A Matter of Life and Death

If our neighbor George were terminally ill, we'd never dream of entering his home at gunpoint to take away a medicine that might save him. Similarly, we'd be furious if a family member had an incurable disease, but George stopped our loved one at gunpoint from taking a medicine that might help. As individuals, we honor our neighbor's choice. If we think our friends are choosing poorly, we might try to dissuade them. However, the final decision has to be left to them, in consultation with a physician, if that's what they wish. After all, it is their health at stake, not ours. Most of the time, they will know better than we what is best for them, and we'll know what's best for us. We practice non-aggression by taking responsibility for our own choices and by letting others do the same. Forcing our choices on others is an attempt to take responsibility for their lives.

When we deal with our community, state, and nation, however, our attitude is entirely different. Somehow, we think that forcing our choice on others becomes transformed into benevolence. For example, we support laws that stop manufacturers- at gunpoint, if necessary-from selling medicine that has not been licensed or approved by the Food and Drug Administration (FDA). We refuse to honor our neighbor's choice; instead, we instruct our FDA to make up their minds for them at gunpoint, if necessary. The effect is the same as if we used such aggression against George. Life-saving medicines are ripped out of the hands of our fellow Americans-literally!

AIDS and the Drug Lag

Until July 1988, customs officials took dextran sulfate away from AIDS victims who were returning to the United States after traveling all the way to Japan to purchase it. (1) At the time, no one knew if dextran sulfate could cure AIDS, but it did prevent the HIV virus from attacking white blood cells in a test tube. (2) If dextran sulfate prevented this attachment in a person's body, it might have stopped the virus from destroying its victim's immune system. Until it was proven to work, the FDA kept it from being sold in the United States-at gunpoint, if necessary.

Many AIDS victims didn't feel that they had time to wait until all the testing was done. Since they were the ones most affected by a decision-right or wrong-they thought we should honor their choice. Unfortunately for the AIDS patients, our laws dictated otherwise. As the Customs officials confiscated their new hope at gunpoint, the true impact of our aggression was unveiled. Our food and drug laws can kill if they delay life-saving therapies from reaching terminally ill individuals.

The spectacle of the AIDS victims being denied drugs that might be beneficial to them has helped us to see the results of our aggression clearly. FDA Commissioner Frank Young courageously began allowing individuals under a doctor's care to import medications from other countries for personal use. (3) Many of these pharmaceuticals are not sold here be-cause of the "drug lag" our laws have created.

Thus, the United States gets most new medications long after they are available in other countries, because our licensing laws are the most aggressive in the world. The FDA requires manufacturers to perform many years of testing, with costs estimated at $200 million. (4) The manufacturer ships truckloads of data to the FDA, which then takes an average of two and a half years to decide if enough testing has been done. (5) Meanwhile, people whose lives might hang in the balance are prohibited-at gunpoint, if necessary-from buying the new drug. Like all licensing laws, regulations governing our pharmaceuticals decrease the availability of new drugs and increase their cost greatly.

We all want the medicine we take to be tested thoroughly to be sure it's safe and effective. We also want breakthrough therapies as soon as possible to alleviate pain and suffering. Testing takes time and delays the availability of a new medicinal drug. If we wait for testing, we may suffer (or even die) for lack of treatment. If we don't wait for testing, we may take a cure that's worse than the disease. How do we decide what's best?

The Marketplace Ecosystem: Honoring Our Neighbor's Choice

Before 1938, Americans decided by themselves, or in consultation with their physician or pharmacist, which medicines were best for them. To aid the consumers and their physicians in evaluating pharmaceuticals, independent groups, notably the American Medical Association and Consumers' Research, first began evaluating and then testing pharmaceutical products. Other evaluations by physicians and pharmacists were reported in their trade journals and special lay publications as information about specific remedies emerged. (6) Intermittent articles appeared in Ladies' Home Journal and Collier's to alert readers to the dangers of specific products, (7) as did books written for the same purpose. (8) In 1904, the General Federation of Women's Clubs sent out thousands of letters, promoted lectures and exhibits, and distributed information to educate the public about specific problems. (9) Even when the modern pharmaceutical industry was in its infancy, the marketplace ecosystem responded naturally to protect the consumer. On the basis of these independent opinions, Americans made choices about which medications to take and honored their neighbor's choice.

