At several labs across the US, researchers use fetal tissue from humans to investigate everything from viral infections to the developing brain. Such studies have been ongoing for decades, as have politically fraught debates about this research, because it primarily relies on tissue donated after terminated pregnancies.
Last summer, President Donald Trumps administration announced that it would be placing restrictions on experiments involving fetal tissue obtained from elective abortions, which included banning government scientists from using this material for research and applying increased scrutiny for National Institutes of Health (NIH) grant proposals from nongovernmental scientists.
Researchers say that the new restrictions on fetal tissue research have required them to change their plans for future work or to search for alternative sources of funding. Its impacted almost all of the facets of the lab, says Carolyn Coyne, a microbiologist at the University of Pittsburgh who uses fetal tissue to study how viruses penetrate the placenta.
Its affected pretty much every grant application that that weve written.
Mana Parast, University of California, San Deigo
One of the main concerns, according to several researchers who spoke to The Scientist,is the lack of clarity regarding what the NIH will require in grant applications for this work. The Department of Health and Human Services (HHS), which oversees the NIH, has stated that it would put together a new ethics advisory board to review such proposals. Last week (February 20), HHS posted a notice indicating its intent to convene the NIHs fetal tissue ethics advisory board in 2020. In a written statement to The Scientist,the NIH states that it is in the process of setting up the Ethics Advisory Board for the purpose of evaluating research proposing the use of human fetal tissue from elective abortion.
Scientists are waiting to find out who will be appointed to the board and how it will evaluate proposals once it convenes. [Well] see whether the administration is going to act in good faith and appoint a decent ethics review committee, or if theyre going to ignore the value of the scientific and medical research that needs to be done in this area and let ideology weigh out over logic, says Lawrence Goldstein, a stem cell scientist at the University of California, San Diego, whose lab has worked with fetal cells in the past. The fetal tissue that were talking aboutif we dont use it for research, it will be discarded. Thats the choice. Discard the fetal tissue in the in the trash, or use it for valuable research.
This is not the first time such a ban has been put in place. In 1988, former US President Ronald Reagan placed similar restrictions on federal funding for fetal tissue studies, which stayed in place until President Bill Clinton overturned them during the first year of his term in 1993.
Fetal tissue used for research is primarily obtained from elective abortions, which women can consent to donate after deciding to terminate a pregnancy. This is because there are some major limitations to tissue obtained through other means, such as miscarriages, according to Anita Bhattacharyya, a stem cell scientist at the University of Wisconsin-Madisons Waisman Center. Supply is limited and the underlying factors that lead to pregnancy loss can complicate experiments. On top of that, such events often happen unexpectedly, meaning that the collected tissue is not always intact. We would worry about using poor quality tissue as a foundation for the work we do, says Bhattacharyya, who uses donated fetal brain tissue to study brain development and disorders such as Down syndrome and fragile X syndrome.
Bhattacharyya says that although her lab currently has the tissue it needs to complete experiments from a prior grant, shes not comfortable submitting proposals for studies that require obtaining new fetal tissue. Its because I dont know whats going to happen. If I spend hours writing a grant that I think is really good science, and I send it to NIH . . . its going to get stuck there, Bhattacharyya explains. Were so busy as scientists that to just write a grant that isnt going to go anywhere is a waste of our time.
As such, her projects may suffer. According to Bhattacharyya, not only is brain development difficult to study in model organisms such as rodents, but fragile X and Down syndrome in particular are difficult, if not impossible, to model in animals. Induced pluripotent stem cells (iPSCs), which can be generated by reprogramming cells from skin or blood in adults, have offered an alternative means of studying the development and disorders of the brain, yet researchers still need to validate the results they obtain, Bhattacharyya says. Really, the only way to do that is using fetal tissue.
