Transgenic Monkeys: Coming to a Lab Near You?

April 30, 2019 • Posted in Blog

D. Joy Riley, M.D., M.A.
Executive Director

 "Genetically-altered" macaque takes a memory test


Above: “Genetically-altered” macaque takes a memory test.

The initial draft sequence of the chimpanzee genome was published in September 2005 – in comparison with the human genome. A few months later, geneticist James M. Sikela wrote in PLOS Genetics, “the genes and genetic changes that are responsible for making the human brain what it is and for allowing it to do what it uniquely does, have long been among the most prized jewels of our genome.” In that paper, Sikela considered how one could locate the changes in the genome that account for “human-specific cognitive abilities.” How could one prove that a certain genomic change is responsible for cognition? That would require functional testing, of course. Sikela argued for a transgenic murine model, since there already existed both cognitive and behavioral tests for mice. He specifically stated, “Transgenic approaches using primates are unlikely to be an option for ethical reasons.”

In other words, if you suspect that a certain human gene or portion of the human genome is responsible for producing human-like ability to think, how do you test it? One way is to take those human genes and transfer them to another animal, and then test the recipient animals to see if their cognition is different from such animals without the transferred genes. Sikela recommended using mice, since there are actually tests to measure mouse thinking and behavior. Sikela advised that using primates, which include monkeys and apes (chimpanzees are apes, but monkeys are not) would not be ethical. He later further outlined his reasons for this view, including the fact that “the challenge of assessing our ethical obligations to “humanized” apes is profound” (see here).

Fast-forward to 2019, and transgenic monkeys – monkeys carrying the human gene MCPH1 are introduced. MCPH1 contributes to brain development in humans, including brain size. Mutations in MCPH1 can result in small brains, or microcephaly. Collaborators from China and the United States worked to produce eleven transgenic macaque monkeys. These monkeys had the human gene, MCPH1, but their brains did not appear enlarged. There were some differences from normal or “wild type” monkeys, however. The transgenic monkeys showed shorter reaction times in certain tests, and “improved short-term memory.” Additionally, the brains of the transgenic monkeys showed a maturational delay of neurons, similar to what is known in humans as “neoteny.”

Importantly, these genetically-altered rhesus macaques are unique, but they are not alone. The data published in 2016 are telling:

China has an abundance of macaques — the mainstay of non-human-primate scientific research. Although the population of wild rhesus macaques (Macaca mulatta) has declined, the number of farmed animals has risen. According to data from the Chinese State Forestry Administration, the number of businesses breeding macaques for laboratory use rose from 10 to 34 between 2004 and 2013, and the quota of animals that those companies could sell in China or overseas jumped from 9,868 to 35,385 over that time.

Whether genetically-altered macaques come to a lab near you, or researchers go to China to utilize the macaque populations there, who is asking the important questions here? While Sikela makes an excellent point about humans’ ethical obligations to “humanized” apes, there are myriad other important questions to ask. What is our ethical obligation to other humans, in terms of maintaining our humanity? How much DNA does it take to make a being a human being? Where is the imago Dei in this? Once again, because we can do a thing, does that necessarily mean we should?

 

Another unsettling video . . .

 

Above: Chimp using Instagram.

Above: Chimp using Instagram.