These are some notes that I prepared during the Christmas vacation in 1996,
after I read a number of cases and books about medical experiments on human
beings. I begin with summaries of facts and my personal comments on several
famous (notorious) cases, then I give my personal draft of a set of rules that
might offer better protection to research subjects than the current system in
the USA.
Improvements in medicine and surgery during the last two centuries have
greatly extended the average lifetime of people and reduced the pain and
disability following various injuries and diseases. Because medicine and surgery
have a strong basis in scientific knowledge, it is absolutely necessary
for medical progress that there be experiments on humans. There can be no doubt
that human experimentation is necessary and desirable. Society owes a great debt
to the many creative physicians and surgeons who have performed ethical
experiments and advanced medical technology. If there be any doubt, I say that I
am definitely in favor of research, but we should also insist on ethical
conduct.
There is also a dark side to human experimentation: a long history of
dangerous and harmful experiments performed on nonconsenting patients.
Not only was informed consent not obtained, but the physician often fraudulently
described the experimental procedure as either a diagnostic procedure or a
treatment for the patient's condition, when the physician had no reason to
believe that the patient might benefit from the experiment. History has shown
that nonconsensual experiments are often performed on captive people in an
institution, particularly people who society has regarded as "less worthy"
(e.g., Jews in Nazi concentration camp, mentally retarded people in
institutions, Negroes, indigent patients, ...). Such people are unable to
decline or reject the experiment and few people will ever know what really
happened.
Regulation of medical experimentation on human beings must consider the
following:
rational need of researchers to have access to human subjects. Experiments
on human subjects are performed after in vitro experiments and after
experiments on animals have shown that a drug or technique has a reasonable
possibility of benefiting human beings. In assessing the desirability and
acceptability of the experiment, one should consider the severity of the
disorder (e.g., terminal illness vs. minor inconvenience) together with the
possible side effects of the experimental treatment.
potential subjects must give informed consent (i.e., consent after
experimenter has made an honest, complete disclosure of risks). Informed
consent is necessary for the personal autonomy of the subject.
researcher's conflict of interest, in which researcher wants a large
number of subjects to consent and then wants all of these subjects to complete
the entire experimental program. However, the researcher, as a physician, also
has an obligation to neither harm nor exploit the patients/subjects.
In my opinion, these three considerations are not to be balanced
against each other, but are to be independently satisfied.
The conflict of interest is worth exploring further, as it is the key to
analyzing much of the ethics of human experimentation. Patients expect safe,
effective treatment for their condition and patients trust their physician to
supply unbiased advice. But, in human experimentation, the relationship
is often not physician to patient, but is researcher to subject. The researcher
gets paid to do the clinical trial or experiment, and may also receive royalty
income from new drugs, devices, or cell cultures that are developed in the
experiment. The researcher may even become famous as the author of a landmark
paper in the archival medical literature, which is a kind of immortality. In
contrast, the subjects get pain and sometimes permanent injury, or even death,
from the experiment.
A copy of the
Nurnberg Code is posted at the U.S. Holocaust Memorial Museum's web site.
Condensed Nürnberg Code
1. Absolutely essential to obtain voluntary, informed consent of every human
subject. Voluntary means without any element of force, fraud, deceit, duress, or
coercion. Before asking his/her consent, must inform of all inconveniences and
hazards reasonably to be expected and the effects upon his health or person that
may come from his/her participation in the experiment.
2. Experiment must be designed to yield results for the good of society,
unprocurable by other means of study.
3. Animal experimentation should precede experiments on humans.
4. Must avoid all unnecessary physical and mental suffering and injury.
5. Do not perform experiments in which there is reason to believe death or
disabling injury will occur.
6. The degree of risk taken by subjects should never exceed that determined
by the humanitarian importance of the problem to be solved by experiment. [Standler's
comment: How do we apply this vague, overbroad principle?]
7. Proper preparations should be made and adequate facilities provided to
protect the experimental subject against even remote possibilities of injury,
disability, or death.
8. The experiment should be conducted only by scientifically qualified
persons.
9. Human subject may withdraw consent at any time if he has reached the
physical or mental state where continuation of the experiment seems to him to be
impossible.
10. Scientist must terminate experiment at any time, if he has probable cause
to believe that continuation of experiment is likely to result in injury,
disability, or death to the experimental subject.
Standler's comment: Nr. 5 and Nr. 10 mean that we can not conduct
experiments with new general anesthetics, nor can we do experimental major
surgery, because of the risk of cardiac arrest. This code also appears to
prohibit innovative treatments on dying patients. Results of such experiments
could be useful to save lives of innocent people. As evidence that the writers
of the Nürnberg Code overreacted, in Nr. 5 they forbade experiments that
involved risk of death or disabling injury "except, perhaps ... the
experimenting physicians also serve as subjects". It is not realistic for the
physicians to be both subjects and also monitoring their condition. Furthermore,
weasel words like "except, perhaps" have no place in a code of conduct. In Nr.
9, a subject should be able to withdraw consent at any time, for any
reason, or no reason at all. I conclude that this Code is only a first
draft, and not a particularly good one.
Society has no problem with asking military personnel to die for their country,
why can't society tolerate people dying during medical research? People
voluntarily engage in risky recreational activities, why can't they consent to
potentially hazardous medical experiments?
The modern version of Nürnberg Code is the 1964 Declaration of Helsinki,
by the World Medical Association. Various codes of ethics for physicians have
been posted by the Center for the Study of Ethics in the
Professions at Illinois Institute of Technology.
