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“Are “Genes Are To Blame” Articles Really Leading the Public Astray?” The Epigenetics of Stress Mechanisms in Disease

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MindHacks” writer Vaughan Bell’s tweet subsequently retweeted by “Not Exactly Rocket Science” Blogger Ed Yong states that the media turns “blame your genes” into attention-grabbing headlines. They worry the headlines are misleading the public into thinking they are no longer responsible for their problems. That the articles are for those who want to absolve themselves of responsibility for badly behaving toddlers or so they can blame their genes rather than themselves for being a lazy couch potato or binge eating. If we can blame our genes then we’re not responsible, right? But where does that thought process come from? Most likely from our instruction that genes are out of our control random things we inherent from our parents. Therefore if genes are to blame, then we, our environment, is not. Those were our choices, either our genes or our environment were to blame for such things.

In defense of the articles, that is not what the authors or researchers seem to be actually saying.  Rather they are conveying an idea that there is a complex gene-environment interaction. The gene loads the gun and the environment pulls the trigger.  What the interaction reflects is that there is some aspect of our heritable selves, our foundational programming that interacts with our environment that creates an undesirable outcome. The public has not caught up with the gene and environment interaction yet, but then again neither have many science writers. Vaughn and Yong are saying that the public are idiots for not understanding the science of genes. Genes being a “thing” that causes a disease we inherit from our parents.  Which is a bit unfair since the public understands the headlines the way they had been taught to understand genetics from books and teachers; that if genes are to blame, we have no responsibility for that other than being born.  This again, isn’t what the articles represent. The articles represent a new science, a science that has yet to be embraced.

Vaughn continues along this same black-and-white reasoning to say that the articles are a farce because genes either play too minor of a role or play too complicated a role (from multiple genes) to be relevant causes.  However with a complexity point of view we’d see a relationship between genes and their environment. However small a gene’s role, the outcome doesn’t happen without the gene’s involvement. The interaction is what creates the outcome, not purely the environment OR the gene but the dynamic together.

This is wholly different than our classic scientific approach of singular blame and singular outcome; the black and white thinking of gene or environment. This is not a whoever or whatever has more influence wins the blame. Rather this is an interaction of a function from a foundational programming that has (or had) a purpose, with that programming coming at a cost of trade-offs in order to maintain balance.  So within an environment of compromised resources, we are burning out quicker, over-reacting more and have more complications when trying to maintain these balances. And that lack of maintaining balance is reflected in our growing number and intensity of diseases and disorders.

Genes are programmed for function

A subsequent twitter response was accusingly put to me implying:  “genes are for FUNCTION? What about the dreaded Huntington’s disease?”

That sounds reasonably insensitive on my part to state that a gene is for a function when we are told that genes are programmed for a disease.  What kind of function is a disease? The gene itself is for function, the disease is the outcome of the environment acting upon the gene (referred to as epigenetics).  Typically the programming may have been meant as a protective measure, but now it has become too much of a compensation and throws our systems out of balance.  This is the change in thinking that changes everything. Our gene correspondence to a disease isn’t that the gene, however responsible, directly meant to program for a disease. It is that they mis-adapt for a function with too heavy of a cost in an environment that “burns them out“. This “burning out” type issues end up being the diseases we know. The more we “mess up” our foundational resources, like diet, the more problems this creates in these compensatory measures.  It’s not direct though, rather its like hundreds of teeter-totters being thrown out of sync creating varying outcomes.

Are diseases just overly protective systems with too high of trade-offs?

Vaughan and Ed are a prime example of scientist and science writers not quite letting go of the old school accepted way of thinking that genetics are merely random mutations and the “stress” either gets us killed or not reproducing. It has been our belief that our genes are “hard wired” and perfectly stable. I see where it’s easy to think we are completely stable structures and stress either breaks us or makes us stronger during our lifetime. However, the more complex situation may be that what we think of as “just random” mutations serve (sometimes just a wild) attempted purpose for and from stress.  And that our stable structure is much more pliable than how we assumed it would work. Not extremely flexible, but slight changes to any highly stable structure can impact how that structure performs in ways we hadn’t thought of or expected. So it could be that some, if not most, mutations are an attempt to adjust to the environment to adjust to stressors (information from the environment). It makes sense that we have very stable genes, like any complex stable structure, but with the flexibility to react to and receive communication from the environment to make small nudges of adjustments— with trade-offs.   It is a tightly controlled system.  But still a system that can be ever so slightly altered by the environment by and how we experience stress, the ‘plasticity” or flexibility we exhibit. It’s most likely we have both: incredible stability, but with a layered and complex flexibility.

