Cheaper than Chimpanzees: Expanding the Use of Prisoners in Medical Experiments

by Gregory Dober

?It is the duty of the doctor to remain the protector of the life and health of that person on whom clinical research is being carried out.? ? Declaration of Helsinki

In June 2006, the Institute of Medicine (IOM) issued a report on simplifying the current federal regulations for conducting medical research in prisons, which included recommendations to increase the use of prisoners as test subjects. The IOM?s ?definition of simplicity? is approximately two hundred pages long while the current regulations, included in the report, account for approximately four pages of the same font size, type and page length.

An IOM Committee was formed in 2005 to investigate possible changes to the federal policies regarding biomedical research in prisons. Those regulations, codified at 45 C.F.R. 46, Subpart C (Research and Prisoners), are intended to protect prisoners as subjects in biomedical and behavioral research. The current regulations restrict researchers to four basic categories of research when using prisoner test subjects: 1) studies involving causes and effects of incarceration, 2) the prison as an institutional structure, 3) conditions affecting prisoners as a class, and 4) research on practices that have the intent and reasonable probability of improving the well-being of the subject. All research studies must ensure minimal risk to the incarcerated test subjects.

Still Cheaper Than Chimps

In her 1973 book, Kind and Usual Punishment, Jessica Mitford said a researcher had confided to her that prisoners are ?... fine experimental material ... and much cheaper than chimpanzees.? Thirty years later in 2003, the Institute for Laboratory Animal Research (ILAR), which includes among its supporters many pharmaceutical companies and governmental agencies, reported the following dilemma in the Institute?s journal. The article, Demands for Rhesus Monkeys in Biomedical Research: A Workshop Report, stated, ?... scientists are facing a shortage of nonhuman primates available for biomedical studies. Through the mid-1970s, the rhesus macaque could be readily imported from India, and the scientific community grew dependent on access to this laboratory animal. Today, however, rhesus macaques can no longer be imported from India. Although U.S. breeding colonies are operating at peak capacity, scientific demand for these and other nonhuman primates exceeds the available supply.
Concerned that shortage of nonhuman primates could seriously impede scientific progress, two components of the National Institutes of Health (NIH) ? the Office of AIDS Research (OAR), and the National Center for Research Resources (NCRR) ? have taken a lead role in addressing this issue.?

High costs, a shortage of primates and intimidation from animal rights activists have caused some researchers to move their biomedical laboratories to countries more conducive to research using nonhuman primates. Based upon the ILAR report, Ms. Milford?s observation of thirty years ago may not be so outrageous. Currently, those who oppose using nonhuman primates in research garner a more influential legislative lobby and more public sympathy than those who oppose the use of prisoners in medical experiments.

Before reviewing the IOM?s proposed changes in prison research regulations, I wanted to satisfy a curiosity and determine if prisoners are in fact cheaper than chimpanzees. Due to space and time constraints I did not calculate financial figures; however, based upon current regulations, prisoners still appear to be less costly. The Guide for the Care and Use of Laboratory Animals, funded by the National Institute of Health and other government agencies, is approximately one hundred and twenty pages in length. A review of the Office of Human Research Protections, IRB Guidebook, reveals that approximately four pages are dedicated to prisoners as research subjects.

In 1966, Congress passed the Animal Welfare Act (AWA), 7 U.S.C. § 2131. The act, and subsequent regulations such as the Improved Standards for Laboratory Animals Act (1985), include such obligations as requiring researchers to provide primates with a ?balanced diet of wholesome food,? ?environmental enrichment? such as toys and regular interaction with other primates, ?minimum requirements ... for a physical environment adequate to promote the psychological well-being of primates,? and ?clean and structural housing? with suggested dimensions. In the suggested enclosure dimensions, two 66-pound apes are required to have more square footage than two human prisoners who share a typical prison cell.

Facilities that house primates must have a full-time veterinarian located on the premises and must establish a program of regular veterinarian care, including medical examinations. The USDA Animal and Plant Health Inspection Service is allowed to make regular and unannounced visits to research facilities. Corrective action for violations can include confiscation of the animals and/or civil penalties imposed on the researcher. However, no such uniform laws or regulations exist that give prisoners enforceable rights related to amount of living space, diet, medical care, living conditions or psychological well-being.

While a need exists for the protection of research animals, it is troubling that the regulatory requirements for working with lab animals are apparently more burdensome and costly than experimentation on prisoners. If a researcher can read and understand the approximately two hundred pages of the IOM report or the hundreds of pages of animal welfare requirements, what seems to be the difficulty in understanding the four pages of current federal prison research regulations?

