http://dept.hist.upenn.edu/phr/spring97/fea1.html Retin-A¹s Wrinkled Past On March 4, 1979, the Philadelphia Inquirer reported that in 1971 the Central Intelligence Agency (CIA) secretly tested a mind controlling drug on 20 "human guinea pigs," five of whom were prisoners in Northeast Philadelphia's Holmesburg Prison. "The tests began," reporter Aaron Epstein wrote, "after the CIA discovered that year that the Soviet Union had been trying to develop an undetectable drug that could incapacitate a victim's mind." (1) Calling for "needed countermeasures" against this "true potential threat to U.S. VIP's and other key personnel," the CIA authorized the Army's Edgewood Arsenal Research Laboratories in Maryland to conduct research similar to that undertaken by the Soviets. Using fifteen soldiers and five Holmesburg prisoners as guinea pigs, Edgewood researchers successfully developed a drug that, according to a 1973 CIA memorandum, "produced delirium and other psychotic behavior lasting from three or four days with subsequent amnesia," and was entirely undetectable in a victim's body. (2) Epstein claimed that such programs "designed to alter human behavior through drugs, poisons, brain surgery, and electric shock techniques, were conducted by the CIA for about 25 years." What he did not mention in that article, however, was that many such programs-in addition to numerous other brands of experimentation on human beings-were also performed by the University of Pennsylvania (Penn) under contracts with both the United States government and the private sector. In fact, most of Penn's experiments were performed years before and included larger numbers of human subjects than the Edgewood program. The main significance of the later program is that it was among the first to catch the media's eye. Various experiments on humans were performed by many different individuals associated with the University. However, in the interest of specificity, we will concern ourselves with the work of then-Professor of Dermatology Albert Kligman. Even a cursory examination of any number of documents or articles reveals that Kligman conducted more experimentation on humans-mainly Holmesburg prisoners-than anyone else at the University, making him an obvious person through whom to trace Penn's suspect experimentation practices. The scope of Kligman's tests demonstrates the scope of testing in general; similarly, Kligman's range of experimentation helps reveal those general trends. Although a dermatologist by training, Kligman often strayed far from his area of expertise into whatever field was the hotbed at the given time. "I like to do the ground-breaking research," he said in 1989. (3) Born in Philadelphia in 1916, Kligman earned his bachelor's degree at Pennsylvania State University in 1939. He received his doctorate and M.D. from Penn in 1942 and 1947 respectively. Kligman began his internship at Albert Einstein Hospital in 1948 and, in 1951, returned to Penn and the Hospital of the University of Pennsylvania to complete his residency. Following that, Kligman accepted an offer from Penn and became a professor in the Division of Graduate Medicine where he served until 1972. (4) It was in this last capacity that Kligman performed the inhumane experiments on unsuspecting prisoners in question within this study. We will examine in detail three of Kligman's more significant experiments on humans: his testing of mind-controlling agents, his experimentation with "skin-hardening" agents, and his experimentation with Dioxin under a contract with the Dow Corporation. Experimentation with Mind-Controlling Agents Between 1964 and 1968, two trailers were parked inside the heavily guarded walls of Holmesburg Prison. Nearly a decade later, the story of what transpired inside the trailers began to surface. "Today it is clear," Epstein wrote in 1979, "that the activities within the trailers, with their padded cells, had nothing to do with crime and punishment. In that three-and-a-half year period, the Army and the University of Pennsylvania were turning 320 prisoners into human guinea pigs in secret chemical warfare experiments." (5) However, to prisoners at the time, the trailers with the white University of Pennsylvania lettering on their sides were a mystery. Donnell Wilson, who was incarcerated at the prison during those years, recalled in an interview how he learned of the trailers at Holmesburg: "I was on 'D' Block. Guys told me that if I wanted money for the commissary, all I had to do was go to 'A' Block, where Penn was testing people. I asked, 'for what?' They said, 'Look, you can go over there and make money. Just go and see what's going on.' So I went over, and saw different doctors in different cells and rooms." (6) What Donnell Wilson was encouraged to "go over there and see" were Dr. Kligman's testing grounds. The 1964 arrival of these trailers