonic stem and fetal cells obtained from hysterectomies be licensed to make them available for research purposes. Guidelines should be established under which these institutions would operate.

I have communicated with a number of sincere and impressively intelligent people on both sides of the murder and non-murder debate.

Those that hold to the belief that stem and fetal cell research are issues of science and reason alone have forgotten the lessons of history.

Science, in itself, is amoral. Newton’s theory of gravity has nothing to do with heaven or hell. It is in the applications of science that the issue of morality arises. Controlling this issue, morality, is the function of the society in which we live.

Take nuclear weapons as an example: Linus Pauling and Albert Einstein feared that the application of nuclear technology would lead to the nuclear bomb and a worldwide holocaust. And they were correct in their belief. As we know too well today, a simple order from the leader of a country with nuclear bombs to push a button or two could make Dante’s Inferno a reality instead of an epic poem.

Those that hold that a legitimate medically indicated hysterectomy for a potentially fatal disease in a pregnant woman is morally unacceptable, I believe, have employed the use of reasoning beyond its legitimate limits to justify such a conclusion. Indeed, the main conclusion of the so-called Age of Reasoning is that the over dependence on reasoning leads us to a moral vacuum. The brilliant David Hume, perhaps the greatest intellect of that era, concluded that we cannot know anything. But he used reason to arrive at this conclusion!

There are more important “other ways” beyond the use of scrupulous reasoning by which we make judgements about life and morality. Tradition, religion, wisdom culled from life’s daily experiences both within and without the family are some of the essential foundations of the vast majority of life’s held values. Love, respect and fairness come from these rich sources of experience and not from simple syllogistic reasoning starting from a tabula rasa.

I’ve attempted to use common sense reasoning to make the point of the moral differences between hysterectomized and non-hysterectomized embryonic and fetal tissue for research purposes. But I have also turned to that “other way” to help make my judgement.

For example, if a man whose spouse is in a fatal coma and knows full well that an embryonic stem or fetal cell-derived therapy developed from hysterectomized embryo or fetal cells in her physician’s syringe would bring her back to normal health, yet would refuse that his loved one receive such therapy, it is important to honestly ask the question, “Who, in such an instance, would be the “murderer?”

Stephen L. DeFelice, M.D.

April 16, 2012

The ideal purpose of our national health policy should be to accelerate the discovery of medical breakthroughs that will cure or much better treat diseases which would a) reduce patient suffering and premature death and b) dramatically and quickly reduce health care costs. One way to do this is to enact the Doctornaut Act which deals with medical discovery only. Cost reduction would then follow due to natural market forces.

To appreciate the rationale of this proposal one must understand the system which brings patients new medical therapies. We, unfortunately, are profoundly ignorant of it. Generally speaking, medical discovery involves two processes- the identification of potential therapies discovered in scientific laboratory studies or based on theory and the clinical testing of them in patients. If, for example, something like aspirin is shown to have pain killing-inflammation reduction potential in animals, it can only be proven to work in clinical studies in patients with headache and arthritis among others. The extremely good news is that, there are, and will be, enormous numbers of potential medical breakthroughs. The very bad news is that our system is almost perversely designed to block the clinical testing of the vast majority of them. The costs and risks are simply prohibitive particularly with natural substances and combination therapies.  And who pays the price?  Defenseless patients!

In addition to the tomes of data that characterize the barriers to clinical studies, I have personally experienced practically all of them. In 1965, as a young doctor at St. Vincent’s Medical Center in Greenwich Village, I conducted the first clinical study in the United States on carnitine. It took me almost 20 years utilizing all of my know-how, including experimenting on myself with a dubious intravenous solution of carnitine, before FDA approved it for Carnitine Deficiency, a rare and often fatal disease in children. And, unlike many therapies for rare diseases, it is inexpensive!

While FDA is thought by many to be the official culprit obsessed by anti-innovative safety issues that permeate our culture particularly regarding clinical research coupled with an unbudgeable cultural blindspot to its essential importance, there is another extremely influential player- the mass media. The death of one patient volunteer during a clinical study evaluating a new gene therapy was trumpeted by the media causing a national uproar causing the FDA to create additional barriers. Yet thousands of Americans are mutilated and murdered each year unnoticed.

The solution is not to reform FDA- have we not learned that it is not re-formable? We must maneuver around it. Given our cultural mindset, the most doable way, in my opinion, is for Congress to enact the Doctornaut Act. “Doctornauts” are physician patients who volunteer to participate in clinical studies conducted by physician researchers under the supervision of their colleagues with minimal FDA involvement as well as waving their right to sue. Let’s not forget that doctors are the most qualified to judge the benefits and risks of clinical studies, not laymen laden committees. If enacted, an array of highly promising candidates would be promptly clinically evaluated and, inevitably, breakthrough hits would soon follow. Who can, with studied reason and altruism, object to doctors taking such chances to help their patients in their battle against disease?  Patients would surely be happy, but would physicians accept the challenge?

FIM, the Foundation for Innovation in Medicine, has a particular interest in encouraging clinical research on natural substances because they offer the greatest promise to combat disease but lack financial backing because of the difficulty in obtaining strong patents. FIM sent a questionnaire to physicians asking “Would you as a physician-patient want the privilege to volunteer for clinical research of natural substances under the supervision of a physician-clinical researcher without FDA, institutional or other restraints?” Over 50 percent agreed. Today there are 800,000 physicians in the United States. If only 20 percent volunteered that would immediately make available 160,000 doctornauts!

You may be wondering how the Doctornaut Act would decrease health care costs. In fact, my colleagues on Capitol Hill believe it would do the opposite! They believe that it would accelerate the testing of new, expensive technologies, raising such costs. Not necessarily so- and here’s why. Low- cost therapy candidates will also be tested and will compete with high- costs ones in the medical marketplace. For example, the annual cost of the renal dialysis sector is well over $30 billion and growing with our aging population.  The largest percentage are diabetic patients. Diabetes is a metabolic disease where the natural biologic processes go haywire. It is not an unreasonable hypothesis to assume that the administration of an inexpensive nutraceutical mixture of logically designed dietary substances along with standard pharmaceutical therapy might normalize kidney function markedly diminishing the need for dialysis and saving billions of dollars. Another example involves cancer chemotherapy. For reasons not clear, anti- cancer pharmaceuticals often have a strong initial effect on killing tumor cells but the latter becomes resistant to them during therapy. Something happens inside those damnable cells. If we can prevent these changes from happening with a combination of an inexpensive non- patented natural substance along with chemotherapeutic therapy, and such a possibility already exists, then patients would benefit soon followed by substantial cost reduction – the best of possible worlds!

It is a reflection of our cultural blindspot that Congress has never had a Hearing on what patients want – to create a system that will generally accelerate medical discovery for all diseases and other conditions that ail us. Paradoxically, there have been numerous Hearings on health care costs and ways to cut them.

Congress has gotten it backwards!

We are currently addressing major health issues.  Doctornauts should be somewhere on the top of the list.

Stephen L. DeFelice, M.D.

July 23, 2012

Dostoevsky, Jefferson and Franklin versus Regulatory Swarm – Somebody Out There: Write a Book- Quickly!

When I was 19 years old I decided I wanted to become an existentialist psychiatrist- whatever that is or was. At that time, existentialism was taking academe and its students by storm, and I read heavily on the subject. I didn’t think much of Sartre and Camus-and still don’t- but one guy, who has been labeled an existential thinker, but I believe he would have no part of official existentialism, immensely impressed me. Fyodor Dostoevsky understood, and experienced, the depths of the mind like none other before or after him who have expressed themselves in public domain. I proceeded to read most of his works and learned a lot about a lot.

I believe it was in his novel, The Possessed, where he described the social dynamics of late 19thcentury Russia. Though he mentioned materialism as a warning sign, he was deeply concerned about the growing prevalence of nihilism when people themselves decided what was right and wrong and were free to do what they wanted. Observing the movement, he correctly predicted and warned of the oncoming of 20th century Russian communism with a single, visionary statement, “Boundless liberty leads to boundless tyranny!” He foresaw a tyrannical central government suppressing the people by various tools of oppression from instilling fear to making them chattels of the state.

I’m sure he was aware of the same concerns of the Founding Fathers of America.  Benjamin Franklin and Thomas Jefferson were keenly aware of the nature of government’s appetite to constantly push the buttons to obtain increased powers over its citizens which concern was reflected in the structure and language of the Constitution. But they, like Dostoevsky, feared the power of a concentrated government. Franklin and Jefferson were fearful of the return of a king like the one they rebelled against. Though it may be recorded somewhere, I wondered what they were thinking when there were rumblings of a push to crown George Washington the “King of the 13 Colonies” after the Revolution. He, like Julius Caesar (who rejected the offer three times and then supposedly fainted), refused the offer.

Like Dostoevsky’s Russia, we are living in an age of materialism and nihilism the latter characterized by changing sexual mores, the replacement of traditional family structure with multiple other types and  the diminishing impact of traditional religion on our individual behavior.

These three great men were not aware of a new type of pervasive state control the magnitude of which still escapes public awareness and scrutiny. No gulags, no concentration camps, no forced labor and no mysterious disappearance of citizens: They are regulations and regulators which are currently controlling much of your life and soon, if unchecked, mostly all of it. Historically, dictators, kings and all the rest, unlike regulators, generally didn’t extend their scrutiny into the smallest, multiple details of the daily life of its citizens. The intent of modern regulations is to do just that; to dictate the rules regarding people and organizations from small to large events. And, if something goes wrong on their part, it’s extremely difficult to correct the fault. It is faceless, elusive and difficult to defend oneself against its power. You cannot charge it with pointed bayonet for it is, in an operational sense, invisible.