Notice that informed consent for medical experiment is different from consent
to diagnostic and therapeutic procedures during regular health care. Before a
medical experiment, the risks must always be disclosed to the subject,
whereas there is often a therapeutic privilege to withhold full disclosure
during regular health care.
Joseph Fletcher, in Experiments on Humans presented to the World
Health Organization in March 1976, lists the following 15 factors to consider:
1. risk for both subjects and investigators
2. avoidance of harm
3. reportage (professional probity)
4. animal studies before tests on humans
5. consent (competence as to freedom and information)
6. benefit (proportionate good to be gained)
7. avoidance of deception of subjects
8. design of experiment to scientific standards
9. privacy, confidentiality
10. motivation of participants, both subjects and investigators
11. cost of experiment, part of risk-benefit calculation
12. fraud (deception in reporting)
13. in-course cancellation by subjects or investigators
14. monitoring
15. peer review, public review
Fletcher also mentions:
16. liability for injuries to subjects
17. guidelines for selection of both subjects and investigators
experimental horrors in USA after Nürnberg Code
The horrors of the so-called medical experiments in Nazi Germany were
repeated many times, albeit on a smaller scale, by physicians in the USA. There
were two provocative articles in New England Journal of Medicine [H.
Beecher, 274 NEJM 1354 (1966); D.L. Rothman 317 NEJM 1195 (1987)] that suggested
that an appreciable fraction of medical experiments in the USA failed to obtain
informed consent. Unfortunately, neither author provided citations for the
allegedly unethical studies, because "citing specific articles would distract
attention from larger points". While that may be true, not providing citations
means that readers can not verify the accuracy of what the author claims, so
these two articles only give an unsupported opinion, and do not serve as a
resource for scholars. One wonders if the author was really trying to avoid
criticism from wounded colleagues, who had conducted unethical experiments and
who now wanted to evade responsibility.
Keep in mind that the following are not horror stories about a few crazy,
wayward physicians. This is mainstream medical research, some of it
sponsored by the U.S. Government, some of it done by famous physicians. The
following American experiments were after the Nürnberg Code was written.
Tuskegee syphilis experiment
The deliberate failure to treat a group of male Negroes in Macon County (near
Tuskegee), Alabama who had syphilis begun in 1932 and ended, by unfavorable
publicity, in 1972. This experiment is difficult to discuss, because so much was
wrong with it. In my opinion, there are three major mistakes. Page citations are
to Bad Blood by James H. Jones, a historian and scholar in bioethics.
The U.S. Public Health Service (PHS) began using penicillin to treat
syphilis in 1943 (p. 178) and penicillin became generally available in 1953
(p. 211). Despite this safe and effective treatment, which would have halted
the progression of syphilis in the subjects, penicillin was deliberately
withheld from the subjects. Not only did the PHS not give penicillin to their
subjects, but the PHS (1) repeatedly distributed lists of names of
subjects to local physicians and instructed the physicians not to give
penicillin to these subjects (pp. 144-45, 162-63) and (2) supplied sham
"treatments" (e.g., aspirin at p. 147, 160) to subjects, in an attempt to
discourage subjects from seeking treatment elsewhere. The failure to treat
this communicable disease violated Alabama law. (pp. 178, 212) In 1950-51, the
PHS knew "that we have contributed to their ailments and shortened their
lives." (p. 182) In the 1970's, the PHS offered the pretexual and lame excuse
that penicillin would have harmed the participants if it had been given (pp.
8, 195), but when penicillin was given in 1973, there were no adverse
reactions (p. 215). If, indeed, there were legitimate doubts about the safety
and efficacy of penicillin in patients with long-term syphilis, administration
of penicillin to these subjects would have made a worthy experiment in the
late 1940's or early 1950's.
Dr. Vonderlehr, of the PHS, practiced a fraud on the subjects by offering
a painful lumbar puncture as a "special free treatment", when, in fact, the
procedure was purely diagnostic and only for the benefit of the researchers.
The subjects were not informed that they had syphilis (pp. 71-74, 219).
Admittedly, informed consent would be extraordinarily difficult, because of
the lack of education of the subjects: most were illiterate and many did not
know their last name (pp. 4, 218). One of the best educated subjects had
completed only eight years of school. To the extent that the subject's lack of
education made informed consent impossible, these people should never have
been allowed to suffer for the benefit of the physicians. It would have been a
different matter if the subjects had been treated benevolently, for example,
given penicillin prior to 1954.
To me, the most important question about the Tuskegee experiment is:
"Why was this experiment begun and continued?"
The project was begun in 1929 as a syphilis control program, using the
standard therapy of 1929-33: a series of at least twenty IM injections of
arsenic compounds, supplemented by topical applications of mercurial ointment.
(pp. 45-90) However, there was not enough money for full treatment, despite the
application of the PHS to private foundations. The subjects received only eight
injections, which cured only 3% of them (p. 119).
There was a very high incidence of syphilis among Negroes in Macon County: 36%,
which should be compared to the national average for Caucasians of only 0.4%.
