The Great Influenza (4 page)

In 1628 Harvey traced the circulation of the blood, arguably perhaps the single greatest achievement of medicine and certainly the greatest achievement until the late 1800s. And Europe was in intellectual ferment. Half a century later Newton revolutionized physics and mathematics. Newton's contemporary John Locke, trained as a physician, emphasized the pursuit of knowledge through experience. In 1753 James Lind conducted a pioneering controlled experiment among British sailors and demonstrated that scurvy could be prevented by eating limes (ever since, the British have been called 'limeys.') David Hume, after this demonstration and following Locke, led a movement of 'empiricism.' His contemporary John Hunter made a brilliant scientific study of surgery, elevating it from a barber's craft. Hunter also performed model scientific experiments, including some on himself (as when he infected himself with pus from a gonorrheal case to prove a hypothesis.)

Then in 1798 Edward Jenner, a student of Hunter's (Hunter had told him 'Don't think. Try.') published his work. As a young medical student Jenner had heard a milkmaid say, 'I cannot take the smallpox because I have had cowpox.' The cowpox virus resembles smallpox so closely that exposure to cowpox gives immunity to smallpox. But cowpox itself only rarely develops into a serious disease. (The virus that causes cowpox is called 'vaccinia,' taking its name from vaccination.)

Jenner's work with cowpox was a landmark, but not because he was the first to immunize people against smallpox. In China, India, and Persia, different techniques had long since been developed to expose children to smallpox and make them immune, and in Europe at least as early as the 1500s laypeople (not physicians) took material from a pustule of those with a mild case of smallpox and scratched it into the skin of those who had not yet caught the disease. Most people infected this way developed mild cases and became immune. In 1721 in Massachusetts, Cotton Mather took the advice of an African slave, tried this technique, and staved off a lethal epidemic. But 'variolation' could kill. Vaccinating with cowpox was far safer than variolation.

From a scientific standpoint, however, Jenner's most important contribution was his rigorous methodology. Of his finding he said, 'I placed it upon a rock where I knew it would be immoveable before I invited the public to take a look at it.'

But ideas die hard. Even as Jenner was conducting his experiments, despite the vast increase in knowledge of the body derived from Harvey and Hunter, medical practice had barely changed. And many, if not most, physicians who thought deeply about medicine still saw it in terms of logic and observation alone.

In Philadelphia, twenty-two hundred years after Hippocrates and sixteen hundred years after Galen, Benjamin Rush, a pioneer in his views on mental illness, a signer of the Declaration of Independence, and America's most prominent physician, still applied logic and observation alone to build 'a more simple and consistent system of medicine than the world had yet seen.'

In 1796 he advanced a hypothesis as logical and elegant, he believed, as Newtonian physics. Observing that all fevers were associated with flushed skin, he concluded that this was caused by distended capillaries and reasoned that the proximate cause of fever must be abnormal 'convulsive action' in these vessels. He took this a step further and concluded that
all
fevers resulted from disturbance of capillaries, and, since the capillaries were part of the circulatory system, he concluded that a hypertension of the entire circulatory system was involved. Rush proposed to reduce this convulsive action by 'depletion,' i.e., venesection - bleeding. It made perfect sense.

He was one of the most aggressive of the advocates of 'heroic medicine.' The heroism, of course, was found in the patient. In the early 1800s praise for his theories was heard throughout Europe, and one London physician said Rush united 'in an almost unprecedented degree, sagacity and judgment.'

A reminder of the medical establishment's acceptance of bleeding exists today in the name of the British journal
The Lancet,
one of the leading medical journals in the world. A lancet was the instrument physicians used to cut into a patient's vein.

But if the first failing of medicine, a failing that endured virtually unchallenged for two millennia and then only gradually eroded over the next three centuries, was that it did not probe nature through experiments, that it simply observed and reasoned from observation to a conclusion, that failing was (finally) about to be corrected.

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What can I know? How can I know it?

If reason alone could solve mathematical problems, if Newton could think his way through physics, then why could not man reason out the ways in which the body worked? Why did reason alone fail so utterly in medicine?

