A recent Trump administration decision to limit funding of research that uses fetal tissue is already disrupting research into major diseases, including AIDS, Down syndrome and diabetes, scientists say.
The controversial federal funding rules, announced seven months ago, are reshaping scientists' research paths and the grants they seek from the National Institutes of Health. Graduate students cannot get training grants if their research involves fetal tissue. Senior researchers are cautioning emerging scientists to avoid this type of research. And a university program that sells mice containing human fetal tissue is forgoing the federal funding it has relied on for nearly three decades, imperiling the work of scores of biomedical researchers who depend on these lab animals.
The disruption is occurring, in part, because the administration has imposed an extra requirement for NIH grant applications that is not yet possible to meet. Under the rewritten rules that took effect early in the fall, a new ethics advisory board must assess all grant requests involving fetal tissue - but the board has not yet been established, and it may not be convened for many months.
"No researcher in their right mind wants to write a grant with fetal tissue right now," said one Boston-area scientist who relies on mice transplanted with such tissue for 85 to 90% of his lab's work, exploring how antibodies could be used to prevent or treat HIV.
The scientist is among several interviewed for this story who spoke on the condition of anonymity because they have received threats from antiabortion activists or have been cautioned by university officials against speaking out.
This portrait of the policy's abrupt impact is based on interviews with more than a dozen senior researchers at nine universities and institutes who use fetal tissue in their studies. Most are speaking publicly about the effects for the first time.
Social conservatives have condemned research involving fetal tissue for decades. The tissue comes from elective abortions, and critics say that it is unethical to use the material and that taxpayer money should not fund any research that is supported by abortion.
Government funding of some uses of the material was forbidden during stretches of the 1970s and 1980s, but it has been consistently permitted since the early 1990s.
The use of fetal tissue in biomedical research dates to the 1950s, when Swedish researchers developed a polio vaccine by using fetal cells. In the late 1980s, researchers pioneered the technique of breeding mice with deficient immune systems and transplanting into them small amounts of immune system tissue from aborted fetuses. These "humanized mice" grow the equivalent of a human immune system, and they have become crucial lab animals in studying certain major diseases.
Fetal tissue has been pivotal to understanding and developing therapies for HIV, cancers, neurological problems, sickle cell disease, eye disorders and other conditions. NIH, by far the nation's largest funding source for biomedical research, has paid for most of this work.
In the fall of 2018, the Department of Health and Human Services launched what officials called an "audit" of fetal tissue use, holding meetings with different constituencies - including ethicists, antiabortion activists and scientists - to explore whether adequate alternative types of cells or tissue could serve the same purpose.
Last June, the administration announced the policy change, making it much more difficult - impossible, some scientists fear - to receive federal funding for research that involves fetal tissue. Officials said the president made the final decision.
The administration's new rules - and researchers' swift response - are delighting social conservatives such as David Prentice, vice president and research director of the Charlotte Lozier Institute, an affiliate of the antiabortion Susan B. Anthony List. "I hope we are well on our way toward better and ethically sourced science," Prentice said.
Grant applications from scientists at universities and other research institutions outside the government are typically evaluated by fellow scientists in a process run by staff at NIH. The new ethics review board, required as part of the fetal tissue funding policy, will add a layer of scrutiny to those fetal tissue applications that have already been ranked high enough to be funded for the first time or renewed. Research underway through existing grants is allowed to continue until the funding runs out, while fetal tissue research inside NIH already has been forbidden under Trump's policy.
According to guidance that NIH issued last July, the new protocol applies to grant applications as of Sept. 25, 2019 but the National Institute for Allergy and Infection Diseases startled scientists a few days ago with a notice that the rules are for any applications starting early last June, when the policy was first announced. NIH spokeswoman Renate Myles said that June timing was the intention all along, but an NIH policy update presentation from early fall specifies the Sept. 25 date.
Asked when the new ethics reviews would begin, NIH did not provide a direct answer. Myles said that NIH is working on "internal activities to stand up" the advisory board. Two days before Christmas, NIH published a notification in the Federal Register saying that HHS plans to publish another Federal Register notice in early 2020 inviting nominations to the board. Between a third and half of its members "will be scientists with substantial accomplishments in biomedical or behavioral research," it noted.
Such notices typically allow two or three months for responses. Then Alex Azar, secretary of the Department of Health and Human Services, which oversees NIH, will appoint the members.
Instead of sending recommendations to NIH, Myles said, the board will deliver its advice directly to Azar, who will have the final say - a process allowed under a section of a 1993 public health law that never has been used before. The board will meet at least once a year, she said, which is less often than NIH's scientific review panels.
Appearing before a House subcommittee in late September, NIH Director Francis Collins acknowledged that this could all take time. "If the board gets set up and can be constituted in a way that they can review [fetal tissue research applications] in a timely manner," Collins testified, "then that is what we expect will happen perhaps in the next year."
One East Coast scientist, who has used fetal tissue for eight years to try to develop therapies marshaling the immune system to cure HIV, said: "Personally, my biggest worry is those ethics panels won't be convened. . . . They may be in the process of being convened, but it could take several years."
Asked repeatedly what will happen if a researcher's current grant ends before the advisory board exists - or between the board's meetings - another NIH spokeswoman declined to answer, saying only that researchers are responsible for knowing when their funding expires and must follow the new rules.
