Thursday, December 13, 2007

The Helsinki Declaration

To some the story of the inexpensive, effective and safe anticancer drug hydrazine sulfate and its suppression by the National Cancer Institute (NCI)--this country's top federal cancer agency--presented in this blog-series, may remind one of the "legendary carburetor" of the 1940s and 1950s, which reportedly got 100 miles to the gallon but which the Detroit automobile manufacturers were burying because of the interests of the oil companies. Is hydrazine sulfate in the same boat as the magic carburetor--that it is as ineffective as the carburetor is non-existent, as the NCI and the auto makers affirm? Or is hydrazine sulfate different--that it is a remarkably effective, safe and extremely inexpensive drug, which is being put down by the NCI only in the interest of the pharmaceutical companies? "Yeah...sure." The Helsinki Declaration presents continuing evidence that in the case of hydrazine sulfate, the drug is real, the controlled clinical trials that have demonstrated its safety and effectiveness are real, and the NCI's power to suppress or approve any medication it wishes--over and above the authority of the Helsinki Declaration--is real.

How many of you have heard of the Helsinki Declaration? Sounds like an international treaty, you might think. Well it is...something like the Geneva Convention. But unlike the Geneva Convention, which is largely ineffective, the Helsinki Declaration, pertaining to the safe and allowable conduct of medical studies involving human beings, is extremely effective and underlies all experimental human research. The Declaration in fact requires all published human studies to state: "This study was conducted in conformity to the Helsinki Declaration."

The Helsinki Declaration is a multinational ratification of principles governing human biomedical research studies, first adopted by the World Medical Assembly, in Helsinki, Finland, June 1964, and thereupon amended by this organization in 1975, 1983 and 1989. This document, to which the United States is a principal signatory, lies at the very heart of internationally accepted standards for biomedical research.

The Declaration, an outgrowth of the Nuremberg Trials (Doctors Trial) following World War II which uncovered in detail the hideous human medical "experiments" inflicted on helpless human beings by the Nazis, was put in place to guarantee that no harmful procedures be used in patients undergoing experimental medical treatment--and is at the very core of all clinical trials and informed consent.

Principle 1 of this Declaration affirms: "Biomedical research involving human subjects must conform to generally accepted scientific principles and...[be] based on a thorough knowledge of the scientific literature." Perhaps most important of generally accepted scientific principles in the conduct of human biomedical research is that no incompatible agents (medications) be used in a drug trial. Why? Because such use can result in the grave illness--or death--of a patient, as well as can cause a negative drug study. For this reason use of an incompatible agent--or one even suspected of incompatibility--is virtually unknown in human biomedical testing.

Principle 1 of the Helsinki Declaration also requires experimental studies to be based on a "thorough knowledge of the scientific literature." In the case of NCI's sponsoring of the hydrazine sulfate studies, is it possible that the NCI did not know hydrazine sulfate was an MAO inhibitor, as so described throughout the medical literature? Is it possible that the scientists responsible for the hydrazine sulfate sponsored studies were not conversant with even the most basic pharmacology textbooks, which for three decades prior to these studies had indicated hydrazine sulfate to be an "irreversible"--powerful--MAO inhibitor? Is it possible that the sponsors of these studies--administrators and scientists--were unfamiliar with the multiple warnings throughout the scientific literature that use of tranquilizers, barbiturates and alcohol was incompatible with MAO inhibitors such as hydrazine sulfate and would result in "sicker patients" and negative studies? The NCI's PDQ publication of October 25, 1999, suggests that NCI was well aware hydrazine sulfate was an MAO inhibitor.

In view of the Helsinki Declaration's prohibition of biomedical studies not in conformity with internationally accepted standards, why did NCI use incompatible agents with a test drug in the sponsored trials of hydrazine sulfate? As indicated in our previous blog, only two reasons underlie such usage: incompetence and deliberateness.

Given the level of scientific expertise available to the NCI, it is hardly likely that NCI did not know hydrazine sulfate was an MAO inhibitor and therefore that incompetence was the reason for NCI's going ahead with its sponsored studies. Was it deliberateness? Knowing full well an incompatible agent in the presence of a test drug acts to produce a negative study, did NCI have reason to deliberately go ahead with its sponsored studies? NCI's twenty-five-year-long adversarial orientation--if not antipathy--to hydrazine sulfate ("We throw away better drugs than hydrazine sulfate"), may well speak to this question.

But NCI's violation of the Helsinki Declaration was not limited solely to Principle 1. Principle 8 of the Declaration states: "Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication." Principle 8 specifies that the NCI-sponsored studies--in their failure to conform to Principle 1 (accepted scientific standards)--should never have been presented for publication in the first place, no less arranged by NCI for sequential publication in the same journal issue (Journal of Clinical Oncology, June 1994). NCI further violated Principle 8 by publishing the results of its studies on the Internet for the public --while at the same time juxtaposing to them false statements on hydrazine sulfate: "There is only limited evidence from animal studies [i.e., no human studies] that hydrazine sulfate has anticancer activity....Hydrazine sulfate has shown no anticancer activity in randomized clinical trials [the "gold-standard" of clinical trials]." (Whereas the truth was that up to the time of the NCI Internet publication, there were ten controlled human studies published in the peer-reviewed medical literature, all known to the NCI since 1975, all showing anticancer activity; and of five Harbor-UCLA studies published in the peer-reviewed medical literature, four were randomized clinical trials, all showing anticancer activity and all known to the NCI.)

The Helsinki Declaration is the international standard for the performance and acceptance of human experimental biomedical research. It has been ratified literally by all nations which participate in human clinical testing, including the United States.

However, in its sponsored studies of hydrazine sulfate the NCI seems to have lost sight of the Helsinki Declaration, of the fact that the United States was a sponsoring signatory to this Declaration, and that this Declaration in regard to human biomedical experimental research is the international "law of the land." This Declaration in fact requires all published human biomedical research to contain a statement of compliance with principles enunciated in the Declaration. But nowhere in the research protocols or in the published NCI-sponsored trials of hydrazine sulfate is there such a statement.

The Helsinki Declaration asserts that by virtue of use of an incompatible medication in the presence of a test drug, a study is in violation of internationally accepted standards of medical conduct. The Helsinki Declaration states that the NCI studies, in violation of Principle 1 and Principle 8, thus have no ethical, scientific or legal standing among the international medical community, that in effect the NCI had no ethical or scientific right to engage in its sponsored studies of hydrazine sulfate as performed, or be a party to their publication.

By NCI's ongoing Internet publication and publicity of the results of its non-conformant hydrazine sulfate studies, by its lack of compliance with Helsinki Declaration directives in these studies, NCI on its part indicates that it can defy any international agreement which this country endorses--to which the United States has given its name--that when it is in its interests, NCI alone is the 'law of the land.'

Monday, November 26, 2007

"Do not use with MAO inhibitors." The NCI acts criminally in its investigation of hydrazine sulfate.

How many times have you heard--usually recited quickly--at the end of a pharmaceutical ad on television, "Do not use this medication with an MAO inhibitor." What's an MAO inhibitor? And why shouldn't the advertised medication be used with it? Because the two together can harm you. Because the two together can even kill you.

An MAO inhibitor is an inhibitor of the enzyme MonoAmineOxidase. Monoamines, such as dopa, play key roles in neurotransmission, and the enzyme MAO keeps these neurotransmitters from accumulating in the brain. MAO inhibitors (MAOIs), on the other hand, can cause an accumulation of these substances in the brain, which accounts for their therapeutic--i.e., anti-depressive--action. But MAOIs can also amplify the side effects of some medications and cause these medications to become a clinical hazard, in some instances resulting in severe illness and even death.

