The 2022 Nobel Prize in Medicine and Physiology honors work that traces humanity's origins—and may one day help us treat Covid.
Our genes encode humanity’s diverse immune defenses. That diversity both helps and harms us.
How have humans lasted this long? After all, extinction is the fate consigned to 99% of species that have ever lived. The answer is a combination of luck and skill.
Consider infections, a major force behind the extinction of countless species though the ages. Until recently, whether humans lived or died in the face of a pandemic hinged entirely on chance. But the odds of our collective survival have been improved by our genetic diversity. Genetic diversity among humans explains, at least in part, why we’re still here. In particular, our genes code for immune systems with dizzying complexity.
Part of the overall “strategy” is to accept some risks in exchange for greater benefits. A classic example is sickle cell anemia. Why would a disease which causes suffering and early death persist in our species? One reason is that the disease progresses relatively slowly. That means that people born with sickle cell disease live into adulthood, long enough to reproduce before succumbing to the disease, thus removing any selective pressure against those who carry the genes that causes the disease. Second, individuals with just one copy of the relevant gene do not develop sickle cell disease (two copies are needed) but are substantially more resistant to malaria than average. In the epochs of human life before we developed anti-malarial drugs, that trade-off was—from a survival of the species standpoint—well worth it. (Today, we'd like to cure it, and are making progress.)
Today, the 2022 Nobel Prize for Medicine and Physiology was awarded to Svante Pääbo for his work assembling the genetic sequences of long-extinct human relatives, an achievement long thought impossible. Pääbo’s work has solved paleontological riddles about where we came from, and how closely we are related to Neanderthals and Denisovans (a branch of the human family tree that he and his team discovered).
In 2020, scientists began looking within the human genome for risk factors that might increase the chances someone might develop severe Covid-19. One major theory (related to blood type) showed promise but has not been borne out in follow-up studies. But another, the linking of severe Covid-19 risk to certain versions of genes found in the 3rd human chromosome, remains possible. The presence of specific DNA codes found within this region of our genetic blueprints may make it easier for SARS-CoV-2 to enter cells that line our airways and lungs, thereby causing worse Covid-19 disease.
In 2020, Pääbo and Hugo Zeberg found that a collection of genes found on that 3rd chromosome appear to have originated from stretches of our genetic portfolios inherited from Neanderthals. This implied that certain populations might be more susceptible to severe Covid simply based on their family tree. Around 30% of people in South Asia carry the genetic sequence linked to severe Covid risk, compared to just 8% among people living in Europe (lower fractions of people in East Asia and the Americas have the sequences, reflecting more distant relationships to Neanderthals). Pääbo and Zeberg found that those with highest likelihood of carrying this genetic risk were people of Bangladeshi origin. In support of this theory, in the United Kingdom, people of Bangladeshi background were found to have died more frequently of Covid than the general population in 2020, though the finding was preliminary, as many confounding variables might have also explained this, including the frequency of other underlying health conditions and access to medical care. Meanwhile, looking at US data, Asian people have had lower rates Covid-19 compared with other groups. However, if you factor out East Asian groups (e.g., Chinese, Japanese, and Korean people) who share very little DNA in common with Neanderthals, a high-risk “Other Asian” group (including those with links to regions of South Asia, like Bangladesh) emerges. Indeed, members of this group have seen higher rates of Covid mortality in the US, compared both to the general pollution and East Asian people. The degree to which these outcomes reflect genetics, societal factors, or a combination of the these remains unknown. Nevertheless, the genetic insights may hold keys to future treatments.
It's also possible that, like sickle cell disease and malaria, versions of genes found on our 3rd chromosomes confer increased risks of severe Covid while simultaneously offering some other as-yet discovered survival advantage with respect to some other important disease or diseases. Work aimed at understanding all of this is underway.
As always, our DNA tells us who we are and where we came from, though not necessarily where we’re headed. Genes—the baggage we carry in our cells and pass on from generation to generation—can benefit us one day and harm us the next, depending on the circumstances. One can never tell which way it will go. Genetic diversity itself, however, offers our species an overall survival benefit, a kind of hedged-bet insurance policy. Many branches of the human family are long gone, perhaps felled by some remote plague that affected members of our species who were exceptionally vulnerable to it; a stroke of bad genetic luck. But our species’ genetic diversity also means that others who didn’t carry such risks survived important evolutionary bottlenecks and continued to survive for eons. Many of those branches are still thriving today. Their descendants—all of us, apparently—did not merely live to tell those stories, but—rather remarkably—went on to discover them.
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