The Facts on Human-Animal Chimeras

Q: Does the National Institutes of Health fund research on human-animal chimeras, or organisms that are part-human, part-other animal? 

A: With some exceptions, the NIH doesn’t fund research on human-animal chimeras. But the agency has proposed a rule to widen the scope of research it funds in this area.

FULL QUESTION

I’ve been seeing some news online about the ban on the development of animal/human DNA hybrids has been lifted. Is this true?

FULL ANSWER

In Greek mythology, a “chimera” is a fire-breathing creature that’s part-lion, part-goat and part-snake. Within science, the term applies to a much less fantastical organism.

According to the Merriam-Webster Medical Dictionary, created in collaboration with the NIH, a “chimera” is “an individual, organ, or part containing tissue with two or more genetically distinct populations of cells.” Normally, all the cells in an organism’s body contain the same genes. But there are exceptions.

For example, a once-pregnant woman could be considered a chimera because she can carry her baby’s cells in her body for years, if not for the rest of her life. People also can be born chimeras if two fertilized eggs fuse in early development. In both cases, a single organism is composed of cells that contain different genes.

One of our readers sent us a question about yet another kind of chimera — one made up of cells from humans and another species — asking whether the “ban” on these organisms has been lifted.

He also forwarded us three sources of conflicting information: a video posted to Facebook in June by the science news outlet Futurism and articles published in the journal Nature and on NPR’s website in August 2016.

The headlines of both the Nature and NPR articles state that the NIH had plans to lift a funding “ban” on human-animal chimeras, but it hadn’t yet done so. The first line of text in the Futurism video says “a ban on human/animal genetic hybrids was just lifted.” This left our reader confused. Has the ban been lifted or not?

To date, it’s still in place. But it wasn’t a complete ban to begin with. The NIH has funded some research on human-animal chimeras and scientists can obtain funding from non-public sources, which they have. The NIH also has proposed to widen the scope of research it supports in this area, though it’s unclear when a final rule will be put in place.

Why Study Human-Animal Chimeras?

In order to understand why the NIH has changed its policies on human-animal chimera research over time, it’s important to understand why scientists study these organisms in the first place.

A great deal of experiments in biology are conducted on non-human animals, from fish to monkeys. Some researchers are interested in the biology of these particular animals. Other use them as a stepping stone, or model organisms, for understanding human biology. This is because there are many experiments that researchers cannot conduct on humans for ethical reasons.

However, research on other animals doesn’t always translate to humans. For example, a mouse’s immune system may be similar to a human’s, but it’s not exactly the same, so very few drug treatments developed in these rodents end up working in people. Along the same lines, experiments conducted on human cells grown in a culture don’t always reflect how those same cells might function inside the body.

That’s where human-animal chimeras come in. They allow researchers to experiment on human cells inside a living organism. The NIH further elaborates on the potential for this kind of research in an FAQ page on human-animal chimera research.

NIH, February 2017: Some scientists hope the human cells will develop into specific tissues or organs for potential transplant purposes, or for drug testing. Other researchers are exploring the developmental nature of particular types of human cells, which may yield important insight into human biology and disease development. Animal models with human cells in the brain can be used to study many human brain diseases, including Parkinson’s, Alzheimer’s, and schizophrenia, and may be useful models for testing new drugs. Furthermore, these animal models could be used to study whether introduction of therapeutic human cells can improve outcomes for diseases that are caused by the death or dysfunction of neural or other brain cells, prior to testing the cells in people.

Human-Animal Chimeras and Stem Cells

The NIH’s changing policy on funding for human-animal chimera research is tied to the agency’s changing policy on funding for stem cell research. This is because human-animal chimeras are created by inserting human stem cells into other animals.

What’s a stem cell? Generally, they are unspecialized cells that can be induced to become specialized cells, which take on specific roles within the body. They’re also capable of dividing to produce more cells for long periods of time.

But there are different kinds of stem cells. Adult, or somatic, stems cells reside among specialized cells of a specific kind of tissue or organ. Their main role is to repair and maintain the tissues in a specific area of the body.

Unlike adult stem cells, embryonic stems cells can become any cell in the body. This makes them pluripotent. Adult stems cells can only become any cell within the organ or tissue in which they are found. Also, unlike adult stem cells, embryonic stem cells can grow easily in the lab, making them the preferred choice for disease treatments and experiments.

In 2007, scientists also developed human-induced pluripotent stem cells by taking adult cells and reprogramming them to take on the characteristics of embryonic stem cells. Using these cells in experiments sidesteps some of the ethical issues involved with using embryonic stem cells, which come from human embryos. Still, it’s unclear whether they’re identical to embryonic stem cells, so researchers might prefer using one type of stem cell in their specific experiments over another.

Changing Policies Human-Animal Chimeras

Researchers first grew human embryonic stem cells in the lab in 1998, and policy on stem cells and human-animal chimeras followed two years later.

