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Genetic Linkage

"Animals Containing Human Material" -- Welcome!

A new biomedical abbreviation debuted July 22, ACHM (for Animals Containing Human Material) in a report of the same name from the UK Academy of Medical Sciences. ACHM will soon replace, I hope, the phrase “humans and animals,” which implies to the taxonomically inclined that we are instead fungus, plant, or microbe. Even the editorial in Nature on the report notes “the distinction between humans and animals.”

Perhaps because I write college biology textbooks that treat Homo sapiens as any other animal species, I’ve long thought a new term necessary. “Non-human animal” is cumbersome. And so I was thrilled at the UK’s acknowledgement of our Kingdom membership, joining us to the others distinguished by our lack of cell walls. But I fear ACHM isn’t catchy enough, and may head straight into the abbreviation graveyard of RFLPs, SNPs, and iPS cells, none of which really caught on beyond the scientific community. Neither will ACHM work as an acronym; it sounds like a clearing of the throat.

Semantics aside, the report is important. It prepares the biomedical community for future use of animals in research that will increasingly include human material. Said Professor Martin Bobrow, chair of the working group, “Our report recommends … a national expert body, within the existing stringent system of animal research regulations, to provide specific advice on sensitive types of ACHM research.”

Of course the cat is already out of the proverbial bag. The Jackson Lab offers a menu of mice harboring human genes, providing models for many human diseases. Huntington’s disease is in fact modeled in mice, flies, zebrafish, sheep, and macaques. Sheep, goats, cattle, rabbits, and chickens produce human proteins in their milk. And at the cellular level, mice harbor bits of humanity, in the form of tumors, pancreatic islets, livers, and the antibody-producing part of the immune system. More disturbing, perhaps, are brains. But rats suffering from stroke, spinal cord injury, brain tumors, or ALS have received human neural stem cell implants without suddenly becoming able to give speeches or play the guitar.

Not surprisingly, this report comes from the UK. They’re always ahead in human reproductive technologies and regulations, from first test tube baby Louise Joy Brown, to allowing study of hybrid human embryos up to the two-cell stage. And recent rapid advances in genome science and stem cell biology illuminated a need to plan for experiments that increasingly mix materials from two species.

Acknowledging that thousands of ACHMs already exist, the report offers a new taxonomy, categorizing these animals into three types: “genetically altered” (transgenics, which have a human gene added, and gene targeted animals, which have a human gene swapped in); chimeras (mixed embryos or transplants, generating cellular mosaics); and true hybrids, with sperm and egg from different sources (horse + donkey = mule).

These three classes of ACHMs come under three levels of review. The first tier includes most ongoing experiments, which require the same oversight as existing experiments using animals. The second level, “extra review,” applies to manipulating brains and sex cells, especially in our closest primate cousins. (Humanizing cetaceans is not specifically addressed, but may also be cause for alarm, as depicted in the film “Deep Blue Sea,” where a crazed shark harboring genes from a human Alzheimer’s patient bites off Samuel L. Jackson’s head mid-speech.)

The third category of oversight is for creatures so unnatural that they are still within the realm of fiction. Precedents include Woody Allen’s crab with the head of a social worker in the film Sleeper, Jeff Goldblum’s The Fly, and mermaids Ariel and Madison. Werewolves and vampires are exempt because they may just be people with a porphyria, an inherited blood disorder that can cause light sensitivity and red eyes.

The report’s examples of experiments in the forbidden zone are an embryo built of human and other primate cells existing beyond two weeks; a non-human primate with enough human cells to develop “human-like” behavior; and human eggs or sperm made in another type of animal, say an aardvark or a stinkbug. But with a nod to Louise Joy Brown and how the IVF that she pioneered is now routine, the report advises type 3 scrutiny “at least until the potential consequences are more fully understood.” Flashback to the Asilomar conference in 1975, where researchers expressed fears of whether recombinant DNA technology might lead to creation of “triple-headed purple monsters,” in the words of one geneticist.

According to the report, the public fears endowing the furry or scaly with human traits such as naked skin, facial expressions, or speech. Certain abilities just cross boundaries, such as when lost astronaut Taylor suddenly proclaims to his simian captor, Dr. Zira in the original “Planet of the Apes” movie, “Take your stinking paws off me you damn dirty ape!”, seen in reverse in the prequel “Rise of the Planet of the Apes.”

The UK report is especially interesting when it imagines what could be. About a third of the way through its 148 pages, the report mentions Stanford University stem cell researcher Irving Weissman’s proposed mouse whose own brain disease would kill it within days of birth. Would an infusion of human neurons rescue it? Even if billions of human brain neurons could connect within the confines of a mouse cranium, how would they interpret incoming signals? Neurons whose evolutionary history had prepped them to control fingers and a face in a colored world would instead find themselves overseeing four feet and whiskers in a dull black-and-white existence. A Planet of the Mice scenario thus seems unlikely, and perhaps mice aren’t perfect models for some brain disorders. But just the thought experiment forced the report writers to tally up the traits that make us human, so we know what to look for in an ACHM endowed (or encumbered) with human brain material: episodic memory, math ability, planning, language, social cognition, and “theory of mind” (belief, intent, desire). That’s us.

Coda: To paraphrase Watson and Crick, it has not escaped my notice that the UK report came out at the same time as The Rise of the Planet of the Apes, depicting the backstory of how chimps, gorillas, and orangutans take over in the future, thanks to decidedly “human behavior.” In the ultimate irony, gene therapy, conducted by us on them, is to blame – the topic of my next book, The Forever Fix.

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