Medical LiteratureMedical Literature

Read not to contradict and confute; nor to believe and take for granted; nor to find talk and discourse; but to weigh and consider. —Francis Bacon (1561-1626)

We need help to "weigh and consider" the information that medical science presents to us. The Users' Guides to the Medical Literature, edited by Guyatt and Rennie, and Sackett's Evidence-Based Medicine: How to Practice and Teach EBM, are two sources to consult in untangling complex clinical literature.^{1 - 2} This list should also include Gehlbach's Interpreting the Medical Literature, first published in 1982. In fact, we may begin our education on a solid foundation with the fourth edition.

Gehlbach's single-author volume handles much the same topics as those that evidence-based medicine has dealt with. There are 13 chapters spread over 296 pages. Study design and its variations, measurements, significance, and interpretation occupy the bulk of the book. Five chapters deal with the design and methods of data collection. The discussions are extensive, starting with simple background, block diagrams of prospective and retrospective designs, and liberal and repeated analyses of published articles and their merits and weaknesses. One chapter, new to this edition, explains how before-and-after trials or time-series trials are an alternative for "real-world" situations in which randomized studies are difficult. Next are four chapters devoted to statistical testing, the null hypothesis, confidence intervals, errors, correlation, regression, sensitivity, specificity, and predictive values. We find a good analysis of types of data sets, especially categorical and continuous. The remainder of the book deals with risk and causation, their measurement and interpretation. Introductory and concluding pages contain general tips about reading articles, editorials, reviews, and letters.

Throughout, Gehlbach analyzes major published epidemiological articles, whether on febrile seizures, osteoporosis, benefits of antioxidants, or screening Pap smears. While complimentary of their contents, he stresses their design strengths and flaws, often comparing one study with another. Data tables are recast and explained. This valuable dissection lends the book a distinctive flavor. There is an informative discussion about traps set by confounding. Interpretation of test performance characteristics finds due mention with an added brief explanation of ROC (receiver operator characteristic) curves. Case control, cross sectional, follow-up, and experimental designs receive great emphasis. The clarity and readability of these sections are the book's forte. I wish Gehlbach had covered the topic of surrogate end points in detail. His writing style would be ideal to alert us to the charms of this beguiling outcome measure. He stays away from details of survival analysis and economic and health policy issues. This is a wise course, because even comprehensive works have scantly influenced policy decisions. Policy making seems to reside safely beyond the pale of science.

In addition to the two aforementioned books, major medical journals have published series on evaluating and interpreting medical publications. A notable series of 10 by Trisha Greenhalgh, "How to Read a Paper," appeared in volume 315 of the British Medical Journal in 1997 and is now available in book and e-book form. The Lancet has just published a series on critical reading of the medical literature by Grimes and Schulz (vol 359, 2002). Another book on diagnosis is also available and being serialized.³ The content and intent of these works overlap considerably. Each emphasizes different facets. Reading them at various times is not unlike experiencing Bach's preludia—the performance and instrumental subtleties seldom induce ennui. There are desirable distinctions; with Gehlbach you sit in a packed auditorium listening to a popular undergraduate course, which glimpses the pleasures that could come with deeper involvement. Sackett is a seasoned teacher who gives leading-edge advice ("Burn your traditional text books," and seek evidence elsewhere) with which it is hard to quarrel. The strength of Guyatt and Rennie's magnum opus lies in the comprehensive treatment of the topics. In Gehlbach's work there is a soupçon of excessive, but not cloying, culinary metaphor. His approach to methodology and design of studies makes delightful reading. We will surely consult these pages as we read more and more papers about mammography, screening tests, and preventive strategies.