Given that these black men were living in distressing poverty (pp. 61-62, 83,
107, 201) and ignorance, it was easy to get them to follow orders from white
physicians. When it was not financially possible to treat these subjects, the
physicians may have looked for other things that they could do with this docile
and relatively immobile group of people. In 1933, the long-term complications of
syphilis were well known in Caucasians, but the common view amongst physicians
was that Negroes responded differently to disease than Caucasians. So,
apparently, the physicians decided to study the progression of untreated
syphilis in Negroes, ending only when all of the subjects had been autopsied. I
say "apparently", because with all of the bureaucratic obfuscation in the
1970's, it is not clear what the motivation really was in 1933.
I get the impression that the PHS saw these subjects as a wonderful
opportunity for an experiment, when the PHS's first choice – a treatment program
– was denied for lack of financial support, they found another experiment to do
with this group of subjects. Support for my view is given by the continuation of
the experiment in 1951: "the widespread use of ... [penicillin] had practically
eliminated the possibility of finding another large group of syphilitic
patients". (p. 179)
Given the unethical aspects of this experiment, why was it allowed to
continue until stopped by public outcry in 1973? Apparently, the long-term
experiment was never seriously questioned – as a matter of bureaucratic inertia
– since it had continued for such a long time and was allegedly valuable.
Further, when new managers were appointed, these new managers were reluctant to
rescind decisions of their mentors. (p. 178, 180)
Bad Blood (at p. 190) alleges that the first physician objected to the
experiment only in 1965. In 1966 a social worker at a PHS VD clinic in San
Francisco objected to the study, and, in 1972, he tipped a reporter at
Associated Press. (pp. 191-193, 203-205). The initial reaction of the PHS was
that they had a public relations problem on their hands, but they had done
nothing unethical. (p. 201) Remember, the Tuskegee experiment was no secret
among physicians who worked on sexually-transmitted diseases: results from this
experiment were published in medical journals. I think it remains an important
and unanswered question of why the entire medical establishment was so
blind to ethics for more than forty years.
other points of Tuskegee experiment
From the viewpoint of 1996, it is shocking that women were omitted from the
study. But, by not treating the men in the study and by not informing the men of
the nature of the disease, the PHS permitted many women to become infected with
syphilis and many infants to acquire congenital syphilis. (pp. 104, 165, 215)
Around 1930, 62% of the men in the study had congenital syphilis (p. 76), so the
PHS simply allowed the disease to continue, nonetheless, one would expect better
of the PHS.
A study of nearly 2000 untreated syphilitics in Oslo, Norway from 1891-1910
had been published and a follow-up study of them was published in 1929. (pp. 10,
92-3, 167, 183) Why did the PHS need to repeat the Oslo experiment? The common
view amongst physicians in the 1930's was that Negroes responded differently to
disease than Caucasians.
Some commentators mention that the PHS paid for the subjects' funeral
expenses as a way of inducing consent to autopsy. I see nothing wrong with such
compensation.
Finally, despite the suffering of the participants, it is uncertain how much
valid, new medical knowledge was published as a result of this study. A 1933
review by the American Heart Association said the results of X-ray examinations
of syphilitic hearts had "very little, if any, value". (p. 139) No one knew the
exact number of subjects. (p. 181) Twelve of the two hundred controls acquired
syphilis in the first six years of the study. (p. 176) Some of the subjects may
have received penicillin for other infections. (p. 202) The autopsies were
conducted until 1952 with "high-grade Neanderthal equipment". (p. 184) And, of
course, these supposedly untreated subjects had received some treatment
in the 1930's, which cured about 3% of them and had unknown effects on the
progression of disease in the remainder. (pp. 119, 131, 173-76, 182, 202) I am
also concerned that chronic malnutrition might induce pathologies of comparable
severity to partially-treated syphilis. So, in the end, this ghastly experiment
tells us nothing about untreated syphilis. And since penicillin is an effective
cure for syphilis, we have no reason to know about the progression of untreated
syphilis.
There was also little valid medical knowledge from the so-called experiments
in Nazi concentration camps. This parallel raises the question "Are unethical
studies also likely to be invalid?". While I acknowledge that technical skills
in biology and statistics are entirely different from knowledge of morality and
ethics, I nevertheless maintain that a competent scientist is zealous about
both technical and ethical concerns. In particular, I don't see how a
physician can work amongst suffering people without being aware of, and
concerned about, their suffering. The moment that the physician sees subjects
(as if they were a inanimate object), instead of patients or people, the
physician has lost some of his humanity. If the physician can't see suffering,
how much else can he not see?
At least 28, perhaps more than 100, of the 399 subjects had died from syphilis.
(pp. 1-2) Litigation against the PHS, et al., was settled in Dec 1974, 18 months
after suit was filed, for $ 37,500 to each surviving participant and $ 15,000 to
each decedent's estate. (p. 217) As yet another piece of exploitation of the
subjects, the attorney who brought the suit received 1/8 of the settlement,
which gave approximately one million dollars to the attorney – quite a nice
income in 1974 for a case that did not go to trial. (p. 217) Interestingly, this
black attorney included neither any predominantly black institution nor any
black physicians or nurses as defendants (pp. 216), although the Tuskegee
Institute and a number of black physicians had been involved in the experiment,
which was operated from the beginning until 1965 by one black nurse. While one
might be reluctant to blame a black nurse for following orders of white
physicians, especially during the 1930's and 1940's (pp. 151-169), "following
orders" was not an acceptable excuse for German war criminals.
