Born This Way: Becoming, Being, and Understanding Scientists

By Richard Lockshin

A senior and well-published scientist describes, through anecdotes, parables, and stories how scientists conceive, ask, and answer questions, and how what they do develops from the culture of their time. Part 1 describes the origins of modern biological science. It addresses issues such as why the story of evolution arose in the 19th C, and not before or after, how the evidence was gathered, and how its misuse led to some terrible decisions by societies. Part 2 describes the rules for experimental science, what constitutes a good versus a poor experiment, how hypotheses, such as the hypothesis or the origin of AIDS, are tested and evaluated. The author goes on to describe the origins of molecular biology and the "cool tricks" that created a billionfold greater ability to analyze living things, leading to the miraculous capabilities that we have today.

• Language: English
• Publisher: Richard Lockshin
• Release date: May 20, 2013
• ISBN: 9780989467407

Richard Lockshin

Richard A Lockshin, born in Ohio, cannot recall a time when he did not want to be a biologist. That worked out, as he received his undergraduate and graduate degrees from Harvard. He taught at the University of Rochester School of Medicine and Dentistry and later at St. John's University in New York, and is currently Professor Emeritus at St. John's. As a research scientist he is known for his studies of programmed cell death or apoptosis, now a major research topic, a field of which he is considered to be a founder. He has well over one hundred research publications, including several technical books in the field. He resides with his wife on Long Island, New York.

Book preview

All children are born biologists. Watch any child between the ages of three and six. They are fascinated with worms, bugs, frogs, and in fact anything that moves. They also need to classify (Is it a boy or a girl?) and understand what they can about it. Some of us never outgrow that childhood curiosity and fascination, and we become the biologists of this world. Why we persist in this stunted stage of development--not outgrowing our curiosity--is a matter for developmental psychologists, but a surprising number of practicing adult scientists had, as children, a nickname something like Questions. Sometimes our parents help, tolerating and even encouraging the incessant questions and vermin brought into the house, as opposed to the parent who, fatigued and exasperated, tells a child Stop bothering me with your questions. But in the end, we survive, asking throughout our lives what things are, how they work, why they are the way they are and not something else, and how they came to be.

Sometimes these questions lead to other questions: Why others don't ask questions; why people argue so adamantly against the theory of evolution, when to deny it means that one has to deny most other parts of science, which they readily accept; and why we keep trying to explain what we do, only to be told that we are geeks, the material is boring, dull, incomprehensible, or yucky, and that normal people are not science junkies.

Therein lies the origin of this book. On a faculty committee reviewing our Core Curriculum offerings, I described my frustration with our typical Biology for Non-Scientists offerings: A watered down version of the standard textbook, raced through in a large class, with multiple-choice tests based on isolated facts. What was in bold-face type on page 432? In other words, Who cares whether you can differentiate between the Ordovician and Devonian? was the way I characterized the tests: a survey of facts unconnected to ideas, the flow of history through science, the exploration of ideas, the questions that were asked and the ingenious ways people invented to answer them: the heart of what science was. No wonder students were bored with what we offered. I wanted to teach a course about the ideas, the questions, the quest. Not only would it be more interesting, it would better prepare students for the developments that were to come in their lifetimes.

So how could we do this? We had to talk about a question of sufficient scope to encompass all sorts of ideas. Although my own research was in developmental biology, the history of the recognition of evolution (or, better, natural selection) was more encompassing. Not only was it the most important idea of the 19th and probably 20th Centuries, it was, in social terms at least, a subject of controversy, something that could always catch the attention of students. One could explore successively why, surprisingly, evolution was not recognized earlier in history, what information gradually accumulated to make its recognition inevitable, how ideas were broached, challenged, tested, and confirmed or refuted, the extent to which social attitudes helped or impeded understanding and sometimes tragically distorted the meanings of discoveries, where we were going, and what lay in the future. Such a subject could reach from self-evident observations such as the similarities and differences among animals to the most abstruse and abstract considerations of molecular biology, and it could provide a forum in which students could evaluate the consequences of current trends, including destruction of habitat and extinction of species to global warming. In short, this would be a course that would teach science as scientists saw it, a realm of question and meaning, and a subject of importance to our species and our world.

