Boston in the Time of Cholera

William C. Dowling (Rutgers University)

I want to talk today about a curious clinical episode I came across some years ago when writing a book about Paris medicine in the 1830s. But let me start by distinguishing among three characters whose names might otherwise cause confusion. The first is Dr. James Jackson senior, who was a Professor at Harvard Medical School and founder of the Massachusetts General Hospital. The second is his son James Jackson junior, who belonged to a brilliant group of Boston medical students who went to France to study medicine in the 1830s. I'll refer to him throughout as the young or the younger Jackson.

The third is Oliver Wendell Holmes, who studied medicine in Paris at the same time as the younger Jackson. His son Oliver Wendell Holmes, Jr., went on to became a famous Supreme Court Justice. In what follows, I shall always be speaking about the senior Oliver Wendell Holmes, the Paris-trained physician.

The story I want to tell concerns a conception of disease that developed when the Paris hospital system was reorganized in the wake of the French Revolution so as to put pathology at the center of medical research. Its significance for American medical history was recognized by William Osler over a century ago.

"Boston in the Time of Cholera," talk delivered to the Medical History Society of New Jersey at the Rutgers Club, New Brunswick, NJ, 11 February 2015

"Among the thousands in the profession of this country who . . . sought light and learning in the older lands," Osler wrote, "the group of young men who studied in Paris between 1830 and 1840 had no predecessors and have had no successors. . . . They more than any others gave an impetus, which it still feels, to the scientific study of medicine in the United States." By scientific study Osler meant the systematic correlation of external signs or symptoms with specific lesions in the internal organs of the body.

As you will all be aware, medicine had been dominated since ancient Greece by what was called humoral theory: the idea that disease results from an imbalance of humoral fluids whose balance the physician might restore by various means, the chief of which was bloodletting. In standard accounts, the Paris medical revolution has mainly been identified with the new anatomico-pathological conception of disease Osler would have had in mind. But for the Boston students, it would also involve a revolution in the realm of therapeutics, a new conception of treatment arising from the work of the great pathologist Pierre Charles Alexandre Louis.

Louis was the inventor of what he and his students called the "numerical method," by which they meant what we'd now call clinical statistics. The younger James Jackson was Louis's most devoted and most assiduous student. Here is Jackson junior writing his father from Paris in 1832. "To draw a description of the natural history of diseases," he wrote, describing the numerical method, "you cannot proceed without it. . . . How often does such a symptom occur? What part of an organ is most often affected in certain diseases? How often is such and such a lesion found after death? . . . These are all questions of immense importance, and they can be decided in no other way than by . . . a counting of them with respect to each point."

The impact of Louis's research upon American therapeutic practice was a direct consequence of the same numerical method. This was his demonstration that the normal methods of what was called "heroic" treatment in medicine—the bleeding, purging, drugging practice whose basis lay in humoral theory—not only did not cure diseases, but in many cases made them worse. Louis's pathbreaking clinical study of treatment by phlebotomy would be translated and published in Boston in 1836 as The Effects of Bloodletting on Inflammatory Diseases.

W.C. Dowling, "Boston in the Time of Cholera"

Its implications for therapeutics were clear: if the bloodletting practiced by physicians on both sides of the Atlantic was frequently harming or even killing patients, might not the same be hypothesized about such remedies as calomel—which contained mercury, known even then to be poisonous to the body—or preparations like tartar emetic, based on antimony?

At the time Louis arrived at these results, American medicine was still under the influence of such advocates of heroic practice as the famous Benjamin Rush, signer of the Declaration of Independence and professor of medicine at the University of Pennsylvania. Rush's remedy for all diseases was repeated and copious bloodletting.

Up to four-fifths of the blood could safely be removed from the body, Rush serenely assured his students. "‘Tis a very hard matter to bleed a patient to death," he told them, "provided the blood be not drawn from a vital part." Here is Rush's account of his therapeutic rationale. "We will suppose the doctor to have a house containing 100 rooms," he once wrote, "each having a different lock. Of course he must have an equal number of different keys to open them—now I am capable of entering every apartment with the assistance of a single key." The key was bloodletting.