Thus the effect of mixing an incompatible medication with an MAOI can be very dangerous to a patient, and if the MAOI in question also has a therapeutic function, mixture of an incompatible agent (medication) can also destroy the therapeutic action of the MAOI; if the MAOI is being used as a test medication in a drug study, mixture of an incompatible agent can result in a negative study.

Pharmaceutical companies therefore do not wish you to use any of their products in the presence of an MAOI--just in case their products happen to be incompatible with MAOIs--or just in case you happen to be in a drug study, or on a drug protocol, with one of their products. These companies simply don't want you to end up incapacitated or a sure death.

Many of you know I--and the Syracuse Cancer Research Institute--am the developer of the anticancer drug hydrazine sulfate. The drug that competently performed controlled clinical trials have shown to be safe and effective in many different types and in all stages of cancer. And that the National Cancer Institute (NCI)--this country's top federal cancer treatment, investigative and funding agency--has found to be ineffective in its sponsored studies. But did you also know hydrazine sulfate is an MAO inhibitor? A powerful--i.e., irreversible--MAOI?

More importantly, did the NCI know that hydrazine sulfate was an MAO inhibitor--a powerful one? In an investigation of the NCI-sponsored studies of hydrazine sulfate ordered by Congress, the NCI claimed--over and over again--that hydrazine sulfate was not an MAOI (inhibitor). Even though pharmacology textbooks over the last three decades indicated it was a potent MAO inhibitor. Even though author of the prominent textbook on drug interactions, A Primer of Drug Action, Robert M. Julien, M.D., Ph.D., an acknowledged expert in the field of drug interactions, indicated hydrazine sulfate was "an irreversible MAO inhibitor" (Dr. Julien's emphasis). Even though NCI received a faxed letter from its Russian counterparts, in response to a specific NCI inquiry, "Hydrazine sulfate is a modulator of biologic reaction and functions as an inhibitor of monoamine oxidase [MAO]." Even though studies throughout the medical literature identified hydrazine sulfate as a specific "mitochondrial MAO" inhibitor.

What was the reason the NCI denied to Congressional investigators that hydrazine sulfate was an MAO inhibitor--despite overwhelming evidence that it was? Because in its sponsored studies of hydrazine sulfate--the only controlled trials to ever show hydrazine sulfate was ineffective--the NCI used tranquilizers, sleeping pills (barbiturates), alcohol--all of which are known to be incompatible with MAO inhibitors. Acknowledgment by the NCI of MAO inhibition by hydrazine sulfate would be tantamount to an admission by NCI that NCI wittingly or unwittingly used known incompatible agents--negative bias factors--in its hydrazine sulfate studies, and thus by definition its studies were intrinsically flawed.

While NCI officials were vigorously denying that hydrazine sulfate could be an MAO inhibitor--challenging established scientific fact--did they really know all along that it was? Was NCI's use of incompatible agents witting or unwitting?

It must be considered that the NCI--as the world's leading cancer agency--had the top expertise available to it and that experts in the field could hardly not advise NCI that hydrazine sulfate was a known and acknowledged MAO inhibitor and that tranquilizers, barbiturates and alcohol could not be used with it. Thus, incompetence could not have been the reason for NCI's use of incompatible agents. But there are only two reasons that investigators would use a test drug in the presence of an incompatible agent: incompetence or deliberateness.

Deliberateness? Did NCI know all along that hydrazine sulfate was an MAO inhibitor? Four years after the Congressionally-mandated investigation of NCI's sponsored studies of hydrazine sulfate had safely passed, NCI issued a multipage newsletter on complementary and alternative medicine, (PDQ Complementary/Alternative Medicine, Hydrazine Sulfate, National Cancer Institute, November 25, 1999), discussing hydrazine sulfate. Its opening line was: "Hydrazine sulfate is an MAO inhibitor..."

Did NCI know all along that hydrazine sulfate was an MAO inhibitor? NCI's level of expertise available to it and its PDQ publication would indicate--beyond the shadow of a doubt--that it knew from the beginning that hydrazine sulfate was an MAO inhibitor. Yet it went ahead and used tranquilizers, barbiturates and alcohol freely with it, knowing full well that the medical literature identified these substances as constituting a "clinical hazard" with MAO inhibitors--capable of making test patients ill or worse, capable of bringing down a (causing a negative) study. In violation of a multinational agreement on the conduct of experimental medical studies. And nowhere mentioned in the informed consent forms patients were required to understand and sign prior to being enrolled in the studies.

Deliberately causing a negative study? Deliberately causing illness and mortality in test patients? Is it possible the NCI would use known incompatible agents with an MAO inhbitor? Is it possible that the NCI did not know hydrazine sulfate was an MAO inhibitor?

Is it possible that the federal government--the NCI--would act to defeat a cancer drug it knows--or suspects--to be safe and effective?

To the extent that the captains of our cancer leadership knew and understood that hydrazine sulfate was an MAO inhibitor--knew and understood that use of tranquilizers, barbiturates and alcohol with it would bring down patients and the study--yet went ahead anyway with this study design-- it seems to me that rather than "disinform" the American people that hydrazine sulfate is useless and thus engage in the worst type of medical untruth imaginable-- they must criminally answer for the pain, suffering and premature deaths they have knowingly and needlessly inflicted, and continue to inflict, on spouses, children, grandparents, uncles and aunts, friends, loved ones, your neighbors--and mine--the world over.

Wednesday, October 17, 2007

Annual report to the nation on the status of cancer

"Cancer Death Rates Plunge." This encouraging news appeared as a front-page, four-column headline in a recent edition of the Syracuse, New York daily newspaper. This headline was repeated in newspapers around the country, in newswire services, in nationwide network television newscasts and on the Internet. Many media emphasized that it was screening tests, public health and preventive measures, not necessarily advances in curative treatments, that resulted in a decrease of both cancer incidence rates and cancer death rates.

This was an annual report to the nation, compiled by the Center for Disease Control and the American Cancer Society. It was not a study published in a journal, subject to peer-review in the usual sense. It is described as a "U.S. government work" put together by 15 authors, one of whom is listed as being "under contract with the Indian Health Service for a portion of her work on this manuscript."

Through cancer registry programs and associations, SEER (Surveillance, Epidemiology, End Results) compilations, NCI (National Cancer Institute) and ACS (American Cancer Society) programs it was estimated that cancer incidence data for this report was available for "up to 82% of the U.S. population."

The report specifies that overall cancer death rates declined 1% from 2002 through 2004, compared to 1993 through 2002 (i.e., 2.1% compared to 1.1%). Breast cancer incidence (therefore death rate) decreased 3.5% a year in 2002-2004, but this drop was indicated to be chiefly due to a discontinuance by women of hormonal replacement therapy (HRT)--which was found to actually cause breast camcer--not to any treatment advance, as discussed in a previous blog.

A decrease in colorectal cancer for both men and women was largely attributed to screening tests, such as colonoscopy and stool guaiac examinations. At colonoscopy benign polyps--which can later become cancer--are easily excised and thus cancer incidence from this disease is
decreased; frank cancer found at colonscopy is usually found at an earlier--and therefore more treatable--stage than would normally be the case, and thus this examination can also lead to a decrease in death rate. Stool guaiac tests are also simple tests to detect occult blood in the stool, which could be coming from a cancerous tumor in the colon; these tests, too, lead to earlier diagnosis which in turn promotes a decrease in the death rate.

Favorable trends in the incidence and mortality from lung cancer in men were largely attributed to "enhanced tobacco control" (i.e., men giving up smoking). In women the death rate from lung cancer has overtaken that of breast cancer in recent years. Incidence and death rates from this cancer in women, unlike men, did not decrease during the 2002-2004 period; the incidence remained flat and death rates actually increased but at a slower rate than in previous years.

