A Brief History of Military Contributions to Ethical Standards for Research Involving Human Subjects

by Arthur O. Anderson M.D.

In the 1700's, individualism, self-determination, national autonomy and desire for a government that acts upon consent of the governed, were high among the reasons why our forefathers fought the war for independence.

Acts of defiance like the Boston Tea party and the Maryland repudiation of the Stamp Act showed how strongly colonists reacted to Britain's enacting laws and levying taxes without representation by the colonists. The need to have information about, and input into, actions that effect a person's life is fundamental to human nature. Autonomy, Self determination and Consent are among the human "rights" that ethicists group under the principle of "respect for persons." It is not surprising that revolutions happen when the state denies the public these rights.

George Washington's experience during the French and Indian War convinced him that Smallpox was a formidable foe, yet he later chose force rather than reason to ensure that all his troops were protected from this disease during the war for independence.

As a Revolutionary War General, George Washington used variolation to stop the spread of a Smallpox epidemic in his troops. Smallpox casualties reduced General Washington's healthy troop strength to half while the British troops, who had either recovered from the disease or had variolated themselves, were already immune to the spreading contagion. Washington proclaimed smallpox to be his "most dangerous foe"; and, by 1777 he had the entire continental army variolated before beginning new military operations in Valley Forge. He also ordered all new recruits to be variolated as soon as they enlisted. Fortunately, for this nation, the end justified the means.

Variolation is not the same as "vaccination." Jenner had not yet discovered and promoted use of cowpox inoculation. Cowpox caused a milder infection in man but resulted in strong cross-reactive immunity to smallpox. Variolation, on the other hand, was the practice of collecting ooze and scabs from smallpox lesions of a person who had a mild case and scratching this material into the skin of other persons who then contracted the disease. Many recipients of variolation became mildly ill with smallpox, but some died following a serious and catastrophic course.

The practice of variolation had become the custom of European aristocracy
(The English aristocrat Lady Mary Wortley Montague was responsible for the introduction of variolation into England. She had an episode of smallpox in 1715). But, the practice had serious risks and was becoming controversial in Europe even as General Washington was deciding that his soldiers had to be variolated.

I misinterpreted this cartoon because I could not read the text

General Washington became the target of controversy because of the risks of variolating his troops and his decision to go ahead despite the concerns of a frightened public. George Washington's Forced-variolation of his troops was criticized by the public despite the Army's intent to benefit, and the fact that the procedure saved more lives than it jeopardized.

When I first viewed a crude copy of Cruikshank's cartoon (Above) I thought that the Hessian soldiers, mercenaries fighting for the British, may have been the "mercenary and merciless spreaders of death and devastation" mentioned in it. They had been captured at various locations in New York, Pennsylvania and New Jersey, transported and held as prisoners of war in stone barracks in Frederick Maryland. And, that prompted me to ask, "Were these POWs the first to receive variolation as a "safety test" before the entire army was inoculated at Valley Forge?

On the other hand, upon seeing the original cartoon it is more likely that it may have been referring to the mercenary Variolators in Europe who persisted with their risky practice of inoculating people with variola for 20 years after Jenner's vaccinia vaccine became available. The Variolators, the group shown on the left of the cartoon would be the "mercenaries who were driven from society" by the relative safety and success of Jenner's vaccine.

Jenner was not without criticism after he introduced cowpox as a vaccine against smallpox. People worried about having cow spots break out on their skin, as lampooned in Gillray's cartoon published by the anti-vaccine society in 1812. It took from 1798 until around 1840 for Jenner's vaccine to be widely accepted.

In any case, the public responds critically whenever they feel something is being done to them that they are powerless to control. It does not matter whether the intention is good or evil. It is just human nature to rebel against such things.

"Informed consent" is a human right. It is one of those inalienable rights like "life, liberty and the pursuit of happiness" that are guaranteed by the constitution. Obtaining a person's consent after providing him with all information about risks and benefits intrinsic to the choice is what informed consent should be. Informed consent embodies the ethical principle of "respect for persons" because it presupposes that the subject has autonomy and a capacity to understand and consider the intent, actions and consequences of the choices that are before him.

