NIH to lift moratorium on human—animal chimera research

The US National Institutes of Health (NIH) is considering lifting a ban on the funding of research to human-animal 'chimeras' and replacing it with an ethical review process. If agreed, the move could result in the creation of animal-chimera embryos for research in the USA.

Guidelines produced in 2009 by the NIH currently prohibit the use of federal funds for research involving the insertion of human pluripotent stem cells into nonhuman primate blastocysts. Researchers are also not allowed to breed animals that have had human stem cells inserted into their germline.

The NIH extended the ban in 2015, imposing a funding moratorium on such research involving pre-blastocyst stage embryos prior to gastrulation (when the three germ layers start to appear), and applying this restriction to all animal embryos. The decision put on hold research to create sheep–human or pig–human chimera embryos to generate organs, explains Science – although no such funding applications had yet been received.

The latest announcement by the NIH marks the start of a one-month consultation on its proposal to replace the moratorium with an internal steering committee, which would make funding decisions on research that involves inserting human stem cells into all vertebrate animal embryos up to the end of the gastrulation stage – except for primate embryos, which would only be considered after blastocyst stage.

The consultation also includes a proposal for special approval for the introduction of any human cell into animal embryos post-gastrulation, except for rodents, where it would contribute to brain function.

'[The panel review] would be an extra set of eyes to make sure we're not triggering any animal-welfare issues,' said NIH associate director for science policy, Dr Carrie Wolinetz, who announced the consultation.

Dr Wolinetz said that advances in stem cell and genome-editing technology have meant that scientists are increasingly interested in the potential of growing human organs for drug testing, disease modelling and – in the future – transplantation, by inserting stem cells into animal embryos. When the NIH imposed the moratorium last year, it felt further policy work may be needed, but since then it has reviewed the science and consulted experts in the field.

Dr Steven Goldman, a neuroscientist from the University of Rochester in New York, said the new guidelines are 'more intelligent from the standpoint of where the science is'. Others have questioned the NIH's focus on the embryo's developmental stages. Dr Ali Brivanlou, from Rockefeller University in New York, said more attention should be paid to the percentage of animal material that is mixed with human cells.

Professor Sean Wu, a stem cell researcher at Stanford University in California, who co-wrote a letter opposing the moratorium last year (see BioNews 827), said the draft policy was a 'step in the right direction', but that 'we still don't know what the outcome will be case by case'. If created, the NIH's ethical review panel would include scientists, ethicists and animal welfare experts, and it would make funding decisions on a case-by-case basis.

While there is no federal legislation that prohibits the creation of chimera embryos in the USA, the NIH's funding policy is considered heavily influential. Dr Wolinetz hopes that proposing to extend the prohibition on inserting human cells into primates prior to blastocyst stage, and to include all human cells – and not just stem cells – in the ban on breeding chimeric animals, will help 'the NIH research community to move this promising area of science forward in a responsible manner'.

In the UK, it is lawful to create admixed embryos (by inserting human genetic material into a denucleated animal egg) under licence from the HFEA. The HFEA has given approval for the creation of cytoplasmic hybrid embryos on three occasions, and the first human–animal hybrid embryo was created in 2008. But since then funding has reportedly been hard to come by (see BioNews 491). The implantation of a chimera or hybrid embryo into a human or its development beyond 14 days is prohibited under statute.