The Laws of Man and Beast

While the mythical Chimera is the stuff of fantasy, researchers across the country are developing their own real-life chimeras – animals that are bred to incorporate the cells of other animals or humans – in an effort to better study human diseases or to create more viable organs for people needing transplants. 

But as scientists continue to create more varied chimeras – especially those that have some amount of human brain matter – questions continue to rise from ethicists, religious groups, and even other biomedical researchers, about the types of limitations that should be set on the scientific community.

Those questions resulted in the National Academy of Sciences (NAS), which advises the government on various scientific matters, releasing a set of ethical guidelines on April 26 for the creation of such hybrid organisms. 

Published as part of a larger report on human embryonic stem cell research – human embryonic stem cells are often implanted in animal embryos to create “chimeras” – the NAS guidelines discourage the transplantation of animal embryonic stem cells into human embryos. Further, the report suggests that researchers should establish and seek approval from as-yet-unformed Embryonic Stem Cell Research Oversight committees, which should include legal and ethics experts, before transplanting human embryonic stem cells into an animal. 

The guidelines also say that any chimera possessing human cells should not be allowed to breed, and that human stem cells should not be put into other primates, such as chimpanzees, where a more human-like brain might be apt to develop. The introduction of human stem cells into the developing embryo of another animal, the guidelines say, should be done only in cases where no other alternatives exist.

While the restrictive suggestions may hamper certain types of research, Dr. Esmail Zanjani, chairman of the Department of Animal Biotechnology at the University of Nevada, sees the recent guidelines as “perfectly legitimate…the dos and don’ts are perfectly clear.”

For Zanjani and his team, these rules wouldn’t restrict the types of research they are conducting. They have introduced adult stem cells from human bone marrow into sheep embryos in hopes of creating a ready supply of organs, particularly livers, which could someday be transplanted into humans. These “humanized” sheep livers would be more likely to regenerate (just like a healthy human liver) and are less likely to be rejected by a human recipient – since they would contain that person’s own human cells.

But creating chimeras isn’t only about curing disease by creating more transplant-friendly organs and blood for human recipients. For many researchers, it’s the only alternative to understanding the workings of human diseases – and experimenting to find possible cures.

Researchers at the world-renowned Mayo Clinic in Minnesota announced last year that they had created pigs with human blood by introducing human stem cells into gestating pig fetuses. Meanwhile, to help in his research to better understand the human brain and develop treatment for degenerative diseases such as Alzheimer’s and ALS, Dr. Irv Weissman, director of Stanford University’s Institute of Cancer and Stem Cell Biology, has made mice that have brains which are one percent human. 

Weissman hailed the guidelines overall as “a significant step forward for the field of stem cell research.” But he also underscored the importance of chimerical animals as “crucial” to modeling human genetic diseases and testing therapies to treat them.

Previous to the release of the guidelines, Weissman had proposed a new project to create chimerical mice that had 100 percent human nerve cells in their brains – a plan that he had already asked a committee of bioethicists and medical researchers to review.  Weissman says he will not pursue further experiments without the agreement of that panel and his colleagues, and that, if he does move forward, he will be careful to “ensure that these mice don’t take on any human characteristics, such as altered brain structures.”

“Experiments like these,” Weissman says, “need societal approval – as well as our scientific enthusiasm for them.”

Indeed, while these guidelines do provide an overarching ethics framework for researchers, they do not regulate their work or impose penalties for violating the suggested guidelines. Some opponents of human-chimera research believe that the United States should set federal limits, with the force of law behind them, or outlaw the creation of chimeras altogether (see The Notebook). Canada has already taken a stand by effectively banning the creation of chimeras last year, with the introduction of its Assisted Human Reproduction Act, which prohibits placing animal cells in a human embryo or human cells in an animal embryo.

The NAS guidelines, though, stop short of recommending those types of sanctions, and leave the door open to lots of potential experiments – and what crosses the line is still up to interpretation. 

But even some within the scientific community are questioning whether these cross-species creations are blurring what should be a distinct line between human and animal. 

Stuart Newman, a developmental biologist with New York Medical College in Valhalla, New York, filed a patent application to create a human-chimpanzee hybrid more than seven years ago, which was turned down by the U.S. Patent Office earlier this year. The idea behind filing the patent, Newman says, was not to actually create a so-called “humanzee,” but to “alert people of some of the more troubling things that [could] come out of this scientific work.”

In recent years, Newman says this field of biomedical research has been “distorted” by the potential for financial gain, in light of the spectacular attention cloning and other areas of bioengineering have received. He’s concerned that these early chimerical developments – many of which he believes are justified – could lead to the creation of animals that border too closely on human, or to creating “custom-made” humans. 

Others in the medical field have expressed a more near-term – and decidedly more ecumenical – disdain for the ambitious development of animal-human hybrids. 

Dr. David Stevens, executive director of the Christian Medical and Dental Associations, based in Bristol, Tenn., believes that the creation of chimeras is all right as long as it does not utilize human embryonic stem cells,  which he sees as morally wrong, and does not “get to the point of changing the nature of the animal or the human being.” 

By this definition, using human adult cells to make pig or sheep organs more viable for transplant to a human recipient – without changing that animal’s natural behavior or appearance – would be acceptable. But to modify an animal so that it would bear any resemblance to a human would not only “create a ‘yuck’ factor,” according to Stevens, it would also violate the moral and ethical teachings of The Bible, which dictate that human beings “have stewardship” over animals, and it could even “alter the essence” of a human being.

The role of God and moral values in science is certainly an area of great debate lately – as witnessed by the current evolution hearings in Kansas, debating how to teach the ideas of evolution versus intelligent design to public school students. Balancing the need for scientific freedom and the pressure to impose tighter ethical restrictions means that these recent guidelines may well be just the first step in a long road to reaching a chimerical compromise. 

Dr. Richard Hynes, MIT’s Daniel K. Ludwig Professor for Cancer Research, and one of the co-chairs of the committee that helped put together the NAS report, says it’s “likely these guidelines will need to be tuned…it just isn’t possible to anticipate what might come up.”

But he believes that putting a basic framework out there will “allay the controversy somewhat…we don’t want people to think of this as just [making] monsters.