Failure to obtain informed consent from an individual before taking some action upon him informs him that his person-hood is not respected. Our representative form of government relies on the same principles that are intrinsic to "informed consent" because our leaders "govern with the consent of the governed." Discussion and debate of the issues in the legislature by representatives of the people must precede voting on, and enactment of, laws. This legislative process assures that informed decisions are made justly. In contract and product-liability law, adequate informed consent about risks is a remedy against Tort claims when harms or injuries result from use. Our courts adapted use of informed consent from British common law.

Despite the widespread use of disclosure and consent (i.e. principle of "Respect for Persons") in business and political life, it did not enjoy use within the medical profession. Beneficence (the will to do good) was assumed to be sufficient according to prevailing concepts of medical paternalism. Medical Paternalism was acceptable to patients who were anxious about making decisions about something they knew little about. Their fear of what they did not know and their willingness to delegate this to physicians negated the need for informed consent. It was assumed that physicians had no interest other than the patient's well being.

In general, physicians determined what tests would be performed, what treatments would be given and even how much a patient would be told about his/her condition. It was also customary for physicians to make all decisions about treatments without input from the patient. Medical Paternalism presupposed that the whole process was for the benefit of the patient and took into consideration how much the patient was able to understand about his/her condition.

John Shaw Billings MD

Johns Hopkins Hospital

William Osler MD

Advances in Military Medicine and Hygiene during the American Civil War were "transitioned" into standards of medical care practice during the latter part of the 19th century. As the twentieth century approached, new medical schools like Johns Hopkins sought out advice about the most advanced patient care facilities and practices, and what was learned by the Army on the civil war battlefields was important. Johns Hopkins Medical School created new academic standards not found at "proprietary" medical schools which Flexner criticized in his widely respected report. Thus the Johns Hopkins Medical School became the pace setter that set the stage for a "modern" era.

John Shaw Billings was an Army surgeon during the civil war who had many gifts besides those immediately related to medicine. He was profoundly interested in advancing knowledge by creating libraries to improve access to books. He also had ideas about hospital architectural design. He is credited with creating Index Medicus and the NY Public Library. In his last military posting, Billings was assigned as librarian for Army Surgeon General George Sternberg. This library, originally created in 1836 by Dr. Joseph Lovell the Army's first Surgeon General, would later become the core of what we now know as the National Library of Medicine.

While working on Sternberg's library, Billings prepared an architectural design for the new Johns Hopkins Hospital. The ventilation systems he incorporated into its design reflected the best contemporary understanding of industrial hygiene. He would later become a member of the Johns Hopkins Hospital board of trustees and, upon the request of William Welch, invite William Osler to join its faculty in 1888.

George Sternberg

William Welch

Walter Reed

George M. Sternberg, was the first American microbiologist to be trained in Welch's bacteriology laboratory in the late 1880s. He was succeeded there by Walter Reed who started this affiliation at Johns Hopkins in 1890 during his assignment to Fort McHenry.

Shortly after Sternberg was appointed Surgeon General of the Army in 1893 he appointed Reed, and Carroll to the Yellow Fever Commission. Reed and Carroll were known to be excellent microbiologists and they shared with Sternberg a belief in the theory that "
Bacillus X might be the causative agent of Yellow Fever. Shortly thereafter Guiseppe Sanarelli proposed that Bacillus icteroides was the cause. However, Sanarelli commenced human studies on subjects who were not told anything about what was being done. The notoriety of those studies are recorded in William Osler's writings.

