DARWIN, MICROFURIES, MACROFURIES, and DYSOX
From Volume 11 or The Principles and Practice of Integrative Medicine

I begin this volume by proposing a model of science which I designate as the "Darwin Principle"—a principle which, in my view, must be held higher than all other principles of science in general, and particularly of clinical medicine. I define the Darwin Principle as a principle of drawing simple conclusions from an extended and integrated study of a large body of observations. The Darwin Principle accepts the validity of each scientific observation but holds that none of them singly be accepted as the definitive evidence of any conclusion about the condition of the whole. The core tenet of the Darwin Principle is: No part can be understood except through an understanding of its relationships with the whole.

I see three principal threats to the human condition: toxic thoughts, toxic environment, and toxic foods. Those threats may be called the three global "macro-furies" of destruction. In the context of molecular biology, the three essential homeostatic mechanisms are: oxygen homeostasis, redox equilibrium, and acid-base balance. Derangements of those mechanisms—oxidosis, acidosis, and dysoxygenosis (dysox), then, may be designated as the three "micro-furies" of human biology.

When I think about the health/dis-ease/disease continuum, I think of the three Furies of Greek Mythology. The ancient Greeks had three evil goddesses: Tisiphone, Megaera, and Alecto. Each evil goddess was assigned the task of spreading a different evil: Tisiphone engages in torture and murder, Megaera is full of malice and causes jealousy in its victims, Alecto fumes with anger, for ever inciting and perpetuating anger in others. In my view, the issues of personal health—the three micro-furies of of human biology—cannot be dissociated from the three global macro-furies of toxic thoughts, toxic environment, and toxic foods.

In 1831, Charles Robert Darwin (1809-1882), started his journey aboard the British Navy ship H.M.S. Beagle around South America. Over a period of five years, he accumulated an enormous number of biologic and geologic samples, studied them intensively, reflected on the interconnectedness of all of them, and formed his simple—yet comprehensive— biological theory of natural selection. In 1850, he published On the Origin of Species which, in my view, is the most significant work in biologic sciences. For me, Darwin's core message is what I designate as the core tenet of the Darwin Principle: No part can be understood except through an understanding of its relationships with the whole.

The Darwin Principle and Integrated Clinical Trials

The clinical application of the Darwin Principle calls for clinical trials which are radically different from the model of double-blind, placebo-controlled drug trials in vogue today. Such trials are designed to address the macro furies (toxic thoughts, toxic environment, and toxic foods), as well as the three micro furies (oxidosis, acidosis, and dysoxgenosis) of disease. Of necessity, such investigations can be conducted only as open, integrated trials in which teams of experienced clinicians enter a sizeable number of individuals with well-defined clinicopathologic entities into trials and then are free to address all macro and micro issues on basis of the needs of individual patients. The trial outcome is determined by evaluation of the results by patients as well clinicians employing objective and subjective criteria. The integrity of outcome is assured by: (1) a sufficiently large number of clinicians participating in the trial who categorically have no financial interest in the outcome; (2) inclusion in the study of all patients treated at the center for the disorder under investigation; and (3) by. adequately extended period of study.

The matter of patients deciding the efficacy of treatment is likely to raise some eyebrows. We have raised generations of doctors who think no clinical trials must be considered valid in which the patients has any say in determining the outcome of the trial. However, who can gauge the quality of sleep or energy—may I ask—better than the patient himself? Or the freedom from toxic thoughts? Or the qualities of mood, memory, and mentation? Or digestive and menstrual health? Or sexual drive? Or absence or presence of dry skin and muscle suppleness? For decades, I have been baffled by hearing otherwise intelligent doctors mindlessly insist that the patient's voice must be vigorously excluded from clinical trials. I return to this subject later in this preface for additional critical commentary.

I have two primary purposes in writing this volume: First to present sound scientific basis and rationale for integrative medical philosophy; and second to present the results of several integrated clinical trials conducted at the Institute.

Ecologic Thinking

We physicians, by and large, are not ecologic thinkers. We need to be. In this preface, I briefly examine what happens when we fail to think ecologically and ignore the Darwin Principle in clinical medicine. In my view, the primary reason why the critical issues of toxic thoughts, environment, and foods are neglected by the Imperial Medicine in the United States, as well as by public health policy makers, is that the Darwin Principle is neither recognized nor heeded. To support my assertion, I ask the reader to pick up any issue of The New England Journal of Medicine and scrutinize it for what it teaches its readers about the three core issues of toxic thoughts, toxic environment, and toxic foods. Or, about the issues of oxygen homeostasis, redox equilibrium, and acid-base balance as applied to clinical care in doctors' offices. There will be no useable information on these subjects in the Journal, which is committed to other goals. As a consequence, the non-integrative doctors are neither sensitive to the clinical problems caused by three macro furies, nor to the possibilities of restoring health by addressing issues of molecular biology created by the three micro furies.