at Holmesburg marked the beginning of a three-and-a-half year relationship between the Army and Penn during a time when military research in chemical and biological warfare was at its peak. It also marked the end of the Edgewood Arsenal scientists' exhaustive search for a university able and willing to test mind-control drugs and other substances on humans. Penn was an ideal choice for the Army, as it already had access to Holmesburg prison from an agreement that provided the University with inmate "volunteers" for drug testing for civilian purposes-namely for contracts with pharmaceutical companies. The new contract, however, had an explicit military focus. According to the agreement Penn researchers were to work with Edgewood scientists at Holmesburg to determine the MED-50-the Minimum Effective Dose needed to disable 50 percent of a given population-of seven different mind-altering substances. Kligman and Dr. Herbert W. Copelan, another Penn physician, were the chief investigators for the University. To this day, the $386,486 paid to Penn by the Army is the largest contract ever for testing on human subjects. (7) By the end of their contract, Kligman and Copelan claimed to have found the MED-50 of all seven compounds. In their final report they wrote: "no subject suffered any [permanent] toxic or harmful effect." It is difficult to refute or verify this statement because the prisoners' names were crossed out in the report and they were not examined subsequent to the testing to determine whether they actually did suffer any "permanent" toxic or harmful effects. (8) However, Kligman and Copelan did include in their report a description of the effects that a few of the experimental agents (referred to as "Agent #_," not their constituent chemicals) had on prisoners. These records certainly reveal that even if the testing did indeed have no "permanent" effects (a claim this study rejects) the testing did have quite devastating effects during the experiments. The following excerpts illustrate those effects: (9) Agent 668: Heaviness of the eyes and unsteadiness were the dominant central symptoms...[The prisoners] felt mildly high or intoxicated...Subjects were slightly drowsy, dozed more and daydreamed a little more than normal... Significant mental impairment was usually evident by 30 minutes...A few visual illusions and rare minimal hallucinations were reported. Occasionally cracks or spots were interpreted as 'insects' or 'faces'...A few subjects reported apparent motion of the walls after one or two hours. The walls 'seemed to be breathing.' Two subjects at intermediate doses had mild transient nausea at about five minutes. Another subject, on the highest dose, became nauseated and vomited at 80 minutes. Agent 302,212: ...Subjects became drowsy and often fell asleep...They swayed on standing and staggered mildly on walking, often brushing against corridor walls...Slight impairment of thinking...Subjects reported difficulty in carrying numbers in arithmetic problems. They felt unsure of answers. Agent 302,196: Within five minutes of injection, subjects often noted a sense of increased effort and clumsiness on motion. Feet and legs felt heavy. Hands felt strange and distant...Later, during the numerical faculties test, it was difficult to move and control the pencil...It was 'hard to make the pencil reach the paper.' Handwriting reflected this...Speech was slightly affected...Thought was slowed slightly and concentration impaired...A few subjects noted optical illusions. Agent 302,368: Hallucinations and nonsensical speech occurred at the dosage when incapacitated effects were produced. One subject developed acute anxiety at this dose level. Agent 1-H: Consciousness during the test appeared dull. Several subjects had symptoms suggesting mild delirium. They reported hallucinations and dreams that were primarily visual and in color...The hallucinations occasionally were frightening. Subjects had difficulty distinguishing reality from fantasy...A few subjects complained of minor symptoms for periods as long as six weeks after receiving the agent. These consisted of difficulty focusing and headache when reading for several minutes...subjects often recalled 'thinking' during the mathematical test that they had completed several problems and then realized that they had finished none. Contrary to Kligman's claim in the report that he and Copelan had successfully determined the MED-50 of all seven agents and had compiled a "perfect safety record," subsequently obtained documents suggest that the experimenters knowingly subjected prisoners to agents capable of irrevocably harming them. In fact, before the study even began, an Army attorney named E.G. Scott wrote a memo questioning any research project intended to produce "irrational or irresponsible" behavior among volunteers. Beneath Scott's memo was a handwritten