Link to Berlin Code of 1900

"Informed Consent" statements were used by Walter Reed when he recruited volunteer subjects from among soldiers and civilians during the occupation of Cuba at the end of the Spanish - American War. The informed consent contract for Antonio Benigno, dated 26 November 1900 is provided here in both English and Spanish versions as JPEG images. Similar documents, signed by the soldier "volunteers" assigned to Major Reed's unit in Cuba are mentioned in individual histories of these volunteers but have not been located among archive collections. For example, in a 1907 presentation to The Congress of American Physicians and Surgeons, Osler said "Risk to the individual may be taken with his consent and full knowledge of the circumstances, as has been done in scores of cases, and we cannot honor too highly the bravery of such men as the soldiers who voluntarily submitted to the experiments on yellow fever in Cuba under the direction of Reed and Carroll."

The Berlin Code is dated 29 December 1900, a later date than that on the Yellow Fever consent document. So, how can there be a connection between the Yellow fever consents and the Berlin Code? The connection may have originated when Drs. William Osler and William Welch were fellows with Rudolf Virchow in Berlin during the decade preceding 1900. These important founding members of the Johns Hopkins Medical School also were present in Berlin when extreme controversy broke out over Neiser's unethical experiments where unsuspecting subjects were inoculated with "convalescent serum" from patients with syphilis. Because consent was not obtained the controversy led to an official written response by the Berlin City Council.

Virchow was a member of the Berlin City Council by mid century. He was in an even higher Prussian Government position when the code was drafted. Osler and Welch worked closely with him scientifically, but they also shared an intense interest in the integrity of medical science and ethics. It is possible that information about what the Berlin city council was considering was communicated by Welch to Walter Reed or George Sternberg who used it in preparing the 20 November 1900 "informed consent" documents used by the Yellow Fever commission.

This possible connection seems reasonable because Major Walter Reed and Army Surgeon General George Sternberg were associated with Johns Hopkins before, during and after the creation of the Yellow Fever Commission. Walter Reed was doing research on Typhoid Fever in Welch's laboratory. Typhoid was a major source of morbidity during the Spanish - American War. George Sternberg, an accomplished bacteriologist, also did research in Welch's laboratory and continued to consult with the Johns Hopkins faculty after being appointed Surgeon General of the Army.

There are numerous references to Reed, Carroll, Lazear and Sternberg in Cushing's biography of Osler, and Osler makes reference to Reed's use of informed consent for participation of both the civilian and military volunteers in documents he wrote at the time of the Yellow Fever studies and later in 1907.

It is theoretically possible that Virchow's "fellows," Osler and Welch, may have had a hand in contributing to the content of the Berlin Code. I first learned about the Berlin Code while reading my issue of IRB. This is the reference citation, "Vollmann, J. & Winau, R. (1996). The Prussian regulation of 1900: early ethical standards for human experimentation in Germany. IRB: A Review of Human Subjects Research, 18(4), 9-11."

Osler's education prior to medical school included attending seminary where he developed a love for Philosophy. His father was a minister and before seeing his calling as a physician, Osler had started study for the ministry.

Osler is regarded as the father of scientific medical practice and for his writings in medical philosophy. Welch was a senior advisor to the Yellow Fever Commission and later advised President Roosevelt on Public Health Issues related to the Construction of the Panama Canal. Certainly, these events must have facilitated his transition from Pathology to becoming a major proponent of Public Health in the United States. Welch remained a close advisor of President Roosevelt's throughout his life.

English and Spanish "Informed Consents" used by Walter Reed in 1900

The person who actually prepared the typed "contracts" I referred to as "informed consent" documents was Major Reed's "Disbursing Officer" (Army Logistics Officer). Although the form of the document was clearly his, it would be customary to have someone like Walter Reed write the narrative. This narrative is the first clearly written exposition of risk and benefit for consideration by human volunteer subjects in the Americas. When English was not the primary language of the subject, the document was written in Spanish, the Cuban subject's primary language.

One could view these documents as simply "personal service contracts" with the exception that they clearly communicated the risks and benefits of participation and described the conduct of the study. They provided compensation for discomfort and accounted for any serious adverse event that may occur, including death. Subjects were paid in gold.

It is not surprising that medical research laboratories within the military and civilian medical communities used the Yellow Fever "Consent" documents as early models of ways to provide adequate informed consent.

