The Story of WI-38, the Other Famous Cell Line

Recently, a news feature published in the journal Nature caught my attention. I was pleased to read such an insightful piece on a key issue for cell biologists—the ethical and effective use of human tissues and cells. Credit goes to science reporter Meredith Wadman who took a closer look at the intriguing “back story” behind a rather famous cell line, WI-38, that was established in 1962 by Leonard Hayflick at the virology powerhouse of the day, the Wistar Institute in Philadelphia1. The twists and turns of the WI-38 story are complex, and I strongly encourage followers of this blog to read Wadman’s feature article, which sets out the facts clearly and yet doesn't duck the implications.

Wi38The WI-38 cell line, shown here in a 1970s transmission electron micrograph (TEM),
is the center of a complex tale of science, ethics, and personal privacy.
TEM courtesy of the Archives of the Wistar Institute.
Suffice it to say that WI-38 cells were derived from human fetal lungs obtained through a legal abortion in Sweden; the fetal lung tissue was shipped from Stockholm to Philadelphia for Dr. Hayflick’s research, which at the time was looking for normal cells—not cancerous like those of the HeLa line—in order to determine whether some forms of cancers in humans could be caused by viruses. The cervical cancer line HeLa was not much use to Dr. Hayflick, so he established this new line, WI-38, which became one of the most important cells lines in history.

Nearly all research biologists have worked with HeLa cells at one time or another in their educations or careers, while a much lower percentage have worked with WI-38 cells (I have not). Despite this “epidemiological” fact, WI-38 cells have made phenomenal contributions to human health because they were used to develop vaccines, which have saved millions of lives. From these vaccines, millions of dollars were made through sales by drug companies and through royalties by research institutions. And this, as it often happens, became an issue—who owns the WI-38 cells? Who has the right to make deals with the pharmaceutical companies? Who should distribute the cells? Did the mother of the fetus consent to the use of the cells in research, which proved to be essential for studying senescence and for developing life-saving vaccines? And finally, throw into the mix the abortion issue, and the Vatican statement urging Catholics to employ every lawful means to make life difficult for those who used the WI-38 cells. It is a story with something for everyone in science, law, and ethics.

As a high school sophomore, I had the good fortune to be taught history by an exceptional teacher, Professor Romano Gromi, who once assigned our class a reading that still remains with me today. It was a book by the French historian Mark Bloch, entitled The Historian’s Craft, which I read in Italian under the title of Apologia della Storia2. Of course as a brainless teenager, I resented having to read such a charming book. If memory serves, what Professor Gromi was trying to drill into our heads through the writing of Marc Bloch was the concept that the job of a historian is to look at the past in the light of the present, and similarly to look at the present in light of what has happened in the past, all without jumping to judgment.

In looking at the history of WI-38, Wadman takes what I call the “Bloch approach.” In a non-judgmental way, she guides the reader through all the complexities of informed consent and intellectual property rights. She considers the deference due tissue donors and also the need to promote effective and efficient scientific discovery. She also makes it plain that certain actions, such as the first establishment of cell lines, happened at a particular time in history and in a given cultural context, while decades later those uses and applications face ethical, legal, and cultural standards that are completely different.

Recently, the National Cancer Institute (NCI) established a “think tank,” coordinated by the Program Director Carol Weil, to address the issue of identifiability of biospecimens3. One of the main quandaries that NCI must address is balancing the privacy and wishes of tissue donors against the benefits of an open framework for research data sharing. ASCB has always been a strong supporter of both goals but this is not a simple issue to resolve. Today the reading of only a few dozen independent SNPs in a patient’s genome can allow re-identification in silico without access to tissues. Establishing a framework where tissue donors are protected, where researchers can effectively secure samples, and where vital research is not hindered is a tough problem, one which I expect will shadow us for years to come.

Two years ago, the U.S. Department of Health and Human Services proposed to revisit the major regulation that governs human subjects in research, the so-called common rule4. These revisions required, among other things, that donors give written consent for the use in research of leftover tissues after surgery or biopsies. The devil is in the details, and the way any such rule change will be implemented must ensure that patients receive the maximum respect for their privacy while researchers continue to have appropriate access to human specimens. It is all too easy to err on one side or the other, needlessly putting patients at risk or overreacting in ways that cripple the research enterprise.

It is not surprising that, two years after the first notice was made proposing changes in the common rule, there has been little progress. I think this policy debate is very relevant for the future of cell biology in the “omics” era. Therefore, I was excited to hear that Meredith Wadman is pursuing the WI-38 cell story as a book project. To do it, Wadman is leaving Nature magazine but I’m hoping that Nature’s loss is Biology’s gain. To see these issues clearly, we must look, as Marc Bloch suggested, both ways in time.

  1. Wadman, M. Medical research: cell division. (2013) Nature 498, 422-426, doi:10.1038/498422a
  2. Bloch, M. The Historian's Craft.  197 (Vintage, 1964).
  3. Weil, C. J. et al.  (2013) NCI think tank concerning the identifiability of biospecimens and "omic" data. Genetics in medicine : official journal of the American College of Medical Genetics, doi:10.1038/gim.2013.40
  4. ANPRM for Revision to Common Rule
Stefano Bertuzzi

Dr. Stefano Bertuzzi is the Executive Director of the American Society for Cell Biology. In this position he is responsible, with the ASCB Board, for strategic planning and all operations at the Society to serve the needs of its ~9,000 members and to promote the field of cellular biology and basic science.

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