The Impact of FDA Regulation on Drug Research in America Today

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Introduction How do you know that the drugs you take are safe? Most people, in response to these questions would reply—"Well—the government takes care of it. I don't have to worry…do I?" Few people really have any idea how the government goes about this task, and still less idea whether the job it does is a good one. The agency charged with the responsibility for controlling the drug industry is the Food and Drug Administration (FDA). The recent Nader report on the FDA covered only regulation of foods; the 292-page report gives strong evidence to support its charges that the FDA, having become a political rather than a scientific entity, is failing miserably at this task:

"The FDA is not a happy place for scientists to work in…Several researchers showed the students 'atrocity logs' in which they kept detailed accounts of 'assaults on their scientific integrity'…The most common complaint was that the FDA 'constantly interferes' with medium and long range research projects, at least partly from fear that the results will embarrass the agency. The students also criticized the FDA for retaliating against scientists who disagree with its positions."1

In an attempt to learn whether the FDA does any better at assuring safe drugs than it does at assuring safe food, the editor of this magazine several months ago requested persons connected with the drug industry to relate their experiences in dealing with the FDA. The president of a small drug firm, among other comments, wrote the following:

"Our company, as are the others, is continually harassed on all sorts of nonsensical inspections by FDA. They take up large amounts of executive and employee time, and generally amount to nothing. The ordinary FDA inspector has become a snooper, assiduously trying to find something he can pin on a drug company at any time, with no apparent thought of the avowed purpose of FDA to cause better drugs to be sold. Thus it is necessary to stay with these boys the whole time they are in the drug plant, for once alone they will rummage through the most personal desk drawers and correspondence. Then if they get thrown out after being caught rifling someone's desk, they go to no end in attempting to pin false criminal charges on the man who threw them out, as was the case of a friend of mine in St. Louis; they well knew that he wouldn't be convicted in court, but also knew that it would cost him many thousands of dollars which he could ill afford to spend."

This man is obviously very bitter about the way a political agency is controlling his business. Yet is there any alternative way of ensuring that people are not poisoned or cheated by dangerous or worthless drugs? To answer this question requires an examination of what drugs are, how they are developed, how they are marketed and prescribed, and how the FDA regulates them. Unlike many other industries, where regulations were frequently asked for by the established firms, the modern drug industry came into being after the federal drug regulations had already been established, primarily to deal with foods. Thus, since there has never really been an unregulated drug market in the United States, it is not surprising that few people have ever considered alternatives to the present system.

A drug can be defined as any noncaloric substance designed to produce some change of body chemistry on a molecular level in a living entity. So far as government regulatory agencies are concerned, drugs fall into two main categories: proprietary drugs, which are sold over the counter without a prescription, and ethical drugs, which are sold only by prescription. Our main concern here will be with ethical drugs.

The definition of a drug says nothing about the specific kind of change in body chemistry that it may produce. A drug may cure disease—or cause it, alleviate pain—or create it. Drugs may heighten or decrease or alter consciousness. abate or accentuate psychological reactions, rearrange genetic makeup, or cause death. Whatever can be done to a human body, eventually drugs could probably be created to do it.

To this date, there is no such thing as a "perfect drug." Differences in human physiology make even the most innoculous drug a potential killer for some people, while certain drugs that mean certain death for "normal" people are an absolute necessity for the survival of others. So far as physiology—and concomitant reaction to drugs—is concerned, all men are created unequal.

Thus aspirin, which by any standards is man's safest pain-killer, can be dangerous to a minority with a certain genetic background. And while large doses of water can cause death in a "normal" person, they mean life for the man with diabetes insipidus.

Nor are the effects of many drugs independent of dosage. Some drugs reach a plateau of dosage, beyond which further administration is useless and generally harmful. A standard dose of aspirin (.65 grams or two tablets), for example, is sufficient to reduce fever, but a larger dose won't help, and may cause gastrointestinal bleeding. Other drugs have no such plateau. The barbituates, for example, tranquilize at low levels, sedate at . moderate levels, and, at high levels, produce coma and death.

