Chapter 11 - More U.S. Research
It was apparent from the beginning of GH3 testing in this country that double-blind tests held the key to acceptance by the FDA. Since the laws of this country call for a certain protocol on the part of the FDA, we must not attach all the blame to this agency in enforcing what sometimes may appear to be misguided laws.
If the late Senator Kefauver and others who were so rightfully concerned with the safety of drugs such as thalidomide, which caused irreparable harm to a few hundred babies, could have known they would be responsible for the establishment of almost impossible criteria for approval of new lifesaving drugs, they would not have reacted so drastically.
Overreaction can be just as detrimental as failure to act. As we mentioned earlier, penicillin and its related compounds would probably never have passed the new stringent laws (not FDA-inspired), because penicillin, though it has saved millions of lives throughout its 35 years of existence (and will save a billion more in the future), affects a few persons who are allergic to it; in fact it has caused a few deaths. Yet who in his right mind would say penicillin should be banned because it is not demonstrated to be absolutely safe for everybody? Should 500 million persons perish because fifty are allergic to penicillin and should take some other remedy? This is the situation, somewhat oversimplified, which American medicine finds itself in today. There are hundreds of worthwhile drugs which have been kept off the market and will continue to be banned as long as the present well-meant but ill-advised laws are in effect.
Take cyclamates, the sugar substitute, for example. In order to induce harm in an animal (the rat), cyclamates had to be force-fed about two hundred times the amount the rat would consume if cyclamates were merely substituted for sugar in its diet. No one bothered to force-feed the rats the same overdose of sugar. As any scientist can look up in a scientifio encyclopedia, such a huge dose of sugar would have killed the rat soon enough, without waiting for the cancer which might develop from a "drowning" dosage of cyclamates. Yet cyclamates were banned, and subsequently saccharin, that wonderful old sugar substitute, has been put under close scrutiny and will probably be banned if the Sugar Trust has its way. Meanwhile, sugar has been definitely linked with heart disease, with hypoglycemia (low blood sugar) and most assuredly with tooth decay.
We return to our original premise: that the GH3 double-blind tests were the real criteria. We consider slight discursions such as the foregoing as being essential to our understanding of the processes of both so-called science and governmental techniques of how to defeat true science and true medicine.
The double-blind tests for GH3 were definitive and were performed by impeccable researchers. There were some other "single-blind" tests and open studies. (See Appendixes and Bibliography.)
One of the valid double-blind tests—with which there can be no quarrel—was conducted by Dr. William W. K. Zung, one of the foremost psychiatrists in the country. (See Appendix 7.) He is now professor of psychiatry at Duke University Medical Center. His list of credits is more than any I have seen since Freud, Jung, and a few other such notables. At any rate, Dr. Zung, in addition to his other credits, established many of the criteria of psychological testing, including the famed Zung self-rating depression test which, through many adroit questions, lets the patient rate himself. It may not seem that this would be effective in determining the degree of depression, but surprisingly, when matched with other tests by doctors and nurses, it turns out that most patients know their own condition instinctively. It just takes ingenuity to bring it out. Of course Zung does not depend entirely on the patients or the researchers opinions to arrive at any conclusions, but employs many standard physical tests, such as blood determinations, physical examinations (heart, blood pressure, urinalysis) and electroencephalographic studies of the brain.
Zung had six other doctors working with him on the double-blind test of Gerovital H3. Patients were volunteers from the geriatric psychiatry group of Duke University Medical Center. When we used the term "double-blind," we really meant triple-blind, because Dr. Zung and his confreres went beyond what is ordinarily meant by a double-blind test—which in itself is supposedly errorproof. A double-blind test means that the proposed remedial substance, such as GH3, will be tested against a "placebo," which usually consists of a harmless, inert substance such as saline water or sugar-coated pills, depending on whether the test will be injectable or oral. Neither the doctors nor the patients know whether the drug or the placebo is being administered; note that the slightest hint from doctor to patient may conceivably affect the whole experiment. We have learned that the placebo effect—the power of suggestion is so potent that it often is more effective than the proposed medication.
Placebos work up to 40% effectiveness for a limited time (rarely indefinitely). They occasionally cause red faces among those who promote a medication when it is found that a placebo is just as, or more, effective. Thus the methods of any investigative group which reports no benefits from a proposed remedy are suspect.
Such was the fate of vitamin E, for example, in the early 1940s and ‘5Os when it was reported by at least six groups of researchers to have no effect at all! Effect zero is inconceivable, but we must understand that these "scientists" were under some duress by the medical official consensus to produce a zero effect. Apparently they were not aware they should have shown at least 20%—40% (the placebo effect) to make their experiments resemble the scientific.