The stated purpose of Interpreting the Medical Literature is to provide a basic understanding of study methodology, analytical techniques, and clinical epidemiology. It succeeds admirably, reaching out to a wide section of health care givers with varying levels of expertise and need. Gehlbach has used the Internet and kindred media extensively in birthing his latest edition. Yet, it is a pity that this book, unlike the others, is not available on CD or a Web site. Gehlbach states correctly that the basic skills of critical appraisal are independent of the method of information acquisition. His aim is not to daunt tentative and curious readers but to escort them. They arrive at the terminus with their own safe interpretation of what they observed en route. If some of us are not yet ready for the other vertiginous rides, then we should start off with Gehlbach; we will definitely step off feeling smarter and "Curiouser and curiouser."

Meeting in Grenoble in 1904, the Académie des Sciences heard Stéphane Leduc explain that the appearance and behavior of the spindle apparatus in mitosis could be simulated with a solution of potassium nitrate and a drop of india ink. With this now largely forgotten episode, Evelyn Fox Keller begins a highly readable meditation on the nature of explanation in the biological sciences.

At least some of Leduc's contemporaries thought that his experiments had genuine explanatory value: they made clear something about the nature of life that had previously been mysterious. The gap between their evaluation and our own exemplifies Keller's general thesis that what makes a biological explanation satisfying is essentially local. Mainstream theories of explanation in the philosophy of science aim at a general account of what makes a good scientific explanation—how good explanations isolate the actual causal connections from a sea of predictive, statistical relationships or how they unify diverse phenomena under a few simple patterns. But Keller focuses on how particular scientific explanations meet the needs of the scientific communities that produce them. An explanation that is profoundly satisfying in one research community, she suggests, may seem barely cogent in another.

Keller explains that Leduc's contemporaries were primarily concerned with whether inorganic chemistry is adequate in principle to define and explain the phenomena of life. She also argues that this is a very recent question, which did not emerge in any recognizable form until Lamarck (1809). However, Buffon's 1749 theory of organic particles seems to have been intended to define life in general via the nature of its chemical constituents, and as early as the 1740s chemical demonstrations were being offered to show that the laws of ordinary matter could fully explain the behavior of "organized bodies." The physicist Maupertuis compared the growth of an organism to the Arbor Dianae—a branching structure formed in a mixture of silver, mercury, and nitric acid. But whatever continuity may exist with earlier debates, the mechanist position certainly became increasingly credible in the 19th century, attracting the interest of laboratory scientists and not merely dogmatic materialist philosophes. By the turn of the century, a final, conclusive vindication of what Jacques Loeb called the "mechanistic conception of life" seemed tantalizingly close, making Leduc's simulations more exciting than earlier efforts.

A major focus of the book is the traditional resistance within biology to highly general, mathematical explanations of the kind valued in physics. "Among many morphologists and systematists," wrote Julian Huxley in 1932, "there appears still to linger a distrust of the application of even such elementary mathematics to biological problems." Seventy years later, it is still an unusual biologist who believes that the kind of mathematical explorations far in advance of any possible experiment that are so characteristic of theoretical physics could have a useful counterpart in biology. This was my favorite part of the book, as Keller herself came to molecular biology after training in theoretical physics, and her personal account of the different attitudes to explanation in the two fields makes fascinating reading.

In her treatment of mathematical biologists like Wentworth Darcy Thompson and the lesser-known Nicholas Rashefsky, Keller aims to help the reader appreciate what they saw as questions and as cogent answers. In contrast, when Keller turns to the conventional, gene-centered explanations of molecular biology, she recognizes that most readers will find these explanations immediately compelling. She works hard to distance us from this comfortable standpoint by uncovering the metaphorical structures that disguise unanswered questions. Later, she suggests that our understanding of molecular systems is now so complete—and so complex—that theoretical mathematical investigations have become an inescapable accompaniment to experimental inquiry. The relation between the two forms of biology, however, remains very different from that between mathematical and experimental physics.

In her final chapter, Keller returns to Stéphane Leduc and compares his work to modern attempts to create "artificial life"—A-life—in the form of self-replicating strings of computer code. Keller reiterates her view that the category of life is a human creation and suggests that A-life advocates are redefining that category, and its accompanying questions and explanations, in a way that serves their own intellectual projects. Although sympathetic to this general treatment of scientific categories, I remain skeptical that A-life represents the sort of profound conceptual shift that accompanied William Harvey's demolition of Aristotle's theory of generation or the introduction of the cell theory of the organism.

