The science of genetics has changed so much over the last 50 years that it is hardly recognizable to someone like me who took my last genetics course in medical school. At that time, we were taught that an individual’s basic characteristics are inherited from his/her parents by means of genes that are carried on 23 pairs of chromosomes, twisted strands of DNA that carries the code for life in the nucleus of all of our cells. Genes were thought to be immutable, fixed for life, except for the occasional mutation. Identical twins were thought to be exactly alike because they carried exactly the same set of genes. So your (phenotype), physical size, skin color, eye color, basic physical structure, susceptibility to various diseases etc. are determined by your genetic make-up (genotype), and this wasn’t thought to change. It was clear, however, that there were other influences on the development of a person. Even identical twins with the same genetic makeup (nature), particularly those raised separately, developed some differences in their characteristics, such as intelligence, athletic ability, health, preferences and accomplishments depending on influences from their environment (nurture).
It was recognized as far back as Aristotle that parents contributed “messages” that led to the formation of a new child. This was a big step from the earliest theories that the male contributes a tiny miniature person to the female who in turn nurtures it in her body until the time of birth. The state of knowledge about inheritance remained pretty much the same until the mid-1800s and the observations and experiments of Darwin and Mendel. The work of these two men began almost a century of observations and experiments to try to determine what accounted for the formation of new life and inheritance. It wasn’t 1944 until that DNA was recognized, through a series of imaginative and exhaustive studies, as the substance that carries the genetic code and that structurally similar RNA reads the DNA genetic template and carries the message from the nucleus to the mitochondria in the cells which in turn manufactures proteins that implement the structures and functions of the body. What has followed is a deep understanding of the structure of DNA, how genes are arrayed on the various chromosomes and how it carries out its functions. We have also learned the effects of genes, far from being static, can be amplified, diminished, activated or turned off that this is the primary mechanism mediating changes in the body’s health and functioning throughout our life time from fetus to old age.
Humans have somewhere in the neighborhood of a billion genes. The numbers which are active at any point in time are a few thousand. In other words we have many sites on the genome that seemingly aren’t doing anything. A discovery of the last decade is that many of these seemingly blank spots are actually switches that turn on and off other genes largely as a result of challenges encountered from the environment. These are called epigenes. So we have many more genes than those that are active at any point in time. In fact, we have vast warehouses of inactive genes that can respond to new or different challenges. We don’t know what all of them are doing, but it has become clear that many of the functional changes that occur during our life times are mediated through epigenes switching on and off the genes that control functions. One example of a functional change that is turning out to be related to changes in gene function is the development of cancers. We have come to understand that many kinds of cancer (perhaps all) are related to genetic functional changes probably through the activation of genes that previously were silent. The development of the body’s many different kinds of cells (liver, blood, heart, etc.) is probably related to which genes have been activated. Since all cells of an individual have the identical gene complement at birth, something has to instruct the cell to become a liver cell or a blood cell, and this is likely to be mediated through epigene activation of the appropriate structures as the embryo develops.
There are many diseases that appear to have a genetic basis. Some genetic diseases show up at birth. In these cases, if you have the causative genes in your cells, the disease develops soon after birth. The metabolic defects that cause sickle cells, cystic fibrosis and inherited immunodeficiency are present and manifest from the beginning. However, there are no apparent problems at birth for those who carry genes for type 1 diabetes (onset usually in childhood), schizophrenia (late adolescence), manic-depressive disorder (adulthood), depression or Parkinson’s disease (late life}. The gene or genes have been present from birth, but they apparently don’t have an effect until they are “turned on”. In some instances, as with the case with cancers, environmental factors interact with genes or epigenes to act as triggers for activation. So the exposure to chemicals, smoking, radiation, stress, nutrition and some habits may be, at least in part, mediated through the activation of genes by epigenes, rather than mutation. One can see how the effects of diet, exercise and a variety of other environmental factors can be mediated through activation or inactivation of genes. What this says is that genetic makeup is much more plastic than we imagined when genes were thought to be immutable, and it opens the door to therapy based on blocking or activating genes.
Genetic research has accelerated. Scientists are discovering ways of identifying specific gene abnormalities and of plucking out disease related genes and replacing them with normal versions. Cancer may turn out to be a genetic disease with a cure that can be achieved by manipulating the genetic code. It is also possible to generate stem cells, cells that are undifferentiated and can transform into anything (heart, liver, kidney, etc.). The hope is that it will be possible to infuse these cells and have them replace damaged or lost functions, like dopamine producing neurons in Parkinson’s Disease or heart cells in someone who has had a heart attack. We are still a long way from being able to turn these theories into active therapies, but it is an area where it seems there are almost an infinite number of possibilities.
For those who want to go from this cursory summary to a more detailed understanding, an excellent book written for the lay public is “The Gene, an Intimate History” by Siddhartha Mukherjee.