Pox

by Michael Willrich

  Humanized virus worked. When properly collected and used, it took “with great regularity” and produced immunity for years. But there were problems. If the vaccinifier was not as healthy as she appeared, the virus could communicate other human diseases, including erysipelas (an acute skin infection) and syphilis. In Rivalta, Italy, in 1861, sixty-three children were vaccinated with material from the vaccinal sore of a single, seemingly healthy infant. Forty-six of the children fell ill with syphilis, several died, and some passed the disease to their mothers and nurses. The risks of arm-to-arm transfer inflamed antivaccination sentiment almost everywhere it was practiced. Herbert Spencer called it “wholesale syphilization.”37

  A second disadvantage of humanized virus was the challenge, even in a densely populated community, of keeping a fresh supply on hand. For a small town or sparsely settled rural area, keeping up an arm-to-arm relay or a good stock of crusts might prove impossible. Moreover, some physicians believed that humanized virus became attenuated or compromised over time, with the ever increasing distance from the original bovine source. Humanized virus had one other major shortcoming, which only became fully apparent in retrospect. There was never much of a market in it.38

  The idea of using cows, instead of people, to manufacture cowpox first took hold in Italy. Throughout the century, in Europe and America, some vaccine propagators practiced what came to be called “retrovaccination”: inoculating heifers with humanized virus, either to mystically restore some bovine quality to the vaccine or to simply make animals do the work. But the production of the stuff that came to be known as “true animal vaccine” or “bovine virus”—and that would launch a new industry and market—did not catch on in Europe until the 1860s. The idea was to inoculate a heifer with seed virus obtained from a naturally occurring case of cowpox (not with humanized virus) and to keep the strain running from calf to calf in a continuous relay, all the while harvesting vaccine for use in humans.39

  Bovine vaccine had none of the problems that plagued humanized virus. As the Italian practice was adopted by France (1864), Belgium (1865), Japan (1874), and Germany (1884), government officials and private entrepreneurs greeted each newly discovered outbreak of cowpox as a wellspring of vaccine. One of the most famous cases of “spontaneous cowpox” came to light in 1866 in Beaugency, in France’s Loire Valley. Although vulnerable to contamination, bovine virus did not spread syphilis. A calf could produce vaccine in far greater quantity than an infant could (while raising fewer qualms). And as doctors, farmers, and druggists soon realized, there was money to be made in bovine vaccine.40

  Dr. Henry A. Martin of Boston introduced bovine vaccine to the United States in 1870. Using seed lymph from the Beaugency strain, which by that time had already passed through 260 heifers in France, Martin established a vaccine farm in suburban Roxbury. Martin may also deserve credit for initiating the American vaccine makers’ practice of tarring rivals’ products. An early advertisement said Martin virus should not be “confounded with the feeble, uncertain, and generally quite worthless product of retrovaccination.” Martin’s family-run establishment operated continuously and with good reputation into the early twentieth century. Others quickly followed in Martin’s footsteps, most notably Dr. E. L. Griffin of Fond du Lac, Wisconsin, and Dr. Frank P. Foster of New York. By the mid-1870s, vaccine farms were sprouting up all over the country.41

  Many of the earliest vaccine producers were men much like Martin and Griffin—reputable local physicians who knew their way around a stable. Some traded on their prominence as members of state or local boards of health. But so low were the barriers to entry—a bit of seed virus, a few cows, and some ivory points—that men on the make from many walks of life entered the business. With equal parts admiration and distaste, the Brooklyn Eagle captured the spirit of the new enterprise. “If it be true that what is one man’s meat is another man’s poison, it is equally true, of course, that what is one man’s poison is another man’s meat,” the Eagle said. “The axiom, as amended, is fully verified in this good city of Brooklyn, where men are deriving handsome incomes from that most disgusting and abhorrent of all diseases, small-pox. A new business of vital importance to the community has been started, and hundreds of thousands of men, women and children are walking about with its badge on their arms.” In 1871, the New York Department of Health became the first municipal agency in the United States to produce its own vaccine. But elsewhere private makers had the field almost entirely to themselves. And as compulsory vaccination and its handmaiden, compulsory education, spread in the late nineteenth century, the opportunities for profit expanded apace.42