Blauer
In Dec 1952, Harold Blauer, a civilian in excellent physical health, but
depressed following his divorce, was voluntarily admitted to the New York State
Psychiatric Institute for treatment of depression. While at the Institute, he
was injected on five different occasions with three different mescaline
derivatives supplied by the U.S. Army Chemical Corps to determine the clinical
effects of chemical warfare agents in a research project that was classified
secret. He reluctantly consented to the first injection, which was fraudulently
offered to him as a treatment for his depression. After each of the first four
injections, the subject told the nurses that he did not want any further
injections, because of his adverse reactions. However, the nurses and staff
motivated him to further participation by telling him that he would be returned
to Bellevue Hospital if he did not continue with the injections. After the fifth
injection, which was 16 times stronger than the previous injection of this new
compound, his body stiffened, his teeth clenched, and he began frothing at the
mouth for 2 hours until he lapsed into a coma and died. The death certificate
attributed the death to "coronary arteriosclerosis; sudden death after
intravenous injection of a mescaline derivative." The subject's ex-wife filed
suit for medical malpractice against the State of New York, which operated the
Institute. There were numerous conferences between the state's attorney, and
attorneys for both the U.S. Army and U.S. DoJ. The state's attorney told the
U.S. that he believed that, if all the facts were disclosed to plaintiff, the
suit was worth at least $ 60,000. The Army then retrieved all of the medical
records and took them out-of-state, so that they would not be discovered in the
medical malpractice litigation. The state never supplied these records during
discovery, despite a court order for production of documents. The malpractice
claim was settled for $ 18,000 after false and misleading statements were made
by the defense: namely that Blauer died because he allegedly had a weak heart
and that the drugs were administered for diagnosis or therapy for Blauer's
depression. The U.S. Government secretly reimbursed the State of New York for
half of the settlement in 1955. The physicians who performed the experiment, the
hospital, the State of New York, the U.S. Army Chemical Corps that sponsored the
research and supplied the chemical for injection all conspired to conceal
evidence or submit false documents. In Aug 1975, 23 y after the subject's death,
the Army contacted Blauer's daughter and issued a press release about finding
the case file in a safe. Blauer's ex-wife had died, so Blauer's daughter
reopened the litigation, which resulted in a complicated series of cases.
Barrett v. State of New York, 378 N.Y.S.2d 946 (1976)
Barrett v. U.S., 660 F.Supp. 1291 (S.D.N.Y. 1987) (awarding $
702,044 to daughter).
Barrett v. U.S., 668 F.Supp. 339 (S.D.N.Y. 1987), aff'd 853
F.2d 124, cert. denied 488 U.S. 1041
Barrett v. U.S., 1991 WL 60365 (attorneys billed $ 1.7 million in
these cases)
A court in 1987 concluded that the LD50 studies in animals were "grossly
inadequate" according to the standards in the early 1950's: the Army found that
all mice died at 100 mg/kg and no mice died at 12 mg/kg, but the Army performed
no further animal experiments. Further, before the judge approved the settlement
in 1955, the state's attorney had an ex parte meeting with the judge, at
which the attorney falsely represented that source of the drug was the Army
Medical Corps, to give the impression that the experiment was therapeutic. The
judge then required that the settlement be increased from $ 15,000 to $ 18,000.
high oxygen concentrations to premature infants
Premature infant in 1953 given high dose of oxygen as part of experiment,
although physician who was responsible for infant's treatment (and aware of
preliminary results that showed high oxygen caused blindness) had ordered oxygen
"reduced ... as tolerated" and infant was doing fine. No attempt to obtain
informed consent from parents. Researchers observed that infant's eyes swelled,
but high oxygen was continued. At trial, plaintiff was totally blind and unable
to find employment. Liability for both hospital and physician who ordered change
to high oxygen. Burton v. Brooklyn Doctors Hospital, 452 N.Y.S.2d 875 (1982)
injections of cancer cells
There were intradermal injections of live human cancer cells into 22
chronically ill, debilitated non-cancer patients in 1963 without their consent
in the Jewish Chronic Disease Hospital case, to learn if foreign cancer cells
would live longer in debilitated non-cancer patients than in patients
debilitated by cancer. Lump at injection site disappeared approximately seven
weeks after injection. Research funded by U.S.P.H.S. and American Cancer
Society. The subjects were not told that the injection contained cancer cells,
because the physicians "did not wish to stir up any unnecessary anxieties in the
patients" who had "phobia and ignorance" about cancer. Physicians claim each
patient gave "oral consent", but a material fact was not disclosed to patient
and many of the patients were not in a physical or mental condition to give
valid consent. Hospital administration tried to cover-up lack of consent, and
some written consents were fraudulently obtained after the fact. Three
physicians at the Hospital resigned when the administration did not seriously
consider their complaints about the experiment. The chief of medicine at JCDH
and the principal investigator were placed on probation for one year by the New
York State medical licensing board, as a result of a unanimous guilty verdict on
fraud/deceit and unprofessional conduct. Two years later, the American Cancer
Society elected the principal investigator to be their Vice-President.
Hyman 251 N.Y.S.2d 818 (1964), rev'd 258 N.Y.S.2d 397 (1965)
(litigation regarding whether director of hospital could have access to
patients' medical records)
Katz, Experimentation with Human Beings (1972) pp. 9-65 recounts
more than you want to know about this experiment, including affidavits of
physicians on both sides.