Much of the drug toxicity observed in those days dealt with side effects that were not predictable from state-of-the-art knowledge. For example, we now know that some drugs are perfectly safe when given once or twice, but can be quite toxic if taken often. Earlier in this century, however, the frequency of this effect was not appreciated. As a result, more than 100 people who repeatedly used local antiseptics containing silver salts developed a blue-gray caste to their skin. (10) Thallium, a component of rat killer, was successfully used to treat ringworm. When applied routinely as a depilatory cream, however, at least 32 women died of its toxic effects. (11) Because of such incidents, multiple doses of modern pharma-ceuticals are tested in animals before recommending even a single dose to humans.

Unfortunately, drug toxicity cannot always be predicted by animal testing. Animals can be unaffected by drugs that can cause devasta-ting side effects in people. Dinitrophenol, used as a diet pill in the early 1930s, caused cataracts in 177 women, but none in the test animals. (12) In the early 1930s, amidopyrine killed 1,600 people in the United States, while the Spanish, with different genetic ancestry, were unaffected. (13) Because of a genetic sensitivity, paraphenylenediamine caused blindness in (1) out of every 120 women who colored their eyelashes with Lash Lure. (14) These idiosyncratic effects are not seen in animal studies and are not readily predictable even today.

The bottom line is that there is no such thing as a drug that is safe for everyone. Even life-saving penicillin has killed those who were allergic to it. The risk of experiencing an unpredictable side effect has to be weighed against the benefits each individual hopes to get. Before the aggression of FDA licensing laws, every individual did exactly that, and let others do the same. Individuals honored their neighbor's choice. Some people were willing to take more risks than others; some did not like the idea of taking any drugs at all. Each person took responsibility for his or her choice and honored the choices of others.

Most manufacturers realized that killing the customer was bad for business, and did safety testing before marketing their drugs. Careful manufacturers wooed the public and increased profits by advertising that "We have never yet had reported a case of sudden death following the use of our Antitoxin," or that their products had been tested and approved by various outside laboratories. (15) Brand name loyalty rewarded the drug manufacturer who always gave the customer what was promised. Manufacturers reaped as they sowed. Producers of questionable products simply had too few customers to stay in business. (16)

However, a few manufacturers were not so careful. Elixir Sulfanilamide was the most tragic example of this. It contained a safe drug, dissolved in an unsafe solvent, which was not tested before its sale in 1937. As a result, 107 people died. (17) The AMA had not granted the Elixir its Seal of Approval;18 the marketplace ecosystem protected those who cautiously awaited further testing, while honoring the choice of those who believed the risk of taking a product that had not been independently evaluated was warranted.

This incident showed Americans how important a critical evaluation of pharmaceuticals could be. Had the marketplace ecosystem been kept free from aggression, the AMA and other independent evaluators probably would have extended their drug evaluations in the wake of the Elixir Sulfanilamide tragedy. Charging manufacturers a fee for examining their products could have funded such a system. Careful consumers could choose to buy only approved products.

Manufacturers who fraudulently misrepresented their products should have been required to compensate victims or their families as described in Chapter 13 (The Other Piece of the Puzzle). Such compensation would not only help to undo the damage, but it would deter future aggression. Even in the case of death, a monetary settlement to the victim's family is better than no restitution at all! Unfortunately, Americans took another tactic. They decided to try to deter aggressors by becoming aggressors themselves. In doing so, they created a cure worse than the disease.

Aggression Disrupts the Marketplace Ecosystem

In 1938, laws were passed demanding that each manufacturer obtain approval from the FDA (i.e., a license) before selling each drug. (19) The FDA relied primarily on its evaluation of the safety testing performed by the manufacturer. If individuals wanted to buy the drug before the FDA was satisfied, government enforcement agents would stop the manufacturer-at gunpoint, if necessary-from selling it to them. As the FDA demanded more and more testing, many small manufacturers of folk remedies closed their doors, eliminating diversity of products and favoring larger firms. As a society, we no longer honored our neigh-bor's choice; instead, we used aggression to force others to do things our way "for their own good." As the number of tests grew, so did the time taken to perform them. As with all licensing restrictions, the availability of new therapies decreased.