One explanation is that Hippocratic and Galenic theory did offer a system of therapeutics that seemed to produce the desired effect. They seemed to work. So the Hippocratic-Galenic model lasted so long not only because of its logical consistency, but because its therapies seemed to have effect.

Indeed, bleeding (today called 'phlebotomy') can actually help in some rare diseases, such as polycythemia, a rare genetic disorder that causes people to make too much blood, or hemachromatosis, when the blood carries too much iron. And in far more common cases of acute pulmonary edema, when the lungs fill with fluid, it could relieve immediate symptoms and is still sometimes tried. For example, in congestive heart failure excess fluid in the lungs can make victims extremely uncomfortable and, ultimately, kill them if the heart cannot pump the fluid out. When people suffering from these conditions were bled, they may well have been helped. This reinforced theory.

Even when physicians observed that bleeding weakened the patient, that weakening could still seem positive. If a patient was flushed with a fever, it followed logically that if bleeding alleviated those symptoms (making the patient pale) it was a good thing. If it made the patient pale it worked.

Finally, a euphoric feeling sometimes accompanies blood loss. This too reinforced theory. So bleeding both made logical sense in the Hippocratic and Galenic systems and sometimes gave physicians and patients positive reinforcement.

Other therapies also did what they were designed to do (in a sense. As late as the nineteenth century) until well after the Civil War in the United States (most physicians and patients still saw the body only as an interdependent whole, still saw a specific symptom as a result of an imbalance or disequilibrium in the entire body, still saw illness chiefly as something within and generated by the body itself. As the historian Charles Rosenberg has pointed out, even smallpox, despite its known clinical course and the fact that vaccination prevented it, was still seen as a manifestation of a systemic ill. And medical traditions outside the Hippocratic-Galenic model (from the 'subluxations' of chiropractic to the 'yin and yang' of Chinese medicine) have also tended to see disease as a result of imbalance within the body.

Physicians and patients wanted therapies to augment and accelerate, not block, the natural course of disease, the natural healing process. The state of the body could be altered by prescribing such toxic substances as mercury, arsenic, antimony, and iodine. Therapies designed to blister the body did so. Therapies designed to produce sweating or vomiting did so. One doctor, for example, when confronted with a case of pleurisy, gave camphor and recorded that the case was 'suddenly relieved by profuse perspiration.' His intervention, he believed, had cured.

Yet a patient's improvement, of course, does not prove that a therapy works. For example, the 1889 edition of the
Merck Manual of Medical Information
recommended one hundred treatments for bronchitis, each one with its fervent believers, yet the current editor of the manual recognizes that 'none of them worked.' The manual also recommended, among other things, champagne, strychnine, and nitrogylcerin for seasickness.

And when a therapy clearly did not work, the intricacies (and intimacies) of the doctor-patient relationship also came into play, injecting emotion into the equation. One truth has not changed from the time of Hippocrates until today: when faced with desperate patients, doctors often do not have the heart (or, more accurately, they have too much heart) to do nothing. And so a doctor, as desperate as the patient, may try anything, including things he or she knows will not work as long as they will not harm. At the least, the patient will get some solace.

One cancer specialist concedes, 'I do virtually the same thing myself. If I'm treating a teary, desperate patient, I will try low-dose alpha interferon, even though I do not believe it has ever cured a single person. It doesn't have side effects, and it gives the patient hope.'

Cancer provides other examples as well. No truly scientific evidence shows that echinacea has any effect on cancer, yet it is widely prescribed in Germany today for terminal cancer patients. Japanese physicians routinely prescribe placebos in treatment. Steven Rosenberg, a National Cancer Institute scientist who was the first person to stimulate the immune system to cure cancer and who led the team that performed the first human gene therapy experiments, points out that for years chemotherapy was recommended to virtually all victims of pancreatic cancer even though not a single chemotherapy regimen had ever been shown to prolong their lives for one day. (At this writing, investigators have just demonstrated that gemcitabine can extend median life expectancy by one to two months, but it is highly toxic.)