In August 2000, under President Bill Clinton, the NIH published a final rule that prohibited funding “[r]esearch in which human pluripotent stem cells are combined with an animal embryo,” along with providing the first guidelines for the kind of stem cell research that the agency would fund.

Since scientists hadn’t yet developed induced pluripotent stem cells, this rule only applied to embryonic stem cells.

On Aug. 9, 2001, President George W. Bush limited the scope of stem cell research that could be federally funded to experiments using embryonic stem cell lines that had been derived prior to that day, among other limitations.

In November 2001, his administration also revoked the 2000 rule. But an NIH spokesperson told us, “The policy that was in place under President Bush did not address human-animal chimeras specifically, and therefore did not prohibit them.”

However, in his 2006 State of the Union address, Bush urged Congress to “pass legislation to prohibit the most egregious abuses of medical research,” including “creating human-animal hybrids.” To date, Congress hasn’t outlawed the creation of human-animal chimeras, though multiple attempts have been made.

In July 2009, under President Barack Obama, the NIH finalized a new set of guidelines for stem cell research that opened up public funding for some human-animal chimera research.

For example, researchers could apply for federal funding if their experiment introduced human pluripotent stem cells into rodent or pig embryos in the very early stages of development. But doing the same experiment on chimpanzees or monkeys couldn’t get federal funding.

Why allow experiments that work with pig embryos in the early stages, but not non-human primates? A 2005 National Academies of Sciences, Engineering, and Medicine report explains why. “These kinds of studies could produce creatures in which the lines between human and nonhuman primates are blurred, a development that could threaten to undermine human dignity,” the report says.

Scientists also couldn’t get federal funding for experiments that entailed breeding human-animal chimeras under this rule, which the 2005 National Academies report also recommended against. But they could get funding for research that used non-pluripotent stem cells, such as adult stem cells.

Then in September 2015, the NIH again scaled back the kind of human-animal chimera research it would fund, at least temporarily. This is the ban our reader asked about.

The “NIH would like to undertake a deliberative process to evaluate the state of the science in this area, the ethical issues that should be considered, and the relevant animal welfare concerns associated with these types of studies,” the rule said.

Under the 2015 policy, the NIH said it wouldn’t fund any research that inserts human pluripotent stem cells into non-human vertebrates, which includes fish to mammals, in the earliest stages of development. Inserting these cells in the later stages of development still could potentially be federally funded though.

In August 2016, the agency then proposed to widen the scope of research it would fund in this area. The new rule, like the 2009 rule, would prohibit funding for experiments that inject human pluripotent stem cells into non-human primates in the very early stages of development, but would allow these experiments in pigs or rodents. Experiments that breed human-animal chimeras still wouldn’t be funded.

The new rule also would establish a steering committee, in addition to the NIH’s grant review board, that would evaluate projects in this area of research. The committee would be composed of federal employees.

Back in August 2016, Carrie Wolinetz, the associate director for science policy at the NIH, told Nature that the agency hoped to issue a final rule by January of this year. But that never happened — the 2015 restrictions are still in place. When we contacted the NIH to ask when this final rule might be released, a spokesperson told us, “At this point, I cannot provide a timeframe.”

The Ethics of Human-Animal Chimera Research

The 2016 proposed rule was born out of a workshop the NIH convened in November 2015 that aimed to evaluate how far the science in this area has advanced, along with any ethical issues that might go along with those advancements.

The proposed rule explains that the experts at the workshop emphasized that the area of research still faces “significant challenges.” Still, there’s “clear interest and potential in producing animal models with human tissues or organs for studying human development, disease pathology, and eventually organ transplantation,” the workshop’s experts concluded.

Along with these advances come “questions regarding where the human cells might go in the developing animal and how they might function,” the rule adds. For example, could inserting human pluripotent stem cells into a mouse or pig in the early stages of development cause the animal to take on human-like cognitive abilities?

Jonathan D. Moreno, a bioethics professor at the University of Pennsylvania, told us in a phone interview that there are actually two kinds of debates experts have when deciding policy on funding human-animal chimera research — an “empirical problem” and a cultural or “symbolic problem.” These two problems often get muddled together by those in public discussions of the research, he said. 

Moreno, who also co-chaired the 2005 National Academies report on stem cell research, said the empirical problem asks what evidence there is to support the idea that inserting human pluripotent stem cells into the developing embryos of other animals would give them human cognitive abilities. Given the infancy of this kind of research, a lot is still unknown, though Moreno doubts the likelihood of producing a “talking mouse” from these experiments. 

The symbolic, or cultural, problem asks whether these kinds of experiments affront human dignity by blurring the line between humans and other animals. However, that line is already blurred, according to the 2005 National Academies report.

The perception that it is unnatural to mix different species is rooted in “the idea that there are fixed species,” the report says. But there’s “general agreement in the scientific community” that categorization of species “are to some extent arbitrary,” the report adds.

Overall, it’s unclear what direction the NIH will go on its human-animal chimera policy under the Trump administration.