At any party, any occasion, my drink of choice is soda water with lime. I’ve never been drunk or even finished a glass of alcohol. The one time I almost did that (thanks to half a glass of mulled wine), my heart rate spiked, the room spun, my face turned red at a stop sign…all of it. After that, I collapsed in front of my university professor at the hospital. academic event.
My genetics are entirely responsible for my aversion to alcohol. Estimated 500 million Other people, most of whom are of East Asian descent, have a genetic mutation called ALDH2*2, which causes them to produce a broken version of an enzyme called aldehyde dehydrogenase 2, which helps the body properly process the toxic components of alcohol. It will no longer be possible to decompose it into So every time I drink alcohol, all kinds of toxins known as aldehydes accumulate in my body, and my face makes everyone aware of my plight.
By evolutionary logic, I and other people who suffer from so-called alcohol flushes (also known as Asian glows) should not exist. Alcohol is not the only source of aldehydes in the body. Our own cells also naturally produce compounds, cause all kinds of havoc If not removed quickly, it has a negative effect on our DNA and proteins. So even at baseline, flashers carry around excess toxins, increasing their risk for many health problems, including esophageal cancer and heart disease. Yet, somehow, our population, with its intense genetic burden, has grown to 500 million people worldwide. Potentially less like in 2000.
The reason, says Helan Darwin, a microbiologist at New York University, could lead to a different line of evolutionary theory driven not by the danger of aldehydes to us, but by the danger of aldehydes to some of our smallest enemies. It is said that there is. As Darwin and her colleagues reported at a conference last week, people with the ALDH2*2 mutation may have particularly good abilities. fight specific pathogensThis includes the insect that causes tuberculosis (TB), one of the most infectious diseases in recent history.
In the current study, Under consideration for publication in a diary science, which has not yet been fully scrutinized by other scientists. And it will likely be difficult to truly pinpoint tuberculosis or other pathogens as evolutionary catalysts for increased ALDH2*2. But if infectious disease can even partially explain the staggering size of the flush population, which several experts have told me it probably does, then it could be one of the most common mutations in the human population. This will bring us one step closer to solving this mystery.
Scientists have long recognized the troubling effects that aldehydes have on DNA and proteins.The compound is carcinogen It literally “damages the fabric of life,” says Keetan J., a molecular biologist at the University of Oxford who studies ALDH2*2 mutations and is considering new research for publication in 2006.・Patel says. science. But for years, many researchers have dismissed chemicals as nuisance waste products from the body’s daily chores. Our bodies produce them as part of our mundane metabolism. These compounds also accumulate during infections and inflammation as byproducts of the harmful chemicals we produce in large quantities. But aldehydes, like so much microscopic debris, are generally swept away by our molecular purification systems.
Darwin and her colleagues now believe that chemicals deserves more praise. When aldehydes are administered to laboratory cultures, they can kill tuberculosis within a few days. In previous research, Darwin’s team also found that aldehydes, including those produced by bacteria themselves, can cause tuberculosis. very sensitive to nitric oxidea protective compound produced by humans during infection; copper, a metal that destroys many microorganisms on contact. (Actually, Darwin told me that the aldehydes found in the body after consuming alcohol don’t seem to worry about tuberculosis all that much.) That’s it. bad It is a result of illness. )
The research team is still compiling the various ways in which aldehydes exert their antibacterial effects. But Darwin suspected that chemical-sensitive insects “would die if they were slashed a thousand times,” she told me at the conference. This makes aldehydes more than just worthless waste. Perhaps our ancestral bodies wisely recognized the universal destructive power of molecules and began deliberately deploying them as a means of defense. “The immune system takes advantage of that toxicity,” says Joshua Woodward, a microbiologist at the University of Washington. Research on the antibacterial effect of aldehydes.
We show that certain cells capture the potency of aldehydes. Sarah Stanley, a microbiologist and immunologist at the University of California, Berkeley, who is leading the Darwin collaboration, says that when immune cells receive a specific chemical signal, infectionthey would Strengthens some metabolic pathways Something that produces aldehydes. Researchers recently discovered that these same signals can prompt immune cells to lower levels of aldehyde dehydrogenase 2. This aldehyde dehydrogenase 2 is an aldehyde-detoxifying enzyme that cannot be produced by mutant genes in humans like me.
If storing that enzyme is a way for cells to increase their supply of toxins and prepare for the inevitable attack, that’s good news for ALDH2*2 carriers who already struggle to get enough enzymes. It may become. In extreme imitation of human flushers, researchers removed the ALDH2 gene from mouse strains and infected them with tuberculosis, and found that the amount of bacteria accumulating in the rodents’ lungs decreased. found.
Accumulation of aldehydes in mutant mice was not sufficient to confer complete immunity against tuberculosis, for example. But even a small bump in defense can be a big advantage when fighting such a deadly disease, says the University of California, Berkeley, who is collaborating with Darwin and Stanley on the project. immunologist Russell Vance told me. Darwin is now interested in whether tuberculosis’ aversion to aldehydes can be exploited in infectious diseases, she told me. For example, it can be used in antibiotic prescriptions by combining Antabuse, a drug that inhibits aldehyde dehydrogenase by mimicking the action of ALDH2*2.
Multiple experts told me that linking these results to the presence of ALDH2*2 in 500 million people is an even bigger leap. There are clues to the link: Darwin and Stanley’s team found, for example, that in cohorts from Vietnam and Singapore, people who carried the mutation were less likely to have active tuberculosis. At least one other study From Korea. But Daniela Breitz, an evolutionary geneticist at the Swiss Institute of Tropical Public Health, said the relationship still feels a little unstable. She pointed out that other studies looking at genetic predisposition to tuberculosis or resistance to tuberculosis have not found a hit on ALDH2 *2. This is a sign that some association may be weak.
The team’s general idea could still come true. “They’re definitely on the right track,” Patel told me. Throughout most of human history, infectious diseases have had the most dramatic impact on who lives and who dies. The pressure is so huge that it has left clear scars on the human genome. The mutation that can cause sickle cell anemia has become very common in parts of the African continent because it helps protect people from malaria.
The story for ALDH2*2 is probably similar, Patel says.he is convinced that Several Infectious agents, perhaps some of them, play an important role in maintaining variation. Tuberculosis, which has a devastating track record, could be a candidate, but it doesn’t have to be. Several years ago, research in Woodward’s lab showed that aldehydes could be… We also conduct a lot of research on bacterial pathogens. Staphylococcus aureus and Francisella novicida. (Darwin and Stanley’s team showed that mice lacking ALDH2 can cope better with closely related mice. Francisella tularensis.) Che-Hong Chen, a geneticist at Stanford University who has studied ALDH2*2 for many years, suspects that bacteria may not be the culprit. He supports the idea that this is also malaria, acting on different parts of our genome in different parts of the world.
Other small perks of ALDH2*2 may have helped the mutation propagate. As Chen points out, drinking alcohol is a huge disincentive, and people who abstain (not all of them, of course) can largely avoid the possibility of liver disease. This is another way that the outcome of my genetic abnormality might not be so bad. Even if at first glance it seems like more trouble than value.