Rather than cover broad samples of regulations, I’d like to describe a few personal samples ofRegulatory Swarm. The State of New Jersey sends out an annual letter to remind its car owners that it’s time to register your car including instructions on how to make payment. Well, one night after I left the local restaurant there was a ticket on my windshield. My registration had expired. I called the police station to explain that I had not received notice from the state, and they told me there’s nothing that they could do. I went to the Motor Vehicles Division, told my story and explained that it was the state’s fault that I hadn’t received the notification for registration. The clerk, expressionless, – no pity for me! –  said, “Well. This happens a lot. It’s not our problem, and you’ll have to contact the state and talk to someone there.” I asked her if she had the contact number for the office. She didn’t. I tried calling the state but gave up after an eternity of waiting. I paid the annual registration fee but didn’t realize that it was only good for six months, the time in which my normal registration would expire. After six months my neighbor told me that my registration had expired. Once more, I hadn’t received the state notice. I went to the Motor Vehicle Division again and had various types of personal identification with me but not one which was considered mandatory and, therefore, they couldn’t process my registration. I pleaded my case that it was obvious that I was I. But they stood firm and told me that, though it was obvious that I was I, they were not allowed to exercise their personal judgment and obligated to follow the regulations of the regulators. I reminded them that once more the state didn’t send the notice. The sympathetic clerk admitted that they’re still having the same problem. I return home for the required identification, returned to the office and once more paid the annual fee. In addition to the regulatory mismanagement, another lesson learned is how we are powerless against Regulatory Swarm. The only good news about this standard regulatory adventure is that I wasn’t ticketed the second time thanks to my neighbor.

Here’s another personal story that should make one shake their head in despair. My daughter died suddenly and left no will. Her son was the sole heir. He had a death certificate and documentation to confirm the latter. We went to her bank with the documentation to find out how much money was in her checking account. We spoke to the manager and were told that she was prohibited by regulations to reveal the amount. We were then told in order to get an official release we had to go to the state court a distance away with the documentation. We drove to the court, located the proper office and were politely accommodated. We were given the legal papers for the release for the bank but there was one proviso. We were only permitted to withdraw up to $99. If the amount were greater we had to return to the court and obtain additional legal papers for the bank to release the remaining sum. I asked her the following question:

Question: “What is the reason behind the $99 rule?”

Answer: “I don’t know.”

Question: “What if there was $100 in my daughter’s account. Could we withdraw $99 and leave $1 remaining without having to come back to the court?”

Answer: “I don’t know. Nobody has ever asked that question before.”

Question: “Is there any way to find out?”

Answer: “I’m not sure who knows about these regulations.”

I decided to leave the court in a hurry in order to protect my brain and heart.

There was $94 in my daughter’s account, and I was relieved. You would think otherwise. After all, money is money, but I just couldn’t go back to that court. This was psychologically interesting and Dostoevsky would understand this. I feared that there was $110 in her account. This would force me to make a decision to return to the court and spend half a day in time and aggravation.  I did, however, finally come up with a creative solution to retrieve the $110 but it would violate a regulation and, in the regulatory swarm book, it would have been a crime.

Summing up the aggravation by incompetent regulators, bad regulations, a system lacking feasible remedies, waiting in lines and on the phone, forced overpayment of my registration fee, loss of time and acceleration of stress and cardiovascular disease- just over vehicle registration: The ticket costs me somewhere near  $100 and the registration process three days of  lost time. Regarding my daughter- do I need to further adumbrate? I work at home so I have some flexibility of time. I wondered, however, how a full-time worker could take the time off, even without pay, without some negative feedback from the boss further accelerating the oncoming of cardiovascular disease and also creating unnecessary tension at home with the family. Now these small regulation fiascos like this one happen millions of times a day in every walk of like.  We all have experienced and heard stories about regulatory overload. Get ready for many more!

On a larger scale, in my previous post, Carnitine and Doxorubicin: Potential Promise for the Treatment of Ovarian Cancer, I described how a single, high level FDA official by taking an independent regulatory action to the Orphan Drug Act led to a company, which had previously agreed to support a clinical study on a potential new therapy that I discovered for ovarian cancer, withdrew its support after the FDA action.  Just imagine my personal costs and time to support and gather all the information required for the FDA application that was rejected but would have been accepted except for the new regulation.   I then was told that it would be extremely difficult and costly to have the decision reversed.  And who pays the ultimate price of this Regulatory Swarm?  They are late stage ovarian cancer patients who have a certain rendezvous with death missing out on a potential new therapy. More than that! This new regulation will discourage other new potential therapies from entering clinical studies. Once more, patients pay the price?

Since President Obama took office regulations have skyrocketed in number, more than in any other administration. The Obamacare law contains about 2500 pages. Regulators are now frenetically writing regulations of each page in order to implement the law. Though we won’t know until the finished product is published, one sources estimated that 170,000 regulations will follow. And whatever the number, based on statistical probability algorithms, there definitely will be mass contradictions and confusion in the law where both individuals and organizations will be defenseless to resolve their problems without great effort, if at all.

The encouraging news is that there is certainly a cultural awareness of the ongoing tide ofRegulatory Swarm but little awareness of its impact on our freedom. Remember the Regulatory Swarm Equation: More laws and regulations = less freedom.

Of course there are other issues to be addressed. For example, regulations are mostly a hidden tax but not all the time. Just ask Supreme Court Chief Justice Roberts. Also, Internet has opened a new avenue on the attack on freedom and Regulatory Swarm will soon become a huge player in this world of vast open information. Also, let’s not forget we’ve entered the Age of Informers who are feeding the regulators. Combine all of these movements and unless there’s something I’m not seeing, we are, unawares, in a highly synergistic rapidly moving Regulatory Swarm phase not only where the state regulates its people from the “cradle to the grave” but as Joseph Stalin said, “From erection to resurrection!”

So where are the leaders? Can it be a presidential campaign issue? At this time, I doubt it. In any event, someone out there should write a brief, simple and persuasive book with representative examples to alert our country of the Regulatory Swarm and the need to draw lines. Also, I believe this is fertile territory for the blogosphere!

Stephen L. DeFelice, M.D.

April 20, 2012

If you’re presently or a future patient, are you aware that our health care system is designed to keep you as a patient with your disease or disability for a long time?

There’s talk about health care everywhere but are you aware that you, the patient, as in the past, has not been included in the discussions? Has Congress, the President’s Administration or high level medical organizations ever asked patients or potential future ones what they want and then what they can do to make it happen?

The questions are simple to predict. Patients would ask for the following. ‘I have my disease (or disability) and want to get rid of it” or “I’m healthy now and I don’t want to have any disease” or “We don’t want free hospitalization or free drugs. We just want to be healthy”.

In medicine we are dealing here with the prevention and treatment of disease to deliver what patients want. And how is this brought about? By the discovery of medical breakthroughs, including cures. Now hold on to your hats for you will find this difficult to both emotionally and intellectually swallow. Congress or any other body that I know of has never had a hearing on ways to establish a general innovative and productive medical discovery system! The inevitable conclusion is the patient is left out in the cold and what’s more unforgivable, nobody has told them this inexcusable omission.

In my recent post, I quote the former Commissioner of the FDA, Dr. Andrew von Eschenbach, who recently wrote an op-ed piece in the Wall Street Journal regarding medical discovery, “Breakthroughs for humans were and still are a long way off.”

In the same post I also referred to my book published in 1972, Drug Discovery; The Pending Crisis where I wrote, “Our present system of drug discovery is almost designed not to cure the great diseases that confront us. There is no doubt that many will be cured in the distant future, but it is unfortunate that many must wait.”

My constant theme is that medical discoveries are made by conducting clinical research or studies. For over a half a century we have and erected frustrating barriers to conduct such research. And, today, the patient has no rights to participate in a clinical study, and they don’t even know it.

That’s why doctornauts or physician volunteers for clinical research, where doctors can more easily participate in clinical studies, would lead to more potential therapies being tested and more breakthrough discoveries made in the near rather than the distant future.

Senator Bill Frist, a distinguished physician and former Majority Leader of the Senate,   understands the need to test more therapies and drafted the Doctornaut Act (www.fimdefelice.org). More about that later on.

By Stephen L. DeFelice, M.D.

Hyperthyroidism

In 1965, I was training to become a clinical pharmacologist at St. Vincent’s Hospital and Medical Center in New York City. One day, my colleague and physician friend, Dr. Sheldon Gilgore, visited my research unit and told me about some European clinical studies which reported that carnitine is effective in the treatment of hyperthyroidism or an overactive thyroid gland. He came to me because I was also trained as an endocrinologist and had much experience in treating patients with thyroid disease.

I reviewed the data and found that the studies were poorly conducted and would not be accepted by quality medical journals. I did, however, notice that, though the studies were not well controlled, certain clinical effects occurred which probably didn’t happen by chance alone.

Since carnitine is an exceptionally safe natural substance, I decided that it was reasonable to test this substance in a few hyperthyroid patients.

Three female patients with classic hyperthyroidism were selected. All had the common manifestations of tremors, weight loss, nervousness, insomnia, heat intolerance, excessive sweating and emotional instability.

I treated them with carnitine, and within a ten-day period all three were virtually without signs and symptoms. (1) Then came the surprise.

The assumption was that carnitine was blocking the production of thyroid hormone by the thyroid gland. Not so. Thyroid function tests still showed hyperactivity continuing to produce excessive amounts of thyroid hormone. I then postulated that carnitine must have-somehow, some way-blocked thyroid hormone activity peripherally.