That of course was a wildly optimistic assumption. Some students of course were confused by the approach, preferring the (to me) much more boring but predictable dreary procession of names and numbers, a necessary and not-expected-to-be-fulfilling drudge in which, given appropriate direction, one could memorize a sufficient number of bizarre terms to pass the course and, none-the-worse, get on with life. The standard offering was a course to which students were sentenced, but my version was also a difficult course to replicate. Many otherwise commendable teachers did not have the experience to draw analogies between 16th C poetry and 16th C scientific discoveries or between the technology of exploration and the development of evolutionary theory, or were uncomfortable straying outside the boundaries defined for the discipline of basic biology. On the other hand, some students were inspired by this approach, and their response encouraged me that it was possible to proselytize for the scientific method and the scientific approach to life. The course became a book, which I and others used (1). I therefore offer this version as a less didactic, more open version of what it is like to be a scientist, with the stories and anecdotes that led, eventually, to our recognition that we are of this earth, with all the aspirations, limitations, and potential hazards of any species. In a second book (2) I hope, likewise with anecdotes and stories, to explain what the rules of science are, including hypotheses, evidence, and control experiments. Maybe after reading these comments, you will look with a closer or more jaundiced eye at television commercials or feel more comfortable with evaluating the almost daily and often conflicting new claims regarding diets, the value of certain medicines, or exercise or lifestyle recommendations. Perhaps you can add your voice with more confidence to discussions about the warming of the earth, the role of humans in that warming, or the relative merits of hybrid cars, nuclear vs wind or solar energy, and the other myriad questions of the day. This is the responsibility of an informed citizenry, with informed meaning having the information AND being in a position to evaluate it. I hope so.

There is another element here. Science is fun and my intention is more to explain why we are scientists. To that end I would rather play the role of raconteur, and run through anecdotes describing how science works, the stories of science. Science is all about puzzles and games and mysteries. In my classes I often used clipart pictures of a detective to emphasize that the hunt for an explanation of how something worked played out exactly like a good mystery, the gradual accumulation of clues, the ingenious experiment (read: the trap that the detective lays for the unsuspecting miscreant), the ruling out of alternate solutions, and the final proof of the hypothesis. It is not nearly the search for Truth or my science is pure and holy style that so often crops up in television mysteries; it's the fun of being the child called to the stage in a magic show, able to watch the magician up close and having the chance to figure out how the trick is done, that drives us. Normally we identify questions that we think have value to mankind, and we set out to find how the system works. Perhaps it is an ancient instinct, derived from our earliest hunter-gatherer ancestors, and reflected in gamblers today. To an early hunter, be it animal or human, there is an advantage to understanding the system: If the antelope came to the spring last evening, it is likely to come this evening. If you talk to anyone who plays the lottery or gambles, it is striking how many of them invest faith in systems that make little mathematical sense: I chose every third odd number, and I was only one number from winning! This too, however illogical, is an effort to understand the system. Scientists too invest considerable emotional energy in trying to find how the system works. The excitement of the hunt makes every new day the most exciting day to be alive and to practice science.

***Note on what you can do with this book: Electronic format has a size limit that does not permit large or detailed pictures. However, this type of science is often best explained by visual techniques, pictures or videos. Therefore most of the pictures are indicated by outlines or sketches and are hotlinked to the source. Some are to web pages, in which case the link is to the page and for some a mirror copy is available on a Flickr® site available for this book. Photos that are taken from the personal collection of Richard A Lockshin and Zahra Zakeri Lockshin are also available via hotlink on the Flickr® site, http://www.flickr.com/photos/ral_bornthisway. Updates and links to additional pictures or material are available at http://bornthiswayblog.net.

I am very grateful to Igor Siwanowicz for permission to use his photographs as a cover for the book and as part of Figures 5.5 and 10.2. I must acknowledge the tremendous tolerance of my wife, Zahra Zakeri, an accomplished scientist in her own right, who has borne with my musings, flights of fancy, and digressions over many years, as well as taking usually much better quality pictures than mine, many of which grace this book; my children, Miriam and Nora, who not only survived the meanderings of my mind but often outreach me in their curiosity; and above all, my late parents, Samuel and Florence Levin Lockshin, who were bemused by my and my brother's explorations, often catching escaped frogs and mantises, or tolerating the various odors of assorted caged animals. I was truly astonished when, after we had caught some tadpoles and were draining the dirty pond water into the sink at a friend's house, my friend's father came home and was furious about what we were doing. Many students over the years also caught that bug. I thank everyone for that tolerance. Curiosity is a wonderful thing, and it keeps you from getting bored in school. I also salute those students who had the courage to follow their curiosity. As I told those who were more worried, I can't imagine a God who would give us curiosity and understanding, and not expect us to use it to better the world.