Sometimes, drugs taken in conjunction with other drugs can produce results quite different from that of either drug alone. A well known example is that of alcohol and barbiturates, a mixture that is an American suicide favorite.

When evaluating drugs, physicians use a therapeutic index: toxic dosage/ pharmacological dosage.2 If the ratio is large the drug is fairly safe to use; if small, the dosage must be carefully controlled. (On the other hand, some drugs take advantage of a low ratio to produce special effects. Anti-cancer drugs, with a ratio of unity, capitalize on the fact that cancerous cells absorb chemicals quicker than normal cells. The tricky and delicate work involves poisoning the malignant cells without killing the organism with the malignant cells.)

The therapeutic index is not sufficient in itself for drug prescription because, as we have pointed out, drug reaction differs from individual to individual, not only quantitatively, but qualitatively as well. One man's medicine may be another's poison. To illustrate: oral contraceptive users have a death rate of 22.3 per million woman years from thromboembolism (fatal blood clot)3—Diabinase (anti-diabetic drug) causes jaundice at a rate of 4 cases per 10004—Chloromycetin causes fatal anemia in 1 per 225,000.5

Some of the factors that account for varied or unanticipated reaction to a drug include genetic differences, aging, sex, multiple or undetected disease, acquired reactions and tolerances developed from previous drugs, other drugs a patient may be taking, psychosomatic disturbances, reactions and tolerances developed from environmental conditions, such as heavy doses of various industrial pollutants, and physical states, such as pregnancy.

There are two types of adverse reactions to drugs: side effects any idosyncracies. If most people respond to a drug with an unwanted reaction, this is called a side effect. If only a few do, this is termed an idiosyncracy. What a drug firm tries to do (in theory), through research, is produce drugs that produce no side effects, while developing tests that alert doctors to the presence of genetic or other differences in patients that could produce adverse reactions. "Have you ever had penicillin before?" your doctor asks you, during a recent bedcall for the flu. He's checking to see that you don't have a sensitivity to the drug before he prescribes it.

Much current controversy and alarm centers around bad drug effects that are not immediately evident as penicillin sensitivity or blood clots from oral contraceptives. Thalidomide, one of a class of drugs known as teratogens that act directly on embryos, is a sedative, which if taken between days 20 and 40 of pregnancy, results in an infant with deformities, while the •mother remains totally unaffected except for the sedation effects.

More subtle still are the mutagens6 which attack a cell's genetic material, possibly causing cancer if somatic (body) cells are affected, or birth defects if germinal (sex) cells are affected. Among some suspected mutagens are LSD, caffeine, cyclamate, sodium nitrite, and tobacco smoke components.

The problem of adverse drug reaction is a central one, not only to pharmaceutical research and retailing and the medical profession, but is the core of the rationale for the existence and activities of the FDA. People—and thus the bureaucrats of the FDA—are concerned about drug effectiveness and safety.

Drug Research Every company doing research has a program detailing what type of drugs it wants developed. The programs are based on estimates of probable results, which are in turn based on accumulated research data, available personnel and their specialties, and facilities. Their decisions are also based on estimates of profitability, and likelihood of government regulation, restriction, or delay on cosmetic or foreign markets.

Because of economic and technological advantages, companies often develop specialties in addition to their standard lines of research. Syntex, for example, concentrates on hormones—Smith, Line, and French, mind drugs—Sandoz, headache remedies.

Seeing the combination of a large market and the relative likelihood of producing a drug to capture that market, a company may attempt to cure some specific disease. Drugs for heart disease, birth control, mental illness, and arthritis are examples of such attempts. A cure for cancer, on the other hand, although there is a market, because so little is known of cancer's cause, would today more likely come by accident than by systematic research.

Generally, companies do not seek out cures for rare disease. Instead, most progress in this area comes either by accident or through the efforts of university research labs, which are often supported by grants from pharmaceutical firms.7 These specialized drugs are marketed at a fraction of actual cost, the loss written off to good will, scientific reputation, and concern for human suffering. If the company can obtain a broad enough patent, other more profitable drugs produced during the same project can sometimes recap such losses.

