and trim, Dr. Stephen L. DeFelice stepped lithely into the medical
office on the Upper East Side he uses for
It was late on a July afternoon, uncomfortably warm outside. Dr. DeFelice
wore a crisp navy blazer. A bow tie, his signature item of apparel,
draped around the unbuttoned collar of his shirt.
I had arrived some minutes before, taken a small elevator to the air-conditioned
conference room on the second floor, and seated myself at an oval wood table
burnished to a high gloss – time enough to feel that an Italian flair
for enjoying life's sensory pleasures directed Dr. DeFelice to choose
this meeting place. The room, elegantly furnished, looked onto the street through
three French windows. A bamboo sapling in a planter stood before each outer
window. One starkly utilitarian furnishing struck my eye: a white chalkboard
on a side wall. Dr. DeFelice tends to scratch words and phrases on the board
for emphasis during extemporaneous presentations, an academic touch. After
meeting him in 1993, I've come to appreciate that at heart he is a physician
who has been searching since 1965 for innovative, quicker ways "to hit
diseases," as he puts it, "that do ugly things to people."
I've published two interviews with Dr. DeFelice in the Townsend
Letter (July and October 2007). The first interview dwelt on nutraceuticals and the
Nutraceutical Research and Education Act (NREA), legislation proposed by Dr.
DeFelice and introduced in Congress by Representative Frank Pallone (D-NJ)
Dr. DeFelice has a knack for coining memorable terms. He dates the coining
of "nurtraceutical" to a leisurely stroll in the Piazza Navona
in Rome in 1989 after a superb dinner topped off with a smooth grappa. (The
Oxford English Dictionary now includes the word "nutraceutical" and
credits him for the coinage.) He had been seeking a single word or sound-byte
phrase that encompassed foods, compounds in food, dietary supplements, herbal
remedies, functional and designer foods, etc., all potentially useful in treating
and preventing disease. He felt that if he could give this nebulous field an
identity, Congress might enact legislation encouraging clinical research on
all of them.
Concluding my first interview with Dr. DeFelice, I applauded him for devising
a pragmatic mechanism – the NREA – for approval of nutraceuticals,
one that fully recognizes that under our free-enterprise system, capital won't
gravitate toward research without a market payoff. I underscored my fundamental
interest in the NREA; if passed, it might bring about a change in the treatment
paradigms for many diseases – from late-stage, invasive, costly interventions
to prevention or early-stage-modulations, which are much less invasive and
much more cost-effective.
My second interview with Dr. DeFelice began with his "Doctornauts" initiative,
a proposal allowing physicians to volunteer as subjects for clinical studies
with minimal restrictions on participation. My interview then concentrated
on what Dr. DeFelice believes is our nation's "cultural blind spot" to
the importance of medical research. As prime factors in perpetuating this blind
spot, he pointed a finger at the FDA, medical ethicists, and consumer groups
focused on the safety of new drugs rather than on the urgent need for more
effective drugs for diseases resistant to current treatment. He especially
decried the intrusion in medical decision-making by third parties, a trend
gaining momentum since the 1960s. Dr. DeFelice largely attributes this policy
development to the notion that the FDA and experts appointed by the FDA are
more competent than patients and doctors in determining access to experimental
treatment. He viewed such intrusions as a "rape of patients' rights" (his
sound-byte phase) and shredded the rationales put forward by medical ethicists
to condone them.
Dr. DeFelice's first book, Drug Discovery: The Pending
in 1972, warned that new medical therapies can only be discovered by conducting
clinical trials, the crucial step in the discovery process. Increase the cost,
risk, and other factors (such as labor-intensive procedures) of conducting
clinical studies, he contended, and fewer medical discoveries will be made.
Ultimately, who pays the price? he asked. Patients!
Recognizing that consumerism and its obsession with safety was on a rapid unstoppable
rise and that the 1962 amendments to the Food, Drug, and Cosmetic Act, which
authorized the FDA to approve drugs on the basis of efficacy as well as safety,
would further hinder clinical research, Dr. DeFelice broached his proposal
for MDs to volunteer as subjects in clinical trials. Twenty years later, he
hit on the memorable word "Doctornauts" for the proposal. That
caught the attention of Senator Bill Frist (R-TN) when Frist was majority leader
in the Senate. (A physician, Bill Frist has since left the Senate and returned
to the field of medicine.) Frist urged Dr. DeFelice to develop the idea for
a Congressional bill. Dr. DeFelice has been working on it, confident that "Doctornauts" would
almost immediately, dramatically, increase new therapies for patients. The
support technology, he has observed, already exists, but a quick means for
clinically evaluating most of these discoveries is lacking.
