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Comments on the Ethics of Research Using Human Cells
Michael Witherell, Vice Chancellor for Research
January 1, 2011
In The Immortal Life of Henrietta Lacks Rebecca Skloot tells several compelling stories. Reviewing the book in the Journal of the History of Medicine and Allied Sciences, Jacqueline H. Wolf writes that Skloot “examines an assortment of histories: race, class, childhood, the family, eugenics, medical ethics, doctors’ ‘benevolent deception’ of patients, the effects of sexually transmitted infections on families, and treatment of the handicapped.” In my role as vice-chancellor for research, I am particularly concerned with issues involving the ethics of research using human cells.
Any biomedical or behavioral research project funded by the U.S. government must now go through a highly structured review of its impact on human subjects. The U.S. first established regulations to protect human subjects in medical research in the 1970s, twenty years after Dr. George Gey started to culture Henrietta Lacks' cancer cells.
As often happens, public policy in this area was developed in response to public outrage. At the end of World War II, an American military tribunal tried German physicians for the medical "experiments" they conducted on thousands of concentration camp prisoners, research which often led to suffering and death. In the wake of this trial, the Nuremberg Code was established in 1948. It made clear that research subjects should be voluntary participants and give informed consent. This code did not carry the force of law, however.
The most well known case of unethical medical research in this country was the Tuskegee syphilis study, carried out in 1932 by the U.S. Public Health Service. The researchers in that study used African-American men from the rural south to study the course of syphilis when it was unchecked by any treatment. Although the men had agreed to be examined and treated, they had been misled about the nature of the research and were therefore not in a position to provide informed consent. Even when penicillin became the standard drug for treating syphilis in 1947, researchers did not offer it to the study participants.
An article published in the New England Journal of Medicine in 1966 called attention to “examples of unethical or questionably ethical studies” that were published in elite medical journals. This very public exposé of the existing practice in medical research led to a memo from the U.S. Public Health Service stating that it would only support research receiving an independent ethics review from an institutional review board. This was the first time that research institutions were required to guarantee to the government that they would be responsible for the ethical oversight of medical research.
A 1972 story about the Tuskegee study by Associate Press reporter Jean Heller led to a national cry of outrage about unethical research. In 1974, Senator Edward Kennedy introduced the bill that became the National Research Act, which created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Commission produced the Belmont Report, which established the principles that guide research on human subjects.
Few government reports in history have had the lasting impact of the Belmont Report. Although the Belmont principles are known throughout the world of biomedical and behavioral research, they are not often mentioned in the popular press. They are important enough to be restated in every discussion of research on human subjects. The principles, each of which was repeatedly violated at Tuskegee, are:
1) Respect for Persons. Individuals should be treated as autonomous agents, and those with diminished autonomy are entitled to special protection.
2) Beneficence. Researchers should take action to maximize possible benefits and minimize possible harms to patients.
3) Justice. The burdens and benefits of research should be distributed across society in a just way.
All biomedical and behavioral research is still measured against these principles by institutional review boards.
The Belmont Report quickly became the foundation of ethical research on human subjects around the world. It does not address directly all of the ethical issues involved in the establishment of immortal cell lines, however. When a sample of cells from Henrietta Lacks was made to divide without limit in vitro, it opened up a new world of research.
Normal human cells can only divide a finite number of times before the process stops. The reason for this senescence is that the telomere, a region of repetitive DNA near the end of a chromosome, becomes shorter with each division. When the telomere is consumed, the cell is destroyed and the process stops. Elizabeth Blackburn, Carol Greider (UCSB '83), and Jack Szostak were awarded the 2009 Nobel Prize in medicine for their discovery of how chromosomes are protected by telomeres and the enzyme telomerase. We now know that the immortality of the HeLa cells is due to their increased production of telomerase.
The use of HeLa cells to test the Salk polio vaccine was the first dramatic example of what this unending supply of human cells meant for research. We now have a large number of human cell lines, many of them associated with specific diseases. The maintenance of cell lines long past the life of the person whose tissue was used to create them raises a series of ethical issues that we are still learning to deal with.
If the Belmont principles had been in place twenty-five years earlier, someone would have had to inform Henrietta Lacks that her cells would be used for research and get her to sign a consent form. What would informed consent have meant, however, when nobody alive at the time could have foreseen all of the ways that those cells have been used to advance medical research and treatment? This is still one of the most difficult questions in all of medical ethics. In 1999 the National Bioethics Advisory Commission issued a report titled Research Involving Human Biological Materials: Ethical Issues and Policy Guidance. In that report, the Commission writes:
A case can be made that current practices concerning human biological materials sometimes fail to treat persons with due respect, because researchers may unintentionally be misleading regarding why materials are being gathered and the uses to which the materials will be put. For example, the person who draws the blood may not know that it will be stored indefinitely and may be used in any number of ways in the future, and therefore, this person may have no intention to mislead. Nevertheless, the institutionalized practice of storing biological specimens for future uses is one for which those who control the practice are responsible, and this practice, as we have seen, apparently does not always adequately inform individuals about future uses of the materials.
Most recently, researchers have realized that embryonic stem cell lines offer new opportunities for medical breakthroughs. An entire new regulatory apparatus has been set up to review whether each woman who donated an oocyte used to generate a line of embryonic stem cells gave appropriate informed consent.
Many lives have been saved by medical research using human cell lines. At the same time, this research raises complex ethical issues. As a society, we need to engage in a deeply informed discussion about how to protect the persons who contribute the tissue used to create cell lines. As the medical research evolves, the ethical discussion needs to evolve with it.