Medical Ethics, Prediction, and Prognosis

Interdisciplinary Perspectives

Mariacarla Gadebusch Bondio, Francesco Sporing, John-Stewart Gordon, Mariacarla Gadebusch Bondio, Francesco Sporing, John-Stewart Gordon

• Publisher: Taylor & Francis
• Year: 2017
• eBook ISBN: 9781351802581
• Edition: 1
• Topic: Philosophy
• Subtopic: Ethics & Moral Philosophy

Recent scientific developments, in particular advances in pharmacogenetics and molecular genetics, have given rise to numerous predictive procedures for detecting predispositions to diseases in patients. This knowledge, however, does not necessarily promise benign results for either patients or health care professionals. The aim of this volume is to analyse issues related to prediction and prognosis as a burgeoning field of medicine, which is revolutionizing the way we understand and approach diagnosis and treatment. Combining epistemic and ethical reflection with medical expertise on contemporary practice and research, an interdisciplinary group of international experts critically examine anticipatory medicine from various perspectives, including history of medicine, bioethics, theories of science, and health economics. The highly complex issues involved in medical prediction call for a far-reaching debate on the value and scope of foreknowledge. For example, which responsibilities and burdens arise when still healthy people learn of their predisposition to diseases? How should health care insurance reflect risky life styles? Is the increasing medicalization of life connected with prevention ethically sustainable and financially possible in the developing world? These and other related issues are the subject of this timely and important book, which not only serves as an introduction to the area, but also proposes many feasible solutions to the problems outlined.

Part I

Individual Challenges

1 Beyond the Causes of Disease

Prediction and the Need for a New Philosophy of Medicine¹

Mariacarla Gadebusch Bondio

In the play Their Days are Numbered, written in 1952, Elias Canetti (1905–1994) depicts a dystopian society in which instead of names, people have a number, the number of their years of life (Canetti 1999). Everyone knows the length of his or her life. Only their date of birth remains a personal secret.

“Ten,” for example, is a child who is allowed to do everything. He does not go to school, he throws stones at people and tells lies. When a man called Fifty asks him why he does not want to learn or what he will do as an adult, he does not answer. The last question Fifty poses to him is decisive: “What’s your name?” He answers: “My name is Ten,” and Fifty understands why the boy behaves as he does (Canetti 1999, 202).

The play premiered in Oxford in 1956. It is difficult to say what induced Canetti to conduct this thought experiment. A world in which humans are predestined to live in the certainty of the moment of their death is a singular one. With the abolition of existential uncertainty, everything changes: instead of compassion or desperation when someone dies, resignation and enlightened acceptance are the usual reactions. The question that emerges when reading or watching Canetti’s play, which he considered his most important work, is how life would feel if lived in the certainty of its unequivocal length.

It may be just a coincidence, but the play premiered at a time when a new approach was beginning to flourish in medicine. Between the 1950s and 1960s, concepts such as pharmacogenetics, the genetotrophic approach, propetology, and predictive medicine were introduced. These concepts were connected with discoveries in genetics, molecular biology, pharmacology, and biochemistry. After presenting some historical developments to help understand the growing need for a new philosophy of prediction in medicine, the challenges owed to the discovery of biomarkers will be discussed. Uncertainties and consequences connected with predictive information will be illustrated with reference to the genetic mutation BRCA1/2.

On the Modern History of Predictive Medicine

At the beginning of the 1950s, the structure of DNA had become the object of feverish research (Franklin and Gosling 1953; Wilkins et al. 1953). In April 1953, James Dewey Watson (born 1928) and Francis Crick (1916–2004) published the news of their discovery of the molecular structure of DNA based on all its known features—the double helix (Watson and Crick 1953). Their model served to explain how DNA replicates and how hereditary information is encoded in it. Parallel to these seminal genetic discoveries, the biochemist Roger Williams published his concept of “genetotrophic disease.” With this title, Williams and two colleagues announced their new approach to diseases in The Lancet.

Based essentially upon recent findings in genetics and biochemistry which have not yet been incorporated into medical thought, the concept of genetotrophic disease may, we believe, lead to an understanding of many diseases whose aetiology is at present obscure.

(Williams et al. 1950, 287)

What Williams and his colleagues presented here was a new concept that during the following years would be developed into a theory. Besides the genetotrophic concept, Williams developed the idea of so-called “biochemical individuality,” to which he dedicated a whole book published in 1956 (Williams 1956).² Williams wanted to make clear that the traditional medical interest in norms and normal values in every single field of research was a distortion of reality:

The existence in every human being of a vast array of attributes which are potentially measurable (whether by present methods or not), and probably often uncorrelated mathematically, makes quite tenable the hypothesis that practically every human being is a deviate in some respects.