The Yellow Fever Commission "informed consent" documents I put on this web page hung on the wall outside my commander's office at USAMRIID when I arrived in the summer of 1974. USAMRIID grew out of what was called the US Army Medical Unit of Fort Detrick after President Nixon's "Swords to Plowshares" speech of 1969 ended the offensive biological warfare program.

I had the opportunity to examine the "consents" in 1994 because they had been damaged and I wanted to have them repaired. I took them to a conservator at the National Library of Medicine who examined them using state of the art technology. She told me they were actually photocopies on laid paper and not original documents.

The technology used to make them was typical of what was done with documents "photo-copied" in the middle 1950s. By performing this scientific evaluation, the conservator was able to provide documentation that the medical researchers at Fort Detrick also must have considered what Walter Reed had done while preparing to conduct the studies referred to as Operation Whitecoat.

Despite this connection from Walter Reed to the military doctors of Operation White coat, the years between the Yellow Fever Commission and the Cold War saw unprecedented involvement of human subjects in military and civilian research, especially to support the WWII war effort. While the public knew about the atrocities in Germany where medical experiments were performed as part of a program of genocide, secret state experiments were also being performed in the US with great urgency.

Ed Regis' book entitled, "Biology of Doom; America's Secret Germ Warfare Program" provides excellent coverage of "WWII years" when concerns about possible use of Biological Warfare by the Nazi's in WWII necessitated emergency R&D measures.

The  War Research Service (WRS), Committee on Medical Research (CMR) was created as a civilian scientific enterprise under George W Merck during the period 1942 - 1952.
See Stimson Ctr for info on BioWarfare.

The Secretary of the Army recruited accomplished civilian scientists from universities and corporations to quickly create a research program responding to the biological warfare threat from Germany and Japan.

Many of the civilian and military participants in this enterprise made huge advances in infectious disease research, development of antibiotics and in advancing, microbiology, immunology and molecular biology at Fort Detrick and in hundreds of laboratories in Universities and Research Institutes. Among the WRS/CMR-supported researchers were extraordinarily talented scientists who would later be awarded the Nobel prize for seminal contributions to their discipline. What these men did during the war, and the geopolitical context in which they did it, is chronicled in Mr. Regis' book. However, it is not clear whether any unifying ethical principles were implemented in the respective universities that performed research for WRS/CMR for developing CBW antidotes, drugs and vaccines. The urgency and secrecy that prevailed in the early years of WWII favored use of utilitarian ethics for developing medical countermeasures to protect the safety and welfare of the US Armed Forces against the perceived threat of chemical and biological warfare.

There was a great deal to do and the urgency of WWII did not leave much time to deliberate about or debate ethical principles for testing drugs and vaccines to protect soldiers. 

Even before the US officially knew what risks lay ahead in BioWarfare, Japanese scientists in 1939 had attempted to obtain virulent Yellow Fever Virus samples from the Rockefeller Research Institute in New York City. However, scientists thwarted these attempts by responding appropriately to their suspicions.

In August 1941 a physician - staffer in the War Department theorized that it was a distinct possibility that yellow fever might be a biological-warfare threat, although he knew nothing of the incident at the Rockefeller Institute. Yellow fever [YF]  and Flu vaccination were made compulsory as the US drew closer to war.

A YF vaccine that was early in development was given to all deploying US troops in January 1942.  By March 1942 tens of thousands of soldiers had hepatitis and scores died. The Yellow Fever vaccine had been given to protect them against possible biologic attack. This YF vaccine was contaminated with hepatitis B virus, as was later found after two AFEB supported studies in residents of state institutions in Virginia and new York. The Lynchburg VA and Willowbrook NY studies involved decisionally impaired vulnerable populations and were deemed unethical and immoral.

The War department was also concerned about epidemic disease threats in areas of deployment. The influenza pandemic of 1918 that was amplified by World War I troop movements, alerted everyone to the need for a flu vaccine for World War II.