notation, probably added by a superior officer, stating, "investigating such mentally incapacitating chemicals is precisely the purpose of the study." (10) Thus, the Edgewood and Penn researchers were not only aware of the implications of the work on which they were to embark, but these implications were the main purpose of their research. Questions of the propriety of these experiments continued after Kligman began his work. For example, at Holmesburg, the Edgewood Army officer charged with overseeing the professor's work expressed extreme dissatisfaction with the tests' procedures and even purpose. Chief of Clinical Research Lt. Col. M.G. Bottiglieri wrote in a 1965 letter to Kligman that Penn's psychological reports were Pure gibberish...absolutely...nothing but a list of clichés seemingly pasted together without consideration of coherence, in an attempt to provide a façade of competence and ability. It seems incredible that a psychologist with...apparent qualifications would attempt to palm off such shoddy and psychologically naive material in response to our request. (11) Despite the complaints, in 1966, about two years into their contract with Penn, Edgewood relinquished full control of the Holmesburg experiments to the University when an Army legal advisor ruled that "the contract cannot be treated as one merely to provide subjects for the use of Edgewood medical personnel." Once Kligman and Copelan assumed full control of the program, they simply reported their results to Edgewood. The aforementioned final report was one of a few such reports that they submitted to Edgewood. After Edgewood removed itself from Holmesburg in 1966, the Army was essentially paying Penn to perform experiments that it would not allow its own scientists to perform, likely on humanitarian grounds or for fear of the possible legal repercussions. These revelations not only call into question the Edgewood researchers' and Kligman's intentions, but also the legitimacy of their results. Because there is no documentation available describing to what use the Army put Kligman's and Copelan's results, it is possible that the prisoners' exposure to the experimental agents-and the attendant health risks-served no purpose whatsoever, especially considering Bottiglieri's statements about the substandard quality of Kligman's work. Kligman's Quest for Skin-Hardening Agents Although the Army's $386,486 Edgewood contract with Penn was the largest and entailed the largest-scale experimentation, there were various other contracts between the Army and the University that used Holmesburg prisoners as subjects. Another noteworthy program, for example, was one whose purpose was, as Kligman wrote, "to learn how the skin protects itself against chronic assault from toxic chemicals, the so-called hardening process." (12) Ostensibly, this program had both offensive and defensive military implications. Kligman and his assistants worked with a variety of blister-producing chemicals, applying them to prisoners' foreheads and backs, and immersing entire limbs in solutions. "An inescapable conclusion ," he wrote in his 1967 report, "from all our studies is that solid hardening is attainable only if the skin passes through a very intense inflammatory phase with swelling, redness, scaling and crusting...Once hardened, the immersions may continue indefinitely without noticeable effect." He wrote that turpentine would be a good skin hardener, except about half the prisoners exposed to it had allergic reactions. "These reactions may be quite severe," he wrote in the same report, "when an entire forearm is involved." (13) Kligman reported some degree of success in hardening his subjects against such chemical warfare agents as sodium lauryl sulfate and chlorinated phenol. Twelve subjects, for example, were hardened to them for an entire year. However, the toxic effects of other agents mitigated his subjects' ability to achieve total insusceptibility to them. For example, all three prisoners exposed to pure ethylene glycol monomethyl ether, a highly toxic gas, "exhibited psychotic reactions (hallucinations, disorientation, stupor) within two weeks and had to be hospitalized." (14) These effects were caused not by contact with the skin, but by inhalation. Therefore, no "skin-hardening" process would prevent or alleviate any psychological effects a chemical agent may cause. Moreover, Kligman concluded that "hardening is short lived, and requires continuing exposures for its peak maintenance." (15) This study ended not when the Army's contract with Penn expired, but when inmates "complained bitterly...After weeks of apparently peak inflammation, the skin exhibited no willingness to become hardened and the willingness of the subjects to go on diminished to zero." (16) Like the report for the program involving mind-controlling chemical warfare agents, prisoners' names in