Dr. Gilgore and I then decided to take the next step. We gave two groups of normal volunteers high doses of thyroid hormone together either with carnitine or placebo. The results supported our belief that carnitine blocks thyroid hormone peripherally. (2)

As with the adriamycin-carnitine story, very little interest was shown in these studies. There were scattered reports in the scientific literature dealing with the carnitine-thyroid hormone connection, but not until the year 2002-thirty-seven years later-was a well-controlled clinical study published which confirmed that indeed carnitine does block thyroid hormone activity. (3)

There are a number of hyperthyroid patients in whom this property of carnitine could be particularly useful such as in pregnancy and patients that are difficult to control including thyroid storm.

Obesity

In the aforementioned second clinical study that Dr. Gilgore and I conducted, we stumbled upon an unexpected finding. It is well known that excessive thyroid hormone, be it produced by the thyroid gland or given as a pill, causes weight loss. Much to our surprise, though carnitine blocked thyroid hormone activity on many clinical parameters, it failed to do so in the case of weight loss. The weight loss was equally as great in the thyroid hormone-treated group as it was in the thyroid hormone-carnitine-treated group.

This raises the intriguing possibility that the combination of carnitine and thyroid hormone may be a means to clinically treat certain types of obesity where the weight loss effect of excessive thyroid hormone is maintained while its side effects are negated.

There are some legitimate concerns that must be considered and evaluated. For example, thyroid hormone increases calcium excretion which may lead to osteoporosis. (4) It has been shown, however, that, in patients given exogenous thyroid hormone, carnitine has a beneficial effect on bone mineralization. (3) This study also supports the weight loss hypotheseis.

With the obesity epidemic in the United States coupled with the reality that exercise and diet have failed to stem this epidemic, it is past time that this promising treatment be clinically evaluated expeditiously.

Comments

Contrary to what you may hear or read, American medicine is, by far, the best in the world. But like many things in life, it can be greatly improved upon.

Educating physicians about non-FDA approved therapies is extremely risky. Our system is based on strong patents that are needed to justify the extremely high costs and risks involved in obtaining FDA approval for an NDA or New Drug Application, which legally permits pharmaceutical companies to spend many millions of dollars to educate physicians about the clinical benefits and risks of an approved product.

The costs to obtain an NDA are generally prohibitive for non- patented products, and it is very difficult to obtain strong patents for most natural substances which are our greatest potential weapons against disease. The large investment required to obtain FDA approval for the carnitine — thyroid combination will not happen simply because both are generic natural substances.

My personal experience with carnitine, magnesium and other natural substances is the reason that I proposed the Nutraceutical Research and Education Act or NREA. The latter is designed to encourage companies to sponsor clinical research on the specific dietary supplements and foods and legally make medical-health claims based on the results of the clinical studies at much reduced costs.

Congressman Frank Pallone (D-NJ) introduced the NREA in Congress in 1999. There was virtually no support from any dietary supplement or food company or their associated organizations. Evidently, they prefer to make marketing medical-health claims on their specific products that they sell that are not based on the results of clinical studies on their products.

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References
1. DeFelice SL, Gilgore SG 1996 The antagonistic effect of carnitine in hyperthyroidism. Preliminary report. J New Drugs 6:351-353
2. Gilgore SG, DeFelice SL 1966 Evaluation of carnitine an antagonist of thyroid hormone. Clinical pharmacology report. J New Drugs 6:349-350
3. Benvenga S, et al. 2001 Usefulness of l-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: A randomized, double-blind, placebo-controlled clinical trial. Journal of Clinical Endocrinology & Metabolism 86(8):3579-3594
4. Rivlin, R.S. Medical Intelligence. Therapy of Obesity in Hormones.
NEJM 292:26-29, 1975.

Stephen L. DeFelice M.D.

March 13, 2003

During the Vietnam war, Major James Vick, a cardiovascular pharmacologist, and I conducted a series of laboratory studies at the Walter Reed Army Institute of Research (WRAIR) which demonstrated that carnitine dramatically prevented or reversed myocardial ischemia, a lack of oxygen to the heart.

Following these studies, we decided to conduct other laboratory studies on whether carnitine could block lethal doses of certain toxins. We evaluated primarily cardiovascular effects and survival. Some of these studies were conducted at other facilities.

Frankly speaking, our hopes of success were not that high, but we thought that, given carnitine’s effect on protecting the heart against a lack of oxygen, it was worth a try. We also had read that other investigators had demonstrated that carnitine protects against lethal doses of diphtheria toxin in animals.

Then came the unexpected surprise. Carnitine, when given as treatment, after the toxicity process was in full swing, reversed the toxicity of the lethal doses of E.coli bacterial toxin, Russell’s Viper venom, palytoxin and adriamycin in almost all of the animals and other laboratory experimental models such as isolated hearts.

Excited by these findings, I contacted a number of pharmaceutical companies about carnitine’s potential for the treatment of sepsis and septic shock which is increasingly common in hospitals. I ran into a stone wall mainly because of the absence of a strong carnitine patent. Our colleagues in the government expressed interest, but the opportunity somehow fell through the cracks. It was probably due to the fact that, because of urgency of the Vietnam war, almost everybody in those days was trying mightily to find therapies to counter malaria infection and radiation damage. The bioterrorism threat was not yet a significant national issue.

I had no choice but to set aside this project, but Major Vick continued to conduct other laboratory studies with carnitine with exciting results.

I then decided to pursue carnitine for the medical condition of myocardial ischemia where the animal data continued to be highly promising. After communicating with approximately thirty U.S. and international pharmaceutical companies, I met Dr. Claudio Cavazza, the proprietor of the privately held, research-oriented Italian pharmaceutical company, Sigma-tau S.p.A.

Based on biochemical as well as pharmacological data, he became convinced of carnitine’s broad medical potential, and invested, and has continued to invest, substantial amounts of money in basic and clinical research including the development of related molecules such as l-acetylcarnitine and proprionylcarnitine.

Time passed and we paused different paths for awhile. When, however, the anthrax scare burst on the national scene and the real possibility that bioterrorism agents which cause septic shock could be used as weapons of mass destruction, I became somewhat alarmed. I then called Dr. Cavazza to discuss this situation and was very happy with what I heard.

In the past, some preliminary laboratory studies in septic shock with l-acetylcarnitine were conducted with promising results. For example, one study reported that l-acetylcarnitine could significantly block the lethal dose of the bacterial endotoxin substance, LPS.

In addition, two preliminary clinical studies were done in patients with septic shock with encouraging results.

In the first study, l-acetylcarnitine was administered intravenously and found to improve the metabolism of body fuel substrates such as fatty acids and branched-chain amino acids. In septic shock patients, the mitochondria, the energy producing parts of the cell, are compromised. Also, there is an increase in blood coagulation, which reduces the blood supply to body tissues and, therefore, much needed oxygen to the cells. This further compromises mitochondrial function leading to a decrease in the cells’ metabolic capacity to generate fuel not only to maintain normal functioning cells but also to keep them alive. Despite the seriously compromised mitochondria and significant decreased in energy output, l-acetylcarnitine managed to increase cellular production of energy.1

A preliminary double-blind clinical study was conducted in patients with septic shock. Both during and after the infusion of l-acetylcarnitine both systolic and diastolic blood pressure were significantly elevated. Also, the clinical investigations reported and improvement in blood oxygenation.2

Now let’s switch gears to some interesting recent findings regarding the central nervous system, l-acetylcarnitine and septic shock patients.

Because of promising scientific data, Dr. Cavazza decided to develop acetyl-carnitine for medical conditions that involve the central nervous system, or brain, as well as the peripheral nervous system. In addition to having the cardioprotective effects of carnitine, l-acetylcarnitine offers additional benefits by protecting nerve cells when they are seriously challenged.

Drs. Wesley Ely and other experts in shock management at the Vanderbilt University Medical Center found that delirium, which is common in septic shock, is an indicator or prognosticator of certain clinical outcomes or how well or poorly a patient does.3-4

It is not commonly appreciated that septic shock patients who managed to survive the life-threatening crisis have serious debilitating clinical sequelae, including those involving the central nervous system. They found that the degree of these debilitating central nervous system effects were proportional to the severity and duration of the delirium. Also, the more severe the delirium, the lower the survival rate and the duration in the hospital is significantly longer.

These data suggest that there is a real possibility that the brain may play a major role in septic shock.

There are a number of laboratory studies that report that l-acetylcarnitine is an active molecule in the brain. For example, a study was conducted in dogs to determine whether carnitine and l-acetylcarnitine protected the dog brain after it was deprived of oxygen by inducing cardiac arrest. It was found that l-acetylcarnitine significantly reversed the neurologic deleterious effects of oxygen deprival, while carnitine did not. The investigators conclude that l-acetylcarnitine works by restoring the brain’s normal aerobic or oxygen-based metabolism, normalizing the production of ATP, or cell energy.5

Similar brain protecting properties of l-acetylcaritine against oxygen deprivation in rats has also been reported.

The brain effects of l-acetylcarnitine have not yet been studied in septic shock animal models or patients. We do know, however, that it crosses the blood-brain barrier in humans. It stimulates the production of plasma cortisol and endorphins and increases cerebral blood flow to certain parts of the brain. It has also been reported to benefit patients with certain diseases of the nervous system.

L-acetylcarnitine’s combined cardiovascular and central nervous system properties offer promise to septic shock patients. I have consulted with a group of experts who, after evaluating all the promising pieces of evidence, agreed that it is worthy of a clinical trial in such patients.

There are approximately 750,000 cases of severe sepsis a year, with about a thirty-three percent mortality rate. Septic shock now kills more patients per year than breast, colon, pancreatic and prostate cancers combined!

