Legal Issues in Medicine

The Nuremberg code was promulgated by the US judges sitting under the authority of the US Army at Nuremberg, Germany, in 19471,2 The defendants in the Doctors trial were charged with war crimes and crimes against humanity for performing both lethal and none lethal experiments on prisoners. Most were found guilty, and seven were hanged. The judges also set forth the Nuremberg Code, a ten point declaration governing human experimentation that was based on "principles of the law of nations as they result from the usages established among civilised peoples, from the laws of humanity, and from the best dictates of public conscience."1 The first and best known principle provides that voluntary, competent, informed, and understanding consent of the subject is "absolutely essential." There is no exception for soldiers or for wartime, and until Desert Shield, the US Army had never argued that there should be such an exception. Current US statutory law also requires that informed consent be obtained for all "investigational use" of drugs, except when the investigators consider it "not feasible, or in their professional judgement, contrary to the best interests of such human beings."3

In the fall of 1990, after the invasion of Kuwait by Iraq, the Department of Defense (DoD) sought a waiver of the consent requirements in the Food & Drug Administration's existing regulations governing human experimentation so that the military could administer investigational drugs and vaccines to the Desert Shield soldiers without their informed consent. The justification for the request was military expediency. In the words of the D0D request: "In all peace time applications, we believe strongly in informed consent and it's ethical foundations....but military combat is different."4 The department argued that informed consent under combat conditions was "not feasible" because some troops might refuse to consent, and the military could not tolerate such refusals because of "military combat exigencies."4

The FDA granted the request and issued a new general regulation, rule 23(d)5 that permits waivers on a drug by drug basis on the grounds that consent is "not feasible in a specific military operation involving combat or the immediate threat of combat."4

Shortly after the new regulation was promulgated, and just before Desert Storm, a suit was brought by the Public Citizen Health Research Group on behalf of an unnamed soldier (John Doe) and his wife to enjoin the DoD from using drugs on troops in the Persian Gulf without consent, on the basis of rule 23(d). At that time, the FDA had granted under rule 23(d) for the use of two agents, pyridostigmine bromide (30mg tablets, for use as a pre treatment for nerve gas attacks) and pentavalent botulinum-toxoid vaccine (to protect against botulism in biological warfare).

The Decision of The District Court

US District Court Judge Stanley Harris made it clear that he had no desire to become involved in military matters. In his words,"The (DoD's) decision to use unapproved drugs is precisely the type of military decision that courts have repeatedly refused to second guess."6 He characterised the decision as one intended to protect individual servicemen and women, and as "strategic" in nature and thus not subject to review by a court. He went on, however, to say that if he thought he had the authority to review the decision, he would uphold it.

Consistent with the Nuremberg Code, the DoD's Authorization Act prohibits the prohibits the DoD from using any of its funds "for any research involving a human being as an experimental subject" unless the subject's informed consent has been obtained.7 This restriction was enacted in response to US Army experiments at the beginning of the Cold War in which servicemen were exposed to radiation or given lysergic acid diethylamide (LSD).2 Judge Harris, however, decided that "the primary purpose of administering the drugs is military, not scientific," and therefore that statutory prohibition was inapplicable.6 The "not feasible" exception to the consent requirement had previously been applied only to subjects who were unable to communicate, unconscious, or incompetent. Nonetheless, Judge Harris decided that the FDA could reinterpret this exception as long as its interpretation was not "arbitrary, capricious or manifestly contrary to the statute."6 Finally, he rejected the claim that forced administration of unapproved drugs violates the Fifth amendment interests of servicepersons in not being experimented on without their consent. Instead, he found that the military's interest in preventing injury to troops and "successfully accomplishing the military goals of Operation Desert Storm" were sufficient to justify the exception to the regulations on informed consent. The Nuremberg Code was not mentioned in the decision.

The Decision of The Court of Appeals

"John Doe" appealed. At the hearing, held in March 1991, a letter was introduced from the DoD to the FDA saying that the military requirements for the use of the two agents without informed consent had ended. The department also informed the FDA that "Central Command has recently reported that the military command in the theatre of operations decided to administer the vaccine on a voluntary basis. The pyridostigmine tablets were used without prior informed consent." The Justice department argued that because of the end of the war and the DoD's letter. the case was moot and should be dismissed by the US Circuit Court of Appeals.

The majority of the court, in a two to one option written by Judge Ruth Ginsburg in July, disagreed.7 The court concluded that even though the DoD had withdrawn its two specific waivers, rule 23(d) remained in effect and the situation could therefor arise again. The court relied heavily on government reports concerning the proliferation of nuclear, chemical, and biological weapons systems, especially among Third World nations such as Iraq.