This column expands Dr. DeFelice's comments on consumer groups who unwittingly
hinder clinical research; it also offers his thoughts on the media's
apparent disinterest in the acceleration of medical research and, particularly,
their penchant for playing up adverse incidents and outcomes unexpectedly occurring
in clinical trials.
I met with Dr. DeFelice in his Manhattan office last July for a briefing on
his theory of how a combination of nutraceuticals, hormones, and antioxidants
might reverse the mental and physical deterioration characteristic of the aging
process, so I'll summarize his theory as well.
MC: In my interviews with you for the Townsend Letter, you recalled meetings
with medical consumers concerned about certain ailments. You were attempting
to enlist them in backing initiatives you had made that could expedite discovery
of treatments for these ailments. Yet they were deaf to your appeals. How do
you explain their behavior? Why this impenetrable block to what might benefit
SD: These people don't do their homework regarding the medical discovery
process and the crucial need for making clinical research less risky and costly.
If they did this homework, they would perceive the importance of clinical research
not only for nutraceuticals, but for pharmaceuticals, medical devices, etc.
MC: In 1974, William Wardell, MD published a paper in the Journal
of the American Medical Association. Titled "Drug Development, Regulation, and the Practice
of Medicine," it contained the following paragraph:
The medical profession should point out
that existing drugs are inadequate to deal with most of the diseases
we face. The object of legislation
in this area should be to protect the public against all diseases,
not just iatrogenic ones. In my opinion, the public interest would
be well served by policies designed to stimulate the development
and introduction of better medicines…Public interest organizations
should be educated to recognize the aforementioned point. The sick
patient who needs more effective or safer therapy than is currently
available will derive cold comfort from the present activities
of the consumer groups who claim to represent his interests. If consumer
fail to represent the patient's paramount needs, a separate organization
is obviously required.
That paper appeared a generation ago. The public
interest organizations with the most clamorous voices sing the same
tune today; safety first,
of better drugs by and by. How do you rate prospects for the emergence of "a
separate organization" that represents "the patient's paramount
SD: The prospects are poor and will continue
[to be] poor because the consumer groups you refer to have a blind spot when
it comes to recognizing that medical
discoveries hinge on clinical research. Again, the underlying reason for
the persistence of this cultural blind spot among these groups is their failure
to do the necessary homework; failing to do the homework, they don't
perceive the link between clinical research and the medical discovery process.
MC: You and I, Dr. DeFelice, have been following
a case working its way up through the Federal courts – Abigail Alliance v. von Eschenbach. Early
in October 2007, the Washington Legal Foundation (WLF), in an amicus curiae
brief, petitioned the US Supreme Court to hear arguments on whether terminally
ill patients have a constitutionally protected right to seek treatment with
a drug not fully approved by the FDA when no other FDA-approved drugs are available.
The Abigail Alliance for Better Access to Developmental Drugs began this
lawsuit five years ago. (The WLF joined in on behalf of the Abigail Alliance
In May 2006, a panel of the US Court of Appeals, District of Columbia, ruled
in favor of Abigail; then, in August 2007, a divided Appellate Court sitting
en banc reversed the panel ruling.
Here are two patients' rights groups petitioning the Supreme Court to
agree that once the FDA has determined, after initial trials, that a potentially
life-saving investigational drug is sufficiently safe for expanded human
trials, the Fifth Amendment's Due Process Clause gives terminally ill patients
(and their doctors) the "right" to try the drug.
Most of these patients have no alternative; they won't survive the entire
FDA 3-phase process of clinical testing and review. [In conversations with
Dr. DeFelice for my interviews with him in Townsend
Letter, he's repeatedly
noted that Phase II trials are the critical test in demonstrating whether
a substance has potential clinical benefit.]
Do you think there's a ghost of chance that the Supreme Court will even
hear this case, much less issue an opinion counter to the FDA's drug
SD: It would be very encouraging if the Court
ruled in favor of the patients. But even if it doesn't, I still think there's
plenty of room for
us to proceed with my Doctornauts initiative in the courts, if Congress won't
pass a law authorizing the proposal.
At 71 years of age, and not being a lawyer, I will need the help of more
vigorous, legal groups. My plan is to find the appropriate group or groups
money to support the effort. Make no mistake, however; I will be the captain
of the ship. I just have too much know-how to walk away.
In the final analysis, who truly represents the patients? We have forgotten
to ask them. If asked, they would say, "If I have a disease or disability,
get rid of it: If I don't, prevent it."
