this is part of a series of videotapes intended to help health professionals understand their responsibilities for protecting human subjects in biomedical and behavioral research one program discusses the criteria used by IRB s for reviewing research another shows how to apply the basic ethical principles which underlie the involvement of human subjects the series begins with this program which looks at the historical backdrop of concern for human subject protection it then follows the evolution of these concerns toward present-day practices in 1926 Paul dick rife published microbe hunters a popular history of biomedicine in it he portrayed researchers such as Louis Pasteur and Walter Reed as independent visionaries struggling alone to understand and conquer disease we start our examination of concern for protecting human research subjects by recalling the crimes popular book because it represents a transition the great researchers of the past worked alone and took sole responsibility for their experiments with humans but the entire scale of research was expanded by the second half of the 20th century science had provided numerous new techniques in the diagnosis prevention and cure of disease public appeal and support encouraged even more research the number of experiments and thus the number of human subjects dramatically increased and scientists were in the forefront of those reminding us of our responsibility to research subjects researchers were increasingly concerned that the growing numbers of subjects receive adequate protection from risk given the increasing complexity and scale of scientific research some began to wonder if possible negative effects from the research might go undetected in many instances independent committees of researchers were formed to review proposed research from an ethical perspective increasingly government scientists and the public agreed on the need for strengthening protection of research subjects today we recognize that human subject protection is the shared responsibility of many clinical investigators institutions government officials and the institutional review boards or IRB the IRB is a committee of scientists and non-scientists at the local level that reviews research protocols and consent forms to ensure that the rights and welfare of research subjects are protected to understand the multi-faceted roles involved in assuring these protections one must look at the recent history of medical and behavioral research part of that history are the key events that resulted in the protective mechanisms we have today there was no clear first step in this evolution of concern for the rights of research subjects antecedents appear during the 20th century and before this consent form from the year 1900 though serves as a point of departure the form was used for the yellow fever experiments that made Walter Reid famous it was provided in both Spanish and English signed by the subject as well as the researcher understands that he in dangers his life to a certain extent but it being entirely impossible for him to avoid the infection during his stay in this island he prefers to take the chance of contracting it intentionally the form was evidence that Reid believed sound ethical practices go hand in hand with research involving human subjects ethical concern has deep roots back to the do no harm principle attributed to Hippocrates protecting research subjects has been a long-standing basic tenet of experimental medicine but medical research is characteristically frustrated by blind leads ambiguous results and negated hypotheses yet there is pressure to continue medical progress and occasionally investigators have been inadequately sensitive to the need to protect the interests of those who are actually at risk the research subjects as we follow the evolving concern for research subjects we will encounter some occasions when subjects were not adequately protected such examples of research constitute a tiny minority of experimental work but they did stimulate researchers and the public to improve systems for protecting research subjects in December 1946 23 medical professionals from Nazi Germany went on trial in Nuremberg they are important because their actions precipitated the first modern effort to formulate an international code of ethics protecting human research subjects the victims of these crimes are numbered in the hundreds of thousands a handful only are still alive a few of the survivors will appear in this courtroom but most of these miserable victims were slaughtered outright or died in the course of the tortures to which they were subjected the offences ranged from subjecting prisoners to extremes of altitude and cold to using them as human typhus and malaria cultures for testing vaccines it is our deep obligation to all the peoples of the world to show why and how these things could happen it is incumbent upon us to set forth with conspicuous clarity the court you are condemning these doctors accepted and codified ethical standards that the defendants had grossly violated these standards came to be known as the Nuremberg code the first internationally recognized code of medical research ethics the codes sought not merely to prevent experimental abominations in the future but to increase the protection of the rights and welfare of human subjects everywhere by clarifying the standards of integrity that constrain the pursuit of knowledge the code was a guide not a law the first of its ten principles stresses the necessity for voluntary informed consent from research subjects it defines the meaning of informed consent and places the responsibility for obtaining adequate informed consent on the researcher other points include experiments should not be random or unnecessary experiments with humans should be preceded by experiments on animals and surveys of the natural history of the disease unnecessary physical and mental suffering should be prevented experiments should be conducted by scientifically qualified professionals subjects should be permitted to withdraw at any time and investigators should be prepared to stop an experiment at any time if the subject is endangered the Nuremberg code enumerated the fundamental principles that ought to guide research involving human subjects but it was not the last word although the role of informed consent seemed clear enough in biomedical experiments this was not always the case for other research involving human subjects in the early 1950s the Wichita Kansas Bar Association became concerned about articles and a nationally syndicated column suggesting trickery when lawyers argue before juries the Wichita lawyers wanted reliable information on how juries deliberate and reach decisions at the same time the University of Chicago received a Ford Foundation grant to study a variety of legal issues including jury behavior in 1953 with the cooperation of the US Tenth Circuit Court of Appeals and approval of lawyers on both