Once an area of research emphasis is chosen, the work of the organic chemist begins. He examines what is known of successful drugs in the area of concern; he then either devises syntheses of slightly different compounds (a process known as molecular modification), or produces radically different compounds until he finds one that looks promising, which he determines via animal testing, proceeding then to further molecular modifications. Twenty-five years ago, devising a new drug was mostly a random affair often involving animal tests ("screening") on any handy chemical, often plant extracts. Today, chemistry and pharmacology have progressed to a point where rational, ordered inquiries are possible. The chemist has large quantities of data which indicate what general chemical structure a drug must have to produce a particular effect. Even so, research and development of a new drug averages about 7 million dollars and requires five or six years from conception to market.8 Please keep these figures, five years and seven million dollars, firmly in mind, for they are extremely significant in judging the actual and probable effects of government regulation on pharmaceutical research and retail.

Once a chemist has produced a reasonable drug prospect (perhaps 30-50 a year) he sends it to the biologists and pharmacologists for animal screening. The first tests establish dose and toxicity levels in the particular experimental animal used, and provide a general idea what biological effects the drug might have. The drug is then screened for specific effect both on the basis of the results of the first series of screens and what the chemist is seeking. These specific tests can be expensive; often specially bred or modified animals and time consuming, involved procedures are required.

If the drug passes the screens, (a rare occurrence), it is then subjected to long term toxicity and teratrongenic tests in several species of animal (including primates). Here is where less reputable firms have been known to cut costs and compromise safety. Only after a drug has come through this process does a reputable drug firm release it for human testing.

Under current Investigational New Drugs (IND) regulations, before humans can use the new drug, or more precisely, before a drug company is allowed to give it to them, an application must be filed with the FDA that sets forth all knowledge of the drug and includes an outline of planned investigation, a summary of investigators' qualifications, and so forth. The investigator must also promise to keep the required records, permit inspections, comply with patient-consent rules. If the proper reports are not made, or if there is any indication that the drug is unsafe or ineffective, the FDA may halt the investigation.9 If a company halts a project of its own initiative, it must give account to the FDA.

The investigation's first step is usually to establish dose and toxicity level, with prisoners and medical students often the volunteers. Later the drug is tested on a small group of patients, primarily with their knowledge and consent (although consent is not required by either law or medical ethics if the physician doesn't think it is in the patient's best interest to know he is receiving an experimental drug), and in the final stages before full marketing the study is broadened to include a large number of physicians and patients.

Once a manufacturer has established a drug's safety and effectiveness to his own satisfaction, he can file a New Drug Application with the FDA and see if it meets their acceptance. The material of an application can fill several volumes. In the past, processing time for a NDA was several months, but, as paperwork piles up, it is increasing. The quantity of new drugs receiving approval each year, therefore, whether original formulations or combinations of old drugs, or molecular modifications of patented drugs, is dwindling.10

History of the FDA The FDA was created in response to the greed or dishonesty of many 19th century food producers and the ability '. of modern science to both aid them and expose them. As the transportation network grew in the U.S. after the Civil War and canned and packaged foods became more common, the manufacturer became more remote from his customers both in physical distance and in the complexity of production. Science provided chemicals to change flavors, prevent spoilage, enhance colors, etc., and while these made possible the enjoyment of all foods in all places, regardless of season, they also made fraud much easier. Strawberry jam could be made without strawberries, rotten eggs could be deodorized, and rancid Putter could be revived.11 Not surprisingly the first pressure for anti-adulteration laws came from farmers who saw their market for real eggs, butter, etc. cut by the cheaper fraudulent stuff—state and federal departments of agriculture soon hired chemists to detect product fraud. One of these chemists—Harvey Washington Wiley—proved to be a real crusader, making even Ralph Nader pale by comparison. Through speeches, books, and sheer force of personality he managed to unite the consumers (who were fearful of fraud and poison) and the manufacturers (who feared the competition of the adulterers and sensed the public's growing mistrust of all producers) behind several omnibus food and drug bills culminating-largely as a result of Upton Sinclair's novel The Jungle12in the Pure Food and Drugs Act of 1906 (also known as the Wiley Act). This Act established the FDA, with Wiley as its director, to protect the consumer from injury, deception, and fraud: it had wide police powers to induce compliance with the law (which was amended frequently, always in the direction of greater control). Dr. Wiley didn't stay with the FDA for very long—in 1908 he conducted some research which proved to him that benzoate of soda and saccharin were harmful and he requested President Roosevelt to ban their use in food and drugs. President Roosevelt had used saccharin himself—"President Roosevelt characterized Dr. Wiley's position in these words: 'Anybody who says saccharin is injurious to health is an idiot.'"12, and he designated a board to run the FDA. (Dr. Wiley joined the staff of Good Housekeeping magazine.)