Below, I present some verbatim text from the November 13, 2005 issue of The New England Journal of Medicine1:

Personal Metrics for Practice —How'm I Doing?

Part of the challenge of being happy in medical practice arises from the difficulty of ascertaining whether we are truly succeeding as doctors. In primary care, we take on complex problems and often feel as if we're failing.

Those are noble sentiments of an internist who is struggling to be a good doctor. Now consider some text that follows the opening passage:

So it was gratifying to learn that ... 90 percent said it wasn't a problem to get prescriptions refilled. Current LDL cholesterol test results were available for 19 of the 21 patients; of these levels, 12 were less than 100 mg per deciliter and 3 were more than 130 mg per deciliter.

What the writer finds gratifying is the high rates of filled prescriptions and what he considers the right blood levels of LDL cholesterol. I read the article carefully looking for any comments about any of the following:

Cholesterol is an antioxidant;
Blood cholesterol levels rise in people who are subjected to incremental oxidative stress caused by toxic thoughts, toxic environment, and toxic foods2,3;
Blood cholesterol levels begin to fall when all issues of incremental oxidative stress are effectively addressed4;
Statin drugs lower cholesterol by inhibiting enzymes in the liver and are known to cause hepatotoxicity and other adverse effects; and

The clinical benefits of expensive long-term statin therapy are questionable. Consider the following quote from The New England Journal of Medicine5:

West of Scotland study found an absolute reduction in cardiac mortality of 0.7 percent after five years of pravastatin therapy (40 mg per day, costing $100 per month). Therefore, 143 men with hypercholesterolemia must spend a total of $858,000 (drug cost only) to delay 1 such death...The problem is that outcome events in primary prevention are always rare, even in coronary disease, leading to the paradox that pravastatin is both highly effective and of very little benefit.

Both highly effective and of very little benefit! That's the reality of the real value of statin drugs for preventing deaths from coronary heart disease.

The internist, quoted above, claimed credit for his finding that "90 percent said it wasn't a problem to get prescriptions refilled." He also congratulated himself for the fact that 12 of his 21 patients had LDL cholesterol levels below 100 mg per deciliter. I want to make three other points here.

First, the credit for filling 90 percent prescriptions goes to the efficiency of pharmacists, not to the doctor writing those prescriptions.
Second, it would be useful to know how many of the patients had demanded that the prescriptions for statin drugs be written specifically for the drug they had seen advertised on TV and print media. That would tell us about the success of direct marketing efforts of drug companies.
Third, who set the standard of LDL cholesterol levels below 100 mg per deciliter, which he is so dedicated to? Also, who was paid and how much by statin makers to establish that standard? To answer those questions, I ask the reader to consider the following three quotes from On the Take,6 an eye-opening book on corruption among the standard setters of American medicine written by Jerome Kassirer who was the editor-in-chief of The New England Journal of Medicine for over eight years:

How much the meeting coordinators and speakers get paid for doing this is a closely guarded secret, but another prominent cardiologist bragged to a young colleague that he had made more than $100,000 at a single meeting of the American Heart Association for these "extracurricular" activities (page 17)

The lead editorial in the October 2002 issue of the Lipid Letter by Dr. Antonio Gotto, the dean of Cornell Medical School in New York and Dr. Peter Libby, chief of Cardiovascular Medicine at Brigham and Women's Hospital in Boston (of Harvard Medical School) and co-chairs of ESLM (Emerging Science of Lipid Management) "challenge[d] the medical community to consider whether our present criteria for therapy [with statins] ate too conservative," meaning that statins should be used much more widely. Both Drs. Libby and Gotto as well as the six "national faculty" listed in the Lipid Letter have financial arrangements with Pfizer (page 97).

Some physicians become known as whores. Whore is a strong descriptor but I heard it repeatedly from colleagues about physicians who tour the country for drug companies, changing their talks repeatedly to hawk the products of the company that is sponsoring their visits. Still, I held back using the "W" word until the wife of a prominent academic physician in a major medical center used it to describe her husband (page 25).