this report are also unreadable. It is therefore impossible to ascertain whether Kligman's subjects sustained any permanent effects from this skin-hardening experiment. The Dow Dioxin Tests There were yet other contracts between Penn-Kligman specifically-and a number of civilian companies that also involved Holmesburg. For example, between 1964 and 1967 the Dow Chemical Company paid Kligman $10,000 to determine how dioxin-a highly poisonous component of Agent Orange and other herbicides-affects humans. Chloracne, an acne-like skin disease, had reached epidemic proportions at a Dow plant in Midland, Michigan, so the corporation commissioned Kligman to determine whether this outbreak was attributable to the workers' exposure to dioxin. (17) TCDD, or 2,3,7,8-tetrachlorodibenzo-p-dioxin, which Kligman applied to the skin of 70 prisoners, is the most potent of about 75 dioxin compounds. (18) Later studies found the extent of that potency: "since the last of Kligman's experiments [under his contract with Dow], TCDD has been linked by scientists to cancer, birth defects, fetal death, and other effects. One Harvard University biochemistry professor even claimed that dioxin may be 'the most powerful carcinogen known.'" (19) In a letter to Dr. Kligman, Gerald K Rowe, a Dow official, wrote that he was sending the TCDD to be used in the tests. He warned that the chemical was: highly toxic, and an oral dose of one-half to one microgram [one one-millionth of a gram] of it is always fatal in laboratory animals, with a typical clinical picture of severe liver and kidney injury...The seriousness of the consequences that might develop from testing with this type of compound require that we approach the matter in a highly conservative manner. (20) Rowe authorized Kligman to begin with a dose of .2 micrograms (applied topically) and to gradually increase doses to 16 micrograms. (21) Rowe believed these amounts to approximately mirror those to which Dow workers had been exposed on a regular basis. In May of 1966, months after having received the TCDD from Rowe, Kligman reported "astonishingly negative results" to Dow. He had applied up to 16 micrograms of the chemical to six groups of ten men, all of whom underwent liver and kidney tests. "No subject developed symptoms that could be related to the treatment," he reported. (22) In a personal letter to Rowe he wrote, "I am grieved that so little has been learned." (23) In January 1968, Rowe received a letter from Kligman. "We followed a specific protocol laid down by you," Kligman wrote. "Unfortunately, not a single subject developed acne nor was there any evidence of toxicity. This encouraged me to proceed more vigorously." (24) And proceed more vigorously he did. In the same letter, he told Rowe that in the year-and-a-half since his 1966 report, he had done further testing on a new panel of ten prisoners. He had increased the dosage to 7,500 micrograms, 468 times that which Rowe had authorized him to administer. The increase had the desired effect; Kligman reported that, "Eight of ten subjects showed acne lesions usually beginning in three to four weeks. In three instances, the lesions progressed to inflammatory postules and papules. These lesions lasted for four to seven months, since no effort was made to speed healing by active treatment." (25) The subjects were given kidney and liver tests for six weeks after the experiment and "in no instance was there laboratory or clinical evidence of toxicity." (26) In 1980, Rowe testified before an Environmental Protection Agency (EPA) committee that neither he nor anyone else at Dow knew of Kligman's subsequent testing (the 7,500 dosage) until Kligman had already completed them. "In January of 1968," he testified, "I was surprised to receive a letter from Dr. Kligman reporting new results." (27) It was in Rowe's testimony before the committee that the EPA-and the public-first learned of Kligman's dioxin experiments. The hearing was about whether Dow's Silvex, which was restricted to some agricultural uses, should be prohibited altogether. Silvex contained chemicals very similar to those tested by Kligman. (28) Like all of Kligman's reports of experiments on prisoners, the one for the Dioxin tests did not include any legible names of prisoners. This omission is particularly significant. After the EPA leaned in 1980 of Kligman's experimentation with dioxin, it searched tirelessly for the 70 prisoners, most of whom were presumably no longer incarcerated. The New York Times reported in 1981 that "information about the Holmesburg tests, apparently an unusual instance of human exposure to controlled doses of dioxin, would be invaluable in resolving the question of how safe the poison is when used in herbicides." (29) The EPA was particularly interested in locating the ten recipients of 7,500 micrograms of dioxin. Two years later, in a report