In both the United States and France, the alternative to heroic practice was what was called "expectant medicine" or the "expectant method," English for the French phrases médecine expectante or méthode expectante. To the Boston students who studied in Paris, the expectant method meant palliative care in which every measure should be taken to aid the body in its natural powers of recovery. Its manifesto would be Jacob Bigelow's treatise Self-Limited Diseases, published in Boston in 1835. Its most outspoken advocate in Boston would be Oliver Wendell Holmes.

"The disgrace of medicine," Holmes told one group of fellow physicians at midcentury, "has been that colossal system of self-deception in obedience to which mines have been emptied of their cankering minerals, . . . the entrails of animals taxed for their impurities, the poison-bags of reptiles drained of their venom, and all the inconceivable abominations thus obtained thrust down the throats of human beings." A remark Holmes made on another occasion would become instantly famous: "If the whole materia medica, as now used, could be sunk to the bottom of the sea, it would be all the better for mankind,—and all the worse for the fishes."

I mention all this as background to the clinical episode I spoke about at the beginning. In the early 1830s the Asiatic cholera reached Paris. It was a new disease unlike anything previously studied at the École de Médecine. There had been a massive outbreak in India in 1827. It then spread to Russia in 1829, and would reach France and the United Kingdom in 1831. For such legendary hospital teachers as Andral and Chomel and Louis, the great mystery was that cholera killed its victims without causing such internal lesions as they had learned to recognize in diseases like tuberculosis and emphysema and pericarditis.

Even worse, it soon became evident that the expectant method was useless in cases of cholera. Here is the younger James Jackson writing to his father in Boston from the wards of the great Paris hospital the Hôtel Dieu. For this new disease, he reports, there is only "one word;—it is death. Truly, at Hôtel Dieu, where I have seen fifty and more in a ward, it is almost like walking through an autopsy room;—in many nothing but the act of respiration shows that life still exists. It is truly awful.—as for treatment, nothing is yet decided."

Just three months after writing these words, however, young Jackson himself would encounter something claiming to be a miracle remedy. In obedience to his father's wishes, he was at that point undertaking a medical tour of Great Britain. In Yorkshire and later in Edinburgh, it was reported that cholera patients were being cured by injections with a common saline solution, so dramatically that they seemed to have been brought back from the brink of death. When the saline solution is injected, Jackson told his father, there is "return of pulse, warmth, and natural color. . . . One woman is well, and now [up and] about, who had fifty-one pounds of saline fluid injected. . . . The truth is, that its immediate effects are so striking . . . . that it is really very difficult to prevent one's mind from receiving an impression in favor of this remedy."

Here, it seemed, was heroic intervention, if anything might be called heroic. Yet after careful investigation young Jackson would conclude that this spectacle did not, after all, represent a serious challenge to the expectant method as based on the researches of his teacher Louis. When I first encountered the episode of the saline injections it was the clinical details that puzzled me. We know today that the violent diarrhea caused by the cholera toxin produces an electrolyte imbalance that leads to hypovolemic shock.

When I read Jackson's reports of the injections, what struck me was their uncanny similarity to modern treatments using either oral rehydration salts or, in patients unable to swallow, injections of Ringer's solution. So why had the saline injections survived only as a curious and isolated episode in medical history?

The trouble, I thought, must have lain in the method of injection. The standard method then was by enema. But in cholera the intestinal epithelium is so compromised by the disease that I decided it must have permitted only enough absorption to produce a temporary reaction. But that left an unresolved problem. A few patients treated by saline injection were reported to have survived for somewhat longer periods.

Only when I suggested the episode of the saline injections for the topic of today's talk did Dr. Michael Nevins give me a push in the right direction. The saline injections, it turned out, had first been administered by one Dr. Thomas Latta of Edinburgh.

