Scientific experiments typically start with a question. Perhaps something like, “I wonder if intervention A will lead to effect B?” This initial conversation leads to brainstorming sessions on how to implement the intervention, and which methods to employ to capture the effect.
However, there are many questions about human physiology wherein the answer could never be justified in seeking. For example, what if someone asked; how does calorically restricting pregnant mothers (a softer way of saying the word starving), effect the long term health and well-being of the child? It is impossible to generate an ethical argument to perform this experiment. Yet, in what is a sad reality, if we look back in time there have been a number of real world experiments that address this question.
The Dutch Hunger Winter (Hongerwinter) of 1944-1945 provides a tragic, but almost perfectly designed human experiment examining what happens to offspring born of a mother who has been calorically restricted during pregnancy.
Following the Normandy landings on June 6th 1944, the Allied forces broke through German lines and gained control of much of France, Luxembourg and Belgium. On September 14th the Allies entered the Netherlands and it was anticipated that the German occupation would soon be over. But the advance of the Allies ground to a halt when attempts to gain control of the bridge across the river Rhine at Arnhem failed.
To support the Allied offensive, the Dutch government called for a strike of the Dutch railways. In retaliation, the Germans instituted an embargo on food transports. In November 1944, an unusually early winter descended upon the country, and despite food transport across water being permissible, it was too late for much of the population. Most waterways were frozen and it was impossible to bring food to the densely populated west from the rural east.
Food stocks in the west of the Netherlands depleted rapidly. As a result, the official daily rations for the general adult population fell abruptly. At the height of the famine from December 1944 to April 1945, the official daily rations varied between 400 and 800 calories. As a reference point, Canadian food menus recommend that adults consume ~2,000 calories per day.
Children born of mothers exposed to this famine have been followed for the past 73 years resulting in The Dutch Hunger Winter studies, the first of which was published in 1975. Following the children of these mother’s, again, although tragic, is a powerful experiment. Remember, the DNA code is set a conception, so whatever the consequences to the offspring, they are not explained by a change in the DNA blueprint.
In general, the children who were in utero during the famine have experienced significant long term health consequences as they have aged. Metabolic disturbances such as increased prevalence to obesity, diabetes, hypertension, and coronary heart disease are observed in this population. Mental health disorders including an increased risk for schizophrenia, major affective disorders, antisocial personality disorders and lower self-reported measures of mental health and quality of life are also observed.
The impact of the famine scales with gestation age. The earlier in gestation the exposure to famine was, the more significant the consequences.
From a scientific perspective, the question is, how is it that a 5 month exposure to famine while in the womb could have such dramatic health consequences? How does the physiology of a 60 year remember something that happened in utero, after their DNA code had been set?
One proposed answer involves a field of study know as epigenetics. Epigenetics describes modifications on the DNA code that changes the expression level of a gene, as opposed to altering the genetic code itself.
A months ago, I described the DNA code as cookbook, a gene as a recipe, and protein as the meal. An epigenetic modification would alter how easily a recipe could be read. It would be as if the typeface on a specific recipe was dimmed to the point you could not read it.
In the children of calorically restricted mothers, epigenetic modifications may have reduced the readability of certain genes, and/or amplified others. It would seem logical that the first adaptation to caloric restriction would be to increase the ability to store nutrients. Given that these children would eventually have access to surplus calories later in life, that initial imprint to store calories would increase the risk of obesity-related complications.
The psychological impact on the offspring from the Hunger Winter moves us away from metabolism and re-focuses on how these pregnant women would have been feeling during that 5 month span. No doubt a significant amount of fear and stress was present, and the horrific experience would have stayed with them the rest of their lives, ultimately influencing their children’s psychology and perhaps initiating epigenetic modifications on the DNA code.
The Dutch Hunger Winter affected 4.5 million people, however, if we look around the world today the number of individuals at risk for starvation is much higher. In Yemen alone, 8.4 million people are at severe risk for starvation. Worldwide, by some estimates, close to 100 million people are at risk for starvation. The full breadth of issues caused by maternal caloric restriction will continue to be studied in the generations to come.
By Brennan Smith, PhD.