On the merits, the Court of Appeal disagreed with the lower court that the case was beyond the scope of court review because it was military in nature. Instead the court defined the issue as a challenge to the FDA's authority to issue a waiver of its consent regulations to the DoD, not as an action challenging military decisions. The Court of Appeals did, however, agree with all the other conclusions of the lower court. Again no mention was made of the Nuremberg Code.8

Judge Clarence Thomas, then a member for the appeals court, filed a dissenting opinion. He agreed with the Justice Department, arguing that because the war was over and because it was virtually impossible for John doe to be subjected to the rule again, the case should be dismissed as moot. He said that the majority "surely overstates" the risk of future chemical warfare, noting that "after all, American soldiers have not been victims of organized chemical attack since the First World War."8 Judge Thomas also stressed that there was no "reasonable likelihood that John Doe, personally" would be involved in any future war involving chemical weapons. In his words, "the majority focuses on rule 23(d) in the abstract - and in the process forgets about John Doe, the plaintiff."8

Ironically, all Judge Thomas' arguments support the proposition that the rule should never have been promulgated in the first place: the risk of chemical and biological warfare in the Gulf seems to have been overstated. and the proper concern should focus on individual soldiers, whom the military (and the FDA) had succeeded in treating as merely the means to accomplish a mission.

The Implications of The Decisions

Since the time of Cicero, it has been said that inter arma silentae sunt - amid the clash of arms the laws are silent. This was certainly true during the forced internment of Japanese - Americans from the west coast during World War Two,9 and it was true of the courts in this recent case as well. While troops are in the field, courts are unlikely to make any decisions that appear to be intefearning with the military. This evidence of realpolitik is disturbing, but not surprising. The brief history of International human rights has, after all, been written primarily in the aftermath of war; the founding of the UN in 1946, the International declaration of Human Rights in 1948, and current efforts to foster human rights in the wake of the Cold War. Neither of the courts in the Doe case was likely to discuss the Nuremberg Code because the waiver rule is a clear violation of it, and acknowledging this violation could have embarrassed the United States. We might have appeared hypocritical because at the time these cases were heard, members of the administration were calling for a Nuremberg - style tribunal to try Saddam Hussein and his military leaders for violations of international law. International human rights laws must, of course, apply to both victors and vanquished.

Even though rule 23(d) authorizes the violation of the Nurmeberg Code, it can be argued persuasively that the code itself was not actually violated during Operation Desert Storm. According to this argument, the code only applies to experimentation or research on human beings, and the DoD was not conducting research. this was not, after all, anything like the Army's secret experiments with radiation or LSD in the 1950's and 1960's.2 What was at stake in the case of pyridostigmine bromide tablets was the use of an approved drug for an unapproved reason.

Such use can be justified in certain circumstances and could even be considered treatment if nerve gas attack appeared imminent, as it did to the commander of XVIII Airborne Corps whose 41,650 soldiers took the drug for one to seven days at eight hour intervals.10

Members of the military have no right to refuse any medical treatment that can make them fit for combat or return them to active duty. The reason it is legally acceptable to require combat troops to be treated if treatment can return them to active duty is that it would be impossible to have an effective armed force if refusal could be used as a way to avoid combat or other risky assignments. The distinction between treatment and experimentation (or research) may seem arbitrary - and at the margin. it often is - but it is based on the following rationale. Treatment is given for the benefit of the individual patient, rather than for the benefit of society or a researcher, and when sufficient data are available to determine whether the intervention is likely to be helpful or harmful to that patient.

Historically, "nontherapeutic experimentation" on healthy volunteers has been the model for research, whereas "therapeutic experimentation" on patients is more and more seen simply as therapy. Thus, if pyridostigmine is a treatment, requiring its use does not violate the Nuremberg Code.11,12

I think this argument is correct, even though data from Desert Storm were collected and analyzed,10 and that it was unnecessary for the DoD to ask for a waiver of the requirement for informed consent by research subjects to administer this agent. The Court of Appeals should have used this rationale for its decision. The Army, Navy and Air Force seem also to have agreed with this view, since they were prepared to dispense pyridostigmine to troops long before the waiver was even sought.13

It is much more difficult, however, to make the same argument for botulinum toxoid vaccine. This vaccine has been used by about 3000 laboratory workers in the past, but its use was discontinued in the mid 1970's (before sufficient data on safety and efficacy had been gathered to qualify it for licensure) and few laboratory workers have used it since. It remains an unapproved agent. and the Centres for Disease Control have an elaborate consent form that explains its experimental nature as an investigational new drug. The reason that the military did not violate the Nuremberg Code in giving this vaccine to troops is not that it can be legitimately considered treatment or therapy, but it was decided to give the troops in the Persian Gulf the right to refuse to be vaccinated. This decision merits commendation, and it would be interesting to know more about how and why military commanders in the field chose not to take advantage of their legal authority to give this vaccine to the troops without consent. No matter what their motivation, however, I do believe that they were correct. They may indeed have taken the principles of the Nuremberg Code more seriously than did the DoD or the FDA, or the two courts in the case.