sides University of Chicago researchers recorded six jury deliberations without the knowledge of the jurors the transcripts were carefully guarded and names in the cases were changed to protect the identity of all involved in 1955 Senator James O Eastland brought this matter before the Senate Internal Security subcommittee how could researchers justify recording jurors without first obtaining their permission behavioral scientists at the University of Chicago defended the study by explaining the prior knowledge of the recording by the jurors would alter their behavior others agreed with the Washington Post a jury imperatively needs to carry on its deliberations in private when it retires to consider the evidence its members must be free from any outside pressure or fear of reprisal after weighing the arguments Congress enacted legislation prohibiting the recording of juries in federal courts behavioral researchers were required to respect the fundamental rights of the public in their research at about the same time the juries were being taped in Wichita the National Institutes of Health was opening a new Clinical Research Center in Bethesda Maryland rules of the new research hospital required a panel of qualified scientists to review the protocol for any research involving healthy volunteer subjects other institutions also were beginning to form committees to review research these were often informal groups convened by the scientists themselves to discuss ethical aspects of research these boards were to some degree an innovation they were not the institutional review boards of today they did not for example include members from the community but they were a step toward the IRB in the early 1960s a new drug thalidomide was introduced for experimental use in the United States it had been prescribed extensively in Germany and England The 1938 Food Drg and Cosmetic Act allowed pharmaceutical companies to distribute new drugs for testing without FDA review in the thalidomide case it is estimated that more than 1,000 doctors in the u. s. administered the drug many of these doctors did not tell their patients the drug was experimental when it was discovered that the lead AMA had taken by pregnant women could produce tragic deformities in the fetus there was a wave of public reaction and the use of the drug was stopped the Kefauver Harris hearings resulted in the 1962 amendments to the Food Drg and Cosmetic Act which included requirements that investigators must inform potential subjects of the experimental status of the drug and obtain consent in requiring consent Congress allowed the physician to decide whether or not obtaining consent was in the best interest of the subject the new amendments and the resulting regulations were a major step in the developing concept of informed consent by subjects the protection described in the Nuremberg code was evolving and becoming mandated through congressional legislation and government regulation in 1963 another landmark incident furthered the evolution of concern for research subjects a group of well-respected physicians from the sloan-kettering Institute approached the medical director of the Jewish chronic disease Hospital in Brooklyn seeking help with a study of the immune system in cancer patients the research protocol required injecting live cancer cells under the skin of feeble and seriously ill patients the injections were given apparently the patients were told their resistance was being tested they were not told the injections contained live cancer cells the story would have remained untold had a non physician on the hospital board not inquired about the propriety of and acting patients with cancer cells and had he not taken the hospital administration to court to obtain access to the patient's medical records once the lawsuit drew public attention the research was severely criticized because of its failure to respect the research subjects had the physicians betrayed their patients trusts we're not the doctors facing conflict between their obligations to their patients and their desire to obtain research results the civil rights movement and the social climate at that time encouraged an increased concern for all human rights whether the subjects were elderly people poor people children in institutions or prisoners researchers could expect criticism if the individuals rights were not respected during the late 50s and 60s dr.
James Shannon director of the NIH conceived a study to determine how to protect research subjects adequately in 1964 he appointed a committee to review the study and design mechanisms to ensure that subjects would be systematically and uniformly protected in all biomedical and behavioral research funded by the Public Health Service about the same time with the public recalling American prisoners of war being brainwashed during the Korean War debate over the safety of psychological research intensified when Yale University investigators published a paper entitled conditions of obedience and disobedience to Authority the situation in which one agent commands another who heard a third turns up time and again as a significant theme in human relations it is powerfully expressed in the story of Abraham the experiment the subject was told to give what appeared to the subject to be an electrical shock to another person for the stated purpose of studying the effects of punishment on learning this allowed the investigator to observe the subjects willingness to carry out orders even if they resulted in pain or harm to others no electrical shocks were actually administered afterwards the principal investigator carefully explained the real purpose of the events to the subject the study caused a furor in the American psychologist dr. diana baumrind a behavioral scientist spoke for many it is potentially harmful to a subject to commit in the course of an experiment acts which he himself considers unworthy particularly when he has been entrapped the subjects personal responsibility for his actions is not erased because the experimenter reveals to him the means which he used to stimulate these actions the subject realizes he would have hurt the victim if the current were on much valuable criticism of research practices has come from within the research community in 1966 dr. Henry K Beecher a Harvard Medical School teacher and respected researcher raised ethical questions in an article in the New England Journal of Medicine from published research papers he cited serious ethical problems in the protection of human subjects in numerous cases in some of them the controls were denied treatment in others risky surgical procedures were attempted dr.
Becher concluded Papworth in england has collected he says more than 500 papers based upon unethical experimentation it is evident from such observations that unethical or questionably ethical procedures are not uncommon also called codes are based on the blind assumption in the same year the work begun by dr.