In passing, it is noted that several hundred postoperative gynecology
patients at Memorial Hospital had the same injections, also without consent, but
there was no fuss about that. (Katz at 11, 23, 27, 37) Why was it necessary to
inject human cancer cells into more than 300 healthy subjects; wouldn't a
smaller number of subjects be adequate? There seems to be a genuine scientific
controversy about whether the injections were dangerous: some cancer experts
said that it was impossible to transplant human cancer cells from one person to
another, as the donee's body would reject the foreign cells. But there is one
documented case of transplantation of melanoma from daughter to mother (Katz at
309). And several physicians testified that the injected cells might
produce cancer years later.
If a physician were to ask healthy people if they would willingly
agree to have live cancer cells injected into them, the healthy people would
certainly say "NO!" The practical result is that, if this research is to
be performed on a large number of subjects, the physician performs his
experiment on nonconsenting patients. This point raises a number of
interesting questions. Is this experiment so important to society that the
requirement of informed consent should be suspended? Is it really necessary to
have a large number of subjects, or could we get adequate information
from experiments on a few brave volunteers? I believe informed consent is always
necessary when subjects are participating in an experiment that can not benefit
them.
hepatitis in retarded children
Severely retarded children at the Willowbrook State Hospital in New York
injected with hepatitis virus. This Hospital did not admit new patients after
1964, unless their parents "consented" to the experiment. Consent forms implied
that children were to receive a vaccine against hepatitis, when the protection
was actually from a hopefully "subclinical" infection. Physician made excuse:
fecally-borne viral hepatitis was so prevalent at the Hospital (because
approximately 70% of children had IQ below 20 and were not toilet trained) that
children routinely became infected 6 to 12 months after admission. But isn't
that like murderer saying that victim was going to die sometime, all he did was
kill earlier and under better circumstances?
Cincinnati radiation experiments
Cancer patients (mostly Negroes of below-average intelligence who were
charity patients) during 1960-72 in Cincinnati were exposed to large doses of
whole body radiation as part of an experiment sponsored by the U.S. military.
None of the subjects gave informed consent, they thought they were receiving
treatment for their cancer. Subjects experienced nausea and vomiting from acute
radiation sickness, pain from burns on their bodies, and some died prematurely
as result of radiation exposure.
In re Cincinnati Radiation Litigation, 874 F.Supp. 796 (S.D.Ohio 1995)
On 5 May 1999, a settlement was announced in which the defendants paid
US$ 5.4×106, but defendants admitted no wrongdoing.
continuing problems
In April 1999, all research projects at the Veteran's Administration
West Los Angeles Medical Center were shutdown after many allegations of medical
research performed on patients who did not consent. An investigation showed that
not only was research being done on patients who had not given informed consent,
but also that research was being done on patients who had expressly refused
consent. Investigators found multiple violations of the government's code of
research ethics. As is typical of government bureaucracies, the proposed
solution was more management and more review, not criminal prosecution,
and not termination of employment of unethical personnel.
my observations
I draw the following conclusions from these experiments.
Physicians are often curious about details of how some disease or disorder
progresses (e.g., syphilis, retrolental fibroplasia). They are not
satisfied to know the cause and cure of the disease – they want to know the
ghastly progression when the victims are untreated.
Some physicians will resort to fraud or deception in order to obtain
"consent"; other physicians look for helpless people in institutions (e.g.,
children, insane adults, prisoners, mentally retarded, chronically ill) to use
as experimental material. The conclusion from this view is that some
physicians see their patients as property under their control, not as
independent lives.
Do physicians choose incompetent people (e.g., insane, mentally
retarded) because it is convenient to perform experiments on subjects who do
not object or because these people are somehow less worthy (i.e., ok to harm
dog or retarded human, but not normal human)? I can find no answer to this
question in the medical literature – apparently, it is too unpleasant a
question for physicians to consider.
These physicians are absolutely convinced that what they are doing
is justified in the name of scientific progress. They resent any implication
that what they are doing is unethical.
The first point suggests that some physicians will continue to do experiments
that society considers as "not worth doing", unless law regulates physicians.
The second and third points suggest that some physicians are both powerful and
arrogant. There is a clear need for non-physicians to review proposed medical
research and restrain physicians, before they hurt their patients.
After the Tuskegee experiment, the U.S. Government issued 45 CFR § 46.101-117
to stop continuing atrocities from physicians in the USA, when federal money was
used for salaries or at least some of the expenses. However, physicians doing
research often regard ethical review as a mere bureaucratic inconvenience.
The number of unethical physicians implicated in the above experiments is
very small, compared to the total number of physicians. However, the existence
of a long series of atrocious examples suggests that many physicians may engage
in informal experiments on some of their patients without any informed consent.
I suspect that very few physicians deliberately devise an unethical
plan. My guess is that physicians are zealous about doing the experiment and
they genuinely believe (perhaps correctly) that the result will be much more
important to humanity than the pain, suffering, and possible death of a few
experimental subjects. This kind of justification calls to mind the cliché, "You
can't make omelets without breaking eggs." On careful, philosophical analysis,
which the physicians do not do, this justification crumbles for several
reasons. First, eggs are property that can legitimately be used as the owner
wishes, but a human being has a fundamental right of autonomy and each patient
has the right to decide what is done with his/her body. As a consequence of this
principle, a nonconsensual touching is a battery, a legal wrong. Second,
stressing the good results from medical research is simply an example of "the
ends justifies the means", which is a bogus philosophical rational.
The practical problem of ensuring that human experimentation be done in an
ethical way is extremely difficult. On one hand, there are already too many
artificial burdens and impediments to medical research (e.g., lack of funding,
inadequate time, obsolete facilities, members of review committees who have no
understanding of research, repressive legislation). But we also can not ignore
the fact that a number of innocent people in the USA have been harmed in the
name of medical research and this abuse of patients must stop.
