Epigenetics and the Process of Discovery

During my undergrad someone noticed that rats born from moms who were proficient in running a particular maze ran that same maze faster than rats born from moms who had never run that maze. We weren’t the first to notice this effect. Lots of studies were done trying to figure out this ‘inherited memory’ process. 

It was later realized that if you used ‘stressful’ triggers, like shock plates, then the ‘memories’ transferred easier. Further research found that it wasn’t the memories themselves that were transferred, it was a process of epigenetic modification where the stressful stimuli affected the offspring and made them more anxious, which increased their awareness and perception of the hazards of the maze, thereby avoiding them easier and finishing the maze faster. But now we know that you can actually induce avoidance of certain stimuli through inherited genetic memory using fear as the induction mechanism - which draws a lot of implications for the importance of treatment for anxiety disorders today. 

The interesting thing about this was, yes, the science, but also the entire process of discovery. From noticing an effect, to the backlash from everyone who called inherited memories pseudoscience and not to waste research dollars on such tomfoolery, to becoming generally accepted, to the very important epigenetics discoveries happening now as a result. 

The ‘inherited memory’ effects have been noticed since the 60’s at least, though you can make an argument for much longer. Point is, it’s taken that long for science to advance enough to allow us to start to figure out what might be causing these effects and for the idea to become accepted enough that it is now considered one of the most exciting areas of research. And research into epigenetic changes continues. There are current studies occurring concerning diet and lifestyle factors on all kinds of animals and what those changes to the mothers do to the offspring, and how far those changes go generationally. More importantly, research is also finding out how to reverse those changes. There are also studies looking at epigenetic changes on everything from yoga to mindfulness to sleep on humans showing how fast our genome responds to our daily activities, giving us control over our own genetic expression. 

This is why I have a hard time when people put up immediate blocks to any scientific inquiry. Calling things pseudoscience and poo-pooing investigations into areas where not a lot of decent research has been done is small minded. Why do you want to ONLY study things that already have an exhaustive backlog of well documented research? That’s an ego thing and a fear of being wrong at play. That’s not discovery. That’s just validation studies. Which, don’t get me wrong, are extremely important. But give me an area of research no one’s taken a serious look at any day. Those are the areas with the biggest potential for genuinely huge scientific breakthroughs that revolutionize society. Those are the areas where discoveries occur where you wind up with streets named after you. Even the failures are remembered as cautionary tales. And a lot of times the research that proves what something isn’t is just as important as those showing what something is. Remember Lamark…? Where would we be if his heavily criticized theories hadn’t caught the attention of Darwin? And, as it turns out, he wasn't that far off the mark...(pun totally intended.)

You want to be remembered as a scientist? Go where no one else is willing to look. Yes, your peers today will throw stones at you for daring to be so bold as to be open to discovery, but future generations will hail you as a pioneer and marvel at your bravery. Or, you know… keep validating what we already know so no one will confront you or tell you that you’re wrong. That’s important too.

Diet and the Epigenome

I have been obsessed with epigenetics since watching the movie Gattaca when I was younger. If you haven’t seen it, I apologize for the spoilers. The movie takes place in a version of the future where messing with your kid’s DNA is trendy and fashionable, all meant out of love and a desire to give them an advantage in life. Those who are born ‘the old fashioned way’ are generally discriminated against for being inferior.  In the movie, the Ethan Hawke character defies this generally held belief by utilizing diet, exercise, and education regimes to alter his phylogenetic expression and prove that nurture can win out over nature. I loved it so much. 

What that means in non-geek speak is that we are born with a certain genome. This genome consists of various genes, but not all of those genes are active at any given time. This is how each of your cells has the exact same DNA, but one cell can be a skin cell and one can be a liver cell. Which genes are active or inactive determines the outcome of that cell. This can also impact us health wise. For instance, you may have a genetic variant that makes it more likely that you’ll get heart disease, like Hawke’s character in Gattaca, but the lifestyle choices you make can determine whether or not that gene ever even gets turned on. The expression of your genome at any given time is your phenotype - the collection of genes that are actually ‘on’ and expressed from that genome. And epigenetics is the study of those changes - how to turn genes on or off. 

Epigenetic studies are finally starting to make their way into the popular media, and this makes me incredibly happy. One of the things that I wish we stressed more often when it comes to health and wellness is the general pliability of our genome. If you can turn genes on, you can turn them back off again, and vice versa. This means that if you’ve started a disease process if you can figure out the correct combination of factors, you can positively influence that process, if not reverse it completely. No one tells you this!! It’s like brain plasticity - if someone tells you that you can’t do anything about your brain injury you tend to just live with it instead of doing specific exercises and training that stimulate and enhance the inherent neuroplasticity of the brain. Which means you’re more likely to live the rest of your life in cognitive decline when there were very simple ways you could reverse some of those problems. Same goes for physiological changes. I use osteoporosis often as an example. Often, women are told to stop physical activity when they get osteoporosis. The problem with that is that osteoporosis is a disuse disease, meaning that bones are constantly remodeling based on the forces put upon them. If there isn’t sufficient weight-bearing on the bone, the body is signaled that you’re not using it anymore and starts to absorb it to use the calcium and collagen elsewhere. The exact same thing happens to astronauts in zero gravity. The difference is that astronauts undergo specialized training programs when they get back to earth to regrow that lost bone mass. So why do we tell women to stop exercising when we know that it’s exercise that keeps their bones healthy and that you can actually rebuild lost bone mass? 

It bears repeating so I’m going to say it again - if you can turn a signal on, you can turn it back off. Which is why I love epigenetics. I mean, yes, some signals for sure likely can’t be controlled by diet or exercise. I would be amazed if we somehow found some combination of diet and exercise that turns skin cells into liver cells, for example - but I’m not going to rule it out until all the data has been collected. 

So what does this mean for you? Well, a lot of research is currently being conducted as to what factors are important to prevent certain disease processes from ever being turned on, even if you have the genes for that disease process. It’s a lot more complex that just a single gene, as more and more evidence suggests it's the interplay of a lot of genetic factors that influence disease processes, not single genes, but we’re going to talk like it’s as simple as one gene gets turned on and you’re screwed, but eat healthy and you keep that gene turned off, for simplicities sake and to highlight my point. The phenotypic expression of any given cell is a constant interplay with the environment that that cell is in. If the cell is in a healthy, happy environment, it’s more likely to keep the happy, healthy genes turned on. If the environment changes to an unhealthy one, it’s more likely to turn on the genes whose job it is to deal with that unhealthy environment. This means that the cell has to undergo a process of transduction - changing phenotypic expression due to a change of environmental factors. Compounding this issue is that now that cell is in an unhealthy environment which is toxic, so you accumulate toxic changes to that cell’s genome, which typically includes cellular and DNA damage. This makes it more likely that your DNA is going to accumulate enough damage that it is no longer able to express itself properly. When that cell replicates, it no longer knows what type of cell it’s supposed to be, so it just kind of best-guesses. This is known as the formation of a cancer cell - an undifferentiated cell that then just multiplies and squeezes out the differentiated ones. 

If you change the environment that the cells are in back to a healthy, happy one, you remove the confusion, and the cells can stop trying to deal with the toxic environment, so they no longer need to aggressively defend their survival by rapidly replicating as this undifferentiated blob. This is the rational behind changing your health and lifestyle habits to help in the treatment of things like cancer. 

So how can you best help your cells and your genome? The anti-inflammation diet seems to help quite a bit. In general, however, there’s still a lot of research to be done. So check back often as I’ll probably write quite a bit on this topic. It’s my favourite, after all!