Early in the year 1930, newspapers in the American South and Midwest began to report on a strange new paralytic illness that was affecting relatively large numbers of individuals. Victims of the disease would typically notice numbness in the legs, followed by weakness and eventual paralysis with "foot drop." In most cases, this was followed within about a week by a similar process in the arms, resulting in many cases in "wrist drop." The disease was rarely fatal, but recovery was very slow and in many cases the damage to the nervous system left the patient with permanent disabilities.

Although the affliction resembled other neurological problems, such as Landry's disease and anterior poliomyelitis, the symptoms did not conform exactly to any known condition. The number of cases of this mysterious ailment reached epidemic proportions over the course of 1930 and 1931, eventually affecting an estimated tens of thousands of individuals in many states, from New York to California.(1)

It did not take long after the first appearance of the illness to link it to the consumption of fluid extract of Jamaica ginger, commonly referred to as "Jake" by many who used the product. This paper examines the ginger extract toxicity episode of the early 1930s, with particular emphasis on the role of pharmacologist Maurice Smith of the National Institute (now Institutes) of Health in solving the mystery of the poisoning.

PROHIBITION AND POISON

Two Oklahoma doctors, E. Miles and W. H. Goldfain, were apparently the first to associate the condition with the ingestion of fluid extract of Jamaica ginger. On February 27, 1930, Goldfain saw a patient suffering from multiple neuritis at the Reconstruction Hospital in Oklahoma City. The condition resembled in some ways the neuritis due to lead poisoning, but there was no known history of exposure to lead and some of the expected symptoms of this type of poisoning were missing. Before that day was out, Goldfain saw four other patients suffering from a similar condition. Among them was a pharmacist who dispensed Jamaica ginger to customers and had taken some himself about ten days before the onset of the symptoms. Another patient gave Goldfain a list of 65 people living in the same geographic area of the city who were similarly afflicted.

Goldfain consulted with City Health Supervisor Miles, and the two of them visited more than 30 of the people on the list. All of them reported having ingested Jamaica ginger about seven to sixteen days prior to the onset of their symptoms. They had all secured their ginger at one of several drug stores located within an area of six square blocks, and several of the employees or proprietors of these stores also suffered from the paralysis. Attempts to identify a toxic substance in the ginger extract were unsuccessful.(2)

Soon reports from other states confirmed that the onset of the disease seems to have been invariably preceded by the consumption of the ginger extract, usually about two weeks before the symptoms appeared. The majority of the victims were adult males. A small percentage of individuals denied having taken the ginger extract, but in many cases it was later found that they had lied about the use of the product.(3)

The fluid extract of Jamaica ginger, or Jake, was a convenient way of imbibing alcohol during the era of Prohibition. It had an alcohol content of about 70% and was readily available in pharmacies, where it was sold as a carminative, headache remedy, and general aid to digestion. A popular method of drinking Jake was to mix the contents of the two-ounce bottle with a soft drink to help dilute the strong ginger flavor.

Alcoholic extracts of ginger had been available in the United States since the 19th century, and, even before the advent of Prohibition, they were popular as alcoholic beverages in "dry" areas of the country. With the coming of Prohibition, only the fluid extract described in the Pharmacopeia of the United States (U.S.P.) was legally marketable. The Prohibition Bureau classified the U.S.P. extract as nonpotable because it contained enough of the oleoresin of ginger to give it a very pungent taste, which made it less desirable as a beverage. Desperate individuals perhaps consumed it anyway, but a variety of illicit preparations labelled as the official fluid extract also began to appear on the market. These products were highly adulterated, substituting ingredients such as molasses, glycerin, and castor oil for most of the oleoresin of ginger, thus greatly reducing the objectionable ginger taste.(4)

Since Jake had been in long use by 1930 and generally did not produce any ill effects other than those that could be attributed to the alcohol, the reason for the sudden appearance of many cases of paralysis of the extremities tied to the product was not immediately obvious. Was the ginger used in this particular extract contaminated with some poison? Had the manufacturer adulterated the extract with some poisonous ingredient not previously used in Jake? Or was some new denaturant in the alcohol the culprit? The symptoms of the disease did not match those induced by poisons known to cause polyneuritic afflictions, such as lead and arsenic, nor were appreciable amounts of these metals found in any of the suspected samples of ginger extract.