The next major revision of the Food and Drug Act came in 1938, again after a period of crusading, led mainly by Consumers' Research organization and the FDA itself. But the S.E. Massengill Company of Tennessee is general conceded most of the credit—in 1937 their "Elixir of Sulfanilamide" came on the market, and while their chief chemist had tested the mixture of diethylene glycol (a relative of permanent antifreeze) and sulfanilamide for appearance, flavor and fragrance, he had neglected to test it for safety: 107 people, mainly children, died from the 11-3/4 gallons dispensed (the chemist made it 108 with his suicide). The FDA seized the rest of the manufactured supply because it was falsely labeled—elixir implies an ethyl alcohol solution. The 1938 revision, therefore, "required a manufacturer to test any new drug for safety and report the result to the Food and Drug Administration. The agency also was authorized to remove from the market a drug it could prove to be unsafe."14 In addition the FTC and FDA were empowered to regulate patent medicine advertising to prevent false or misleading claims.

The most recent major amendments were those introduced by Kefauver and Harris in 1962. Among other things they required that a drug be shown by the manufacturer to be "substantially efficacious" as well as safe: the FDA, however, was denied the power to sit in judgment of efficacy—the law dealt only with the quantity of evidence a manufacturer must supply before marketing a new drug. A far-sighted observer commented at the time: "Once more we find the Congress refusing to abridge the basic philosophy of our drug law by recognizing again that in the long run the physicians of this country must be the judges of a drug's efficacy and of its safety. The Congress, however, has not stopped (the FDA's usurpation of power] and we can certainly look forward to further expansion by the FDA of its jurisdiction in opinion areas, through the promulgation of regulations and various other administrative techniques including the use of the vast punitive sanctions that are at its disposal."15 In 1966 the FDA had the National Academy of Sciences and the National Research Council (a group of scientists but not M.D.s or pharmacists) review nearly 7000 previously licensed drugs for effectiveness. By 1969 the HAS-NRC evaluation was completed and at least 90 drugs were ordered to be withdrawn from the market, with many others being severely restricted in their advertising, despite the fact that physicians had been prescribing them for years. In essence the FDA is practicing medicine. Congress not withstanding.

In taking these drugs from the market the FDA is using some of the strongest enforcement powers of any government agency. "For any given violation of the Food, Drug and Cosmetic Act, the FDA has a variety of enforcement weapons, from a mere suit for an injunction to an outright seizure of the offending drug before trial and even to criminal prosecution. These remedies can be invoked whether or not the drug itself is safe and effective in fact, for the manufacture of a safe and effective drug by unapproved methods or its marketing with unapproved labeling or advertising is sufficient to violate the Act, whether or not the violation is intentional."16 The FDA can't lose—a drug manufacturer can't make a cent without the FDA's approval, and he'd better think twice before fighting the FDA, no matter how arbitrary the sanction they have brought against him. In addition those few with the temerity to take the case to court really haven't much chance to win—between 1938 and 1964 only one manufacturer requested a hearing to protest the withdrawal order of a previously approved prescription drug—he lost.17 (The FDA has very persuasive lawyers—what judge wants to be responsible for thousands of deaths if he OK's the drug against the FDA's judgment?)

The Costs of FDA Protection The FDA, like many government bureaus, represents a basically sound idea—protection against fraud—perverted by means of political power into a fiefdom which literally rules the drug industry, arbitrarily deciding what products to approve and disapprove. Certainly there is a consumer demand for information on the relative safety and effectiveness of drugs: but are the

FDA's coercive methods the proper way to provide this information? Emphatically not.