Loring Conant, MD, WCD, Michael Nevins, MD

Latta had indeed begun by trying rectal injections. When they had no effect, he tried inserting a tube into the basilic vein of a terminally ill patient and injecting large amounts of saline fluid. So far as I know, Latta's was the very first use of intravenous therapy. Here is Latta's account of the effect on a female patient: "She had apparently reached the last moments of her earthly existence," he reported . . . "Ounce after ounce was injected, but no visible change was produced. . . . [But then] she began to breathe less laboriously, soon the sharpened features, and sunken eye and fallen jaw . . . began to glow with returning animation; the pulse, which had long ceased, returned to the wrist; . . . and in the short space of half an hour, when six pints had been injected . . . her extremities were warm, and every feature bore the aspect of comfort and health." But such comfort and health turned out to be no more than transitory. Most patients went on to die within a short time.

Some years ago I happened to discuss this episode with Sherwin Nuland. His idea was that the treatment might have failed because no one in Latta's day knew the correct concentration of salt for physiological saline, which has to be perfectly balanced in order not to bollix up—in Dr. Nuland's delightfully characteristic phrase—the correct proportions of potassium, sodium, bicarbonate, and chloride in the blood. Getting this wrong, he pointed out, would have brought about hemolysis and destruction of red blood cells. That is as far as I got with the clinical puzzle.

Only in thinking back over the episode during the years that followed did I begin to see that its real significance could be taken to lie not in the failure of Latta's injections but in the way young Jackson dealt with what he saw. For the circumstances were far more complex than Jackson could possibly have realized. He was, after all, standing on the very cusp of a modern therapeutics in which rehydration would become the standard means of preventing hypovolemic shock, and isotonic fluids would be routinely administered through IV.

Yet, no doubt thinking of the extravagant claims for heroic intervention that still dominated American medicine, young Jackson chose to remain steadfastly skeptical. His ultimate conclusion would be that "the injection undoubtedly produces a temporary excitement, but as yet we have no proof that it arrests the disease. It does not strike at the cause; and how can we suppose that it would? This chemical rage enrages me."

The story of James Jackson junior now takes a sad turn. Having come home to Boston late in 1833, he would die of a typhoid fever contracted while treating patients at the Massachusetts General Hospital. He was 25 years old. His father and friends were grief-stricken. His death was seen as a calamity for Boston medicine. But it was not viewed that way—and this is an important point—because any of his medical colleagues yet identified him with the new Paris gospel of médecine expectante.

For at the time of young Jackson's death Boston had in fact heard little about the expectant method. The controversy surrounding it would become heated only several decades later. By that point, one has to admit, things had become sufficiently bitter. Today, for instance, everyone remembers Holmes's remark about how deadly the remedies used in heroic treatment would be to the fishes in the ocean. What is seldom remembered is that the medical society to which Holmes delivered his address voted the next day to dissociate itself publicly from his views.

Among Holmes's listeners when he made his remark about the fishes was James Jackson senior, who after his son's death had passed through what can only be imagined as a period of painful self-questioning. For his son's letters from Paris make abundantly clear that the younger Jackson, whose filial piety was deep and sincere, had gradually come to have serious doubts about his own father's therapeutic practice.

"Have we . . . deduced our results," he asks in one letter, "from all, or from a selection of facts? . . . Do we know how large a proportion of cases would get well without any treatment . . . ? When a disease is destined by nature to be long, do we very often diminish it? . . . What I have seen here of disease and its issues, has rather inclined me to believe that I individually overvalued the utility of certain modes of treatment in America."

In recent years, some historians of medicine have wanted to reduce the nineteenth-century controversy over heroic practice to little more than a struggle on the part of regular physicians to maintain their professional status. The real contest, on this account, would not be about the use of the lancet to drain four-fifths of the blood from a patient's body, but about idea of giving up modes of treatment long associated in the public mind with medical authority.

But what any serious study of the correspondence between the senior and junior Jacksons demonstrates, I think, that the underlying issue goes far deeper. What was at stake was a belief that is today increasingly accepted as having played an unrecognized but wholly legitimate role in medical practice since the time of Hippocrates and Galen. This is nothing other than the necessary belief of physicians in their own power to heal. A recent study puts it this way: "The physician's belief in the treatment and the patient's faith in the physician exert a mutually reinforcing effect; the result is a powerful remedy that is almost guaranteed to produce an improvement and sometimes a cure."

