Suppose someone developed a revolutionary surgical technique that could save tens of thousands of lives every year. Suppose also that the technique required the use of a specific new chemical.
Although a doctor can employ any new surgical technique he finds useful, involvement of a chemical throws the entire procedure into the lap of the Food and Drug Administration (FDA). And since the substance cannot by law be used without FDA clearance, it becomes automatically illegal to use the surgical technique without FDA approval. Thus, in our scenario, the revolutionary surgical technique could not lawfully be used, regardless of its lifesaving possibilities, until the FDA had approved at least an Investigational New Drug Exception (IND)—and later a New Drug Application (NDA)—for the chemical involved.
Now suppose that for some ill-defined reason concerning potential undesirable side-effects—already disproven many times by leading medical investigators and taken seriously by few outside the agency—the FDA refused to issue the needed NDA. What could anyone do about it? What could even the most renowned surgeon do to get around FDA refusal to license the chemical even in the light of abundant evidence indicating that its qualms were unfounded? The answer is nothing.
Unfortunately, this scenario is not hypothetical at all. It is exactly what has happened in the case of a group of chemical bonding agents known in technical terminology as cyanoacrylate* tissue adhesives.
Put simply, these chemicals glue body tissues together in much the same way model-airplane glue binds plastic. Cyanoacrylate is a monomer glue that rapidly polymerizes (forms long chains of molecules much like the intertwining of short fibers of wool or cotton to form thread) upon contact with body fluid and adheres firmly to bleeding tissue. There, it forms a flexible temporary seal beneath which natural healing takes place. The substance erodes gradually and is eliminated from the body.
Over the past 25 years, cyanoacrylate glue has been effective in saving lives in a staggering variety of cases. Used primarily as an aerosol sprayed on open wounds, the glue proved itself as the most significant surgical breakthrough of the decade during the Vietnam war, when Army doctors were able to save hundreds of lives in the field and in military hospitals at home.
Since then, the substance has been perfected for application through an endoscope, a sophisticated long, flexible tube run through a patient's nose or mouth and down the esophagus to gain direct access to the esophagus, stomach, and intestines. In this way it can be used to seal bleeding internal abrasions and cuts—primarily ulcers—in seconds, enabling them to heal rapidly without interference from digestive acids.
With a green light from the FDA, there is no reason why endoscopically applied cyanoacrylate couldn't render the treatment of ulcers a problem of the past. In terms of the alleviation of human suffering, the implications of this use alone are inestimable. And this is only the beginning.
More recently, techniques have been perfected for applying cyanoacrylate almost anywhere in the body through micro- and macro-catheters—fine, flexible plastic tubes inserted directly through veins and arteries to reach specific parts of the body far inside. The aim? To block malfunctioning blood vessels—without surgery.
Again, further applications are just beginning to be realized: control of malignant tumors, for example, or destruction of all or parts of malfunctioning organs (such as appendix or spleen) where surgical intervention is impossible or difficult. Cyanoacrylate has also been used successfully since 1965 for reinforcing and preventing rupture of aneurysms (tiny blood vessels whose weakened walls threaten to burst and cause fatal hemorrhaging), particularly in the brain.
There are conventional agents similar to cyanoacrylate, such as methacrylate, the synthetic agent used most often for sealing aneurysms. But cyanoacrylate has a big advantage: because it can form its protective coating in the presence of water, it can be used while bleeding is still active. All other agents require that bleeding be stopped first. In wet tissue, the liquid glue congeals into a bleeding-stopping film in about 90 seconds.
Considering these and other available applications, even the most casual observer must wonder where this medical "miracle" is today. Why aren't there spray cans of it on the shelves of every American emergency room or operating room and in every ambulance, ready to save lives in otherwise hopeless situations? It's easy to spell out the answer: F-D-A.
Since the years of the Thalidomide panic and the subsequent Kefauver congressional hearings, the Food and Drug Administration has consistently refused to license cyanoacrylate glue for any medical use, including dental work. And it has done so in the face of 27 years of use in laboratories in American medical schools and research institutions and in the US armed forces and despite 10 years of intensive general surgical use overseas, in nations where drug regulatory agencies have long considered cyanoacrylate innocuous.
