Is That a Fact?

Frauds, Quacks, and the Real Science of Everyday Life

ECW PRESS

Contents

IN THE BEGINNING

Is That a Fact?

"Is that a fact?" "They say that ..." "I heard that ..." Just listen in on a few conversations around the water cooler and it won't be long before one of these phrases rings out. After all, this is the Communication Age. We are connected through cell phones, radio, TV, and, of course, the web. We talk, we Tweet, we link, we text, we Facebook. We are informed. But in many cases, unfortunately, we are also misinformed.

We suffer from information overload. Just Google a subject and within a second, you can be flooded with a million references. It is therefore more important than ever to be able to analyze those references and know how to separate sense from nonsense. And that's where learning comes in. Information has to be scrutinized in the light of what is already known. But learning must be coupled with critical thinking. Confucius said it very well: "Learning without thought is labor lost; thought without learning is perilous."

The University of Google is well stocked with information, but its students are left to flounder when it comes to determining whether that information is reliable. Accounts of miraculous cancer cures, the rants of anti-vaccine activists, the exploits of so-called psychics, and the claims of various alternative healers may sound very seductive, but stand to lose their luster in the light of scientific education. It would, however, be incorrect to suggest that education is the vaccine against folly. The annals of history are replete with examples of educated people who have succumbed to nonsense. Sir Arthur Conan Doyle, a physician by training, believed in fairies and in communicating with the dead. Curiously, he was the creator of Sherlock Holmes, who was a logician extraordinaire and eschewed such silliness.

Indeed, it was Holmes who reminded us, "It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories instead of theories to suit facts." These days, those of us who follow Holmes's dictum and put evidence-based science on a pedestal often get criticized for challenging claims we consider to be unscientific. "They laughed at Galileo," the promoters of such claims say, "and at Columbus, and at the Wright Brothers." But, as Carl Sagan pointed out, the fact that some geniuses were laughed at does not imply that all who are laughed at are geniuses. They also laughed at Bozo the Clown.

Our best bet in order to differentiate the Bozos from the prospective Galileos is to push for more science education at all levels, with a strong emphasis on the importance of critical thinking. Furthermore, it should be realized that when it comes to separating sense from nonsense, mental prowess is not enough. Benjamin Franklin was right on when he opined, "Genius without education is like silver in a mine." Indeed, the value is there, but the silver is not of much use until you extract it. But how do you go about this extraction? How do we know who is right and who is wrong? How do we know what is a fact and what is not? How do I know what I claim to know? that is a question I had to contemplate recently when a student innocently asked me, "And how do you know that?"

I had just finished a lecture on toxicology in which I had described the problem of cyanide poisoning by cassava, a tuber similar to the potato that is a staple in some parts of Africa. However, with some varieties of cassava, there's an issue: if not properly processed, it can harbor a lethal amount of cyanide. (This is not the case with the cassava grown in the Caribbean.) But soaking the peeled tuber in water for several days releases enzymes that degrade the cyanide-storage compound linamarin, causing the toxic cyanide to be dissipated into the air as hydrogen cyanide. Unfortunately, cases of acute cyanide poisoning have occurred when famine conditions forced a shortening of the soaking time. Since even proper processing doesn't remove all the cyanide, chronic low-level exposure can lead to goiter or even konzo, a type of paralysis.

I've described the cyanide connection in lectures numerous times, but never before had I been asked a question about how I had acquired this knowledge. It did start me thinking. Indeed, I've never been to Africa, have never even seen a live cassava plant. I've never carried out any testing of cassava for cyanide. Truth be told, I wouldn't even know how to go about it, although I think that with a little digging, I could figure it out. I do have a vague recollection of once eating fried cassava somewhere in the Caribbean, but that's as close as I've come to experimenting with the tuber. So, in fact, how do I know about its chemistry? It all comes down to reading various accounts of cassava poisoning in toxicology and chemistry texts.

And how do the authors of these texts know what they are writing about? Chances are they haven't had any closer encounters with cassava than I have. But they have read the peer-reviewed literature on the topic, have digested the facts, have managed to piece together the story. They would have read a paper in a medical journal about how the symptoms of konzo were traced to cyanide poisoning and about how a link to cassava was discovered. Then, in a chemical publication, they would have learned that the actual culprit, linamarin, is present in unprocessed cassava but not in the soaked version. Finally, a paper likely published in a biochemistry journal would have revealed the action of enzymes on linamarin. Basically, then, what we call scientific knowledge is gained through a distillation of the relevant peer-reviewed literature. And that literature is the altar at which scientists worship. But, as with religion, there is faith involved. Faith that the peer-reviewed literature can be trusted. That faith, however, cannot be blind. It must be tempered with a dose of skepticism.