This report constitutes truly encouraging news. It means that cancer incidence and death rates can be controlled--by preventive measures, such as women's discontinuance of HRT and avoidance of the use of tobacco products, both of which are causative or contributive agents for breast, lung and other cancers. Also, use of screening tests, such as those employed for colorectal cancer, can result in a marked decrease in cancer incidence/mortality in various organ systems.

The negative side of this report, however--what this report also states--is that very little, if any, of the improvements in cancer incidence/death rates during this period is due to the advancement of cancer therapy per se. Once established in the body, major organ cancers--colorectal, pancreatic, lung, brain, breast and others--are extremely difficult to cure. The report, by omission, calls attenion to this deficit in innovative therapies which may significantly and beneficially alter the course of established cancers. What in fact this report silently screams is the need for new ideas, the need to implement old ideas that have not been adequately explored and the need to move away from the centralization of power and money as the determinants of cancer thought and therapy.

Tuesday, October 2, 2007

Don't bet on this cancer communique

In our initial commentary it was stated that this blog will be devoted to truth in medicine and exposing misrepresentations wherever they exist.

Some months ago almost every cancer doctor in the Syracuse, New York area--11 oncologists in a group private practice and others in an academic setting--jointly published a letter-to-the-editor in The (Syracuse) Post-Standard calling attention to the pending cancellation by the National Cancer Institute--the federal government--of a nationwide study of drugs "that could reduce breast cancer incidence by more than 50 to 70 percent."

What? Prevent up to 70% of all breast cancer? But this is astonishing! If there were any drug or drugs or treatment that could prevent even one-tenth that amount of breast cancer--5% to 7%--that would be considered a major victory!! But 50% to 70%? And the National Cancer Institute (NCI) itself--this country's and the world's bastion of defense against cancer--cancelling a study that could virtually wipe out breast cancer? That doesn't even make sense.

Lest you think this was an isolated letter in a single newspaper, similar letters appeared in newpapers throughout the country, submitted by oncologists in all locales. These were spurred by chairman and principal investigator Norman Wolmark, M.D., of the National Surgical Adjuvant Breast and Bowel Project (NSABP), which had charge of this proposed study. Dr. Wolmark stated, "We believe [this study] has the potential to prevent the incidence of breast cancer by up to 70%," and any decision not to go ahead with this study could wreak havoc with the nation's ability to test new drugs.

The name of the drug study was "P4-STELLAR"--"P-4" for short--which sought to test two drugs, letrozole and raloxifene. The letter detailed that although the proposed study, which "could ultimately prevent thousands of cases of breast cancer," underwent a "rigorous review process" at the NCI, including "seven different approvals" by various NCI committees, "the NCI's director abruptly halted activation of the [P-4] trial and now continues to delay trial commencement."

The doctors stress that "200,000 American women will be diagnosed" with breast cancer this year and "more than 40,000 will lose their lives to this disease." It urges women to contact the NCI, to demand that this study be activated. "Time is of the essence," the letter urges. "We must persuade the NCI to release funding for this critically important [drug] trial...or risk losing...this opportunity to dramatically reduce the toll of breast cancer....forever." Thousands of women, taking heed of the oncologists' letters, responded by writing letters of their own to the NCI urging that the study be activated.

But the NCI--apparently not in agrement with the letter writers' exhortation that the P-4 study could "dramatically reduce the toll of breast cancer"--did indeed cancel this $130 million clinical study, citing its exessive cost ("there are other priorities that are very [more] important," an advisory panelist stated), as well as "troubling complications."

The study would have entered 12,000 women who would have received either letrozole or raloxifene, but not both together. Each drug acts to target--to reduce--the production of estrogen, which promotes the growth of cancer cells. However, each of these drugs had already been tested individually and many of their effects were already known. For example, raloxifene had already been tested in 37,000 postmenopausal women in the STAR (Study of Tamoxifen and Raloxifene), RUTH (Raloxifene Use for the Heart), MORE (Multiple Outcome of Raloxifene Evaluation) and CORE (Continuing Outcome Relevant to Evista [Raloxifene]) trials. Tamoxifen, an anticancer drug used for many years in breast cancer, and raloxifene were compared in a large trial and found to have about the same level of effectiveness in preventing cancer. Letrozole, also, had undergone clinical testing in thousands of women--in comparison to the anticancer effectiveness of tamoxifen (BIG 1-98 Trial) and by itself. It was found in one study that letrozole was only slightly more effective than tamoxifen.

In its cancellation letter of June 19, 2007 to the study's principal investigators at the University of Pittsburgh (as reported one day later in The Washington Post), the NCI cited the "relatively small number of women--3 or 4 out of 100--who benefit from [the proposed two test drugs]."

Only 3 or 4 out of 100? That's nowhere near "50% to 70%." That's nowhere even near 5%. What about the potential "virtual obliteration" of breast cancer, as indicated in the NSABP chairman's statement and as set forth in the doctors' letters?

The NCI letter of June 19 also cited the "troubling complications of the two cancer prevention drugs [letrozole and raloxifene] in its cancellation decision. "The danger of introducing these drugs," the letter stated, "with their many side effects [sudden chest pain, coughing up of blood, sudden change or loss of vision, vomiting, diarrhea, breast and stomach pain, headache, vaginal bleeding and irritation, dizziness, etc.] outweighs their potential until we are better able to determine who will benefit from [them]."

Could it be that the chairman of the NSABP and the letter writers did not know that the P-4 trial's two drugs, raloxifene and letrozole, had no hope of preventing--could not possibly prevent--"50 to 70 percent" of breast cancer? Could it be that these individuals did not know that these two drugs had many and significant side effects and their introduction into the general population constituted a potential hazard until it could be determined who might benefit from them?

But the chairman of the NSABP and the letter writers were privy to the same information--the same prior study results--as the director of the NCI and his panel of advisors. They well knew that there wasn't a chance that the two test drugs could prevent '50 to 70 percent' of breast cancer--or anywhere near these figures. Then what was their motivation in stirring up the hopes of the American people that so great a proportion of breast cancer could be prevented? What was their motivation in mobilizing the women of America to contact the NCI and demand that the P-4 trial be activated?

Dr. Wolmark, the NSABP's chairman, provides an answer. "Due to the cancellation of this trial," he writes, "the infrastructure of more than 500 trial centers we have built up over the last 15 years will cease to exist."

500 trial centers? These are the test sites where oncologists, members of the NSABP, test drugs on cancer patients. Dr. Wolmark's remarks in essence state that activation of the $130 million P-4 study guarantees that the NSABP nationwide network of trial centers--established over the last 15 years and characterized as of "importance" to the "advancement of science"--will be maintained. "The National Surgical Adjuvant Breast and Bowel Project has been successfully conducting multi-center breast cancer prevention trials since 1992, advancing the knowledge base and testing new prevention options through its clinical trials," the doctors' letter in The Post-Standard reiterates. "We must persuade the NCI to release funding for this critically important P-4 trial."

Critically important? It can't be critically important to the prevention of 50% to 70% of breast cancer--both the NSABP chairman and the doctors know that's an impossibility. Clearly, it is critically important to the maintenance of the NSABP's trial centers. That they don't melt away. That these testing mills--processing millions of dollars annually--remain functioning. That these money machines keep on rolling.

And this is the real reason for the doctors' letters. The real reason for mobilizing the public to pressure the NCI into "activating" the P-4 study. The crass motivation for making shabby use of millions of American women, raising their hopes and medical aspirations that the disease of breast cancer might be largely silenced forever by this P-4 study, only to guarantee the maintenance of the NSABP's trial centers--its "centers of excellence"--that have produced no treatments that have significantly altered the course of breast or bowel cancer since their inception.