For the uninitiated: The FDA licensing procedure involves the reluctant issue of Investigational New Drug exceptions to specific doctors and their research groups, who are then enabled to use a drug or substance in specific clinical situations—but only on patients who are almost certain to die anyway or are unacceptable candidates for conventional surgery. The burden of proving the drug's safety for general use, along with the expense of financing the detailed studies necessary to convince the FDA, falls on the medical community and private corporations. In the case of cyanoacrylate, even the large numbers of specialists convinced of its safety and efficacy have found that mustering evidence sufficient to satisfy the FDA is a formidable, costly, and slow process.
American surgeons familiar with the tissue adhesive and aware of its amazing healing capability are anxious for the FDA to license it for general surgical use. It could, they believe, become a hospital mainstay, saving countless lives by enabling the rapid sealing of hemorrhaging in accident victims or providing instant fluid-loss protection over large areas of the bodies of bum victims.
But these researchers remain powerless. Be it out of simple ignorance or out of a desire to play it safe and protect its image and its track record—a record of few errors of commission despite countless fatal errors of omission, usually from doing nothing—the FDA's stance on licensure of cyanoacrylate is so typically and tragically haphazard that the glue may never be widely—and legally—available.
WHAT CAN BE DONE WITHOUT THE FDA
The earliest form of cyanoacrylate was developed by Eastman Laboratories, which in 1955 first reported its remarkable ability to glue ruptured body tissue until natural healing processes could take place. This form of the glue, called Eastman 910, was perfected for a wide variety of uses during the late '50s and early '60s at Walter Reed Army Institute of Research (the Defense Department's center for medical research and treatment of VIP Defense personnel). The Walter Reed work was done under the direction of Dr. Teruo Matsumoto, then chief of experimental surgery, with the G. Barr Company cooperating in development of the aerosol delivery system for use on open wounds. As the story of cyanoacrylate unfolds, it will become clear how important it was that, as part of the military, both Matsumoto and the institute were exempt from FDA controls.
The Eastman glue was used extensively during the war in Vietnam—at Walter Reed and at the Third Surgical Hospital in Bien Hoa—under the direction of Capts. John Collins and Paul James. Its performance in the field was nothing short of miraculous. Medical World News reported on it in July 1967: "Military surgeons have developed a novel technique to stop bleeding.…A small aerosol bottle that delivers a fine spray of adhesive has saved the lives of critically wounded US infantrymen in Viet Nam. The spray put an end to massive hemorrhages of the kidney or liver that could not be controlled by any other technique. Within seconds after the adhesive was sprayed onto the ruptured organs, a crust formed and bleeding stopped." The article quoted Col. Robert M. Hardaway III, then director of Walter Reed's surgery division: "So far, follow-up studies on the men treated for massive bleeding have not revealed any unfavorable side effects."
Other significant advances had been made using cyanoacrylate outside the military—largely without benefit of INDs from the FDA, which was much less strict in the years before Thalidomide. Between 1956 and 1973, for example, 45 terminal patients at the University of Minnesota and affiliated hospitals were successfully treated with the glue. But because civilian researchers could not find corporations wealthy enough to underwrite their battles against FDA intransigence—a problem the military didn't have to bother with—these advances have seen little publicity.
Much of the early pioneering work was done by Dr. Shelly Chou, head of neurosurgery at the University of Minnesota, and Dr. Charles Carton of Cedars-Sinai Hospital in Los Angeles. In the mid-'60s, Dr. Chou and his group worked with a version developed in Japan, testing it on cats to determine whether there are any long-term effects in the brain. After three years the animals showed no effects. At autopsy, no brain or nervous system effects from the glue were found, and it was pronounced totally innocuous—that is, to have no side effects.