It is important to note that bioterrorism toxic agents cause septic shock or damage the brain or do both. In my opinion, the possibility that l-acetylcarnitine may counter some of these toxic effects should be pursued either alone or in combination with other promising agents.

References:

Gasparetto A., Corbucci G.G., DeBlasi R.A., Antonelli M., Baqiella E., D’eddio
S., Trevisani C.: Influence of acetyl-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. INT.J. CLIN. PHARM.RESX1(2)83-92 (1991)

Nanni G., Pittiruti M., Giovannini I., Boldrini G., Ronconi P., Castagneto M.: Plasma carnitine levels and urinary excretion during sepsis.
JPEN9: 483-490, 1985

Ely, E.W., Jackson, J., Shinitani, G.S., May, L., Truman, B., Dittus, B., Gautam. S., Bernard, G., Speroff, T., Hart R. Long-term neuropsychological deficits following delirium in mechanically ventilated ICU patients. Am. J. Respir. Crit. Care Med. 165(8):A30, 2002. (now in press at Crit Care Medicine after peer review)

Ely, E.W., Shintani, A., Bernanrd, G., Jackson., J., Gordon, S., May, L., Truman, B., Gautam, S., Inouye, S., Dittus, B., Speroff, T. Delirium in the ICU is associated with prolonged length of stay in the hospital and higher mortality. Am J. Respir. Crit Care Med. 165(8):A23, 2002. (now under review at NEJM)

Rosenthal, R.E., Williams, R., Wells W., Fiskum, G., Post-ischemic administration of acetyl-l-carnitine (ALCAR) prevents neurological injury following prolonged cardiac arrest in dogs, Abstract No. DV9, Pharm. Of Cerebral Ischemia ’92, Marburg, Germany (1992).

Stephen L. DeFelice, M.D.

The vast majority of Americans are correct in their belief that modern technology offers enormous medical promise. They are unaware, however, that the barriers to deliver this medical promise are also enormous. For decades we have been told about exciting potential medical breakthroughs, but such news is invariably followed by the message that it will take a significant amount of time before these potential breakthroughs become available to doctors to patients. But, unbelievable as it may seem, not once have I heard the question asked, “Why are they taking so long to arrive?”

My answer to the question is that the American system is misanthropic in that, like a stealth bomber, is effectively designed to block the clinical testing of these therapies without being noticed. The result? Many millions of patients have or are needlessly suffering and dying before they should.

I have had a long career in scientific-medical research and have experienced, firsthand, the formidable barriers to medical discovery. For this reason, I decided to create this column in order to both offer ways to effectively diminish these barriers as well as discuss potential new therapies themselves.

Occasionally, guest authors will contribute to this column. I do invite comments and criticism from the readers. But, unfortunately, because of the volume, I am not able to respond to all. I will, however, select a few which will follow each column.

Stephen L. DeFelice, M.D.

 

Health care costs are accelerating, the 75 million baby boomers are coming, and no solution is in sight! Doctornauts could be a significant part of the answer of this critical national dilemma. The passage of the Doctornaut Act as proposed by FIM (visitóDoctornaut Act Proposal on the FIM website), is a wonderful, simple and straight forward opportunity to reduce such costs. Though the concept is not complicated, the dynamics behind the rational of the proposal require education on a national level. This is best achieved by holding a Congressional hearing.

A doctornaut is a physician who has the right to volunteer for clinical research with substantially fewer restraints than non-physician volunteers, take greater risks and wave the right to sue. Current technology alone, not to mention future technological advances, offers a cornucopia of potential medical remedies that may either cure or prevent disease — if they can be clinically tested! And this is where the problem is. Formidable barriers, costs and risks, continue to block clinical studies of many potential medical breakthroughs.

And this is exactly where the value of establishing a category of doctornauts comes in; more therapies can be clinically evaluated, accelerating the medical discovery of low cost remedies.

Many believe that doctornauts will lead to the discovery of high cost therapies. Not true! One reason we have high costs therapies is due to the high cost to discover and develop them. The later is exemplified in the sudden drop of FDA approved drugs in 2005 and the recent attempt by FDA to lower the barriers to early clinical research by permitting the administration of very small, non- therapeutic doses of drugs to determine whether they are absorbed and also arrive at their proper targets in the body. The later is indeed a step in the right direction but falls far, far short of what is needed.

Doctornauts will lead to the rapid discovery of both high and low cost therapies which will compete with themselves in the health care marketplace leading to a much desired goal and a reduction of the prevalence of disease and its destructive consequences as well as health care costs!.

Let’s examine a potential low-cost therapy: There are more or less 14 million diagnosed diabetics in the United States that account for approximately 135 billion dollars of annual health care costs. One huge problem related to the devastating complications of diabetes is due to the blockage of very small vessels which carry oxygenated blood to body cells, robbing the latter of much needed oxygen. There is good reason to believe that a low-cost nutraceutical (dietary supplements) combined with a low-cost standard pharmaceutical will make these cells function more normally, even when they are deprived of normal amounts of oxygen.

Let’s assume that this medical approach results in lower costs of thirty per cent. The annual savings would approximately 40 billion dollars, a substantial amount for only one disease! If this could be repeated with the other major diseases such as cardiovascular, mental and malignant tumors, the reduction of total health care costs would be enormous.

On the other hand, it is fair to wonder whether the opposite would occur. Yes, the short term costs would be reduced but this may lead to a longer life span. In this situation the basic costs of diabetic care would not only continue but these patients would be assaulted by other disease such as Alzheimerís nullifying the original cost reduction.

The answer to this argument is that during the initial phase of cost reduction, cures and other low-cost therapies will be discovered for these diseases which will undoubtedly be discovered with the help of doctornauts.

The truth is that we cannot precisely know what impact doctornauts will have on health care costs for future events will color the outcome. I am reminded of the great Pericles. When the Spartans were approaching Athens, a walled city by the water, he summoned the cityís citizens to the main square to announce his war strategy. All of Athenians would remain in the barricaded, walled city until the Spartans tired and returned back home.

One of the anxious citizens asked, “Pericles, Pericles, are you sure your strategy will work?” Pericles paused and replied, “How the heck do I know? What I do know is that we must do something ñ soon!”

So also, we must do something to reduce health care costs as well as help patients-soon. And doctornauts should rate high on the list.

Alzheimer’s disease and Septic or Toxic Shock as Examples

Stephen L. DeFelice, M.D.

The Panalba controversy took place in the 60’s when I was a young doctor. Panalba was a fixed antibiotic combination used to treat a variety of infections. FDA, strongly supported by academic scientists and doctors, established a policy requiring that each ingredient of a fixed combination not only be individually tested but each potential combination of them. It is interesting to note that the strongest advocate supporting this policy was Maxwell Finland and its strongest opponent, Louis Lasagna, both distinguished physicians and members of my board at the time. I listened carefully and closely, first hand, to their opposing arguments.

This policy led to our era of scientific clinical research (SCR) not only for fixed combinations but other types of clinical studies and relegated medical clinical research (MCR) to the sidelines.

The result? Medical discovery has been powerfully retarded and those patients that are currently ailing as well as future ones, will pay the heavy price of needlessly suffering from their diseases and other maladies let alone die before their natural allotted time. How come? SCR has enormously increased the personal effort and costs, both formidable barriers, to conduct a clinical study, the critical step in discovering new medical breakthroughs. Increased barriers to clinical research, whatever they may be, decrease the discovery of new therapies. This point should be self- evident but, for certain cultural reasons, has eluded the health policy leaders and the media.

Both SCR and MCR share the common purpose of determining the outcome of a clinical study. Does a drug work and is it acceptable safe? But SCR, in addition, insists on knowing more about the scientific details of the study. Let’s return to combinations, as an example: If there is a possibility that a combination of three drugs will be effective in the treatment of Alzheimer’s disease, a SCR protocol will require that the individual drugs alone and all combinations thereof must be tested as described above to determine what are their individual contributions. A MCR approach would not, unless necessary, require such scientific details and would directly evaluate the combination only to determine its medical benefit. In other words, the benefit to the patient, not science, is its primary medically justifiable concern.

Now let’s look at the cost to conduct an SCR versus an MCR clinically designed study in Alzheimer’s patients and assume that the study would take a year at a cost of $30, 000 per patient. The average placebo response in medicine is 15-30%. To be convincing we should look for at least a 50% treatment improvement over placebo, so let’s say 25% placebo response and 37% treatment response. Skipping over other statistical considerations, the total cost of A SCR approach would be $97,440,000 while that of a MCR $13,920,000!! But there are and will be other potential combinations for the treatment of Alzheimer’s and most all other diseases. It is sadly self- evident that they will never be tested unless our policy changes.

Furthermore, it is ironic that the SCR approach, like the MCR one, includes the evaluation of the combination itself! Why, therefore, are the other components required particularly when this requirement will prevent the clinical studies from ever being done and patients deprived of new therapies?

Let’s take a look at potential new therapies for Alzheimer’s disease that are currently available such as Lipitor, sage extract, leuprolide, huperzine A and raloxifene: Clinical studies are now being conducted on each substance alone. It makes compelling medical sense to select three of these substances with different modes of action and evaluate all three together in an MCR type of study in order to increase the probability of success within a short term period. There are currently 4.5 million Alzheimers patients in the United States, and we owe it to them to accelerate the discovery of new therapies for this condition.

