Genetics in Medicine: A Game of Odds

Each of us begins life as a single cell. The chromosomes within, formed out of long chains of DNA called genes, carry all the information necessary for the formation of a human being. The entire complement of  DNA, including long segments that have no known function, must replicate itself billions of times over the course of development of the baby and the life of the individual who emerges from the womb.  If there were never any errors in the original DNA,  if there were never any errors in replication of DNA, and if genes did not turn on and off in response to environmental factors, aging would not occur and human misery would be confined to infectious diseases and trauma. Now that the human genome has been decoded, can we look forward to a disease free world and to extension of the seemingly fixed lifespan of 110-120 years? Not likely, but the focus on the genetic contribution to disease will change medicine, for better and for worse, in the years to come.

Visible genetics: the family history

Doctors have always taken a family history as part of the initial evaluation of a patient. Physical features, health and ailments that run in families are visible genetic information. Height and body shape, nose shape, bunions, baldness, premature white hair all “run in” families. So do a variety of illnesses. Family history tells the story of genes that have expressed themselves already. Laboratory analysis of an individual’s genes attempts to predict what may happen in the future.

Laboratory genetics

In a few rare illnesses such as cystic fibrosis, sickle cell disease, and some devastating neurological degenerative disorders resulting from errors in very small parts of the genetic code, the genetic information is clear cut – the individual has an abnormal gene, and they have or will eventually show signs of the disease. These diseases, along with problems of chromosome breakage or duplication such as Downs syndrome, are the object of prenatal screening tests.  For the most part, however, genetic results are statistics – the odds that a problem will eventually appear. Potentially damaging treatments applied to healthy people, based only on future odds,  is the “for worse” change that may come with the addition of genetic information in the practice of  everyday medicine.

 The problems with statistical medicine 

Statistical predictions apply to large numbers of people, not to individuals. Not all people who have a gene associated with Alzheimer’s dementia will get the disease, but since more people born with that particular gene will develop Alzheimer’s than those born without it, the gene is said to increase the risk for the Alzheimer’s disease. The prediction of a strongly hereditary trait – one associated with an 85% likelihood that some kind of illness or cancer will appear by a given age – gives the impression that the illness is almost inevitable for every member of the family. But from the standpoint of an individual within the family, the risk is always 50%.  Either they will or will not be affected.

The importance of treatment availability when disease risk is high

What does knowing that there is an increased risk of suffering a given disease do for you? If there is a treatment that prevents the evolution of the disease, and it has no adverse effects, then it would be reasonable to gamble on undergoing treatment based on worry that the disease will appear, rather than waiting to see if one is in the lucky percentage that escapes. Women who undergo removal of their breasts and or ovaries because they have a genetic trait that greatly increases risk for cancer in these organs have made this judgment.  (They also must accept the minuscule risk that breast or ovarian cancer can still occur even after surgical removal of the organs.)

In the case of the devastating brain degeneration known as Huntington’s disease (HD), people usually know they are at risk because one parent has developed the characteristic dementia and movement disorder in midlife. Because of the so called dominant inheritance pattern of HD, half of the offspring of the parent, statistically, will also be affected.  But no one knows which children carry the gene unless testing is done. Now available and definitive, the genetic test for this disease is a double-edged sword. Life is normal for the carriers of the gene until middle age. The knowledge of what is coming might convince the bearer of the gene not to reproduce, but also make living a full and happy life seem out of reach.

The role of genetics in common diseases

What about the prediction of increased susceptibility to more common diseases, such as heart disease and some cancers?  This aspect of genetic testing may help people with their motivation to lose weight, exercise, eat well and get their routine colonoscopies. Genetic analysis of cancers that have already developed is already proving helpful in the design of specific treatments for specific tumors. All tumors of lung or liver or brain are not alike and “one size fits all” treatments, the only type available in the past, will give way to individualized plans and drugs. An individual’s responses to drugs for conditions such as high blood pressure and heart disease, including both desired and to adverse effects, is also based on genetic makeup.  Personalized treatments are already increasing for these problems.

Genetics and aging

Genetic studies are also teasing out at least some of the pathways involved in aging. Will advances someday lead to immortality? Very unlikely, and a bad social idea anyway. But understanding the way the genes gradually fail in their the mission of cellular repair may well lead to better old age. The key will be to use the knowledge early in life. So far it looks like preventing the errors in DNA replication that contribute to the diseases of old age depends on the same old things that your grandmother might have advised – eating modest amounts real food, preferably from fresh sources in all food groups, avoiding sugar and other refined carbohydrates, drinking little alcohol, avoiding sunburn, keeping in motion, sleeping enough, and most importantly,  avoiding the biggest DNA error trigger of all – cigarette smoke.  Of equal importance is recognizing that no matter how much we know and try to prevent, life will eventually wind down. Living one’s individual allotment well and fully is as important as avoiding cancer – and may actually help genes replicate correctly.

(For readers especially interested in how the genetic code works, Francis Collins’s The Language of Life, and Matt Ridley’s Genome: The Autobiography of a Species in 23  Chapters are good starting points.)


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