Evolution Of Biomedical Research Codes

It was after the experiments conducted by Nazi researchers on concentration camp prisoners during World War II that a formal code of research ethics was created. Subsequently, various international and national codes, laws and regulations have been implemented with the intent to guide proper ethical conduct relative to biomedical research studies.

In 1947, the Nuremberg Code established a set of written principles in response to human experimentation by Nazi doctors during the Second World War. The Code addresses such important principles as absence of coercion, properly formulated scientific experimentation, and informed consent. In response to the dissemination of the Nuremburg Code, the World Medical Organization in 1964 developed the Declaration of Helsinki, which reiterated many of the significant principles embodied in the Code.

On July 12, 1974, President Nixon signed the National Research Act. This law created a commission to identify basic underlying ethical principles to be used in conducting biomedical research. In 1979 the results and recommendations of the commission were published in the Belmont Report, which established ethical guidelines for informed consent, beneficence, justice, assessment of risks and selection of human test subjects.
Notably, the Belmont Report, which addressed human research subjects, was published thirteen years after the AWA was enacted to protect animals.

The National Research Act required codified regulations to protect human subjects during medical research in the United States. This resulted in 45 C.F.R. 46, Regulations for the Protection of Human Subjects in Biomedical and Behavioral Research, which established standards for matters such as informed consent, selection of research subjects and Institutional Review Boards (IRBs). In 1978, federal regulation 45 C.F.R. 46, Subpart C was issued specifically for the protection of prisoners as vulnerable subjects in biomedical and behavioral research. Two years later the Food and Drug Administration (FDA) adopted 21 C.F.R. 50.44, which prohibited the use of prisoners in Phase 1 clinical drug trials.

In 1991, 45 C.F.R. 46, Subpart A, Basic HHS Policy for the Protection of Human Research Subjects, became known as the ?Common Rule.? Seventeen federal agencies agreed to adopt the principles of the regulations and consistently apply them to subjects in all federally funded research.
However, as the IOM report notes, only three federal agencies have chosen to follow the more rigid regulations for protection of prisoners in medical studies. These three agencies are the National Institute of Health (NIH), Central Intelligence Agency and Social Security Administration. Since the NIH distributes most of the nation?s university research grants, those institutions must abide by the federal regulations on prisoner research. Ironically, before adoption of the regulations it was the CIA and its proxy, the Department of the Army, that carried out various experiments on prisoners, ranging from toxic chemicals to mind altering drugs.

In 2003, Karena Cooper, a representative of the Office for Human Research Protections (OHRP), made a presentation that addressed the difficulties encountered by researchers in understanding and complying with the current prison research regulations. OHRP requested guidance on the regulations, including issues of adequate inclusion or exclusion of prisoners as subjects, appropriate background for a prisoner representative on an IRB, and the challenges of working within the four categories of research permitted for prisoner test subjects. A subcommittee was formed to investigate the OHRP request. The subcommittee presented a list of recommendations and commissioned the IOM to study the recommendations and issue a report regarding changes to existing prison research regulations. The report was finalized and published in June 2006.

The Sordid Legacy Of Prison Research

The IOM report states, ?Advances in ethical thinking about protectionism suggest a new regulatory model. In particular, the committee rejects strong protectionism because it discounts the notion that researchers can be trusted to act virtuously in the protection of the subject.? In past decades, however, improper research in prisons has seemed to be the norm despite ethics regulations.

Following the issuance of the Nuremburg Code, biomedical researchers during the period of the 1940s through the 1970s used prisoners as a primary source of research subjects. In 1962 the FDA began requiring pharmaceutical drugs to undergo three human clinical trials before approval; as a result, from 1962 to 1980, when the regulations were changed, up to 85% of Phase 1 clinical trials were performed on prisoners.

Many hazardous research trials were conducted on prisoners without proper informed consent or minimal risk to the test subjects. Two high profile cases were the Oregon and Washington State prison radiation studies and the non-therapeutic biomedical research studies at Holmesburg Prison in Philadelphia. [See: PLN, March 1999, p.1].

In the early 1960s, Dr. Carl G. Heller and Dr. C. Alvin Paulsen received $1.6 million in funding from the U.S. Atomic Energy Commission to perform radiation studies on the male reproductive system. The testing consisted of irradiating hundreds of prisoners? testicles with large doses of radiation. The prisoners were paid $5 a month and $10 per biopsy to be subjected to these experiments, plus $100 at the conclusion of the study.
High-dose radiation experiments continued on prisoners until 1970 in Washington and 1973 in Oregon. As a result of this research the prisoner test subjects suffered severe burns, testicular inflammation, painful biopsies and bleeding into the scrotum. The informed consent forms signed by the prisoners did not mention an increased risk of testicular cancer, radiation poisoning or other long-term effects. In a 1976 deposition, Dr. Heller admitted he ?didn?t warn them of all the dangers because I didn?t want to frighten them.? At least four prisoners who did not get vasectomies reportedly fathered children with birth defects after their release.