This is the context, it seems to me, in which we must imagine the dilemma of the senior James Jackson when, after his son's death, he found himself reading through the younger Jackson's letters from Paris. "I ask myself, honestly," young Jackson had confessed at one point, referring to the heroic measures favored in American medicine, "how far can I trust all this? Do I believe that bleeding arrests inflammation, as I believe that a certain combination of symptoms indicates such and such a lesion? . . . I assure you, my dear father, in the present state of my knowledge . . . I believe that we admit many things in America as axioms, which are very far from being proved. . . . But when we are hoping, and our patients are hoping, we are deceiving ourselves, and often the patients themselves and us also."

The starkness of the dilemma is obvious. To repudiate heroic practice would be not simply to give up one's use of the lancet to draw blood, but also to give up one's belief that one had ever actually cured a patient by using such measures.

Jackson senior, not in a position at his age to take so radical a step, but also wanting to honor his son's fervent advocacy of the expectant method, hit upon an effective compromise. Putting aside his own views on therapeutics, he sat down to compose a memoir of his son that would include the younger Jackson's letters from Paris, letters that not only argued for a renunciation of heroic measures in therapeutics but looked forward confidently to a day when medical practice would be based on sound clinical research. In the Memoir of James Jackson, Jr. M.D., readers would listen to the living voice of a young Paris medical student who, along with his studies of anatomy and physiology, had come to envision a medical future in which the physician's belief in his or her power to cure disease would be entirely warranted.

In the years that followed, the expectant method would retain its association with Boston. Nor can it be doubted that the memoir sent forth into the world by James Jackson's father played a major role in its acceptance there. Writing some twenty-five years after the death of the younger James Jackson, Oliver Wendell Holmes would be able confidently to declare that "we who are on the side of ‘Nature' please ourselves with the idea that we are in the great current in which the true intelligence of the time is moving."

At the point Holmes made this remark, opponents of the expectant method had taken to denouncing it as the "nature-trusting heresy." Holmes was undismayed. "If there is any state or city which might claim to be the American headquarters of the nature-trusting heresy, provided it be one," he declared with unrepentent pride, "that state is Massachusetts, and that city"—by which, of course, he meant Boston—"is its capital."

Given the subsequent influence of the Memoir of James Jackson, Jr., M.D. on medical opinion in Boston and beyond, it seems to me, the episode of the saline injections may ultimately be understood as one in which young Jackson reached an entirely reasonable conclusion for what we can only now see to be the wrong reasons.

So far as he was inclined to see the injections as simply the latest in a long succession of heroic measures for which false or even dangerous claims had been made, he was no doubt mistaken. Doctor Latta was closer than Jackson could have realized to a genuine breakthrough in therapeutics. But to the degree that Jackson's response withheld assent from claims unsupported by any systematic analysis of clinical results, it seems to me that it must be taken in its own historical moment as an entirely principled therapeutic skepticism.

A serious cholera epidemic would break out in Boston in 1849, some fifteen years after young Jackson's death. There was still nothing like a promising treatment in view. "The symptoms are of the most fearful and distinct character," a writer in the Boston Medical and Surgical Journal would lament, "setting at defiance all the remedial agents of such vaunted power elsewhere."

Among the remedial agents vaunted elsewhere during this second epidemic were assafœtida, calomel, camphor oil, castor oil, cod liver oil, oil of turpentine, creosote, opium, mustard cataplasms, sulfate of quinine, sulfate of zinc, hydrocyanic acid, magnesia, decoction of hemlock bark, and bleeding to the amount of 16 to 20 ounces.

But by then, for those who had eyes to see, the days of heroic practice were already drawing to an end. At Harvard Medical School, where Oliver Wendell Holmes was now teaching as Parkman Professor of Anatomy and Physiology, and in the wards of Massachusetts General Hospital, where younger physicians whose reading had included the Memoir of James Jackson, Jr., M.D. were putting the médecine expectante of the great Paris hospital teachers into practice, a future might already have been foreseen in which medicine would in time derive its power to work seemingly miraculous cures by cooperating at the deepest level with nature itself.