Lines That Divide

Untangling Moral Complexities Related to Fetal Tissue Research

Dr. Susan Mackinnon, an internationally renowned nerve surgeon, sometimes consults a medical textbook written and illustrated by Nazis who used specimens from their victims in their research. She did not know about the book's sordid history until she came across essays by Gerald Weissman and David Williams. This posed a moral dilemma: The Atlas of Topographical and Applied Human Anatomy is still considered one of the best medical reference works on the peripheral nervous system because of its exquisite illustrations.¹ It has helped Mackinnon during difficult surgeries, but its origins are morally abhorrent. Mackinnon's dilemma is not unique, but it is illustrative of a broader ethical question about complicity with evil.

This is the question we at the Center for Bioethics & Human Dignity and the Charlotte Lozier Institute wrestled with in producing a collaborative report on the ethics of fetal tissue research.² I served as managing editor for this report. We invited authors from Orthodox, Catholic, and Protestant Christian traditions, with backgrounds in law, theology, biology, public policy, and bioethics, to address the ethics of using fetal tissue for research. In some ways, the topic was easy. All the contributors adhered to a sanctity-of-life ethic, so there was broad agreement that research requiring "fresh" fetal tissue from elective abortion is unethical.

However, the views became more nuanced when we moved from discussing research using fetal tissue to the related, although legally and ethically distinct, topic of using continuous cell lines that were originally derived from a fetus aborted several decades ago. In this article, we'll look at the similarities and differences between research using fetal tissue and research using cell lines.

Research Using Fetal Tissue from Recent Abortions

Research using fetal tissue dates back to the 1920s, but it was not until the 1960s and 1970s, with the legalization of abortion in Europe and the United States, that research using fetal tissue became more widespread.³ Demand for fetal tissue for transplant purposes declined in the 1990s, not long after a law was passed allowing federal funding for research using fetal tissue. Several experiments involving the transplantation of fetal tissue into Parkinson's patients to relieve their symptoms had poor and sometimes negative outcomes. As a result, the National Institutes of Health (NIH) has not provided federal funding for the transplantation of fetal tissue since 2003.⁴

However, "fresh" fetal tissue, also called primary fetal tissue, is still used in some research. Between 2010 and 2014 about 0.2 percent of NIH funding went toward research involving primary fetal tissue, and more recent numbers show similar funding.⁵

One use of primary fetal tissue is to make "humanized mice," or mice that have been engineered to have a humanlike immune system. These chimeric mice are made using human cells. In some of these chimeras, the human cells came from aborted fetal tissue; in others, they came from non-fetal sources, such as adult bone marrow, the spleen, lymph nodes, or umbilical cord blood. In our report, Tara Sander Lee, David Prentice, and Maria Feeney described alternatives to creating humanized mice that do not involve the death of a fetus.⁶

Fetal tissue is used to study neonatal diseases, such as Zika, and to understand developmental disorders. It can also involve extracting cells from various fetal systems and then growing the cells in culture in a lab for use in research studies. In all these cases, the research is inextricably tied to current and future abortions, making these research practices ethically problematic.

A question we explored in our report is whether a person who has pro-life ethical convictions is essentially "cooperating with evil" by using products of, or by benefiting from, research that used fetal tissue. Ethicists agree that a researcher is responsible for the kind of research he or she conducts, but what about consumers, or even other researchers, who benefit from research done using fetal tissue but who do not personally use fetal tissue in their immediate work?

A colleague likened this to buying or using products or components that may have involved the use of forced labor in their manufacture or at some point in the supply chain. Two proposed solutions are to incentivize ethical practices and to offer alternatives.

The ethics of abortion aside, there are several reasons why scientists might prefer alternatives to using fetal tissue. One is that fetal tissue is expensive and difficult to obtain. Another is that there are more up-to-date techniques in use that don't involve using fetal tissue. Currently, the NIH requires applicants for grants for research requiring primary fetal tissue to justify why their goals cannot be met using alternatives, such as induced pluripotent cells not developed from HFT (human fetal tissue), organoids not developed from HFT, neonatal or adult human tissue, HFT not derived from elective abortion, animal models, in vitro models not developed from HFT, or computational models.⁷

The Ethical Ambiguity of Immortal Cell Lines

The ethics of research using primary fetal tissue is more straightforward than research using cell lines derived from tissue originally collected several decades ago. Two cell lines that are ubiquitous in medical research are the HEK293 lines, derived from a fetus aborted in the 1970s in The Netherlands,⁸ and HeLa cells, derived from cancerous cells obtained in 1951 during a biopsy on a woman named Henrietta Lacks, and then cultured without her consent.⁹ Both HEK293 and HeLa cells were originally obtained in ways that might be considered ethically questionable today.¹⁰ Both are continuous cell lines (also called immortal cell lines), which means the cells can replicate in perpetuity without the need to obtain more cells. The original cells for the HEK293 line were genetically modified to make them grow indefinitely in culture like HeLa cells do, a technique called oncogenic transformation.¹¹

There is also the PER.C6 cell line, a proprietary continuous cell line owned by Johnson & Johnson that was made in 1985 with retinal cells from an aborted eighteen-week-old fetus. Another cell strain, WI-38, was originally made in the 1960s from an aborted three-month-old fetus to study rubella.¹² Although WI-38 is a "finite" cell strain, meaning it has a finite lifetime, researchers can, using careful culturing techniques, make each generation produce more cells.

