Science Fiction Project - Free Culture
Analog - All editorials - John Wood Campbell
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THE LESSON OF THALIDOMIDE
The thalidomide disaster is, of course, by no means finished; it will continue to be a disaster at least as long as any of the affected babies are living. And the lesson the human race can learn from that thalidomide disaster should go on... well, really, forever.
Unfortunately, I have not seen the proper lesson of the thalidomide results published anywhere; what I have seen published has, in every case, been exactly the wrong lesson.
Many thousands of years ago now, Man first learned - first of all animals - the correct lesson from being burned by fire. The lesson had to do with how you could handle fire; the other animals only learned to fear fire.
The importance of that difference is that they are still animals - and this is Man's world.
The basic lesson to learn from the thalidomide problem is, simply, that human beings were, are, and always will be expended in the process of learning more about the Universe we live in - and that we'd be wiser to acknowledge that, and accept it. When you do true exploration into the Unknown - some explorers are going to die. John Glenn stated very flatly that men were going to be killed in the effort to penetrate space - that he was lucky, but that deaths were inevitable.
The human race just expended several thousand babies in a battle against disease and misery; this has happened before, and we would be most wise to recognize quite clearly - as clearly as Glenn recognized his danger - that it will most certainly happen again.
And there isn't one thing we can do about it.
Human life is not sacred; it is expendable for cause. The Universe doesn't hold it sacred, quite obviously; if we do, we're unrealistic - which means essentially, "neurotic".
Let's take a solid, rational look at the story of thalidomide.
In the first place, Dr. Frances Kelsey acted in a whimsical, arbitrary, illogical, and unscientific manner in failing to license thalidomide for distribution in this country. Her course of action - actually, her course of inaction - was absolutely unjustifiable.
The fact that it was completely correct and right has nothing whatever to do with the question of whether or not it was logical, scientific, or justifiable. It may have been a case of pure "woman's intuition" working with illogical, but magnificent accuracy. It may have been a case of precognition - of seeing the future accurately. If either were the case, it would have been totally unscientific, illogical, indefensible... and right.
It might have been simply someone with a constitutional inability to make a decision who kept thalidomide off the market in the United States - one of the type who simply can't bring themselves to make a definite decision.
Such a person would have been just as helpful, in this case, as Dr. Kelsey.
Fundamentally, Dr. Kelsey had absolutely no scientific reason - no defensible justification - for not granting thalidomide a license. Her actions with respect to the ethical pharmaceutical company seeking to produce it were arbitrary, whimsical, and unjust.
All of those statements remain one hundred per cent true despite the fact that she saved hundreds, or thousands, of personal tragedies by her inaction. The only circumstance under which it could be held that her actions were logical and just are that you hold that Dr. Kelsey had clear, reliable, dependable extrasensory perception by which she perceived clearly and reliably the future facts that, at the time, were not available.
And that is, basically, why we must acknowledge and accept that the thalidomide type disaster will recur so long as human beings seek to explore for a better way of doing things.
Study the history of thalidomide briefly: it was synthesized first by a Swiss pharmaceutical firm. Tests of the new compound were made on animals, and it was found that thalidomide had no effects - either positive or negative. It was an "inert ingredient" so far as the animals were concerned; the substance was abandoned in 1954.
Then the West German company, Chemie Grunenthal, started further investigations on it. Their careful tests also showed that it had no pharmacological effects on animals. The only reason they persisted was that thalidomide had now acquired a "crucial experiment" importance, practically. According to the best theoretical understandings, that particular type of molecular structure should have sedative effect - and if thalidomide did not have any effect the theory needed some serious reworking.
So Grunenthal tried it on human patients - on epileptics as a possible anticonvulsant. It did not act as an anticonvulsant, but did act as an excellent sleep-inducer, in human beings. It gave restful, all-night sleep without after-effects, and was remarkably safe - so safe it could be sold without prescription. It was, literally, safer than aspirin; would-be suicides have succeeded by taking sufficiently massive quantities of aspirin - but would-be suicides who tried massive doses of thalidomide simply woke up after a somewhat prolonged sleep. It was far safer than the barbiturates; Marilyn Monroe's death by barbiturates would not have succeeded, had thalidomide replaced the barbiturates as tranquilizer-sedatives.
The "goofball" addiction would not be able to replace barbiturates with thalidomide; it doesn't act that way.
Thalidomide, as of 1960, had proven itself to be by far the safest, gentlest, most nearly fool-proof sedative pharmacology had yet discovered. Even by intent, a man couldn't hurt himself with the stuff!