This commentary, as stated previously, is devoted to truth in medicine and exposing misrepresntations wherever they exist. The shameful orchestration of power by the NSABP and its affiliates, presented here, illustrates perhaps most indelibly the degree to which the medical profession is capable of a lack of truth. How--falsely portraying the therapeutic potentials of a study--elements of the cancer establishment literally wipe their behinds with the public.

Tuesday, September 4, 2007

Is bigger better? The evolution of large-scale cancer research organizations

In the early summer of 1956, a newly graduated M.D. from the State University of New York Upstate College of Medicine at Syracuse, I found myself on the campus of Berkeley, California, as a post-doctoral fellow in the Department of Physiological Chemistry at the University of California School of Medicine. My two-year fellowship, which I was just beginning, shared my time between basic science on the Berkeley campus and medicine across the bay in San Francisco.

Shortly after my arrival my boss, Dr. David M. Greenberg, a celebrated biochemist and head of the department, informed me that he had arranged for me to attend the annual scientific meetings of the American Association for Cancer Research (AACR), to take place in Chicago.

That first meeting of the AACR to which I was exposed made an indelible impression on me. At the time, there were only several hundred members of the AACR worldwide, and it was difficult to gain elected membership.

At that meeting I was to hear the first presentation of Dr. Charles Heidelberger, who as a medical biochemist had had the brilliant idea of substituting a fluorine atom for a hydrogen atom on the 5-position of the nucleic acid base uracil--important to rapidly dividing cancer tissue--with the thought that this new molecule (drug) would 'gum up' cancer cells' ability to multiply, with the result of a true chemotherapeutic--anticancer--effect.

The new molecule was called 5-fluorouracil or 5-FU for short. Dr. Heidelberger synthesized this molecule himself, tested it on cancer-bearing animals himself and then tested it on humans himself. Of course, he had assistants and helpers in these endeavors, but it was his concepts alone that led to this scientific and medical breakthrough. Such was Dr. Heidelberger's erudition and creativity, that 5-FU has remained a mainstay in cancer chemotherapy--for colon cancer, ovarian cancer, breast cancer and many other cancers--for the last 50 years.

Dr. Heidelberger's published papers bore his name exclusively as the innovator of his therapy. At the time it was common in medical science to see published papers (studies) with one author alone--or perhaps two or three. Papers with single--or few--authors signified original research. They were the product usually of one person's brain. One person's creativity. Years later, in 1969, when I was elected to membership in the AACR, it was still part of the membership requirements that an applicant show original work by at least two different single-authored papers published in the peer-reviewed scientific literature relating to cancer, as well as have the written endorsements of several well-established senior investigators, known for their own original research. At that time single-authored papers--and scientific innovation in general--proceeded at a brisk pace, were actually common, especially in the cancer field.

Today, in the cancer journals--in the peer-reviewed medical literature as a whole--it is rare to see a single-authored paper. Or a paper with two authors, even three. Instead, in the most prestigious, leading journals it is common to see a paper with 20--25--even 30 authors! What? So many brains 'collaborating' on a single project? Is there a new idea here? Whose? Is there a Charles Heidelberger buried in these lists of investigators?

Concomitant with the multiple-authorship of published papers is the slowdown in cancer treatment innovation. No more brilliant innovations. No more wrenching from nature its deeply buried secrets. No more new directions. No more products of a single brain. One that has apprehended something no other brain has thought of.

Today we have the team effort. The team project. Perhaps not with the payoff that a briliant new idea can bring, but with an improvement--hopefully. A bettering of an understanding of science--and perhaps a more modest payoff therein.

And a lot of different authors get their names on a paper. You know--publish or perish? And a lot of different 'important' investigators get their names on many papers. How do you think department heads or their equivalents get their names on--publish--'100 papers' in a single year (yes, that happens--one investigator, reputedly, on 300 papers in one year)? If I were engaged in original research involving six different projects, I would find it a chore writing 6 different, adequate and complete papers for publication in one year--maybe 2 years. But some department heads and senior investigators simply tack their names on every paper sent out in their department for publication or by their junior investigators, justifying their doing so by reading through and commenting on their manuscripts before publication. In some departments a junior investigator would not dare send out a paper for publication without listing his/her boss as a co-author. (Guess who gets the money?)

But there is a reason for all this. A 'structure' which makes multiple-authored publications both possible and necessary.

In the mid-1950s, when I first attended the meetings of the AACR and heard the Heidelberger paper, as previously stated there were some 300-to-400 members of that organization. Today the membership is 24,000! No longer are the requirements for active membership proof of original research, but only 2 years' experience doing scientific work resulting in articles published in the peer-reviewed medical literature. Instead of the multiple, written letters of recommendation of several well-established, senior investigators, what is needed now are merely the signatures of "two nominators" on the membership application itself. And rather than scientists and clinicians only, active membership is now also open to 'administrators' and 'educators' in the cancer field. Also the application for membership must be accompanied by a fee, currently $255.

24,000. That's quite a bunch! With the diluted membership requirements one wonders whether all one has to do is appear in an open doorway of a basic research laboratory, and poof!--you're in--as long as you pay the fee. Of course, this is a simplification, but one wonders exactly how dilute the qualifications are today for becoming 1 of 24,000 cancer "experts."

And it is not the AACR alone whose ranks have swelled from earlier, more modest--but creatively vibrant--beginnings. It is the AACR's sister organization, the American Society of Clinical Oncology (ASCO), charged with investigating questions in clinical cancer medicine, whose ranks have become similarly enlarged (25,000 members at present).

The AACR and ASCO, as well as like research/clinical organizations worldwide, have become businesses. One look at their structure--their arms of research, clinical medicine, journal sponsorship, even foundations (to which members and readers of their journals are invited and exhorted to contribute monies, trusts, legacies, etc.)--and this aspect of their operations is readily apparent.

Have these hordes of researchers, these armies of researchers--the 20,000+ membership of these organizations--acted to dilute the 'brilliance quotient' when membership was in the several hundreds, composed of provably outstanding scientific minds whose 'track records' for original scientific thought--even as young investigators--was abundantly apparent?

When organizations numbered in the hundreds in membership, there were in general adequate funds available from cancer funding sources. If a "Manhattan Project" developed, requiring markedly additional funds, these materialized easily. But with research organizations numbering 20,000 or more in membership, a wholly different complexion developed.

Research salaries are paid by faculty or institution salaries or research grants, but whether grants or salaries, by far most of these funds derive from the U.S. National Cancer Institute, as appropriated directly from Congress in each budget year. This annual appropriation of the NCI budget by Congress in general limits the amount of cancer funds available each year.

Consider the funding dynamics of a cancer research organization of 20,000 members. Each member--researcher, administrator, educator--receives a salary, research project grant funds, travel allowances, in some cases institutional overhead, totaling well over $100,000 on average (in some instances of senior investigators, hundreds of thousands). That's a minimum of $2.4 billion annually. That doesn't even include the billions spent each year on institutional grants and contracts, cancer centers, large-scale studies and special multicentric (sometimes multinational) epidemiologic projects, NCI operations, and the like. The NCI budget as appropriated by Congress for 2007 only totals $4.75 billion--which is more than oversubscribed. Thus large-scale cancer research organizations contribute significantly to exhausting the reservoir of available cancer funds.

Organizations such as the AACR, in order to support a membership of 24,000, have had to grow from a small, mainly professional group to an immense, complex and powerful business enterprise--its business interests at times seemingly eclipsing its research operations. Frequently this organization importunes its membership--all 24,000 of them--to contact Congress in favor of more cancer appropriations--or for passage of certain legislation favorable to increased cancer funding. The leadership of these organizations stresses to Congress that they and their membership--all 24,000--speak with one voice: that the more cancer monies, the more new ideas to be explored. But many in these organizations do not believe as the "one voice" of its leadership. Because with each increase in the annual cancer (NCI) budget mandated by Congress, the reality is that a smaller percentage of approved research grants has been funded.