Hundreds of samples of the fluid extract of ginger, many of them positively declared to have caused paralysis, were sent to the Treasury Department's Bureau of Industrial Alcohol for analysis early in 1930. The Bureau's chemists soon discovered the presence of a cresol compound, a substance that they had never before encountered in adulterated fluid extracts of ginger. According to Bureau chemist Peter Valaer, it was certain by early March that the compound was tri-ortho-cresyl phosphate (TOCP) and that this substance was present to the extent of about 2 percent in samples allegedly associated with paralysis.(5)

Valaer also stated that TOCP "almost escaped blame because reference books on therapeutics failed to list this ester as a poison or mention that it would cause paralysis."(6) TOCP was an industrial chemical that was sold in large quantifies as a liquid plasticizer. It was used extensively in such products as lacquers, leather dopes, and airplane finishes.(7) Proof that TOCP was the culprit in the poisonings came from the work of scientists affiliated with another component of the Treasury Department, the Public Health Service, specifically in the Division of Pharmacology of the National Institute of Health.

MAURICE SMITH AND THE TOXICOLOGY OF TOCP

In 1930, the National Institute of Health (NIH) was just being created out of the Hygienic Laboratory, which had been established by the Public Health Service (PHS) in 1887.(8) A Division of Pharmacology was authorized for the Hygienic Laboratory by legislation enacted in 1902, and pharmacologist Reid Hunt was appointed in 1904 as the first head of the division. He was succeeded in 1913 by Carl Voegtlin, who still held the position at the time of the ginger extract or Jake paralysis incident.(9)

Maurice I. Smith, Senior Pharmacologist in the Division of Pharmacology, had the primary responsibility for the pharmacological and toxicological studies on Jake. Smith was born in Russia on November 17, 1887, and became a naturalized U.S. citizen at the age often. After obtaining his B.S. degree from the College of the City of New York in 1909, he attended the Cornell University Medical School, where he earned the M.D. degree in 1913. He then taught pharmacology at the medical schools of the University of Michigan and the University of Nebraska for the next few years, also briefly holding a post as a pharmacologist at the Hygienic Laboratory for part of 1918.

In 1920, Smith joined the staff of the Hygienic Laboratory on a more permanent basis, spending most of the rest of his career in the PHS. He left the PHS for a brief period in 1925 to become Director of the Glandular and Pharmaceutical Department of Lederle Laboratories in Pearl River, N.Y. In his letter of resignation, Smith praised the working conditions at the Hygienic Laboratory but explained that "the compensation is so inadequate and the possibilities for future advancement seem to be so uncertain" that he was compelled to take a more remunerative position. His annual salary at Lederle was almost $2,000 more than he earned in the PHS, $5,500 (plus royalties) as opposed to $3,600. In 1926, he was lured back to the Hygienic Laboratory as Senior Pharmacologist at a salary of $5,000. He remained with the PHS, holding the title of Principal Pharmacologist at NIH from 1931 until his retirement in 1950. Smith died on January 26, 1951.(10)

Maurice Smith traveled to Cincinnati and to Johnson City, Tennessee to examine personally some of the victims of Jake poisoning. Ginger extract was sold in Cincinnati under at least eight different brands and in Johnson City under at least four. Paralysis could not be definitely associated or dissociated with any particular brand. These facts suggested to Smith and others that it was probable that the poisoned "fluid extract" had come from one source at a fairly definite time and had found its way into various brands.(11)

There was nothing in Smith's clinical descriptions of the victims that had not been reported by others. His contribution to the problem came in the laboratory, where he obtained experimental evidence that TOCP was the cause of the poisoning. He was assisted in the chemical side of the work by NIH chemist Elias Elvove, as well as by Valaer and others at the Bureau of Industrial Alcohol and the Prohibition Bureau.

Obtaining samples of the product consumed by the victims for the studies of Smith and Elvove turned out to be a difficult problem. Most of the patients had completely consumed the contents of the two-ounce bottles that had brought on their illness. Even if they had not, it was not always easy to locate the discarded bottles. For example, many of these bottles had been discarded in outdoor toilets, and a number of these were retrieved by methods that are not specified. Eventually 13 samples were collected for Smith and Elvove. Several of these had been seized from distributors and were suspected of containing the poisonous ingredient. But a number of the samples were clearly associated with patients suffering from the disease and could thus provide more conclusive evidence as to its cause. Two of the samples were believed to be harmless and presumably served as a control.(12)

In their first communication on the subject, presented at a conference in June 1930 and published in Public Health Reports the following month, the NIH scientists reported that the suspected adulterated ginger extracts all showed the presence of some kind of phenol compound, whereas the samples believed to be harmless and the official U.S.P. fluid extract tested negative for phenols. In addition, the samples that tested positive for phenols were the same ones that proved toxic to rabbits in moderate doses in laboratory experiments. The other samples failed to produce toxic effects.(13)