Addictions have been considered a proper subject for medical interest because of the pernicious effects they can have on individual health and because of the success, albeit limited, that the medical model has had in preventing and ameliorating these effects. However, for widely varying reasons, some physicians and allied critics reject the notion that addictions should be labeled pathological.

Some of these critics believe that addictions are legitimately the exclusive province of ethicists, theologians, or lawyers. Others are uneasy as the boundaries of addictions spread from unhealthy use of habit-forming drugs to uncommon variants of such typical human activities as eating, sex, and gambling. Still others view medicalization of aberrant behavior in a strictly political context in which manipulation of categories of thinking is used by one segment of a culture to dominate another. The Australian author of What's Wrong With Addiction?, who has a social research background, represents this last approach, arguing that addictions are inappropriately labeled as illnesses by our modern "enterprise culture" to strengthen its hold over people's conduct and desires.

Keane introduces this theme by examining the medical approach, which ties substance dependence to defective physiological processes. She considers and rejects the reality of this link and concludes that it "promotes the translation of the unusual, anomalous or deviant into the abnormal or pathological." She believes that by considering addiction a disease in need of cure, patterns of behavior destabilizing to entrenched and powerful institutions can be contained: "addiction . . . is a notion through which specifically liberal forms of political power and government regulation operate efficiently and seductively."

Keane next devotes several chapters to considering the medicalization of specific behaviors, such as nicotine dependence, eating disorders, and sex addiction. She views individuals with these habitual behaviors as victims of a culture that rejects the idea of smokers who are "willing gamblers . . . who prefer the benefits of smoking," that insists persons with bulimia are deficient in "a normative level of self-control" resulting from a "disturbed inner self," and that counsels the sex addict to set a goal of having "sex in conformity with an already existing model," which "disavows the heterogeneity of people's values and interests."

The author then extends her analysis to various self-help recovery movements with their emphasis on the "ideals of the self—autonomy, responsibility, individual fulfillment and happiness." She views these ideals as imposing a rigid and narrow view of the self, which requires specific types of normal behavior and "right living." She asks, "why is the ‘well rounded' individual any more admirable or any better ‘functioning' than the passionately obsessed?" and then judges that "recovery discourse not only pathologises the addicted and the compulsive, but rejects the existence of benign eccentricity." Returning to her original theme, she affirms that recovery ideals are supported by the dominant culture because they are a "justification of the regulatory programs and operations of power which characterize modern government" and are coercive in that "any desires or beliefs" expressed by the addict "can be dismissed as an expression of disease."

The author ends by urging conceptualization of addiction as habit, not disease. Habit forms the basis of entry into and exit from addictions. Focus on habit as the basis of addiction eliminates the need for development of inner selves or for pathological views of individuals as good or bad, or sick or healthy, and requires only that, although difficult at times, those addicted modify their distressing habits. Such a stance, she believes "has the benefit of seeing the addicted subject as other than defined by life-long and all-encompassing sickness" and will no longer allow coercive practices, which ignore the wishes of the individual. She does reluctantly acknowledge a possible benefit of the medical model—"for some the outcomes can be positive"—but more important in her view is that "for others . . . the medical . . . interventions [are] far from benign."

An annoyance of the book is that the author intermittently slips into jargon and the writing becomes turgid, eg, "A Deleuzian understanding of embodied human subjectivity as assemblage enables a refiguration of the encounter between drugs and the body away from the dichotomy of the artificial and the natural." However, in general, Keane is intellectually consistent, reasons well, knows her subject matter, and understands the philosophical and medical concepts involved in the debate about the meaning of addictions. However, her book is not relevant to practicing physicians who must engage suffering patients in the culture in which they exist and who must do their best to help ease their patients' burdens, whether the result of aberrant biological tissues or habits gone astray.