Overseas, applications of cyanoacrylate proliferated rapidly. By the early '60s it was already in general clinical use in Japan for sealing wounds, mending torn intestines and broken bones, neurosurgery, and gynecological surgery. It was also gaining wide acceptance in clinical surgery in Germany, France, Switzerland, and Canada.
A glance at Index Medicus, the "bible" of current American medical research, for any year since 1970 reveals at least a half-page of cyanoacrylate citations for uses ranging from hemorrhage control to eye surgery. In the United States, most of these applications have been developed on lab animals, only to be forbidden for human use by the FDA. The October 26, 1973, issue of Medical World News reported the sad situation: despite its numerous uses, manufacturers of cyanoacrylate adhesives "evidently feel it is not worth their time, money, and effort to win FDA approval."
It's not that they haven't tried. In the early '60s several companies were working on perfecting cyanoacrylate. But when the FDA found signs of tissue toxicity (tendency to cause inflammation in surrounding tissue and to activate the body's rejection mechanisms) in one of the three types under investigation, licensure was refused for all three until the companies developing the other two were able to submit proof that the toxicity was not common to theirs as well.
A few years later, American industry again tried to break through FDA blockades. In the late '60s several major drug firms, including Eastman, Ethicon (now owned by Johnson & Johnson), and the Surgical Products Division of Minnesota Mining and Manufacturing (3M), focused on potentially lucrative dental applications of cyanoacrylate tissue glue. This, they thought, was an area in which they might be able to commercially justify use of the time and money needed to meet FDA standards.
Unfortunately, FDA tests revealed tissue toxicity in the Ethicon type, and the toxicity bogeyman was again foisted on all three companies. Later, Eastman and 3M were able to prove independently that their versions of the glue were not toxic, and dental INDs, allowing use only in the mouths of humans already dying from some other malady, were approved for Eastman 910 and 3M's version, MBR 4197.
But then, in 1972, FDA tests showed that large aggregations of the adhesive implanted in lab animals sometimes caused malignant fibrosarcomas (cancerous masses of scar tissue). At that point, the agency indicted cyanoacrylate as "possibly carcinogenic," ordered an immediate halt to any use of the glue, and rescinded all outstanding INDs.
Although convinced that their products were not carcinogenic and that the FDA's results were insignificant, Eastman and Ethicon dropped out. They simply could no longer bear the financial burden of proof. That left only 3M, which held on and undertook another costly series of carcinogenicity tests to prove the safety of MBR 4197.
A CLEAN RECORD
Even at that time, however, the fibrosarcoma test—long the most popular test with the FDA and AMA for determining the propensity of a substance to cause cancer—had been discredited. The FDA's labeling of cyanoacrylate as "possibly carcinogenic" was taken seriously by few nongovernment investigators outside the AMA.
And long before the FDA's questionable reports of carcinogenicity and the industry's expensive "counterstudies," the experience with cyanoacrylate had given no indication that it can cause cancer. At the top of the list was the 15-year use of the glue at Walter Reed Army Institute of Research.
In 1977 I asked Lt. Col. Arthur Fleming, director of surgery at the institute, to make a complete search of all records of soldiers treated with cyanoacrylate. After receiving the necessary clearance from Walter Reed security headquarters to release the information, Fleming reported: "My evidence is that there was no carcinogenesis associated with the cyanoacrylates that were being used at Walter Reed.…The man who did the original histo-chemical studies [of effects on the body's normal biochemical activity] was with Walter Reed in the 1960s and found no evidence of carcinogenesis."
It has, unfortunately, proven impossible to learn the name of that man. According to Lt. Col. Fleming, "He is with the FDA now, and could not comment due to 'conflict of interest.'"
Dr. Larry Johnson, chief of gastroenterology at Walter Reed then and now, had this to say about the FDA's unilateral action of 1972: "I hadn't…seen any patients treated with the cyanoacrylate who had any side effects from the glue. In 1972 we had substantial evidence that it was not carcinogenic, and no results suggesting that it might be."