Thousands of the soldiers deploying for World War II were vaccinated against flu with an experimental vaccine. This actually was a successful venture. An epidemiological survey of the use of this vaccine was used as evidence of efficacy and the vaccine was approved for marketing by the FDA in 1944 on the strength of the Army data. 

Germany actually had an an excellent code describing ethical conditions that must be met for humans to be used in medical research in 1931, but victims of Nazi genocide were excluded from the protections of the German Reichsrundschreiben, Human Experimentation Code, according to a memo signed by Hitler that took away their rights as citizens.

Nazi doctors were convicted for acts of torture, barbarism and murder rather than unethical use of humans in research, but these atrocities conducted under the ruse of medical research indirectly helped focus on what might be needed for such research to be regarded as ethical.

The risk of being stigmatized by what the Nazi doctors did, motivated DoD scientists to find the high road for research conducted to develop products against Nuclear, Biological and Chemical agents during the Cold War.  The Wilson Memorandum, which incorporated the principles of the Nuremberg Code, was provided to each branch of the military. The Army adopted it as a directive, cs-385, in June of 1953 and this became the first government-promulgated "regulation" for protecting human research volunteers.

Publication of the Nuremberg Code in 1947 provided a clear statement of what was regarded as the conditions that should be met before a person might ethically be used as a subject in medical research. Although the Nuremberg code never was used by the military tribunal that was prosecuting Nazi war crimes, it acquired a stigma by its association with the wrongs committed by Nazi physicians who performed medical atrocities upon concentration camp inmates. Publication of these atrocities after the war caused concern about whether it would be possible to ethically advance medical knowledge. Despite the stigma attached to it, The Nuremberg code clearly described an ethical framework for conducting medical research.

The US Army participated in disseminating Nuremberg Code principles for ethical use of human subjects of research by including the code in directive (cs-385). Cs-385 was based on the memorandum signed by Secretary of Defense Charles E. Wilson, which became known as the Wilson Memorandum of 1953.

Operation Whitecoat was created as a feasibility study to demonstrate that medical countermeasures against biological warfare could be developed and tested in human subjects while complying with the ethical principles of the Nuremberg Code. (See the ACHRE Report section on DOD, the Nuremberg Code and Informed Consent.)

Link to Nuremberg Code

The Wilson Memorandum was implemented by the Army as
"directive" cs-385 on 30 June 1953.

cs-385 was released to civilian contractors in 1954,

Henry Beecher and other academicians rejected it because
the Nuremberg Code principles were too restrictive.

FDA Regulatory History Linked to Incidents in Civilian Sector

Operation Whitecoat
Human Subjects Research during the "Cold War"

At the end of September 1998, the Frederick Seventh Day Adventist Church (SDA) held a reunion for the "Operation Whitecoat" volunteers. Whitecoats were SDA "Conscientious Objectors" who agreed to serve in the military in noncombat positions. Many entered active duty in the Army as Medics and served as clerks, photographers and lab technicians at Fort Detrick, when they were not participating as human volunteer subjects in research protocols.

Between 1954 and 1973 over 2,300 SDA served as volunteer subjects in 137 protocols directed at developing and testing vaccines and therapeutic drug candidates against Q fever, Tularemia, various viral encephalitides, Rift Valley Fever Virus, sand fly fever and Plague. The story of their personal heroism as volunteers in research was chronicled in a History Channel program entitled Dangerous Missions: Human Guinea Pigs.

William D Tigertt, the commander in charge of Operation Whitecoat visited Seventh Day Adventist leaders to discuss the planned research and to obtain concurrence about recruiting volunteer subjects from among their young men. An affirmative "Statement of Attitude" regarding the program by the SDA General Conference brought healthy and altruistic volunteers to Fort Detrick but it also brought a interested  community to whom the Army scientists remained accountable from 1954 until 1973.

The SDA conscientious objectors, serving at Fort Detrick as non-combatants, participated as volunteers in studies testing human vulnerability to biological warfare agents in realistic scenarios, and multiple new products for defense against biological warfare and hazardous infectious diseases were developed with their participation.