Here’s another example that not only deals with patients in very serious trouble but also with a potential national disaster: Septic or toxic shock is a condition with about a 30% mortality rate that is caused by bacterial and other toxins. It is becoming increasingly common in our hospitals, particularly in the elderly, post-surgical populations with compromised immune systems. There has been a number of promising natural substances isolated by the biotechnology industry that have shown much promise in laboratory animal studies in the septic shock state but have, unfortunately, failed in clinical studies. Apart from economic considerations, the next step, according to the MCR approach, would be to select, let’s say three of these substances with different modes of action, which could complement each other. In addition to shock, multiple deleterious effects take place such as increased blood clotting, general decreased oxygen availability to body tissues and significant brain damage in the survivors. As with Alzheimers, a combination of three drugs directed to treat each condition would then be administered to those septic shock patients who have a highly probable rendezvous with death. There’s little to lose and much to gain.

Also, lethal toxins such as those produced by small pox or plague that can be used by terrorists cause septic or toxic shock. This alone, should awaken us to the critical necessity of the MCR approach!

The conclusion is that the SRC policy is clearly harmful to the patient and must be modified. After all, in the actual practice of medicine alls types of combinations are commonly and justifiably administered by physicians to treat patients with diseases ranging from rheumatoid arthritis to congestive heart failure unequivocally supporting the reasoning behind the MCR approach. The good news is that there are encouraging signs of change. The FDA has recently approved a cocktail of three pharmaceuticals for AIDS patients without requiring the prohibitively expensive SCR approach to assess its full therapeutic evaluation. But we must have a clearly defined national policy to encourage MCR for all appropriate conditions requiring medical treatment.

In the final analysis, when we’re dealing with ways to conquer disease to benefit the public, we should keep in mind the Chaos Theory which believes that small events can lead to bigger ones be they positive or negative. For example, the theory accepts the possibility that if a tourist on Alcatraz casts a pebble in the Pacific Ocean the ripple could somehow resonate to such a degree as to eventually cause a highly catastrophic Tsunami somewhere in the Far East.

The SCR policy can be equated to that pebble.

Stephen L. DeFelice, M.D.

 

During 1965, while conducting the first clinical trial in the United States on the natural substance carnitine, I became interested in the aging process and ways to reverse it or slow it down. My interest arose because the most obvious hallmark of aging is the loss of energy from body cells. Since carnitine naturally increases cell energy, I wondered whether it and other natural substances could replenish the lost energy of the aging cell. Also, many disease states are characterized by a loss of energy, and I saw no reason not to consider aging like any other treatable disease. In those days, however, it was difficult to find a single colleague who would agree with me. It was simply too out of the box an idea to be accepted in the academic medical – scientific world, let alone our society in general.

Leaping forward four decades, the scenario has changed dramatically. We now know lots more about the aging process which has opened exciting doors and opportunities. Laboratory studies on genes, the epigenetic environment and caloric restriction clearly indicate that someday new anti – aging discoveries will be made.

However, though I may be wrong, they are not on the near term horizon. But there is one near – term possibility based on what I label, The Nutraceutical “Rejection – Need” Theory of Aging. A nutraceutical is a food or part of a food that has a medical – health benefit primarily with respect to the prevention and treatment of disease. Bottom line, we are talking about dietary supplements be they in a pill, liquid or food dosage form.

Let’s return to carnitine. This natural substance has significant positive clinical effects in a number of diseases ranging from the FDA approved fatal condition of carnitine deficiency in children to renal dialysis patients. It has also been demonstrated that, in a number of clinical studies, it effectively protects the heart against the lack of oxygen due to coronary heart disease. Unfortunately, it has not been developed for FDA approval for this cardiac condition, the number one killer in the United States, because of prohibitive economic reasons. It is important to note that all of these conditions are associated with cellular carnitine deficiency. When, however, carnitine is given to normal or healthy people there is little or no effect.

I first observed the latter in my second clinical trial with carnitine in 1966, which observation has since been confirmed in other studies. A number of years later, after some of the aforementioned clinical studies were published, it first dawned on me that carnitine is clinically effective only when there is a cellular “need” and “rejected” when there is not. The cells are deficient, ergo, the “need” and the rationale for the resultant activity.

But, in those days, I was thinking of carnitine alone, not of other substances, until the first large, controlled clinical study evaluating the effect of vitamin C on the common cold proved to be negative. Then came the second dawning: I thought that, like carnitine, there is no cellular “need” for vitamin C in common cold patients as there is in those with scurvy, a vitamin C deficiency state, which responds dramatically to supplementation with this vitamin. And the “rejection-need” phenomenon may be true of many other nutraceuticals.

Then there followed disappointing clinical results of beta carotene for lung cancer and vitamin E for cardiovascular disease, among others, most likely due to the absence of a “need” and, for that reason, were “rejected” by the cells.

During the aging process the furnaces of the cells, the mitochondria, where nutrients are metabolized to produce the ATP molecule or energy, progressively produce less energy with the passing of time. Free radical or oxidant activity is thought to play a significant role in this process. The rationale behind the Nutraceutical “Rejection – Need” Theory of Aging is to increase the energy levels in the mitochondria of old cells by creating a “need” for these cells to use nutraceuticals that are involved in ATP production and availability as well as reduce oxidant activity. One way to accomplish this is to stimulate them with substances such as growth hormone and testosterone given along with the nutraceutical formula containing substances such as carnitine, magnesium and CoQ10, all three substances involved in ATP activity, and carefully selected antioxidants. Proper dosing of all ingredients is critical in order to optimize the chances of success.

The encouraging news is that, in clinical studies in the young and old, both of these hormones have shown “stimulating” activity including increasing the size and number of muscle cells and improvement in cognition. The theory is that the nutraceutical formula will add to these effects by being utilized by the cells due to the stimulant condition.

The following is a revealing sequel: During mid 2005, I decided that there were sufficient scientific and medical data to justify a clinical study to test the theory in elderly volunteers to determine whether both the physical and mental deterioration of the aging process can be reversed to some degree. The next step was to consult with a number of experts on the merit of the theory and the design of the clinical study. All were helpful, most highly enthusiastic, and the one that had intellectual doubts about the theory still urged me to go forward with the clinical study.

Then I met with one of the world’s leading clinical researchers located at a major U.S. university. He was quite excited about the theory, and he designed a highly sophisticated aging – reversal clinical study that would give us many answers regarding the effectiveness and safety of the treatment.

Because of the promise that the treatment may work to help the elderly, a clinical study to test the theory is urgently needed. I have placed this article on the FIM website with the hope that it will be pursued.

A Special Message for Congressman Frank Pallone

by Stephen L. DeFelice, M.D.

It’s time to revisit the Dietary Supplement Health Education Act (DSHEA). Any new legislation and subsequent regulations, however, must be based on a solid, rational foundation to accomplish well-defined objectives. Unfortunately, this was not sufficiently done when the current law and regulations were written over a decade ago.

Both healthy individuals and those who are ill take their dietary supplements primarily for the prevention and treatment of diseases particularly the major ones such as cardiovascular, cancer and Alzheimer’s. This self- evident fact has been confirmed by a number of surveys. Of course, dietary supplements are also used for other health conditions that are not recognized as diseases such as fatigue and aging skin. These uses, however, are clearly of secondary importance. To put it simply, people take supplements to get rid of their diseases, if they have them, or to prevent them if they don’t. When Americans are asked what they want to know about the products they consume, the results of surveys are wisely in harmony with what physicians and other health care professionals agree upon.

They want to know the following:

1. Are the dietary supplements effective for the reasons consumed?
2. Are they acceptably safe?

3. And is the information available to them truthful?

The critical question then is, “How can we deliver these THREE NUTRACEUTICAL OBJECTIVES?” The unequivocal answer is by conducting clinical studies on the particular products sold. We can only know that penicillin works against bacterial lobar pneumonia; that insulin reverses diabetic coma; that niacin lowers blood lipids and that cranberry juice reduces the severity of urinary tract infections in women — and that all are acceptably safe – from data generated by clinical studies.

What does DSHEA do? Just the opposite! It effectively discourages clinical research which results in the following: People do not know whether the supplements they take are effective. They do not know if they are acceptably safe. They are denied access to truthful information regarding the effectiveness and safety of products.

The construct of DSHEA was an attempt to accommodate many players in the very complicated dietary supplement sector. In a real sense, it was a breakthrough milestone in our health sector because, for the first time, the government permitted companies to legally make claims about dietary supplements concerning bodily function. One well-intended objective was to reduce the rampant practice of making unsubstantiated and false claims regarding the beneficial impact of supplements on many diseases. The Congress handed the FDA a very difficult assignment and, for reasons too complicated to discuss here, an impossible task to carry out.

The major FDA attempt was to establish two types of claims categories — “health” and “disease” related. Companies are prevented from making the latter ignoring the fact that good ìhealthî largely depends on the prevention and treatment of disease. As an example of this epistemological chaos, if a company sponsors a well-controlled clinical study on a mixture of dietary supplements that shows that the product lowers cholesterol, the company cannot state the truth, namely, that it ìlowers cholesterolî because FDA considers this to be a ìdiseaseî claim. The company can, however, claim, “That it benefits the body’s cholesterol” or “Can contribute to a healthy heart” which not only confuses the consumer but deprives him or her of the truth.

If, in a follow-up clinical study, the product is administered along with a cholesterol-lowering pharmaceutical which work together to significantly reduce the size of coronary artery plaques more than the pharmaceutical alone, and the company wants to make this claim, it cannot for two reasons. First, it is considered a disease claim. Second, simply by the fact that it is given along with a pharmaceutical, it also falls in the disease category.

Given the restrictive ground rules regarding claiming, what company would make a substantial investment to sponsor clinical studies on its products when it is not allowed to educate the public, let alone physicians and other health care professionals, about the truth but, instead, it is pushed into making misleading and/or confusing claims? The company will, instead, like water, take the path of least resistance to the marketplace.