Like Dr. Kassirer, I have also heard some doctors described as whores. I find such comparison grossly unfair to whores. Hookers are always forthright in presenting their wares. They are forthcoming in the exact cost of their services. They deliver what they promise, and at the pre-determined. They risk their own lives in the practice of their profession, not those of others. Dr. Kassirer and I cannot say the same about many doctors of Imperial Medicine. I discuss the larger subject of intellectual bankruptcy of doctors of Imperial Medicine in my book The Rooster, the Flu, and the Imperial Medicine of the New Empire.

There is another aspect of medical standards established by the prestigious medical journals. To illustrate one of those problems, I will consider the case of Herceptin, the antibody that blocks the human epidermal growth factor receptor, and which is used to treat breast and other types of cancers.

Herceptin and The New England Journal of Medicine

Mark Twain had a way with words. Concerning statistics, he said, "There are lies, damn lies, and statistics." This phrase from the celebrated wordsmith comes to mind when I read reports about "major breakthroughs" in cancer treatment. In this section, I include brief commentary on two articles and an accompanying editorial about the use of the drug Herceptin for treating breast cancer which were published in the October 20, 2005 issue of The New England Journal of Medicine.7-9 First consider the following quote concerning those articles, the first being by the lead author of one of these two articles:

The results of these studies represent in quantitative terms the largest improvement in outcome for any group of women with breast cancer in 25 years.10

In 1991, I didn't know that we would cure breast cancer and, in 2005, I'm convinced we have.

A cancer expert at the National Cancer Institute.

Now consider how an editorial in the Journal celebrated the great cancer treatment:

The strength of the evidence is so overwhelming at this point that it would be almost impossible to withhold this drug from the appropriate group of patients."
Editorial, The New England Journal of Medicine.9 9

The author, according to Townsend Letter, received between $10,000 and $90,000 from the drug maker.

Next, consider how some others chimed in to salute what was being projected as a great medical advance in the treatment of breast cancer:

For some women, breast cancer drug could equal a cure.

Writer of the above editorial quoted in Houston Chronicler

We don't have to wait ten more years for data. The data is here today. So I'm happy. I am also humble to be part of this great study.

Another cancer expert paid by the drug maker, speaking on CBS News

Major breakthrough (describing Hereceptin for breast cancer).

ABC Evening News

Reality Check

The real story was dramatically different. When I read the two articles that prompted the above quotes, I wondered how many doctors who read The New England Journal of Medicine would have the curiosity to look beyond the hype. Consider the following quote from an editorial written in response to the Herceptin papers in the British journal, Lancet (www.thelancet.com / Nov. 9, 2005):

The best that can be said about Herceptin's efficacy and safety for the treatment of early breast cancer is that the available evidence is insufficient to make reliable judgments.

Herceptin is known to be toxic to the heart. Furthermore, cardiotoxicity of the drug is significantly potentiated by the cardiotoxicity of adriamycin and cytoxan, two drugs that are often prescribed along with Herceptin. The oncologists and the journalists on the Herceptin bandwagon had little, if any, time to warn the frightened and gullible women with breast cancer against the heart toxicity of the drug.

What might—one may ask—can be made of all that hoopla among the American oncologists and in the American media in view of the editorial in Lancet? The simple answer is that the Herceptin maker stood to rake in an estimated $1 billion a year from the sale of the drug. The drug costs nearly $40,000 a year for a single patient. The drug maker hopes to use its paid oncologists to recruit 30,000 or more women to take the drug. What is a mere few hundred thousand paid out as bribes to oncologists for their exultation!

The above story becomes even more remarkable when we consider the following quote from the authors of the Journal articles themselves:

"Overall survival of the two groups (the one receiving Herceptin and the other used as a control) was not statistically significant."
The New England Journal of Medicine.7

Translation: Women may not expect to live longer if they take Herceptin. That's the Imperial Medicine.

Vioxx and Calcium Channel Blockers

Next, let us consider the celebrated case of Vioxx. The drug maker first withheld crucial information about drug toxicity and then paid editors of major journals to write exuberant editorials extolling the virtues of the drug. Next, it intensely marketed it to the ill-informed body of doctors who take editorial advice about drug therapies as divinely ordained. Vioxx rapidly became a darling drug of doctors. Later there were many drug-related deaths. Then lawyers swarmed the courts for their loot. Doctors were saved from liability suits by the "deep pocket" strategy of lawyers who know where the real money is. Victims of the ill-advised use of the drug saw limited compensation.

The Vioxx story is replayed every day in doctors offices, albeit without much media noise. Occasionally there are reports of drug toxicities but they soon die out. Consider the following quote from a report about calcium channel blocker drugs published in Time magazine of September 11, 2000:

Many patients suffering from high blood pressure were probably surprised last week to hear that one of the most popular class of drugs for treatment of their conditions—calcium channel blockers—was being blamed for some 85,000 avoidable heart attacks and heart failures a year.