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PART ONE: STORIES FROM EVOLUTION

In Biology, nothing makes sense except in the light of evolution--Niko Tinbergen

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Chapter 1: The Theory of Evolution

The view from 1800

We can begin to look at science by looking at the theory of evolution. Although until recently it was not an experimental science, there are several reasons to consider it a paradigm. The theory of evolution is, arguably, the most important idea of the 19th and perhaps 20th Centuries. It has led directly to some of the most dramatic advances in 20th and 21st C biomedical sciences, including genetics and the understanding of DNA, as well as, unfortunately, some of the worst social moves of all time. The language by which evolution is described, at least in its earlier forms, is neither abstruse nor hermetic. And the story of why such an important idea developed in the mid-19th C, neither earlier nor later, describes quite clearly the interaction that always exists between science and the conceptions and understanding of the society in which scientists work.

Two corrections right off the bat: First, we call it a theory not to suggest that it is a random guess, in the sense of I have a theory as to why the team lost the game, but to mean, in the scientific sense, that there is an infinitesimal but not zero chance that a better hypothesis will come along to replace or substantially modify it. As Einstein said, No amount of experimentation can ever prove me right; a single experiment can prove me wrong. Second, it is not the theory of evolution for evolution is a series of data indicating the change in form and types of creatures throughout the history of the earth. Darwin's theory is more properly called the theory of natural selection or descent with modification–the mechanism that is purported to explain the evolution that has occurred.

There are many issues to address: evidence that living things have changed in the history of the earth; the extent to which people appreciated these changes in early times; the reason why the subject became an important issue in the 19th century; how Darwin's hypothesis explains the data; what is not explained by Darwin's hypothesis; and why this idea unlike many others is considered controversial.

It is not at all obvious that the world changes. Suppose that you have no ability to travel, to read, or to receive any radio or television communications about any other country–in short, suppose that you are living as an individual in any time prior to the 15th century. A river might flood and cut a new channel, there might be a landslide on the mountain, or the winter might be warmer than you ever remembered it. Nevertheless, from your childhood until your old age, the river is still there, the mountain is still there, and someone always will remember a warmer or colder winter. This city may expand or shrink and people and wars will come and go. Overall, the world has not seriously changed. You have no reason to assume that the mountain or river will disappear, or that the land could ever be covered with ice. Now let's take a look at the animals and plants around us. For simplicity's sake, let's just consider birds. I live in a suburban community in the northeast of the United States. I can expect to see on my lawn the following birds: robins, cardinals, mourning doves, starlings, various sparrows, blue jays, chickadees, and finches. Migrating through, I might see Baltimore orioles, Canada geese, an occasional duck, red-shouldered and sparrow hawks, and, circling overhead, an osprey. Closer to the seaside…but you get the idea. The point is that I can identify each of these birds and that I will typically not confuse one species with another: the species are distinct and fixed. I will not confuse a dove with a robin, or mistake a pigeon in the city, even though pigeons come in many colors. The Greeks described this certainty as an idea (in the original sense that we now use the word ideal--a perfect form of, say, pigeon-ness, to which each individual pigeon aspired. Some would come closer than others.

Even extinction is likely to pass unnoticed. Consider a species of fish sought after and netted beyond its capacity to reproduce. It becomes more and more rare, gradually becoming so rare that fishermen expect to catch it only very occasionally. Finally, it is forgotten. The last people to have seen it assume that one day they will see it again, except that they never do. Finally, a new generation of fishermen arises, and they have never seen the fish, and this continues until it is finally forgotten. Species do not go from massive numbers to extinct within one person's memory, at least at a time when hunting is not terribly efficient and books do not typically describe rare species.

Thus, to our hypothetical citizen in pre-15th Century mode, there is no reason to assume that either the physical world or the biological world changes. To the monotheistic world of Judaism, Christianity, and Islam, it is perfectly reasonable to assume that all creatures existed on earth since creation and that they will persist until eternity. Some creatures do not live in my land. I have heard of lions, and have even seen reasonably accurate depictions of lions, since the Romans brought them from south and east of the Mediterranean, but I have no more reason to believe in lions than I do to believe in mantigores, griffins, basilisks, or dragons. If lions are not seen in Europe, it is because they choose not to come. They could easily walk to Europe around the eastern end of the Mediterranean.

