How Your Grandparents' Famine Could Be Written in Your DNA
By Science Insights | Published: October 2023
We've long been taught that our destiny is written in a double helix code we inherit from our parents. DNA is the unchangeable blueprint of life, right? Well, prepare to have that story rewritten. A fascinating field of science called epigenetics is revealing that our experiences—trauma, diet, stress—can leave molecular "notes" on our DNA, and astonishingly, these notes can be passed down to future generations . It's not a change in the genetic script itself, but a change in how it's read. This isn't science fiction; it's a biological reality, powerfully demonstrated by one of the most compelling natural experiments in human history.
To understand this revolution, we need to distinguish between two layers of our genetic information.
This is your DNA sequence—the A, T, C, and G nucleotides you learned about in school. This script is essentially fixed at conception and is passed down through generations largely unchanged.
Imagine your DNA script is handed to a director covered in sticky notes. Some notes say "READ THIS PART LOUDLY!" while others say "IGNORE THIS PAGE!" These are epigenetic marks. They are chemical modifications, like methyl groups, that attach to DNA and its associated proteins, turning genes on or off without altering the underlying sequence.
These annotations are dynamic. They respond to your environment, diet, and experiences. The truly mind-bending part? Some of these annotations, acquired during your lifetime, can be inherited, giving future generations a biological head start—or handicap—based on events they never lived through .
While the concept was once controversial, a tragic historical event provided the perfect conditions for proof. Towards the end of World War II, a German blockade led to a severe famine in the Netherlands, known as the Dutch Hunger Winter. For about five months, daily rations dropped to as low as 500 calories. This period of acute starvation was followed by a rapid liberation and return to normal food supplies.
For scientists, this created a perfectly defined natural experiment:
Researchers, decades later, tracked down the children who were in the womb during this famine.
Dutch Hunger Winter famine occurs during WWII
Initial studies identify health patterns in famine-exposed children
Epigenetic analysis begins on preserved samples
Landmark study published showing epigenetic changes at IGF2 gene
This long-term study aimed to answer a critical question: Did prenatal exposure to famine have lifelong health effects, and if so, could epigenetics be the cause?
Scientists identified individuals born in specific cities in the Netherlands just before, during, and after the famine. They grouped them based on the timing of their mother's pregnancy relative to the famine period.
They gathered decades of health records for these individuals, focusing on long-term outcomes like rates of obesity, heart disease, and schizophrenia.
Decades after the famine, researchers took blood samples from these now-adult children. They used advanced genomic techniques to scan their DNA, specifically looking for DNA methylation patterns.
The methylation patterns of those exposed to famine in the womb were meticulously compared to those of their unexposed same-sex siblings, providing a powerful genetic control.
The results were stunning. The prenatal famine exposure had left a permanent, measurable mark on the children's epigenome.
Individuals exposed to famine in early gestation had higher rates of obesity, coronary heart disease, and other metabolic disorders in later life.
When analyzing their DNA, researchers found significantly lower methylation levels on a key gene called IGF2, a gene crucial for growth and development. This gene was effectively "overexpressed" because the silencing marks were missing.
The scientific importance is profound. This was direct evidence in humans that:
| Exposure Period During Pregnancy | Increased Risk of Obesity | Increased Risk of Coronary Heart Disease | Schizophrenia Rates |
|---|---|---|---|
| Early Gestation | 2.1x Higher | 2.7x Higher | No Significant Increase |
| Mid Gestation | 1.4x Higher | 1.8x Higher | No Significant Increase |
| Late Gestation | No Significant Increase | No Significant Increase | 2.0x Higher |
| Unexposed (Control) | Baseline | Baseline | Baseline |
Data shows a clear link between the timing of famine exposure and specific adult-onset diseases, suggesting critical windows of developmental programming.
| Study Group | Average Methylation Level at IGF2 | Statistical Significance (p-value) |
|---|---|---|
| Prenatally Exposed Individuals | 48% | < 0.001 |
| Their Unexposed Siblings | 52% | (Reference Group) |
This demonstrates a persistent, statistically significant epigenetic difference six decades after the initial exposure, directly linking the famine to a change in gene regulation.
How do researchers uncover these invisible marks? Here's a look at the essential tools.
The gold-standard method. Treating DNA with bisulfite converts unmethylated cytosines to uracil, but leaves methylated cytosines unchanged. Sequencing the DNA afterward reveals exactly which cytosines were methylated.
A faster, targeted technique to check the methylation status of a specific gene. It uses primers designed to bind only to methylated or unmethylated DNA sequences after bisulfite treatment.
Proteins called histones package DNA. Specific antibodies can be used to pull down histones with certain modifications (e.g., acetylation for "gene on"), allowing scientists to see which genes are associated with them.
The cutting edge. Instead of cutting DNA, these modified CRISPR systems are used to add or remove epigenetic marks (like methylation) at precise locations, allowing scientists to test the direct effects of these marks.
The findings from the Dutch Hunger Winter and subsequent studies have fundamentally changed our understanding of inheritance and health . We are not just the product of our genes, but also the lingering echoes of our ancestors' experiences. This knowledge is both a warning and an opportunity. It highlights the profound importance of prenatal and public health. But it also offers hope: if negative marks can be passed down, perhaps so can positive ones from healthy lifestyles. The story of our biology is far more complex, intergenerational, and wondrous than we ever imagined. The final commentary on our genes is that their story is still being written, with annotations from the past and, potentially, from the choices we make today.
Epigenetics reveals that our life experiences can leave molecular marks on our DNA that may be passed to future generations, fundamentally changing how we understand inheritance and health.