The Illusion of Protection: Thalidomide

New drugs usually appeared on U.S. pharmacy shelves many years after they had been sold overseas in countries with less-aggressive licensing laws. Sometimes this drug lag protected us from pharmaceuticals with side effects that were difficult to predict through animal studies. Thalidomide, for example, was marketed in Europe for several years as a sedative while its manufacturer sought approval to sell it in the United States. In the early 1960s, the sensitivity of an unborn child to drugs that are quite safe for the mother was not widely appreciated, so doctors began prescribing thalidomide to pregnant women, even though no safety testing had been done in pregnant animals. Thalidomide prevents normal development of arms and legs in unborn humans, monkeys, and a single strain of rabbit. (20) If animal testing had been performed in standard test animals (rats and dogs), thalidomide probably would have appeared to be safe. Unfortunately, for human babies, it was not. Approximately 12,000 European children were born with deformed limbs. (21) Few American babies were affected, because only a few test samples had been distributed in this country. The FDA physician who had delayed its approval was given a Presidential award. (22) By such feedback, we instructed the FDA to give us safety by aggression-at the cost of our very lives.

While other countries did not react to the thalidomide tragedy by changing their licensing laws substantially, Congress gave the FDA a mandate to use more aggression. Manufacturers had to complete extensive human tests to demonstrate that their drugs were effective. (23)

Naturally, manufacturers already did such tests, but not the elaborate way that the FDA demanded. Longer and larger studies had to be undertaken. Foreign testing was only infrequently considered acceptable to the FDA, forcing manufacturers to repeat studies that had been done elsewhere. In the meantime, manufacturers would be stopped-at gunpoint, if necessary-from selling such drugs.

Did these additional tests save us from drugs that were ineffective? Apparently not! Studies suggest that consumer waste from purchasing ineffective drugs changed little after the additional studies were mandated in 1962. (24) Evidently, patients and physicians are usually able to tell if a drug has the desired effects and will stop using it if it doesn't work. Companies desiring the positive feedback of profit quickly find that they must please their customers.

Did the 1962 regulations save us from more side effects? Apparently not: the percentage of newly approved drugs taken off the market in the United States was the same as in Great Britain, which did not substantially change its licensing procedures in the immediate aftermath of thalidomide. (25)

Paying with Our Lives

While the British continued to enjoy many new drugs to treat their illnesses, only half of these were available to Americans, and only after many more years of waiting. (26) One of these new drugs denied to Americans was propranolol, the first beta-blocker to be used extensively to treat angina and hypertension. In the three years between introduction into the United Kingdom and the United States, approximately 10,000 Americans died needlessly every year, (27) because it was against the law for their doctors to treat them with propranolol. Even in 1968 when propranolol became available in the United States, it was approved only for minor uses. Advertising propranolol as a treatment for angina or hypertension was illegal until 1973 and 1976, respectively, so countless other Americans died because their doctors hesitated to prescribe the drug for a use that was still unapproved by the FDA. When the FDA finally gave approval, it was criticized by a congressional committee for exposing the American public to a drug with potential side effects! (28) Since every drug has side effects in some individuals, asking the FDA to license only drugs that are completely safe is asking them to approve no drugs at all!

Our aggression, applied to this single drug, cost at least 30,000 American lives. Britain also practices the aggression of licensing laws, but to a lesser extent than the United States. Thousands more lives might have been saved if no aggression were present at all.

Deaths We Can Only Guess At

The more tests that a pharmaceutical firm has to perform, the longer it takes. Extra years of testing mean that drugs cannot be sold until the patent on them has almost expired. Thus, companies focus on drugs that can be used widely, and do little research on cures for less widespread diseases. Unpatentable therapies, such as vitamin and mineral regimens, are not studied or developed, because the manufacturer cannot recover the cost of FDA-mandated testing without some exclusivity.

