How Science Works: Evaluating Evidence in Biology and Medicine

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I should emphasize that my interest s in these topics are those of a pract icing scient ist, not of an authorit y on philosophy or statistics.

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I like to talk about the details of a few key studies, including their assumpt ions, methods, limitations, and implications for future work , rather than summarizing result s from a large number of st udies. Several years ago, I was asked to develop a core course in research design for graduate students in ecology, evolution, and conservation biology at the Universit y of Nevada, Reno.

I shared this bibliography with my students, sometimes to their amazement at the obscure references I had found, somet imes to their consternation that there was so much to be learned. I also became increasingly concerned about the inadequate and even misleading treatment of these ideas in political discourse, in the news media, and even in basic science educat ion. This seemed especially unfortunate because many of the decisions that indiv iduals and societ ies must make these days depend on better understanding of how science work s.

No doubt my advancing age contributed to this concern, and an unk nown but shrink ing amount of t ime left on Earth e. Hazen and J. I completed most of this book while on sabbatical leave from the University of Nevada, Reno, and I thank the Board of Regent s of the University and Community College System of Nevada for grant ing me this leave.

Thomas Nick les prov ided stimulat ing discussion and key references during the early stages of the project. I am grateful to many people who prov ided valuable informat ion or helpful rev iews of indiv idual chapters: Matthew Jenk ins Chapters 1, 2, 4, and 6 ; John Basey 2 and 9 ; Christ ie Howard 2 and 6 ; John Worrall 2 ; A my Barber, I.

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I also appreciate the comment s of Marc Mangel and several anonymous rev iewers of my proposal for the book and of an early version of Chapter 6. Their enthusiast ic response to my writing was heartening. I thank Grant Hok it for prov iding the photographs used in Figure 4.

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Martens et al. I thank my editor at Oxford University Press, Kirk Jensen, for his early encouragement and cont inuing enthusiasm for this project and for his valuable editorial suggest ions.

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My father, Dr. Ward S. Jenk ins, has spent a lifetime exploring ideas, and I appreciate the example he set. My mother-in-law, Ann O. Pleiss, inquired about my progress week ly, which prov ided important moment um. I dedicate this book to the memor y of my mother, Elizabeth Howell Jenkins, art ist and env ironmentalist.

Reno, Nevada Contents 1. Introduction 3 2. Why Are Frogs in Trouble? Strong Inference by Testing Alternative Hypotheses 73 6. What Causes Cancer? The Complexit ies of Causat ion 92 7. Why Do We Age? Different Levels of Causat ion as Complementary Explanat ions 8.

How Does Coffee Affect Health? Combining Result s of Mult iple Studies 9. Models and the Perils of Predict ion You may be a young person wondering about a possible career in science. You may even be a practicing scient ist curious about how I w ill present a topic that is already quite familiar to you. I hope to stimulate a diverse group of readers, but my main goal is to tell some stories about science that are richer in detail than most science report s in the popular press.

How Science Works: Evaluating Evidence in Biology and Medicine

Thus I am writ ing for people who may have great interest in science but little or no technical training and who get most of their informat ion about science from the news media. If you are a beginning biology student, I hope this book whet s your appet ite for more detailed st udy of the principles that underlie these stories. If you are doing research in one of the areas I discuss, you w ill undoubtedly think of important details I should have included or different points I should have emphasized, but I hope you conclude that my translation of your story for a nontechnical reader is accurate and fair.

Science stories are regular feat ures of the daily news, although usually not as prominent as stories about war and peace, politics, economics, and especially sport s and entertainment.

The scientific method

In it s coverage of science, my local newspaper, the Reno Gazette-Journal, is probably fairly typical of newspapers in all 3 4 How Science Works but the largest cit ies in the United States. I haphazardly selected 13 issues, published bet ween 2 August and 2 September to examine it s coverage of science. The stories ranged in length from about to words. Another major source of science stories in the popular press is reports released by government agencies or commissions, as in the report about cloned animals being safe to eat. The f undamental problem w ith almost all of these stories is that they emphasize the conclusions of researchers but give scant attention to the methods used to reach these conclusions.

There may be a brief explanat ion of a key piece of ev idence but rarely any discussion of the assumpt ions made in interpreting this evidence Rensberger The reason for this weak ness is simply lack of space or t ime to develop the details of the stories. Science of ten gets only cursor y attention in the media because it competes for attention with many other topics. There are several unfort unate consequences of the approach to science often taken in the news media. First, it reinforces the belief that science is a unique act ivity and scient ists are fundamentally different from the rest of humanity.

This belief can be called the cult of the expert. It is rooted in the assumption that a great deal of technical training is necessar y to become a scientist, and therefore scient ists are the only ones who can truly understand what other scient ists do. Based on the cult of the expert, the role of the news media is to transmit pronouncement s of scient ists to the general public. Neither reporters nor consumers of news are responsible for evaluat ing these pronouncement s. Instead, when different scient ists make contrasting pronouncement s, the issue is which scient ist has the strongest credent ials, and therefore should be considered most credible, or which scient ist is the maverick challenging an orthodox v iew, and therefore should be favored because of his or her status as an underdog.

The cult of the expert has a second negat ive consequence: news about science can be conf using when successive stories about a topic report different Introduction 5 conclusions. W hich conclusion should we believe? The most recent, simply because new research always trumps older research? The st udy done by a member of the Nat ional Academy of Sciences because of the reputation of that senior scient ist?

On a more pract ical level, should we drink more red wine or less? A third unfort unate consequence of science report ing is that readers miss the fun and excitement that were part of the discover y process when stories focus on the end result s. For example, it might promote more rational discussion of social and political decisions that relate to science.

