Preface to Part 2–The Rise of Molecular Biology

PREFACE: SCIENCE AND THE SINGLE HUMAN

How can we be both science-exacting and science-ignorant?

We run our lives by science. We expect our medicines, our physicians, the robots that we use for surgery, our food and our water, to be 100% free from harm, and we sue should we find that they are not perfect. We depend absolutely on our GPS systems and on the physics by which machines as big as a 20-story building carry us seven miles above the surface of the earth, half way around the earth. We rely on our meteorologists to predict bad weather and we fire politicians who do not address the storms. We revel in growing varieties of flowers and food plants in many different environments. We demand seedless fruits, vegetables in multiple colors, weed-free lawns, and insect-resistant flowers with huge blossoms with many layers of petals. We marvel that computer-guided weapons can destroy property and other people without putting American lives in danger. We clamor for the latest wonder drug, including “designer drugs” tailored to the specific disease and genetics of the patient, and we adore the new breeds of dogs and cats. We subject ourselves to chemical and surgical body-enhancing procedures, and athletes seek out hormones and growth factors that will enhance their abilities. Many of us rapidly adapt to the latest scientific argument, eagerly buying products that are claimed to suppress “free radicals,” enhance “metabolism,” or remove “toxins”. We argue vehemently about the use of “fossil fuels” and the different means of extracting them, as opposed to nuclear energy and solar energy.

And yet many of us deny science.

Half of us do not believe that humans evolved from similar species over periods counted in millions of years.

Some think that the earth is flat.

A majority do not accept all the documentation that the earth is warmer than 100 years ago, consider that humans have not affected the climate, or do not accept the predictions of the biological and geological consequences of the changing of global temperature.

Some of this comes about because science appears so foreign–hermetic, arcane, filled with complex calculations, torture of animals, unpleasant and disagreeable chemicals, impossible words, and basically incomprehensible babble. No music, no songs, no touchdowns or home runs, in short, the heart of boring geekdom.

And yet…

Science is within reach of everyone. Everyone, in one way or another, is a scientist, asking questions, wanting to know how things work, exploring relationships of cause and effect. Scientists themselves enjoy life. We enjoy dancing, singing, parties, sports. Most importantly, we can explain what we are doing, and why we do it. We work on the assumption that we can best understand cause and effect by using our logic and our senses to test our hypotheses. It is something that everyone does in one form or another. Sometimes our rules are a little different. What we ask is that we, scientists and lay, explain to each other what we understand to be the rules.

So what is it like to be a scientist? Think ten-year old at a magic show, invited onstage to see how the magician performs his tricks. Alternatively, we all try to understand “the system”. This must have been a priority for the earliest hunter-gatherers: “If the antelope came to the waterhole last evening, it is likely to come back this evening.” Lottery players rely heavily on working out ways to beat “the system”, coming up with complicated formulae for choosing numbers. Even in our everyday chicanery (how to find a parking meter with unexpired time) we take pleasure in outsmarting “the system”. This is how a lab scientist spends his or her days, trying to find ways in which we can trick nature into revealing her secrets. To find a new secret, to reveal a new mechanism through which an organism accomplishes its goals, is a source of enormous pleasure. We spend our days matching our wits with the most imaginative resources that God or evolution could devise.

Of course, it is also possible to consider the work of a scientist to be filled with excruciating boredom or frustration. The truly satisfying or elegant (see next paragraph) experiment is a rare bird indeed. Most of our time is spent reading about what others have found and considering the options and permutations of those results, or in trying to improve experiments. Experiments usually do not work (at least in the biomedical sciences; for large-scale physics experiments, the cost is so high that all limitations have to be identified well in advance). In the biomedical sciences, the initial results of an experiment are often ambiguous or not clean enough for publication, and we invest considerable effort in asking questions like, “It is possible for the experimental value to be too low but not for it to be too high. It is also possible for the control value to be too high. What can I do to make sure that the control value is not artifactually too high, so that I can reveal the difference?” And we spend days trying minor variants of the same experiment, tweaking the system to make the results a little better. As I often tell students who aspire to a career in research, the personality of a researcher is that he or she must simultaneously abhor and tolerate ambiguity. One has to tolerate it, because initial experiments are often not clear enough to come to a precise conclusion. On the other hand, one has to abhor ambiguity enough to keep going, to be committed to resolving it.

At the end of the day, one strives to carry out an “elegant experiment”. Elegance is highly prized among researchers. The term connotes an experiment so pure and clean, so efficient, that there can be only one conclusion: Quid Erat Demonstrum. Einstein’s eclipse experiment (p. 46) was elegant. In a similar fashion, Karl Landsteiner’s prediction of the shape of an antibody molecule could be considered to be elegant because his interpretation of the meanings of the properties of the molecule proved to be correct. Briefly, he considered that, when antigen (the protein that reacts with an antibody) was added to a constant amount of antibody, when there was too little antigen, there would be no precipitate. When the amount of antigen relative to antibody was approximately 1:1, there would be a precipitate; but when the amount of antigen exceeded the amount of antibody, there would be no precipitate or a previously-formed precipitate would dissolve. He concluded that the antibody must have two binding sites, allowing it to form chains or polymers when the ratio of concentrations was correct (Fig. p1a). When the structure of antibody molecules was finally elucidated, about 50 years later, it was truly gratifying to see the prediction verified (Fig. p1b). (Landsteiner also identified the major blood groups—Rh factor, A, B, and O—for which he was awarded the Nobel Prize.) Other elegant experiments would include Lederberg’s demonstration (p. 104) of bacterial sex, Watson and Crick’s elucidation of the structure of DNA (p. 90), and Crick’s demonstration that the genetic code was linear (p. 100).

