The Patterns of the Genes

With its multitude of colored fields juxtaposed in a seemingly chaotic arrangement, the computer monitor of Dr. Florian Böhl looks like a patchwork quilt. In fact, the colored fields on a white background show millions of measurement results obtained from the DNA strand of a chicken. “I used to think that in the field of animal diagnostics everything had already been discovered,” says Böhl, who holds degrees in biology and business management and worked in Sweden, Germany, England, and Switzerland before joining Creavis six years ago. At this unit, Evonik is transforming future-oriented technologies into new business activities. “However, after I took a closer look, I discovered the uncharted territories on the map. That activated my natural affinity for scientific research.”

The decoding of the human genome 20 years ago was a sensational achievement. It seemed as though every aspect of genes was now known. But that was a mistake. Today it’s clear that DNA is not the only factor that determines what a living organism looks like and how it behaves. The organism’s environment has an influence on its genes—and thus on its appearance and behavior, as well as the speed at which it ages. This influence is so strong that these changes are passed down to subsequent generations. Scientists call this phenomenon epigenetics. Some researchers are investigating the epigenetics of human beings, while others are decoding the DNA of crayfish or wild animals. Florian Böhl was intrigued by chickens. Together with his team and colleagues at various locations, Böhl, who is now 49, is decoding the epigenetic patterns of this species.

Healthy nutrition is a current trend. And Böhl was already wondering years ago how it could be possible to help shape this trend in livestock farming. But how can we find out how well a chicken is doing at any given moment? By measuring the level of stress hormones in its blood? Böhl believed that would not be sufficiently precise. He thought back to his time at Cambridge University, and suddenly he had an idea. “As a cell biologist, I was investigating how genes could be shut down or activated,” he says. Böhl, who had originally conducted research with yeast and fruit flies, decided to apply the knowledge he had gained to broiler chickens—in the special field of epigenetics.

As early as the 19th century, the French biologist Jean-Baptiste de Lamarck realized that living organisms obviously transmit acquired characteristics to their descendants. Back then, no one took him seriously; this idea contradicted the recently discovered science of heredity, and Lamarck himself could not explain his theory with sufficient plausibility. The concept only picked up speed shortly after the turn of the millennium, when researchers were suddenly able to analyze DNA. Initial studies revealed that the experiences of forebears had an effect on the genes of their descendants. Elizabeth Blackburn, who received the Nobel Prize for Medicine in 2009, was one of the first researchers to investigate the hypothesis that stress alters the genome.

Epigenetics is known as the link between the environment and the genes. It is the field of biology that deals with a living organism’s physical appearance. “We look different at various points of time during our lives—depending on how old we are,” says Böhl. “But this cannot be explained in terms of the genes, because they always remain the same. It can only be explained via epigenetics.” Epigenetics reveals the biological age of a human being, which depends, among other things, on whether the person has had lifelong healthy nutrition, smoked heavily, practiced sports or frequently drunk alcohol.

Epigenetics also helps to explain why overweight and diabetes are strongly increasing in many countries that used to be underdeveloped. In phases of famine, the individuals who can store energy effectively have the best chances of survival. If sufficient food then suddenly becomes available, their descendants gain weight faster than the average. In animal experiments, the descendants of underweight mice had a higher risk of diabetes even two generations later.

To make sure that the “chicken clock” could be used as a health check, Böhl’s team analyzed the methylome of chickens with a gut infection. “It showed that the immune system correlated with our measurements,” he says. The inflammatory reaction changes the methylation—and that too is a new discovery. Its main advantage is that this molecular biology tool can be used for every kind of tissue. “We can make the measurement in the animal’s loin, its leg or a part of its gut—on principle, it doesn’t matter where,” Böhl says.

One of the most important partners in Böhl’s far-flung network is Professor Frank Lyko, a former fellow student of his at Heidelberg University, who is now the head of the Division of Epigenetics of the university’s German Cancer Research Center (DKFZ). At some point, Böhl told his former fellow student about the chicken epigenome. Even though at first sight this topic has little to do with research on human cancer, Lyko was interested. The two scientists’ initial joint experiments eventually grew into close cooperation. Böhl uses the infrastructure of the DKFZ, and Lyko benefits from Böhl’s findings.

Today, unlike a few years ago, we know that cancer is triggered not only by mutations in DNA but also by other factors, says Lyko. Now, he explains, it’s clear that “epigenetic mutations on the DNA, which are known as epimutations, also play a role.” Lyko adds that authorization has been received for initial cancer tests based on epigenetic markers, and even for the first medications that work by means of epigenetic mechanisms. “The way that the environment interacts with the epigenome is a significant element of our understanding of cancer, but it’s not easy to investigate it in human beings,” he says. As a result, animal models are playing a major role—especially models of animals that are genetically homogeneous and grow up under standardized conditions, but are nonetheless subject to a variety of environmental factors. Chickens fulfill these requirements.