In 1995 the Clinton administration and universities involved in radiation research experiments issued an apology to the test subjects. Regardless, an unapologetic Dr. Paulsen maintained that no wrong had been done. In fact, a follow-up program was considered subsequent to the irradiation experiments in Washington that would have provided medical exams to the prisoner test subjects at two or three-year intervals. Dr. Paulsen criticized such exams, saying they were ?not indicated for medical reasons.? He also questioned the legality of contacting the former prisoner participants and opined that former subjects would want to ?disassociate themselves from the prison experience.?

Questioned about his prison research, Dr. Paulsen said, ?If our work was unethical then you?d have to say that all the committees that approved it in those days were completely unethical, and so, no, that?s not true. But I don?t want to talk about it any more.? The U.S. Dept. of Energy, commenting on the Washington and Oregon prison irradiation studies, called them ethically flawed ?even by the standards of the time.?

Allen M. Hornblum, in his 1998 book Acres of Skin [distributed by PLN, see page 46 for ordering details], documented the longest known case of prison experimentation in the United States. The studies were conducted at Holmesburg Prison in Philadelphia. From the 1950s through the 1970s, Dr. Albert Kligman, then a young and aspiring dermatologist at the University of Pennsylvania, conducted various experiments on inmates. His studies eventually led to the discovery and patent of Retin-A, an anti-acne cream. In addition he performed hundreds of experiments on prisoners for Johnson & Johnson, Dow Chemical, the U.S. Army and his own corporation, Ivy Research.

At Holmesburg, Dr. Kligman?s research trials varied from the innocuous to the mutilating and dangerous; they ranged from the use of lotions and creams to poisonous chemicals and radioisotopes. He was paid $10,000 by Dow Chemical to test the effect of dioxin, an ingredient in Agent Orange, on prisoners? skin. Many of the biomedical trials conducted at Holmesburg had research protocols that were neither of a therapeutic nature nor of benefit to the test subjects. Some resulted in lasting injuries.

In 2006, after the IOM committee issued its report, Dr. Kligman was asked by New York Times reporter Ian Urbina for his opinion on revising the federal regulations to increase the use of prisoners as research subjects. ?My view is that shutting the prison experiments down was a big mistake,? Dr. Kligman said. He cited his breakthroughs for the development of Retin-A and ingredients for many of the topical creams used to treat poison ivy, and stated his belief that such experiments resulted in overwhelming benefits to the public. ?I?m on the medical ethics committee at Penn,? Kligman noted, ?and I still don?t see there having been anything wrong with what we were doing.? [See: PLN, Oct. 2006, p.14]. Which is not surprising, considering that his experiments generated overwhelming personal benefits. In 2000, Dr. Kligman donated $2 million to create fellowships for graduate students at Penn State University ? money that he likely made, in part, from his profitable prison studies.

Some in the research community claim that cases such as Drs. Kligman, Paulsen and Heller, while infamous, are isolated and rare. To test that hypothesis I went to a medical library and randomly pulled journals from the ?gilded era? of medical research. Within forty minutes I found numerous articles involving prisoner test subjects. John R. Neefe and Joseph Stokes, Jr., et al. published one of these not-so-famous studies in the March 1947 issue of the Journal of Clinical Investigation. The authors describe the blending of hepatic liver and hepatic feces in a Warring Blender to create ?liver suspension in sterile beef heart infusion broth? and ?feces pool.? The study ?volunteers? were male prisoners with no history of jaundice or hepatitis from the New Jersey State Prison in Trenton. The researchers described the inoculation of these volunteers: ?On each of 4 successive days, 5 ml. of feces pool ... was administered in chocolate milk to each of the five volunteers. ...
The five men of the third group, each ingested in milk, 20 ml. of liver suspension ....? Experiments such as these, infecting otherwise healthy people, with contagious diseases may well have helped spread hepatitis and other diseases among the IV drug using and prisoner population where it is currently concentrated.

In other early experiments, Harvard biochemist Edward Cohn injected 64 Massachusetts prisoners with cow blood in a 1942 study sponsored by the U.S. Navy. More than 400 Illinois prisoners were used as test subjects in malaria experiments conducted by Dr. Alf Alving of the University of Chicago Medical School between 1944 and 1946; the prisoners were not told they were being infected with malaria. One prisoner died and two developed hepatitis in a 1944 study conducted by Captain A.W. Frisch at the state prison in Dearborn, Michigan. In 1950, 200 female prisoners were injected with viral hepatitis in a University of Pennsylvania experiment. Two years later, Chester M. Southam at the Sloan-Kettering Institute injected live cancer cells into Ohio State Prison convicts to examine the progression of the disease. Half of the test subjects in Southam?s NIH-sponsored study were black, raising concerns of racism.