So how does the peer-review process work? A principal investigator (PI), who may be an academic, industrial, or government researcher, designs a study, let's say on how a novel weight-reducing drug affects mice. The work may be carried out by himself or by other members of his research group. He or she then writes a paper with the results, adds an appropriate discussion, and submits it to a journal that is geared toward such subject matter. The journal's editor, who has a general command of the science normally featured in the publication, then sends the paper on to two or three referees who have expertise in the specific research area in question. These referees, usually researchers themselves, critique the paper and often ask for clarification or even for more work to be done. The paper then goes back for comments to the original author, who is unaware of the identity of the referees. This process can go back and forth several times before a paper is either accepted for publication or is rejected. Once published, other scientists may weigh in with their opinions or criticisms, which then might appear in subsequent issues as letters to the editor.

Some researcher may, upon reading the paper, wish to extend the work, perhaps by mounting a human trial of the drug. First, though, repetition with more animals may be in order. If the repetition is successful, the drug starts to get more traction and invites further research. By the time it is approved for human use, it will have been the subject of a good number of peer-reviewed papers. Then we can say "we know" it works, albeit with some apprehension.

Why apprehension? Because the peer-review process is not perfect. First, the referees of course cannot repeat the work, which is often the result of years of research. They have to assume that what the author says was done really was done, that it was done well, and that the results have been accurately reported. The pi has to assume the same as far as his research group goes. But humans are, well, human. Some work may be sloppy, and results that do not seem to "fit the curve" may be deemed to be erroneous and therefore ignored. There may also be discrepancies or outright fraud that are not detected until years after a paper has been published. A case in point is Andrew Wakefield's infamous publication in The Lancet suggesting a link between autism and vaccination. Twelve years passed before it became clear that the work could not be reproduced, prompting the journal to withdraw the paper, noting that "elements of the manuscript had been falsified." By that time, an increase in measles fatalities attributed to a decrease in vaccination rates had already been noted.

Problems may eventually crop up even with research that was properly carried out. A side effect of a medication that affects a fraction of a percent of patients will not be detected in trials, but will become obvious when millions take the drug. So peer-review isn't the end-all. But remember what Churchill said about democracy? "It is the worst form of government except for all the others that have been tried." Ditto for the peer-review process. Peer review, however, is the final stage in a scientific investigation that usually begins with an observation that prompts a comment along the lines of "gee, that's funny." And that observation may happen in a serendipitous fashion. But in the words of Louis Pasteur, "Chance favors the prepared mind." That oft-quoted expression is a great springboard for our dive into the pool of science.

Chance Favors the Prepared Mind

I had my tonsils removed in 1954. In those days, a few bouts of tonsillitis, and out they came. I remember being plied with chloroform before the operation and with ice cream after. I also remember being given a special gum, "imported from America," to chew. It was probably some version of Aspergum, which contained aspirin and was supposed to relieve the sore throat. The idea of using the gum after a tonsillectomy was introduced in the 1940s by Lawrence Craven, a California physician, who made an interesting observation: patients who chewed the gum bled more, leading Craven to speculate that aspirin had an anti-clotting effect. It was already known at the time that heart attacks and strokes could be caused by blood clots, and Craven began to treat his adult coronary disease patients with aspirin. He noted a reduced frequency of heart attacks! Craven published his findings, but because he had no controls, they were mostly ignored until British biochemist John Vane clearly demonstrated aspirin's effect on the blood in 1971. Today, aspirin is standard therapy for people at risk for disease, tracing back to Lawrence Craven's serendipitous finding.

The word "serendipity" was introduced into the English language in the eighteenth century by writer Horace Walpole, who was taken by the ancient Persian tale of the "Three Princes of Serendip," who during their travels made a number of discoveries "by accidents and sagacity of things they were not in quest of." "Serendipity" came into common use as a description of a "lucky turn of events," and Walpole's original link to sagacity, defined as "penetrating intelligence, keen perception, and sound judgment" was ultimately forgotten. Walpole's intent was to convey the idea that an accidental discovery doesn't amount to much if the discoverer is not astute enough to capitalize on the chance finding.

