Tag: genetics

Addiction, Genetics and the Human Genome Project

“We cannot hope to fully understand the human brain and mind because the tool that we must use is the very thing that we want to understand.” – Doug Cwienk

I apologize for being MIA for so long.  I said that I would write again when I had something meaningful to say but the truth is, I have had something to say, just not the will to sit down and write it.  As you know, we lost our youngest son two and a half years ago to opiates.  Grief is an odd thing, just when I thought that I was handling things, it smacked me upside the head and stole much of my drive.  I am trying to take that control back now and get back in the habit of writing.

We know that genetics has a very strong impact on addiction, so understanding genetics can help us understand the impacts of addiction.  For that reason, I have been trying to understand genetics in a broad sense, so this post is somewhat scientific but not beyond the reach of anyone.  This then begs the question, “if we understand genetics so well, why can’t we fix the impact of genetics on addiction?”.  Actually, we have learned a lot about genetics but the more we learn, the less we understand.

I also want to point out that while I believe that genetics plays a large role in addiction, I do not believe that it is the only factor.  The likelihood of developing a substance use or behavioral disorder is also influenced by environmental factors, such as how and where we were raised, how we were treated and particularly trauma.  While genetics can help us understand a great deal about addiction, I do not believe that any one thing can solve the very complex riddle of addiction.

The Science Nerd Cannot Remain Hidden

I read an article about a professor of Neuroscience at Bucknell University that has also been in recovery for many years.  I reached out to her, hoping to get some good feedback about my blog but most of what she had to say was “read my book”.  I was disappointed, but I took her advice and it turned out to be very good advice.

Back in the spring, I finished the book titled “Never Enough” by Judith Grisel and I highly recommend it to anyone who would like to understand the impact of drugs on your brain.  Her book discusses the neuroscience of addiction with the added benefit of the perspective of someone who has experienced addiction.  I found the book and Dr. Grisel’s insights fascinating and enlightening.  I did not; however, write this post to gush about this book and its author.  Instead, I want to talk about some new insights that I have gained by reading this book and digging a little more into genetics.

The book supports the information that I have presented in this blog and it adds to that a more detailed discussion of the mechanisms by which many drugs impact your brain.  The author provides a good deal of information about marijuana (a topic that I have avoided because of controversy), a drug with which she had a very special relationship.  Near the end of the book, Dr. Grisel addresses the genetic component of addiction and our attempts to solve the addiction problem.  In this discussion, she addresses the human genome project, its promise, and why it failed to solve the problems we hoped it would.  This really struck me and got me thinking more about genetics, epigenetics, and how complex this really is.

Human Genome Project

Just to refresh your memory, the Human Genome Project (HGP) was a large-scale scientific undertaking that included many university researchers and laboratories from several countries.  The purpose of this project was to map the entire human genome, that is to take our genes apart and understand what each segment was controlling.  Before this project, we kind of looked at our genes from the whole city scale but this project would look at our genes on the individual address scale.  For example, instead of just knowing that there are segments of our genes that code for hair color and which colors were dominant, the HGP would tell us the addresses of those segments.  Armed with this information, we would then be able to identify genetically controlled conditions or diseases and “fix them” by editing the bad segments out.

The Human Genome Project was a huge success but rather than solve a world of genetically associated ailments, it showed us just how little we really know.  The project quickly achieved its goal of mapping our genes, but it turns out that the map revealed less of what we expected and more complexity in areas that we had not considered.

Just Enough About Genetics for Our Discussion

Our genes are in part, made up of strands of DNA that provide the instruction book for what each of us will be like.  Notice that I said “instruction book”.  Our genes do not define us because that instruction book is interpreted based on our experiences and environment.  The strands of DNA are made up of base pairs and there are three-part segments of these pairs that code for specific proteins.  They are called triplets.  There are also long sections of our DNA that we thought were inert, they didn’t code for anything.  This is likely to be comparable to your office, some people do the work and some just take up space.  Based upon the variability in humans, we were able to estimate the number of coding triplets that should be present in the DNA within our genes.  Identifying the location and purpose of each triplet is where we saw the tremendous promise of the HGP.  We would map all of these coding triplets and then set to work understanding each triplet and what it controlled. 

As we contemplated this undertaking the theory of epigenetics that had been developed in the 1940s came back to the forefront.  As we have discussed before, epigenetics tells us that our genes are not a rigid definition of who we will be.  We know that environmental factors (physical or psychological) can turn-on/turn-off some genes or cause them to make a different protein.  We also know that some of these changes can be passed on to our offspring in that altered state.  Epigenetics would complicate our understanding of the results of the HGP but this was not too great of a hurdle.

It’s Just Not That Simple

The first thing that we discovered from the HGP is that there were far fewer base pairs that form coding triplets than we thought.  In fact, we have many times fewer base pairs than a potato.  That was quite a slap in the face, surely, we are much more variable and complex than a potato.

We have discovered that some segments of our DNA that we thought were inert actual do code for a protein but not in the way that we understood.  Some areas in our DNA are simply repeating sequences and they do not repeat the same number of times in every person.  I do not think that we have discovered the actual mechanism, but we have learned that the number of times that the sequence repeats can cause differences in people.

An example of something we expected to learn from the HGP is sickle cell anemia.  We have identified the exact location within our genes that codes for sickle cell anemia and this could lead to genetically based treatment.  On the other hand, we found that multiple sclerosis is much more likely in individuals that have longer repeating sections in specific places in our genes.  We thought that these repeating sequences did nothing, like your coworkers, but put enough of them together and something bad happens.

Obviously, we overestimated the number of base pairs that form coding triplets because we though that they accounted for all of the variability.  In reality, there are things in our genetic code that we thought did nothing that actually code for proteins in ways that we did not predict.