on the EPA's inability to locate the 70 former inmates, EPA Pesticides Investigator Frank L. Davido wrote, "The agency believed that records relating to Dr. Kligman's studies could have provided additional information on the risks associated with the uses of 2,4,5-T and Silvex because the precise dermal dosages of TCDD in the studies were apparently known." (30) When Epstein first disclosed the dioxin tests in the Philadelphia Inquirer in a January 1981 article entitled "Human guinea pigs: Dioxin tested at Holmesburg," forty prisoners and former prisoners contacted the EPA, believing they had been among the tested. But after nine of the men were interviewed, Davido concluded that it was hopeless to try to determine which of them were actually Kligman's subjects. (31) In addition to aiding the EPA in their evaluation of the danger of certain herbicides, locating the prisoners and former prisoners would have been important for two other reasons. First, the individuals subjected to dioxin in the 1960's may have been suffering in the 1980's (and perhaps are today) from long-term health effects that, if detected in a timely fashion, could have been treated successfully. There were, of course, no follow-up medical studies after the experiments. (32) Second, the United States Air Force sprayed about 12 million gallons of Agent Orange-of which dioxin is a key component-during the Vietnam Conflict to defoliate five million acres of Vietnam countryside. Locating Kligman's subjects would have been of particular interest to the group Vietnam Veterans Against the Federal Government and Chemical Companies, who sued the government and five chemical companies for the effects they believed Agent Orange had on them and their children. They claimed their exposure to the defoliant produced tumors and other ailments in them and birth defects in their children. (33) Dr. Kligman's failure to record the names of his Holmesburg subjects rendered his dioxin experiment all but useless. His tests were of little help to Dow, as his only subjects to develop symptoms were exposed to vastly more dioxin than the Dow employees. (Perhaps the failure of the first sixty inmates-who were exposed to the authorized amounts of dioxin-to develop Chloracne indicated that the outbreak in the Dow plant was attributable to something else.) Although his experiment could have been invaluable to the EPA and Vietnam veterans, the absence of the subjects' names on the report precludes it from being of any help. Thus, it is likely that 70 human beings suffered, or are suffering, unnecessarily from any number of effects of the testing (possibly even leukemia), and their suffering did not even lead to a better understanding of the toxic chemicals being tested. Kligman, however, dismissed his responsibility for any suffering. In a brief telephone interview with William Robbins of the New York Times, Kligman said of this possibility, "All those people could have leukemia now-about one chance in 20 billion. And I could be hit by an asteroid when I walk out on the street, but I don't think I will." (34) Revealing Allegations Dr. Kligman may have hoped that removing the prisoners' names from reports of his Holmesburg experiments would diminish the likelihood that any effects that the tests would have on people in the future be linked to him. But in addition to the increased media coverage and availability of once-classified documents, another factor has enabled historians to attribute to Kligman various consequences of his tests: his subjects' stepping forward, mainly in the form of law suits. Although some of the suits referenced experiments performed by Kligman not mentioned in this discussion, they will all serve as examples of Kligman's utter disregard for his subjects' well-being and his subordination of their health and safety to his advancement within the scientific community. Further, these suits can also serve as the follow-up examinations that Kligman failed to perform. Let us look at a few allegations. In January 1980, the Daily Pennsylvanian reported that James Walker was suing Penn for "barbaric" medical experiments performed by Kligman. Walker contended that his lifestyle was permanently changed after he suffered "severe reactions to the experiments, which were conducted from 1964 to 1968 by University dermatology professor Albert Kligman under a [Dow] contract with the University." (35) A year later, Walker learned from the EPA that he was probably one of the ten prisoners to receive 7,500 micrograms of dioxin. Speaking for Walker, his attorney said, "His life is ruined. He has lupus, a skin disease, and whenever he is exposed to the sun his breasts grow. He now can work only at night, and can't enjoy his children. He can't play ball with them or go to the beach. This is hardly a normal life." (36) In November 1981, another five former Holmesburg prisoners