The most important defect lies in the very nature of the FDA as a political entity. As such, entrusted with the absolute power of the state, the FDA is subjected to a vast assortment of competing pressures—from Congress, consumer organizations, and drug firms—in the hope that it will come up with a set of rules and regulations which precisely define which drugs are "good" and which are "bad". Vet, as has been shown previously, there exists no preordained dividing line of this sort: the nature of drugs and the nature of human physiology are such that the effectiveness of any drug must be described as a continuum or frequency distribution, from "very harmful" though "no effect" through "very beneficial," depending upon the individuals' unique biochemistry, state of age and health, the size of the dosage, etc. Experimentation can and does establish the nature of this distribution of effects: given this knowledge and data on the particular patient in question, the physician can weigh the benefits and risks, and decide on an individual basis whether or not it is wise to administer the drug.

But the FDA does not operate in terms of individuals—its concern is with the "public interest," i.e., the supposed welfare of the "population as a whole." For this reason, despite the fact that it is impossible, the FDA seeks to define and enforce a black- and-white judgment that a drug is either "effective" or "ineffective." Attempting to put this impossible aim into practice results in several characteristic modes of FDA behavior:

1. The uppermost concern of the bureaucratic mind is rules and procedures, expressed in countless official forms and paperwork. The inference, in the FDA's case, is that if the bureaucrat does not know how to ensure that a drug is "effective," the next best thing is to require such a mountain of paperwork that the bureaucrat is "covered" at every possible turn. As a result, since the FDA began requiring "effectiveness" documentation, the length of time it takes to get a New Drug Application processed has tripled.18 Preparing the monumental paperwork adds millions of dollars to a drug firm's research budget—which has the effect of discouraging smaller (perhaps more innovative) firms from even attempting to get new drugs approved. In 1968 only 14 new drugs were approved, compared with 63, 45 and 41 in 1959, 1960 and 1961,19 the last three years before the "effectiveness" requirement went into effect.

2. A second characteristic of this mentality is the FDA's strongly conservative position with respect to radically new drugs. Since the FDA's black or white verdict on effectiveness is taken by most people as the last word, the bureaucrats are naturally very cautious about which drugs they will "endorse." Thus, promising new drugs which come from sources other than the most prestigious companies or which are based on fundamentally new principles are extremely suspect in the FDA's view. The cases discussed here further on provide some indication of the serious effects of this policy in keeping new drugs from people who would willingly assume the risks associated with their use.

3. The third aspect of the FDA's mentality is merely the ultimate consequence of its simplistic good/bad view of drugs—the forcible intervention in the marketplace to prevent the sale or use of "bad" drugs. The FDA has absolute, unchallengeable power to declare illegal the manufacture, sale, or use of any drug which it deems ineffective by its arbitrary general welfare standards. This means that the essential scientific and medical judgment of the doctor and patient as to the value of a particular drug in a particular case is thrown aside in favor of a government decree, backed up by force. The following cases illustrate the effects of this policy.

Krebiozin There is little point in debating the by-now familiar story of cancer victims and their doctors vs. the FDA over the issue of whether this alleged wonder drug is or is not an effective cancer treatment. The FDA claimed that the developers of krebiozin were quacks and that the drug is worthless; a number of cancer victims have claimed otherwise. It is true that krebiozin was developed by a group of non-prestigious researchers; it is also true that they did not go through the FDA's paper mill of documentation. Nevertheless a non trivial number of cancer patients claimed that the drug had substantially benefited them. Thanks to the FDA, however, krebiozin is now illegal.