Research using these cell lines does not require new fetal tissue, because the cells being used in the present are merely the "descendants" of cells derived decades ago. A virus may be grown using one of these cell lines, for example, to produce a vaccine, but the vaccine that is produced does not contain those cells.

Referencing Dignitas Personae and the Vatican's statements on Covid-19 vaccines, as well as the writings of Rev. Kevin Flannery and other theologians, Edward Grant outlined in the report why using products made from immortal cell lines does not constitute cooperation with evil.¹³ However, his article, as well as others in the report, makes a distinction between vaccines, pharmaceuticals, and therapies that use continuous cell lines to test for efficacy early in the research process and those that require the use of cell lines in the manufacture of the vaccine or pharmaceutical. For example, in their Nobel Prize-winning research, Enders, Weller, and Robbins used fetal tissue to grow the polio virus, but Jonas Salk did not use fetal cells to make the polio vaccine.¹⁴ Similarly, HEK293 cells were used during the early research phases to test the Covid-19 mRNA vaccines, but they are not used to manufacture the vaccine.

Perhaps Dr. Mackinnon's decisions about the Nazi-era textbook can help us think about our responsibility in these dilemmas. She no longer assigns the text to her students, and ideally, she would have the option to use another equally detailed text with images that were ethically produced. Until then, she keeps the text in her surgery locker in case she needs to refer to it, but she also keeps the essays with it, as a reminder of where the drawings came from.

Similarly, while it may be morally permissible to use products made from cell lines that have a distant association with abortion, ideally there would be options available that not only allow us to choose therapies aligned with our moral convictions but that also provide a better alternative to those cell lines.

Notes
1. See Susan E. Mackinnon, "When medical information comes from Nazi atrocities," BMJ (2020): bmj.com/content/368/bmj.l7075; Sharon Begley, "The surgeon had a dilemma only a Nazi medical text could resolve. Was it ethical to use it?" STAT News (May 30, 2019): statnews.com/2019/05/30/surgical-dilemma-only-nazi-medical-text-could-resolve.
2. As of this writing, the special report is in press and will be available at https://cbhd.org.
3. Edward J. Grant, "Fetal Tissue Research: Enduring Controversy, New Contexts," CBHD, Special Report on Fetal Tissue Research (in press).
4. David A. Prentice, "Regulation of Human Fetal Tissue Research in the United States," CBHD Special Report on Fetal Tissue Research (in press).
5. Ibid.
6. Feeney and Sander Lee, "The Science of Human Fetal Tissue Research," CBHD, Special Report on Fetal Tissue Research (in press).
7. "Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research," Notice Number NOT-OD-19-128 (July 26, 2019): https://grants.nih.gov/grants/guide/notice-files/NOT-OD-19-128.html; "Update on Changes to NIH Requirements Regarding Proposed Human Fetal Tissue Research" NOT-OD-21-111 (April 16, 2021): https://grants.nih.gov/grants/guide/notice-files/NOT-OD-21-111.html.
8. See transcript of a meeting of the Vaccines and Related Biological Products Advisory Committee, FDA Center for Biologics Evaluation and Research (May 16, 2001): https://web.archive.org/web/20170516050447/https://www.fda.gov/ohrms/dockets/ac/01/transcripts/3750t1_01.pdf. Whether the original fetus came from an abortion or miscarriage is unclear, but likely from aborted fetal tissue.
9. HEK293 cells are second to Chinese hamster ovary cells in biopharmaceuticals and second to HeLa cells in biochemical studies. See "Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives," Crit Rev Biotechnol (Nov. 1, 2016): ncbi.nlm.nih.gov/pmc/articles/PMC5152558.
10. See Rebecca Skloot, The Immortal Life of Henrietta Lacks (Crown, 2011), for more on the origins of HeLa cells.
11. Harvey Lodish et al., Molecular Cell Biology, 4th ed. (W.H. Freeman, 2000), 183–186.
12. See L. Hayflick and P. S. Moorhead, "The Serial Cultivation of Human Diploid Cell Strains, Experimental Cell Research (1961): https://cogforlife.org/Hayflick1961ExpCell.pdf; see also "Human Cell Strains in Vaccine Development": historyofvaccines.org/content/articles/human-cell-strains-vaccine-development.
13. Edward J. Grant, "The Ethics of Fetal Tissue Research: Catholic Perspective" CBHD Special Report on Fetal Tissue Research (in press); Congregation for the Doctrine of Faith, Dignitas Personae (Sept. 8, 2008): https://www.vatican.va/roman_curia/congregations/cfaith/documents/rc_con_cfaith_doc_20081208_dignitas-personae_en.html; Congregation for the Doctrine of Faith, "Note on the Morality of Using Some Anti-Covid-19 Vaccines" (Dec. 21, 2020): https://www.vatican.va/roman_curia/congregations/cfaith/documents/rc_con_cfaith_doc_20201221_nota-vaccini-anticovid_en.html.
14. Grant, ibid.