The situation then was that a drug which could replace the very useful, but somewhat dangerous, barbiturates had become available - a drug so safe small children could use it - and so safe small children getting into the forbidden medical cabinet wouldn't kill themselves with it.
As of late 1960, then, Dr. Kelsey's whimsical, arbitrary, and unjustified action - or inaction - was keeping from the American public a drug which could replace a definitely dangerous, definitely toxic, and somewhat habit-forming drug, the barbiturates.
Thalidomide had been tested again and again by major ethical pharmaceutical houses, had been approved for non-prescription sale by government after government, and had been widely and safely used by many millions of people all through Europe.
Dr. Kelsey was, by nit-picking and dillydallying tactics, blocking the licensing of a safe, proven, and cheap replacement for a known-to-be-somewhat-toxic drug.
Logically, that position was totally unjustifiable.
It had all the earmarks of a petty Civil Servant tyrant, fussing endlessly, delighting over the power red-tape gave...
At this time - say January, 1961 - there was no scientific reason to doubt that thalidomide was one hundred per cent safe, and a very successful drug.
In early 1961, some reports of a polyneuritis effect due to long-continued massive dosing with thalidomide began to appear. Its symptoms were a tingling "leg's gone to sleep" sort of feeling in hands and feet; discontinuation of the thalidomide dosing cleared up the cases usually, fairly promptly.
Be it remembered that the barbiturates, which thalidomide sought to replace, were favorite suicide pills, were habit forming, and had plenty of not-so-good possibilities latent in them. Of the two, thalidomide was far and away the safer... on the basis of all available data.
But that slight tendency to peripheral neuritis when overused for long periods was the only slightest indication that thalidomide had any untoward effects.
Dr. Kelsey promptly used that data as a basis for more, and more elaborate nit-picking and inaction. She demanded more reams of then-unobtainable data. Her position was, at that time, for the first time, faintly logical - slightly defensible on the basis of scientifically acceptable data. But it would still be rated as poor judgment and exaggerated caution. The American pharmaceutical company seeking to market thalidomide, naturally, was growing quite impatient with the unjustifiable and indefensible, and thoroughly illogical delaying tactics that were blocking them.
Neither "womanly intuition" nor "a strong hunch" has ever been held to constitute adequate grounds for governmental rulings, and precognition isn't considered to exist.
A German doctor was the first to suspect thalidomide of its actual disastrous characteristic - and it was November 15, 1961 that he first warned the Grunenthal company that he suspected their thalidomide preparation of being responsible for the "sealbaby" epidemic then appearing in Germany. At this time his data was still too scanty for him to make a definite statement. His first public discussion - "public" in the sense that it was made to an official medical group meeting in Germany - was on November 20, 1961 - and then he was not in a position to state that thalidomide was responsible, but merely to say he strongly suspected a certain drug, which he did not name.
At this point in the development of the problem, data came in very rapidly; within a month thalidomide's danger was clearly recognized... and only then did Dr. Kelsey's inaction on the licensing application become absolutely defensible.
That the United States was saved from this disaster was not - repeat not - due to any scientific, logical, reasonable or even justifiable action. It was due to those totally indefensible and anathematized things, "a hunch" and/or "woman's intuition".
That Dr. Kelsey's hunch was one hundred per cent valid has nothing whatever to do with whether it was logical; for all I can know, she may have perfect and reliable trans-temporal clairvoyance, so that, in 1960, she was reading the medical reports published in late 1961, and basing her decisions very logically on that trans-temporal data.
The essential point is that no possible logical method can prevent another thalidomide-like disaster.
If the Federal Drug Administration can recruit a staff of expert crystal-ball gazers, tea-leaf readers and Tarot-card shufflers, it might be possible for the F. D. A. to rule correctly on all future drug licensing applications. Nothing short of genuine precognition can prevent such disasters completely.
Let's imagine the most completely and perfectly conservative, cautious, experimental program we can think of that will still allow some progress in medicine.
Suppose we require the following steps:
1. Careful and complete animal testing before any human testing is permitted.
2. A two-year test period on a very limited number of human beings so that, if there is some joker in the deck, it will afflict only a small number of people at worst.
3. A second two-year test on a larger number of patients - say about ten thousand people.
4. Released as a prescription medication only for another two-year period, so that close observation can be maintained.
Sounds reasonable and conservative? And yet there are a few known instances where a substance has a time-bomb effect so delayed that as much as fifteen years may elapse before the deadly effect appears. Beryllium dust poisoning is one example of a time-delay bomb. If you inhale BeO dust, it definitely won't hurt you a bit right away - and cases of a fifteen-year delay have been reported.