DMSO Within the last several years another case similar to krebiozin's has develop ed, this time more significant because the benefits of the drug-dimethyl sulfoxideare extremely well documented. Again as with krebiozin, DMSO was not discovered by a large pretigious drug firm; it is a common commercial solvent, a byproduct of pulp manufacture, whose medicinal properties were first discovered in 1963 by Robert Herschler of Crown Zellerbach Corp. and Dr. Stanley Jacob of the University of Oregon Medical School. DMSO is applied directly to the skin, rather than orally or by injection; its effectiveness is well-documented for treating bursitis, arthritis, scleroderma (a fatal skin-hardening disease), and useful as a local anesthetic. Most important, there is strong evidence that DMSO is effective against leukemia, cervical cancer, and possibly other types of cancer.20

Without warning, however, on Nov. 25, 1965, the FDA banned all clinical testing of DMSO, due to the fact that laboratory dogs, rabbits, and pigs developed changes in the lenses of their eyes when fed huge doses of DMSO. No such changes were found in the eyes of rhesus monkeys, nor in any of the many human patients who had received the drug. No animals developed lens changes when the DMSO was applied to their skins, as it had been with humans, rather than being given orally; moreover, the humans received only 1% of the proportional dose which caused the animals' lens damage.

But to the bureaucratic mind in its impossible quest for certainty DMSO was a dangerous chemical (i.e. one which the bureaucrats might conceiveably be blamed for someday). It was not until a year later, after DMSO was regularly used in Germany and Austria, that the FDA backed off slightly and allowed limited testing to be resumed—under stringent FDA controls requiring each study to be specifically approved in advance.

DMSO's developer, Dr. Stanley Jacob, commented, "Under the current law and its interpretation, were the cure for cancer discovered tomorrow, it would not be available as a prescription drug in the United States for at least seven years. How many people would needlessly die of cancer while the drug was going through FDA red tape?"21—if in fact it made it through at all.

Thalidomide Everyone is aware of the FDA's heroic actions in saving America from the deformed babies produced when the tranquilizer is given to pregnant women. Very few people, however, realize the full impact of the FDA's action in this case. The FDA did not merely warn pregnant women; it enacted and enforces a total ban on the sale of thalidomide within the United States—to anyone, male or female, married or single, young or old, for many of whom thalidomide might be the optimum tranquilizer.

But a recent Associated Press story reveals an even more important use of thalidomide which is being kept from the public by the FDA; it appears that thalidomide is useful in treating leprosy. Under a special FDA exemption, with thalidomide donated by the Merrell Co., doctors at the U.S. Public Service Hospital in Louisiana have reported "very successful results" in halting or arresting extreme leprosy reactions which lead to the crippling, deformity, and paralysis associated with the disease. So far the drug has been used on only 22 patients. "If we had sufficient quantities, we probably would use it in more cases," reports Dr. John R. Trautman, the hospital director.22 The article goes on to say that "the doctors decided to use thalidomide on the basis of other evidence from other countries that the drug, despite its bad reputation, is beneficial in halting leprosy reactions." (Italics added) "We shouldn't let something like [the fetus deformities] throw out a medicine completely," states Dr. Carl D. Enna, chief of the hospital's clinical branch.23 Yet for the duration of the five year Louisiana study, thalidomide will continue to be totally banned, everywhere else in the U.S. And people with leprosy will continue to suffer unnecessarily.

Oral Contraceptives Despite the emotionalism of the recent Senate hearings on the Pill, the fact . remains that pregnancy is over ten times times more dangerous than treatment with oral contraceptives (based on all available figures of comparative death rates per million people).24 Despite this, in recent years the FDA has imposed more stringent requirements on oral contraceptives than on virtually any other drug. For example, toxicity studies with very high daily doses must be made for seven years in dogs and ten years in monkeys before any female contraceptive agent can be tested on humans. This, despite the opinion of many researchers, including the World Health Organization Scientific Group,25 that extrapolation of experimental animal data to human females is of questionable value when dealing with contraceptives—due to the animals' different sex cycles and the difficulties in defining comparative dosages. Dr. Carl Djerassi, one of the pioneers of oral contraception, reported last October that these FDA requirements "have resulted in the recent discontinuance of at least two clinical trials of promising compounds. Even more serious is the fact that, as a consequence, this experience with FDA's practical power to determine scientific protocol has led one of the largest of American drug companies (which does not market any contraceptive agent) to discontinue virtually all research on contraceptive agents chemically related to female steroids."26 Dr. Djerassi adds, "There is little doubt that if the present climate concerning clinical testing of contraceptive agents had existed 15 years ago, none of the steroid oral contraceptives now being used would ever have been developed."27

