Professor Michael Skinner in his lab at Washington State University. (Michael Skinner)
There’s been a paradigm shift in the field of genetics. Instead of relying solely on DNA and inheritance, the field of epigenetics now demonstrates how environmental factors can also determine diseases in our future, and in our children and grandchildren’s future. Host Bruce Gellerman talks with epigeneticist Michael Skinner, a professor at Washington State University.
GELLERMAN: A failed laboratory experiment led to an accidental discovery that is changing the way we understand genetics. It happened in Professor Michael Skinner’s lab at Washington State University. Skinner was studying DNA—the genetic code of life…when he found, by chance, that environmental factors can change the way our genes work for generations far into the future, without damaging the DNA. Professor Skinner is what’s called an epigeneticist and he joins me from Pullman, Washington. Welcome to Living on Earth.
SKINNER: Thank you very much.
GELLERMAN: So, Professor, I looked it up and ‘epi’ is Greek for ‘on or around’ and genetics means ‘source or origins.’ So epigenetics – around the source, yeah?
SKINNER: Correct. So epigenetics would be things around DNA that regulate DNA activity but are independent of DNA sequence, thus, epigenetic.
GELLERMAN: So, something’s gumming up the switch, it’s not destroying the DNA.
SKINNER: Correct, correct. And so basically, sometimes it’s the structure of the DNA, how tightly it’s coiled, or loosened up, that can actually change what genes are turned on and off. And the thing that we study the most is the chemical modification of the DNA, called methylation. A small chemical gets put on the DNA, and that can also regulate what genes are turned on and off. All of this can be influenced by the environment, has nothing to do with changing the DNA sequence.
GELLERMAN: So tell me about you experiment, what did you do?
SKINNER: So we were studying early embryonic development and the process of sex-determination- so whether you get a male or a female. And, so what we did is we exposed animals, at the time of sex determination- to a couple of environmental compounds that are commonly in the environment- one was a heavily used fungicide in agriculture and one was a heavily used pesticide. And what we found was that we did not change sex determination. So, the experiment that we did for the purpose we did it actually failed.
However, we did see an interesting observation that the offspring, the embryos that were exposed, as they became adults, developed a high rate of disease. And then there was an accident in the lab and actually one of the fellows bred those animals to make the next generation- so this would be the grandchildren of the mother that was exposed during gestation- and they also had the high level of disease. So we followed that up and took it out four generations, and had the same high level of disease onset. And, it turns out the only way that that can happen is through an epigenetic-type-process.
GELLERMAN: And, you know for a fact that you weren’t damaging the DNA or the gene?
SKINNER: DNA sequence mutations occur at extremely low frequencies, usually less than 0.1 percent. And, they also occur randomly, they don’t reoccur at the same place at the same time, and so experiments would not be reproducible, and they would occur at extremely low frequencies. We see extremely high reproducible frequencies and so we knew that this was probably not a genetic mutation event.
In addition, we have actually done studies to show that we do not have an increase, apparently, in point mutations or chromosomes where the genetics does not appear to have any major affect.
GELLERMAN: Is there any population evidence to suggest, historically, that we’ve detected this happening?
SKINNER: So, almost every region of the world has different disease frequencies. So, for example, in Japan they have a very high rate of a stomach disease, and a very low rate of a prostate disease. In North America, we have a very low rate of stomach disease, but a very high rate of prostate disease. If you take someone early in life from Japan and put them in the United States, they will develop generally the North American disease frequency and have prostate disease and low levels of stomach disease. This suggests an environmental impact on disease. And so there’s a lot of epidemiology experiments like that which support that kind of concept.
GELERMAN: So give me an example of something that my mom might have been exposed to that wouldn’t have caused a mutation in me, but would have affected my genetic expression, if you will.
SKINNER: First of all, the most logical one is nutrition. There’s lots of nutritional elements that can regulate programming of the embryo and different tissues. In addition, in our society today, most people are exposed to a wide variety of environmental compounds. Whether it be the bisphenol phthalates (sp?) from the plastics, whether it be agricultural compounds like the fungicide that we used called Encloselin, most people are exposed to these types of compounds on a pretty routine basis. And so these compounds have the ability to alter the epigenetics as well.
GELELRMAN: So we should really be looking at pregnant women.
SKINNER: Pregnant women are definitely the most sensitive population for influencing the fetus’ adult onset of disease. So, yes, these early life events causing later life disease is something we need to think about more, in terms of medicine. What you are is to a large degree determined what your mother did during pregnancy.
GELLERMAN: So are there a lot of epigenticists around? I’ve gotta admit that I’d never heard of it before.
SKINNER: It is a growing field. And I think it does address a lot of our unanswered questions using genetics. For established scientists that have grown up and been trained in genetics, it is a difficult shift in their thinking to consider that there may be something else. And so I think it’s going to be more the younger generation coming in that pushes the epigenetic area.
GELLERMAN: Well, there’s a certain poetry to that isn’t there? I mean, here you are, your studies of epigentics is affecting future generations of scientists.
SKINNER: I mean, anytime you’re in a paradigm shift, there’s always some opposition and push back, and definitely it always takes time for it to integrate into that mainstream sort of science.
GELLERMAN: Well Professor Skinner, thank you very much, I really appreciate it.
SKINNER: Thank you very much.
GELLERMAN: Michael Skinner is an epigeneticist at Washington State University.
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