Q-fever and Tularemia were approved for these antibiotic and vaccine efficacy studies because safety criteria were met and cure was certain.

Oversight for the program came from various external advisory groups including the Armed Forces Epidemiological Board [AFEB] comprised of civilian leaders in academic infectious disease research, a committee of the National Academy of Sciences, Institute of Medicine and a Medical Policy Setting Board at the level of the Army Surgeon General that included personnel from the top military medical leadership. These oversight groups were intent on safely obtaining the needed data without causing harm to any of the volunteers.

The 230 Operation Whitecoat volunteers who returned to Frederick for the reunion formed a representative group randomly representing all periods of the program between 1954 and 1973

Information that was exchanged between investigators and research volunteers of the US Army Medical Unit at Fort Detrick confirmed my belief that the "process" of informed consent, and respect for the principles of the Nuremberg Code as required by cs-385, were effectively implemented. Some features of the ethical process of subject recruitment and informed consent are listed below:

USAMU and USAMRIID conducted human subjects research for 50 years with only 1 claim of disability, no deaths and past and present subjects are openly positive about their experiences in numerous News Articles, Radio and TV Reports, and also Scholarly Reports by a Policy Analyst who reviewed the original documents while serving on the President's Advisory Commission on Human Radiation Experiments. See: Lessons Learned A Half-Century of Experimenting on Humans - U.S. Army experiments Humanist, Sept, 1999, by Jonathan D. Moreno

Accomplishments of the Operation Whitecoat Program that ensured that it was conducted ethically, morally and legally were:

  • Application of the 10 Nuremberg Code Principles in the Ethical Design and Conduct of Human Volunteer Subjects Research.
  • Subjects were awarded autonomy (acknowledgment) prior to recruitment to any protocol.
  • The informed consent process was staged in three or more events with days to weeks in between and written consent was not solicited until the end of the process.
  • The Institute environment strongly supports all phases of ethical development, review and audit of research.

Many of the volunteers who attended the reunion heard about the fruits of this research for the first time since they were at Fort Detrick. I was amazed that all of them knew intimate details of individual protocols and that they were volunteer subjects in medical research experiments. Half of them remembered specific details of the experiments such as what test agents they received, whether they got placebo or vaccine and what the vaccine was called 25 - 34 years after the actual event. Although other non-clinical research programs at Fort Detrick were classified, no human studies of vaccines, drugs or infectious diseases at the US Army Medical Unit were classified. This was necessary because the names of the agents against which the vaccines were created were inextricably linked to the information that had to be shared with volunteers for informed consent to be adequate. Therefore, even during periods of intense secrecy in other areas of Fort Detrick, the human subjects research was not secret.

I had examined all documents related to the human subjects research and the informed consent statements used for these cold war experiments around the time of the President's Advisory Commission on Human Radiation Experiments which generated the ACHRE report. I found that the 'consents' were short and clearly written. Some of the consent forms looked very similar to those used by the Walter Reed Yellow Fever Commission. Others showed progressive improvements to comply with regulatory requirements that were evolving. Later on in the 1960's the "consent" forms were complete but there was little or no written information about what they were being informed about on forms. However, my examination of the subject record files and conversations with some of the original volunteers revealed that they were given the whole protocol to read. This was in addition to a verbal presentation and other documents they read before deciding to meet with the PI about signing the consent document. I spoke with Whitecoat volunteers who still live in the Frederick Community and contacted several of the investigators who prepared and executed these studies in order to reconstitute what practices took place during those early years.

I was told that the Whitecoats attended an oral presentation about a study that was given by the principal investigator. No one was asked to volunteer immediately. They had 2 weeks to think about what they had heard. If anyone wished to volunteer for a study, he would meet one-on-one with the P.I. to discuss the risks, benefits, conduct and other aspects of the study. All of their questions were answered during that dialogue. After this process reached a point where the subject wished to volunteer, he would sign the consent form; or, if he chose not to volunteer he would leave without any further questions. About 80% of any year group of Whitecoat subjects actually volunteered for any studies and that statistic consistently appears among our military volunteer subjects today.