filed suit against Penn and Kligman, alleging that Kligman gave them, "potentially harmful drugs during experiments [he] conducted in the 1960's...The suit reportedly charges that the prisoners were not told the nature of the experiments and suffered from outbreaks of rashes following their participation in the studies. They are also allegedly suffering from what they refer to as 'cancer phobia,' or the fear that they will eventually contract cancer." (37) These claims indicate that Kligman's claim that "no subjects suffered any permanent effects" warrants scrutiny. The Issue of Consent This discussion would be unduly prejudiced if no mention were made of the fact that all of Kligman's subjects did sign consent forms and were monetarily compensated for their efforts. But did they know what they were signing? Did the consent forms clearly and accurately describe the risks concomitant to the experiments? And were the prisoners justly compensated? That the experiments were performed on prison inmates immediately diminishes the exonerating prowess of a consent form. Why did Kligman not ask Penn students, who were abundantly available to him, to subject themselves to his experimentation for a payment? Would it not have been more convenient, more pleasant and safer for Kligman to perform his experiments on Penn's campus rather than inside the walls of a maximum-security prison? Probably, Kligman decided to capitalize on the desperation pervading Holmesburg rather than deal with the incisiveness of Ivy-leaguers. When someone is serving multiple life sentences, a pack of cigarettes from the prison commissary is rather appealing. Having said that prisoners are extremely vulnerable, let us briefly examine the consent forms they signed, the context in which they sign them, and how much they were told. Allan Lawson, of the Prisoners' Rights Council and a former Holmesburg inmate testified that, "The only way a prisoner can earn money is by participating in the medical testing program conducted in the prison by the University of Pennsylvania." He conceded that all subjects did sign consent forms, but likened them to "hieroglyphics." Another former inmate, and prisoners' rights advocate Leodus Jones added that "people go into [the tests] in the blind. They don't know nothing about nothing." (38) In the aforementioned court case involving five inmates, the five also alleged that they were not forewarned of the possible effects of the testing. Finally, the payment system for experiments was likewise dubious. No cash or checks were ever paid to "volunteer" prisoners. They were instead issued up to $20 per week in commissary credit, depending upon the severity of the experiment(s) to which they agreed. (39) Contracts usually included funds specifically designated for this purpose. The multiple levels of these arrangements makes the proposition that prisoners did not have "full information" when they entered into these contracts seem patently true. The Relevance of Retin-A In 1990, the Daily Pennsylvanian reported that Edward Farrington, a former Holmesburg prisoner, filed a $6 million law suit against the University and other defendants, claiming he developed leukemia as a result of Penn-conducted radiation research at the Prison in 1967. Incidentally, he alleged that he had been assured that the experiments would not have any short- or long-term effects. He claimed that radioactive material was injected at seven points along his arms and back, and were marked with permanent tattoos. These marks, he alleged, were periodically examined with a Geiger counter. (40) In an article about a week later, the Daily Pennsylvanian reported that Associate General Counsel for the University Neil Hamburg said of Farrington's suit, "We're trying to figure out what this person is talking about. If he gave more information, we would have some idea where to look. (41) This appears to be a rather naive statement from one of Penn's attorneys, considering the media exposure that Kligman's experiments have gotten in recent years. Even if the experimentation performed on Farrington actually had nothing to do with Kligman, Penn attorneys were certainly aware of the possibility that Farrington's suit had relevance to Kligman's work. In April 1992, the Daily Pennsylvanian reported that the University and Farrington reached a settlement. According to the article: Plaintiff Edward Farrington was paid an undisclosed sum in order to avoid the costs of litigation and to buy peace,' Associate General Counsel Neil Hamburg said...Farrington said in the suit that he could not recall what department of the University oversaw the alleged experiment, and could not produce any names of workers, except 'McBride.' ...Lawyers for the University acknowledged in legal briefs that a person named McBride had worked for the University in 1967. But they firmly denied that