The three princes of Serendip certainly exhibited sagacity after accidentally coming on some strange animal tracks on a road. When they later learned from a merchant that he had lost a camel, the princes give him a remarkable description of the animal. "The camel is lame, blind in one eye, is missing a tooth, carried honey on one side and butter on the other, and was ridden by a pregnant woman." When asked how they could possibly have come up with such an accurate description, the princes explained that grass had been eaten from the side of the road where it was less green, so the camel was blind on the other side. Because there were lumps of chewed grass on the road the size of a camel's tooth, the princes inferred they had fallen through the gap left by a missing tooth. The tracks showed the prints of only three feet, the fourth being dragged, indicating that the animal was lame.

The fact that butter was carried on one side of the camel and honey on the other was evident because ants had been attracted to melted butter on one side of the road and flies to spilled honey on the other. There was also an imprint in the dirt from which they deduced the camel had knelt to let down a rider. And why was the rider a pregnant woman? There was some urine nearby, along with some handprints that suggested a woman had needed to use her hands to get up after urinating, her extra weight requiring a push. Shades of Sherlock Holmes. Maybe Sir Arthur Conan Doyle had serendipitously read about the princes of Serendip.

The Persian tale may be somewhat far-fetched, but the story does make a point. The three princes of Serendip were able to capitalize on their chance observation when they heard about the lost camel. And talking about chance, let's return once more to Louis Pasteur's famous comment that "In the field of observation, chance favors the prepared mind."

Pasteur himself furnished a great example of a serendipitous discovery. By 1878, he had formulated his germ theory of disease and had turned his attention to chicken cholera, a problem that plagued the French poultry industry. He managed to isolate a microbe from sick chickens he believed caused the disease and showed that injecting it into healthy birds led to their demise within a day. Scientific evidence requires repetition of an experiment, but a summer vacation intervened. No problem, Pasteur thought, he would just store his bacterial culture. To his astonishment, injecting the culture that had been stored for three months had no effect on the chickens!

He tried again with a fresh culture, and the chickens remained disease free. While many would have concluded that in the original experiment the chickens must have been affected by something other than the suspect bacteria, Pasteur hypothesized that perhaps storage for three months had altered the microbes in a way that resulted in offering protection against infection by fresh bacteria. As it turned out, Pasteur had managed to immunize the chickens with an attenuated microbe! It didn't take long to prove that a weakened form of an infectious organism could impart immunity against the disease normally caused by a more vibrant version. The French chemist then went on to produce vaccines against anthrax and rabies, laying the foundation for the science of immunology, all because his mind was prepared to exercise sagacity when his chickens serendipitously survived an injection of a supposedly deadly microbe.

One of the most famous drugs in the world is also the result of serendipity. Witty advertising and a clever name conjured up to suggest power (from "vitality" and "Niagara") have helped make Viagra a bestseller. Of course, it helps that the drug actually works. But Viagra did not start out life as a treatment for erectile dysfunction. That was a serendipitous finding. The little blue pill was first developed by the Pfizer pharmaceutical company as a possible treatment for angina. In clinical trials, the effects on the heart were less than heartening, but some male patients began to report a surprising uplifting effect. Pfizer researchers were perceptive enough to recognize that they had stumbled upon a potential gold mine, and managed to introduce Viagra to the marketplace within six years, where it has enjoyed stirring serendipitous success in spite of stiff competition.

The Chemistry of Our World Is Too Complex to Be Simplified

We live in a large chemistry lab. A very large one. It's called the universe. It may not have shelves stocked with neatly labeled bottles, but everything in it is made up of chemicals. Including us. Indeed, the human body is nothing but a large bag of chemicals —thousands and thousands of them. And they are constantly engaged in all sorts of reactions, which, taken together, constitute life. Amino acids join to make proteins, glucose is "burned" to produce energy, DNA instructs cells to make enzymes, neurotransmitters are synthesized, hormones are cranked out, toxins are eliminated, and thousands of other processes churn out a stunning array of biochemicals necessary to our survival.

It stands to reason that, when dealing with such a complex system, sometimes a wrench gets thrown into the works. It may be a photon of ultraviolet light that causes a break in a strand of DNA, a virus that takes over a cell's machinery, a compound that disrupts hormonal function, a bit of pollen that triggers inappropriate immune activity, a bacterium that spews out toxins, a metal ion that poisons nerve cells, or a chemical that causes cells to multiply irregularly. In fact, the more one learns about the goings-on in the body, and about everything that can go wrong, the more remarkable it becomes that anyone is ever healthy.