Making Manimals

By William Saletan
Sunday, June 24, 2007

If you've been laughing at those Neanderthal presidential candidates who still don't believe in evolution, it's time to sober up. Every serious scientist knows we evolved from animals. The question now is whether to put our DNA and theirs back together.

We've been transplanting baboon hearts, pig valves and other animal parts into people for decades. We've derived stem cells by inserting human genomes into rabbit eggs. We've created mice that have human prostate glands. We've made sheep that have half-human livers. Last week, Britain's Academy of Medical Sciences reported that scientists have created "thousands of examples of transgenic animals" carrying human DNA. According to the report, "the introduction of human gene sequences into mouse cells in vitro is a technique now practiced in virtually every biomedical research institution across the world."

Why have we done this? To save lives. If you can't get a human heart valve, a pig valve will do. If you can't get human eggs to clone embryos for stem cell research, rabbit eggs will do. If you can't use people as guinea pigs in gruesome but necessary experiments on human tissue, guinea pigs will do. All you have to do is put -- or grow -- the human tissue in the guinea pigs. You're free to inflict any disease or drug on a human system, as long as that human system lives in an animal.

In stem cell research, moreover, human cells are the therapy. Under FDA rules, they must be tested in animals before they're tested in people. That means implanting them to see how they change the animals. Meanwhile, we're using hamster cells to make a human protein to treat anemia. We're using mice to make humanized antibodies that produce cancer drugs. We've grown human kidney tissue in rats.

So far, our mixtures are modest. To make humanized animals really creepy, you'd have to do several things. You'd increase the ratio of human to animal DNA. You'd transplant human cells that spread throughout the body. You'd do it early in embryonic development, so the human cells would shape the animals' architecture, not just blend in. You'd grow the embryos to maturity. And you'd start messing with the brain.

We're doing all of these things.

According to the British academy's report, "researchers have constructed ever more ambitious transgenic animals" -- some with an entire human chromosome -- and it's "likely that the process of engineering ever larger amounts of human DNA into mice will continue." We're transplanting pluripotent stem cells, which proliferate and grow many kinds of human tissue. We're doing it early in mouse embryogenesis, and we're implanting the resulting embryos in "foster mice" so they can develop.

We're not doing these things because they're creepy. We're doing them because they're logical. The more you humanize animals, the better they serve their purpose as lab models of humanity. That's what's scary about species mixing. It's not some crazy Frankenstein project. It's the future of medicine.

Now comes the brain.

Neurological disorders affect 1 billion people and kill nearly 7 million per year. To study these disorders, we're doing to brain tissue what we've done to liver and kidney tissue: We're replicating it in animals. We've made humanized mice with Alzheimer's symptoms. We've put human neural stem cells in monkey brains. We've added human stem cells to the brains of fetal mice and grown them into adult mice with human neurons. According to the British academy, it's now standard practice to test human neural stem cells by assessing whether they "integrate appropriately into mouse or rat brain."

Last month, ethicists from Stanford University and the University of Wisconsin detailed a proposal by a Stanford scientist to substitute human brain stem cells for dying neurons in fetal mice. "The result would be a mouse brain, the neurons of which were mainly human in origin," they reported. The payoff, if the fetuses survived, would be "a laboratory animal that could be used for experiments on living, in vivo, human neurons." Imagine that: a humanoid brain network you can treat like a lab animal, because it is a lab animal.

The Stanford experiment wouldn't actually produce a human brain. Most brain cells aren't neurons, and the experiment called for inserting human cells after the mice had constructed their brain architecture. But last year in the journal Developmental Biology, researchers proposed to insert human stem cells in mice before this architectural stage. The resulting "mouse/human chimeras," they argued, "would be of considerable value for the modeling of human development and disease in live animals."

When Stanford's ethicists first heard the proposal for humanized mouse brains, they were grossed out. But after thinking it over, they tentatively endorsed the idea and decided that it may not be bad to endow mice with "some aspects of human consciousness or some human cognitive abilities." The British academy and the U.S. National Academy of Sciences have likewise refused to permanently restrict the humanization of animals.

If you want permanent restrictions, your best bet is the senator who tried to impose them two years ago. He's the same presidential candidate now leading the charge against evolution: Sam Brownback, a Kansas Republican. He thinks we're separate from other animals, "unique in the created order." Too bad this wasn't true in the past -- and won't be true in the future.

William Saletan covers science and technology for Slate, the online magazine at

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