(Williams 1956, 3)

The ubiquity of variation in organisms and the significance of variability in humans had been facts, strictly speaking “a sine qua non of evolution” since Darwin; facts which could not be ignored if a serious understanding of human pathologies was to be sought (Williams 1956, 1). Although the importance of the individual constitution had already been noticed by the ancient physicians Hippocrates and Galen, this variability, according to Williams, had been neglected in biological sciences and medicine. He was convinced that the time had come to change medical thinking in this regard. Genetics was gaining ground quickly and conscious of this, Williams presented a systemic concept of disease capable of countervailing the impending threat of genetic determinism: According to an individual’s genetic constitution, various aetiological factors with genetothropic origins had to be considered. These included cancer, diabetes, rheumatoid arthritis, disseminated sclerosis, and mental diseases as examples of pathologies in which the confluence of hereditary, “racial,” and nutritional factors had been observed or could be supposed (Williams et al. 1950, 288). In 1961, he published a short, but no less programmatic article on “propetology,” which he characterized as a “new branch of medical science” (Williams 1961, 325). What did Williams mean by this unusual term?

The tools and the impetus to develop expertness in determining, in advance, what people are prone to contract any specified disease are now at hand; the new science needs only to be developed.

(Williams 1961, 325)

Williams explains what had hindered the development of propetology until his time: an immature view of heredity and life was the reason for the rejection of the notion that many diseases have genetic roots. By means of the prevention of the development of mental impairment in babies prone to phenylketonuria, Williams illustrates how, by implementing diets low in phenylalanine, the effects of the pathology could be kept under control. The knowledge of the hereditary origins of this disease had helped to find a solution based on the management of environmental conditions. By propetology he was concerned to emphasize that people “merely lean toward” certain diseases without inevitably contracting them (Williams 1961, 325). Understanding the roots of resistance was a central aim: Why were some individuals able to escape the diseases they were prone to, while susceptible subjects became ill?

People who are prone to have arthritis or stomach cancers or to become alcoholics or mental cases would not need to suffer from the respective diseases if the proneness were recognized early and if appropriate measures (largely unexplored up to now) could be taken to overcome it.

(Williams 1961, 326)

The development of new measurements of “potential prognostic value” were the basis of this new field of medicine. Rather than standard tests, accurate and individualized prognostic research techniques were called for. At the end of his editorial, Williams announced a pioneer study in the area of propetology. The study was based on a series of tests on 500 young and healthy people over a period of years, and pursued the aim of identifying the types of maladies they were prone to. This study was characterized by a new methodological design: Individual patterns had been brought into focus and the concept of normality had been abandoned. In this regard, Williams’ project was not singular by any means: The problem of norm and normality in medicine, in clinical practice, and more generally in biology was recognized by theoreticians and practical physicians (Murphy and Abbey 1967; Mainland 1969).

In Germany, this had been the topic of vehement debates since the 1920s on (Harrington 1996; Lawrence and Weisz 1998). Theodor Brugsch (1878–1963) and other proponents of so-called constitutional medicine proclaimed the necessity of an individualized approach, of a “biology of the person” (Brugsch and Lewy 1926–1931; Kaiser and Hübner 1979; Brugsch 1986; Konert 1988). The reasons for the attention to individual variations were manifold. Between the First and the Second World War it had been observed that some people under similarly hard conditions (hunger, exhaustion, inadequate hygiene) fell ill and some did not. Of those who fell sick, some were able to recover, whereas others died. These were fundamental findings at a time in which therapeutic tools were limited. It was obvious to suppose that an inborn individual condition, such as a certain susceptibility to disease, had to play a role in the pathogenesis. From the 1920s on, studies in which the concepts of norms, normal values, and normality were questioned multiplied in German medical circles (Rautmann 1921; Grote 1922; Kaup 1926; Hau 2000; Timmermann 2001).

Discussions and critical views of normative tendencies in biology and medicine would find fertile ground from the 1950s onwards, both in the U.S. and in Germany (Ivy 1944; Murphy and Abbey 1967; Mainland 1969; Sunderman 1969; Gadebusch Bondio 2015).