I recognize that the long-term use of drugs can never be completely safe. However, the issue highlighted in the above quote is different. How many internists diligently consider the issues of toxic thoughts, toxic environment, and toxic foods that cause hypertension before prescribing calcium channel blockers to their patients with hypertension? Indeed, how many internists—one might ask—are set up to effectively address any of those three issues? I often hear that there is no proof that non-drug therapies work for hypertension. That can be true only for those internists whose entire study of medicine is limited to the use of drugs, or those who do not have the courage to try and test some non-drug therapies.

The Dysox Model

There is but one fundamental difference between a healthy cell and an unwell cell: a healthy cell has a well preserved oxygen homeostasis. A healthy cell utilizes oxygen well, without incremental oxidative stress (oxidosis) and without accumulating organic acids (acidosis). In contrast, an unwell cell cannot utilize oxygen well and gets clogged up with Krebs cycle metabolites and other organic acids —much like an automobile engine which gets clogged up rapidly when it cannot burn its fuel completely. The presence of the cellular dysox state can be readily documented by the measurement of 24-hour urinary excretion of organic acids. This subject is presented at length in the chapter entitled, "The Dysox State."

Science and Drug Use in Imperial Medicine

I often hear claims of the scientific method by doctors practicing essentially drug medicine. Such claims bring to mind the complexity of genetic, enzymatic, and mediator pathways of human biology. There are an estimated 30,000 genes and 100,000 proteins in the body. I do not know a single internist who can even name 100 genes or 125 proteins. With that profound level of ignorance, it is hard for me see any merit in the claims of "scientific" medicine of doctors who regularly and completely ignore all issues of toxic thoughts, environment, and foods. How often do those who measure their effectiveness by the percentage of filled prescriptions ever consider the critical issues of oxidosis, acidosis, and dysoxygenosis in their office practices?

Evidence-Based Medicine

For several years, evidence-based medicine has been a euphemism for pharmacologic medicine in which issues of toxic thoughts, environment, and foods are consistently and completely neglected. Nor is any consideration given to the three primary issues of molecular biology: oxidosis, acidosis, and dysoxygenosis. For an equally large number of years, I have been amused by the use of the evidence-based medicine phrase by doctors whose total commitment has been to first finding the name of a disease then prescribing the "drug-of-choice" to treat that disease. That becomes even more remarkable when we recognize that nearly all clinical drug trials are conducted by doctors on the payroll of companies that make those drugs. That is considered good science while astute clinical observations of physicians, who have no conflict of interest, are dismissed as unscientific.

The following are several serious problems with the double-blind, placebo-controlled clinical trials in use today:

Blinded trials begin with a carefully selected patient population entered on the basis of highly exclusive entry criteria;
The drugs under investigation do not remain blinded for the patients for long since they have pharmacologic effects experienced by patients;
The drugs under investigation do not remain blinded for the doctors for long since they are generally astute enough to recognize whether the patient is responding to the drug or not;
The drugs under investigation reveal their identity because they alter the results of laboratory tests performed as integral parts of the trial;
Patients almost never just take the trial drugs and persistently refuse natural measures (including nutrient supplements and self-regulatory approaches) for the entire duration of the study;
Each patient is a unique individual with unique set of life circumstances that profoundly influence his response to the drug under investigation; and most importantly
Trials for individual drugs are conducted as single agents for some months but doctors prescribe the drug concurrently with two, three, four, five, or more drugs for years.

For the above seven reasons, I do not believe double-blinded, placebo-controlled drug trials can be accepted as valid science. That model serves drug makers well but poorly the doctors. As for patients, they suffer in silence, often totally unaware that they are victims of reprehensible perversion of science.

Human Intellect, Holism, and Integration

Human intellect evolved through spiritual, philosophic, and scientific explorations. Those three forms of explorations were integrated by the following three simple notions:

First, all exploratory beginnings occurred as mere imaginings—speculations in the contemporary vernacular;
Second, the natural order of things could not be understood unless it was regarded in its settings as a whole; and
Third, the exploratory endeavor had to be continued beyond the established knowledge at any given time.

The above three simple notion appear to be as old as human consciousness. Science, defined here as the aggregate of physical observations is then designated as the conquered territory of philosophy and spirituality. It follows from that science must be considered true only when it seeks to be holistic—Darwinian.

