In any gathering, I always choose to drink soda water with lime juice added. I’ve never been drunk, not even finished a whole glass of alcohol. The only time I almost got drunk was at an academic event when, after drinking half a glass of warm red wine, my heart rate soared, and I started feeling dizzy and flushed before ultimately collapsing in front of a university professor.
My complete aversion to alcohol can be entirely attributed to my genetics, just like approximately 500 million other people—most of whom are of East Asian descent—I carry a genetic mutation known as ALDH2*2, which results in an inability in my body to produce a full aldehyde dehydrogenase 2, and thus an inability to break down the toxic substances produced during alcohol metabolism. So whenever I drink alcohol, various toxic aldehydes accumulate in my body, and the flushing of my face announces to those around me the trouble I’m in.
From an evolutionary logic standpoint, I and others with alcohol flush should not exist. Alcohol is not the sole source of aldehydes in our body. Our own cells also naturally produce these compounds, and if they are not cleared promptly, they can damage our DNA and proteins. So even without consuming alcohol, people with alcohol flush still have extra toxins in their bodies, making them more prone to a range of health issues, including esophageal cancer and heart disease.
However, over two thousand years, this group of individuals (including myself) has grown to 500 million despite this significant genetic burden. Heran Darwin, a microbiologist at New York University, believes that the reason may be related to another evolutionary logic—while aldehydes can threaten our health, they also attack pathogens in our bodies. As Darwin and colleagues pointed out at a conference, people carrying ALDH2*2 may be particularly adept at resisting certain pathogens, including the bacteria that cause tuberculosis (which has been one of the biggest infectious killers in modern history).
This research has been published in the journal Science, but it has not yet been experimentally validated by other scientists. It may be difficult to confirm whether tuberculosis or any other pathogen has caused an increase in the number of individuals carrying the ALDH2*2 mutation. However, as several experts have said, if contagious diseases can partly explain the existence of the massive alcohol flush population—then the secret of this very common genetic mutation in humans may be further unveiled.
Scientists have long realized that aldehydes can destroy DNA and proteins. Ketan J. Patel, a molecular biologist studying the ALDH2*2 mutation at Oxford University, says these compounds are carcinogenic and “disrupt the structure of life.” He wrote a comment article for this new study published in Science. For years, many researchers have dismissed these chemicals, considering them to be junk produced by the body’s everyday metabolism. In fact, these chemicals are part of natural metabolism, accumulating during infections or inflammation periods and are byproducts of some toxic chemicals produced by the body.
In the subtleties, scientists explore the mysteries of medicine, discovering a new possibility, namely using a molecular cleaning system within the body to combat pathogens. Researchers found through in-depth study that specific aldehyde compounds can kill the deadly tuberculosis bacillus within days. This discovery stemmed from meticulous observations of the mechanisms by which aldehyde substances affect the behavior of tuberculosis bacilli. Aldehyde substances, especially those produced by the bacteria themselves, not only increased the tuberculosis bacilli’s sensitivity to nitric oxide but also enhanced its sensitivity to copper; both substances have a strong antimicrobial effect.
This research suggests that tuberculosis bacilli and other various pathogens may be unable to survive in environments rich in aldehyde substances. Indeed, our ancestors may have realized the potential of these compounds during evolution and thus incorporated them into the human immune defense system. Interestingly, as an example of alcohol-induced flushing, genetic mutations in certain human populations make it difficult for them to process these compounds under the influence of aldehyde dehydrogenase 2 (ALDH2), potentially enhancing their resistance to certain pathogens.
The immune system evolves in constant battles, learning to use various toxic compounds against invaders. It is notable that immune cells can respond to certain chemical signals that indicate the body has encountered an infection, thereby accelerating the production of aldehyde substances. Further research has revealed that restricting the level of the enzyme ALDH2 appears to be a way to enhance the supply of antimicrobial toxins.
This phenomenon is particularly evident in carriers of specific gene mutations, who typically flush after drinking, suggesting that aldehyde substances in their bodies are not easily cleared. Inspired by this, scientists have mimicked this genetic mutation and found that mice with ALDH2 gene knockout had fewer accumulated bacteria after tuberculosis bacillus infection, but were not completely immune.
Given these complex interactions and findings, researchers are attempting to leverage these insights to improve medical treatments. One potential strategy is to include anti-ALDH2 drugs in antibiotic treatments to mimic the effects of specific gene mutations. If the research results can be linked to the specific genetic variant ALDH2*2, which is widespread in the global population, this would represent a significant breakthrough in the fight against infectious diseases.
Scientific research has begun to reveal evidence of connections between genetic variation and disease resistance. A group of researchers observed in samples from Vietnam and Singapore that people carrying the special mutation ALDH2*2 seemed to have a lower incidence of tuberculosis, a finding in line with related research in Korea.
However, Daniela Brites, an evolutionary geneticist at the Swiss Tropical and Public Health Institute, is skeptical of this correlation. She believes that since other research looking into the genetic susceptibility or resistance to tuberculosis did not find the involvement of the ALDH2*2 gene mutation, this might mean that the connection is actually weak.
Despite doubts, the main idea of the new study’s team is considered worth pursuing. Experts point out that infectious diseases have been a primary determinant of life and death throughout most of human history, leaving profound marks on the human genome. For instance, a gene mutation commonly found in certain regions of Africa is associated with sickle cell anemia, but it may also provide residents with resistance to malaria.
The ALDH2*2 gene mutation may also be the result of a similar natural selection process. Experts speculate that certain pathogens—perhaps several—may have played a significant part in the preservation of this gene mutation in humans. The known potent pathogen Mycobacterium tuberculosis could be one of these candidate pathogens.
Moreover, a study from Woodward’s lab a few years ago showed that aldehydes could play a role against some bacterial pathogens, like Staphylococcus aureus and Francisella novicida. Stanford University geneticist Che-Hong Chen suggests that the reason for the persistence of this gene mutation may not be the bacteria themselves, but rather the mutation’s ability to deter individuals from alcohol consumption, indirectly avoiding potential liver issues caused by drinking.
In conclusion, although certain gene mutations may be considered disadvantageous in some contexts, their cultivation during the evolutionary process might have unexpectedly positive effects on human resistance to pathogens.