MC: You set off on a media tour in 1972 to promote Drug
Discovery: The Pending Crisis. You expected the media to comprehend that medical discoveries depend
on clinical research. Their reception of the book's message didn't
match expectations. What is most memorable about that tour?
SD: I studied very hard in preparation, and at the end, the media hadn't
grasped the message at all. They narrowed in on the risks involved in clinical
research. I don't recollect anybody in the media who supported clinical
research or pursued its benefits.
They received me with suspicion, almost hostility. Sometimes subtly, sometimes
not, the media treated me as a throwback to the doctors who tortured people
in experiments during the Nazi and Stalinist eras.
MC: Disappointed yet not daunted, in 1976, you established the Foundation for
Innovation in Medicine (FIM), a non-profit organization, and you sought exposure
in the media again. How did they respond on your second go-around?
SD: FIM seemed to me a brilliant idea. Its primary mission was to educate the
mass media about the importance of clinical research. I assumed the mass media
had an extremely high level of interest in health matters, so I figured they
would see the light, so to speak, and create a mighty wave of public opinion
that would move Congress to enact laws effectively diminishing barriers to
clinical research, thus spurring the discovery of new medical therapies.
I ran into the same stone wall I ran into on my media tour four years earlier,
affirming my initial impression. Our nation and the media have no conception
of the centrality of clinical research in the discovery process; it's
not on either one's radar screen.
My attempts to obtain contributions for FIM's mission reflect that clinical
research is nowhere near appearing on the national radar screen, much less
the media's – then and now. I estimate that a grand total of roughly
$25,000 in contributions have been donated to FIM since it was formed to the
present (2006) – 30 years, less than $1,000 annually.
Aware early on that this would be the case, I decided I had no choice but to
fund FIM's efforts personally until Congress stepped in with supportive
legislation. I paid for the services of a number of public relations firms,
for holding conferences, and for putting out books, position papers, and other
media vehicles. The mass media remained stubbornly and inexcusably resistant.
MC: Despite two encounters with the media that would have soured most people,
you tried them again in the 1990s. Any difference this time?
SD: I was on the verge of aborting efforts to stir interest in accelerating
clinical research. Then, another idea on how to draw attention to the importance
of clinical research popped into mind, one I thought was truly brilliant, which
could not fail to engage the mass media and prompt Congress to pass legislation.
I conceived the Nutraceutical Research and Education Act (NREA).
Between 1993 and 2000, FIM held high-level nutraceutical conferences yearly,
most of them at the Waldorf Astoria in New York City, a few in Washington,
DC. Manhattan was the media center of the world, Washington, DC not far behind,
so I expected heavy media coverage. FIM invested substantially in a publicity
campaign to attract the media to these conferences. The result? With perhaps
two exceptions, no mass media folks attended; thus, the media exposure necessary
to support passage of the NREA never materialized.
What puzzled and disturbed me most was that virtually all the mass media people
in both New York City and DC were only a short cab ride away, yet they didn't
see enough in these conferences to pay the fare. This finally persuaded me
that, barring something unusual, any attempt to convince the media of the enormous
importance of clinical research was destined for failure.
MC: I attended all but one nutraceutical conference at the Waldorf, including
the last in 2000, when Congressman Frank Pallone announced that he had introduced
the NREA in Congress. I always checked the list of attendees, full of upper-echelon
representatives from the food industry, pharmaceutical companies, and medical
academia. They were certainly willing to ante up the hefty fee for attendance.
That the media ignored all this puzzled me too.
Eventually, I concluded that the media couldn't find a story in the conferences.
To them, the presentations must have all seemed educational. Even Pallone's
announcement wasn't newsworthy to them; they know well that bills are
forever being introduced in Congress, but few make it out of committee to floor
debate, and relatively much fewer get passed and signed into law. Convene a
conference to announce passage of the NREA – that might rate coverage.
How do you account for the media staying away?
SD: Marcus, I hate to say it publicly, but the media folk who cover health
matters are an intellectually lazy bunch. By far, the most common question
asked by my media colleagues is, "Where is the story?"
Here it is. Modern technology offers us definite opportunities, opportunities
only now opening, to increase our medical weapons against disease and disability – if
we can put them through clinical trials more easily and quickly. The NREA is
one means to accomplish this. I lean these days toward Doctornauts as the most
effective means of getting this done. Tens of millions patients are needlessly
suffering and prematurely dying. Doctornauts is a solution with a strong probability
of significantly helping such patients. If that's not a story worth covering,
MC: The stories about health matters that the media seize on often deal with
serious adverse effects of drugs in trials or with negative outcomes in tests
of dietary supplements. That indicates to me more than laziness; I question
whether the reporters possess basic knowledge about clinical trials.
