The daily ration fits on one small table: a little bread, a few potatoes, almost nothing else. On average 667 kilocalories a day. In the winter of 1944–45 the occupied western part of the Netherlands was under a German food embargo and the rations were set weekly, the same for everyone. History remembers it as the Hunger Winter.
During those same months children are conceived. They are born at normal weight, they grow, they get old. And six decades later their blood still keeps a record of that winter: the chemical marks on one of their genes sit differently from those of their own brothers and sisters.
A tragedy with exact documentation
The Hunger Winter is a rarity for science for a grim reason: the famine is precisely bounded in time, and the Netherlands never stopped keeping records. Births were registered, the rations were documented week by week, the hospitals kept working. Decades later researchers can find the people conceived exactly in the famine months and set them against the closest comparison possible: their own siblings of the same sex, conceived before or after the famine.
That is exactly what the team of Bastiaan Heijmans and Lambert Lumey did in 2008 with 60 such pairs. The measure is methylation: the small chemical groups on the DNA that help the cell decide which genes to read and how strongly.
Six decades later
The participants are about 58 years old when they give blood. The researchers measure the methylation of a key stretch of the IGF2 gene, which governs growth and is one of the best-studied epigenetically regulated genes in humans.
In those conceived during the famine the stretch carries on average 5.2% less methylation than in their brothers and sisters. In 43 of the 60 pairs the lower value belongs to the person conceived in the famine months. To be sure, the researchers repeat the whole procedure from scratch in 46 of the pairs: the difference shows up again, almost the same.
The window is narrow
The strongest part of the study is the second group: 62 people who spent at least the last ten weeks of their mothers' pregnancies in the famine but were conceived before it. They were born on average 296 grams lighter than the babies from before the famine: the undernutrition marked them in the visible way. In their methylation, though, there is no difference at all.
Those conceived during the famine are the reverse: born at normal weight, with no visible trace, but with permanently changed marks on the DNA. The visible harm is measured on the scale and passes. The invisible one is written in the first days after conception, when the epigenetic marks are only just being laid down, and it stays.
How much is 5.2%?
In the same study, ten years of aging are linked to about 3.6% lower methylation of the same stretch. The record from a few famine weeks at the very beginning of life is deeper than the imprint of a whole decade of living.
What exactly carved it, the authors say carefully: the most likely mechanism is the shortage of building material for the methyl groups, including the amino acid methionine, though the cold and the stress of that winter cannot be ruled out. One thing, however, is firmly measured: a passing condition in the first days of development left a record in human DNA that can be read 60 years later.
The mice with the yellow and the brown coat showed the same mechanism in a laboratory. The Hunger Winter showed it in people, with dates, rations and registries. The marks on the DNA are written deepest at the very start, with the material the body has at hand in that moment.
Sources
- Bastiaan T. Heijmans et al., Persistent Epigenetic Differences Associated with Prenatal Exposure to Famine in Humans, Proceedings of the National Academy of Sciences 105(44), 2008: 17046–17049.
- L. H. Lumey et al., Cohort Profile: The Dutch Hunger Winter Families Study, International Journal of Epidemiology 36(6), 2007: 1196–1204.
- Robert A. Waterland and Randy L. Jirtle, Transposable Elements: Targets for Early Nutritional Effects on Epigenetic Gene Regulation, Molecular and Cellular Biology 23(15), 2003: 5293–5300.