With the wealth of evidence prior to 1972 indicating that cyanoacrylate is not carcinogenic, with all the use it had seen before 1972 among civilians in Europe without even the suspicion of carcinogenicity, and with American researchers involved since 1955 unanimous in their conviction of its safety, the FDA's 1972 shutdown of all work on cyanoacrylate adhesive applications is difficult to make sense of. My own search for an explanation, via calls to the head of the FDA department responsible for the fibrosarcoma tests, has been fruitless. The department head claims that he cannot comment without clearance from the FDA's public relations officials, and that office has refused to grant a clearance—and refused to give any reason for its refusal.
CANCER THE FDA WAY
Outside of the FDA, there is no such unwillingness to discuss those tests. William Walsh is a senior specialist with the clinical research group of 3M's surgical products division. His comment on the 1972 research shutdown and the FDA's continued lockup of cyanoacrylate? "The rodents used in these [fibrosarcoma] studies are very prone to develop these tumors—much more so than humans. It is simply an innate characteristic of the animals. They will develop fibrosarcomas when practically any foreign body is implanted in delicate tissue.
"Even in Germany, when the cyanoacrylates first came on the market, the German Ministry—the analog of our FDA—raised the same questions raised by the FDA here. But German toxicologists had little trouble convincing the German Ministry that it was due to a trait in the lab animals. In the United States it isn't nearly so easy…but we have to deal with the political reality that the FDA has absolute authority to keep any drug—no matter how life-giving its primary action and no matter how unlikely the possibility of untoward side effects—off the market."
Dr. Stephen Silvis has worked with cyanoacrylate at the Minneapolis Veterans Administration Hospital. His comment? "The FDA became concerned…when they got some fibrosarcomas in lab animals. But these fibrosarcomas didn't prove it was carcinogenic. In their tests, they formed a hard ball with the glue and, when implanted in the lab animals' tissue, it gave a typical foreign-body reaction. Fibrous tumors surrounded them. But this reaction is not necessarily specific to the material implanted."
Dr. Gerald Shklar, head of the department of oral medicine and oral pathology at the Harvard University School of Dental Medicine and a foremost cancer study expert, was retained by 3M to do further carcinogenesis tests on MBR 4197 after the FDA revoked 3M's IND in 1972. The results?
"Our model was very good," reported Dr. Shklar. "We used the cheekpouch of the Syrian hamster—a very delicate mucous membrane. We painted this tissue with 3M's cyanoacrylate homologue three times a week for six months. If the cyanoacrylate was carcinogenic, it would have caused cancer in the hamster. It did not. There was not a single tumor. The results were completely negative."
"We also applied the glue to open wounds in the hamster's mouth," added Shklar, "with the same conclusively negative results. We did not observe even any precancer stages. I would be quite confident that the glue would prove equally innocuous in any part of the body."
I asked Shklar what he thought of the FDA 1972 fibrosarcoma studies. "I'm not familiar with their particular studies, but the only way I could foresee that you could get a tumor would be if you built up a bulk of the material in an implantation [exactly what the FDA did]. You could then get a physical irritant and a fibrosarcoma could result. But by this method, you could get a tumor with practically any foreign substance, including glass and sugar."
The FDA is, of course, aware of the ambiguities of the fibrosarcoma test. While outside experts maintain that the test is irrelevant in this case, the FDA stands by it as a statistical indicator of degree of carcinogenicity related to the number of tumors produced. What the outside experts have in their favor is that cyanoacrylate is simply never used in a manner that would permit sizable deposits to develop. Autopsies performed on thousands of lab animals since 1955 have shown no tendency in the adhesive to concentrate in body tissues. The glue is so effective, and is used so sparingly, that it would be a rare case indeed in which the amount applied would be sufficient to form an aggregation even close to the size of the FDA test implants.
Put bluntly, then, it appears that the test which halted work with a chemical substance known since 1955 to be effective and safe was one that virtually forced lab animals to develop tumors—as a nonspecific reaction to an implanted foreign body. And because the foreign body happened to be a cyanoacrylate aggregation, the FDA ignored all evidence to the contrary and banished a miraculous lifesaver to confinement in the bowels of its labyrinthine bureaucracy.