As the Court of Appeals noted, the DOD had argued in court that these agents had not previously been tested in controlled clinical trials "because humans cannot intentionally be exposed to chemical or biological (warfare) agents in order to test the efectivness of a drug."8 This is true primarily because such exposure violates another dictate of the Nuremberg Code; "No experimentation should be conducted where there is a prior reason to believe that death or disabling injury will occur."14 General Norman Schwarzkopf and his medical command seem to have understood that one cannot pick and choose which items of the Nuremberg Code to take seriously.

The Role of Military Physicians

What should physicians in the military do when asked to administer investigational agents without the informed consent of the soldiers ? Even if such administration is legal (as the courts have ruled), many would find it unethical, and as the Nuremberg trials affirmed, "following orders" is no excuse for unethical conduct, even in combat. The only justification a physician could have for participating in the administration of experimental or investigational agents without soldiers consent is that he or she sincerely believes the agents are therapeutic under combat conditions. This is, of course, a difficult position to take, since war does not change the nature of a drug or vaccine. Such a decision would also be contrary to military regulations, which hold that, although a serviceperson must accept standard medical treatment or face court martial, soldiers have no obligation to accept interventions that are not generally recognized by the medical profession as standard procedures.14,15

A related question is a whether military physician is primarily responsible for the health and well being of the soldiers under his or her care (as in civilian life) or whether he or she must subordinate the medical interests of soldier - patients to the military mission. Remarkably, there is no written policy or standard view on this question in the military. The issue deserves critical attention in peacetime, since it is not susceptible to rational analysis in wartime. An unequivocal policy upholding traditional patient - centred ethics, although not legally required, seems the most responsible position for US military physicians who do not serve in combat situations to take.

The experience with rule 23(d) during Operation Desert Storm illustrates the difficulty of making distinctions between experimental interventions and treatment, the difference between law (especially as enunciated by the courts during wartime) and ethics,and the potential conflicts between the best interests of a physicians patients and the interests of a physicians employer.

Although it was designed to resolve these conflicts, rule 23(d) primarily served to highlight them, and to reverse a 44 year old policy of following the Nuremberg Code. The rule not only turned out to be militarily unnecessary but also called into question the seriousness of the United States' human rights agenda.

1. Trials of war criminals before the Nuremberg Military Tribunals. Tribunal 1 case 1. The military case: United States of America v Karl Brandt et al. Vol 2, Washington DC; Government Printing Office 1950

2. The Nazi doctors and the Nuremberg Codes, human rights in experimentation, New York , Oxford University Press 1992; 61- 129,188-208

3. 21 USC sec 355(1)

4. Informed consent for human drugs and biologies; determination that informed consent is not feasible. Fed Regs,1990; 35-52,814-7

5. 21 CPR sec 50.25(d)

6. Doe v Sullivan, 756F supp 12 (DDC 1991)

7. 10 USC sec 980

8. Doe v Sullivan, 938 F,2d 1370 (DC Cir, 1991)

9. Currie DP. The constitution in the Supreme Courts, the second century, 1888 to 1986, Chicago, Chicago University Press, 1990, 280-307

10. Keeler JR, Hurst CG, Dunn MA. Pyridostigmine used as a nerve agent pre-treatment set under wartime conditions. JAMA 1991;266,693-5

11. Waivers for military use of investigational agents. AM Hosp Pharm 1991;48,1525-9 .

12. Howe EG, Martin ED. Treating the troops, Hastings Cent Rep 1991;2(2) 21-8

13. Treatment of chemical agent casualties and conventional military chemical injuries; FM 8-285, NAVMED P-5041, AFM 160-11, Washington DC, Headquarters, Departments of the army, navy and air force, February 1990;sec 2-15-2-19

14. Johnson WH. Civil rights of military personnel regarding medical care and experimental procedures. Science 1953;117,212-5

15. United States v Stanley, 483 US 669 (1987)