Over 15 years ago, FIM proposed the NREA, or Nutraceutical Research and Education Act, as way to accomplish the aforementioned critical THREE NUTRACEUTICAL OBJECTIVES. <(1) A nutraceutical is a food or part of a food that has a health benefit including the prevention and treatment of disease. It includes dietary supplements, foods, and functional foods which are really dietary supplements in food dosage forms. The core principle of the proposed NREA is to offer attractive economic incentives for companies to sponsor clinical research or studies on their specific nutraceuticals that are marketed.

I came up with the concept of the NREA as a result of my long and extensive experience with carnitine, which is legally both a pharmaceutical and nutraceutical. My work with carnitine has taken me deep into virtually all aspects of innovation in our medical system. For example, there was evidence that this natural substance was effective in the treatment of the rare condition, carnitine deficiency, which is a debilitating and oftentimes fatal disease in children. But the high cost of obtaining an NDA or FDA approval of the drug, coupled with the very, very small market size, discouraged any company from pursing its development. After the Orphan Drug Act was approved, however, my colleague and proprietor of Sigma Tau, S.pA., Dr. Claudio Cavazza, invested the time and money to successfully obtain FDA approval for carnitine though no profit would come of it.

The Orphan Drug Act basically does two fundamentally positive things; 1) it grants a company the exclusive right for seven years to make a disease claim ñ sort of a methods patent — based on the results of the clinical studies; and <(2) it substantially reduces the amount of clinical data and total cost required to obtain FDA approval. These two provisions effectively spurred companies to invest in clinical research, and the Orphan Drug Act has been a gratifying success.

It is both puzzling and disturbing to note that the general message of the critical importance of encouraging clinical research, clearly demonstrated by the Orphan Drug Act, has escaped notice by Congress and the pharmaceutical and nutraceutical sectors where the difficulties of conducting clinical studies continue to inexorably rise retarding medical discovery. But, unfortunately, it is not surprising.

In 1976, I formed and funded FIM with the sole objective of educating the public and the key players in the health sector, concerning the importance of encouraging clinical research. I relied heavily on the mass media to carry this message forward. FIM held numerous high-level conferences, made proposals, spent large sums on public relations firms and other parties to spread the message. The result? Virtually a zero response except for modest coverage from the industry media. The mass media was nowhere to be seen. We have a definite, almost unbudgeable cultural blind spot when it comes to clinical research. In fact, our society views it with suspicion.

The FIM NREA proposal is based on the same principles of the successful Orphan Drug Act. If a company sponsors clinical studies on its product and FDA approves it, that company will have a seven-year claims exclusivity period. I was mistakenly convinced that, because of our nation’s “exuberant enthusiasm” about nutrition, the key players in the health sector arena, particularly the mass media, would want to learn about and accept the general clinical research message necessary to deliver the promise of nutraceuticals to the people. FIM’s educational effort, once more, did not resonate in any quarter.

It has always puzzled me why the business health sector that can market nutraceuticals has powerfully resisted changes when the changes involve delivering to the customers what they want as confirmed by multiple surveys. In addition, they are blind to the fact that the potential nutraceutical OTC market is far larger and more profitable than the current health food one coupled with much lower costs to market nutraceuticals. The marketing approach is unique and substantially different than the classic OTC industry. <(2) Over ten years ago I was fortunate enough to meet Representative Frank Pallone (D-NJ) who is quite knowledgeable about the promise and problems of the nutraceutical sector. We discussed the importance of clinical research in achieving the THREE NUTRACEUTICAL OBJECTIVES. He became highly interested and we had a few more meetings. At one of our FIM conferences he, as a speaker, announced he would introduce the Nutraceutical Research and Education Act in Congress. And so he did on October 1, 1999. <(3) The result? Very little interest or support, and, because of this, the Act was temporarily laid to rest.

The following are a few points that should be considered in any new legislation.

The issue of safety: Justifiable concerns with safety played a major role in DSHEA and will also if it is revisited. Dietary supplements, when compared to pharmaceuticals, are vastly safer. For example, if all FDA approved pharmaceuticals were made freely available as dietary supplements, a large percentage of Americans would be deathly ill or no longer with us within a very short period of time! This is not to say that dietary supplements are without risks, but they do not compare to pharmaceuticals.

National placebo: To the skeptics who do not believe that dietary supplements, themselves, offer much promise, there is another important and little appreciated side of the coin. Nutraceuticals are our nation’s freely available placebos. Up to 50% of millions of Americans who suffer from a broad variety of conditions experience significant placebo improvement when taking them. We now know that something definitely happens to the brain’s machinery during a placebo response which somehow, through a natural mechanism in the body, leads to a beneficial response in these millions.

Cost reduction: And here’s another little appreciated but definite benefit: Those millions whose conditions improve find no need to visit a doctor’s office to receive a prescription for expensive pharmaceutical drugs and/or undergo costly medical tests. Though not yet sufficiently quantitated, there is little doubt that this results in an enormous reduction in health care costs.

In the final analysis, whether DSHEA is revisited or not, the enactment of the NREA not only compensates for some of the major deficiencies of DHSEA, but also presents a wonderful opportunity for Congress and the nutraceutical industry to deliver the promise of nutraceuticals to Americans—soon. To repeat, the NREA will lead to clinical trials that clinically demonstrate the effectiveness and safety of nutraceuticals related to disease and other conditions. Physicians and other healthcare professionals respect clinical data as the gold standard of acceptability and will recommend products that meet these standards to their patients. As a result, the NREA generated proven nutraceuticals largely will replace DSHEA’s unsubstantiated clinically unproven ones.

Regarding the NREA’s impact on the future nutraceutical industry, it will divide it into two general sectors similar to the ethical and generic pharmaceutical industries, but with important differences. The former, similar to the NREA industry, because of the exclusivity given to the claim, develops proprietary, high profit margin products which generate sufficient funds to sponsor clinical research while the latter, similar to the DSHEA industry, is a commodity, nonproprietary industry with low profit margins with little incentives to invest in clinical research.

Recently, Congressman Pallone has been appointed as Chairman of the Energy and Commerce Subcommittee on Health. For this reason and the reasons supporting the NREA, FIM urges Congressman Pallone to reintroduce his NREA. After all, Congress should be comfortable with the concept behind this proposal because it is the same as with the successful Orphan Drug Act that it enacted.

References:

1. FIM Rationale and Proposed Guidelines for the Nutraceutical Research & Education Act – NREA.

2. Clinical Research and Nutraceutical Brand names and Trademarks.
Clinical Research & Nutraceutical Trademarks
December 20, 1999 commentary by Stephen L. DeFelice, M.D.

3. “Bill H.R.3001 – The Nutraceutical Research and Education Act.

The Foundation for Innovation in Medicine (FIM), as described on this website, believes that a very simple new law, the Doctornaut Act, will effectively both accelerate the discovery of medical cures and breakthrough therapies and significantly reduce Medicare-Medicaid costs beginning in the short term.  The gateway to achieve both objectives is to relax the barriers to clinical research by having physicians more easily volunteer for clinical studies, which the Doctornaut Act will permit.

Regarding physician volunteers for clinical research or doctornauts, FIM has expended lots of efforts for over three decades without much success, and you may legitimately wonder why.  Frankly speaking, so do I. We have a definite cultural blind spot to the importance of clinical research.  Only recently have a few bold and visionary doctors and scientists, such as NIH Directors, Drs. Elias Zerhouni and Francis Collins along with a small number of supporters, stepped forward to make the case for Translational Science and the critical importance of clinical research. But the problem of the barriers to clinical research began about half a century ago so why has it taken Congress so long to act? Also, the media coverage of the Translational Science movement was meager, which bespeaks of our cultural blind spot. Though I applaud this movement, it is limited in scope and impact.

You may believe that the proposed solution of the Doctornaut Act is just too simple to be true. Well, I can assure you that the more that you read and think about what’s written on this website, you will at least come to the conclusion that it might have merit. To add to your motivation to consider the Doctornaut Act, what proposals are out there on effective ways to robustly increase our medical discovery system and reduce health care costs except by reducing services?

I spend lots of time reviewing exciting new therapeutic leads.  Two recent laboratory studies reported exciting promising findings for the treatment of multiple sclerosis and cerebral palsy. In a mouse-multiple sclerosis model, four lipids, which are natural components of the lining of nerves, were injected and found to both limit and reverse the severity of  some aspects of this condition. Rabbits with an induced form of cerebral palsy were injected with an anti-inflammatory drug hooked on to a tiny nanoparticle which helps deliver drugs to cells. Normal movement was nearly fully restored. Regarding cardiovascular disease, nanoparticles were injected into pigs and rats after they underwent laboratory- induced heart attacks where heart cells are damaged. The treatment produced the growth of new heart blood vessels followed by a significant improvement in cardiac function.

Make no mistake about it, because of the formidable barriers to conduct clinical studies, particularly for creative individual physicians, it will take a long time, if ever, before these and other very promising medical modalities discovered in animal studies will be tested in humans.  Doctornauts will insure that many of them will be.

Some have the impression that doctornauts will only volunteer for high- risk studies. Not so. They will participate in blood level studies to cell implants in the failing heart.

How will Americans react to physicians willing to take greater chances to volunteer for clinical research studies in order to discover better therapies for them? A joint venture, wide-ranging survey between Research! America and JZ Analytics reported what I find both surprising and highly encouraging, Most Americans would be willing to pay more taxes to increase spending for medical research. There are other findings which strongly support Americans concern about their health.

