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Ever since the age of Darwin — and especially since the discovery of DNA — scientists have thought of biological inheritance as something permanent. You inherit the genes that your parents gave you, and that's what you'll pass down to your children.
But in recent years, scientists have begun to realize that genetic inheritance may be more complicated than that.
Experiments have shown, for example, that the experiences of a parent might lead to molecular changes that aren't encoded in DNA but can still be passed down to children, affecting the health and behavior of future generations.
These findings fall within a field known as epigenetics — and research in this area has turned up a few tantalizing results. Perhaps most famously, a recent study appeared to show that mice can inherit experiences of fear from their grandfathers — something traditional genetics would have suggested is impossible.
For researchers who believe that epigenetic inheritance is a real phenomenon, the implications are a big deal. "The ramifications in terms of human health are enormous," says Sarah Kimmins, an epigenetics and reproductive biology researcher at McGill University. "What you're doing and how you’re living your life is going to have consequences not just for your child but for your grandchildren."
But epigenetics remains controversial. While some researchers are making some very big claims, others think that there's a lot of weak data, hype, and wishful thinking. So here's a guide:
What is epigenetics?
Before we get to a definition of epigenetics, it's worth backing up a bit. Every organism has genes that essentially act as an instruction book for creating various traits and life functions. The human genome, for example, has about 21,000 such genes.
Some DNA contains particular instructions for building particular proteins. But other parts help direct exactly when and where those genes should build those proteins.
That guidance is crucial — it's how our genes "know" to make certain proteins for muscle cells in one part of the body and other proteins for brain cells in another, for example. The parts of DNA that give these kinds of directions essentially interact with various environmental factors to turn genes on and off.
By the middle of the 20th century, scientists began realizing that DNA sequences weren't the only things telling genes what to do. Some instructions were also coming from the epigenome — basically a collection of other chemical markers and signals that interact with DNA and influence its activity.
Scientists have discovered that these chemical markers can also be affected by the outside environment. One good example involves bees. The difference between a queen and worker honeybee isn't their DNA sequences. Instead, larvae that end up becoming queens are fed more of a food called royal jelly, which contains ingredients that seem to regulate certain genes through epigenetic markers. In a similar fashion, scientists have found that some dietary choices in humans seem to turn cancer-related genes on or off.
Now here's the controversial part. Over the past decade, some scientists have suggested that epigenetic signals from the environment can be passed on from one generation to the next.
If that's the case, it would be a big departure from what scientists previously believed. Researchers have long known that the environment in the womb can alter fetal development. And they also have known that environmental factors, like radiation, could directly alter DNA that then got passed down. But environmental effects that only changed the epigenome — and not DNA itself — weren't thought to be heritable. (Scientists believed that these epigenetic markers were wiped clean and reset with each new generation.)
If this sort of inheritance is possible, though, it would mark a significant change in how we think about health. It might mean that the impacts of, say, diet or other environmental factors could be passed down for generations.
So how is epigenetic inheritance different from regular inheritance?
In the classical genetic model, you get genes from mom and dad, and they got them from their parents, and those genes stay almost identical from generation to generation — with the exception of a few random mutations here and there. Inheritance is mostly a solid and unchangeable thing.
But epigenetic inheritance suggests that a person's experiences could lead to directed molecular changes on top of his or her genes in very specific places. And those molecular changes could, in turn, get passed on. It suggests that someone can inherit experiences.
Epigenetic inheritance is an extra layer suggesting that someone's experiences may affect how his or her children and grandchildren use their genes. That clashes with everything that has been understood about inheritance since Darwin and Mendel.
So why are we talking about epigenetics now?
There has been a boom in all kinds of epigenetics research lately, as scientists have adopted new tools that allow them to more easily find epigenetic markers:
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Relative frequency of journal articles with titles containing epigenetic(s) vs. genetic(s). (Haig, D. International Journal of Epidemiology, Volume 41, 2012)
How does epigenetics work, exactly?
(National Institutes of Health via Wikimedia Commons)
The details of epigenetics' mechanisms are still up for debate. Scientists are currently looking into various non-DNA molecules that might be able to turn genes on and off (and possibly get passed down from one generation to the next).
One mechanism that gets a lot of study involves reversible molecular tags called methyl groups that attach to DNA and can potentially turn certain genes off. Researchers have shown that these methyl groups can be inherited, too.
However, there are several other types of molecules that might also be involved in epigenetics, and they aren't necessarily mutually exclusive with each other. Methyl groups and other small molecules also attach to histone proteins (which DNA is wound around), which may affect how particular genes are used. Scientists are also studying other molecules, including small RNAs.
What are the big, possible findings in epigenetics research?
In the past decade or so, scientists studying epigenetics have begun to put together a few broad findings that could drastically change how we think about health.
1) Grandparents might be able to pass on their experiences to grandkids: Some epidemiological studies that track health over several generations seem to suggest that the experiences of grandparents can somehow get passed down at least two generations, to grandkids. And this inheritance doesn't appear to be due to genetic mutations — but rather something else.