Edmund Pellegrino recently wrote that medicine is experiencing "an unprecedented state of confusion about its identity." He should know. Through four decades, as healers have strived fruitlessly to reconstruct and repair their vocation, Pellegrino's call to service has echoed through medicine's scaffolds—sometimes lonely, frequently maligned, but always clear and never wavering. In the aptly named "postmodern" age—in which people define themselves by what they repudiate—Pellegrino has courageously focused on what he affirms. He professes healing.

Dr Pellegrino's account of healing begins with the "fact of illness," occasioned by a person's "perception of an altered state of existence" in which body and/or mind no longer function as they should. Despite its fluidity, subjectivity, and susceptibility to divergent interpretations, this perception is the sole and invariant condition for clinical medicine. Apart from the experience of illness, there can be no basis for a science of pathology, much less for medicine. The distinctive nature of illness, as an assault on the personal identity, wholeness, and being of the afflicted person, begets the (essentially involuntary) transition to "patient," and dictates the nature of the genuine healer's response.

The healer is one who undertakes an "act of profession"—the second moment in Pellegrino's account—consisting of a claim to possess healing knowledge and skill, and of a promise to use these assets on the patient's behalf. This promise is essential to the act of profession, given the patient's vulnerability and the importance of trust in the clinical relationship.

The final, crucial element is the "act of medicine," in which the physician and patient collaborate in determining what is wrong, what can be done, and what should be done. The final question provides the ultimate focus for any healing relationship. It is an inherently moral query that hinges not merely on medical indications, but also on the patient's particular experience, values, and judgments. Pellegrino writes: "The end of medicine, formally considered, is therefore a right and good healing action taken in the interests of a particular patient." A decision is "right" insofar as it accords with medicine's canons of technical proficiency (correctly applied to the particular patient) and "good" insofar as it reflects the patient's authentic wishes and values.

Bucking fashionable appeals to the mutable, socially constructed nature of medical morality, Pellegrino attends to what is permanent and nonnegotiable. The fact of illness, the act of profession, and the act of medicine, with its characteristic focus on healing, reside at the core of any legitimate healing profession, constituting its essential structure. Although Pellegrino lacks formal philosophical training and often states that he is not a philosopher, his appeal to "essence" rings loudly with philosophical overtones. Unabashedly, he confronts the contemporary, antiessentialist philosophical orthodoxy. In this sense, Physician and Philosopher is aptly named. Throughout his career, Pellegrino has cultivated and championed a distinct account of the philosophy of medicine that is grounded on a conception of the healing encounter. His version of the philosophy of medicine is a branch of inquiry that

seeks to understand the nature and the phenomena of the clinical encounter, i.e., the interaction between persons needing help of a specific kind relative to health and other persons who offer to help and are designated by society to help.

This account differentiates the philosophy of medicine from "medical philosophy," which consists of unsystematic, informal reflections on the practice of medicine (Osler's work often being a prime example), "philosophy in medicine," which applies standard philosophical tools to specific medical problems (a typical approach in "bioethics"), and "philosophy and medicine," in which medicine and philosophy enter into dialogue while remaining distinct and independent (an example being Plato's allusion to medicine as an illustration of techné).

Physician and Philosopher is an important addition to the medical literature insofar as it mines Pellegrino's more than 500 publications for the most cogent, readable, and compelling accounts of his distinctive philosophy of medicine and integrates these selections into an enticing exploration of clinical practice, healing virtues, medical education, and professional social responsibility. Although Pellegrino provides three very important earlier books, written with philosopher David Thomasma, this volume provides a unique and comprehensive tour through his multifaceted career as a philosopher and humanist of medicine.