Not so with more sophisticated researchers: it's harder to fake double-blind experiments than it was twenty or thirty years ago. It is still possible, as was proved recently at Sloan-Kettering Memorial Hospital in New York City. In an immunology experiment, a researcher faked his results by painting the undersides of laboratory rats with certain dyes to indicate (falsely) that they were immune to cancer. After being caught, his excuse was that his chief demanded more and better results. The incident proved the sad state of American medicine today. It also proved that one should never trust proofs unless they are buttressed by many, many collaborating reports.
What we are leading up to in the case of Zung et al. is that Zung decided that a double-blind test was not enough. Therefore, he inaugurated the triple-blind test. This consisted of GH3 being tested against not just a placebo (saline water), but also against a well-known remedy for depression: imipramine. While imipramine is efficacious in the treatment of old-age depression, it has limitations and side effects, especially in long-term treatment. It is probably the best and safest of the medicines used to treat depression today in the United States.
The ampules were prepared so that no one could tell them apart. No one could tell what was in the small amber-colored vials. No human knew: the knowledge resided within a giant computer, which alone could say which ampules contained medication or nonmedication. Its knowledge would be unlocked by only one man, who had fed the machine random numbers, which it could and would assort when the time came for unscrambling the code.
This man was Dr. Sidney Cohen, three thousand miles away from Dr. William Zung in Durham, North Carolina, who was responsible for setting up the double-blind tests so that the possibility of error—by either human or computer—would be so unlikely as to be unthinkable. It would take the computer that had devised the test to compute the tiny probability of error! Dr. Cohen had set up similar double-blind studies, one in Palm Springs, California, following the same infallible method.
Dr. Zung and associates selected outpatients sixty years old and over, with no upper limit of age or restriction of sex, who had depressive disorders varying from mild to moderate. But since his own descriptions are easily understood, let us take his own words as to the qualifications of the patients:
In this study, a depressive disorder is operationally defined as manifesting: 1. A mood disturbance which is chazacterized by pervasive feelings and complaints of being depressed, sad and tearful. 2. Physiological symptoms which include diurnal variation, disturbances of sleep, decreased appetite, decreased weight, decreased libido, constipation, tachycardia and unexplainable fatigue. 3. Psychomotor disturbances which are either that of retardation or agitation 4. Psychological disturbances which include confusion, emptiness, hopelessness, indecisiveness, irritability, dissatisfaction, personal devaluation and suicidal rumination. The following patients were excluded from the study: 1. Actively suicidal patients. 2. Patients who were incapable of spontaneous conversation end activity. 3. Patients who were severely demented. 4 Patients who were schizophrenic, or had evidences of a thought disorder. 5. Patients who were on the following medications: sulfonamides, neostigmine or physostigmine. Lastly, patients were to have been free of all psychotropic drugs for at least seven days prior to entry to the study protocol.
The results of Zung s experiment were even better than had been anticipated by GH3 proponents. The study showed that not only was GH3 superior to a placebo, but it was superior to the drug of choice for depression, imipramine. We will not go into details of the results here (for those interested in details, the whole study is reprinted in Appendix 7); but we will quote a sentence or two from Zung's conclusion:
"...pretreatment to post-treatment differences showed GH3 to be superior to imipramine. . . . Both imipramine and GH3 were superior to the placebo.. ." (which, however, did have some effect, as it always does in any well conducted study, as we have pointed out.) The power of the human brain/mind/soul is always astonishing to those "scientific" materialists who have never managed to escape the 19th century's concept of the human being.
Another highly significant double-blind study was conducted by Drs. Morton L. Kurland and Max Hayman. (See Appendix 8.) Both have credentials without which they would not have been accepted by the testing committee of GH3. Dr. Kurland is associate clinical professor in psychiatry at the University of California School of Medicine; Dr. Hayman is professor in research psychiatry at UCLA, now retired, and medical director, Desert Alcoholism Coalition, Palm Springs, California. Both are associated with the Desert Hospital in Palm Springs, California, as well as being in private practice.
Dr. Sidney Cohen also spelled out for them the details of their double-blind test, conducted on 60 patients. (They now are treating approximately 125 patients, with the same results as were achieved in the double-blind test.)