It took three years for 3M to rescue cyanoacrylate from the FDA's questionable verdict. In 1975 it won approval of a second IND for oral applications of MBR 4197.
Later in 1975 Dr. Stephen Silvis, then chief of gastroenterology at the Veterans Administration Hospital in Minneapolis and professor of medicine at the University of Minnesota, secured an IND for the 3M glue applied with an endoscope for gastrointestinal (GI) problems. Silvis soon became the leading—in fact, the only—researcher legally using cyanoacrylate to save human lives. (Several others elsewhere continued to use it without FDA approval. Had they been caught thus saving lives, they could have been prosecuted and found guilty of a federal felony and jailed.)
One striking example of cyanoacrylate's efficacy in GI cases concerned a man admitted to the Minneapolis VA Hospital in 1976, after attempting suicide by swallowing Drano. The man was hemorrhaging massively from lesions (lacerated tissue) throughout his esophagus and upper GI tract. By conventional medical standards, he was as good as dead. Luckily, under the existing IND, Dr. Silvis and his colleagues were able to use an endoscope to spray the lesions with cyanoacrylate. Eighty percent of the bleeding was stopped within minutes, and a second application took care of the rest. There was no further bleeding, and the man was discharged a week later. Now, after more than three years, the patient is still healthy and has displayed no side effects from either the glue or the lesions, which have healed completely.
Two other advanced methods to stop bleeding—electrocoagulation and lasers—are now under investigation. But cyanoacrylate, again, has an advantage: it causes no further tissue damage, whereas both electrocoagulation and lasers can cause extensive damage to surrounding tissue.
In 1977, Dr. Silvis's studies were expanded into a multicenter investigation involving several hospitals across the nation. Walter Reed Institute became involved in the use of the glue for the first time since Dr. Teruo Matsumoto left in the mid-'60s, putting an end to his research. (Matsumoto, now at Hahnemann Medical College, has refused comment on his own cyanoacrylate work—or anyone else's.) Under this study, 100 patients received cyanocrylate treatment, with results similar to those obtained by Silvis in his earlier research.
An IND has also been granted to researchers to try one other application of tissue glue: blocking of blood vessels by applying the glue through a fine tube fed through the vessels to the appropriate spot (transcatheter embolization). Dr. Martin L. Goldman, director of vascular research at the Albany (N.Y.) Medical Center Hospital, has had considerable success using the glue for "medical splenectomies" (killing a lethally infected spleen in place—without surgery—by blocking the blood vessels feeding the spleen and its infection). Again, cyanoacrylate is not only successful but superior to alternatives. More than half of all conventional nonsurgical destruction of infected spleens (done with Gelfoam or other particle embolizers) lead to abcess of the organ, notes Dr. Goldman. Cyanoacrylate, on the other hand, has shown no tendency to promote abcessing.
At the Mason Clinic in Seattle, Dr. Patrick C. Freeny has used this material to block malfunctioning blood vessels in some 40 patients made "legal" subjects under FDA doctrine because they were high surgical risks. He too concludes that the glue has significant advantages over conventional methods. "With particle embolization," he reports, "you inject into the blood stream, and the particles go where the blood stream carries them—you hope, where you want them. Sometimes they can go off and fatally block an artery you don't want blocked, such as one bringing blood to the heart. But with the cyanoacrylate we can use a silicone micro-catheter to go way out in the peripheral circulation and plug the vessel exactly where we want to."
And Dr. Freeny's work has turned up still more evidence of the safety of cyanoacrylate. Autopsies of patients who died of the terminal condition that made them legal for use in the study have shown that the glue has about the same, negligible, tissue toxicity as nonabsorbable silk suture. And, notes Freeny, the vessel blockages have proven permanent enough to achieve the desired lifesaving result.
TOO LITTLE, TOO LATE
There is some hope that the FDA is coming to the realization that its longstanding suspicion of cyanoacrylate may be unfounded. In early 1979, in a guarded and unpublicized letter to William Walsh of 3M, the agency allowed that, for oral applications, it seems likely that the glue is not significantly carcinogenic.