In addition to cells and tissue from the fetus itself, the restrictions on NIH funding were also applied to other biological materials obtained in the process of abortions, such as umbilical cord, placenta, and amniotic fluid. While some of these can be useful to scientists when collected after birth, placental tissue obtained in this way has limitations. Full term placentas are actually aged tissues, explains Coyne. If were studying a full-term placenta post-delivery, the gnawing question is: Has that placenta changed from the placenta that exists in the first or second trimester?
Mana Parast, a stem cell and placental biologist at the University of California, San Diego, who studies placental development and disorders, tells The Scientist that while the policy change has left ongoing projects unscathed, its affected pretty much every grant application that that weve written since then. While Parasts team has used fetal tissue in the past, they are now focusing on using iPSC-based models. However, like Bhattacharyya, she notes that this isnt the perfect solutionas these models are fairly new and not yet broadly accepted, it is still necessary to validate them with cells from human placentas.
Coyne says that in addition to limiting access to grants for her research, the restrictions have also made it more difficult to procure tissue. A lot of major medical schools have federally funded tissue banks, Coyne explains. Our institutional tissue bank has been affected by this such that we cant obtain tissue from elective terminations anymore.
For researchers who have been able to obtain funding from alternative sources, such as philanthropists or private foundations, the effects of the restrictions have been minimal. Thomas Reh, a biologist at the University of Washington whose team uses fetal tissue to study the developing retina, says that his groups work is currently supported by a grant from the Open Philanthropy Project, a nonprofit organization. When the political climate gets more restrictive, private donors will often step in, Reh says. I wont say that works for everybody, or that it works all the time. At least in my own case, this is whats allowed me to sort of fill these gaps when [restrictions on fetal tissue] happen.
Its the next generation of trainees that are going to be most impacted, not just because they cant get funding, but if I were one of them, I would think to myself, is this really an area that I want to specialize in?
Carolyn Coyne, University of Pittsburgh
Andrew McMahon, a stem cell scientist at the University of Southern California, still has about a year left before he needs to apply for more funding, and hes started looking into potential alternatives to NIH. My understanding is that its not entirely clear at the moment what that process is going to be, McMahon says. Ive been using the time to obtain non-NIH funding to support aspects of the research that I would have tried to get NIH funding [for] in the future.
Private funds are not available to everyone, and can be more difficult for researchers in some fields to obtain than others. For some of the disorders that I work on, the major private funding foundation does not allow fetal tissue research, Bhattacharyya says. And sometimes the foundation funding can be quite a bit less than NIH funding.
For researchers in some states, nonprofits are not the only option. In California, the states stem cell agency, the California Institute for Regenerative Medicine (CIRM) has provided funding for stem cell studies using fetal tissue since it was founded in 2004. That fund is about to run out, but a bill that would provide $5.5 billion in funding to CIRM will come before voters in November.
That will hopefully provide funding for areas of fetal tissue research that involves stem cells, Goldstein says. But . . . its ridiculous to rely on one or two states to self-fund, because we dont have all of the best and brightest [scientists], and it means lots of students and postdocs will train in areas where federal training support will be unavailable to them.
Goldstein isnt the only one concerned that the most profound effect of the governments restrictions will be on early-career investigators and trainees. While established researchers may be able to circumvent the effects of the restrictions in the short term, the ramifications for trainees in this field will likely be much longer-lasting, Coyne says. Its the next generation of trainees that are going to be most impacted, not just because they cant get funding, but if I were one of them, I would think to myself, is this really an area that I want to specialize in and get into?
One scientist, who asked to remain anonymous for fear of being harassed by anti-abortion activists, tells The Scientist that the restrictions have been a source of huge stress and anxiety for his lab, which he only established a few years ago. He adds that while his team has pivoted to using animal models and organoids generated from iPSCs, these are imperfect models of the developing human brain, which is the focus of his work.
It makes no sense to limit this research, given that the tissue from abortions will get discarded now that donation is not an option, Parast says. Were not talking about encouraging this procedurewere trying to use the material from patients who have already decided to undergo this procedure in order to be able to help other women.
Diana Kwon is a Berlin-based freelance journalist. Follow her on Twitter@DianaMKwon.
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