Modern science is undoubtedly complex, but I believe that many aspect s of this complexit y are accessible without extensive technical training. News about science is of ten confusing because different k inds of ev idence point in different direct ions. The essence of science is not some nugget s of informat ion about the nat ural world but rather an ongoing process for gradually learning how the world work s, with occasional breakthroughs in the form of major discoveries.

Scient ists have learned to tolerate such uncertainty and even relish the challenges it offers. This challenge applies to both personal choices about health and nutrition and choices societ y must make about env ironmental regulations and other public policies. Perhaps my most important goal is simply to show you the pleasure that can be had from thinking rigorously and critically about how scient ists try to solve problems.

But my underlying goal is to draw you into each story because of the topic itself and then have you discover that the real excitement is in the various approaches of researchers in answering key questions. However, I see this book as a supplement to daily news about science, not an alternative. Many science journalists do an excellent job, especially when they have an opport unity to write longer stories about topics that they have invest igated in depth.

But one goal of this book is to help you read f uture stories about science in the popular press w ith more understanding and insight. For example, the Human Genome Project, in which the ent ire genet ic code of human beings was determined, would not have been possible w ithout the development of automated sequencing machines for reading the informat ion in long strands of DNA. The human genet ic code consist s of about 30, genes distributed among 24 different chromosomes. The letters of this code Introduction 7 are the four nucleot ide bases of DNA, and each gene consist s of a unique sequence of these bases.

In humans, the total number of nucleot ide bases on the 24 chromosomes is about 3 billion. To be sure, this traditional approach depends on hard work , perseverance, detailed k nowledge to provide a context for interpreting new observations, and somet imes good luck. For example, Philip Gingerich, Hans Thew issen, and others found a series of fossils in Pak istan and Egypt during the last 30 years that clearly established how whales evolved from even-toed ungulates, the group of mammals that includes cows, sheep, hippos, and related species Thewissen ; Sutera ; Wong The sequence of intermediate forms bet ween terrestrial mammals adapted for running and marine mammals w ith no external limbs, nostrils on the tops of their sk ulls, and other adaptations for living in water is a truly amazing illustration of an important evolut ionary transformat ion, yet demonstration of this transformat ion was primarily a low-tech effort.

These common feat ures are mainly ways of thinking about problems, that is, mental tools rather than technological tools. I believe that this aspect of how science work s is accessible to anyone willing to exercise his or her brain, regardless of technical background. Therefore, I use examples that illustrate some of the basic analytical methods that underlie all areas of science, rather than examples that show the contribution of gee-whiz technology.

Evaluating Evidence in Biology and Medicine

A bit more considerat ion of the Human Genome Project may help clarify this point. A lthough decoding enormous quantities of DNA required the development of automated machines and computers capable of analyzing large amount s of data, it also depended on thorough understanding of the structure of DNA and clever experiment s to tease apart how DNA molecules are synthesized. The design of these experiment s was no different in principle than the design of any experiment s in biology and medicine, even ones in which result s could be obtained by simple observation of experimental subjects, such as human volunteers in medical experiment s.

Designing critical experiment s to discriminate clearly among alternat ive hypotheses is essen- 8 How Science Works tially the same process whether the hypotheses are about effect s of v itamin C on colds Chapter 2 or about the structure of molecules such as DNA, although experiment s on the latter may require highly specialized equipment for obtaining and analyzing result s. PLAN OF THE BOOK Scientists use t wo fundamental approaches for answering questions about nature, including human nat ure: nonexperimental methods involv ing pure observation and measurement, and experimental methods involv ing manipulation of nat ural processes.

In both t ypes of st udies, a comparative framework is usually important for interpreting result s. In medical experiment s, for example, responses to a new treatment experimental manipulation in one group of people might be compared to responses in a control group that did not receive the treatment. In nonexperimental studies, health might be compared in t wo groups of people w ith different habits, such as smokers and nonsmokers.

Chapter 2 uses several st udies of the health effect s of vitamin C and similar compounds to illustrate both nonexperimental and experimental approaches in medical research. I introduce this approach by discussing t wo experiment s to test the effects of large doses of v itamin C on the common cold. These examples illustrate some of the basic decisions that must be made in designing any experiment, such as what to use as a control treatment for comparison w ith the experimental treatment and how to measure responses to the treatment s.

Studies of the effect s of v itamin C on the common cold demonstrate some of the pitfalls of designing effect ive experiment s. Although the hypotheses being tested in these experiment s were straightforward, the procedures were relatively simple, and the analyses of result s were uncomplicated, certain aspects of the experiment s contributed to uncertain conclusions. In Chapter 2 I also introduce purely observational st udies of the longterm effect s of vitamin C and similar compounds on aging.

One of the key studies asked whether elderly people in Basel, Sw itzerland, w ith high levels of vitamin C in the blood had better memor y abilities than people w ith lower levels of v itamin C. This and related examples illustrate the ambiguit ies that arise in interpreting results of Introduction 9 nonexperimental studies, which are often more problemat ic than the pitfalls of interpreting experimental result s.

I revisit this theme in Chapter 8, which compares experimental and nonexperimental studies of the effect s of caffeine on blood pressure. Short-term effects were st udied with some well-designed experiment s, but understanding the consequences of a lifetime of coffee use required a purely observational approach. I compare experimental and observational methods in several other chapters also.

Chapter 3 describes the special challenges and rewards of using experiment s to study animal behav ior, in particular the ability of dogs to identify indiv idual human beings by smell.