Predictive Diagnosis and Genetic Screening: Manipulation of Fate?

PREDICTIVE DIAGNOSIS AND GENETIC SCREENING: MANIPULA TION OF FA TE ? WOLFRAM HENN* Let us consult What reinforcement we may getfrom hope If not what resolution from despair. —Milton, Paradise Lost 1:196. These lines from Milton were one of Sigmund Freud's favorite epigrams, and he chose them as the motto of the first manuscript ofhis book in which he developed the idea of repression as a physiological mental mechanism [I]. There is no doubt that repression of troublesome or frightening thoughts from consciousness is a prerequisite for an unburdened life: Carpe diem is more popular than Memento mori. The most obvious but also most keenly repressed of all facts in human life is the inevitability of death. We all know we have to die, but we do not like to think of that, and least of all do we want to know in advance when it will happen. It is a logical but not at all reasonable consequence that we tend to avoid situations that could disturb our quiet slumber. Nobody really likes to go to a medical checkup because it might end up with a bad surprise ; on the other hand, it is a trivial truth that early recognition of a disease can save the patient's life. This paradox limits the acceptance of preventive medicine, and makes me wonder if every physician who professionally promotes cancer prevention regularly goes to the checkups in his or her private role as a patient. The community of interests between doctor and patient, which aims at undelayed diagnosis and therapy, is generally taken for granted but actually works only under the pressure of somatic symptoms that force the patient to seek immediate relief. Preventive medicine, however, does not have the driving force of pain on its side. This is particularly true for the genetic counselling of persons who are possibly at risk for an inherited disease *Institute of Human Genetics, Saarland University, Bldg. 68, D-66421, Homburg-Saar, Germany .© 1998 by The University of Chicago. All rights reserved. 0031-5982/98/4102-1048$01.00 282 Wolfram Henn ¦ Genetic Screening disposition. Here, we often have to deal with an unspoken conflict of interests between the physician's rationally motivated efforts to find a diagnosis as rapidly as possible and the patient's irrational but nonetheless understandable wish to maintain his light-heartedness through ignorance. The rapid progress in medical technology, particularly in molecular genetics , makes early diagnosis available for more and more diseases. It happens more and more frequently that the first to become aware of a breast carcinoma is not the patient through her physical symptoms but the radiologist through a mammogram, and then the bad news for the patient comes from the doctor and not from inside. And here we are faced with a major problem of early diagnosis: the personal experience of disease, in other words, the rational and emotional knowledge of being sick, is artificially advanced by the diagnostic procedure. This results in a iatrogenic loss of unburdened life. This loss is a heavy price, and the patient has the right to expect an appropriate value for it—above all, a better chance ofa successful treatment. After the first shock by the unexpected diagnosis of breast cancer , the patient will be grateful for it if an early operation can save her life. All established methods of early diagnosis have in common that they allow the recognition of a disease before the onset of symptoms but after the beginning of the biological disease process, for example, after the growth of a detectable amount of tumor cells. Thus, disease prevention in the proper meaning of the word is not feasible through early diagnosis but would require the detection ofan individual, particularly genetic, predisposition to a disease. The rapidly progressing deciphering of the human genome is now about to provide fundamentally new insights into pathogenetic mechanisms and, at the same time, new strategies for the recognition ofgenetic risk factors. These revolutionary developments have only recently gained public attention through discussion of the BRCAl gene which predisposes to a (originally vastly overestimated) portion of breast and ovary carcinomas [2]. For an as yet limited but increasing number of hereditary diseases, it...