The Riddle of the Hungry Winter

Darwinian selection takes place in the womb

Alexey Aleksenko, "Snob"

Sometimes in science it is useful to be a dogmatic dogmatist. "The only reason for the existence of all life and all its properties is natural selection," says Darwin's dogma. But biology is a complex science, there is still a lot of incomprehensible in it, and often this incomprehensible develops into such bizarre shadows, as if, besides selection, there is someone else there.

To some biologists, from fans of mystical thrillers, it even seems fascinating: what if it's true? Few people have enough stubbornness and narrow-mindedness to just clench their teeth and repeat the mantra about selection, no matter what images they see in the semi-darkness. And since we ourselves do not like all this mystical nonsense, we were terribly pleased with a note by Dutch scientists published recently in Cell Reports (Tobi et al., Selective Survival of Embryos Can Explain DNA Methylation Signatures of Adverse Prenatal Environments).To share the joy with readers, we will have to explain everything in order.

Hungry Dutch

In the winter of 1944-45, an economic collapse occurred in Holland. The country was cut off from all supplies by fronts and a naval blockade. From November to spring, there was a real famine in the tiny country, which claimed almost two tens of thousands of lives. The diet has decreased to 500 calories.

However, life goes on despite the twists and turns of history: some of the good Dutch women were caught during pregnancy during these months, and someone even managed to get pregnant right in the midst of a cataclysm. Then, after the allies came in the spring and fed everyone to their full, children were born. And it was these children who asked the biologists a riddle.

Those that were born first – that is, they were conceived in the summer – turned out to be somehow smaller than usual. It is understandable: underfed. But the next wave of children – from those who were caught by hunger at the moment of conception or the first months of intrauterine development – surprised everyone: they were significantly fatter and larger than the average human infant. Interestingly, they remained like that for the rest of their lives. Even more interesting is that they passed this quality on to their descendants.

The history of mankind, it would seem, provided scientists with a lot of opportunities to experiment with hunger. There were the Ukrainian Holodomor and the Leningrad blockade in our region, the Great Chinese Famine of 1959-1961 and the famine of 1975 in Polpotovo Kampuchea in Southeast Asia. However, the Dutch "experiment" turned out to be unique for two reasons. Firstly, it lasted for a strictly fixed and short time, and before and after that, the food was completely normal. Secondly, we are talking about a civilized country with developed medicine: the fates of all the children of the hungry winter, as well as their children and grandchildren, have been tracked and documented up to today.

The most interesting part of the story is the overweight children (and later people) born in the late summer and autumn of 1945. In addition to body weight, other statistical anomalies were found in them, for example, a tendency to hypertension and certain mental disorders. And most importantly, they partly inherited these properties to their own children. The acquired qualities were inherited – contrary to Darwin, in exact accordance with the teachings of Jean-Baptiste Lamarck and Academician Lysenko.

Epigenetics, the Flood and Babylon

If someone does not like spoilers, you can read a wonderful book by Nessa Carey, where it is slowly and tastefully told about how biologists unraveled the mystery of the Dutch hungry winter and what fundamental discoveries it led to. But it will be enough for us, in view of our fussiness and haste, to know that epigenetics is to blame for everything. In the most popular presentation, the case looks like this: hereditary information is contained in genes, that is, in a sequence of "letters"-DNA nucleotides. However, adjustments can be made to this information: the body puts additional labels (chemical groups) on some letters, specifying exactly how these genes need to work.

In the early 2000s, Dutch scientists more or less formulated their hypothesis: the main difference between children of a hungry winter is precisely in epigenetic marks. In particular, they affected the insulin-like growth factor (IGF) gene. One of the authors of the study, Bastian Heymans, suggested that "epigenetics may be a mechanism that allows a person to quickly adapt to changed circumstances." That is, human embryos, caught by hunger in the womb, deftly rearranged their epigenetics so as to adapt to deprivation. Since the hardships were short-lived, this restructuring brought them harm rather than benefit in adulthood. However, they passed on some epigenetic marks to their children. Voila! We have a mechanism of directed hereditary adaptation that contradicts the concept of natural selection.

Nessa Carey, a very serious biologist, alien to ideological problems, ends her story about the Dutch winter with the following phrase: "The generation of the Dutch hungry winter shows that, paradoxically, Lamarck's heretical doctrine of heredity can, even sometimes, hit the mark." And those who are much more stupid than Carey, quite unashamedly declared that epigenetics "challenges the holy cows of Darwinism." "Could the color of skin, feathers and fur be the result of epigenetic pre–programming activated after the Flood in animals and after Babylon in humans?" - yes, now, of course, it could, seven troubles – one answer, since Darwin so pointedly got into a puddle with his vaunted theory.