any such individual was involved in the kind of experiments described in Farrington's suit. (42) Three different facts make this case worthy of further investigation: first, it is somewhat curious that Penn would agree to pay a settlement to a plaintiff whose case was as weak as Farrington's appeared to be. Second, Sol McBride not only worked for Penn in 1967, but was also intimately involved in Kligman's experiments, contrary to Hamburg's statement. Third, and perhaps most importantly, Penn's agreement to pay Farrington came only weeks after they resolved a two-year court battle (between themselves, Kligman, and Johnson & Johnson) over the rights to sell Retin-A, a popular acne drug, as an anti-wrinkle cream. During the peak years of Army contracts for human experimentation, Kligman founded "Ivy Laboratories" in an attempt to procure for himself some of the massive research grants available. He experimented on prisoners both under Ivy Laboratory contracts and under Penn contracts. Regardless of under what auspices he was performing tests, he was a professor of dermatology in the employ of Penn. The 1975 report of the Inspector General of the Army reported that "Ivy research used at least 94 inmates to test choking agents, nerve agents, blister agents, vomiting agents, incapacitating agents, and toxins." (43) These tests were actually charged with causing a prison riot and fire in 1972, at which time Ivy was banned from Holmesburg altogether. It was at this time that McBride became important. In addition to being a professor at Penn, McBride also held the title of "Medical Administrator" in Kligman's Ivy Laboratories. (44) Although he probably performed experiments in this capacity, he certainly was involved to some extent in Kligman's experimentation. It would seem too coincidental that a prisoner suing Penn would luckily throw out the name McBride as Hamburg suggested. In reality, Farrington was almost certainly among the 94 inmates cited in the Inspector General's report, and Hamburg probably realized the overwhelming probability of this. So how does this relate to the notorious and lucrative anti-acne and anti-wrinkle cream? In January of 1990, the New York Times reported that Penn was suing Kligman, Retin-A's inventor, as well as the Johnson & Johnson company. Penn claimed that Kligman violated his employment contract and the University's conflict-of-interest policies by striking an independent deal with Johnson and Johnson. The University claims in its contract with professors the rights to virtually all patents acquired if they were developed on University time or on University property. When Kligman developed Retin-A as an acne cream in 1967, Penn signed an agreement with both him and Johnson & Johnson. But the University filed the law suit when it learned that Kligman had obtained a second patent in 1986 to use Retin-A to fight wrinkles; the previous patent only enabled Retin-A to be sold as an acne cream. Penn claimed that Kligman never revealed this 1986 patent, but instead struck a secret deal with Johnson & Johnson. The University claimed that Kligman discovered on University time Retin-A's wrinkle-fighting properties. (45) After a two-year court battle, a compromise was reached in March 1992, which gave Johnson & Johnson exclusive ownership of the patent rights to Retin-A. But Johnson & Johnson agreed to pay Penn all future royalties if the Food and Drug Administration approves a Retin-A compound,-which is similar to Retin-A and will be sold under the tradename Renova-as a treatment for sun-damaged skin. In other words, if the FDA approves Renova, Penn will acquire full rights to the Retin-A patent. This will translate to hundreds of millions of dollars for the University. Meanwhile, Kligman is working to better his relations with the University outside of the courts. As of 1992, Kligman had donated $15 million to the University's dermatology department, and he has promised to donate more. (46) Thus, a few weeks after Penn learned that they stood to gain hundreds of millions of dollars from a drug that Kligman developed in 1967-when his experimentation at Holmesburg was as its peak-University officials hastily settled a seemingly weak case filed by an incarcerated convict. (Farrington was still incarcerated when he filed his case.) The conclusion? Hamburg et al. realized that there actually was foundation to Farrington's case. A trial could have revealed that Kligman developed Retin-A from his experimentation on Holmesburg prisoners; for example, his "skin-hardening" tests seem to have obvious application to the development of an acne cream. If this is actually what occurred, it would call into question Penn's standards for scientific research. Hamburg's reaction to a preliminary ruling favorable to Penn early in the court battle would have been ironic if eventually a judge or jury had found