Where a bad gene may be a good thing

My neighbor Pagan Kennedy is a multifaceted writer. When I met her two decades ago, she was writing mainstream novels, one of which received the Orange prize, a major honor for women writers in the United Kingdom and other English-speaking nations. In one of her first nonfiction books, The First Man-Made Man: The Story of Two Sex Changes, One Love Affair, and a Twentieth Century Medical Revolution, Kennedy went where other writers hadn’t.

These days, Kennedy is filing articles about science, technology and innovation for the New York Times, and her latest article concerns dementia. In “An Ancient Cure for Alzheimer’s?” Kennedy suggests that indigenous populations in Bolivia could lead researchers to a new understanding of Alzheimer’s, and how it might eventually lead to a cure. Back in 2011, the anthropologist Ben Trumble spent extensive time in the Bolivian jungle, collecting vials of saliva from tribesmen to gauge their testosterone levels. In return, Kennedy noted, Trumble agreed to field-dress the kill. The aim was to see if without industrialization, there might be different outcomes concerning dementia.

Trumble himself was touched, indirectly, by Alzheimer’s. He learned that a favorite uncle had been diagnosed with Alzheimer’s, and was declining rapidly. The uncle died in 2015. As Trumble commented, “We know almost nothing about how dementia affected humans during the 50,000 years before developments like antibiotics and mechanized farming.”

Researchers understand that Americans who carry two copies of the APOE4 gene are ten times likelier to develop later-onset Alzheimer’s compared to the people of the Tsimani. And here’s the surprise: “The Tsimane people have the cleanest arteries that have been studied.” Even more counterintuitive, “Many of those with an extra copy [of the gene] seemed to do better on the cognitive tests.” As Kennedy speculated, “Perhaps the APOE4 gene provided a survival advantage in ancient environments.”

Back at his office in Arizona State University, Trumble discovered what appeared to be a large pimple on his nose. But when the growth continued to enlarge, he recognized for what it was: a flesh-eating parasite. As Kennedy noted, “Chemotherapy saved his nose, and perhaps his life.” Trumble went on to review the data from the Tsimane volunteers. “Sure enough, he found that the Tsimane with infections were more likely to maintain their mental fitness if they carried one or two APOE4 genes. For them, the ‘Alzheimer’s gene’ provided an advantage. For the minority who’d managed to elude parasitic infection, however, the opposite was true.”

Kennedy speculated that the APOE4 gene served as a means of survival in a prehistoric period. “Today only about a quarter of us have a single copy of the APOE4 gene, and only about two in a hundred carry a double dose. But DNA analysis of ancient environments shows that thousands of years ago, the APOE4 genotype was ubiquitous.”

Given my shallow understanding of genetics—I did poorly in high school biology—I suggest that those of you who are interested in the topic, google “Pagan Kennedy ancient care for Alzheimer’s.” The article is worth reading in its entirety.