The solution is not to teach physicians about ethics. Everyone who
enters medical school already knows not to perpetrate a fraud on patients and
already knows not to regard "less worthy" people as proper subjects for
experiments that are dangerous to them. The solution is to control zealous
researchers who do not seriously consider ethics, because the experiment must be
done at any cost. At the end of this essay, I suggest some specific rules to
protect patients, while allowing research.
discuss experiments on prisoners
During wars, many young men are drafted, then put in harm's way. Society
tolerated this dangerous involuntary servitude, because it was necessary for the
greater good and a better future.
This same argument was used to justify medical experiments on criminals in
prison [Rothman 317 N.E.J.M. 1195 (1987)] during World War II. Because a person
is in prison does not relieve him of an opportunity to serve his country and
human progress, by participating in medical research. "Every man must do his
part."
If there currently is no draft and no military conflict to endanger normal
people, we can still use this argument, because disease always threatens
society.
It seems to me that nonconsensual medical experiments are wrong. The
fact that young men are killed in wars to which they did not consent is a
separate injustice, which is technically irrelevant to discussing medical
experiments.
However, I think that it is permissible to conduct medical experiments on
prisoners, if they volunteer and provide informed consent. Prisoners who are
sane still have some rights of self-determination and autonomy; it is
paternalistic to declare that no prisoner can consent to research.
Prisoners have harmed society and participating in medical experiments is one of
the ways that they can volunteer to help society, as a way of clearing their
conscience. The prisoners should not receive a reduction in their
sentence as the result of participation in medical experiments, since their
participation is not part of their punishment, but an independent act.
Further, the possibility of reduction of sentences would inject an element of
coercion into the prisoner's decision. However, it is acceptable to pay the
prisoners money for their participation. Yes, there are ethical concerns about
allowing medical experiments on prisoners who volunteer: there is always a
question of the sincerity of their voluntary decision, but this question is
present with any subject of a medical experiment, as discussed in the
next paragraph.
It is strange that liberals who object to allowing prisoners to voluntarily
participate in medical research don't blink an eye at allowing seriously ill
patients to participate in research. There can be no doubt that someone who is
seriously ill is frightened, perhaps fearful of his/her life. By characterizing
the experiment as a "new treatment", the experimenters can exploit the natural
desire of the patient to receive the newest [and presumedly the best] treatment
possible. Participating in an experiment is also a way to get admitted to a
superior hospital or to be treated by outstanding physicians (e.g., professor of
medicine). See Ingelfinger, 287 NEJM 466 (1972).
Just as most lawyers don't blink an eye at helping "guilty" criminals go
unpunished, most physicians are not bothered by death. Professionals' insular
view is not shared by the community. Most people have no experience
making difficult decisions.
coercion
Technically, coercion requires that threat/harm must come from coercer. It is
not coercion either to refuse to help someone or to put conditions on the
help, provided that the person refusing or making conditions did not cause the
victim's predicament. For example:
1. Poor student applies for educational loan from bank. Bank's conditions, or
refusal to provide loan, is not coercion, because the bank caused neither
student's poverty nor student's need for money.
2. Man drives woman out into desert and then gives woman a "choice": consent
to sex or be abandoned in middle of desert. Man coerced woman, because man
caused woman's plight. Coercion invalidates any "consent" that might be given.
Standler's draft code
Note: This draft has no legal significance.
It is only a sketch of what I believe the law should be.
experiments on animals first
Animal experiments must be conducted before any human experiments. Animal
experiments may demonstrate that new treatment is ineffective or dangerous
(i.e., effective, but high incidence of death from treatment), and therefore
human experiments may be avoided. Animal experiments may also disclose
specific side effects that can be expected in human subjects, so that
experimenters may monitor for these effects.
only do new experiments
The researchers must do a through search of the medical and biological
literature before doing any human experiments. Work that has been
previously reported should not be repeated, unless there is a significant
improvement in methodology or reason to suspect fraud or mistake in previous
work.
design of experiment
The expected benefit to society should outweigh the foreseeable risks to the
subjects. The benefit to society should be judged by attorneys and clergy,
not by the experimenters themselves, and not by other physicians,
to get some objectivity. The approval of an experimental protocol should be
made by a review committee whose members actually voting (including neither
abstain ballots nor absent members) have a majority of nonphysicians.
The experiment should be conducted in a scientific manner, with a
double-blind fashion, with a control group. A competent mathematician with
experience in both medical/biological experiments and statistics
should review the experimental design.
It is unethical to give a control group of people a placebo when the
members of the control group are suffering from a disease for which there is a
treatment or palliative that has been proven to be more effective than
placebo. Beyond ethical issues, society would be better served by comparing a
new drug with standard drug, so that physicians know the "best" treatment, and
not merely have a collection of drugs that are known to be "more effective
than placebo".
ASIDE: Obviously, drug companies will resist such a proposal,
since it is more likely that their new drug will be found to be "more
effective than placebo" than found to be "better than the standard drug" for
the condition. Drug companies are in the business of making money, and they
can make much more money from a unique new drug that is protected by patent,
than from selling a drug for which there are inexpensive generic competing
versions available. Perhaps the resolution is to have a three-way experiment:
compare the new drug against both placebo and the standard therapy.
