Genetics: More complex than we are told

[sue_frantz]

While it had been common for astronauts to spend six months at the ISS, NASA wanted to know what happens when humans spend even longer in space. Depending on the orbit trajectory chosen – which depends on how much fuel you want to take with you – a trip to Mars could take 7 to 9 months (Carter, n.d.). And then once you get there, you probably want to spend some time there. Heck, I spend more than a few days in Australia when I travel there, and that’s just 7,744 miles/12,462 km. And then you have to travel home from Australia – I mean, Mars.

If you’re NASA and you have identical twin astronauts, there’s only one reasonable thing to do. You put together a team of researchers who are experts in human physiology, behavioral health, microbiology, and epigenetics to find out everything you can about the twins today. Next, you send one of them into space for twelve months. When the astronaut comes back to earth, repeat the measurements for both astronauts. This is NASA’s Twin Study. Mark Kelly* was the twin who stayed on earth; Scott Kelly was the twin who spent a year aboard the International Space Station (ISS)**.

In January, 2018, NASA shared some preliminary research findings from their twin study.  

Another interesting finding concerned what some call the “space gene”, which was alluded to in 2017. Researchers now know that 93% of Scott’s genes returned to normal after landing. However, the remaining 7% point to possible longer term changes in genes related to his immune system, DNA repair, bone formation networks, hypoxia, and hypercapnia.

This makes it sound like Scott’s genes underwent some kind of change. Journalists grabbed hold of this and declared that Scott and Mark were no longer twins since their DNA was not the same. This was not what the researchers meant. NASA clarified:

Mark and Scott Kelly are still identical twins; Scott’s DNA did not fundamentally change. What researchers did observe are changes in gene expression, which is how your body reacts to your environment. This likely is within the range for humans under stress, such as mountain climbing or SCUBA diving.

What changed were not Scott’s genes, but rather his gene expression – in other words, his epigenetic code.

A Brief History of Everyone Who Ever Lived by scientist and science writer Adam Rutherford is a nice summary of what we know, what we don’t know, and what we would like to know about genetics and, to a lesser extent, epigenetics.  Our epigenome is what turns genes on and off. Women who have two X chromosomes (that’s most of us) have all the genes on one X chromosome in each of our cells turned off. “In mammals, epigenetic modifications tend to get reset each generation, but some, very limited, rare epigenetic tags appear to be passed down from parent to child, at least for a couple of generations.”  Pregnant women who starved in the Netherlands during the winter of 1944 gave birth to low-birthweight babies (no surprise) who then grew up to give birth to babies who were high-birthweight (surprise). Other research in a rural Swedish community with variable harvests found that boys who experienced a lean year just before entering puberty were more likely to have grandsons – yes, grandsons – who lived longer. But most epigenetic changes are temporary (Rutherford, 2017).

In the case of reporting that astronauts Mark and Scott Kelly were no longer identical twins, the journalists were merely reporting what they understood the NASA press release to be saying, so I’m not going to fault them.

Earlier this month we read headlines declaring that despite years of research showing that the adult human hippocampus produces stem cells that grow into new neurons, that a new study declares that’s not the case at all. I was poised to pounce on journalists for getting this wrong. But I can’t. Once again, it’s the Public Relations department, this time at the University of California at San Francisco.

Now UC San Francisco scientists have shown that in the human hippocampus – a region essential for learning and memory and one of the key places where researchers have been seeking evidence that new neurons continue to be born throughout the lifespan – neurogenesis declines throughout childhood and is undetectable in adults (Weiler, 2018).

Rutherford (2017) reminds us that “[j]ournals are not all equal, and publication in a journal is not a mark of truth, merely that the research has passed the standard that warrants entering formal literature and further discussion with other scientists.” This is worth hammering into the heads of our students, our students who are the future writers of press releases, the future writers of news articles, and the future readers of those new articles. Our science journals are just one huge chat room. "Hey! This is what I found!" "Huh. How did find that?" "What if we looked at it this way instead?" "Anna used this other method and found something different. Anyone know why that would produce different results?"

With additional research, we may discover that, indeed, the human hippocampus does not produce new neurons. And we may discover that living in space where a person is subject to the radiation equivalent of 10 chest x-rays a day (Kelly, 2017) does indeed change one’s genes, and not just the epigenetic code. Those who turn to science for definitive answers may find the responses couched in probabilities less than satisfying. But that’s how science works.

Here’s a cautionary tale: Everyone knows that tongue-rolling is genetic. If you can roll your tongue, you have the dominant allele for tongue-rolling. As it turns out, everyone is wrong. The research was easy to do. Find a bunch of identical twins and see who could roll their tongues and who couldn’t. If tongue-rolling were completely genetic, each twin pair should be, well, identical in their tongue-rolling ability. Philip Matlock (1952) looked in the mouths of 33 pairs of twins. In 7 pairs, one twin could tongue-roll while the other one could not. And, yes, that date is right; he did this research in 1952. Similar studies in the 1970s found similar results (Martin, 1975; Reedy, Szczes, & Downs, 1971).

If you had asked me last week, “Hey, Sue, is tongue-rolling simply controlled by our genes?” I would have said yes. But now my response is more nuanced. “There’s likely a gene or set of genes that controls it, but there is also probably an epigenetic code that turns that gene or genes on or off for different people. Let me tell you about this interesting research done with identical twins…”

The more I learn, the less confidence I have in what I have always known to be true.

“Half of what I’m going to tell you is wrong, but I don’t know which half.” I love this quote (or paraphrase?) as it nicely captures the moving nature of science, but I can’t find the origin – and I find that very fitting. My memory says it was something Paul Meehl said to his students, but I can’t find any such reference. A Psychology Today blogger credits an uncited and unnamed surgeon. If you know the origin, please contact me.

References

Carter, L. (n.d.). If Mars is only about 35-60 million miles away at close approach, why does it take 6-8 months to get there? (Intermediate). Retrieved from http://curious.astro.cornell.edu/physics/64-our-solar-system/planets-and-dwarf-planets/mars/267-if-m...

Kelly, S. (2017). Endurance: A year in space, a lifetime of discovery. New York City: Knopf.

Martin, N. G. (1975). No evidence for a genetic basis of tongue rolling or hand clasping. Journal of Heredity, 66(3), 179–180. https://doi.org/doi.org/10.1093/oxfordjournals.jhered.a108608

Matlock, P. (1952). Identical twins discordant in tongue-rolling. Journal of Heredity, 43(1), 24. https://doi.org/https://doi.org/10.1093/oxfordjournals.jhered.a106251

Reedy, J. J., Szczes, T., & Downs, T. D. (1971). Tongue rolling among twins. Journal of Heredity, 62(2), 125–127. https://doi.org/doi.org/10.1093/oxfordjournals.jhered.a108139

Rutherford, A. (2017). A brief history of everyone who has ever lived. New York City: The Experiment.

Weiler, N. (2018). Birth of new neurons in the human hippocampus ends in childhood. Retrieved March 24, 2018, from https://www.ucsf.edu/news/2018/03/409986/birth-new-neurons-human-hippocampus-ends-childhood

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*Mark Kelly’s wife is Gabrielle Giffords, the US Representative from Arizona who survived an assassination attempt in 2011.  

**”at the International Space Station” – I had a hard time deciding on the right preposition to use. Can one be on a space station if one is really floating inside it, except when Velcro-ed to a wall? In seemed to be a better choice, but felt clunky when I read it. I was ready to settle for at. NASA dodges the entire question and uses “aboard the ISS.” If aboard is good enough for NASA, it’s good enough for me. I’m confident we’ll get this figured out before we head to Mars.