Catharsis

Of course, science is obliged to follow the facts without regard to how an idiot can interpret these facts. Nevertheless, almost all biologists who had to retell this epigenetic epic to a wide audience could not do without some kind of polite curtsey towards Lamarckism or at least the "incomprehensible complexity of life" (which ultimately always hides some kind of Flood, Babylon, faithful Michurintsy or the memory of water).

But, thank the universe, someone was still very angry about this situation. Among them were the very Dutch biologists whose work started the hype. It was they who published an article this month that brought a little more clarity to our story.

The Dutch had at their disposal not only the medical data of the descendants of the hungry winter, but now also the detailed results of studying their "epigenomes" – the pattern of DNA methylation. They also had a good computer and three alternative hypotheses. First: the epigenetics of the descendants of the hungry winter is the result of a directed adaptation to a lack of nutrients during intrauterine development (this is what Bastian Heymans said, quote above). The second hypothesis: the change in the methylation pattern in the victims of hunger is just a side effect, an error, a glitch, a kind of "scar" on DNA (this hypothesis was expressed by another researcher and author of that article, Elin Slugbom). Finally, the third option: everything that happened to large babies born in 1945 is a consequence of Darwinian natural selection, and there is no need to multiply entities.

Then there was computer modeling and comparison of the model predictions with the observed results. The second hypothesis could be discarded immediately: if the hungry embryos simply had a malfunction in the methylation system, one would expect that they would have a greater spread of different variants than in the control group. But in fact it was significantly smaller.

A slightly more detailed analysis allowed us to reject the first hypothesis. All the data were perfectly consistent with the last option: the observed pattern is the consequences of intrauterine natural selection of spontaneous variations in DNA methylation.

The situation is as follows: when DNA is methylated at an early stage of embryo development, natural variations occur – the same spontaneous "small changes" as in the classical Darwinian paradigm. On the same days, the fate of the embryo is being decided: will it pass its way through the tubes into the uterus, will it reach the desired stage by the end of the path, will it attach, will it not be aborted in the first days or weeks? It is obvious that in unfavorable conditions (including in the winter of 1944-1945), these issues were particularly acute for the embryo. It must be assumed that this selection favored one particular variant of DNA methylation. It was he who led to the fact that the type of methylation prevailed in children born immediately after the test, leading to the very consequences that prompted biologists to draw a heretical conclusion from all this.

Let us repeat once again: providence did not intentionally adapt these unfortunate babies to anything. There was no instruction originally laid down: "If you are starving, do this and that with your IGF gene." Nature acted in its usual cruel way: to make a lot of random differences, then kill everyone who does not fit. It was this mechanism that best corresponded to the totality of statistical data on the epigenomes of the descendants of the hungry winter.

Moralizing

Probably, if the scientific community had shown a little more stubborn, dogmatic, non–reasoning faith in Darwinism, it could have come to this idea a little earlier. However, in order to prove their case, the selection fanatics would still have to wait for a certain level of bioinformatics development, so no one lost anything. Fans of Six–Day and other alternative biological concepts got the opportunity to scratch their tongues - well, they are already doing this without asking anyone for permission, and, obviously, they will continue in the same spirit, since there are a lot of incomprehensible things left in biology. For example, the first generation of Dutch undersized babies: it seems that they really have some kind of resource-saving program, albeit not inherited. At least, it is not possible to reject this hypothesis yet.

Of course, if this result had appeared a little earlier, perhaps some dead-end lines of thought would have dried up by themselves. Thus, inspired by the story of the "Dutch winter" in its Lamarckian interpretation, in the 1990s, the British doctor David Barker put forward the idea that the nutrition of the mother (and even the father!) during conception and pregnancy, it greatly affects the fate and health of children. The audience enthusiastically accepted this idea, which is quite consistent with the popular religion "the main thing in life is not to eat something wrong." With all due respect to the late Dr. Barker personally, it would be more pleasant for us if scientific ideas that feed the self-esteem of dieting ignoramuses were refuted a little faster, and put forward less often.

The fact that there are many misunderstandings left in the Dutch study, the authors themselves say in the conclusion to their article. Here, for example, is one of them: is it enough for the natural selection they discovered in the womb to simply assume the differential survival of embryos? Or maybe we should allow another kind of competition – between individual cells of the embryo (at the blastocyst stage, that is, a pouch of almost identical cells)? It is well known that such competition is taking place. It is also obvious that the epigenetic labels in these cells may differ. What is unclear is how to take into account all these options in computer models and whether this will affect the results.

However, scientists are paid money for that, so that they understand all sorts of difficulties. But no one pays us, the general public, money to make stupid, but at the same time unshakable ideological conclusions from misunderstood or distorted scientific discoveries. So why are we doing this all the time?

The author of the article is the scientific editor of Forbes.

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