  To distinguish their products on the open market, vaccine makers appealed to the late nineteenth-century romance of the pastoral and the era’s penchant for pedigree. Americans had a fascination with animal breeding and family genealogies, informed by the transatlantic flourishing of hereditarian ideas in the age of Darwin and Galton. Dr. W. E. Griffiths of Brooklyn boasted that his stock derived from a case of spontaneous cowpox discovered in Central New York. Dr. J. W. Compton & Son of Indiana advertised “pure Beaugency cow-pox lymph, non-humanized.” In 1885, John Wyeth & Brother, Philadelphia druggists, announced their entry into the field with a full-page advertisement in Drugs and Medicines of North America. Calling its new Chester County farm “the model vaccine propagating establishment of the United States,” the Wyeth Company obtained its seed virus from the Belgian government. Like many vaccine ads, this one pictured a cow: a healthy looking heifer, bound to a table beneath a lace-curtained window; on the calf’s lower belly were several rows of incisions, where the seed had been introduced. Vaccine companies’ claims to exalted origins for their products were greeted with jeering from some quarters. Dr. J. W. Hodge insisted, to everyone who would listen, that no vaccine maker had “any definite or exact knowledge as to the real nature, composition or original source of the complex poisonous mixture which they foist upon gullible doctors as ‘pure calf lymph.’”43

  Hodge had a point. In an era when neither smallpox nor cowpox could be seen under the most powerful microscope, the manufacturers’ genealogical claims were beyond verification. It was not until 1939 that a British scientist established that most vaccines contained neither smallpox nor cowpox, but a related orthopoxvirus called vaccinia. At some time between Jenner’s first experiments with cowpox in 1796 and the 1930s, vaccine makers had started working with this different virus, which also occurs naturally in cows. No one knows when the exchange occurred, though the late nineteenth century would seem a good bet. In any event, vaccinia worked. Like cowpox, when introduced in the human system it caused an immune response, usually mild, that conferred a lasting (though not permanent) immunity to smallpox.44

  The makers’ claims to product purity were easier to test than their pedigree claims. In 1895, Walter Reed of the Army Medical Department presented a paper to the District of Columbia Medical Society entitled “What Credence Should Be Given to the Statements of Those Who Claim to Furnish Vaccine Lymph Free of Bacteria?” His answer: none at all. Reed had examined points from several leading U.S. makers. The number of bacteria per point ranged widely, from 43 to 89,000. Most of those germs appeared to be harmless, but others were pathogenic, capable of causing sore arms and infections. Bovine virus was liable to contamination from the common bacteria, such as streptococci and staphylococci, that thrived upon calves’ skin or in the stable.45

  The following year, the Pennsylvania State Board of Health dispatched one of its own bacteriologists, Dr. R. L. Pitfield, to inspect American vaccine farms. Of the fourteen farms Pitfield visited, he could recommend only four. Amidst the wildly various production standards, Pitfield found a common ground of rank commercialism and “a tenacious adherence to original and old and rather preaseptic measures.” In one Missouri establishment, a worker used his own fingernail to remove the crust; in another, the heifers were kept in a “dusty and dirty apartment,” with urine streaming in from the operating room on the floor above
them. Even at the New York City Health Department, one of America’s leading scientific establishments, Pitfield found “the accommodations are not as good as they should be.” Among the many troubling statements in Dr. Pitfield’s detailed report was this one: “In many establishments, tetanus bacilli might find their way to the vesicle and thence to the points and tubes, because dust in large quantities abounds in the incubating stables.”46

  In the late 1890s, American vaccine makers adopted a new production technique that reduced the problem of bacteria-ridden vaccine. For decades, European makers had added glycerin to their product to keep it from decomposing. In 1891, the Englishman Sydney Monckton Copeman established that glycerin not only preserved vaccine but gradually killed unwanted bacteria without damaging the virus. Glycerin also acted as a diluent, allowing makers to stretch lymph and thus greatly increase the number of vaccine units that could be produced from a single calf. By 1898, glycerinated calf lymph had become the international standard of vaccine, widely preferred by the leading local, state, and federal health officers in the United States.47