Drs. Kurland and Hayman selected 64 patients, 45 and older, men and women, who had depressive disorders of at least mild severity, which was determined by a Clinical Global Impression Scale (CGI), the standard psychiatric test for measuring depression. They excluded patients who were severely demented, who could not carry on brief conversations, or were obviously schizophrenic; those who had active diabetes, tuberculosis, or cancer; and those who were being treated with sulfonamides or related anti-infective drugs. In addition, to make the test even more valid, the subjects were to be free of all major and minor tranquilizers. Thus no variable factors were allowed to obfuscate the conclusions, and thus permit critics to say that other medications were responsible for the outcome—or that a combination of factors were responsible. If GH3 worked, it and it alone would do the job.
The pretest procedures described for the Zung experiments were followed in the Kurland-Hayman tests: physical and mental examinations before, during and after the test period, which lasted four weeks. For those interested in the method and findings of the Desert Hospital's experiment with GH3, a report is reprinted in Appendix 8. Here we will partly summarize the findings: "The results demonstrated," wrote Drs. Kurland and Hayman, "that Gerovital 113 was significantly better than placebo. . . Minimal side-effects (such as a metallic taste in the mouth experienced by two patients) were evident in both the Gerovital H3-treated and the placebo-treated groups. Therefore," concluded the authors, "from the data presented, Gerovital H3 is an efficacious drug in the treatment of depressive disorders in an adult population, and it is also a safe drug."
In subsequent interviews with Drs. Kurland and Hayman, as well as with many of their patients, I learned that the doctors—in their praise for GH3—went far beyond the actual wording of the report, which was after all a study narrowly circumscribed by the FDA to ascertain only effects on old-age depression. (According to this criterion, the rest of the body's and mind's welfare doesn't exist—only that part which somehow concerns itself with the depression of old age. This attitude is a joke among doctors and patients who have tried GH3 or any other substance which operates on many levels. How can you dissociate the beneficial effects which may be apparent in other bodily aspects, as well as in renewed interest in life? Answer: You can't. GH3 probably is easiest to test in a period of four weeks on old-age depression—although that amount of time is not sufficient for adequate testing, it can give an indication--—and an indication it did give in every truly scientific test to which it has been subjected.)
Drs. Kurland and Hayman found about the same favorable results with GH3 therapy in their double-blind study as did Zung and associates. Both groups, separated by three thousand miles, not knowing each other except by reputation, obtained the same results. They were united only by the computer system which Dr. Cohen had devised for the double-blind testing of GH3.
Since every recent test whether double-, triple-, or single-blind, or longitudinal, substantiates, augments, and reinforces statements we have made in this book regarding Gerovital's efficacy, the reader will understand our position in asserting the value of GH3.
Not being content with medical reports, which are scientific but can be dreadfully dry, I visited most of the doctors and many patients involved in the Gerovital studies. The doctors I visited were most intelligent and anything but dull, and I must say that both Drs. Kurland and Hayman carry on a conversation which shows they are aware of the state of the world, exclusive of their own specialties. In this endeavor they are aided most adeptly by Dr. Kurland's charming wife Adrienne, who keeps close contact with the patients and maintains their records.
Most patients can feel and see the improvement in themselves, and can evaluate their own condition. Alertness, lifting of depression, wanting to "live" again, improvement of skin elasticity--the improvements are so obvious that the doctors had to promise the patients who did not receive GH3 that they would get it when the initial experiment was concluded, or when a sufficient period of time had elapsed so that the GH3 patients—then without GH3—could slip back into their original status. (Most of them did after three months or less, thus further establishing the merits of the drug.) For another paper on Gerovital H3's use in old-age depression see Appendix 9.
The researchers have now added to their original groups of patients by multiples of 25 or more (some over 100), and are also making sure that their former placebo-treated patients are receiving GH3. These patients are responding as the GH3-treated patients did in phase two of the double-blind studies.
Since most of the placebo patients in the strict double-blind tests are receiving GH3 with the same effect as the others, the continuing "open" experiment studies are corroborating what the double-blind studies proved. They are, in effect, more than just Phase III, in which numbers of patients are being treated to rule out side-effects and to prove efficacy on a considerable number of persons. (We have discussed the Romaman experiment in Chapter 9; for further corroboration, see the Appendixes and Bibliography.)
Drs. Cohen and Ditman, Zung et al., and Kurland and Hayman are following up their initial successful findings, also with favorable results. These are longitudinal studies. As Ana Aslan and many other researchers point out, the longitudinal method is fully as effective as the double-blind test, although it takes longer, naturally, and is more difficult of execution, as the researcher has to follow the patients for years instead of months.