Unforeseen adverse effects can occur in testing new treatments, especially
when the number of subjects greatly expands. Negative results in studies on
dietary supplements, particularly where previous studies have reported benefits,
may be due to a number of factors: differences in study design, differences
in the make-up or doses of the substances tested, differences in trial periods,
etc. I suspect ignorance rather than laziness.
SD: The media are obsessed with describing, in great detail, stories of suffering
and death from toxic reactions to investigative drugs. Not infrequently, these
news stories imply evil doing by doctors and pharmaceutical companies. The
extensive coverage of a single death after insertion of a gene in a human volunteer
in a clinical study at the University of Pennsylvania, the dangerous adverse
effects of Vioxx after marketing are representative of such stories.
Often, the media blame the FDA, which brings intense political heat upon the
agency. The FDA responds by creating new, stringent requirements – ostensibly
to insure safer studies. What is the inevitable result? The costs and risks
of clinical research rise, further retarding medical discovery and diminishing
patients' rights. The media hardly ever follow up on these critically
Dr. DeFelice's Theory of Nutraceutical
Rejection-Need in the Reversal of Aging
At my meeting with Dr. DeFelice in his Manhattan office last July, he briefed
me about his theory on how to reverse the mental and physical deterioration
of aging. Studies he conducted in the mid-1960s on carnitine, a naturally occurring
substance, had been the take-off point for the theory.
Carnitine transports fatty acids into cells to produce energy. Energy loss
resulting mostly from a reduction in number and size of the mitochondria is
a main sign that a person is aging. (The mitochondria in cells can be likened
to furnaces where sugar and fats burn and ATP forms, generating energy to power
all the body's activities; ATP is a molecule essential for producing
Dr. DeFelice wondered if carnitine, taken with other energy-producing nutraceuticals,
could help replenish the energy lost by aging cells? Over three decades, his
own findings in studies on carnitine, and studies in the research literature
on beta carotene and vitamins C and E (among other dietary supplements), had
suggested to him that if the cells of the body need these nutraceuticals, they
accept them; if not, they reject them.
Studies he found in the literature on growth hormones and testosterone showed
that these increase production of ATP and that certain nutraceuticals (carnitine,
CoQ10, and magnesium among them) also step up ATP production. Giving these
nutraceuticals together with hormones to older people, he reasoned, could raise
energy production in their mitochondria to levels necessary to retard the deterioration
brought on by aging.
But there was a problem, he realized, involving ATP: free radical activity
rises with ATP production. In addition to nutraceuticals and hormones, then,
an anti-aging formula had to include selected antioxidants. It was also necessary,
he determined, to vary the doses of nutraceuticals each day, so the body would
absorb the right amount. In the end, he designed a seven-day formula varying
the doses daily, which maximized ATP production and the antioxidant effect.
In 2005, Dr. DeFelice felt that medical and scientific data justified a clinical
trial of his theory, using his formula. Consultations with experts confirmed
the merit of such a study and his study design. He's now looking for
funds to conduct a clinical study that would definitively test his theory.
Dr. DeFelice is funding a study of L-acetylcarnitine at his own expense. Researchers
at Vanderbilt University Medical Center (Tennessee) are assessing the potential
of L-acetylcarnitine to counter septic shock caused by infection and bioterrorism
Approximately 750,000 cases of severe sepsis occur annually in hospitalized
patients, observed Dr. DeFelice. A third of these patients succumb, he said,
noting for emphasis that septic shock takes more American lives per year than
breast, colon, pancreatic, and prostate cancers combined. L-acetylcarnitine
may protect the cardiovascular and nervous systems against this condition.
Bioterrorism pathogens can cause septic shock, and they can damage the brain.
By itself or in combination with other substances, L-acetylcarnitine may protect
against these toxic effects as well. It's noteworthy that Dr. DeFelice
had first observed this protective effect in sepsis during his studies of carnitine
and L-acetylcarnitine at the Walter Reed Army Research Institute back in 1965-66.
Dr. Stephen DeFelice, Novelist
Dr. DeFelice recently published two novels. In He
Made Them Young Again (www.AuthorHouse.com),
one of the protagonists, Sigismondo Malatesta, could well be Dr. DeFelice in
fictional guise. Dr. Malatesta speaks like Dr. Stephen L. DeFelice; his voice
has the same bite. A representative excerpt follows:
Sigismondo believed that many diseases
could be better treated, or even cured, if one knew what was going
on inside the body's cells.