This information about the volunteering process and the fact that at least half of the Whitecoat volunteers still remember numerous details presented to them during the "informed consent" process attests to the importance of the "process" even if written documentation of what constituted informed consent may have been insufficient.

This stands out in contrast to observations made by surveyors commissioned by ACHRE who found that many research subjects today sign highly detailed informed consent statements and promptly forget that they are subjects in medical research. They often express the belief that they are awaiting "treatment" when it is not certain if they will be receiving a test drug, a control drug or a placebo.

These studies took place during the cold war, and it is understandable that there may be a lack of written records. However, I was able to locate the approved protocols, the minutes of meetings at which these protocols were approved, individual subject records and a host of memoranda describing the origin conduct and completion of this program. Furthermore, all of the records of these studies are retained in study charts for each subject that are held in the USAMRIID records room continuously since they were created. Included in the records is the consent form, the whole protocol and any documents, clinical records or results that pertain to that study.

Whitecoats were assigned to Fort Detrick for 2 year tours, after which they could leave the service or pcs to another assignment as a medic. Some Whitecoats remained in the Army and saved lives as medics in Viet Nam. A few were recipients of the Congressional Medal of Honor. Many Whitecoats left Fort Detrick having learned a trade, or earned entry into college or graduate school to pursue biomedical sciences as their life's work.

AR70-25 was published as an Army Regulation on 26 March 1962.
It had the same content as cs-385 but in Army Regulation format

Link to Declaration of Helsinki 1964 plus updates through 2002

The Nuremberg Code principles continued to govern Army human subjects research from 1953 until 1981 when the Belmont Report and 45 CFR 46 led to changes in AR 70-25 that brought it closer to what regulated civilian clinical research involving human subjects, but it also introduced practices that began to limit the military's capacity to respond quickly to national emergencies. For example, the Nuremberg Code did not prevent physicians from using investigational drugs, biologics or devices for patient care or for responding to a national emergency. 

The Declaration of Helsinki and The Belmont Report replaced the Nuremberg Code for civilian medical research because they "allowed" research in clinical settings whereas the Nuremberg Code was primarily for situations where healthy individuals contemplated volunteering for protocols that held no direct benefit for them. On the other hand, nothing is as strong a coercion as is the "therapeutic misconception". The Declaration of Helsinki is now undergoing another revision.

AR70-25 (31 July 1974) had the same content as that of the 1962 version
but final approval transferred to the Surgeon General

Link to The Belmont Report of 1979

The MRVS Program of the "All Volunteer Army"

Two issues that have had a lot of play among IRBs recently are interactions with the community from which research subjects are "recruited/taken" and the burden of paperwork we are all suffering from. It is not surprising that the Inspector General has determined that we are beginning to fray at the edges in our ability to protect research subjects. I think there are some lessons I learned in the relative isolation of my unique situation of being IRB chair in a military laboratory that develops vaccines and drugs designed to protect soldiers from high hazard biological warfare agents. Our community is comprised of young healthy men and women who serve in an "all volunteer Army." They regularly put their lives on the line, in their "military" jobs to protect our freedoms yet they do not normally have autonomy over decisions regarding their own health care.

This lack of autonomy was one of the first problems I had to consider when I was asked to chair the USAMRIID Human Use Committee in 1975. How can you have informed consent when there are regulations that describe how much force or punishment may be applied to cause someone to submit to diagnosis or treatment.

Within our research institute, I took measures to assure that our Medical Research Volunteer Subjects (MRVS) would have the freedom to decide whether or not to be a volunteer in research. It was not until 1981 that specific clauses were added to AR70-25 (the Army regulation governing ethical use of human subjects in research) that prohibited use of the uniform code of military justice (UCMJ) from being applied in situations where subjects were volunteers in research. Application of UCMJ penalties to cause someone to volunteer or to prevent someone from withdrawing from participation in a research protocol are absolutely forbidden by AR70-25.

