Sharon Kim, Carter Lee, and Becca Weintrob


Introduction

Samuel L. Jackson is one of America’s biggest movie stars, starring in iconic films such as Star Wars, Jurassic Park, Iron Man, and many more. He has fought snakes on a plane, has been titled the Master of the Jedi High Council, and has enlisted Tony Stark to create a secret organization of superheroes called the Avengers. Jackson has rightfully earned his fame and success throughout the years, with films that have grossed over $8 billion. However, his road to success was not as glamorous as one may predict. At a young age, Jackson lost his father to alcoholism and has struggled with the disease himself. With the start of his career in the early 80s, Jackson found his addiction worsening and taking control of his life.

Now, there is a reason why Jackson became so susceptible to alcoholism. However, unlike a lot of factors that are passed down from parent to child, alcoholism is a long-lasting disease that is controlled not only by genetics, but the environment as well. It is important to understand that there is not a specific gene that is coined the “alcoholic gene.” Instead of passing down the disease of alcoholism, the chances of becoming susceptible to the addiction is much higher in the offspring of alcoholics. According to the National Institute of Alcohol Abuse and Alcoholism, “genetics only accounts for about 50% of the chance of alcoholism.” The other 50% is accounted for by environmental influences, such as alcohol availability, social influences, or everyday stressors. The role of the environment on the development of alcoholism, or any disease, is part of a booming field in research that scientists have called “epigenetics.”

What exactly is epigenetics and how does it play a role in the susceptibility to alcoholism? Think about constructing an essay for your English class…where do you start and what is it composed of? Most of the time, you open Microsoft Word, stare at the blank screen for a while, and wait for the light-bulb to go off in your head. After a little bit of procrastination, you start typing. As you type, you see black letters appear on a white page as it starts to form sentences with proper spelling, grammar, and punctuation. Usually, you format it so that it appears as black, 12-point font in the Times New Roman style. After a while, you finally finish your paper and you are left with a final draft. Let’s call this your genome. Your genome is what holds all of the information that makes you who you are. With Samuel L. Jackson, his genome holds information that says that he will be tall, have dark complexion, and black hair. Your genome might say something different, which makes sense because no two essays are the exact same, as no two unrelated people are the exact same.

On the other hand, we have the epigenome. Let’s say that you take your final draft and decide to change things up a little bit with the style size, font, and color. The content of the paper is the same, which means not a single word is different. However, let’s say you take a sentence and bold one word, italicize another, underline another, and change the font color of another. Imagine your final draft with all of these font changes…that is your epigenome. Absolutely nothing about the content has changed, but there are style changes that alter the perception of the paper. The different types of changes to the font of the paper can be looked at as the chemical changes that occur to your genome, which altogether make up the epigenome.

With that being said, there are tools that induce these changes. To bold a word on Microsoft Word, you must press the button that indicates that function. The same goes for italicizing, underlining, and even change the font color. These different tools are reflected in the human body as well. There are molecular tools in the human body that help start the chemical changes that occur in order to produce epigenomes.

Now, it is very well-known that genes are carried across generations to reflect certain characteristics of the parent. However, what is sometimes overlooked is the ability for epigenetic changes to also be passed onto offspring. Overall, there are two ways that this can happen, which will be discussed in the context of Samuel L. Jackson. Keep in mind, these two ways could be looked at as a parallel to the famous contrast of nature v. nurture.

Let us say that during pregnancy, Jackson’s mother consumes excessive amounts of alcohol. Mrs. Jackson’s behavior leads to a toxic uterine environment during Jackson’s fetal development, hindering the prenatal care that he receives and inducing these epigenetic changes that were initially absent. Ultimately, strictly as a consequence of the poor maternal care he receives, Jackson’s epigenetic changes lead to the development of Fetal Alcohol Syndrome (FAS). This is an example of epigenetic changes that are not due to the mother’s genes…these are strictly dependent on the behavior of the mother, which ultimately affected the genetic nature of the offspring. These types of changes can be thought of as nurture, in a way.

However, in reality, Jackson’s father was the one that consumed heavy amounts of alcohol, which led to Jackson’s increased chance of falling to the addiction. So, what happened there? With his father’s continued exposure to alcohol (an environmental signal), his sperm cells acquired epigenetic changes that were ultimately passed on to his son during fertilization, when the egg and sperm meet. An important aspect here is that Jackson, himself, was not directly exposed to the alcohol before birth; this was strictly passed on through the epigenetic effects on his father’s sperm due to his exposure to alcohol. Although not exactly, this can be thought of as nature. This example shows the passing of epigenetic changes that are found in the father’s genes, through his sperm.