Allow the new drug to be marketed if it is more effective than placebo,
because the new drug might be a rational choice in some patients for whom the
standard therapy is undesirable.
consent
All facts known to the experimenters that would be relevant to a reasonable
person's decision to participate, must be disclosed in advance of consent.
Are there any anticipated side effects to subjects? Will any of the
experiments or diagnostic procedures be painful?
Is there any foreseen possibility of death or permanent injury?
Do any of the researchers have a financial stake in the outcome? (e.g.,
royalties from patent, investment in manufacturer)
If subject is a patient of a physician who is not participating in the
experiment, then the experimenters shall also make a full disclosure to the
attending physician, as a condition of taking his/her patient. This rule
increases the chances that disclosure will be understood and that experiment
is actually reasonable.
The disclosures and consent must be in writing with two originals (one
retained by subject, the other retained by experimenter), with subject's
signature witnessed by at least one person employed by neither experimenters,
financial sponsor of research, nor institution in which experiment takes
place. Suitable witnesses may be subject's spouse, adult children of subject,
officer at bank where subject has checking account, subject's attorney.
Failure to obtain such written consent with an independent witness shall be
considered as a presumption that informed consent was not obtained.
Each subject shall have not sign a consent form until at least 24 hours after
it was given to the subject, so that the subject can carefully consider the
risks and benefits, and make a choice without influence by the experimenters.
If the subject is incompetent (e.g., minor, insane, mentally retarded,
intoxicated, unconscious, in severe pain, etc.), then the disclosure and
consent form must be signed by either subject's legal guardian, subject's
spouse, or agent named in subject's durable power of attorney for health care.
If the first person approached by experiments to give consent for incompetent
refuses consent, then the experimenters may not request consent from
others (e.g., alternate agents).
Children and incompetent adults (i.e., retarded, insane) should generally
not be subjects of experiments, because they can not personally give valid
consent. However, if children or incompetent adults need treatment for their
condition and there is reason to believe that the experimental
treatment will be at least as effective as the conventional therapy, then
their guardian may be asked to consent.
People who refuse to be subjects in an experiment are still entitled to
receive conventional therapy for their disease. It is not ethical to
motivate someone to "consent" by giving the person a Hobson's choice of
experiment or no treatment. However, the experimenter does not need to provide
the conventional therapy if there is another physician in the vicinity who is
competent to provide conventional therapy.
The consent must be obtained by a physician who is named as one of
the investigators in both the proposal for funding and in the
experimental protocol that was approved by the ethics committee. The job of
obtaining consent may be delegated to neither a nurse, resident,
intern, nor medical student.
experiments on normal people
It is ordinarily not acceptable to subject normal people (i.e., not suffering
from disease that is subject of experiment) to experiments that have a risk of
death or serious injury. However, there are exceptions to this rule, which are
discussed below. Normal people should be used for physiological research, but
not for research on the effects of drugs or therapies. Normal people
don't take drugs, so there is no point in learning the effect of drugs on
normal people.
After informed consent, small numbers of normal people may be
exposed to organisms that cause disease, to measure the response of their
bodies to the disease and the initial progress of the disease. Once symptoms
appear that make the patient uncomfortable, the patient must be given
appropriate medical treatment (e.g., antibiotics, analgesics, antipyretics) to
relieve suffering and prevent serious injury.
It is not acceptable to cause injury to a subject just to study the
response to the injury. The experimenter must have a proposed treatment
for the injury and there must be objective reasons to believe that the
proposed treatment will be better than any accepted treatment.
It is acceptable to cause death or injury to small numbers (e.g., 3
or 4) of normal people when the results of the experiment are important
to medical science and the knowledge can not be obtained in any other way. For
such experiments, subjects should be paid an amount of money that is adequate
to induce their consent. Will such payments coerce unemployed or disadvantaged
people to consent? No, because the experimenters did not cause the
unemployment or disadvantage, so coercion is not technically present.
Should criminals in prison be all allowed to participate? Yes [Accord
Bailey v. Lally, 481 F.Supp. 203 (D.Md. 1979)], provided that they are
sane and their consent is voluntary. Prisoners should be compensated with
money for their participation, but prisoners should not receive a
reduction in their sentence as a result of their participation in medical
experiments.
Even if they are not able to give legally-binding consent, children and
incompetent adults should have the right to refuse to participate in any
experiment that is painful and is not a treatment for a disease that
they have. Their right to refuse might be expressed as reluctance to go to the
room where the experiment is conducted, by crying or screaming, or by bodily
motions that indicate extreme discomfort.
experiments on victims of disease or injury
Treatments, including drugs, should be tested on a group of people who are
suffering from the disease, injury, or condition for which the treatment is
appropriate and potentially beneficial.
A neutral observer should periodically, depending on frequency of
observation of patients, monitor the treatment group in the experiment for
both (1) any evidence of serious side effects and (2) any evidence of
startling benefits. If the treatment group is experiencing a high number of
serious side effects and the disease for which they are being treated is not
serious, then the experiment should be terminated early. If the treatment
group shows extraordinary benefits, then it is unethical to continue the
experiment, thereby continuing to deny the benefits to the control group.
It is acceptable to perform experiments having a risk of death or serious
injury on patients who have an injury or disease that is likely to be fatal.
