Application Of Gene Modification In Mental Illness

Who we are is a combination of our inherited genetic identity, or genotype, and our observable physical characteristics, or phenotypes. Our phenotypes include things like height and hair color, but also influence our overall health and behavior. For example, are you a relatively calm person by nature? Or wound up? Do you struggle with gaining or losing weight? These are all examples of phenotypes. While genotypes influence our phenotypes, not all phenotypes are a direct result of our genes. Unique life experiences which individuals endure also contribute to the formation of many of our phenotypes. Epigenetics is the study of inheritable phenotype changes that do not necessarily modify our underlaying DNA sequences. These are inherited traits over, or outside of (epi-) our genes. These changes occur in response to environmental influences, such as nutritional stress (famine), psychosocial stress (early life adversities, child abuse), social inequalities, war/conflict or drugs/chemical exposures.

There are an endless number of experiences that can modify an individual’s phenotype, which then has the potential to be passed trans-generationally. Just because an individual may hold these inherited genes, however does not necessarily mean the traits will be present. Gene expression is the process by which the instruction in our DNA is converted into a functional product, such a protein (yourgenome. org, 2016). This process allows a cell to respond to its changing environment and dictates active genes from inactive genes, making each of us unique. Now, consider a world in which science has the ability to control the genetic composition, and gene expression, of the species that coinhabit our planet. Where the very molecules of life could be rewritten in any way, to radically alter evolution as we have come to understand it. Imagine the potential to impact and improve human health and overall well-being, by erasing psychiatric illnesses such as schizophrenia or depression in our children, or Alzheimer’s Disease and Parkinson’s in our elderly. As things currently stand, rates for individuals who require medication continues to grow straining healthcare costs.

The theory of natural selection would dictate that evolution is based on survival of the fittest. This would possibly lend to a natural reduction in family lines afflicted with psychiatric illnesses. Rather than waiting for this to occur over an indeterminate amount of time, what if scientists were able to employ the use of their knowledge pertaining to epigenetics. If our inherent genetic ability to modify our own DNA includes a protective response to aid us and future generations from the impact of trauma, nutritional stress, psychosocial stress, or other environmental factors, can we also use this genetic ability by consciously introducing factors designed to eradicate mental illness in future generations? Gene function became elaborated at the molecular level between 1950 and 2000. It wasn’t until the 1970’s that DNA became engineerable and the idea was confirmed that DNA was a modifiable text that dictated the form and function of organisms. Since that time, scientists have been successful at exploring one of the types of epigenetic modification to DNA, during a process called methylation. This process physically changes the ability for a gene to be transcribed and translated into a protein, and ultimately influences how our genes function and express themselves.

As technology has allowed researchers to collect more data on how the brain works in individuals down to a molecular level, the fields in which this knowledge can be applied have expanded. There are some psychological disorders that are hereditary, while some aren’t as clearly passed. In only factoring behavior and previously believed etiology, there was no way to explain why one child may have developed addiction and their sibling did not. By factoring in epigenetics scientists have another means of explanation available for consideration. The studies here indicate that epigenetics provides insight into behavior and psychology that may be embedded in one’s DNA. These studies provide examples of how this scientific information can be applied to better understand culture, evolution, and how we might be able to use this information moving forward. Scientists evaluated potential for factors such as pollution, nutrition and traumatic experience, to become molecularly embodied, affecting gene expression, and inducing durable changes in behavior and health (Landecker, H. & Panofsky, A. , 2013).

The authors provide data from various human genome studies to support the rise in awareness that gene function and expression contribute to behavior. They further explain that external environmental factors can influence changes in genes. If scientists are successful at linking epigenetic biomarkers to social exposures, there is a possibility that in studying the outside and inside of the body together we can identify meaningful links between social and biological elements and health and behaviors. Health disparities such as nutrition, psychosocial stress, and environmental toxicant exposure, have effects that in some instances may be transmitted to offspring via epigenetic inheritance. Reversibility of the effects of these stressors already experienced by present generations, was explored in efforts to determine if it was possible to avoid impacting genes passed to future generations (Thayer, Z. & Kuzawa, C. , n. d. ).

In this research, the authors investigated three case studies. The first looked at nutritional stress and the influence on epigenetic profiles by inhibiting enzymes that catalyze DNA methylation. The second case study looked at psychosocial stress and the ability to induce epigenetically-based changes in gene regulation linked to changes in physiology and behavior. The third case looked at environmental toxicants and the role they play in epigenetic mechanisms as links between biological functions and health. Researchers found that even though epigenetic changes are durable that it didn’t mean that under changed conditions, the impacts could not be fully or partially reversed. , as shown by the negative metabolic effects of prenatal undernutrition in mice can be reversed by exposure to the fat-derived hormone leptin immediately after birth. If reversibility is an option, what about taking it further? Can gene expression be controlled to begin with? Studies have shown that this is possible. One research introduced nutrients, specifically sugar, at various stages of fruit fly larvae development, as a means for modifying survival outcomes (Zinke, I. , Schütz, C. S. , Katzenberger, J. D. , Bauer, M. , & Pankratz, M. J. , 2002).

The outcomes revealed that nutritional stress did have a marked impact on survival. While starving the larvae after a 70-hr post-egg laying did have an impact on growth size, it did not show an impact on survival. However, starvation prior to the same 70-h mark, significantly impacted length of life (over a week as compared with ∼2 days). A second study explored the use of rats and evaluated maternal nutrition effects on offspring (Lillycrop, K, Phillips, E. , Jackson, A. , Hanson, M. , & Burdge, G. 2005). Researchers were once again successful at using genetic transcription during DNA methylation by means of nutrition, resulting in changes in gene expression. Researchers have taken the ability employ epigenetics as a means to manipulate gene expression to an even higher level. If reversing gene changes and controlling gene expression were possible, the next logical step for science was to silence certain genes all-together. Researchers explored epigenetic gene silencing in cancer during early stages of human tumor development/progression (Baylin, S. & Ohm, J. , 2006).

