By Meredith Wadman
Biological scientists currently have no better alternatives to using fetal tissue to give mice human-like immune systems, concluded scientists who convened yesterday at a National Institutes of Health (NIH) workshop to discuss the issue. Such humanized mice “remain the ‘gold standard’” for many kinds of studies, the scientists said, and any alternative animal model should be tested against such mice before being widely adopted, according to a report on the closed-door workshop issued tonight by the Department of Health and Human Services (HHS), NIH’s parent department.
The workshop came amidst a growing storm surrounding humanized mice, which are often created using human fetal tissue from elective abortions that would otherwise be discarded. Anti-abortion groups are pushing President Donald Trump’s administration to stop funding research involving human fetal tissue. And they are calling on Trump to fire NIH Director Francis Collins, who last week spoke out on the need for such research.
In response to pressure from abortion opponents, this past September HHS announced it was launching a review of federally-funded fetal tissue research. It cancelled one contract that the Food and Drug Administration relied on to generate humanized mice for drug testing. It has also taken steps to stop some NIH laboratories from acquiring new fetal tissue. And earlier this month, NIH announced that it would be spending $20 million over the next 2 years to study alternatives to humanized mice and other uses of fetal tissue in research.
Those potential mouse alternatives were the subject of yesterday’s workshop in Rockville, Maryland, which was sponsored by NIH’s National Institute on Allergy and Infectious Diseases (NIAID) and attended by several dozen scientists. According to HHS’s workshop report (see below), the researchers said a “preponderance of data” supports a preference for using humanized mice to test certain kinds of drugs and explore diseases including HIV/AIDS. That data, it states, indicates that the mice are superior to other mice that don’t rely on engrafted fetal tissue, because the transplanted tissue takes root better, differentiates better, and survives and functions better.
But this conclusion, HHS emphasized in its statement, “is not intended to pre-judge the outcome” of the department’s ongoing review of fetal tissue research.
In an additional statement tonight to ScienceInsider, an HHS spokeswoman also contradicted a report published yesterday by the Washington Post that the department has reversed a decision to limit one relevant federal contract. Earlier this month, HHS told researchers who execute a key NIH contract to develop humanized mice at the University of California, San Francisco (UCSF), that their funding would be renewed for just 90 days, not the usual 1 year. The Post reported that restriction was being lifted. But HHS said today that the UCSF “contract remains on the 90-day extension to ensure continuity of service until the audit is completed and a final decision can be made about the contract.”
In response to a question from ScienceInsider, an HHS spokesperson again declined to address whether the HHS review, being led by Assistant Secretary for Health Brett Giroir, will next examine the scores of NIH grants to university researchers that involve fetal tissue. These extramural grants represent about $80 million of the roughly $100 million that NIH estimates it spends on research projects that use fetal tissue.
The HHS spokesperson confirmed that Giroir, in addressing the scientists at yesterday’s workshop, told them that the administration had not decided to halt any NIH funding. Rather, he said, the question is under review.
But according to one workshop participant, Stanford University immunologist Irving Weissman, who joined the meeting by phone, an NIAID official assured the scientists at the meeting that their research is not in danger. That official, Dan Rotrosen, Director of NIAID’s Division of Allergy, Immunology and Transplantation, told participants that “NIAID will not pause or ban funding of fetal tissue research so long as there is no profit motive, so long as there is proper informed consent for the disposition of the fetal remains for research, and so long as the consent laws are consistent within each individual state’s laws on the issue,” Weissman wrote in an email. (The NIAID funds many, but not nearly all, of the scores of NIH research projects that rely in some measure on fetal tissue.)
Those statements, first reported by the Post, provoked outrage today among abortion opponents. “This is the second time that senior NIH officials have jumped ahead of the Administration’s ongoing audit process – both times reaching conclusions that are out of step with the President’s pro-life agenda,” said Marjorie Dannenfelser, the president of the Susan B. Anthony List in Washington, D.C., in a statement. “If these statements are allowed to stand, and policy continues unchanged, it would be the first time the Trump Administration has broken with the pro-life movement. Pro-life voters do not want to foot the bill for any research that involves harvesting the body parts of unborn children from induced abortion.”