Time magazine reported in July 1963 that a drug trial program at the Oklahoma State Penitentiary was being ?drastically overhauled.? The prison?s medical director, Dr. Austin R. Stough, and his partner, Dr. Cranfill K. Wisdom, were paid an estimated $300,000 annually by pharmaceutical companies to use prisoners as test subjects. They also ran a profitable prison blood plasma operation; a similar program in the Arkansas prison system was the subject of an award-winning 2005 documentary called ?Factor 8.?

In 1967, sixty-four California prisoners were paralyzed with succinylcholine, a neuromuscular agent that restricts breathing. Succinylcholine has since been used in lethal injection protocols. When several of the prisoners refused to participate in the experiment, researchers were given permission to inject the recalcitrant prisoners against their will.

Radionuclide tests using prisoner subjects were sponsored by the University of Utah ? blood samples were taken from the prisoners, exposed to a radioactive form of phosphorous, and then re-injected. The university conducted 13 human radiation experiments between 1954 and 1972 that involved 640 people, almost half of them prisoners. Doctors involved in those studies later wrote research papers indicating that irradiated phosphorus contributes to some forms of bone cancer.

Many of the above examples, and other egregious experiments performed on children, pregnant women, the mentally disabled, military personnel and the uninformed general public, are detailed in Andrew Goliszek?s 2003 book, In the Name of Science. It is apparent that such studies were not so rare or isolated, nor ethical or humane. Note that the Neefe and Stokes hepatic feces study was conducted contemporaneously with the high profile Nuremburg trials, when American prosecutors were seeking death sentences against Nazi doctors accused of unethical medical research.
Ironically, in 1971 the Children?s Hospital of Philadelphia named the Joseph Stokes, Jr. Research Institute after its former physician-in-chief and co-author of the hepatic prison research study. During the Nuremberg trials the Nazi doctors cited the University of Chicago?s prison malaria experiments to defend their own biomedical testing on concentration camp prisoners. Perjured testimony by American prosecutors disclaimed any similarity between contemporaneous Nazi and American experiments on prisoners. 16 of the 23 doctors were convicted and seven hanged.

Drs. Kligman and Paulsen, in their subsequent comments regarding their research protocols, have shown no apparent remorse or responsibility for the pain and suffering they inflicted on prisoner subjects during or after their experiments. Both researchers continue to maintain their ?ethical innocence.? Revising or expanding prison research regulations will not eliminate immoral or unethical researchers and their behavior, and if history is a predictor of human proclivity then the OHRP must embrace ? not reject ? strong protectionism on behalf of incarcerated test subjects.

This is true because questionable clinical trials involving prisoners are not relegated to the distant past. In 1997, Stanford University sponsored psychiatric drug tests on 61 juvenile prisoners at a California Youth Authority facility in Stockton. The test subjects were 14 to 18 years old and had committed violent crimes; they were given doses of Depakote, a drug used to control epileptic seizures. The study was conducted without the knowledge of the CYA director or the agency?s legal office, and may have violated a state law that barred most medical research involving prisoners. Consent forms were mailed to the juveniles? parents; if the parents didn?t respond within 30 days, the CYA gave consent on their behalf. The experiment had been approved by Stanford?s Human Subjects Committee. [See: PLN, Dec. 1999, p.11].

Further, a March 19, 2000 article in the St. Petersburg Times detailed pharmaceutical trials involving HIV-positive Florida prisoners. State prison officials, cautious about such research, created a watchdog committee to protect the prisoner test subjects; however, the committee was disbanded and replaced months later with a panel composed almost entirely of prison employees. The prison system?s director of health services, Dr. David L. Thomas, a proponent of the drug trials, previously had been listed as a consultant and speaker for two pharmaceutical companies that produced anti-HIV medications used in the research studies. Both companies stated they had paid him honoraria for his advice on AIDS-infected prisoners. The Florida prison studies were funded by NIH, Glaxo Wellcome, Merck & Co., and Pharmacia & Upjohn, Inc.

?I?m sure you will find someone, whether it?s a prisoner rights advocate or a so-called expert on medical ethics, to criticize us, especially on the issue of informed consent,? said Florida Dept. of Correction spokesman C.J. Drake, who referred to questions from a Times reporter as ?nitpicking issues of secondary importance.? Prisoners who volunteered to participate in the drug trials cited better healthcare and amenities at the treatment unit such as air conditioning and comfortable shoes as inducements. One pris