To critically assess Pellegrino's offering, it is necessary to engage the philosophical details. Pellegrino gives what philosophers would call a "teleological" account of medical morality. The telos, in such accounts, is an authoritative end or aim that structures subsequent moral judgments and categories. It can be described as a human activity (as in Aristotle's account of happiness) or as an organic state (as in utilitarian accounts of pleasure, physiologic accounts of good health, and psychological accounts of decision). Pellegrino refers to both an "immediate telos of the clinical encounter" and an "ultimate telos of healthcare." One of the problems in his account is vacillation on whether these ends are activities or states. Sometimes, for instance, his immediate telos is described as a right and good decision (a state) and sometimes as a specific healing action that proceeds from such a decision (an activity). Likewise, medicine's ultimate telos is described alternately as health (a state) or as the restoration and cultivation of health (an activity). The most consistent usage designates the telos as an activity. Pellegrino seems to lapse into the popular vernacular of "state" talk mostly when he is speaking on an informal level.

This distinction has important consequences (which I can only touch on here). First, if the state of health is medicine's telos, and physicians must (as Pellegrino advises) defer to patients' particular conceptions of a good life and health, then the philosophy of medicine as a teleological enterprise shifts into a pluralistic, public domain—from a philosophy of professional practice to a philosophy of human flourishing. This shift would transform and probably thwart Pellegrino's quest for agreement about the essence of clinical medicine. On the other hand, if the telos were an activity of physician and patient together, Pellegrino might gain the traction he needs to articulate a distinctly professional ethic with a defensible ethical core.

But, then again, perhaps not. My second concern is that even if Pellegrino intends to portray the telos as a joint activity of healers and patients, as I maintain, the problem of moral pluralism is still bound to creep in. Pellegrino focuses most of his attention on the clinician's role. This angle makes sense given that the clinician is a constant, recurring presence in the succession of joint partnerships that characterize clinical medicine. In attending to the clinician and the clinician's responsibilities, however, Pellegrino gazes selectively at one aspect of the wider clinical picture. Despite frequent allusions to the centrality of patient perceptions, values, and concerns, these characteristics tend to be viewed abstractly, as sources of professional obligation. When we bring the patient more fully and concretely back into the picture, things get muddied. What to do, for instance, about the patient (perhaps a Filipino subscribing to the moral vision portrayed by Alora and Lumitao)¹ who rejects Pellegrino's statutes about "restoring autonomy" and his conception of wholeness (centering on a "capacity to make autonomous choices based on knowledge and free of coercion")?

The problem is that Pellegrino has developed his conception of clinical medicine by focusing on only one axis of the bidirectional dialectic between professional and social ends. He abstracts health care from its existing context in broader social relations, isolates the clinician-patient relationship from the broader context of health care (though certain health care activities are very hard to squeeze into the clinical paradigm), and then focuses his analysis on the role and obligations of physicians specifically—as if these could be judged apart from the bigger picture. This selective emphasis on clinical experience vitiates discussions such as his critique of market competition in health care (just as, conversely, market advocates are frequently afflicted by one-dimensionally economic theories of human flourishing).

All this being said, I believe that Pellegrino overtakes impartial holists by the sheer, resounding force of his humanity. Reading Pellegrino's compelling and often beautifully written meditations, one is struck by the moral primacy of help rendered to defenseless and vulnerable persons. One of his essays, "The Book of Job," is particularly apt. In the world of medicine, Job often presents as the afflicted patient—debilitated, lonely, and confused about the meaning of his suffering. Though Job must face his afflictions on his own terms, the terrain is ultimately shared by all. It is in the sharing, perhaps, that illness and dying are rendered less ghastly. Pellegrino notes, "Job's friends spent a week with him in silence. Considering their later clumsy attempts to console him, this was perhaps the best thing they did. Their presence was a genuine act of empathy. It is the first step we, too, must take—to be with the sick, to listen to their soliloquies, to say just enough to show we are there, and to allow their hurt to show itself." Can we truly be with our patients when we allow ourselves to be pulled in contrary directions as gatekeepers, entrepreneurs, and self-promoters? Can clinical medicine reach its potential when trust is anything less than absolute? Dr Pellegrino says no.