Is more better? Are cancer research organizations with membership in excess of 20,000 better equipped to deal with the complex problems in medicine today than in earlier times when membership was much smaller? On the positive side of this question, team efforts are definitely needed to solve the problem, for example, of the human genome and the genetic basis of disease, which can lead to many treatment advances and a new understanding of disease processes. On the other side, before the advent of large-scale research organizations, it was, for example, a few individual, brilliant, competing investigators--Watson, Krick, Franklin--who unraveled the double-helix structure of DNA and thus figured significantly in the important scientific and clinical benefits to result from this discovery. And working by himself, a lone researcher--Nobel prize winner Kary Mullis-- conceived of the polymerase chain reaction, which literally opened the door of the entire field of genetics to researchers, scientists, clinicians, pathologists and others the world over.

One cannot ignore the fact that in cancer medicine particularly, with the advent of large-scale organizations, important treatment advances have slowed considerably. One wonders: Are the armies of researchers in these organizations--who do not have to show proof of capacity for original research--creating funding or other shortages for the truly gifted, for young investigators whose ideas may be "outside" current cancer concepts--whose scientific thinking may harbor the truly great discoveries to come?

Is bigger better? Or is big brother somehow, invisibly, paradoxically, acting to smother--to exclude from opportunity--the most gifted of its ranks?

Thursday, August 9, 2007

Hydrazine sulfate, does it work--or not?

Many of you know me as the developer--the "inventor"--of the anticancer drug hydrazine sulftate, a drug that combats cancer cachexia, the weight loss and debilitation seen in advancing cancer, induces tumor stabilization and regression and promotes increased survival time and quality of life. There has been much pro and con talk on the internet about this drug. The question is--does it work or not?

On one side of the line is the NCI--the U.S. National Cancer Institute. The NCI says its studies--published in a well regarded, peer-reviewed cancer journal--show hydrazine sulfate is ineffective. On the other side, Harbor-UCLA Medical Center and the N. N. Petrov Research Institute of Oncology (St. Petersburg) say their studies--published in equally prestigious, peer-reviewed cancer journals--show that this drug is safe and effective in many different types of cancer and at all stages.

What else does the NCI say about hydrazine sulfate?

NCI has not seen fit to confine its point of view about hydrazine sulfate to cancer journals, but has gone directly to the American (and world) public. It currently states on the internet:

"There is only limited evidence from animal studies that hydrazine sulfate has anticancer activity."

The clear meaning of this statement is there have been no human studies that have documented the anticancer activity of this drug, and its proponents are hanging on to slim evidence generated solely from animal studies--and who should know better than this nation's top cancer agency?

But in actual fact there have been ten (10) controlled human studies of hydrazine sulfate, all showing anticancer activity, all known to the NCI since 1975. A sampling of these studies follows:

"A definite stabilizing effect exerted against tumor growth was noted in 21% of patients. Antitumor effects were observed in a total of 19 of 95 (20%) of patients. The symptomatic [anti-cachexia] action of the drug...was expressed in appreciable improvement of general status and appetite, reduction of severe weakness characteristic of the pretreatment period, reduction or complete elimination of pain." (Gershanovich, et al., Cancer Treatment Reports 60:933-936, 1976.)

"This experience with hydrazine sulfate in an advanced cancer population points to a...role for this drug in maintaining weight in patients with cancer cachexia." (Chlebowski, et al., Cancer 59:406-410, 1987.)

"Our results suggest that hydrazine sulfate can favorably influence the abnormal metabolism associated with weight loss in patients with cancer." "The proposal that cancer patient survival may be increased by improving host metabolism represents a fundamentally new direction in cancer management." (Chlebowski, et al., Cancer Research 44:857-861, 1984; Chlebowski, et al., Journal of Clinical Oncology 8:9-15, 1990.)

"Hydrazine sulfate resulted in tumor stabilization and regression in 71% of 38 patients with glioblastoma [brain cancer]....Hydrazine sulfate prolongs patient survival and improves quality of life in this category of cancer patients." (Filov, et al., Voprosy Onkologii 40:332-336, 1994.)

"Treatment with hydrazine sulfate resulted in complete tumor regression in 6 of 740 patients (0.8%), partial [>50%] tumor regression in 25 patients (3.4%), up to 25% tumor regression in 47 of the patients (6.4%), tumor stabilization in an additional 263 patients (35.5%) and accompanying symptomatic [anti-cachexia] improvements in 344 (46.5%) of the patients." (Filov, et al., Investigational New Drugs 13:89-97, 1995.)

No human studies? No anticancer activity?

But the NCI wanted to make sure doctors got the message of no valid anticancer activity in human studies, so they added:

"Hydrazine sulfate has shown no anticancer activity in randomized clinical trials."

Randomized clinical trials--better known as RCTs--are the "gold-standard" of clinical trials. In actual fact, 4 out of the 5 Harbor-UCLA trials, published in the peer-reviewed medical literature, were randomized clinical trials, all of which showed anticancer activity, and all of which were known to the NCI. A sampling illustrates:

"Using a randomized, placebo-controlled, double-blind [study] design...hydrazine sulfate treatment resulted in significant improvement in the abnormal glucose metabolism [i.e., cancer cachexia] seen in patients with weight loss and cancer." (Chlebowski, et al., Cancer Research 44:857-861, 1984.)

"These data demonstrate an association between...hydrazine sulfate administration and body weight maintenance [i.e., anti-cachexia effect] in patients with cancer." (Chlebowski, et al., Cancer 59:406-410, 1987.)

"Hydrazine sulfate [combats] subnormal protein synthesis in skeletal muscle, believed to be the primary cause of loss of muscle mass and weight loss [i.e., cachexia] in lung cancer patients." (Tayek, et al., The Lancet 2:241-244, 1987.)

"In a randomized clinical trial...a statistically significant increase in median survival time was associated with hydrazine sulfate addition to chemotherapy." (Chlebowski, et al., Journal of
Clinical Oncology 8:9-15, 1990.)

Thus, NCI's internet message to the public--that only animal studies (no human studies) have hinted at the anticancer activity of hydrazine sulfate--is misleading, incorrect and false.

Why would the NCI misrepresent this easisly verifiable information to the public? Because it knows the public will take its 'authoritative' word and won't go to the medical libraries--or do an internet search--to look up the studies themselves. Because it wants the public to believe the curative effect of hydrazine sulfate is a "myth."

An unsolicited letter-to-the-editor in an upstate New York newspaper reads: "The cure of hydrazine sulfate for cancer is not a myth, but a fact. I was given a death sentence in 1994 by three top doctors and three top hospitals in Syracuse and Rochester. I had a cancerous tumor that was squeezing my bile duct and was inoperable because of its location. All the doctors told me I had two months to live and to prepare myself for my funeral.

"Shortly after starting on the hydrazine sulfate, my appetite returned. The weakness lessened and I regained my strength slowly but surely. That was 10 years ago. The tumor has completely disappeared and I'm feeling marvelous." (Syracuse Post-Standard, April 7, 2004).

Is it possible that the federal government would thwart a cancer drug that it knows--or suspects--to be effective and safe? Would go on the internet with misrepresentations at every turn to the public?

It would appear to be medical schizophrenia to answer "yes" to the above question. For the federal government--in this instance the National Cancer Institute--was put in place to help guarantee effective treatments for the disease which torments people the world over. Why would the NCI want deliberately to squelch a drug which competent studies indicate shows promise as a safe and effective treatment for all kinds of cancer?