Yet the outlook for cyanoacrylate is still bleak. Even if the FDA made an across-the-board declaration that the substance is not carcinogenic, the time-consuming and stringent tests required for licensure constitute an undeclared war of attrition against the glue, its manufacturers, and its longtime proponents. And even if the FDA could be convinced to approve a New Drug Application, the road to approval for general surgical use remains long. If 3M obtained a cyanoacrylate NDA for gastrointestinal use, notes Dr. Silvis, "doctors would be able to use it only for the gastrointestinal applications specified in the detailed restrictions circular qualifying the NDA. All other uses would require a step-by-step process similar to the one we've gone through. First, extensive studies of that specific use on lab animals; then, approval of an IND; then, more extensive controlled studies on terminal patients under the IND."
Absurd as it may seem, each specific use of tissue glue—as with all new medical chemicals and drugs—must fight its own lonely battle through the bureaucracy. For each, a corporation must be found that is willing and able to bear the financial portion of the burden of proof.
And as one researcher notes, "In dealing with the FDA on these carcinogenesis tests, it's extremely expensive to convince them that a substance has no serious side effects. A drug company must justify enough economic return from estimates of potential sales markets in order to sink so much money into it. These economic constraints are probably the major thing that differentiates between the advance of modern medical breakthroughs into wide-scale public use in the United States from the advances in other nations, where the regulatory agencies are not nearly so difficult to satisfy—or where the regulatory agencies must assume the burden of proof that a substance does have harmful side effects before they can refuse to allow it on the open market."
The sizable potential sales needed to offset the costs of maneuvering the FDA course put cyanoacrylate in a particularly bad position. The very nature of the glue requires that it be used in only limited amounts. And since repeated applications are unnecessary, it appears that no matter how many uses of the glue are approved, it would still sell in very small quantities. A single drop goes a long way.
And so even 3M, which continued for so long to work on a promising new product in spite of uncertain returns, late in 1979 finally put cyanoacrylate "on the back burner," in the words of a disappointed William Walsh. Like the other American companies that have done cyanoacrylate work in the past, 3M has turned instead to the nonmedical arena, producing thousands of gallons of a nonmedical form of the glue for sale in department and dime stores as the household "super glues." Eastman markets its 1955 version under the original name, Eastman 910; 3M has resorted to selling MBR 4197 under the commercial name Super Glue; other companies produce brands like Krazy Glue.
The simple fact that these household adhesives are in such wide use today further discounts one of the FDA's reasons for keeping it off the medical/surgical supply lists: that it is allegedly "too dangerous to apply," that physicians might accidentally get it on tissue other than that for which it was intended, with disastrous results. When household cyanoacrylate first came on the market in the early '70s, Consumers Union expressed similar misgivings, worrying that consumers might inadvertently bind their fingers together and "require surgery to separate them." The Consumer Product Safety Commission responded by recalling 10 brands of the glue, but tests quickly satisfied both Consumers Union and the CPSC that their fears were unfounded. An acetone like simple nail-polish remover will quickly dissolve the glue if it accidentally binds to fingers or other tissue.
A DEADLY GAME
The history of cyanoacrylate at the hands of the FDA leaves us with the hypothetical question posed earlier—and now carrying the urgency of reality: What can a doctor do for a patient who is bleeding to death or who has another condition that cyanoacrylate can alleviate without significant risks of deleterious side effects? If the physician is to obey FDA regulations, he or she can still do nothing. The evidence marshaled here, however, makes a strong case for another response—civil disobedience. This would solve the patient's problem; it would provide no remedy for the larger problem at the root of cyanoacrylate's sad history: the untenable position medical research has been placed in by the FDA.
To render the Food and Drug Administration more sensitive and humane, to increase its understanding of the risk/benefit analysis individuals would themselves make when faced with new drugs and unforeseen side effects, to speed up its response to escalating rates of technological and medical progress, would require total reorganization under congressional supervision. Yet this too would offer only superficial relief. The same forces that turned the FDA into the monolithic morass of self-justification it is today, and which all federal regulatory agencies tend to become, would ensure that in a decade or two we would be right back where we started.