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Another explanation for the failure of logic and observation alone to advance medicine is that unlike, say, physics, which uses a form of logic (mathematics) as its natural language, biology does not lend itself to logic. Leo Szilard, a prominent physicist, made this point when he complained that after switching from physics to biology he never had a peaceful bath again. As a physicist he would soak in the warmth of a bathtub and contemplate a problem, turn it in his mind, reason his way through it. But once he became a biologist, he constantly had to climb out of the bathtub to look up a fact.

In fact, biology is chaos. Biological systems are the product not of logic but of evolution, an inelegant process. Life does not choose the logically best design to meet a new situation. It adapts what already exists. Much of the human genome includes genes which are 'conserved' i.e., which are essentially the same as those in much simpler species. Evolution has built upon what already exists.

The result, unlike the clean straight lines of logic, is often irregular, messy. An analogy might be building an energy efficient farmhouse. If one starts from scratch, logic would impel the use of certain building materials, the design of windows and doors with kilowatt hours in mind, perhaps the inclusion of solar panels on the roof, and so on. But if one wants to make an eighteenth-century farmhouse energy efficient, one adapts it as well as possible. One proceeds logically, doing things that make good sense given what one starts with, given the existing farmhouse. One seals and caulks and insulates and puts in a new furnace or heat pump. The old farmhouse will be (maybe) the best one could do given where one started, but it will be irregular; in window size, in ceiling height, in building materials, it will bear little resemblance to a new farmhouse designed from scratch for maximum energy efficiency.

For logic to be of use in biology, one has to apply it from a given starting point, using the then-extant rules of the game. Hence Szilard had to climb out of the bathtub to look up a fact.

Ultimately, then, logic and observation failed to penetrate the workings of the body not because of the power of the Hippocratic hypothesis, the Hippocratic paradigm. Logic and observation failed because neither one tested the hypothesis rigorously.

Once investigators began to apply something akin to the modern scientific method, the old hypothesis collapsed.

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By 1800 enormous advances had been made in other sciences, beginning centuries earlier with a revolution in the use of quantitative measurement. Bacon and Descartes, although opposites in their views of the usefulness of pure logic, had both provided a philosophical framework for new ways of seeing the natural world. Newton had in a way bridged their differences, advancing mathematics through logic while relying upon experiment and observation for confirmation. Joseph Priestley, Henry Cavendish, and Antoine-Laurent Lavoisier created modern chemistry and penetrated the natural world. Particularly important for biology was Lavoisier's decoding of the chemistry of combustion and use of those insights to uncover the chemical processes of respiration, of breathing.

Still, all these advances notwithstanding, in 1800 Hippocrates and Galen would have recognized and largely agreed with most medical practice. In 1800 medicine remained what one historian called 'the withered arm of science.'

In the nineteenth century that finally began to change - and with extraordinary rapidity. Perhaps the greatest break came with the French Revolution, when the new French government established what came to be called 'the Paris clinical school.' One leader of the movement was Xavier Bichat, who dissected organs, found them composed of discrete types of material often found in layers, and called them 'tissues' another was René Laennec, inventor of the stethoscope.

Meanwhile, medicine began to make use of other objective measurements and mathematics. This too was new. Hippocratic writings had stated that the physician's senses mattered far more than any objective measurement, so despite medicine's use of logic, physicians had always avoided applying mathematics to the study of the body or disease. In the 1820s, two hundred years
after
the discovery of thermometers, French clinicians began using them. Clinicians also began taking advantage of methods discovered in the 1700s to measure the pulse and blood pressure precisely.

By then in Paris Pierre Louis had taken an even more significant step. In the hospitals, where hundreds of charity cases awaited help, using the most basic mathematical analysis (nothing more than arithmetic) he correlated the different treatments patients received for the same disease with the results. For the first time in history, a physician was creating a reliable and systematic database. Physicians could have done this earlier. To do so required neither microscopes nor technological prowess; it required only taking careful notes.