However, the experiment must offer some hope of personal benefit to the
subject. For example, one may try a new anti-neoplastic drug on a cancer
patient. One may not put a cancer patient in a tub of ice water and
measure how long it takes for the patient to become unconscious, for a
research on survival in icy seas.
take care of subjects after the trial After the experiment, the experimenters continue to have an obligation
to disclose to the subject any risks that the subject experienced as a result
of the partial participation in the experiment. Accord,
Mink v. University of Chicago, 460 F.Supp. 713 (1978) (1000 pregnant women
given diethylstilbestrol during 1950-52 to test its ability to prevent
miscarriage, women not informed that they were part of experiment, risk of
cancer in children known as early as 1971, but university made no attempt to
notify subjects until late 1975, court approves battery theory)
Should some adverse event occur to subject(s) during experiment, subject is
then entitled to both medical and disability payments:
a. free medical care for the remainder of his life for any disorder that has
at least a 10% probability of being related to the experiment
b. payment of loss wages that he could otherwise have reasonably earned
(including financial support of spouse and children after subject's death),
and
c. funeral expenses.
Should research that is not funded by the government be required to
purchase insurance for subjects, or post a bond, to ensure that the subjects
are adequately protected?
publish results
The results of the experiment, regardless of the result, should be published
in an archival medical journal, so that the entire community can benefit from
the knowledge gained in the experiment. If the tested drug or treatment is a
failure, it is particularly important to publish the results, so that future
experimenters can avoid repetition of the research and avoid suffering of more
human subjects.
If work remains unpublished three years after the end of collection of
experimental data, then experimenters should pay each subject an additional $
100/year until such work is published in a peer-reviewed archival journal. The
amount of this payment may be increased by a judge/jury if there is liability
for unethical conduct of the experimenters.
subjects share in reward
Human subjects have a right to share in financial rewards from experiment,
because their participation is essential. Subjects should be paid for
their time and inconvenience during the experiment, plus reimbursement of
their expenses and lost wages.
If cells removed from human subject are the basis for a profitable
commercial product, then subject who is the original source of cells should be
paid a royalty as a percentage of gross sales. In addition, human subject has
the right to have his/her name attached to any cell line that results from
cells removed from his/her body; subject must either consent to naming, or
waive this right, in writing.
Aside: I believe that Moore v. Regents of the University
of California, 793 P.2d 479 (Calif. 1990) was decided wrongly: Moore
suffered from painful bone marrow aspirations and repeated travel from Seattle
to Los Angeles, so that his physicians could make hundreds of thousands of
dollars from Moore's cells. Further, Moore's physicians deceived Moore about
purpose of visits and procedures.
withdrawal of consent
A subject may withdraw consent to continued participation in the experiment at
any time, for any reason, or no reason. The subject need not declare a reason
to the experimenters. After the patient withdraws, the experimenters continue
to have an obligation to disclose to the subject any risks that the subject
experienced as a result of the partial participation in the experiment.
may publish unethical experiments
Sometimes physicians may (improperly) perform experiments without first
obtaining informed consent or by making fraudulent statements to the subjects.
The punishment for such lapses in ethics is civil liability for the
experimenters. However, if there are any valid scientific results from the
study, the work should be published in an archival, peer-reviewed journal. The
publication should contain a brief note that the reviewers found the study to
be unethically performed and the reasons for this judgment briefly
recited, as an additional sanction against the authors. (If the authors fail
to publish in a timely way, see Nr. 8 above.) There is no reason to have a
second group of subjects suffer pain and inconvenience to repeat the research
in an ethical way. Indeed, the deterrent value to physicians who are tempted
to be unethical may be greater if they are known to the profession as having
conducted an unethical experiment. Further, the publication in a medical
journal serves as a reminder to physicians who are designing experiments,
unlike mention in a court proceeding, law journal, or newspaper.
monitor experiment
An independent physician should be appointed to monitor the experiment and
stop the experiment if the treatment group has either (a) high incidence of
side effects that are intolerable when compared to the potential benefit or
(b) the treatment group is receiving a benefit that is extraordinarily better
than the control group, so it would be unethical to continue the experiment
and deny the benefit to the members of the control group. "Independent" means
that the monitoring physician's name does not appear in the list of
authors of the published research and the payment to the monitoring physician
is the same, regardless of the results of the experiment.
posted on the Internet at: http://www.rbs2.com/humres.htm
created Dec 1996, minor revision 8 May 1999, links revised 18 June 2000
ALL INFORMATION, DATA, AND
MATERIAL CONTAINED, PRESENTED, OR PROVIDED HERE IS FOR GENERAL INFORMATION
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OF THE PUBLISHER, AND IS NOT TO BE CONSTRUED OR INTENDED AS PROVIDING MEDICAL OR
LEGAL ADVICE. THE DECISION WHETHER OR NOT TO VACCINATE IS AN IMPORTANT AND
COMPLEX ISSUE AND SHOULD BE MADE BY YOU, AND YOU ALONE, IN CONSULTATION WITH
YOUR HEALTH CARE PROVIDER.
"A foolish faith in authority is the worst enemy of truth."
-- Albert Einstein, letter to a friend, 1901
"I know of no safe depository of the ultimate powers of the society but the people themselves, and if we think them not enlightened enough to exercise control with a wholesome discretion, the remedy is not to take it from them, but to inform their discretion by education."
-- Thomas Jefferson, letter to William C. Jarvis, September 28, 1820
"What's the point of vaccination if it doesn't protect you from the unvaccinated?"
-- Sandy Gottstein
"Who gets to decide what the greater good is and how many will be sacrificed to it?"