One place where the discussions took place was in the emerging field of pharmacogenetics, at the intersection between genetics, biochemistry, and pharmacology (Humangenetik in Heidelberg 1991). Its pioneers were the Jewish-German-American physician and geneticist Arno G. Motulsky (born 1923), the German pharmacologist Werner Kalow (1917–2008), working in Toronto, and Friedrich Otto Vogel (1925–2006), a human geneticist and professor at the Freie Universität in West Berlin (Motulsky 1957; Vogel 1959; Kalow 1962). Motulsky, Kalow, and Vogel wanted to understand the role genetic factors played in the metabolism of drugs. They observed that only in cases of genetically susceptible individuals were specific drugs the specific agent that caused disease (drug reaction). Unexpected and unexplained reactions to drugs now could be explained. This made pharmacogenetics a discipline of importance for pharmacology, for therapeutics, and for medicine in general. But it took more than thirty years (until the late 1990s) to demonstrate the validity of the concept, and for it to be accepted by the scientific community. In his Handbuch der Humangenetik, Vogel dedicated one and a half pages to the “biochemical individuality of men” (with reference to Roger Williams), but considering the volume of the whole work (753 pages), the space allocated to it was negligible. While Williams emphasized the need to focus on individual variations, to remain reserved about the role of genes, and to maintain awareness of the complex array of extra-genetic factors interwoven with genetic factors, he maintained a critical and quite discriminating attitude to the emerging field of genetics (Vogel 1961, VI; Williams 1960, 96; Vogel and Motulsky 1979).³ In an article dedicated to the history of pharmacogenetics published in 2002, Arno Motulsky put Williams’ contribution into perspective: “He was admittedly not knowledgeable about genetics even though he strongly emphasized the role of heredity” (Motulsky 2002, 687). Motulsky’s late critical judgment gives reason to suppose that Williams’ genetotrophic approach had provoked skeptical reactions among the exponents of pharmacogenetics.

No list of the diverse pioneers of personalized and predictive medicine would be complete without Emanuel Cheraskin (1916–2001). Cheraskin was a physician and dentist. Following his monograph, Predictive Medicine, A Study in Strategy, which he wrote with W. Marshall Ringsdorf, the term “predictive medicine,” which had already emerged in the 1960s, became programmatic (Cheraskin et al. 1966; Cheraskin and Ringsdorf 1973). In his immense publication output (approx. 700 titles!), Cheraskin insisted again and again on the multifactorial nature of health and disease (Cheraskin and Ringsdorf 1971). The classical, Hippocratic and Galenic idea of the gradual scale interposed between the limiting poles of health and disease is central to Cheraskin’s concept of predictive medicine. Predictive medicine—according to Cheraskin—has its focus in the space between the endpoints of health and disease and “finds justification in the anticipation rather than simply in the identification of disease” (Cheraskin and Ringsdorf 1971, 511).

For Cheraskin and his colleagues, the research into predictive medicine becomes fundamental. The topic was discussed in the Journal of the American Geriatric Society, where Cheraskin and Ringsdorf both contributed with a series of articles on different aspects of predictive medicine in 1971. That medicine was in need of a new philosophy was now certainly recognized. The problem lay in identifying reliable indicators of health and disease which would enable prediction and allow preemption. Biochemical measurements had to be conducted within large groups of “presumably healthy” subjects of different “race,” age, and sex (Cheraskin et al. 1966, 3). A higher incidence of cancer had been observed, for example, by subjects with a higher blood glucose level combined with advanced age and overweight measurement (Cheraskin et al. 1969). Cheraskin based his concept of predictive medicine on the predictive possibilities of the so-called “biochemical profile.” He based his research program upon three theses:

First, health and disease are a function of the interplay, in a product relationship, of host state and environmental stressors. Secondly, the oft-observed variability of response in terms of health and disease to similar environmental challenges is largely due to differences in constitution. Thirdly, host resistance and susceptibility is in part reflected and can to a degree be quantitated, by biochemical profile.

(Cheraskin et al. 1966, 3)

The conviction that biochemical mensuration had predictive potential and prognostic value led the group, headed by Cheraskin, to combine traditional biochemical tests with new interpretations and understandings of physiological limits. A flavor of the still lively discussions about “normal” physiological values, and about what could be considered normal and healthy from a medical point of view, are recognizable when Cheraskin briefly describes the predictive value of his biochemical mensurations:

The evidence suggests prognostic worth in utilizing traditional biochemical tests with conventional physiologic parameters; the data indicate greater predictive value employing traditional chemical procedures but with interpretation by presently unconventional physiologic limits. One could only speculate that more sophisticated physiologic standards derived from more sensitive biochemical instruments would likely further enhance predictability in the health sciences.

(Cheraskin et al. 1966, 11)

In the following four decades, Cheraskin became one of the most popular nutritionists and a prolific author of best sellers (such as Vitamin C: Who needs it? or Human Health and Homeostasis). He never stopped trying to develop an operational predictive medicine program and stressing the need for a philosophy of prediction in medicine (Cheraskin and Ringsdorf 1973, 41–2). This was connected with the awareness of the need for new terminology. The redefinition of the concept of health and disease as a gradual and continuous alternati...

Table of contents

• Cover
• Title
• Copyright
• Contents
• Introduction: Predictive Medicine—An Interdisciplinary Approach
• Part I Individual Challenges
• Part II Social Challenges
• Part III Research Challenges
• Selected Bibliography
• List of contributors
• Index