against Kligman: "The judge's decision is important because the University is in the business of advancing society through research, and the money the University obtains under its patent policy will go back into research for the betterment of society." (47) Kligman's Work from an Historical Perspective When history is discovered, the discoverer often finds himself ashamed and perplexed at how a previous society could tolerate practices that are presently abhorred. Such were the feelings of those discovering Kligman's dubious testing practices. However, Dr. Kligman's tests, as reprehensible as they may seem today, were far from enigmatic-let alone objectionable-when they were performed. Between 1950 and 1975, the Army spent $78 million on drug testing on human subjects alone. (48) That considered, Kligman's tests were but a minuscule portion of those done around the country at the time. Beginning in the 1950's Penn competed with such institutions as New York University, the University of Maryland, the University of Utah, the University of Washington, Tulane, the University of Michigan, and even the New York State Psychiatric Institution to secure Army grants for human testing. (49) Also, regulation against such experimentation was at best mere formality. Although the Nuremberg Code of 1947 had forbidden the Army from experimenting on soldiers, the Organization of the Army Act of 1950 allowed the Army some flexibility. In addition to prisoners, the Army tested-or contracted tests for-various nerve agents and other chemicals on more than 7,000 soldiers. (50) This was all part of the government's Cold War agenda and their attempt to keep pace with the Soviet Union in every aspect of warfare development. Eventually, permanently damaging human experimentation testing ended in the mid-1970's when people began to question it on both moral and humanitarian grounds. Most of Kligman's subjects were young black men. In October 1994, Harriet A. Washington published a comprehensive study in Emerge magazine detailing blacks' history with medical experimentation. She mentioned, for example, the Tuskegee Syphilis Experiment of 1932-72, during which black men were purposely exposed to syphilis. She also discussed the world-renowned case of Henrietta Lacks, who was dissected without her husband's or family's permission, and her body sold for millions. Washington also wrote that the Virginia Commonwealth University exploited blacks in local hospitals, by subjecting them to radiation burns and phosphorus-32, a radioactive substance. (51) Blacks and other socially marginalized groups (other minorities and the handicapped, for example), understandably-but unconscionably-have had the most experience with devious medical experiments. However, as society progresses, so too do all groups within the society, diminishing their marginalization. In 1966, for example, Kligman said to a reporter, speaking of his access to Holmesburg prisoners, "All I saw before me were acres of skin. I was like a farmer seeing fertile field for the first time...[It was] an anthropoid colony...which wasn't going anywhere." (52) It is doubtful that a researcher would think, much less say to a reporter, that statement today. Protections Against Dubious Experimentation Today One wonders with a healthy amount of skepticism whether a Kligman experiment could happen today. Thankfully, we tend to learn from those historical episodes that we would often like to forget. Certain modern guidelines have been created for the very prevention of repetition of previous crimes. Specifically, Penn distributes a half-inch thick book of guidelines to all of its medical research called the Guidelines for the Preparation of Protocols for Review. This manual was prepared by the University of Pennsylvania Institutional Review Board Committee on Studies Involving Human Beings and outlines an intricate protocol that all researchers must follow before performing any experimentation on humans. Such guidelines are direct results of public pressure exerted on institutions to curb inhumane testing on humans. (53) Dr. Kligman Dr. Kligman is now Professor Emeritus of Dermatology. At age 79, he is a world-renowned expert on the aging of the skin, and has appeared in varied publications from Seventeen to Time to the New England Journal of Medicine. A millionaire several times over, he lives in a New Jersey suburb of Philadelphia with his wife, who is also a dermatologist. To this day, Kligman remains only the second researcher in the FDA's history to be banned from its approved list of researchers entitled to test investigational drugs on human subjects. This ban was reported by Time in August 1966, before the Army granted him, Penn, and his Ivy Research Laboratories about $500,000 in research contracts to test human beings. Dr. Kligman refused to discuss any of the information contained herein.