"This policy is as clear as mud as to how this is going to work," said Scott Kitchen, director of the Humanized Mouse Core Laboratory at UCLA, which was the first of its kind when it was created in the early 1990s and now provides such mice to 70 scientists on campus and around the country. "I've asked my way all the way up the ladder" within NIH's National Institute of Allergy and Infectious Diseases and the National Cancer Institute. "I don't think the people I am talking to know."
The lab gets half the money for its basic operations through the university's Center for AIDS Research. But last summer, when the AIDS center applied to NIH to renew its longtime grant, the center's leader and Kitchen made the wrenching decision to leave out the usual request to provide money for the humanized mice.
"We didn't want to risk sinking the entire grant," Kitchen said.
About three-fourths of the researchers who buy mice from the lab rely on NIH grants, Kitchen said. Scientists from private companies can continue their work with the mice, Kitchen said, but the price will rise once the $125,000 from the AIDS center's grant no longer is defraying the cost of transplanting and tending to the animals.
At the University of Wisconsin at Madison, Anita Bhattacharyya studies human brain development and neurological disorders, including Down syndrome. Her lab lately has been using brain cells made from adult stem cells, verifying the results against mice implanted with fetal tissue.
Late in the summer, her grant that covered the fetal tissue work expired. Bhattacharyya has another project in mind that requires fetal tissue, but she has not yet reapplied to NIH. Her concern, she said, is whether the members eventually appointed to the ethics advisory board will be "completely opposed to fetal tissue research so it will not get past the board. So people like me are hesitating to submit anything before we know who will review it."
Another UCLA researcher, Amander Clark, studies infertility and early miscarriages. Like Bhattacharyya, Clark uses fetal tissue as a comparison point - to verify whether the reproductive cells her lab makes from adult stem cells are a good mimic of naturally occurring cells.
Last year, when one of her two major NIH grants came up for renewal, she was mindful that conservatives were pressing the Trump administration to halt fetal tissue funding. "That's when I wrote out the fetal tissue," Clark said. Her other large grant expired in November, and she is in the midst of trying to renew it. "My goal is to write fetal tissue out of that grant, too," she said.
Her lab has four postdoctoral fellows, three graduate students and two technicians. "My concern is that, if I lost the entire grant because there is fetal tissue in it, I need to lay off students and staff. . . . That could be the end of their career. Or, I've brought a trainee from another country, and they've brought their family. I worry about the human toll on the people in my lab."
Clark figures that she will need to fundraise for private money she can spend on fetal tissue research. So far, she has not found any.
The new rules also require researchers to obtain documents from the place that provided the tissue, guaranteeing that it had secured the informed consent of the woman who had an abortion.
In submitting the complex new consent form, "it's not clear to me whether you're allowed to obscure the identity" of the facility, said the Boston-area scientist, who said that abortion clinics and tissue banks might be deterred from donating to science if it becomes easier for the opponents of such work to find out who they are.
For more than a year, the Trump administration has been urging scientists to use alternatives to fetal tissue. NIH has devoted $20 million worth of grants to develop such alternatives.
During a private NIH workshop 13 months ago for invited scientists, HHS's assistant secretary for health, Brett Giroir - who recently was appointed acting commissioner of the Food and Drug Administration until Stephen Hahn assumed office in mid-December - acknowledged that there is currently no adequate substitute for some research.
"I'd like nothing more than to find an alternative," said the Boston-area researcher, who received a slice of the $20 million. His lab is trying to use tissue from adult cadavers, without much success. It is exploring whether tissue could be used from miscarriages - unrestricted under the new rules - though he fears it could be too degraded by the time it reaches his lab.
"We're sort of trying all different fronts," the researcher said. "Everything we've tried so far has not been as good."
Even before the extra ethics scrutiny was to have begun, two scientists say they faced unusual questions about their projects' fetal tissue use. One is a senior researcher at a New England university with large NIH grants that help support his lab's efforts to create the entire human immune system in mice as a path toward treating cancers and infectious diseases.
The researcher was startled when an NIH officer who handles grants asked before the new rules began: What would your alternative approach be if fetal tissue was not available? The researcher replied that he would try to compare new findings with his lab's earlier data, although that "won't get you to an answer as quickly or robustly," he said. He still is waiting to learn whether his renewal has been approved, even though it was submitted before the policy was even announced and reviewed before the rules began.
Megan Sykes, a Columbia University researcher who uses fetal tissue in studying organ and cell transplantation and diabetes, decided to wait beyond a July deadline in hopes of having stronger data for a grant renewal cycle - including data on an alternative to fetal tissue her lab has been trying to develop.
When NIH announced its new rules in July, "I had some severe kicking of myself going on," Sykes said. If the efforts to create the alternative do not yield good results, "I really don't know what I'm going to do."
As scientists - especially those depending on NIH funds - rethink their long-term research plans, they wonder about their field's future.
Sykes is uncertain about funding for a graduate student in her lab who applied for an NIH grant for trainees before the new policy, which prohibits any use of fetal tissue in research supported by training grants.
Jerome Zack, director of UCLA's Center for AIDS Research, said trainees have been attracted to his lab because work with humanized mice "was a flagship technique of ours." Now he worries that a scientist from his lab who he expects to be offered a faculty job within months is "going to have to redirect their program, because the model they've used may not be available."
As for new students eager to do their doctoral work in his lab, Zack said: "I might not put them on a humanized mouse project. . . . Even if the mice were standing in front of you, you can't do it if the grant says you can't do it.
"It's not a small thing. My career has been based on using these tissues," Zack said. In deciding to remove funding for the transplanted mice from the AIDS center's grant, he said, "it was my research going down the drain."