AR70-25 originally included the Nuremberg Code as its principles when it was first published in 1962, and in subsequent versions until 1981. The clauses about subjects having the freedom to withdraw without penalty, and descriptions of the conditions which define "voluntary consent," i.e. all of the conditions for informed consent, including mental capacity to understand, legal capacity to give consent, freedom from coercion and the receipt of all the information about risks, benefits and what would happen during conduct of the study allowed subjects to make choices freely, with all required information and without coercion. This information also was not supposed to include "over reaching" or other transmogrifications of the facts that we routinely call "marketing" today.

I learned from my research into what took place during "Operation Whitecoat" that the US Army Medical Unit (the forerunner of USAMRIID) prepared an "Acknowledgement" document for potential "Whitecoat Volunteers" to sign as they decided to be assigned to Fort Detrick's Medical Unit. This document was a sort of "informed consent" document that described what would be expected of the subject and what would not be expected. More importantly, it clearly defined the soldiers right to autonomy in decisions about participating in any specific research protocol.

The only requirement the Whitecoat soldier had was to attend the briefings given by Principal Investigators. If after hearing the proposal the soldier felt he did not want to volunteer, that would be the end of it. The "Acknowledgement" document also described the commitment of the institution to uphold these freedoms. The document did not bind the soldier but it did appear to bind the institution. A similar document, lacking the promise of "non-combatant" duty has been in use at my institution for as long as I have been there (ie 1974 - the present).

Soldiers who sign this Acknowledgement document during recruitment from "Medic School 91B" at Fort Sam Houston Texas are called MRVS or Medical Research Volunteer Subjects.

Other soldiers assigned at USAMRIID have not signed this document but may also participate in research protocols. Language in the informed consent statement confers upon that soldier the protections of his autonomy that are initially granted by the Acknowledgement. The only difference between the two sources of research volunteer, then, is that MRVS do not have to ask permission from their supervisor before agreeing to participate as a subject in research, whereas other soldiers need to discuss work load considerations with their supervisors before volunteering. If any coercion occurs, it usually is directed at a subject not volunteering because his service is needed elsewhere in the institute.

This brings me back to the topic of a soldier's autonomy about participating in research protocols or in making his own health care decisions. The Army does not grant soldiers the right to make their own health care decisions through its existing regulations. These regulations are now making headlines because of the soldiers who have refused to take the Anthrax vaccine.

The Anthrax vaccine is a licensed product, in the military health care system that means that no "informed consent" is necessary. This issue illustrates how broadly American culture has changed in the years since military health care regulations were written. In civilian medical practice "informed consent" is negotiated with the patient before instituting almost all treatments regarded as "standard of care." It has taken a long time for paternalism in medical practice to yield to the principle of "respect for persons."

At the time I started medical school in 1966, doctors still held onto the belief that the doctor made all the health care decisions for his patient. This included whether or not to tell the patient the truths of his condition or to inform him about his therapy or even involve him in choices of therapy that may be applied.

All of that is changed now in the civilian health care system, although some of the choices patients have may be eroding as non-clinically trained managers for HMOs intercede with decisions which conflict the needs of the patient with pragmatic and profit interests. During the current years of progress in patients rights and changes in cultural expectations, the military health care system still uses a paternalistic practice where the health care provider determines what is best for his patient.

See: Human Subjects Protection in National Biodefense Research: Ethical Dilemmas and Dichotomies and Importance of Animal Models in Biodefense Research for more information about how the evolution of FDA Regulations influenced the ability to respond quickly with effective biodefense countermeasures in a time of national emergency.

Cleared as: RPP-03-104, "Ethical Dilemmas and Dichotomies in National Biodefense Research;" RPP-05-240, "Scientific and Ethical Importance of Animal Models of Human Disease in Biodedefense Research;" RPP-05-352, "Biowarfare to Biodefense: Operation Whitecoat & USAMRIID History;" TR-06-003, "Ethical and Legal Dilemmas in Biodefense Research"

The information and opinions stated in this website are my own personal ideas and must not be construed to represent any official position of any agency of the US Government.