In a way, I guess that we were arrogant.  The universe will not give up its secrets so easily.  Combine the complexities of genetics and epigenetics with the even greater, hidden complexities of the human mind and it is no wonder that addiction has proved to be such a powerful adversary.  BUT with support and understanding and very hard work we win sometimes.  As a friend of mine always reminds me, “People succeed in recovery every day.”

Part Va – Nature and Nurture Revisited

 “Don’t be ashamed or proud of your genetics, for you have no contribution towards it.”  ― Mehnaz Ansari

It is often in the darkest skies that we see the brightest stars.”  ~ Richard Evans

I hope that I never stop learning and I hope that the same desire fills you. Way back in Part V of the Science of Addiction, I discussed nature versus nurture with regard to becoming an individual with a substance use disorder, the proper term for an addict.  I have learned more that slightly changes my discussion on the impacts of environment and heredity on the likelihood that an individual will become addicted.  Please join me in Part Va – Nature and Nurture Revisited.

Epigenetics

My education is in oceanography and geology and that is by design.  I studied oceanography because I wanted to be Jacque Cousteau, but that name was already taken.  I didn’t want to study living things, least of all people, because they have free will and are very confusing to me.  So, I focused on geological oceanography because rocks and sediments just do what physics says they must.  Therefore, genetics was not something that I had more than a cursory exposure to and that was fine with me.  But as I looked into the impact of genetics with regard to addiction. I encountered a concept that was new to me, epigenetics.  BEFORE YOU LEAVE THIS PAGE, BEAR WITH ME FOR A LITTLE, I WON’T GO INTO DETAIL.  Truth is, I am not sure that I understand the details.

My understanding is that epigenetics says the concept that genes are rigid, static things that determine what you will be like is not entirely true.  Genes cause proteins to be made that cells use to create an outcome, whether it be simple like eye color or more complex like an autoimmune disease.  We used to believe, based on Mendel’s research (Google it), that heredity was a static expression of certain genes.

I am sure you noticed (and were probably annoyed by) my use of the term static.  I used that term because the concept of epigenetics is not static, it says that the result of a certain gene is not predetermined.  This idea makes sense when we consider how diverse humans are, even within a given family.

Epigenetics says that certain genes may be “expressed” (turned on) or “silenced” (turned off) by environmental factors.  This makes perfect sense to me with regard to things like PTSD.  Some people develop PTSD from a trauma that appears to be much less than the trauma needed to cause PTSD in others, and still others don’t seem to develop PTSD at all.  If it was simply a static gene, either you would get PTSD from trauma or you would not.  Some people conclude that this means some people are just “stronger” than others but that doesn’t fit what we observe.  If the response is not a reflection of character but rather a gene that is turned on or not due to environmental conditions (trauma), that better explains what we observe.

Epigenetics says that it is even more complex than just “expressed or silenced”, that genes may interact.  It says that the protein made by one gene may change how another gene acts, either by turning that gene on or off or causing it to produce a different protein.  This is getting a little complex for me but what I get from it is that there is a lot more room for variability than allowed by the original concepts of genetics.  Also, epigenetics says that some changes may persist long after the thing that caused the change is gone.

Epigenetics and Addiction

Reading about epigenetics was a “holy crap” moment for me and I hope that I can do it justice for you.  Based on the model of epigenetics we can now understand some of the complexity of addiction.  My previous explanation said that your environment (your upbringing and possible trauma) could possibly put you on the pathway to addiction and heredity would determine at what point you will become addicted.  I had concluded that these two things both contributed to addiction, with heredity being somewhat more important. 

Now I see that heredity and environment interact, that each changes the other.  Instead of your experiences leading toward the path of addiction, I understand that your experiences my cause a gene that leads to addiction to be expressed or a gene that protects you from addiction to be silenced.  Some environmental risk factors, like trauma, abuse, neglect, etc., are well known but perhaps there are others that are less obvious, that may change whether a gene produces a certain protein, resulting in addiction.

We oftentimes talk about people who do not understand addiction and think that it is weak-will, a character flaw and we bemoan how wrong they are in that belief.  Part of their misconception comes from what they see. What we don’t see is the complex role that genetics, modified by environment, plays in addiction.  Addiction is far more complex than simple “common-sense”, and this is why people who have not experienced or been educated about addiction do not understand.  This is why we must educate people, so that we attack this crisis with knowledge rather than “common-sense” that is incorrect, due to a lack of information.

Epigenetics and Recovery

When I mentioned my newfound understanding of epigenetics to a psychiatrist friend, he challenged me to consider what that means for recovery.  Obviously, I do not suggest that we should move away from abstinence, support, and cognitive behavioral therapy (12-step programs).  In past posts, I did mention gene therapy and my concerns with editing genes to address addiction.  Instead, epigenetics says maybe we can find the gene or genes that are not in the correct state (on or off) and provide the correct chemical signal to change that state.  That is a long way off, but when we figure out how to isolate the genes and change their state, we could “turn off” the addiction.

If the concepts that I have shared with you in my discussions of how addiction changes your brain are correct, the pathways to addiction that you built would still remain.  Therefore, once you became an addict, you would still never again be able to use abusable/mind altering substances, but your daily battle would be much easier.  We might possibly be able to turn off your brain’s misinterpretation that you need your drug of choice to survive and thereby reduce some of the greatest hurdles to recovery, like cravings, triggers, panic attacks and drug dreams.

I hope that you made it this far and I hope that I succeeded in correcting my ideas of heredity and environment for you.  More importantly, I want you to see hope for the future and a possible pathway to success in the battle with addiction.