Shelley Berger was on vacation in Costa Rica, walking through the rainforest, when she noticed the long highways of leafcutter ants leading away from and back to their nest.
It was far more than a curiosity to Berger. She has a doctorate in cell and molecular biology, and she had spent years studying epigenetics — basically, how the DNA and genes we were born with, and thus our bodies, are influenced by external factors. She instantly thought about how all the ants she was seeing had basically the same genetic material. Yet different ants in the same nest — the same species — looked dissimilar and did different jobs.
It was, as she later recalled, “a eureka moment.” She knew she wanted to study ants, work that ultimately shed light on humans, who have largely the same genome, but also have markedly different looks and behavior.
Berger is now director of the Penn Epigenetics Institute and co-leader of the Tumor Biology Program at Penn’s Abramson Cancer Center. She and her team have published research looking at what ants can tell us about social behavior and aging. She recently spoke to us about her work.
Let’s start with humans. We begin as one cell that divides, divides again, and so on. The DNA is the same in every cell in our bodies. And yet we have 200 different cell types – skin, eyes, organs. The way that happens is that the same DNA is used differently in different cells. Some of it is turned on, in effect, and some of it is turned off to make different cells. That’s called gene expression.
To understand epigenetics, let’s look at identical twins. They come from one single initial embryo that is then divided, so the DNA is absolutely the same in two identical twins. At birth, they are virtually identical. But as they age, things change. They begin to look different. They may age differently. They may die of different diseases. That’s where the environment comes in: what you eat, how much you sleep, what toxins you are exposed to, how much you exercise, all sorts of things. These things also affect what parts of our DNA and genome are turned on or off. Without getting into any mechanisms, the basic overarching idea of epigenetics is that the environment has a big impact on our development, on disease, on aging.
What’s interesting about epigenetics, and the reason it’s of great interest now, is that these epigenetic processes can be reversed. Diabetes is a good example. Let’s say you inherit a mutation for diabetes. That’s genetics. That’s not going to be reversible. But we have a huge incidence of Type 2 diabetes, due to poor diet and obesity. That’s epigenetics — changes to our cells because of external factors. And we are finding that the changes are reversible. If a diabetic loses weight to control the disease, it’s not just that you are reversing obesity. You are changing the way your cells are working.
I was on vacation in Costa Rica with my husband and daughter when I saw the highways of the leaf-cutter ants. The leaf-cutters are very complex in terms of their social system. They have more than 10 behavioral and morphological “castes,” as they are termed, yet they all have the same genome. The ants are exactly like the cells in the human body, but on a whole colony level. So, as in our cells, they can use or turn off different parts of their genome to make ants with completely different behaviors and tasks — one that’s a soldier, say, or one that’s a forager.
I got so excited. I thought, “Oh gosh, that’s a complex social system all based on epigenetics, not genetics.” I started to look into whether we could study it and manipulate it in the laboratory. I met with another epigenetic scientist I knew and we started to build the whole experimental system from scratch.
We had to find an experimental species that would be good to bring into the lab. Instead of the leaf-cutters, with 10 complex castes, we went with carpenter ants, similar to what you might see around your house. They have just two castes of workers: soldiers and foragers.
By the way, this is a departure for my lab. We study cancer, the brain and aging, in mice and cell systems. The ants are just one part of my lab. The beauty of studying epigenetics is that you can study its impact in different areas of human biology. The ants represented to me a way to study complex sociality.
We have an ant room in my lab set up with plastic boxes with ants living in them. Simple. But we’re using sophisticated techniques normally used in brain or cancer research to study them. We inject the ant brains with specific drugs to induce epigenetic changes.
This is a golden time for biological research because there are so many ways to ask extremely rigorous questions about the differences between cells. We’re doing this with the ants now. You can take single brain cells and understand how they are changing in the different behaviors. That’s really amazing.
Our biggest discovery has been that we can use epigenetic manipulation to change a soldier ant into a forager ant — note that both castes are female, not male. She still looks like a soldier. She still had a big head with giant mouth parts for cutting and biting. But we change her behavior into a forager that searches for food.
That’s a really interesting finding. But there are also a couple of aspects that we think are of wide interest beyond the ants. One thing is that when we do this epigenetic manipulation, it has to be done very early, right after the ants hatch. Even though they look like adult ants, their brains are plastic, still open to changes, much like our brains are at birth. It’s early enough that we can still change the genome before parts of it become permanently “open or closed” to make the soldier brain.
In fact, we now know exactly the time at which the ants’ genome is no longer plastic: 10 days. We have found that the genome is the most susceptible to change at five days.
Now that we’ve figured out the precise epigenetic mechanism that is taking place, we want to figure out in what cells, in what part of the brain, all this is happening. Maybe this will help us to understand what parts of the human brain are involved in behavioral changes.
And now, we have added leaf-cutter ants to the lab. We want to understand on a bigger scale, with dramatically different castes, what kind of changes there are in the brains of these ants, and what that can tell us about humans. In humans, we don’t have two behaviors, we have hundreds of behaviors.
You never know what’s going to turn out to be of medical importance 10 to 15 years from now. What kinds of fascinating biological mechanisms are out there in the universe? Whether they become of relevance or value, both medically and commercially to humans, is hard to predict.
However, I will say that with this ant study, we are using a very simple system to try to reduce some of the complexity in human behavior to a much simpler thing. Soldier or forager? It’s so binary. It’s so simple, so elegant.
I want my research ultimately to have value to society. I feel responsibility to try to apply some of my work to human biology and human medicine.