Consider the scenario: It was learned by a small number of doctors that certain fruits, eaten in sequential order, possessed anticancer qualities that none of the fruits had separately. This was discovered from the dietary habits of an isolated Tibetan community located at an elevation of eleven thousand feet in the Himalayas that had no cancer. The doctors--environmental oncologists--had visited the community as a result of an international medical exchange program.

When the doctors returned to their home base in the U.S., they determined to--quietly--test a small number of patients with the diet. Twenty patients--with different types of progressive cancer--were administered oranges, bananas, strawberries, kiwi, kumquats and mangoes sequentially, and instructed to repeat this every three days.

At the end of one month the doctors looked at each other warily. Their patients, still with cancer, displayed none of the progressive features of their disease apparent one month ago. At the end of two months, none of the 20 patients had any findings of clinical cancer. The doctors sent their 20 patients to 5 different scanning facilities, so as not to arouse suspicion. All C-T scans, MRI scans and PET scans showed no signs of cancer in any of the 20 patients.

The environmental oncologists became very excited and highly enthusiastic. They realized they had hit on a cure for the most vicious disease the world had ever known. And consisting of common and plentiful foods, to boot! No more dangerous, harmful and ever-more expensive cancer drugs! No more big regional cancer centers! No more need for cancer education and fund-rasing organizations. No more need for ever-greater cancer appropriations from Congress. No more seats of individual cancer power and authority to dictate treatments that are largely ineffective. No more need for cancer specialists, cancer administrators, cancer czars.

The environmental oncologists were aware, however, that they had tested their treatment in only 20 patients. What they needed was a test in thousands of study patients. A double-blind, placebo-controlled, prospectively randomized multicentric epidemiologic clinical test. A test that could only be funded by the National Cancer Institute--involving large numbers of cancer clinicians and scientists and administrators--in what could possibly be their last job. Of course, the justification by the small group of environmental oncologists for this large study was that if the clinical results obtained in the first 20 patients held up in the thousands of patients, cancer could be erased from the face of the earth.

Do you think the NCI would approve a grant application for such a study? That the large private-sector cancer centers, the cancer hospitals and clinics, the national cancer education and fund-raising organizations, the pharmaceutical industry, the cancer research and treatment organizations, the leadership of cancer doctors, cancer nurses and cancer administrators--a $200 billion conglomerate in the U.S. each year, which maintain close liaison with the NCI--would give their concurrence?

This is the first blog on hydrazine sulfate. There will be many more. For the antipathy of the NCI to this drug extends over 30 years. And its message to the public has always been--from the very beginning--that of an adversary.

Monday, July 30, 2007

What's wrong with cancer medicine? (Cont.)

A front-page story from The New York Times, "Drug Sales Bring Huge Profits, and Scrutiny, to Cancer Doctors," published in its Sunday, January 26, 2003 edition, details how cancer doctors--oncologists--make most of their money. "At a time when overall spending on prescription drugs is soaring," the article begins, "cancer specialists are pocketing hundreds of millions of dollars each year by selling drugs to patients." The article goes on to describe the "cancer concession," the practice by cancer doctors of obtaining cancer drugs at low prices from multiple sources and administering--selling--them to their office patients at exceedingly high "mark-ups." The article states that cancer doctors "can make huge sums--often the majority of their practice revenue" from the difference between what they pay "wholesalers, discounters and pharmaceutical companies" and what they charge "patients, insurers and government programs." It has been estimated, the article states, that "oncologists in private practice typically make two-thirds of their practice revenue" from the "cancer concession."

That's a lot of money, considering that cancer doctors often just out of residency can generate upwards of $500,000 for their practice annually. Naturally, the more expensive cancer drugs that are administered, the more income generated. Administration of cancer drugs such as Avastin, Lucentis, Revlimid, Sutent, Vectibix and Erbitux--at average per-patient costs of $51,000, $48,000, $67,000,$46,500, $36,000 and $18,000 (per month), respectively--can generate large sums of money.

The New York Times article equally points out that this practice by cancer doctors "creates a potential conflict of interest for oncologists, who must help patients decide whether to undergo or continue chemotherapy if it is not proving effective"; that the "inappropriate" sales of chemotherapy to patients in the last stages of cancer was rife within oncology practice (for example, it was found in an audit of a Massachusetts study that "a third of the patients received chemotherapy in the last six months of their lives, even when their cancers were considered unresponsive to chemotherapy"); that the reason for this widespread practice was possibly related to the profit motive. "All evidence suggests that doctors do respond to money," a clinical faculty member at the University of Michigan Medical Center was quoted.

Today the treatment of human malignancy has become big business. It has been estimated that the conglomerate of cancer therapy, cancer research, cancer care, cancer administration and cancer pharmaceuticals totals $200 billion per year in the United States alone. The treatment of patients, in a real sense, has become business-driven. Gone are the days when cancer doctors would tailor individual treatments to patients as they deemed necessary or desirable; today instead, patients are placed on what are called 'protocols'--single or combinations of anticancer drugs that are usually experimental in nature. The 'protocols' very frequently emanate from the National Cancer Institute (NCI), which in turn subsidizes oncology group practices throughout the United States--to the tune of hundreds of millions of dollars each year. This puts great pressure of individual oncologists to put away their own treatment initiatives in favor of one or another protocol. Typically the cancer drugs used in a protocol--commonly newly developed from pharmaceutical companies or from the NCI--are very expensive.

Oncologists who are confronted with a choice of treating a patient individually, perhaps with an inexpensive new agent, or placing the patient on a protocol, frequently opt for the latter. Not wishing to risk the disfavor of their colleagues, they may be reluctant to place the patient on any new agent--inexpensive or not--that may threaten the lucrative incomes their practices have come to generate and thus kill the goose that lays the golden egg.

It is precisely with the advent of 'big business' as cancer practice that loss of innovation--and diversity of effective cancer treatment--has occurred. In this regard the public is regularly deceived. Every week news broadcasts, and headlines, trumpet new cancer breakthroughs. But where are they? How do these stories get on television? The answer is--that they are put there. By hired medical publicists or skilled public relations people. And if one looks carefully enough, many of these 'breakthroughs' are being publicized at the very time the medical groups responsible for them are being considered for major grants from the federal government--the NCI or National Science Foundation. Or a branch of the federal health establishment is petitioning Congress for increased budgetary appropriations. And while the 'hope' generated by these news stories so often vanishes, their underlying fundamentals usually succeed. For the reasons behind these broadcasts and headlines frequently have nothing to do with innovative advances, but with exerting public pressure on funding mechanisms to increase the 'business' of cancer research and treatment. The 'big breakthroughs' fade. But 'big business' prevails.

Today we have experienced a "shift" from high scientific achievement to big money achievement in cancer. Individual cancer practice is corrupted by money, and cancer science has become corrupted by money. It is this factor--big money--that is one of the two chief reasons underlying the woeful lack of progress and significant treatment advances in cancer medicine.

The other chief factor for the lack of innovation in cancer treatment is the NCI--the National Cancer Institute, part of the federal government.

The National Cancer Institute is the single, largest, most powerful cancer institution on the face of the earth. Its budget--received directly from Congress since the National Cancer Act of 1971--currently exceeds $4.75 billion annually, dwarfing by far the annual budgets of all cancer research, cancer treatment, cancer education and cancer fund-raising agencies in the private sector combined. While twenty-five years ago organizations with smaller budgets but with prestigious scientific staff in the private sector were, to an extent, the 'tail that wags the dog' (the NCI), this is no longer the case. With its almost exponential growth in budget, program and funding, the NCI has emerged as the dominant force in all phases of cancer investigation and treatment.