 

Figure p1a (left). Landsteiner’s prediction. The antibody can link to the antigen through two points. When the ratio is approximately 1:1, it can form insoluble chains of antigen-antibody-antigen-antibody-antigen… as in center of graph. If there is more antibody than antigen (left of graph), each antibody molecule can bind only one antigen, and the chain will not form. If there is more antigen than antibody, each antibody molecule will be saturated with extra antigen, and the chain will not form. Figure p1b (right): The basic structure of an antibody molecule (here highly simplified). It proved to be a two-headed molecule, as predicted. One region is constant, while the heads, to which antigens bind, come in many forms, allowing us to make antibodies that can identify many different types of antigens. The whole story of how this is done is fascinating and worthy of retelling at length.

Elegance is recognized in most walks of life. For instance, at one point in my life I was writing computer code. I would write a program that would do what I wanted, but it had some workarounds and patches (what computer people call “kluges”) because I didn’t know how to address one issue. In nearly addictive fashion, I would work (unnecessarily) on the program until it was lean, linear, and flawless. We all do this in one way or another: fold shirts perfectly, arrange a bookshelf in a specific order, make sure the silverware is perfectly aligned on the table, confirm that there is not a stray bubble in a painted object or a fold in a caulk line… It is part of demonstrating mastery of “the system”, demonstrating that one understands the workings so as to be in perfect control of them. Such are the sentiments of researchers.

And what about those who are not scientists? Well, that would be a very small proportion of humankind, if any exist at all. We are all scientists when we query how things work, and we are all so hugely affected by the impacts of our curiosity that we cannot avoid, as we use the artifacts of our civilization that derived from scientific ideas (computers, electricity, to name the most complex, but also including virtually every crop or domesticated animal, none of which remotely resemble their wild forms), or we contemplate headlines every day: to vaccinate or not; use genetically modified organisms (GMO) as food or not; the extent to which climate change is real and will affect us; what types of fuel to use for energy; the effect of nerve gases; the science and morality of fertility and the beginning of life; the science and morality of stem cell research; the extent to which the end of life should be regulated; mechanical and laboratory-grown replacement organs; the value of space exploration…

Many of these questions involve highly technical discussions, but the basic premises and assumptions are well within the range of understanding of any reasonably educated and curious adult. What is typically missing is recognition that scientific analysis follows common logical structures and that, by accepting a few rules and approaches commonly used by scientists, any individual can grasp the gist of the arguments and assess the valuations proffered. Thus here I attempt to describe how science works and how scientists operate. Once we get beyond the slogans, shibboleths, and propaganda, we can all contribute to and guide that great human enterprise that is driven by curiosity.

*****

SCIENCE AND THE SINGLE SPECIES

Science knows no country, because knowledge belongs to humanity, and is the torch which illuminates the world. Science is the highest personification of the nation because that nation will remain the first which carries the furthest the works of thought and intelligence.“ (Louis Pasteur)

“Consider again that dot. That’s here. That’s home. That’s us. On it everyone you love, everyone you know, everyone you ever heard of, every human being who ever was, lived out their lives. The aggregate of our joy and suffering, thousands of confident religions, ideologies, and economic doctrines, every hunter and forager, every hero and coward, every creator and destroyer of civilization, every king and peasant, every young couple in love, every mother and father, hopeful child, inventor and explorer, every teacher of morals, every corrupt politician, every “superstar,” every “supreme leader,” every saint and sinner in the history of our species lived there – on a mote of dust suspended in a sunbeam.

 

The Earth is a very small stage in a vast cosmic arena. Think of the rivers of blood spilled by all those generals and emperors so that in glory and triumph they could become the momentary masters of a fraction of a dot. Think of the endless cruelties visited by the inhabitants of one corner of this pixel on the scarcely distinguishable inhabitants of some other corner. How frequent their misunderstandings, how eager they are to kill one another, how fervent their hatreds. Our posturings, our imagined self-importance, the delusion that we have some privileged position in the universe, are challenged by this point of pale light. Our planet is a lonely speck in the great enveloping cosmic dark. In our obscurity – in all this vastness – there is no hint that help will come from elsewhere to save us from ourselves.

The Earth is the only world known, so far, to harbor life. There is nowhere else, at least in the near future, to which our species could migrate. Visit, yes. Settle, not yet. Like it or not, for the moment, the Earth is where we make our stand. It has been said that astronomy is a humbling and character-building experience. There is perhaps no better demonstration of the folly of human conceits than this distant image of our tiny world. To me, it underscores our responsibility to deal more kindly with one another and to preserve and cherish the pale blue dot, the only home we’ve ever known.”

 

—Carl Sagan, Pale Blue Dot: A Vision of the Human Future in Space, 1997 reprint, pp. xv–xvi

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