Representational image. (AFP)
Representational image. (AFP)

Scientifically Speaking | Identifying genetic superpowers in people

We have entered the realm of precision medicine, in which clinicians are starting to tailor treatments for people based on their genetic profiles
By Anirban Mahapatra
PUBLISHED ON JUL 14, 2021 12:30 PM IST

In Manoj Night Shyamalan’s film, Unbreakable, the protagonist David Dunn (played by Bruce Willis) survives a train crash, and soon learns that he is gifted with unique superpowers. Dunn has super-strength and can read the minds of others.

While the movie is fictional, I often wonder about people who have more mundane genetic superpowers. We all know people who can get by on a few hours of sleep, seemingly eat whatever they want to without gaining weight, learn a new language rapidly, run fast without breaking a sweat, and avoid taking sick days from work.

It’s quite difficult to pin down what proportion of genes, environment, and stochastic processes (in plain speak, dumb luck) play a part in our own lives. It’s also very difficult to move from a correlation between factors to actually finding a cause and effect for an observation.

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But one of the things we can do in the age of big data is to start with an observation and then see what is associated with it. With the availability of massive amounts of genetic data, scientists are now able to scour through sequenced genomes for links between genes in bodies and outcomes in people. Often, the process yields no results, because there isn’t a clear association between one or few genes and an outcome. But this brute force approach is beginning to bear fruit.

We have entered the realm of precision medicine, in which clinicians are starting to tailor treatments for people based on their genetic profiles. We are also just now starting to see powerful tools such as genome editing with CRISPR be used to fix genes that cause genetic diseases causes by single mutations.

Much of this effort has rightly focused on identifying what predisposes people to or exacerbates illnesses such as heart diseases, cancers, obesity, and infections. For example, just last week, researchers published a paper in Nature that identified human genetic variants that increased the susceptibility of those unfortunate enough to carry them to severe Covid-19.

But some scientists are taking a different approach altogether by trying to identify genes that make people less vulnerable to unfavourablehealth conditions. This is kind of like mining for genetic superpowers.

There’s a large-scale undertaking called the Resilience Project led by scientists at Icahn School of Medicine at Mount Sinai in New York. This project “aims to discover why some people are more able than others to resist or recover from challenges to their health and escape disease”, and it has already identified people who have mitigated cardiovascular disease risk despite have a high LDL cholesterol level and have resisted Alzheimer’s disease despite have an activating gene. The project has also identified people who keep HIV at very low levels or even never test positive for HIV (or develop full-blown AIDS) despite being exposed to the virus many times.

Scientists at Regeneron have another goal. They have been searching for genes in people who seem to not gain weight. Regeneron sequenced all the protein-coding genes in genomes of around 650,000 people chosen at random. But instead of trying to identify genes in people who had severe obesity, they looked for genes associated with leanness.

Reporting in a paper in Science published on July 2, they found that variants in the GPR75 gene confer some resistance to obesity. People who have a different variant of GPR75 than the rest of us were 5.5 kilograms lighter and had less than 54% chance of obesity. But before you get excited, you should know that this superpower is relatively rare and found in only one out of every 3,000 people. What makes this study interesting is that it opens avenues to look for anti-obesity drugs that regulate GPR75.

What about other superpowers such as not needing to sleep a full night? Lack of sleep tends to cause many health problems and often this is due to the misalignment between our internal circadian clocks and the natural light-dark cycle outside. We don’t blame Thomas Edison for poor memory, heart disease, inflammation, and obesity, but it is estimated that the invention of the light bulb has led to two hours less sleep on average. And keeping the smartphone or tablet next to the bed isn’t helping us get a proper night’s rest either.

But there are people who not only get by, but thrive on four or five hours of sleep every night. Researchers have started to identify genes that are associated with these superpowers. Mutations in ADRB1 and NPSR1 genes change neurotransmitters in the brains of some people allowing them to sleep less. Another variant in DEC2 lets short sleepers stay awake longer.

Often when associations between a genetic variant and a biological trait are found, the next step is to clone the variant and to breed it in laboratory mice. Mice are by no means a substitute for people, but they offer a controlled way to test for possible genetic effects quickly. For example, mutant mice with the sleep-related variants were able to sleep for fewer hours.

As we identify variants associated with desirable superpowers, we can improve our understanding of basic biology and clinical medicine. We can also appreciate the expansive genetic tapestry of humanity. But we should also understand that life is seldom as simple as it seems. We may find that there may be additional genes that we don’t know about and alternate biological pathways that don’t involve the genes of particular interest that confer superpowers to some people.

Finally, any discussion of the identification of the genetic basis of observable traits in people is not complete without considering the ethics of such endeavours. On the one hand, we know that race is a social construct and not a biological one. On the other, there will certainly be people who try to find a genetic basis for traits with the purpose of discriminating against other humans. Biology does not have a stellar track record in this aspect, but we must never allow the racist and bigoted tendencies of the eugenics era to be repeated again.

Anirban Mahapatra, a microbiologist by training, is the author of COVID-19: Separating Fact From Fiction

The views expressed are personal

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