The Alcoholic Individual

While noting the role of epigenetics, it is important to identify some of the ways in which these changes arise originally in the father. Drinking habits affect the brain, leading to tolerance and dependence, along with physical and mental health issues. Alcohol has these effects through a variety of different mechanisms. Before looking at an example in which a change to DNA relates to depressant and dependent effects of alcohol, it is important to have a grasp on the method of change known as methylation. Methylation can be thought of as a variation to your English paper that we referred to as the “genome.” As mentioned, there are many ways to edit a paper. In the case of methylation, imagine changing the font of a word in a sentence from black to white. The word still exists but it is invisible against a white background. Just like changing the font to white, methylation has the same effect on DNA and typically hinders the ability of a sequence to be read. Omitting some words in a sentence can be irrelevant; similarly, DNA methylation can occasionally also have no effects. However, certain words are necessary to the comprehension of a sentence and omitting these can completely change the meaning of that sentence. Refer to the example below.

Example:
Original Sentence: The quick brown fox jumped over the lazy dog.
Omitting Irrelevant Words:      quick         fox jumped over     lazy dog.
Omitting Relevant Words: The quick brown                       over the lazy     .
Black Background: The quick brown fox jumped over the lazy dog.

Overall, the example above can be translated molecularly to explain a vast shift in a person’s behavior due to the changes to their genetic sequence.

How exactly does drinking alcohol increase the methylation of DNA? DNA methylation patterns are created and maintained in the body by molecular tools. These tools make edits to DNA in the same manner that you edit the font color from black to white in your English paper. These tools are called DNA methyltransferases (DNMTs). In a study of chronic alcoholics, it was found that they had a decreased amount of these molecular tools2. In general, these molecular tools have a variety of functions. However, in this case, they are relevant to the ability to learn and create new memories. When you take away the tool that is used to make changes to your paper, you are taking away the ability to change the meaning of sentences. In the context of alcoholism, this leads to the limitation of an alcoholic to function properly. Another finding from the study was that the amount of alcohol in a person’s blood was related to an increased likelihood that these changes would occur. Think of this as updating Microsoft Word and realizing you now have the ability to add more font variations to the paper in addition to white, such as yellow and grey. This is significant to a person’s performance because now there are more font modifications available to mix in throughout their English paper.

The effects of methylation are widespread and do not just influence the mental and physical function of the consumer. These effects also roll over to determine the effects of craving and increased consumption in an individual such as Samuel L. Jackson. Alcohol has reinforcing effects, making it extremely difficult for alcoholics to remain sober for long periods of time. The effects are attributed to a link between alcohol consumption and its reaction to a system in the body that is also activated when people take opioid drugs, such as painkillers. Opioid drugs can target specific areas in the body, which include certain pre-existing transporters in the body that are readily received and naturally processed. There are two types of opioid transmitters in the body: joyful and unpleasant. These unpleasant ones are linked to depression and prolonged alcohol seeking (dependence). When consuming alcohol, these transporters are triggered in order to make the crucial font changes in a paper that are necessary for the interpretation of the sentence. There are initial words in a sentence that are vital for comprehension, but just as susceptible to font changes as the rest of the words in the sentence. These words are known as the promoter regions in a DNA sequence. Changing the font from black to white in this region is associated with the visible symptoms of the addiction to alcohol4. According to the study by D’Addario et al., these changes in this important region of the sequence is related to the symptom of prolonged alcohol seeking4 (dependence). Dependence, along with other deficits in the ability to think and perceive, is not only important to the alcoholic’s life but that of others. Methylating DNA and other various changes can be long-lasting and passed down through generations, just like we saw in the Jackson family. Exploring this gives us an understanding of the underlying effects of alcohol and its ability to pass down DNA edits to future offspring.

The Next Generation

It is widely known that having alcoholic parents increases an individual’s risk for struggling with substance abuse in adulthood – just look at Samuel L. Jackson and the 15 million other American adults struggling with alcoholism today. Previously, nurture was commonly blamed for this – it was thought to be a learned behavior to cope with everyday life. However, studies on multigenerational inheritance – how changes made by the “molecular tools” mentioned above are passed down from parent to child – provide support for the proponents of the nature side of the nature v. nurture debate.

Passing down these traits from parent to child occurs when an individual is exposed to an external stimulus, in this case continuous alcohol consumption, and their body acquires changes that have effects on the function of the individual. Take the English essay example from above – think about the father as the first edition of the paper and his child as the second edition. During the writing process, whatever edits that the first edition contains will be passed down to the second edition, where further edits will be made. Now, in the context of an alcoholic, if the father is an alcoholic, the “molecular tool” that changes the font color to white, and therefore, “silencing” that information, can be passed onto his offspring. When the individual has kids, the content that makes up his own essay will be copied and passed down to the child. When this occurs, it is possible that the changes to the font style from his paper are also passed down to the child – the child’s paper may reflect the same changes, reflecting a similar epigenome to the father (the second edition). If this were the case, then some of the words would be changed to a white font in the essay, and those words would not be read during DNA processing, like that of the father. This child’s development is affected by the presence of these changes passed down by the parent, even in the absence of the change-inducing alcohol during development, as would be the case in FAS, or a form of nurture affecting development.