  While some companies (such as the Martin Vaccine Farm and the Washington, D.C.–based National Vaccine Establishment) still dealt chiefly or exclusively in smallpox vaccines, other industry leaders had a much larger footprint in the marketplace. Firms like Parke, Davis and Wyeth Company sold a growing number of biological products as well as compounded drugs of almost infinite variety. Even as firms opened branch houses in major U.S. cities and overseas, their vaccine lines required that they keep one foot planted on the farm. H. K. Mulford Company, one of America’s most reputable manufacturers of biologics and drugs, still adorned its vaccine ads in 1901 with a healthy heifer standing contentedly by a gentle stream and thought nothing of running those vaccine ads directly beneath another for pint bottles of “Mulford’s Pre-Digested Beef.” That both products might come from precisely the same source was a fact worth publicizing. Field, laboratory, and slaughterhouse were stages of an industrial life cycle that bound urban life, as ever, to the domestication of rural animals and landscapes.48

  For the H. K. Mulford Company, “Manufacturing Chemists,” a newcomer to the vaccine market in 1898, dealing in biologics meant reversing the expected American trajectory. Mulford was born in the city and moved to the country. The company got its start in the late 1880s when twenty-one-year-old Henry K. Mulford bought the “Old Simes” corner drugstore in downtown Philadelphia. At first, Mulford seemed poised to follow the conventional road of the entrepreneur in Philadelphia’s robust drug trade, the largest in the United States outside of New York. He introduced his own line of medical preparations, including elixirs, lozenges, liquors, tinctures, antiseptics, and soda fountain syrups. In 1891, with new financial backing, Mulford incorporated and began its swift transformation from retail druggist to nationally prominent manufacturing firm. Henry Mulford and an associate patented their own machine for tableting watersoluble pills, and by 1893 the company, with two Philadelphia laboratories and a branch office in Chicago, was marketing no fewer than eight hundred medical products.49

  In 1894, the Mulford Company entered the biologics market at its cutting edge, racing to become the first U.S. firm to produce diphtheria antitoxin. Germany’s Koch Institute was already preparing the lifesaving antitoxin, which like smallpox vaccine was an animal product. (A horse was inoculated with diphtheria toxin and given time to produce antibodies; later the horse was bled and the antibodies separated from the serum.) The New York City Health Department was developing its own antitoxin. To develop a commercial product, Mulford hired Dr. Joseph McFarland, a bacteriologist who had trained in Heidelberg and Vienna and who was at that time employed by both the University of Pennsylvania and the Philadelphia Board of Health. In a display of the public-private cooperation that drove biologics innovation in the 1890s, the New York City Health Department bacteriologist, Dr. William Park, provided McFarland with the cultures necessary to start his laboratory in a West Philadelphia stable. The University of Pennsylvania’s new Laboratory of Hygiene agreed to test lots of McFarland’s antitoxin. By 1895, Mulford had placed America’s first commercial diphtheria antitoxin on the market. The following year, the company moved its biologics department to newly constructed stables and laboratories in rural Glenolden, eight miles outside Philadelphia. In 1898, the company hired Dr. W. F. Elgin from the National Vaccine Establishment and put him to work making glycerinated vaccine. By 1902, Mulford’s annual sales topped $1 million.50

  Mulford benefited from all of the innovations that had taken place since Martin brought bovine virus to America in 1870. According to Mulford marketing details, the company’s stables and laboratories were state-of-the-art operations modeled after “the leading vaccine establishments in Europe and America.” The company used suckling female calves, just four to eight weeks old, tested for tuberculosis. “The animals are kept at all times under the most rigid sanitary surroundings in buildings all the materials of which—stone, cement, metal, slate, and porcelain-finish—permit of immediate and thorough disinfection.” The calves were fed sterilized milk, their excretions “disinfected and removed as soon as voided.” The inoculations and collection of the virus took place in a special operating room set apart from the stables.51