We may never know how many other promising, life-saving drugs have been held up or canceled because of the FDA. Suffice it to say that the over all effect of all of the FDA regulations and legal weaponry is to make a manufacturer think several times before even taking a drug out of his lab. Why should he go through the bother of filling out the huge IND forms, the even larger NDA forms, pay for testing, manufacturing, and advertising?—His drug stands a slim enough chance in the very competitive drug field anyway without having to face constantly expanding regulations and police powers. Many companies handle the problem by canceling a drug rather than developing it;28 others seek out less regulated foreign markets29—either way patients and doctors in the U.S. lose a chance to try a new and possibly better drug.

Some Thoughts on an Alternative The most subtle—and perhaps most damaging—aspect of FDA regulations is not their effects on the drug industry, but their effects on the general public and physicians. Everyone, including the doctors, feels that "someone" is seeing to it that drugs are safe and production standards high. The result is an uncommon amount of ignorance and misplaced trust. As Morton Mintz points out in Therapeut, Nightmare (a very pro-regulation book), the FDA simply isn't doing the protecting that everyone assumes it is. Thalidomide was their big and nearly only coup.

As has been pointed out, fraud is a proper concern of the law; whether the specialized knowledge required to deal with drug fraud implies the need for a special, full-time agency (rather than merely allowing suits against the drug companies), is an interesting question which this article will not attempt to cover. What is of concern, however, is to investigate how an unregulated market could deal with the issue of relative safety and effectiveness.

In his article, "The Assault on Integrity,"30 Alan Greenspan points out that reputation is a major tool in an unregulated economy and that manufacturers would vie to have a reputation for honest dealing and quality products. Unfortunately he chose the drug industry as his example; even in a free economy this industry is one of the least amenable to rating by the consumers. Specialized knowledge is needed in order to judge the quality and purity of the product; the consumer is generally using the product under orders from someone else (i.e., the doctor), and in many cases, he may not be in a condition to make a carefully-reasoned judgment—he may be sick or frantic with worry about someone else who is. This does not excuse the consumer, particularly one with chronic medicinal needs, from being as well informed as possible (most people today can't even identify by name what they are taking let alone know what side effects to be alert for or what to do in case of accidental overdose); this suggests, however, that for the purposes of judging drugs the doctors are the ones who count as consumers. This is certainly true today when drugs can only be gotten via a doctor's prescription (and the doctors are the objects of all prescription drug advertising), but even in an unregulated market most people still would go to a doctor simply because he has the specialized knowledge and they do not (just as people currently consult lawyers even though a lawyer is not officially required in most cases). Certainly then it would be in the doctor's interest, as a man of professional integrity and also as a businessman who wants to keep customers, to prescribe the best drugs he could.

At the present time the doctor gets most of his information through drug company salesmen, the Physician's Desk Reference (the PDR)—in which drug companies do their own product write-ups, the AMA's New and Non-Official Drugs (produced once a year by the Council on Drugs), or, if he has the time in his busy practice, from journal articles and letters. It should be obvious that over half of his information is coming from a biased source—the companies themselves. It is common (in some groups) to think of all industrialists as virtuous capitalists, and many are; but it must also be remembered that the FDA was originally set up with the legitimate function of detecting fraud and mislabeling, and even in recent years some drug companies (e.g. Merrill in the case of MER/29) have been convicted of falsifying data and suppressing knowledge of severe drug reactions.

What is needed, and what would almost certainly exist in the absence of the FDA, is an independent agency similar to Consumer's Union that would evaluate company claims and tests, run tests of its own where necessary, keep abreast of the medical literature, col lect physician reports of drug reactions (the AMA is currently working on a computerized system), and then dispense the information to its subscribers (or members, if the AMA were to expand its Council on Drugs). Certainly it would be in the interest of physicians and some laymen to use such a service. In today's regulated environment, in which the government is presumed to be taking care of everything, only one-eighth of all U.S. physicians subscribe to the one modest newsletter which reports systematically on drug side-effects.31 The fortnightly, nonprofit "Medical Letter" costs only S12.50 per year and has established an excellent reputation—but most doctors continue to rely on company sales brochures and the FDA as their primary sources of information.