The problem with conservative "reform" of the FDA is that, like many regulatory agencies, its "crime" is inherently passive. It need do nothing to withhold new drugs from the public. They are assumed a priori to be dangerous and remain illegal until the FDA gives its blessing. Potential developers of cyanoacrylate, along with countless other miracle medicines, are presumed guilty until proven innocent. And so the products they could be offering remain buried in Index Medicus and reports on investigators' shelves.
But this is not a fluke reflecting FDA arrogance or anachronism. This question of burden of proof is at the heart of setting up regulatory agencies as guardians of the public welfare. It is the only way the FDA—or the CPSC, EPA, or OSHA—can play the regulatory game. But in the FDA it is far deadlier than in other agencies. Each flaw and inefficiency translates more or less directly into an unnecessary loss of life or increase in human suffering.
And the patients at risk, and the doctors involved, have no recourse. That's what protection by regulatory fiat means. Guilt is assumed, innocence must be proven, and there is no court of appeals. Neither individual patients nor their doctors have any place to argue in their own behalf, to appeal even for one-shot exceptions based on the suffering that could be alleviated or death that could be averted.
Evidently, simply because a new drug is involved, Congress and the FDA consider doctors and patients unqualified to weigh the risks and benefits. And so the right to informed consent, held inviolable in all other domains of medical treatment, is withheld.
The paternalistic role of regulatory agencies can sound very nice in theory. Fatherly Uncle Sam is to look out for our interests, protecting us from undue risks and, in popular parlance, from greedy capitalist robber-barons who may be negligent or, at best, mistaken about safety. All of our lives are thus to be made easier. This parental image of government is the only conceivable justification for the immense, unilateral powers that the FDA and other regulatory agencies exercise over individual liberties. But it is the very antithesis of the free choice necessary for democracy.
And, to add insult to injury, the idea of paternalistic regulation doesn't even work out in practice like it is supposed to in theory, as the story of cyanoacrylate and any number of other case studies make crystal-clear. But as long as people delude themselves into believing that picture of an all-protective government, they absolve themselves of any responsibility for taking the trouble to think and become educated about the various aspects of modern life that have come under government control. Ironically, regulatory agencies monopolize the protection business, severely reducing the incentive for agencies in the private sector—such as Consumers Union—to come forward to do a better job. Informed consent is thus not only prohibited but made nearly impossible.
How have we become a nation in which nearly everything we do is regulated to our disadvantage by some government agency? The evolution of the FDA illustrates how those agencies turn out to be, not the well-intentioned bodies Congress may well have in mind when it creates them, but Frankensteins over whom the individuals they are meant to serve have no control.
PROTECTION THAT ISN'T
The only reason the FDA exists today is that Congress, via the Constitution, was given the power to enact laws to protect the "health, safety, and general welfare" of the public. Congress, one would assume, had this mission firmly in mind from the time of the original Food and Drug Act of 1906 right through 1931, when the FDA became an independent regulatory body under the Agricultural Appropriations Act.
Since that time, Congress has added various amendments to the FDA's enabling legislation, but the agency was not allowed to become the truly repressive force it is today until the great Thalidomide panic of the early '60s. Out of the resulting congressional hearings came a vast increase in the FDA's regulatory powers.
Unfortunately, the wave of hysteria and journalistic sensationalism inspired by Thalidomide was quite out of proportion to the actual number of deformed infants born. Drug companies were characterized as nothing but money-hungry capitalists anxious to increase profits by shoving all manner of untested drugs down American throats. They needed firmer regulation by fatherly Uncle Sam.
Of course, those congressional hearings did reveal pharmaceutical industry cover-ups and irresponsibility regarding possible drug side effects. But could that justify an automatic presumption of guilt for all firms and all new drugs? Does it change the fact that it may well be unconstitutional for any regulatory agency to have such powers over individual choice?
