The definition of humanity is sacrosanct to many people. As science does, that line continues to blur. Stem cells have long been an ethical minefield for scientists to navigate for funding. Even something as common as an organ transplant was initially met with significant ethical concerns.
Most recently, the National Institutes of Health (NIH) has proposed changes to their policies controlling the funding for stem cell research creating human-animal chimeras. On the surface it may be hard for the general public to imagine that combining human and animal cells could result in anything other than mythical creatures of Homer’s Iliad. Human chimeras are much more common than one may believe, and the reason to allow studies on these models is to further our understanding of diseases and how to treat them.
What is a genetic chimera?
First, a little background about chimeras, hybrids and mosaics. You may be surprised to learn just how common all of these conditions are in everyday life.
- A hybrid is an organism with a single genotype resulting from the crossing of two species—for example, a mule.
- A mosaic is an organism with two or more genotypes resulting from errors in cell division (among other causes), deriving from a single zygote (fertilized cell) that was created by two gametes (egg and sperm).
- A chimera is an organism with two or more genotypes resulting from the fusion of two or more zygotes. This also includes multiple genotypes arising from organ and bone marrow transplants.
The result of a genetic mosaic or chimera can be the same, such as two different eye colors or two different blood types. In both cases, each cell has only one genotype, but groups of cells (or tissues or organs) can have different genotypes. Physical differences are more likely to be seen in chimeras due to a greater chance of genetic variance. Some people may go their entire lives not knowing they are in fact a chimera. For example, Loubiere et al. found that 39% of women carried some cells derived solely from their mothers (that is, not a genetic mix of mother and father), and at least one person found out during the course of a failed paternity test.
Why do scientists want to research chimeras?
Quite simply, researching chimeras is likely to help save human lives. Diseases can be very complicated and their treatments need to be specific enough to target the afflicted cells without damaging the healthy cells. Ninety percent of drugs that enter phase 1 clinical trials are discontinued because they are ineffective or harmful to humans. Why might that be?
Before an investigational drug is given to a human, researchers must first test the drug in animal models. A drug that is effective in mice is not likely to be effective in people because (duh) mice aren’t people. Testing with pigs, monkeys and other animals is necessary to demonstrate a broad consensus of efficacy, yet all this testing can require hundreds of animals per drug and only 1 in 5,000 preclinical drugs will reach FDA approval. Furthermore, all these failures are a large contributor to the $2.6 billion necessary to develop a new drug, which is commonly cited as a reason for high prescription costs.
Chimeric animal-human models may be the solution to reduce the number of animals needed for testing new drugs while also increasing their success rate because chimeras would be more representative models of human disease pathology.
Ethical considerations with chimeras
The promise of using chimeras to better understand and treat disease is great; however, the question must be asked at what cost can we make these gains? It is obvious that reckless experimentation on sentient beings is unethical. Any induced pluripotent stem cells (iPSCs) that develop into the brain of an animal chimera would assuredly give us all the heebie-jeebies. We are still in the early stages of understanding human development, so it is not clear if eliminating the genes for a pancreas in pigs will guide iPSCs to mature solely into pancreatic cells or if they will proliferate in other types of tissues, for example. This is a gap in our knowledge. The best way to determine if chimeras may be useful for research is to conduct experiments to see where the human cells go. This can be done before the nervous system matures but after rudimentary biological structures form. The proposal to lift the ban on chimeric stem cell experiments is not a proposal to give scientists free reign to become Victor Frankenstein. The policy is likely to be revisited after scientists are able to gather some initial data on how readily they can guide the maturation of iPSCs in animal chimera cells.
Do the proposed guidelines ensure scientific progress can be made while maintaining the ethical treatment of animals? The NIH wants to hear from you.