Brief History of Milestones

Human Subjects Protection - A Brief History

In order to understand how we protect humans that participate in research, it is important to look back at some of the major historical milestones that led us here.

Below is a timeline in the history of human subjects protection. Select any of the events below for a brief description of their significance.

1938 - Food and Drug Act

Requires that drugs be shown to be safe before marketing, ultimately leading to the need for human trials.

1947 - Nuremberg Code

The research atrocities performed on prisoners in the concentration camps of Germany resulted in the Nuremberg Code, the first internationally recognized code of research ethics principles and the first mention of voluntary consent of the human subject (i.e. research participant). The elements of the Nuremberg Code are:

  1. Voluntary consent of subjects
  2. Anticipation of scientific benefits
  3. Benefits outweigh risks
  4. Animal experiments need to be conducted first
  5. Suffering is to be avoided
  6. No intentional outcome of the research should be death or disability
  7. Protect the subject from harm
  8. Subject is free to stop participation at any time
  9. Investigators need to be qualified
  10. Investigator will stop if harm occurs
1951 Henrietta Lacks

We cannot talk about human research protections without talking about Henrietta Lacks. In 1951 doctors removed samples of a cervical tumor from Henrietta Lacks and were passed along to a researcher without her knowledge or permission, as was common practice at the time. Researchers had been trying to grow human cells outside the body for years, with no success. Henrietta’s cancer cells (labeled “HeLa” based on her initials) revolutionized medical research, as they were found to be capable of surviving and dividing in the laboratory indefinitely. In fact, HeLa cells are still used today in research. Use of HeLa cells in biomedical research became extremely lucrative over the years, while the Lacks family received no financial benefits, lived in poverty, and had limited access to health care.

The story of Henrietta Lacks has been a catalyst for policy change, including major regulatory changes proposed in the United States surrounding informed consent.

Click here to read more about Henrietta

1962 - Kevauver-Harris Bill

The Kevauver-Harris bill, often referred to as the “Drug Efficacy Amendment”, established the scientific safeguards used today by the Food and Drug Administration (FDA) to ensure that consumers will not be the victims of unsafe and ineffective medications. The amendments authorized the FDA to require drug companies to conduct and submit tests determining safety and efficacy. In addition, the FDA now had to preclear all human trials, drug advertising, and labeling.

The push for this bill came amidst the thalidomide tragedy, when the request to approve the drug for use in the United States was brought to the FDA. In the late 1950’s thalidomide was marketed in 46 countries (including Europe and Canada) as a means of alleviating morning sickness, amid the manufacturers claims that it was “completely safe” for everyone, even during pregnancy. By 1961 it was found that this so-called harmless compound interfered with fetal development and was the cause of thousands of stillbirths and devastating birth defects, prompting the FDA to take a closer look at the requirements for testing, approval, and marketing of drugs in the U.S.

1964 - Declaration of Helsinki

Though not legally binding, this document was adopted by the 18th World Medical Assembly in 1964 and is regarded as the cornerstone document of human research ethics. It serves as a guiding statement of ethical principles for doctors other involved in medical research involving human subjects. Medical research involving human subjects includes research on identifiable human material and identifiable data.

1932 – 1972 The Tuskegee Syphilis Study

Before moving on to other milestones in human research protections, it is important to know about the The Tuskegee Syphilis Study, a study funded by the Public Health Service to evaluate the natural history of untreated syphilis in black males. The research population included mostly indigent African American sharecroppers in Macon County, Ala., as this it had the highest syphilis rate in the country at the time. Because there was no known treatment for syphilis when the study was developed, it was considered scientifically important and ethically justifiable.

The men were told they were being treated for “bad blood”, a term used to describe various ailments, and did not know they were part of a research study. In exchange for taking part in the study, they received free medicals exams, free meals, and burial insurance. Many thought they were receiving beneficial medical care. In actuality, the subjects were untreated, even after penicillin was shown to cure syphilis (1947), while researchers followed the progression of their disease.

The study was stopped in 1972 after public outrage over the blatant exploitation of this vulnerable segment of society, which led to the Assistant Secretary for Health and Scientific Affairs appointing an Ad Hoc Advisory Panel to review the study. The panel concluded that the study was “ethically unjustified” and the study was stopped.

Click here to read more about the Tuskegee Syphilis Study

1974 - National Research Act

Subsequent to the The Tuskegee Syphilis Study, the National Research Act was signed into law, creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and legislating the formation of Institutional Review Boards (IRBs)***.

***An IRB is a board designated by the organization to review, to approve the initiation of, and to conduct periodic review of research involving human subjects. The primary purpose of such review is to assure the protection of the rights and welfare of the human subjects. The IRB may be assigned other review functions as deemed appropriate by the organization.

1979 – Belmont Report

The Belmont Report was created and released by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. It was entitled Ethical Principles and Guidelines for Research Involving Human Subjects and pointed out the differences between "practicing medicine on patients" and "performing medical research on human research subject volunteers." It cautioned researchers to think about what hat they were wearing at any particular time. It identified three basic principles to guide researchers to provide safer medical research: respect for persons, beneficence, and justice.

1994: National Bioethics Advisory Commission (NBAC)

The NBAC was created by President Clinton to advise the National Science and Technology Council and other government entities on bioethical issues arising from research on human biology and human behavior.

1999 Death on Gene Therapy Trial

In the fall of 1999, 18-year-old Jesse Gelsinger died as a result of his participation in a gene therapy trial. Jesse had a rare metabolic disorder, ornithine transcarbamylase deficiency syndrome (OTC), which was being controlled with diet and medication. Researchers were testing an innovative technique using adenovirus gene therapy. Shortly after treatment Jesse experienced multiple organ failure and subsequently died. This case catapulted research with human subjects into the national media. Serious concerns related to conflict of interest, data safety monitoring, and informed consent have made the Gelsinger case the most contemporary illustration of continued doubts about the ethical integrity of research with human subjects. This case has instigated deliberations on all these controversial topics at the national level.

Click here to read more about the Gelsinger case.

2000 The Office of Human Research Protections (OHRP)

OHRP was established with the US Department of Health and Human Services to increase the focus on protecting human research participants.