Is stress having a greater influence on us than we realize? 

Depression in this way could be seen as an “energy-saving” mode and over-eating an “energy-seeking” mode.  Stress is a call to action and a need for resources. Stress attempts to adapt us in the best way in the context of our individual differences by finding resources or protecting from excessive use.  Ultimately stress is information about what is important and what we must pay attention to in order to prepare, protect and adapt to our environment. Information and reaction like this is ultimately a good thing.  However, when our resources are lacking and we are require to excessively adapt; covering one challenge may leave us vulnerable to other challenges. Push the system too far, switch up stress resources too quickly, and we get more and more stressed out systems and environmental reactivity that overwhelms us.  The on-the-go adaptations no longer benefit us. The price is too high. Like an engine that has run too high for too long. We can no longer pay the expense. We get disorder and dysfunction.

The Case of Huntington’s Disease

Vaughn’s response states that Huntington’s is a gene you inherent from one of your parents. If one of your parents has it, you have a 50/50 chance of getting it. If you get the gene you get the disease. That’s it. Well, I am sure he’s simplifying for the public, because that’s not precisely the way it works. It is a rare single gene disorder but that doesn’t mean there wasn’t an environmental influence acting on it before and after birth. Everyone has the gene for Huntington’s; it’s in the mutation within the gene having more repetitions of its amino chain or CAGs that creates the disease. (Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation: Source). Those repetitions can then be inherited, passed on by parent to child. However, there could be several pathways that modify this gene influencing the repetitions and mutations, like stress. That’s where the original function of the gene and how it reacts to its environment (stress) comes into play. The Huntington gene (Htt) serves a purpose. It is considered “essential for embryogenesis“, which means its serves a very important purpose in our development. So let’s assume these genes are constantly checking out the environment and adjusting to it (maybe epigenetically). And we might think that some individuals have this gene alteration reflecting a particular development path meant for good things. They are wired in a particular way that worked for them; be it family, community structure or individual skill-set. It’s one way in which the brain programs for various strategies which can reflect resource needs, information processing (personality) and strategies for handling stress.  The Huntington Gene is a gene that programs for brain and nervous system development. This gene may create a more responsive system. It may be this particular system’s strategy or flexible programming. When this system is exposed to stress this may create a greater use of energy and a quicker burning out of energy reserves. A “gain of function” disorder along with a “loss of function” disorder. A neurodegenerative as well as a neurodevelopmental disorder. It’s a stress trade-off.

Another disorder if looked at a different way could be Diabetes Type 1. Instead of looking at it purely as a programmed disease, we might look at it as a programming for sugar -handling that will make certain individuals more susceptible to “burning out” their sugar processing. It may not be random. It may be that their sugar needs, because of their processing needs, are more specific to sugar than others with other processing needs. This is where genetics, environment and endocrine profiles connect and give us various but predictable outcomes. Not a program for a disease, but a program for a function that becomes a disease in stressed environments.

Huntington’s is unique in stress literature because it is deeply engrained into the genetic programming and is passed from one generation to the next through these replications as a dominant inheritance. But it’s not exactly as we have pictured it occurring as random luck-of-the-draw selection. Rather it may be that the “knowledge” within the gene is passed on and while there is a HUGE 50/50 luck factor there is also the more stress they experience the higher the replications or mutations and then the more intense the disease.  The greater the replications within that gene the quicker they burn through resources the more stress they experience and the more susceptible to other stress disorders they become. There is even reason to speculate that the stress could have created some of these extreme versions of the gene in the first place.

This makes logical sense. You have a gene that programs a function. An environment of stress that informs the system it needs to be more protective or more reactive. And you get function and protection, overly so, and it presents as a disease. Another potential example of a gene with not-so-great tradeoffs is Sickle Cell Disease. There is reason to believe that this gene could be protective against malaria which is common in tropical areas. Sickle cell is more common in those with a native African heritage. So the genetic “advantage” of a protective function survived through generations, but this survival benefit has a trade-off in functioning that creates greater susceptibility to oxidative stress and a multitude of other issues.  It’s not only logical, it’s supported by science and evidence. Not your typical straight-line science, but a more fuzzy and dynamic stress “Chaos” nonlinear interaction science.  It might be that it’s time to see what happens if we start expanding evolutionary theory to discuss how “random” is instead or also influenced by stress and these stress dynamics. Stress can still produce “random” but it offers us purpose, possibilities and patterns we have yet to recognize.