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Figure 1.1. From left to right, top to bottom: Basilisk (3), Mantigore (4), Dragon (5), Griffin (6).

Thus there is no need for a concept that the world is different from what it once was or that it changes. Artists typically illustrate Biblical figures in the garments of the day, and with the physical characteristics of the artists' people. This neatly structured world began to disintegrate in the 15th C owing to several causes. Books began to proliferate, providing a basis on which to extend knowledge in time and in location. It was becoming possible to think about whether Romans, Greeks or, for that matter, the Arab or Persian world understood the world in the same manner that Europeans understood it. A growing technology, involving boats, materiel of warfare, and large buildings, necessitated an efficient search for minerals, raw materials, fuels, and--so that royalty could demonstrate their wealth--jewels. To support this growth, explorers had to understand the world more thoroughly, to predict where resources might be found. And, finally, explorers began to bring back samples and tales of far-off lands, including creatures never seen in Europe. All of these activities converged into a sense that the world was far more complex than Europeans to that point had understood.

European and other societies had some inkling of all the components of the theory of natural selection, but until the mid-19th C no one had assembled the components into a comprehensive theory. To do so required recognition, to the level of comfort, of both the ideas that the earth was very old and that species were not fixed and could change. Both of these ideas challenged the written Word (as translated from Hebrew through Aramaic through Greek through Latin into vernacular) and therefore acceptance of the possibility that the Bible, if accurate, was at the very least allegorical rather than literal. All of these realizations were gradually taking hold by the 19th C, so that by the time that Darwin wrote, he and other intellectuals were excited by the possibility of resolving a major question, that great fact--that mystery of mysteries--the first appearance of new beings on this earth. But to do so required turning this curiosity into a true scientific question, that is, to formulate a hypothesis: a mechanism by which one phenomenon, natural selection, could explain another, descent with modification. These words, rather simple and deceptively easy to comprehend by themselves, in combination imply complex and elaborate mechanisms: natural selection, overbreeding of all populations, competition among individuals for resources, survival of those best adapted to use the resources, and further breeding by only those better-adapted individuals who, passing their better characteristics onto their children, would by descent with modification, leave future generations better and better adapted to their station in life, thus changing the species. Could such a mechanism explain even the creation of new species? This was the breathtaking possibility faced by Darwin and Wallace. We write Darwin and Wallace because, contemporaneously with Darwin, Alfred Russel Wallace generated nearly the same hypothesis. In fact, a manuscript he sent to Darwin (7) precipitated the effort by the friends of the scrupulous and obsessively thorough Darwin to force him to publish his ideas. Wallace was less well placed than Darwin and more diffident, and he did not follow through with his research into evolution as Darwin did. He is therefore less well known to the public, but the coincidence raises another hugely interesting question: why in science does more than one group make many great discoveries nearly simultaneously? We will encounter another such coincidence in the nearly simultaneous rediscovery, by three laboratories, of Mendel's work nearly 40 years after it was published. The answer is that the questions are always there--where do species come from?--but until the questions can be formulated as hypotheses they cannot be answered by science. To formulate hypotheses, one needs sufficient evidence, which must be seen with sufficient clarity to describe a cause; one needs to define a process or mechanism with sufficient precision that one can determine a result or effect that cannot be easily explained by any alternative mechanism; and one needs to define the effect with sufficient accuracy that the explanation is not drowned in ambiguity. To accomplish this goal, for the mechanism of evolution, we needed a profound knowledge of the age of the earth, of the biology of species, and of mechanisms of competition. These separate understandings coalesced in the mid-19th C, making it possible for Darwin, and for Wallace, to formulate a hypothesis concerning the origin of species. Since then, scientists have elaborated the hypothesis, documented its validity in the most stunning and unexpected ways, and occasionally polished the edges by amending aspects of the mechanisms, but by and large have confirmed the hypothesis to such an extent that we now describe it as a theory: a hypothesis so tested and confirmed by so many different types of experiments and observations that we would be truly astonished if we were to find a contradiction. We grace broad hypotheses with this title, such as the Theory of Relativity, which has been used to build nuclear reactors and bombs, to explain the heat of the sun, and to conceptually reach deep into the heavens. Any potential challenge to a theory is sufficiently astonishing to trigger an intense and sometimes newsworthy search to find what is wrong with the challenge. If a theory is