Watching the chimeras
By DAVID MAGNUS
Question: I recently read about researchers who put human cells into mouse brains and encouraged them to develop.
Is this research ethical?
Answer: Creating animals that have human cells in their brains conjures up bizarre images, such as a human consciousness trapped in a mouse’s body. Like you, this research gives me pause.
My concerns are eased, though not eliminated, by the fact that part-human chimeras have been used in science and industry for decades. The term chimera, used among biologists to describe a being consisting of cells from two different kinds of animals, comes from a creature in Greek mythology. The beast has a fire-breathing lion’s head, a goat’s body and a snake’s tail. In reality, chimeras in labs are not as monstrous as all that.
Genetically engineered bacteria are an example of one common type of chimera.
Virtually every diabetic uses the products of humanized bacteria — insulin made by bacteria carrying the human insulin gene. Animal models for studying disease are another example. These are animals, usually mice, that are made susceptible to human disease, often through the addition of a human gene. These kinds of chimeras raise few objections, as the benefits of the research and clinical applications easily outweigh vague objection of “unnaturalness.”
The new type of chimeras you’ve asked about, though, take blending animal with human one step further. Instead of placing human DNA into mouse cells, researchers place human stem cells into mouse embryos — in some cases directly into an embryo’s developing brain.
Though I believe this can be done ethically, I have some reservations. One concern I have is the possibility of creating a human embryo whose parents were both mice. In theory, this could happen if mouse embryos implanted with human stem cells developed the ability to produce human sperm or eggs — and then mated with one another. The chances of this happening are astronomically small, but not zero.
The second worrisome scenario, also very unlikely, is that animals carrying human cells could develop morally significant human traits, such as self-awareness. The Disney movie The Secret of NIMH, about super-intelligent mice, was entertaining — but in real life, we do not want to see mice with features of human intelligence.
The National Academy of Sciences guidelines on stem cell research address these concerns by prohibiting the breeding of mice and most other animals that carry human stem cells. The guidelines also bar transplanting human stem cells into the embryos of our closest evolutionary cousins — non-human primates — to reduce the chances that they will become too humanized. Failure to abide by these rules could lead to loss of funding and inability to publish; they also violate state laws that are enacting the NAS guidelines as regulations.
But your question was about experiments in mice, so what about them? Science regulators say it’s OK to place human stem cells in mouse brains, but only if the mice are closely monitored. This makes sense to me. Mice humanized by stem-cell transplants offer fantastic opportunities for testing drugs and understanding human disease — because the more human the mouse, the better research model it makes. But a mouse with a small number of human cells in its brain is still a mouse.
Still, this work is very preliminary; no one knows for sure how human cells will influence their new hosts. As a result, scientists doing these experiments must keep an eye on the way these animals behave and how their brains develop for signs that the research is entering ethically treacherous waters. If the mouse brains start exhibiting a more human organization, that would be a good time to stop.
David Magnus, PhD, directs the Stanford Center for Biomedical Ethics.
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