After giving a talk recently about CRISPR at my children’s former high school in Lexington, Massachusetts, a student stumped me by asking if I’d read Margaret Atwood’s MaddAddam trilogy, set in a hyper-capitalistic late 21st century. In the first book of the trilogy, Oryx and Crake, a brilliant geneticist named Crake usurps natural selection to conceive and create a superspecies adapted to thrive in a post-pandemic society, on a planet ravaged by climate change. They replaced socially normal mating customs with features beneficial to procreation and survival. The Crakers had beautiful skin of many colors resistant to sun damage and able to repel insect bites and infection. They also boasted bovine-like digestive systems requiring only nutrients provided by ubiquitous weeds.
The ability to eat weeds isn’t high on anyone’s wish list (yet) but some of us do possess extraordinary “superhuman” traits. Take seventy-year-old Jo Cameron, who lives near Loch Ness in Scotland. Her life has been free of pain and anxiety—she barely felt any discomfort giving birth, although has suffered plenty of serious bruises and burns. She didn’t appreciate her superpower until undergoing hip surgery in her sixties, managing the pain with just a small dose of acetaminophen. In 2019, researchers found a variant in one of Cameron’s genes called FAAH-OUT, which raises levels of anandamide, an endogenous cannabinoid, and makes her almost unable to feel pain.
The first example of a pain-resistance mutation was described in 2006 in members of a consanguineous (inbred) Pakistani family, incriminating a gene that codes for a sodium ion channel called NaV1.7, involved in the propagation of nerve signals.13 One boy in particular was a well-known street artist, painlessly walking on hot coals or stabbing his arms with knives. On his fourteenth birthday, he jumped off a house roof and fell to his death. Pain has its purpose enabling humans to comprehend and internalize risk. The English team that made that gene discovery learned about another extraordinary family from Siena, Italy, featuring people who cannot feel extreme pain or temperature. For example, Letizia Marsili shrugged off a nasty crash while skiing, only to discover that evening that she’d sustained a broken shoulder.14 The Marsilis carry a mutation in a gene called ZFHX2, and now have a syndrome named after them. This discovery could eventually turn into a powerful nonaddictive pain reliever.
Marvel creator Stan Lee made an entire television series devoted to real superhuman genetic outliers—echolocation, extreme endurance, temperature resistance, mathematical wizards, and people with eidetic or photographic memory.15 The actor Marilu Henner is the most famous person (although all told there are only a dozen) with total memory recall, a condition called hyperthymesia or highly superior autobiographical memory (HSAM). Scientists are eagerly trying to untangle the neural basis of this extraordinary ability and its possible genetic underpinnings.
Julian Savulescu, a philosopher at Oxford University, can reel off a list of traits he’d like to see engineered into humans that would have made Stan Lee blush. Bat sonar. Hawklike vision. Enhanced memory. Radical life extension. Increased IQ to the point that we become a separate species. Humans have been seeking to enhance the quality of life for years. We add iodine to salt and vitamin D to milk, and calcium to orange juice. We take Ritalin to improve concentration, hormones to improve vitality, and undergo Lasik surgery to dispense with spectacles. We perform IVF, prenatal diagnosis, and PGT, what some term liberal eugenics. “Parents should be allowed [to undertake embryo editing] provided they don’t harm their children or other people,” Savulescu suggests.
George Church is somewhat agnostic about germline editing but supports using the protective effects of known gene variants to aid human health and longevity. The ends are more important than the means. For years, Church has compiled a set of gene variants that offer potential physical, medical, or behavioral advantages—some call it the transhumanist wish list (see table on the next page). Some of these gene discoveries are already fueling drug discovery advances. But if germline editing was ever offered in the future, these would be some of the first genes on the clinic menu.
CCR5 was on this list long before the JK scandal, as resistance to viral infection is in principle a highly desirable trait. That was true even before the COVID-19 pandemic began.16 We don’t yet know of a gene variant that confers resistance to SARS-CoV-2, but such protective polymorphisms likely exist. The FUT2 receptor is the cellular foothold for the norovirus, which afflicts hospitals and cruise ships with regularity. Immunity to the winter vomiting bug would be nice but knocking out FUT2 appears to increase risk of Crohn’s disease and colon cancer. There are few free lunches in the human gene pool.
Table: A list of gene variants that offer potential medical or other advantages
GENE
MUTATION
EFFECT
CCR5
-/-
HIV resistance
FUT2
-/-
Norovirus resistance
PCSK9, ANGPTL3
-/-
Low coronary disease
APP
A673T/+
Low Alzheimer’s
GHR, GH
-/-
Low cancer
SLC30A8
-/+
Low T2 Diabetes
IFIH1
E627X/+
Low T1 Diabetes
LRP5
G171V/+
Extra-strong bones
MSTN
-/-
Lean muscles
SCN9A, FAAH-OUT, ZFXH2
-/-
Insensitivity to pain
ABCC11
-/-
Low odor production
DEC2
-/-
Reduced sleep
What about protection against dementia or premature aging? We’ve already seen how one version of the apolipoprotein E (APOE) gene on chromosome 19—APOE4—is associated with a roughly tenfold increased risk of developing Alzheimer’s. Editing the E4 variant to the E2 or E3 form might lower disease risk and is worth exploring. In Colombia, a huge extended family suffers from a rare hereditary form of early-onset Alzheimer’s caused by a mutation in the gene for presenilin. About 1,200 family members harboring this mutation are affected—except one.17 It turns out this seventy-three-year-old woman carries another mutation in the APOE gene called APOE-Christchurch, originally discovered in the 1980s by a team in Christchurch, New Zealand.18 This variant codes for a protective nonstick version of the normal protein, reducing the prevalence of protein aggregates in the brain.
There is also evidence that elevated levels of a protein called Klotho, sometimes dubbed the longevity gene, can improve cognition and protect against Alzheimer’s—at least in mice. A Japanese group named the gene after Clotho, daughter of Zeus, and one of the three Fates in Greek mythology. Several biotechnology companies—seemingly driven by Silicon Valley billionaires contemplating their own mortality—are desperately seeking genes that might slow down the aging process.