Yesterday, other anti-abortion groups also called for the ouster of NIH Director Francis Collins, who last week made comments defending fetal tissue research. “Director Collins must be replaced with someone who recognizes that children who are killed by abortion should be mourned, not experimented on,” Lila Rose, the director of the abortion-opposing group Live Action said in a statement yesterday. “Collins’ actions are inconsistent with the pro-life policies of this administration and with the consensus of Americans who oppose entangling taxpayer dollars with abortion. It is time for his departure,” said Jeanne Mancini, President of March for Life in Washington, D.C., in a statement.
So far, those calls have not elicited any public response from HHS or the White House.
Here is the HHS summary of the workshop:
The following is a summary of the workshop, Recent Advances and Opportunities in the Development and Use of Humanized Immune System Mouse Models. This summary reflects the opinions of the meeting participants. It does not represent the official position of the U.S. Department of Health and Human Services nor the National Institutes of Health.
On December 18, 2018, the National Institute of Allergy and Infectious Diseases (NIAID), in coordination with the National Institutes of Health (NIH) Office of the Director and the U.S. Department of Health and Human Services (HHS), conducted a workshop to assess recent advances and opportunities in the development and use of humanized immune system (HIS) mouse models, in which the immune system of the mouse is partially replaced with human immune cells and tissues.
Participants included leading scientists in the fields of immune system development and function, transplant immunology, autoimmunity, and infectious disease research. Adm. Brett Giroir, Assistant Secretary of Health at HHS, welcomed the participants and described HHS interest in this area, including a clearer understanding of the limitations and adequacy of existing HIS models, and the possibility of developing scientifically validated alternatives to the use of human fetal tissue. Dr. Daniel Rotrosen, Director of NIAID’s Division of Allergy, Immunology and Transplantation, provided an overview of the workshop goals and expected topics of discussion, including: evaluation of the features, strengths and limitations of current HIS mouse models; procedures to compare HIS models made from fetal and non-fetal tissue sources; and studies that would be required to fully characterize and standardize these models. Dr. Lawrence Tabak, NIH Principal Deputy Director, provided brief introductory comments on behalf of NIH.
Dr. Leonard Shultz of the Jackson Laboratory provided a comprehensive summary of HIS mouse model development and usage from 1988 to the present. In the breakout sessions that followed, participants discussed the strengths and limitations of various HIS mouse models and provided opinions on ways to optimize HIS models for the development of vaccines and therapeutics for infectious and immune-mediated diseases and cancer. The meeting participants reconvened for reports from the two breakout groups and a final discussion that resulted in the following summary points:
- Major scientific advances have been made in understanding infectious disease pathogenesis and development of therapeutics using HIS mouse models made with human fetal tissue.
- No single humanized immune system model is universally appropriate or optimal for all applications.
- Various models can recapitulate key aspects of human T cell immunity; existing models are less able to recapitulate human innate immunity and antibody responses regardless of tissue source. Improvements in modeling antibody responses should be a focus of future work and may be particularly important for advances in vaccinology and in modeling infectious, autoimmune, and allergic diseases.
- Few direct comparisons have been conducted of HIS mice derived using fetal vs. non-fetal human tissue sources.
- Meeting participants included investigators working on fetal tissue-derived and non-fetal tissue-derived HIS models. Considering published data and other information shared at this meeting, participants expressed the opinion that fetal tissue-derived HIS models remain the “gold standard” to which other model systems should be compared. This preference is based on the preponderance of data indicating superior engraftment, differentiation, survival and function of the adaptive immune cells (particularly T cells) in fetal tissue-derived models.
- Following the breakout sessions, there was strong opinion that work should proceed on a variety of models derived with fetal tissues or from alternative sources.
This summary is not intended to pre-judge the outcome of the HHS audit.
Source: Science Mag