It is important to note that all of these changes to the child’s copy of the essay are not easily transferable through sperm. There are waves of changes that bring the font color back to black (de-methylation) during development, working to erase the previously made changes. This could cause abnormal development with a loss of a vast majority of these changes on the sperm3,6. In other words, when a copy is made of the father’s essay to pass onto the child, it is almost as if the format is not conserved when it is pasted, and the changes that cause some of the text to be changed to white are not conserved – the changes are all set back to normal. However, there are instances when the changes to the child’s copy of the essay are directly transferred from the dad and cannot be touched. These are called imprinted genes, which seem to be protected from this sort of “paste without formatting” tool and are passed down to the next generation. This is where the changes that are produced by alcohol occur, in these areas that are protected from further change. Think of this as making changes to a paper after you have already hit “save.” All of the changes that were made by alcohol before hitting “save” are officially saved on the document – these are your imprinted genes. Now, any changes to the paper after saving would still be present. However, if you were to send this document to someone else without any additional saves, the original document that lacked any new changes would be the one that the other person received.

Some of the earliest research on children receiving these changes due to the father’s chronic alcohol exposure found that in animal models where the father was “alcoholic” and the mother was healthy and sober, the offspring were defective. This meant that the effects of alcoholism were equally present in the offspring as in the father, although the offspring were never directly exposed to alcohol11. But what does this mean for humans? Like the animals in the study previously mentioned, studies show that the children of alcoholic fathers showed symptoms similar to those with FAS, even though they were not directly exposed to alcohol during the development in the mother’s uterus. However, researchers unfortunately do not yet know what, specifically, is occurring to cause these changes. One idea that they have is that chronic alcohol exposure lowers the activity of the molecular tool that changes the font from black to white in sperm, changing the way that the sentence is read and comprehended. Additionally, while there is some support for the idea of an overall decrease in the changes on the sequence of imprinted genes in sperm of alcoholic males, the way in which this affects development of the baby has not yet been identified3,6.

Conclusion

The way that these changes are passed down from parent to offspring suggests that there is only one outcome for the children of alcoholic parents. However, contrary to popular belief, Samuel L. Jackson’s success shows that the increased chance of becoming a victim of alcoholism can be overcome. Jackson received the same edition of the paper that his father had and unfortunately maintained some of the changes in the second edition of the paper. However, he was able to add more to his story by becoming one of the most successful actors in American history. Although Jackson likely inherited the changes to his genome outlined above from his father, it is important to remember that there is no “alcoholic” gene. The development of this disease is a combination of both genetics and environment. Luckily for Samuel L. Jackson, he was ultimately able to manipulate the environment in order to have positive effects on his genetic background. Samuel L. Jackson overcame the fight against his own genes by allowing himself to focus on his interests and prioritizing is family and career, rather than the toxic stimulus that is alcohol.

References

  1. “Alcohol Facts and Statistics.” National Institute on Alcohol Abuse and Alcoholism, U.S. Department of Health and Human Services, June 2017.
  2. Bonsch D, Lenz B, Fiszer R, Frieling H, Kornhuber J, Bleich S: Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm 2006, 113: 12991304. 10.1007/s00702-005-0413-2
  3. Chastain, Lucy G., and Dipak K. Sarkar. “Alcohol Effects on the Epigenome in the Germline: Role in the Inheritance of Alcohol-Related Pathology.” Alcohol 60 (2017): 53-66. ProQuest.
  4. D’Addario C, Shchetynsky K, Pucci M, Cifani C, Gunnar A, Vukojevic V, Padyukov L, Terenius L (2017) Genetic variation and epigenetic modification of the prodynorphin gene in peripheral blood cells in alcoholism. Prog Neuropsychopharmacol Biol Psychiatry 76:195–203.
  5. Galivan, Anne. “The Homeschooler’s Guide To Writing A Research Paper.” The Homeschooler’s Guide To Writing A Research Paper | Homeschooling 911, Homeschooling 911, 24 Aug. 2011
  6. Mead, Edward A., and Sarkar, Dipak K. “Fetal alcohol spectrum disorders and their transmission through genetic and epigenetic mechanisms.” Frontiers in Genetics 5 (2014). Web.
  7. Ouko, Lillian A., Shantikumar, K., Knezovich, J., Haycock, P., Schnugh, D.J., Ramsay, M. “Effect of Alcohol Consumption on CpG Methylation in the Differentially Methylated Regions of H19 and IG‐DMR in Male Gametes—Implications for Fetal Alcohol Spectrum Disorders.” Alcoholism Clinical & Experimental Research, 33:9, (2009): 16151627.
  8. “Samuel L. Jackson.” IMDb, IMDb.com
  9. “Samuel L. Jackson From Addiction to Long-Term Sobriety.” Elevations Health, Elevations Health, 9 Aug. 2016
  10. Starkman, Bela G., Amul J. Sakharkar, and Subhash C. Pandey. “Epigenetics—Beyond the Genome in Alcoholism.” Alcohol Research: Current Reviews 34.3 (2012): 293–305. Print.
  11. Stockard, Charles R. “The Effect on the Offspring of Intoxicating the Male Parent and the Transmission of the Defects to Subsequent Generations.” The American Naturalist, 47:563, (1913).