As a researcher in a major pharmaceutical firm, I have been intimately involved with the licensing laws governing the marketing of therapeutic drugs. Some of my work dealt with the natural prostaglandin hormones or their synthetic analogs, which could partially prevent the deleterious effects of various toxins on the liver. (29) More than 100,000 people die each year from alcoholic liver disease for which bed rest and abstinence are the only, and often ineffective, treatments. I approached management with a win-win idea: test whether prostaglandins added to alcoholic beverages would lessen the chance of alcoholic liver disease. My employer would profit while it helped to prevent illness and death.

Unfortunately, the FDA would never permit such a thing, for it would appear as if we were encouraging people to drink. A major distiller was reputed to have tried to add vitamin B-1 to alcoholic beverages with the same end in mind and was met with a negative reception by the regulatory agencies. (30) We might be able to develop the prostaglandin as a pill to be taken daily by the drinker, but it would require a prescription; people who were ashamed to tell their doctor they drank a lot might forgo the medication. If we decided to go ahead, we still had to do the studies that the FDA required to show that it worked with 95% certainty. Since alcoholic liver disease takes years to develop and probably many years to cure, we would have to sÿÿ
hundreds of individuals over several years. Not only would this be costly, but heavy drinkers don't always take their medicine regularly. To ensure that we had enough individuals who actually got the prostaglandin, we'd need even more study participants. Furthermore, we weren't sure exactly how to measure our progress, other than waiting for people to die, because no other drugs had been successful in alleviating this damage. We might collect data for years only to find out that we had only enough patients to show that it worked with only 80% certainty-not good enough for the FDA. Meanwhile, our patent would be close to expiration. Without patent protection, we could not re-cover the cost of all these studies. Generic manufacturers would undersell us because they would not need to recover the gargantuan cost of testing. The win-win situation evaporated with the aggression of licensing laws, since we could not legally sell the prostaglandin as a drug that might work. My employer lost only a source of profit; people with alcoholic liver disease continue to lose their lives, perhaps needlessly.

Unfortunately, this story is not unique. Aspirin deforms the unborn young of almost every animal species but humans (31) and could not be marketed today if it had to go through FDA evaluations‡ÿøa new drug! Penicillin, digitalis, and fluroxene might have met a similar fate, (32) costing thousands upon thousands of lives. Many more lives have probably been lost by the aggression of licensing laws than have been saved.


A Lose-Lose Situation

We never intended that licensing laws should kill. We wanted only to protect ourselves from selfish others who might sell us something that would kill instead of cure. What went wrong?

We chose the aggressive means of licensing laws, which led us to health care poverty. Just as physician licensing limits the number of practitioners, and thereby lowers the quality of care delivered, so too does licensing of drugs lower the availability and raise the cost of life-saving pharmaceuticals.

A two-year delay in a cancer therapy that reduces mortality by only 10% would cost about 66,000 American lives (33)-many, many more than have died from all the drug toxicity in this century. The great loss of life caused by the delay of the single drug, propranolol, was a tragic, real-life example of the fruits of aggression. Before licensing laws, the largest example of manufacturer neglect was the unnecessary deaths of 107 people taking Elixir Sulfanilamide. The marketplace ecosystem, when free from aggression, is the best consumer protection of all.

Just as physician licensing created a cartel that excludes innovators and keeps fees high, so too do large pharmaceutical firms profit at the expense of the small ones. The increasing cost of development imposed by our aggressive regulations puts the smaller firms at a disadvantage. (34) As requirements increase, mergers become necessary and the number of firms decreases. A few large firms dominate the industry when newcomers are excluded by the high cost of satisfying the FDA. The price of each drug that is marketed reflects these incredible costs.

The advantage of the large pharmaceutical firms is largely an illusion, however. Their taxes are increased to pay the salaries of the law enforcement agents, who produce no new wealth. Creation of wealth is compromised as the health of the nation deteriorates. Even if the large manufacturers have a bigger piece of the Wealth Pie, its absolute size is less than it would be without aggression. Nobody wins.