  Dr. Elgin detailed his procedures in a presentation, complete with lantern slides, to the 1900 meeting of the Conference of State and Provincial Boards of Health of North America. After having its underside shaved, the calf was strapped to an operating table where “the operator,” clad in a sterilized gown and wielding an aseptic scalpel, made a series of linear incisions along its lower body. Glycerinated lymph (harvested from a previous calf) was slathered over the entire area and rubbed into the incisions. A worker removed the animal to the sanitary stable, returning the calf to the operating table six days later. Along the incisions had risen a line of vesicles covered with “a slight crust or scab.” Using sterilized water, the crust was softened and then removed, “leaving behind rows of pearly white vesicles,” which the operator scooped out (using a tool of the trade called “Volkman’s spoon”) and deposited in a sterilized box. This “pulp” was then placed on glass rollers in a grinding machine and mixed with glycerin. The mixture was stored in large stock tubes and placed in an icebox while the glycerin did its work. Finally, glycerinated lymph was placed in capillary tubes (each containing enough for a single vaccination), hermetically sealed, and prepared for shipping. Mulford followed the practice at the best firms of killing the calves immediately after the collection of vaccine and conducting a postmortem examination to ensure that the animal was in fact healthy; if the exam showed otherwise, the company discarded the vaccine. The postmortem was a costly practice, not universally followed. Some makers still sold their used calves to the local stockyards.52

  In most European countries, the government controlled vaccine production, either through licensing or through outright government manufacture. Regulating the manufacture of potentially hazardous goods fell well within the ambit of the American police power. But little regulation of vaccines existed. Just seven states had laws providing for some supervision of the vaccine manufactured or used in the state. The Massachusetts statute, the nation’s strongest, declared that “All vaccine institutions in the commonwealth shall be under the supervision of the state board of health”; but even that law specified no penalties for bad practices. Several of the states governed the use of humanized virus, which had fallen out of favor in most places anyway. Even these measures showed a narrow conception of the rightful powers of government in this area. Florida banned humanized virus outright; Maryland made physicians liable for “knowingly or willfully” using humanized virus that spread disease to a patient; and Michigan required that only bovine product be used in public vaccinations.53

  In the late 1890s, the first glimmerings of a new regulatory approach appeared when a few state and local governments started inspecting vaccine farms, testing the virus in the laboratory, and publishing the findi
ngs. In an industry that had relied on the endorsements of public health boards to market their products, this must have been for many makers a most unwelcome intrusion. In addition to the Pennsylvania Board of Health, some of the nation’s most advanced municipal health departments—Chicago, Minneapolis, Brooklyn, Charleston, Denver, and St. Louis—began using their new bacteriological laboratories to test vaccines for potency or purity. At the most dramatic level of control, the city of New York manufactured its own virus—still in 1901 the only city in the country to do so. The New York health board rankled commercial makers by selling limited amounts of its well-regarded virus on the open market.54

  American vaccine makers were regulated almost exclusively by their reputations, their commercial “trustworthiness.” This encouraged nasty advertising practices. In a 1900 article titled “The Pot Calls the Kettle Black,” the Indianapolis physician W. B. Clarke observed that vaccine advertisements published in the medical journals had become a scandalous “squabble literature.” “In their greedy commercialism,” Clarke wrote, the manufacturers “have fallen out, and are each vying with the others in desperate attempts to show the medical profession that theirs is the one pure virus, and that all the others are dangerous and unfit for the use even of a health (?) officer.” Dr. Clarke was an antivaccinationist (the giveaway was that parenthetical question mark), but he did not exaggerate. As early as 1898, an Alexander Company advertisement had thrown down the gauntlet: “At the beginning of this second century [of vaccination] the tendency is to propagate impure virus, in order to meet the demand for great discounts, thus lowering the price and making it impossible to propagate in a proper manner.” Even assertions of product purity were phrased so as to condemn rivals’ wares by implication: “This Vaccine is Entirely Free from Blood Corpuscles,” a distributor for the New-England Vaccine Company proudly announced. Parke, Davis did not wait for the Camden crisis to cool down before taking a swipe at Mulford (unnamed) in its advertising. “The most successful vaccination is not the vaccination that inflicts the most suffering upon the patient,” said one Parke, Davis ad. “The best virus is our Aseptic Vaccine. It effectually protects against smallpox—it does not infect with disease-breeding organisms.” And then came the kicker, underscored and printed in boldface type: “Not a single fatality was ever charged to our Vaccine Virus.”55