Inasmuch as we now have pretty good indication that genetic information is carried as a chemical code on protein molecules, it's conceivable that a substance might be discovered which affected only the genetic cells of unborn babies. That one would first begin to show its effects about eighteen years after it went into use (yes, some girls affected by the stuff would start having babies at thirteen or so... but not until a large number of affected individuals had babies would the statistical numbers become large enough for credibility and identification).
So even a very, very cautious five-year system wouldn't catch all the time-bomb drugs.
And we can't run a fifty-year program like that! If someone finds a cancer cure today, will the world wait until our grandchildren demonstrate that it has no hidden menace, do you think?
And as to that cautious, two-year-plus-two-year program... thalidomide would have been licensed with flying colors!
Test 1 is the animal test. Thalidomide proved completely harmless - in fact completely ineffective! - to the usual laboratory animals (since the blowup, it's been found that enormous doses of thalidomide will not make a rabbit sleep... but will cause a pregnant rabbit to produce abnormal young. Equally massive doses of barbiturates don't do that; they kill the rabbit. It wouldn't have indicated anything to the investigators except that thalidomide was safer than barbiturates! And it has now been discovered that, for reasons so far known only to God, thalidomide does make horses sleep! But who uses horses as "convenient laboratory animals for testing new drugs"? And why should they; horses are herbivores, with a metabolism quite a long way from Man's. Monkeys are expensive - and they don't really match Man).
Test 2 - trying it on a small group of patients first.
Now the first slight indication that thalidomide could have some bad side-effects was that neuritis business. It results from prolonged overuse of the drug.
The doctors administering the first test-use of the new drug would, of course, regulate it carefully. There would be no long-continued overuse under their administration - and therefore thalidomide wouldn't have produced any neuritis.
On that first, limited-sample test, there would be an inevitable, human tendency to avoid pregnant young women as test subjects for so experimental a drug.
Result: thalidomide would have checked in as one hundred per cent safe and effective.
The final two-year test was several thousand people. On this one we don't have to guess; we've got the statistics.
During the time thalidomide was being considered by the Federal Drug Administration for licensing in this country, selected physicians in the United States were sent supplies of the drug for experimental use.
Under this program, 15,904 people are known to have taken the pills. Certainly that's a good-sized second-level testing group for our proposed hyper-cautious test system.
Of those nearly 16,000 people, about 1 in 5 - 3,272 - were women of child-bearing age, and 207 of them were pregnant at the time.
There were no abnormal babies born, and no cases of polyneuritis reported.
Thalidomide passed the cautious tests with flying colors.
Now the abnormalities that thalidomide does cause are some kind of misdirection of the normal growth-forces of the foetus. The abnormalities are of a type that was well known to medicine long before thalidomide came along - abnormal babies have been produced for all the years the human race has existed, remember.
Suppose that in our test, some women did bear abnormal babies. Say three of them were abnormal, and lived (a goodly number of the thalidomide-distorted babies died within hours. It doesn't only affect arms and legs; thalidomide can mix up the internal organs as though they had been stirred with a spoon).
So...? So what? Aren't a certain number of abnormal babies appearing all the time anyway? And with all this atomic-bomb testing going on... and this woman was examined repeatedly by X ray during pregnancy... and remember that in the normal course of nine months of living, she will have taken dozens of other drugs, been exposed to uncountable other environmental influences, perhaps been in a minor automobile accident...
Not until the drug is "tested" on literally millions of human beings will it be possible to get sufficiently numerous statistical samplings to be able to get significant results. Toss a coin three times, and it may come heads every time. This proves coins fall heads-up when tossed?
Another drug was introduced for experimental testing some years ago. The physicians who got it were told to check their experimental patients carefully for possibilities of damage to liver, stomach and/or kidneys, the expected possible undesirable side-effects of the drug. Practically no such damage was found - the drug was effective, and only in the very exceptional patient caused sufficient liver, stomach or kidney reaction to indicate it should be discontinued.
Only it caused blindness.
The reaction was frequent and severe enough to make the drug absolutely impossible as a medicament - and was totally unexpected. It had not caused any such reaction in any of the experimental animals.
No - the lesson of thalidomide is quite simple.
So long as human beings hope to make progress in control of disease and misery, some people will be lost in the exploration of the unknown.
There is no way to prevent that. There is no possible system of tests that can avoid it - only minimize the risk.
We could, of course, simply stop trying new drugs at all. The animals never did try the pain and the risk of fire. They're still animals, too.