Such is the pervasiveness of government regulations and the mentality that trusts them—it is no wonder that people scream that if the FDA were to be abolished we'd all be poisoned: if people were to continue to use so little caution and intelligence in selecting drugs and physicians to advise them, that could very well happen. Any industry needs an incentive for excellence if the thugs are not to take over. The FDA provides an incentive based on fear, via a government-backed gun. If the FDA were abolished, physicians and consumers, by means of testing labs and computerized information systems, could provide an incentive based on reputation. Doctors and patients would at last be free to make their own decisions about what risks to take in using a particular drug, free of government coercion. And one's full ownership of his body would advance another step towards being a legal reality.

Lynn Kinsky spent 1½ years as an organic chemist working in the medicinal chemistry section of a large international drug firm. She got her BS degree in chemistry from the University of Wisconsin in 1966 and has done graduate work in organic chemistry at Dartmouth College. The section of this article dealing with the costs of FDA protection was researched and written by contributing editor Robert Poole.

Footnotes
1. "Nader's Raiders on the FDA: Science and Scientists 'Misused' ", Science, 17 April, 1970, pp. 349-352.
2. Green and Goldberger, Molecular Insights into the Living Process, p. 363.
3. Morton Mintz, The Therapeutic Nightmare, p. 277.
4. Ibid, p. 18.
5. Ibid, p. 9.

6. See "Chemical and Engineering News", May 19 and June 2, 1969.
7. This industrial support is likely to be lost if the government persists in its policy of not allowing patents for anything resulting from government funded work, no matter how minor the government support. The drug industry is vitally dependent upon patents, but few university projects are without NIH, NSF, NIMH, of PHS grants of some sort. The impact will most likely be felt in the development of rare disease drugs, and in the clinical testing of industrially developed drugs (the largest clinics are generally part of a medical school).
8. "Key Facts About the U.S. Prescription Drug Industry" -Pharmaceutical Manufacturers' Association publication.
9. Proceedings, Commission on Drug Safety, James H. Luther speaker, 1963.
10. "Drug Industry," May 9, 1969, p. 509.

11. Young, "Social History of American Drug Legislation," Drugs in Our Society, p. 218.
12. Exposing the filthy conditions in meat packing houses, Young (p.223) reports that the sale of meat fell by half!
13. Klumpp, Proceedings; Committee on Drug Safety, p. 157.
14. Therapeutic Nightmare, p. 49.
15. Klumpp, op. cit., p. 165.

16. Lloyd Cutler, "Practical Aspects of Drug Legislation," Drugs in Our Society, p. 153.
17. Ibid, p. 154.
18. The Value Line Investment Survey- Drug Industry, May 9, 1969, p. 510.
19 Ibid.
20. Jacob, Dr. Stanley W. and Donald C. Wood, Ph.D., "Dimethyl Sulfoxide (DMSO)—Toxicology, Pharmacology, and Clinical Experience," American Journal of Surgery, September 1967.

21. Mosely, Hazel, "A Case of Overprotection," Analog, April 1970, pp. 61-71.
22. "Thalidomide Combats Leprosy," Associated Press dispatch, as reported in the Boston Globe, June 29, 1969.
23 Ibid.
24 Djerassi, Carl, Ph.d., "Prognosis for the Development of New Chemical Birth Control Agents," Science, 24 October, 1969, p. 470.

25. "Hormonal Steroids in Contraception," World Health Organization Technical Report Ser. No. 386, 1968.

26. Djerassi, op. cit.
27 Ibid.
28 The author's company recently pulled a promising cardiovascular drug out of clinical testing after an FDA staff scientist reported at a conference that a structurally similar drug caused mutations in bacteria.
29. "Drug Industry," May 9, 1969, p. 510.
30. Alan Greenspan, "Assault on Integrity" in Ayn Rand's Capitalism, The UnKnown Ideal, 1966.

31. Joseph Garland, "Dissemination of In formation on Drugs", Drugs in Our Society, p. 209.