One key group of epidemiological studies focused on a century's worth of health records in an isolated community in Sweden — where, in some years, people often wouldn't have enough to eat (due to, say, a bad harvest). A study published in 2002 found that the men in this region who had plenty of access to food between the ages of 9 and 12 went on to have male grandchildren with higher rates of diabetes and heart disease. This multiple-generation effect is an intriguing correlation, suggesting that something is being inherited that's not DNA.
Other researchers have found that the grandchildren of women who were pregnant during the Dutch famine of 1944 to 1945 were more likely to be fat as newborns. A possible mechanism for this is that the famine interfered with the normal process of embryos stripping epigenetic marks off of their DNA to start off fresh.
However, these kinds of epidemiological studies have some inherent weaknesses. One is that it's impossible to fully account for all the different variables that might change if someone has gone through starvation. For example, people who live through a famine might end up raising their children differently, which could in turn affect how their kids raise their own sons and daughters. (In other words, this might be due to upbringing and social learning rather than epigenetic inheritance.)
2) Animals might pass experiences on for two generations — and maybe through epigenetic changes: Animal studies can sometimes allow researchers to better tease apart cause and effect, because scientists can control more of what's going on in a laboratory than they can with people living in the real world.
Some interesting recent animal studies include a paper published in December 2013 (by Sarah Kimmins and colleagues), showing that male lab mice fed a diet low in folate had different epigenetic markers on DNA in their sperm and had babies with more birth defects.
And this summer, a paper published in the high-profile journal Science showed that female mice that were starved during a key period in pregnancy had children with low birth weight and metabolic problems and had grandchildren with metabolic issues, too. What's more, the mothers' sons had different epigenetic markers on their sperm DNA, suggesting that's how the health problems are getting passed down.
Perhaps the most intriguing animal paper so far is a study published online in the winter of 2013 that appeared to show that fear memories can be inherited. Researchers from Emory University trained male mice to associate an odor with an electrical shock, so that they would get startled simply by smelling the odor by itself. Surprisingly, the scientists found that the smell also startled the next two generations of mice.
And this behavior was inherited even if the mice were conceived through in vitro fertilization — which seems to rule out any social learning between generations. However, this study has been controversial: some experts have questioned the part of the analysis that claimed to show epigenetic changes on the gene for the relevant nose scent receptor.
3) Childhood experiences might affect adult health — possibly through epigenetic changes: The idea that one's childhood experience can affect one's health as an adult doesn't seem all that surprising. But studies are beginning to show correlations between childhood experiences, health later in life, and epigenetic markers on DNA.
These markers could help researchers understand why certain health effects show up — and maybe even help people undo adverse effects.
One key study showed that baby rats fostered by mothers who provided less care have epigenetic changes on a gene related to stress. Child abuse in people has been correlated with similar epigenetic changes, too. Name a health condition — cancer, diabetes, schizophrenia — and there's a decent chance that someone's found some kind of correlation to an epigenetic marker.
But there are plenty of caveats here: the causal data isn't that strong. And it's unclear how big the effects might be.
Why could epigenetic inheritance be such a big deal?
If some parents' life experiences are being physically passed down to subsequent generations, this could drastically change the way we view a lot of health issues.
It means that choices that parents made, possibly decades ago, might affect not only their own health, but their children's health as well. (This includes choices made by both mothers and fathers.) It would also mean that certain environmental stresses, like poor nutrition associated with poverty, might be partially inheritable.
The flip side, however, is that understanding epigenetic inheritance could lead to ways to prevent or lessen the disadvantages that might be written onto children's genetic material.
What's the controversy over epigenetics?
The big controversy is whether these epigenetic markers are actually being passed down through multiple generations. This idea is known as transgenerational epigenetics. And the idea is still fairly young and not fully sketched out.
"It’s sort of 'Wild West' days," says Michael White, a geneticist at the Washington University School of Medicine. "A lot of the hype is due to technology, and it’s going to take a while to sort it all out."
The field is currently popular with big journals, the press, and the public's imagination because of the possibly huge health implications.
Some researchers say that transgenerational epigenetics is absolutely real. They're just looking for the exact mechanism of how experiences are written into someone's eggs or sperm and then how those molecules avoid getting cleared away in the womb.
But others don't buy that transgenerational epigenetics has been adequately demonstrated.
"It’s not impossible that there are transgenerational effects, but I haven’t seen any really compelling example," says Tim Bestor, a genetics and development researcher who focuses on epigenetics at Columbia University Medical Center. "I mean I have no bias against it. It’s just the studies that claim transgenerational inheritance have been of such poor quality."
So am I doomed if something bad happened to my parent or grandparent?
Not necessarily. First of all, it's important to remember that epigenetics is still a fairly young field of research. No one really knows how much epigenetics influences future generations. It could be a lot, or it could be very little, or maybe it's not happening at all.
Also, remember that these epigenetic molecular tags are physically reversible. They're not necessarily a permanent form of inheritance, the way that DNA is. It's possible that you could inherit some problematic molecular tags, but then your own life experience would change them for the better.
It's also possible that behavioral changes or drugs could someday be used to undo unwanted epigenetic states. That is, there's the possibility that scientists could actually strip disadvantageous epigenetic markers off of people's DNA.