The whole is the reality, was the central theme of Hegel's (Georg Wilhelm Friedrich Hegel 1770-1831) Encyclopedia of Philosophic Sciences. However, Hegel was a Johnny-come-lately. The notion of wholeness was the prize bequeathed to us by the pre-Socratics. Parmenides (515-450 B.C.), the greatest of the Eleatic school and celebrated by Plato, taught that reality is unchanging, the entire world of being. The mathematical philosophers—yes, mathematics was spawned by philosophy—of the Pythagorean school held that all things were numbers. Socrates could answer questions only by raising more questions—a telling evidence of his preoccupation with the relatedness of everything with everything else, which is seldom, if ever, recognized among ecologists. In Plato, we see merging of the ethical and the scientific. Centuries later, the Persian physician al-Razi (Abu Bakr Muhammad ibn Zakariyya al-Razi, 841-926 A.D.) addressed that subject with the following words:

The truth in medicine is a goal that one cannot attain, and everything that is written in books is worth much less than the experience of a physician who reflects and reasons.

There have also been some dissenting voices. The core tenet of wholeness of the human condition and its place in the continuum of human explorations was challenged by Rene Descartes (1596-1650), who disavowed all his prior thinking by proclaiming Cognito ergo sum (I think, therefore I am). His celebrated duality of the soul and body can be traced to the following words with which he expounded his philosophy:

...that is to say, the soul by which I am what I am, is entirely distinct from body, and is even more easy to know than is the latter; and even if body were not, the soul would not cease to be what it is.11

Descartes's words puzzle me. Evidently, humans were humans long before Descartes conceived the notion of Cognito ergo sum. However, how much of his professed essential dichotomy had to do with his fear of the righteous of his time remains unknown. He must have known about the fate of Giordano Bruno (1548-1600). Bruno believed in the indivisibility of all matter and supported Copernican thought, for which he was burnt on stake by the lieutenants of the Pope.

The connectedness of everything in all imaginable realms was the central and recurrent theme in the wisdom of the East—millennia before any documented notions of relatedness among things in the West. Specifically, the problems of the human condition—physical and emotional included—were not seen discrete from the matters of the soul, nor from the cosmic considerations in the ancient Indian, Chinese, and Tibetan schools of philosophy and spirituality. However, until recently, there was little, if any, appreciation of this in the West. Consider the following words from the Nobelist Bertrand Russell (1872-1970):

For in some vital respects the philosophic tradition of the West differs from the speculations of the Eastern mind. There is no civilization but the Greek in which a philosophic movement goes hand in hand with a scientific tradition.
The Wisdom of the West10a

That is a remarkable statement from one of the most celebrated the twentieth-century literary figure of the West. One can only wonder how serious students of the ancient literatures of the East might respond to that. Let us consider the wisdom of the West in this matter.

Doing Clinical Ecology and Dysox Medicine

Clinical ecology is completely neglected by the practitioners of drug medicine. That is so because their thought leaders do not practice it. Those thought leaders do not practice it because it does not fit into their placebo-controlled, double-blinded methodology of what they consider to be the only acceptable form of science in medicine. The ecologic dynamics—interaction of environmental elements with human metabolism, in common language—of course, cannot be blinded. Nor can people, I might add here, be blinded to what they eat, nor to the presence or absence of physical fitness with exercise. Another lament I have heard from some thoughtful physicians is that the ecology cannot be brought into a doctor' office. Why? Because The New England Journal of Medicine does not permit it.

The only way to find out what philosophy is, is to do philosophy.
Bertrand Arthur William Russell, in Wisdom of the West10b

Russell in the above quote, of course, was struggling with the problem of defining philosophy. He contended philosophy cannot be defined, since any definition of philosophic exploration confines it to some specific philosophic attitude. So, he concluded that one had to do philosophy to know philosophy. Taking Russell's lead, I suggest the following to the practitioners of drugs and scalpel medicine:


The only way to find out what clinical ecology is, is to do clinical ecology. The only way to find out what detox medicine, is to do dysox medicine .

No amounts of mere reading can give any clinician a clear sense of what dysox medicine is and how it can prevent illness, reverse disease, and ameliorate suffering. What is required is deep reflection and courage to embark upon a journey of exploration of the fundamental energetics of cells and molecular dynamics of the health/dis-ease/disease continuum presented in this volume. I also present in this volume a large body of data obtained with integrated clinical trials conducted at the Institute. It is my hope that such information can help readers break the myopia of the mind created and perpetuated by blind subservience to the placebo-controlled, double- blinded model—seldom really blind for long, in real life. Then they can go on to develop an ecologic, integrated, and synoptic view of clinical medicine.

References
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11. Humphery N. A History of the Mind. 1992. New York. Simon & Schuster.