Then the doctor could give a specific formula of natural substances
to correct the imbalance and, by so doing, eliminate or ameliorate
He used vitamin and mineral deficiencies as examples to support his
postulated that multiple deficiency states in cells are the cause of many diseases
including diabetes, heart disease, cancer, arthritis, and Alzheimer's,
but modern science and medicine hardly make a great effort to discover them.
Sigismondo disdained what he considered the current rigid and sterile nature
of modern medicine and its appalling lack of imaginative ways to defeat disease.
I have two afterthoughts about this column. The first pertains to consumer
groups more concerned with the risk of adverse effects in clinical trials than
on promotion of clinical trials to accelerate medical discoveries. These groups
have been prominent since the 1960s. They have consistently supported the most
extensive FDA regulation of virtually any substance that has a medical use.
They have staked out a claim to represent the public on FDA matters, and Congress
and the media have accepted their claim.
Congressional proponents of a tougher FDA have invited and continue to invite
the leaders of these organizations to testify at hearings on bills to strengthen
the FDA's hand in the approval process for new drugs and medical devices,
and on bills that would authorize the FDA to regulate nutritional substances
as restrictively as this agency does new drug treatments. When serious adverse
effects occur unexpectedly in clinical trials or when a new test of a nutritional
supplement previously thought safe surprisingly appears to show the opposite,
the media quote the heads of these organizations, who invariably call for tighter
FDA control of the clinical trial process or for strict FDA regulation of supplements.
But these consumer groups represent only certain segments of the public, and
on occasion, they may even represent less than half of the public on FDA policy
issues. Case in point: passage of the Dietary Supplement Health and Education
Act, 1994 (DSHEA '94). Letters from citizen groups around the US supporting
lobbying efforts by supplement industry coalitions cascaded into the offices
of Senators and Representatives, sweeping away opposition to DSHEA '94.
Readers curious about the campaign to pass DSHEA '94 should get a copy
of my interview with attorney Antonio Martinez, II, for the background and
specifics of that campaign (Townsend Letter,
July 2007). Here, I'll note that the sector of the public supporting
DSHEA '94 included a host of
Americans who take nutritional supplements, and the "citizen" groups
they formed to back this legislation were mainly reacting to a belief that
the FDA intended to remove many dietary supplements from health food stores
and other over-the-counter sources.
Once DSHEA '94 became law, these citizen support organizations fell
silent for the most part. No item on their political agenda had ever
issue at the center of Dr. DeFelice's thinking – speeding up medical
discovery through promotion of clinical research. The majority of these groups,
I feel, polled on Dr. DeFelice's NREA initiative, would shy away, fearing
that the process it provides for approval of nutraceutical claims could be
twisted by the FDA into a means of limiting access to supplements. That the
NREA, if enacted, would greatly multiply data on the effectiveness of nutraceuticals
(data that's lacking, according to Dr. DeFelice) appears to be of secondary
interest for these groups; what matters primarily is over-the-counter availability
My second afterthought touches on groups cited by Dr. DeFelice (in
my October 2007 interview with him) who represent patients and families
diseases resistant to available treatment. Why are they "blind" to
the importance of clinical research in speeding up discovery of better treatments
for such conditions? Dr. DeFelice contends that these groups don't do
their homework regarding the plus side of clinical research. I'll add
to his contention that physicians who serve as expert consultants to these
organizations often have a hard time comprehending – and accepting – clinical
research that doesn't fit "inside the box." Patients and
families belonging to these organizations tend to follow the experts.
In my second interview with Dr. DeFelice, on Doctornauts and the rape
of patients' rights (Townsend Letter, October 2007), he
tells a story about his attempts to persuade
oncologists specializing in ovarian cancer to administer the nutraceutical
carnitine together with the cancer drug Adriamycin. Adriamycin's ability
to kill cancer cells is offset by its cardiotoxicity. Carnitine reduces the
drug's cardiotoxicity, so combining it with Adriamycin would enable doctors
to give stronger doses of the drug, increasing its destruction of cancer cells.
He couldn't budge the oncologists, couldn't even get them to ask
their patients to agree to try the combination. Dr. DeFelice ended this story
by saying that if his Doctornaut initiative had been instituted 30 years ago,
when the combination was first shown to be effective, some physicians with
ovarian cancer would have volunteered to test it, and subsequently, many women
who succumbed to this cancer could have survived.