Genetic Links Say Little for Complexity of Diseases

Mr. X sits motionless at the edge of his bed. His eyes are closed. He does not talk, and makes only occasional sounds. His wife tells me that he has had other periods when he is “very silent.” A concerned friend noted that Mr. X has worked many years as a busy executive for an insurance company.

In some societies Mr. X might be a religious figure, given to intermittent meditation and trances. In others it could be assumed that he used mood-altering roots or other drugs taken on holidays or during social functions. In some communities his behavior might be labeled unproductive, anti-social and possibly subversive, and his liberty might be restricted by a governing body.

But in our country he most likely will be told that he has a common illness--manic depression. We will label him with a disease that, although sometimes severe and life-threatening, can have symptoms of too much silence at inappropriate times.

In the Feb. 27 issue of the scientific journal Nature, researchers reported finding a variation in a piece of DNA that seems in some cases to be inherited along with manic depression. The press reports that this is the first “gene test” for a psychiatric illness. Mr. X may now be found to have a change in his hereditary material, his genes, as an explanation of his strange and “sick” behavior.

Physicians and medical scientists help to alleviate suffering by studying and intervening in diseases. Yet the urge to reduce explanations of disease to causation by single, possibly replaceable, genes springs primarily from two impulses in those who study and care for affected individuals.

Simple explanations of disease are more intellectually satisfying, even if they are fundamentally incomplete or flawed, than complex “softer” theories. Non-genetic descriptions of disease might include social, political, economic and cultural influences on illness.

Hereditary disability in families is a curse, shadowing the unborn and generations of the already dead. Genetic illness is often chronically disabling, deforming, can produce mental incompetency and may inevitably be fatal. Human geneticists are exposed regularly to the unique sadness and tragedy of the family manifesting a hereditary condition. The wish for an easy explanation of these families’ burdens, using highly sophisticated laboratory tests, may reflect a response in scientists and physicians to the deep fears evoked by the basic nature of genetically influenced disease.

Clearly, some individuals have a biological disorder resulting in thoughts and behaviors that limit their pleasure and ability to function happily within any society. Careful examination of close relatives of these individuals will, in a minority of cases, reveal other identically “affected” individuals. This may suggest hereditary elements interacting with environmental factors, producing disease with psychiatric manifestations.

The powerful new tools of molecular biology, applied in the manner as reported in Nature, may help redefine psychiatric diagnoses. This research will establish that most depressed people are not genetically affected. Only a few of the individuals now correctly labeled as manic depressive will have the identical genetic change as that described in the report. This work may aid us in tailoring therapies to more specifically responsive groups of patients and reduce the incidence of illness created by the treatments given to affected individuals. It should reveal that individuals inheriting a gene found linked with a psychiatric symptom in others will frequently be normal and well-adjusted people.

It would be a great tragedy if the general public would come to accept the simplification that variation in a single gene causes diseases. The complex interaction of the individual with his environment--which over time can result in the pain, suffering and isolation of disease--will never be successfully explained or dealt with if our understanding is reduced to explanations dealing only with sub-microscopic chemicals called genes.

The new tests that promote genetic explanations of disease have limited applicability and benefits. Multiple factors modify the experience of ill health for the individual in our society. Non-genetic factors such as quality of housing, income, availability of health insurance, employment status and education are usually more important to the ability to cope with infirmity and flourish than are one’s genes. To study the complexity of human emotion and behavior, along with psychiatric illness, will always reveal the limited role of genetic effects on life experience. It will also place those who take the time to appreciate this diversity and complexity at the center of humanity.