The NCI directly funds all officially-designated cancer centers in the United States--and the personnel and projects ongoing in these centers; without the NCI these centers--and their programs--wouldn't exist. The NCI makes institutional grants available to medical centers, universities and academic institutions nationwide; without the NCI much of the faculties of these institutons--and their projects--would dry up. The NCI is the major granting agency for young scientists with innovative ideas as well as for established scientists with many ongoing projects; without the NCI these projects--and scientists--would disappear. NCI officials sit on the editorial boards of virtually every important cancer journal in the nation--and thus exercise strong influence as to what appears in the mainstream cancer literature. NCI has become a virtual tsunami, whose waves crash against the shores of all cancer research and treatment projects worldwide.

But the NCI is also a monopoly. And it does what all monopolies do--acts in restraint of trade. Acts in restraint of true innovation. For who on NCI's dole would dare challenge current scientific thinking and directives of those who occupy NCi's highest echelons and formulate policy? Where is the incentive for individual scientists to excel and what if their endeavors lead them in directions that are not welcome at these top levels of power?

Monopolies usually tend to quash incentive. That is because incentive is a function of competition. There is no competition in NCI operations--except for monies and position advancement. But monetary and position improvement have nothing to do with true scientific innovation.

True innovation is a function of competition of thought. There must be no single monolith. No single source of power so great as to intimidate scientists from submitting grant proposals that are 'unpopular,' proposals outside current mainstream scientific thought--frequently brilliant, unrestricted, challenging traditional scientific concepts--and often the source of large steps forward.

There must be several 'NCI's--each independent of the others--that would be in competition with one another and would be rewarded according to their discoveries. The most immediate--and fundamental--advantage of such a structure would be that no one person--or group of cronies--would have absolute control over what research gets funded, what drugs get tested, what papers get published.

Naturally, there would be drawbacks to such an arrangement. It could be argued, for example, that there would be much duplication of work--and thus waste of tax dollars. But duplication of work is not necessarily a bad thing. For different scientists working on similar projects can come up with far different results, depending on the mind-set of the scientist, serendipitous occurrences, etc. On more than one occasion individual scientists or a group in competition with others--working on the same project--have 'cracked the code' of discovery and cure, such as the isolation and purification of insulin, the development of the polio vaccine, the identification of human immunodeficiency virus (HIV) and more.

The brilliance of scientific discovery bringing large public benefits has always been based on a milieu of competition and incentive--the competition of ideas and the incentive and freedom to carry them out. Until the NCI's concentration of power is lost--and with it the inhibition of these aspects of human inquiry in which great discoveries reside--there will be little and few signifcant steps made in the defeat of cancer.

Thus big money and the NCI, our best hope for protection against cancer, are largely responsible for the treatment abyss surrounding this disease of the last 30 years. Big money has corrupted--and acted to dethrone--the primacy of high clinical and scientific achievement in favor of high money achievement. The NCI, and its centralization of power, paradoxically has acted to stifle new ideas, new advances and true innovation.

In my opinion, it is these two factors which have contributed majorly to the lack of progress in cancer medicine.

Thursday, July 19, 2007

What's wrong with cancer medicine?

In recent decades there has been a plethora of clinical advances--in heart medicine, in stroke, in diabetes and other endocrine diseases, in respiratory illnesses, in infectious disease, in orthopedics--but very little progress in the treatment of cancer. One only has to look around--at his neighbor, at his family member, at his workplace acquaintance, at his friend or loved one afflicted with such major cancers as lung, brain, gastrointestinal, even breast cancer--to know that those major killers have hardly been indented by modern medicine.

To be sure there have been scientific and clinical advances--duly reported by the medical media--made in the field of cancer research, but most of these advances have not resulted in any "transitional" gains that have really advanced clinical cancer treatment.

Yet the public has been made to think we are making great strides in the treatment of cancer. Night after night, week after week, our electronic media announce new scientific discoveries that "promise" to advance cancer treatment. And every so often we are reminded of the large "victories" being made in cancer survival. But one of these victories in overall survival is in "skin" cancer. What we are not told is that included in this category of cancers are "basal cell tumors," comprising by far the great majority of this group of cancers. The survival rate of basal cell cancers is almost 100%, no matter what medical action--if any--is taken. If one subtracts basal cell tumors from overall cancer survival, the overall survival rate dramatically decreases.

Several months ago it was announced that a major advance had been made in breast cancer, decreasing the incidence of this disease in postmenopausal women. But it turned out that this decrease was not due to any new advance but to tens of thousands of women giving up their monthly hormonal replacement therapy (HRT) which was being shown--contrary to their physicians' prior belief--to actually cause breast cancer. Thus this scientific "advance" was not a treatment advance at all but merely a deletion from therapy of a medication causing breast cancer.

Closely related to advances in the treatment of breast cancer are mammograms. Women, especially over 40, are recommended to have yearly mammograms. Mammograms are radiation and this form of radiation is well known for its life-saving benefits, in the form of early diagnosis. What is not so well known--and is at the heart of the continuing heated debate in the medical profession as to whether especially younger women should receive mammograms--is that radiation can also cause breast cancer. Even in the low doses in mammograms. Thus, while mammography's usefulness in the field of early diagnosis is not in dispute, it has been estimated by some epidemiologists and cancer statisticians that a single mammogram actually increases the cumulative likelihood of breast cancer in a woman by 0.3%.

Regional and national cancer fund-raising events--"walkathons," "marathons," "bike-athons," "races," "relays"--and the publicity given them also act to give the impression that the cure to cancer can be imminent. These events attract thousands of participants who contribute funds to the sponsoring organizations, believing sincerely that their efforts may help to bring about the "cure." But the tired truth is that the funds these events raise--reinforcing and strengthening the sponsoring organizations--frequently find themselves in the hands of the same old scientists and researchers, who sit on the same old federal and large private-sector granting (peer-review) committees of our cancer agencies, frequently for the same old projects or variations thereof.

In contrast to the rosy picture painted by our periodic promising communiques in the medical literature and medical media, qualified cancer experts have in fact affirmed that overall cancer survival has not significantly changed in the last 30 years.

What accounts for this woeful lack of progress?

There are two major causes of this tragic situation. One is money, the other is the way cancer funds are distributed. These will be discussed in detail in our next blog.

Wednesday, July 11, 2007

"Ask your doctor..."

So frequently we see or hear this catch phrase either in a four-color pharmaceutical company magazine ad or in a dramatized prime-time television network newcast ad. These ads are of drugs--usually expensive ones--that pharmaceutical sponsors aim toward large numbers of potentially new, frequently older, patients who are not aware of the benefits these drugs can bring to them.

What most viewers, readers, do not realize is that pharmaceutical companies have advertising budgets that usually far exceed even their research and development budgets. So the pharmaceutical company wants to get the biggest "bang" for its advertising dollar. It has found that it cannot do that by straight advertising in medical journals or medical publications, simply because most readers of such journals--doctors--are in the know about these drugs and may not necessarily be in agreement concerning their "merits."

Adertising directly to the consumer through the media, however, has greatly increased the sales of their products, drug companies have found.

An ad on a prime-time network television newscast goes something like this: Frequently a well-known actor appears and states: "I have (XYZ) malady"--the implication is that you, too, may have it, but either you don't know about it or perhaps you're too uninformed (dumb) to know what to do about it. The actor continues: "I use (ABC) product. It gives me the freedom I've long missed. I don't have to restrict my lifestyle anymore. My symptoms have largely disappeared, and I only have to take one pill a day (week, month)." As the actor recites this, he/she is depicted in social situations, showing that the illness no longer is restrictive of normal activities. As the actor beams the benefits of the drug, what is equally recited are the sometimes horrendous side effects of the drug, in some instances dwarfing the medical reasons for the drug. "Yes, this drug for minor bee stings can produce fatal heart attacks, strokes, pneumonia and terrible sore throats, but you'll never be troubled by these pesky insect bites again! Just ask your doctor..."