These journal articles and research papers all explored existing data, or use of rats and fly larvae, leaving minimal need for ethical conversations. It isn’t until we begin to consider applications for control of gene expression and gene silencing in humans that we begin to feel the potential for an ethical dilemma. Ethics in biopsychology and epigenetics is similar to that of other areas in psychology. Any time there is a manipulation of a person’s mind, the benefits must outweigh the harm. Epigenetics research raises some ethical concerns surrounding privacy and confidentiality, particularly since data obtained today will potentially affect future generations. Some of the data provided may pertain to the likelihood of an individual to develop health problems, mental illness, or addictions and the probabilities that they will transmit the risks to their children. Possessing this knowledge places a new responsibility on the holder of that knowledge in that they need to best determine how to use this information.

Research on how gene modification is influenced by environmental factors and the potential for those changes to be passed to future generations continues to shed valuable light. Future studies could explore how our DNA might be capable of being consciously modified by the introduction of external factors or interventions designed to reduce likelihood, or eliminate all-together, psychiatric illnesses such as Alzheimer’s Disease, schizophrenia, depression or anxiety. So, would it be possible to intervene in the natural course of evolution and passing along of genomes and phenotypes? Can science actually use our inherent natural ability to heal and genetically modify in order to adapt to our changing environments, to decrease frequency of mental illness in future generations? One new process that may provide another means of accomplishing this through recent discovery and technological advancements. Scientists have identified a cluster of repeating DNA in bacteria called, Clustered regularly interspaced short palindromic repeat, or CRISPR for short (Mohn, 2017). These repeats are small copies of virus DNA used to help detect the presence of an invading virus. Cas9 is an enzyme that acts like a small pair of molecular scissors that can cut DNA at a specific location in the genome so that pieces of DNA can be added or removed (yourgenome. org, 2016). Bacteria is able to fight off viruses by deploying a small piece of guide RNA (gRNA) to its matching sequence of DNA, while Cas9 follows closely behind. Once in place, Cas9 cuts both strands of DNA. The cell will recognize that the DNA has been cut and damaged and will attempt to repair it, however this is prone to error, leading to mutations that can disable the gene, allowing researchers to further understand its function.

Increased accumulation of transcribed protein from damaged DNA and reduced DA repair capability contributes to numerous neurological diseases for which effective treatments are lacking (Kolli, N. , Lu, M. , Maiti, P. , Rossignol, J. , & Dunbar, G. , July 2017). Neurodegenerative diseases such as Parkinson’s disease or Alzheimer’s disease, are diseases that stand to gain significantly from the CRISPR-Cas9 system of gene-editing technology. By efficiently excising the defective genes contributing to the progression of these diseases, and then sending a second gRNA with a healthy copy of the gene possessing the desired sequence, there may be an opportunity to counteract certain genetic defects associated with neurological diseases.

CRISPR can be used to target many genes at once, which is a big advantage for studying complex human diseases that are caused not by a single mutation but by many genes acting together, such as schizophrenia. These methods are being improved rapidly and will have many applications in basic research, in drug development, in agriculture and perhaps eventually for treating human patients with heritable diseases. Optimization of the current process for delivery of gRNA and Cas9 enzymes needs to occur, paving a path for methods that allow for optimal specificity before applications in the brain are attempted. Improved methods for stimulating gene insertion and correction must be established (Heidenreich, M. , & Zhang, F. , 2016).

Genome-editing technologies offer an opportunity for genetic modification of almost any cell of any organism. Looking forward, in-vivo genome-editing offers the potential for personalized therapies to address brain disorders. However, with these exciting discoveries, opportunities and technological advancements come an entirely new set of ethical concerns. We are on the brink of an era where science will have the technology, knowledge, and ability to irreversibly alter life as we know it. However, mixed in with all of the potential this system has to improve our world, there is the risk of it being used for evil. How do we safeguard against this? As one of CRISPR’s pioneering inventors has pointed out, “tinkering with the genetic underpinnings of our ecosystem could have unintended consequences. We have a responsibility to consider the ramifications in advance and to engage in a global, public, and inclusive conversation about how to best harness gene editing in the natural world” (Doudna, J. , 2017).

The CRISPR-Cas9 system will offer lifesaving opportunities, but it also possesses the power to be wildly dangerous in the wrong hands. It will be of great interest to see how the ethics debate surrounding the use of this system in humans develops. Science aims to seek understanding and to explain things we previously had no explanation for. Biopsychology is a science that seeks understanding of how our brain, neurotransmitters, and other aspects of our biology influence our thoughts and feelings. As is the goal with any of the sciences, discovery is exciting and offers potential that overlaps into other areas. Goals of research are guided by ethics and bound by the concepts of beneficence and nonmaleficence – or do good/do no harm. With the understanding that with any treatment, there is some degree of anticipated potential for harm, at the minimum, the harm should not be disproportionate to the benefit. Some may view the idea of gene controlling, gene modification or gene silencing, too much like “playing God”, or being too risky in that we have no idea what the implications might be. To that I would say, isn’t that what most advancements in medicine have been based on?

Someone gets sick or complains of an ailment, and a doctor prescribes a compound of chemicals that was discovered in a lab to make them feel better. Science and medicine in beginning to venture in to a new approach to treating diseases at a genetic level. While it is scary because it is new, that does not mean we should not explore this potential. Provided the process can be perfected and safeguards can be implemented to protect against misuse, there appears to be substantial evidence supporting a real potential to dramatically reduce the occurrence of mental illness.