Genes Change in Your Brain. Do They Change You?

A startling discovery of enormous implication has just been reported in the premier research journal, Science. Despite the accepted dogma that all of a person's cells have the same genetic coding, it turns out that this is not true, especially in neurons. The DNA in each nerve cell (we don't know about sex cells) has hundreds of mutations of the A-T, C-G nucleotides that constitute the genetic code for the neuron. Thus, no two neurons are alike. The study was conducted by 18 research teams at 15 U.S. institutions, formed as a consortium by the National Institute of Mental Health to examine neural genetic coding, using repositories of postmortem brain tissue taken from both healthy people and those with various mental diseases.

The scientists have no explanation at present for what is causing so many mutations and why each neuron has a different genetic profile. The most obvious possibility might seem to be that the mutations occurred as transcription errors during cell division. But there is a major problem with this explanation. We don't know when these mutations occurred. Except for granule cells in the hippocampus and cerebellum, neurons generally do not divide after the first few days after birth. So, if cell division is the cause of mutations, it must be due to what happens during the early post-natal period.

If the mutations occurred sporadically throughout a lifetime, a likely cause for mutation might be DNA damage caused by the free radicals that are generated in ordinary metabolism. Environmental toxins are another possible cause. The point is that the DNA changes are likely to affect how a neuron functions, and that change can last a lifetime.

We know that mutations can cause brain cancer and even certain other brain diseases. The research consortium was commissioned to see if the genetic variants predisposed to neuropsychiatric disease. Obviously, the vast majority of people have these diverse genetic codes in their neurons that do not cause disease. What do they cause? Can the mutations affect which neurons participate in which circuits? Can mutations affect how well you reason, or memorize, or your emotional responsivity? Nobody knows.

A whole new field of research has now been opened. Scientists need to examine different neuronal cell types to see if they are equally affected by mutation. Obvious comparisons needed are between granule cells and all the other neuron types that do not divide.

There is a related aspect that is not considered in this context. That is the likelihood that each neuron differs not only in its genetic code, but also in which genes are expressed. The new field of "epigenetics" has revealed that environmental influences, ranging from drugs, toxins, metabolites, and perhaps even lifestyles can affect the expression of genes, even when there is no mutation. In the case of brain, there is the distinct possibility that one's mental life can affect gene expression. This needs to be studied.

So far, what I have said about gene change and expression refers to single individuals. But what if some of these gene mutations or epigenetic effects that occur in neurons also occur in sex cells? That would mean that traits acquired during one's lifetime could be passed on to future generations. I would hope that the research consortium that has made this monumental discovery about brain cells will extend its charter to also examine sperm and ova.

Recent research on the genetics of the classic animal model of brain function, C. elegans, reveals that epigenetic inheritance of neuronal traits does occur. Gene expression was modified by exposing the animals to high temperatures, and the genetic change was conveyed via both ova and sperm to offspring that had no exposure to high temperature. The epigenetic change was still present some 5-14 generations later.

To the extent that the findings of both of these studies can be extrapolated to humans, we must now consider the possibility that personal lifestyle, environmental, and cultural influences on people may be propagated to successive generations of their children. Bad environments and lifestyle choices may extend well into the future, magnifying the deleterious consequences through multiple generations. We now have to consider that medical and behavioral problems, poverty, and degenerate cultures can arise not only when people make poor choices but that the effects can be genetically propagated to subsequent generations.

These issues may seem to present a challenge to the notion that humans have free will. We are programmed by things that happen to us. But do we not have a choice in deciding much of what we expose ourselves to? The issues are explored in my recent book, Making a Scientific Case for Conscious Agency and Free Will (Academic Press).

Sources:

McConnell, M. J. et al. (2017).Intersection of diverse neuronal genomes and neuropsychiatric diseases: The brain somatic mosaicism network. Science.  356(6336), 395. doi: 10.1126/scienceaa1641.

Klosin, Adam et al. (2017). Transgenerational transmission of environmental information in C. elegans. Science. 356 (6335), 320-323.

Victim of Biology and Circumstance?

An area of controversy in the life sciences relates to the relative roles of genetics and the environment. Confusion commonly afflicts politics. For example, early Communists glommed on to the discredited genetic theory of “inheritance of acquired characteristics.” This theory holds that changing a person’s attitude and behavior would somehow result in changes to his or her genes, which would allow for genetic transmission of the changed attitudes and behavior to his or her children. For this idea to be true, outside influences on the brain would have to change the genes not only in brains but also in the sex cells (sperm and egg cells). The idea was held in ancient times by Hippocrates and Aristotle, but it gained scholarly imprimatur with formal publication in 1809 by Jean-Baptiste Lamarck. In the 1930s, the Russian president of the Soviet Academy of Agricultural Sciences, Trofim Lysenko, applied the doctrine to Soviet agriculture with disastrous results. At the same time, Soviet political leaders extended the mistaken doctrine to inheritance of educational and social experiences; that is, changing human nature by government policy. They expected that indoctrinating the current generation in collectivism would genetically transfer collectivist attitudes and behavior to all future generations. Cuba, North Korea, and China showed that collectivism can be transferred culturally but not biologically.

In the United States, much political angst arises from disputes over whether more effective educational and social policies will succeed in lifting people out of poverty and dysfunctional behaviors. When I was a child, I often heard the axiom, “You can take the boy out of the country, but you can’t take the country out of the boy.” Today, the corresponding axiom would seem to be, “You can take the boy out of the ghetto, but you can’t take the ghetto out of the boy.” The reality is that you can take the country or ghetto out of the boy, but this won’t transfer to his children by his genes.

What we are now discovering is that environment and experience affect the expression of genes. Whether or not genes are accessible for readout often depends on the environment. People have underestimated their capacity to sculpt their own brains, attitudes, and behavior by controlling experiences that affect gene expression. Though people may control to some extent how their own genes are expressed, there won’t be any biological transfer to their heirs. Environmental and cultural influences do of course transfer, so one’s heirs can be taught how to likewise exert control over how their genes are expressed.

Having the right chemicals in the right environment at the right time is believed by most scientists to be all that is needed for creating life and shaping the mental life of the individual. To them, life seems like a highly improbable occurrence. But it did happen, and even more improbable, there may be a life force that sustains it.

Many scientists also think of the brain’s conscious mind as an emergent property of brain function. Emergent properties follow the rule that the whole is greater than the sum of its parts. Another way of saying this is that the properties of the whole cannot be predicted from what you know about the properties of the contributing parts. Yet, paradoxically, most scientists believe that as they learn more and more about less and less, they will somehow explain the whole.

Emergent properties apply both to molecules in a primordial soup that generate simple living organisms and to the 87 billion or so neurons of a human brain that generate a conscious mind. A physical world that can generate emergent properties is a mysterious and magical world indeed.

What gets left out in such consideration is the capacity for personal control over one’s biology, which is an important theme. I contend that at the level of the individual person, mind itself—especially conscious mind—is a major force of natural selection that drives creation of mental capacity and character. The implications for daily living could not be more profound. Accepting one’s biology and circumstance breeds helplessness and fatalism. So, it boils down to one’s belief system. Either you are “captain of your own ship, master of your own fate,” or you are shackled by the belief that change is not possible. What you think and do shapes your brain's function.

Excerpted from Mental Biology. The New Science of How the Brain and Mind Relate, by W. R. Klemm. New York: Prometheus. See rave reviews at WRKlemm.com, click on "author."