To my knowledge, Congress has never had a hearing on ways to create a “general” productive medical discovery system. Now is an excellent opportunity to do so and hear what others have to recommend, as well as a good time to evaluate the Doctornaut Act.

“Certitude is for fools”, wrote the great Scottish philosopher, David Hume. But my father told me a number of times, “Son, there’s an exception to every rule.” Regarding the Doctornaut Act, I agree with my father.

Stephen L. DeFelice, M.D., Founder and Chairman of FIM, The Foundation for Innovation in Medicine, who brought carnitine into the United States, speaks out on the current carnitine controversy.

L-carnitine is a natural substance found in high concentrations in the heart. It transports fatty acids into mitochondria, the furnaces of the cell, to be metabolized and produce energy. Because the heart requires high levels of energy it primarily uses fat which has more calories per unit than sugar.

I’m the physician who brought L-carnitine into the United States in 1965 to conduct the first clinical trial in patients with hyperthyroidism. Later on, I was stationed at WRAIR, the Walter Reed Army Institute of Research, and, for certain reasons, believed that L-carnitine could both prevent and treat myocardial ischemia, a lack of oxygen supply to the heart, even during a heart attack. At the institute I was fortunate to meet an expert cardiovascular pharmacologist, Major James Vick. Together we conducted a number of animal studies supporting my hypothesis. When hearts were made ischemic, arrthymias and cardiac arrest ensued. When given before, during or after the ischemic phase, L-carnitine dramatically prevented and reversed these events. We also found that L-carnitine reversed hearts that were in congestive failure.  Subsequent laboratory studies by other investigators confirmed these findings. In other animal studies, including monkeys, we showed that L-carnitine protects the heart against a number of toxins including the septicemia- producing bacterium, E.coli, and the anti-cancer drug, doxorubicin.

In an animal experiment, scientist Austin Shug of the University of Wisconsin,  as a member of a research team, discovered that L-carnitine leaks out from the ischemic portion of the myocardium. He and I then met with cardiologist James Thomsen of the same university and planned a clinical protocol in patients with coronary artery disease. The study was conducted and demonstrated that L-carnitine protects the human heart against myocardial ischemia (The American Journal of Cardiology in 1979). Then Dr. Shug teamed up with physician, Vera Regitz, at the German Heart Institute. In a series of clinical studies conducted in patients with congestive heart failure, cardiomyopathy and coronary artery disease they discovered that, in these conditions of cardiac stress, cardiac muscle levels of L-carnitine are very low while blood levels are significantly higher than normal. (View the publication here.). This indicates that the high blood levels are due to leakage from the myocardium or heart muscle. Elevated L-carnitine blood levels, therefore, is a highly promising biomarker for of serious cardiac distress and due to and not a cause of atherosclerosis as misinterpreted in the Cleveland clinical study. (This offers an interesting opportunity for an innovative medical device company). From a medical therapeutic point of view, high doses of L-carnitine should have been administered to these patients. In animal studies Vick and I first showed that much higher than normal blood levels of L-carnitine are needed to prevent and reverse ischemia as well as having other beneficial cardiac effects. This observation has been subsequently confirmed by other investigators in multiple animal and clinical studies.

On April 13 of this year- last week- the findings of a multicenter clinical study were published in Mayo Clinic Proceedings reporting that L-carnitine, when administered after a heart attack, significantly reduces death from all causes as well as causing a significant reduction of ventricular arrthymias and angina attacks when compared to placebo or a control group.

You may wonder with the abundance of published laboratory and clinical studies reporting the cardiac benefits of L- carnitine, why does it remain a “secret” to doctors particularly since it is approved for such uses in other countries. Generally speaking, doctors learn about pharmaceuticals after FDA approval which is followed by promotional-educational programs by pharmaceutical companies. In the early 70’s I did make an attempt to launch a clinical program with L-carnitine to obtain FDA approval for coronary artery disease. The Thomsen study was part of that effort. It was my first lesson of medical economics; L-carnitine lacked a patent. In addition, since it is a natural substance, it is difficult to obtain a strong patent. But based on  laboratory studies which I sponsored, I managed to obtain use or methods patents for a number of cardiac conditions. Though such patents are not strong ones, I did manage to obtain initial interest of support until D,L carnitine appeared in the health food stores freely available for purchase by the consumer. Understandably, the support was withdrawn. Later on L-carnitine distribution in these stores shortly followed which was the final nail in the coffin.

Because of the Orphan Drug Act, however, I teamed with the late Dr. Claudio Cavazza, the proprietor of Sigma tau, Inc. and a good man, to obtain two FDA approvals – Primary Carnitine Deficiency, a fatal disease in children and for patients undergoing renal dialysis. So both the intravenous and oral forms of pharmaceutical quality are now available to physicians by prescription to administer to patients for heart conditions.  But there is still that dilemma that no company is permitted to launch an educational program without FDA approval. On the other hand, doctors are permitted to prescribe without such approval. Bottom line, the cardiac promise of L-carnitine is too important to be withheld from the medical community.

(There is confusion regarding whether L-carnitine is a dietary supplement or FDA approved pharmaceutical. It’s both).

Getting back to carnitine as a cause of atherosclerosis, children with Primary Carnitine Deficiency experience life-threatening heart failure which is reversed by L-carnitine which restores its cardiac levels. Many of these children have been on very high doses of L-carnitine for long periods of time without any signs of atherosclerosis. It is FDA approved as a drug and also in many other countries where long-term animal safety studies at high doses are required . These studies show no signs of atherosclerosis. The FDA approved package insert lists no serious side effect of L-carnitine.

Many parents of children who are being treated with L-carnitine are now legitimately concerned about the safety of carnitine. Hopefully, this brief review will lighten their burden. Its efficacy and safety have long been established.

Modern technology is expanding exponentially giving us the tools to discover cures for diseases and disabilities, let alone provide us with major non-curative, low cost breakthroughs. One would have to be a bona fide Luddite to deny this. Also, it is difficult to refute that the most effective and preferred way to reduce Medicare-Medicaid costs would be to cure or eliminate major diseases ideally beginning within the near future. Farfetched? Of course not!  The challenge is to create a system which will spur on the medical creativity of our researchers by reducing the multiple barriers which keep them in limbo.  The Foundation for Innovation in Medicine has launched the Cure Care Initiative and proposed the Doctornaut Act as one rapidly effective solution to accelerate medical discovery and dramatically reduce health care costs.

I don’t pretend to be conversant with the world of economics but I did some homework and, as far as I could tell, what struck me is that Medicare and Medicaid cost projections have not significantly, if at all, factored in the discovery of cures. For example, it is estimated that a discovery of a cure for Alzheimer’s made today will lead to a savings of 20 trillion dollars over the next forty years. Because of the epidemic of diabetes, particularly in the elderly and obese of which a high percentage is on Medicare and Medicaid, costs are skyrocketing. The estimated annual costs for diabetic management in 2020 are $500 billion. As a rough estimate, if we multiply this figure by 40 years, we arrive at $20 trillion!

The absence of factoring in the “cure factor” in cost projections is a huge, incomprehensible error in economic planning impacting not only our medical planning but also our country’s future.  We’re legitimately concerned about the costs of these entitlements for they rob us of the funds necessary for positive expansion such as modernizing our infrastructure and streamlining our educational system.

Someone out there should calculate the reduction in Medicare-Medicaid costs by assuming that the 10 current most costly diseases will be cured tomorrow, ten and twenty years from now. Maybe we’ll be so surprised and, yes, even elated by the magnitude of the cost reduction that it will convince the Congress to enact the Doctornaut Act which will, without doubt, hasten the discovery of such cures.

In my first book, Drug Discovery, The Pending Crisis, published way back in 1972, I wrote, “Our present system of drug discovery is almost designed not to cure the great diseases that confront us. There is no doubt that many will be cured in the distant future, but it is unfortunate that many of us must wait.” In the book I pointed out that one critical reason that drug discovery was and would be in the future dramatically inhibited was due to governmental barriers to conduct clinical studies. Penicillin and insulin were not medically discovered in scientific laboratory studies but in patient studies. Block that step and you block medical discovery. Unfortunately, history has proved me correct. Ask yourself, “With all our modern marvelous technology, when was the last cure?”

Later on, in order to reduce the barrier to clinical research, I proposed the Doctornaut Act which would permit doctors or doctornauts to volunteer to participate in clinical studies much more easily than non-doctors (www.fimdefelice.org). This would immediately open the doors for more potential medical breakthroughs to be tested resulting into the discovery of superior therapies and cures. For a number of reasons we have a cultural blind spot regarding the importance of clinical studies, and, in fact, view them with suspicion, and I have run into stone walls trying to educate health policy makers and the media how doctornauts can delay death and reduce patient suffering on a wide scale. There was one exception.  Physician and former Senate Majority Leader Bill Frist agreed with the doctornaut concept and had a preliminary draft of the Doctornaut Act circulated. He also ran into a stone wall, and it was cast into the dust pin of current history- very bad news for patients, indeed.

Not too long ago, Australian physician, Barry Marshall along with his pathologist colleague, Dr. J. Robin Warren, who discovered in gastric ulcer patients an unusual bacterium later named, H. pylori, worked together to follow the unheard of possibility that a microbe may be the cause of gastric ulcers. When Dr. Marshall tried to gather support both for his idea and to conduct a clinical study, he, like Senator Frist, also ran into a stone wall. So the good doctor decided to experiment on himself. He performed a biopsy on one of his patients, isolated the H. pylori bacterium, placed into a broth to ferment and swallowed it himself. He then experienced serious symptoms and proved that his bacterium is a cause for gastritis, gastric ulcer and offering the promise to prevent gastric cancer. He won a Nobel Prize for this historic clinical study.