The real tragedy affects everyone, including those in the pharmaceutical cartel and the FDA itself. When our loved ones are dying of "incurable" diseases, we all pay the ultimate price for our aggression. Perhaps we should consider a better way.

The Easy Way Out

If licensing laws do us more harm than good, how do we ensure that our drugs are safe and effective?

If the aggression of licensing laws ended, patients and their physicians could buy whichever drugs they felt might be helpful, regardless of the stage of testing. Since they could not competently evaluate every drug for themselves, they would probably rely on a professional or consumer's group for a status report on pharmaceuticals they were considering. Patients and physicians could choose to defer to one of these "authorities," but none could force adherence to their verdict.

Such advisory groups operated in this country before the introduction of the licensing laws. The AMA's Seal of Approval Program and Consumers' Research actually tested pharmaceuticals and cosmetics in their own laboratories instead of simply reviewing manufacturer testing, as the FDA does now. Elixir Sulfanilamide had not been approved by the AMA; (18) patients and/or their doctors who waited for the Seal of Approval before purchasing new drugs were protected from its lethal effects. The marketplace ecosystem protected them without aggression and without denying access to life-saving pharmaceuticals that they may have chosen before AMA approval.

Modern testing or evaluation groups might be funded by concerned citizens such as the Women's Clubs of the past, operate for the benefit of its members as the AMA and Consumers' Research did, charge the manufacturer an evaluation fee, or provide information to individuals for a small charge. The positive feedback of profit would encourage testing by several groups. We would have independent evaluations, rather than an examination of the manufacturer's data by the FDA alone.

An example of modern day independent drug evaluations is the Medical Letter on Drugs and Therapeutics, whose revenue is derived totally from subscriptions to doctors, medical students, pharmacists, and pharmaceutical companies. (35) By reversing the aggression of licensing laws (i.e., deregulation), we would enjoy a much wider range of safe and effective therapeutic drugs than we do today.

However, the benefits of deregulation can be sabotaged by the aggression of fraud. Drug companies that attempt to deceive consumers by falsely claiming that they have certification or seals of approval perturb the natural balance of the marketplace ecosystem. In Chapter 13 (The Other Piece of the Puzzle), we'll learn how the second principle of non-aggression-righting our wrongs-restores the balance while deterring future aggression. Before examining this concept in detail, however, we need to explore more fully the problems that our own aggression creates.

We're not prepared to march into people's homes like the Gestapo and take drugs away from desperately ill people.

- Frank Young, former FDA Commissioner

...the penalties imposed by the marketplace on sellers of ineffective drugs before 1962... have left little room for improvement by a regulatory agency.

- Sam Peltzman, REGULATION OF PHARMACEUTICAL INNOVATION: THE 1962 AMENDMENTS

...the U.S. system of approval, in spite of greater restrictiveness and insistence on detail, has not proved markedly superior in the prevention of marketing drugs that are subsequently discontinued in light of safety questions.

- Olav Bakke et al., Center for the Study of Drug Development, University of Rochester, N.Y.

...rarely, if ever, has Congress held a hearing to look into the failure of FDA to approve a new entity; but is has held hundreds of hearings alleging that the FDA has done something wrong by approving a drug... The failure to approve an important new drug can be as detrimental to the public health as the approval of a potentially bad drug.

- Alexander Schmidt, former FDA Commissioner

...according to George Hitchings, co-winner of the 1988 Nobel prize in medicine, FDA's five-year delay in approving the anti-bacterial drug Septra cost 80,000 lives.

- Sam Kazman, Competitive Enterprise Institute

...the pattern of intervention into science from a combination of local, state, and federal sources has moved from reasonable control to something close to chaotic strangulation.

- Donald Kennedy, former FDA Commissioner

If even one new drug of the stature of penicillin or digitalis has been unjustifiably banished to a company's back shelf because of excessively stringent regulatory requirements, that event will have harmed more people than all the toxicity that has occurred in the history of modern drug development.

- William Wardell, Professor, University of Rochester, N.Y.

...economic studies have been virtually unanimous... FDA regulation certainly cannot be proved "safe and effective"-thereby flunking its own approval criterion.

- Dale Gieringer, Wall Street Journal