As I know Ed Yong expresses, and I agree with him it’s important that the general public does not misinterpret gene involvement with the sometimes media’s exaggerated claims that things like obesity are “in the genes” and therefore out of our control.  Where I expand on this is that it is also important to understand the myriad of stress factors like he mentions diet, social and media influences, and dozens of others like microbiota influences, which I describe in my house analogy for metabolic obesity and the degradation of these factors can have on stress resiliency.  How these factors create and act upon our genetic expression or epigenetic influences. It is complex to say the least, but they are not beyond our knowing if we see these influences and balances through the utilization of stress dynamics.

The “Your Genes are to Blame” stories aren’t scientifically empty because they have no meaning, rather they are scientifically empty because and until we start using the correct science to understand them.

So are scientists and science writers willing make this monumental change in perspective taking?  As simple as it may sound it is a monumental change of the fundamental assumptions and ways to plug in evidence to make sense of the mysteries and “we just don’t knows”.  The new gene-environment playground of chaos stress dynamics. It is my sincerest hope and belief that if we move to these dynamics it will give us more productive forms of research, education and exploration of diseases and disorders.  I’d like to see it be part of the conversation.

 

References:

Huntingtin’s Neuroprotective Activity Occurs via Inhibition of Procaspase-9 Rigamonti D1, Sipione S, Goffredo D, Zuccato C, Fossale E, Cattaneo E. Processing. J Biol Chem. 2001 May 4;276(18):14545-8. Epub 2001 Mar 5. http://www.ncbi.nlm.nih.gov/pubmed/11278258

Understanding and Combating Oxidative Stress in Huntington’s Disease. http://robbwolf.com/2013/03/ 13/understanding-combating- oxidative-stress-huntingtons- disease/

The Normal Function of the HTT Gene. http://ghr.nlm.nih.gov/gene/HTT

Selective Roles of Normal and Mutant Huntingtin in Neural Induction and Early Neurogenesis. Giang D. Nguyen, Solen Gokhan, Aldrin E. Molero and Mark F. Mehler. PLoS One. 2013; 8(5): e64368.  doi:  10.1371/journal.pone.0064368. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653864/ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653864/

Functions of Huntingtin in Germ Layer Specification and Organogenesis. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3742581/#B72

Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Mali Jiang; Jiawei Wang; Jinrong Fu; Lin Du; Hyunkyung Jeong; Tim West; Lan Xiang; Qi Peng; Zhipeng Hou; Huan Cai; et al.

HTT haplotypes contribute to differences in Huntington disease prevalence between Europe and East Asia. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083615/

Growing Prevalence of Huntington’s Disease. http://www.ncbi.nlm.nih.gov/m/ pubmed/23482661/

Society for Neuroscience. “Drug reduces brain changes, motor deficits of Huntington’s disease.” ScienceDaily. ScienceDaily, 26 November 2013. <www.sciencedaily.com/releases/2013/11/131126191636.htm>.

Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington’s disease age of onset. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC373491/

Glutathione peroxidase activity is neuroprotective in models of Huntington’s disease.
Mason RP1, Casu M, Butler N, Breda C, Campesan S, Clapp J, Green EW, Dhulkhed D, Kyriacou CP, Giorgini F.Nat Genet. 2013 Oct;45(10):1249-54. doi: 10.1038/ng.2732. Epub 2013 Aug 25.Nature Medicine. 2012;18(1):153-158.

Energy deficit in Huntington disease: why it matters http://www.jci.org/articles/view/45691

Juvenile Huntington’s Disease The Cruel Mutation. http://blogs.plos.org/ dnascience/2013/05/30/ juvenile-huntingtons-disease- the-cruel-mutation/

Epigenetic transgenerational inheritance of altered stress responses. http://m.pnas.org/content/109/ 23/9143.long

Epigenetic mechanisms of neurodegeneration in Huntington’s disease. Lee J, Lee J, Hwang YJ, Kim KY, Kowall NW, Ryu H.
Journal. Neurotherapeutics. 2013 Oct;10(4):664-76. doi: 10.1007/s13311-013-0206-5. http://www.ncbi.nlm.nih.gov/m/pubmed/24006238/

Epigenetic approaches to psychiatric disorders. Carolyn Ptak,. Dialogues Clin Neurosci. Mar 2010; 12(1): 25–35.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181944/

Development and neurodegeneration: Turning HD pathogenesis on its head. Karen Marder, MD, MPH and Mark F. Mehler, MD. Neurology August 14, 2012 vol. 79 no. 7 621-622. doi: 10.1212/WNL.0b013e3182648bfe

 

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Author: Lori Hogenkamp

Lori's passion is for food, the brain, science and stress shifting perspectives .

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