But these ads do not concern bee stings. They concern abdominal illnesses, headaches, osteoporosis, high blood pressure, heart ailments, stroke prevention and a myriad other conditions that large segments of the population--potential, new customers--worry about.

Most viewers, readers will discount the side effects, thinking if the advertised drug can do for me what it has done for (the character in the ad), I'd like to find out more about it. "Ask your doctor..." is exactly what the patient will do.

The psychodynamics of this situation tip the scale greatly in favor of the pharmaceutical company. Here's how it works.

The patient confronts his/her physician. "You know, doctor, I have these stomach upsets, especially after a spicy meal, and I've seen this ad on television of (ABC) drug that can help. Can I have this drug?" The doctor, perhaps well aware of the patient's condition but reluctant to prescribe the drug for other medical reasons, nevertheless realizes that if he doesn't agree to prescribe it he may well lose a patient. The patient may merely go to another physician until he/she gets the drug.

"Ask your doctor" advertising works because it empowers the patient to ask the doctor directly about a drug it would not occur to the patient to take, were it not for the ad. The doctor would not normally want to incur the risk of losing--or not accommodating--a patient, so the doctor agrees, although perhaps with some reservations, to prescribe the drug.

Drug companies justify these ads by saying they are performing a service--giving information to the public that may be of great benefit to them. What they are actually doing is successfully hooking hundreds, if not thousands, of new customers.

When these ads advise you to "ask your doctor," it is actually like a noose being thrown over your head and being yanked tight. If you follow the drug companies' advice, you may find yourself taking an expensive and unnecessary medication, incurring the risk of serious illnesses as a result of the drug, corrupting the doctor-patient relationship, i.e., your welfare, in favor of pharmaceutical company interests. By agreeing to the pharmaceutical company's recommendation, you will have unwittingly put yourself in the role of a pawn in the fight for your dollar and your medical well-being.

Thursday, July 5, 2007

Compromised medical information

A study hits the medical media--prime time television news, newspapers nationwide, the internet--talking of new advances in medicine: a new drug for cancer, for arthritis, for heart disease, for Alzheimer's. It's been published in the current issue of a presigious medical journal.

But is it true? Is it factual? Is it even honest? These aren't insignificant questions. There are such things in medicine as 'conflicts of interest' and unfortunately they frequently infect our medical studies. Even the ones published in respected medical journals.

Today the cost of clinical studies is generally very high. Hospitals, medical centers--even federal health agencies with large budgets--find it difficult to finance a study. Frequently it is the pharmaceutical industry, or medical equipment manufacturer, that finance a clinical study.

Here's how it works. Drs. Jones and Smith and their associates at XYZ University or Medical Center wish to test a new drug on patients manufactured by ABC Pharmaceuti-
cals. Or ABC Pharmaceuticals seek out Drs. Jones and Smith to test its new drug. If the test turns out positive, ABC will earn a lot of money. ABC therefore underwrites the cost of Jones' and Smith's study.

But, you see, there's a catch. Because ABC pays for the study, it 'owns' it. That means that in order to publish their findings, Jones and Smith must first have the 'approval' of ABC Pharmaceuticals. In other words, ABC has 'first crack' at the study. If there is anything about the study or its outcome that ABC doesn't like--usually concerning side effects or drug efficacy--frequently ABC can choose not to have the study published. Period. The data are suppressed. The public will never learn of the findings or find out what ABC is objecting to. Or ABC can suggest to Jones and Smith that they remove data unfavorable to the drug and then go ahead and publish.

But why would Jones and Smith agree to do that? Because they are "on the take" from the drug company. They actually receive financial remuneration from ABC for doing the study. How about the hospital, the medical center, the research facility in which the study is done? Wouldn't they be equally outraged by ABC's tactics? But frequently enough they, too, are "on the take." Part of the deal of the ABC study is that the medical research institution in which the study is done is itself financially compensated.

This is a "classic" conflict of interest. At first, medical journals required authors to state whether they had financial ties to the company whose drug they were testing. If so, the editors of the journal would either reject the paper for publication or require a statement in the published paper that the authors--and/or medical institutions--were receiving financial compensation. But,in recent years, because this kind of conflict of interest has become so common, many journals no longer reject such papers or require such a statement.

How does this affect you? In 2006 a scandal broke concerning the drug VIOXX. The authors of this pharmaceutically-sponsored drug study published their results in the prestigious New England Journal of Medicine but prior to publication removed data unfavorable to VIOXX which indicated this drug could produce fatal heart attacks in otherwise healthy patients. It is unknown how many patients suffered fatalities or heart-damaging effects, but lawsuits against the pharmaceutical sponsor still persist.

How many VIOXX's are there out there? How many clinical studies are there out there that are not quite what they say they are? How many patients are there out there who are taking drugs in good faith that are not doing them any good or are positively and unrecognizably dangerous--until such time as fatalities or serious side effects break out? We don't know.

Well-known syndicated columnist Paul Krugman suggests that clinical studies and their results are to be considered "suspect" because of the "deep financial links" between doctors, hospitals, research institutions and drug companies.

The basic question here is: How reliable are our published clinical studies? And the media bally-hoo behind them?

Whenever a clinical study is published or publicized without it being known whether the authors of the study or the medical institution in which the study was done were being financially compensated by the sponsoring drug company--whenever this possible conflict of interest is not spelled out in detail--the study must be considered
"phony." Unless proven otherwise.

On the evening network television news, every week there are stories of "ground-breaking" new clinical studies--new drugs or medical advancements. Where are they? Where are the results of these well-publicized and dramatic developments?

Needless to say, today there are a lot of "phony" studies...

Until we have a system in which no doctor, no research institution, no hospital, no medical center can receive incentives from sources that have a proprietary interest in the drug or equipment under test--until we can eliminate the conflicts of interest
that are choking the truthfulness of our clinical studies--they will always be subject to ethical compromise and we will never have an accurate impression of their true clinical value.

Thursday, June 21, 2007

Background and statement of purpose

I have been an observer and participant in science and clinical medicine for over 30 years. I was elected to membership in the American Association for Cancer Research (AACR) in 1969, when there were only several hundred members worldwide (today there are more than 20,000). I am the recipient of several U.S. and worldwide patents, one on the synthesis and production of dl-glyceraldehyde-3-phosphate, an important biochemical which opened up the entire field of basic and clinical research in energy metabolism, previously closed. I am the discoverer and developer of the very inexpensive anticancer medication hydrazine sulfate, that restores appetite and weight loss in cancer patients, inhibits tumor growth and promotes increased quality of life and survival time--and which has been opposed for many years by the cancer establishment; more about that later.

During all this time I have observed a marked deterioration in truth in medicine--lies and dishonesty concerning the meaning and outcome of scientific studies, the "dumbing down" of medical information routinely given to the public, the shifting in medicine from scientific achievement to "money" achievement, the obscene amounts of money being dumped into the hands of pharmaceutical companies, causing a severe financial dislocation to patients (some have to choose between their monthly food budgets or medicines). This basic decrease in ethics and incresase in medical corruption has had profound destructive effects on the welfare of patients with all types of disease, especially cancer.

From time to time, therefore, this public forum will discuss one situation or another--some touted by the medical media, some in which the medical media are strangely silent--in which the public gets the short end of the stick.

Wednesday, June 20, 2007

The first entry

This blog will be devoted to discussing medical ads on television and in the print media, stories of new medical discoveries, dishonest and/or misrepresented studies, and what has euphemistally come to be known as "conflicts of interest" in clinical medicine and their potentially extremely destructive effects on the public health.

These commentaries will strive to provide truthful and factual information to the public in regard to cancer and other medicine, drug action, drug trials, medical PR and medical politics.

Although at times disheartening, our commentaries will frequently contain an element of humor.