Recently, one of our great medical writers, Gina Kolata, wrote a fascinating and beautiful articlefeatured on the front page of the New York Times regarding how physician Lukas Wartman was in the final stages of acute lymphoblastic leukemia and how his colleagues came to the rescue. His colleague, Dr. Timothy Ley, gathered his team of gene experts and told them that they had come up with a creative treatment for their friend soon. He told them, “It’s now or never. We will only get one shot.” They explored the cancer cell and healthy genomes using a technique known as genome sequencing and discovered there was a normal gene in the leukemic cells responsible for the production of a protein which was fueling the tumor’s growth. And, both luckily and happily, there was an approved drug already available for the treatment of late-stage kidney cancer that could be effective in controlling the gene’s activity. Dr. Wartman volunteered for the study. He received the drug and responded dramatically. In addition to his response, it added a boost to gene sequencing research where the genes and not the tumor cells themselves are the targets for therapy.

It took only two doctornauts, one healthy and the other at death’s door, to make possible two major discoveries. There are approximately 800,000 physician doctors in the United States. Let’s assume the Doctornaut Act was passed by Congress and only 10 percent of volunteered to be doctornauts which would make 80,000 available for clinical trials! Now use your imagination of the potential discovery of new medical breakthroughs that could follow- very soon.  It’s breathtaking!

 Click here to encourage your elected official to support the Doctornaut Act.

Another Case for the Passage of the Doctornaut Act

We are increasingly questioning the benefits of weapons used in medical practice ranging from diagnostic tests to drug therapies. Recently, a coffee shop friend and mother of a 12-year-old male child told me that her son was diagnosed with ADHD and placed on Adderall. She was also told that he would be on the medication for a number of years. Though the initial clinical response was encouraging she was more than concerned about his future. She asked me what the long- term benefits versus risks of taking the drug  are when taken chronically. I told her I would call my colleague who is an expert in this field. As I suspected, the overall benefit –to- risk evaluation, even with dramatic improvement of the clinical symptoms, is not clear.

A recent, thought- provoking op-ed piece in the New York Times by physician, H. Gilbert Welch, clearly spells out the dilemma that we face which will continue for a long time to come. He mentions how hormone replacement therapy to healthy middle-aged women was standard practice until long- term studies raised concerns over cardiac and breast cancer risks. He also claims that routine testing of P.S.A. levels in men has led to unnecessary surgery for prostate cancer and to complicate matters, the results of which may not have reduced cancer deaths. As another case in point, he describes how mammograms are increasingly detecting microscopic breast tumors, D.C. I. S.  or ductal carcinoma in situ. The appropriate treatment is unknown. Some doctors treat it aggressively and some don’t. All concerned are awaiting a clinical outcome study which leaves the patient in a hell of a mess.

Dr. Welch also raises an example of costs in outcome studies when comparing colonoscopy, are very expensive, versus the testing of occult blood in the stools, which is very inexpensive, to detect colon cancer. The Affordable Care Act or Obamacare established The Patient –Centered Outcomes Research Institute whose mission is to fund clinical studies to evaluate such comparative treatments. A study is planned to evaluate these two cancer detection modalities in 50,000 patients! No cost is mentioned but take a guess! It will take almost forever to organize and complete the study and perhaps too late to save the lives of a number of patients if, for example, one test is inferior to the other. But, even if the study is completed, there’s a good chance that the results may be questionable not only with this but other outcome studies.

The Greek physician, statistician and meta-researcher, John Ioannidis is generally recognized as the world’s expert on exposing the faulty conclusions of clinical studies. They include those conducted by the highest-level physicians whose studies are published in the most prestigious medical journals. He claims that up to ninety percent of published information which doctors rely on either in conducting research or in the practice of medicine, is somehow flawed and oftentimes incorrect.

The man must have enormously high concentrations of cellular mitochondria and carnitine for he has published papers with 1,328 co-authors at 538 institutions in 43 countries. Last year he was invited to speak at 1000 events but only managed to handle 5 per month. His research covers a broad spectrum of categories including those which deal with prayer and heart surgery. One study reported that prayer is beneficial to patients with respect to survival while the other detrimental.

Many studies are difficult to design because the outcomes are not clear cut such as those with insulin in diabetic coma, penicillin in lobar pneumonia and the polio vaccine. Also, the problems with conducting studies are not limited to medicine but are common in all sectors such as physics and particularly economics.

Conclusion:  We can only resolve the benefit-risks, clinical outcomes of a relatively small number of medical modalities. To test most of them would take forever, bankrupt our treasury and produce lots of equivocal results and the patient pays the price. That’s the reality that none has faced and we must stop fooling ourselves.

What then is the solution?  One irrefutable solution is to significantly cure a number of diseases which will markedly decrease the need for medical outcome studies. The Foundation for Innovation in Medicine has launched the Cure Care Initiative to enact the Doctornaut Act which will accelerate the discovery of medical cures.

Dear Congressman Lance,

I salute you for your support of MODDERN, the Modernizing Our Drug and Diagnostic and Regulatory Network Cures Act. I noticed the word “cures” is in the title. I’m sure you’re aware that our track record for finding cures for disease and disabilities is a pretty abysmal one. One major and puzzling reason being that Congress has never considered, let alone enacted, a national cure policy. It has, instead, exclusively on a health care one. Witness today’s national debate where there is no mention of cures.

Though we met before, I’d like to introduce myself. In 1965, I brought carnitine, an unpatented natural substance, into the United States from France. Working with others in academic medicine and the pharmaceutical industry, I managed to obtain two FDA Orphan Drug approvals, one of which has saved the lives of children and the other for renal dialysis patients. I’ve personally experienced, unlike anyone in the United States who I’m aware of, almost all the barriers to medical discovery in my carnitine adventure. For this reason I formed my educational foundation whose primary mission is to accelerate medical discovery.

To the point: One unrecognized formidable barrier to medical discovery are the costs, risks and frustrations to conduct clinical studies the critical step in medical discovery for all dis- eases and disabilities be they rare, chronic, acute or subacute. To effectively decrease these barriers I proposed that doctors be able to more easily volunteer for clinical studies by enacting the Doctornaut Act. My colleague physician friend and then Majority Leader, Bill Frist, agreed and circulated a draft of the Act, which is posted on my foundation’s website. For certain reasons, it did not move forward. In an attempt to re-introduce the Act, I’ve met with Congressmen and pharmaceutical industry executives who are concerned about health issues such as my old colleague, Senator Tom Harkin and, your colleague, John Crowley, both good people, to garner support for the Act.

Here is a potential historic challenge for your consideration: Gather a very small group of experts to address three simple questions. Firstly, “What are the costs, risks and frustrations which retard clinical research?” Secondly, “How can we ’acceptably and simply’ reduce such risks, costs and frustrations beginning in the very near term?” and, thirdly, “Making the obvious assumption that, if barriers to clinical research are significantly reduced and the discovery of cures speeded-up, how much will health care costs be reduced?” As an example, if a cure of a single disease, Alzheimer’s, were discovered today, The Alzheimer’s Association estimates the cost reduction over the next 40 years at $40 trillion.

In my day, I’ve chaired dozens of think tanks let alone conferences, and I would estimate that, with the proper preparation, this gathering would take a day and a half.

Congressman Lance, this may sound too good to be true but, because of the huge potential outcomes, I believe that a day and a half of your time is worth the effort. Think about it.

Stephen L. DeFelice, M.D. Chairman, FIM, the Foundation for Innovation in Medicine

April 19, 2012

In the April 16, 2012 Wall Street Journal, one article dealt with an ALS (Lou Gehrig’s disease) patient having problems having access to a new potential therapy which is being clinically studied in a specific ALS population therapy. The patient is too far advanced to qualify as a volunteer for the study. Even if the results of the ongoing study are positive, he will probably not be alive by the time of the FDA approval. So what did he do? He somehow found out what he believes to be the new therapy, and it is now taking it through his feeding tube.

Awhile back I designed and managed a multi-clinic study in patients with ALS who were treated with brain extract nerve growth factors called gangliosides. I included a broad spectrum of patients, including late stage, because there is not much of a placebo response and positive effects could be easily detected in a small number of patients. Regarding late stage patients, the rationale is based on the assumption that there still are viable neurons in the brain but they are not functioning because they are in the late stages. If we could make them function again then we would hopefully see a dramatic, reversal effect which would then speed-up the process of FDA approval and availability to patients. If doctornauts or physician volunteers for clinical research with late stages of disease were not permitted in the current clinical study, then the drug could be studied in them increasing the probability of success within a shorter period of time.

An interesting historical note: In my studies, one of the ALS patients was a famous physician who had lost power in his hands along with other neurologic manifestations. He told me, and I cannot confirm this fact, that he was the doctor who treated Lou Gehrig. It defies probability.

In the op-ed section of the WSJ there’s a piece by Andrew von Eschenbach, former Commissioner of the FDA, making the argument that FDA needs more resources to speed up medical discovery. He wrote, “Breakthroughs were and still are a long way off.”

In my first book published way back in 1972, I wrote, “Our present system of drug discovery is almost designed not to cure the great disease that confronts us. There is no doubt that many will be cured in the distant future, but it is unfortunate that many of us must wait.”

So Dr. von Eschenbach and I agree. After 40 years little has changed. I’ll discuss whether increasing FDA resources will speed up medical breakthroughs discoveries in a future posts. But, though this was not his intent, he makes a powerfully strong argument that the discovery process is stalled due to FDA regulations. A simple, rapid and effective way to remove these regulations is to pass the Doctornaut Act where doctor patients can directly volunteer for clinical studies conducted by doctor clinical researchers.