While Congress might be forgiven for not understanding then the implications of bestowing such powers upon a hard-line bureaucracy, those implications should be obvious by now to anyone who has the courage to face them. The overreaction of Congress was immense—and tragic. There is little excuse for Congress not to take prompt action to remedy its constitutional error.
The public today has demonstrated, in fact, that it does not want the FDA dictating its choices just because risky matters are involved. The reaction to the saccharin controversy is a fine example, and the message could not be more clear if a national referendum were taken. Clearly, modern Americans believe that they can make responsible assessments of risk independently of government.
Vast changes have taken place in the level of public awareness of medicine and medical advances since 1906, 1922, and 1931, when the FDA was taking shape. Even if at those times most people were too far from understanding the risks and side effects to be able to give reasonably informed consent regarding treatment with new drugs, in today's climate of an enlightened, educated public, FDA paternalism is undesirable and unjustifiable. It is, in fact, detrimental to the health, safety, and general welfare of the American public, as the cyanoacrylate experience makes abundantly clear.
If cyanoacrylate tissue adhesive is finally approved by the FDA for general surgical use, it will be interesting to see who will be called to account for the thousands of lives lost and the suffering prolonged during the years that it was withheld—years during which available methods were wholly inadequate to the tasks doctors faced. And it would be enlightening to see what the response of the Supreme Court would be if a citizen ever sued the FDA on behalf of a relative who died in an emergency room or ambulance for want of a lifesaving cyanoacrylate adhesive application. It would be interesting, indeed, to see how anyone could justify that as being helpful or effective in promoting anyone's health, safety, or general welfare.
David A. Mathisen, a resident of Minneapolis, is a science journalist, environmental engineer, and novelist. He was formerly a contributing editor to Medical Dimensions.
OTHER DRUG LAG VICTIMS
Accident victims, ulcer sufferers, and others denied access to cyanoacrylate glue are not the only victims of the FDA's hypercaution. The agency's drug approval regulations have led to a "drug lag" of massive proportions: beneficial, even lifesaving, drugs are approved and in use far more rapidly in Europe than they are here.
Who is losing out? Dr. William Wardell detailed the scope of the problem in testimony before Congress last June:
• Heart attack victims have been denied a drug that prevents death after heart attacks, alprenolol, which has been available in Sweden since 1967 and approved for this specific use since 1976. Another, practolol, could be saving 10,000 to 20,000 lives a year. Many drugs to control high blood pressure have been approved for use in Britain—but for 11 years the FDA held them all off the US market. A single FDA employee held up for six years one company's plan to study the value of aspirin in preventing subsequent heart attacks.
• Ulcer and gallstone sufferers have been denied carbenoxolone and chenodeoxycholic acid, and access to three other such drugs was delayed for years.
• Epilepsy victims have a limited choice of drugs. Of 11 drugs approved in Britain or the United States from 1960 through March 1979, only one became available earlier here than in Britain. One drug, sodium valproate, was held up for over a decade.
• Depression sufferers have to depend on a limited range of products, also. In Britain they have many more choices, some of which, like viloxazine, are much safer or, like mianserin, have fewer side effects.
• Migraine patients in Britain have available such products as clonidine, propranolol, and pizotifen, which are unavailable here or became available years sooner in Britain.
Overall, Wardell and colleague Louis Lasagna have found that Britain has an overwhelmingly higher rate of pharmaceutical innovation, evidenced by the number of drugs being introduced exclusively—four times as many in Britain as in the United States. And the most significant time lags—frequently on the order of four to six years—occur in the crucial areas of cardiovascular, peptic ulcer, and central nervous system drugs. A similar picture emerges from comparisons with other advanced European countries such as Switzerland and West Germany. Concludes Wardell, "In terms of new medicines to treat diseases, therapeutic advances are overwhelmingly first available and used abroad, not in the US."
FDA commissioners alternate between denying that a drug lag exists (or ever existed) and claiming that they have taken steps to eliminate it. Meanwhile, the needless suffering continues.