Smith and Elvove obviously believed that the phenol compound involved was tricresyl phosphate, which had already been identified as a constituent of adulterated Jake. They prepared a fluid extract of ginger that approximated in composition the suspected gingers (with tricresyl phosphate as one of the ingredients). This formulation produced in rabbits the same symptom complex, including paralysis, as did the suspected gingers. The results were the same when a 2 1/2% solution of tricresyl phosphate in 80% alcohol was administered to rabbits.(14)

Nevertheless, in this preliminary report, Smith and Elvove were hesitant to definitely identify tricresyl phosphate as the agent responsible for Jake poisoning. They were troubled in part by the fact that monkeys and dogs, unlike rabbits, did not develop the symptoms of poisoning when given the suspected gingers or the tricresyl phosphate solution. Various experiments led them to suggest that perhaps the phenolic compound was not directly toxic in the form of the phosphoric acid ester, but had to be broken down in the body to liberate the toxic agent. They speculated that rabbits might break down the compound with ease, whereas monkeys and dogs might be unable to do so. This difference in reaction between species caused them to frame their conclusions in very cautious terms.

"The precise relation of this phenolic compound either by itself or in combination with the other ginger constituents to the multiple neuritis in man is as yet not clear. Before we can be certain of the etiologic relationship it will be necessary to find means of reproducing the human disease in animals more faithfully than we have been able to do so far."(15)

In an addendum to the published version of this paper, however, Smith and Elvove were able to provide additional evidence which they argued "proves almost conclusively our tentative conclusions as to the etiologic relationship of the phenolic ester to the multiple neuritis in man." Using facilities provided by the Department of Agriculture's Bureau of Animal Industry, Smith and Elvove carried out experiments on calves that confirmed their results with rabbits, thus strengthening the confidence of the NIH scientists in their conclusions.(16) The suggestion to use calves apparently came to them through a country veterinarian in the midwest who had given fluid extract of ginger to his ailing calf patients. The extract used unfortunately contained the poisonous adulterant, and the calves developed paralysis.(17)

In a second paper published in October 1930, Smith and his colleagues reported on further studies that specifically identified the ortho isomer of tricresyl phosphate as the cause of the motor paralysis of the extremities. They also established that at least some of the differences in species susceptibility to the compound were due to differences in absorbability from the alimentary canal.(18) The scientists felt justified in concluding that: "The etiologic relationship of tri-ortho cresyl phosphate to the recent epidemic of so-called ginger paralysis is thus definitely established."(19)

Smith and his coworkers published several other papers on tri-ortho cresyl phosphate and related compounds in the early 1930s. In an effort to better understand the mechanism of action of these substances, they carried out experiments on the hydrolysis of phenyl and cresyl phosphoric esters and the relationship of their pharmacological activity to their chemical structure.(20)

THE FDA'S ROLE IN THE GINGER JAKE PARALYSIS EPISODE

The toxic ginger extract was adulterated and misbranded and thus subject to prosecution under the 1906 Federal Food and Drugs Act. The Food and Drag Administration (FDA), in cooperation with the Prohibition Bureau and state health officials, seized various lots of the contaminated product. One estimate is that FDA seized 87 different shipments originating from at least 27 firms.(21) In most of these cases, either no claimant appeared in court, and the shipment was thus condemned and forfeited, or the defendant pleaded guilty or "nolo contendere" and received a small fine.(22)

The product was sold under a wide variety of brand labels, and some of the firms involved existed in name only. John Morgan has noted that:

Often these companies were not traceable, and all sellers involved had numerous names, mailing addresses, and fronts. In more than one state, a grand jury indicted one `S. A. Hall' of Brooklyn as a conspirator in the traffic (Cincinnati Times Star, April 17, 1930, p. 1). This was a mail-drop office used by a Brooklyn seller and was so named because it stood next door to a Salvation Army installation.(23)

In spite of the confusion surrounding the distribution of the product, investigators found that the bottles of poisonous Jake could almost always ultimately be traced back to a particular finn in Boston, Hub Products. Federal grand juries in several cities returned indictments against Hub President Harry Gross and his brother-in-law, Max Reisman, a part owner of the firm. In February 1931, the various cases pending against Gross and Reisman were consolidated for trial in Boston. The two men were charged with conspiracy to violate both the Prohibition act and the food and drug act. The conspiracy charge was used because conspiracy was a felony and could lead to a jail sentence, whereas violation of the food and drug act was classed as a misdemeanor and was punishable in the case of a first offense by a fine only (and usually a small one at that). Violation of the Prohibition act carried greater penalties, but Federal authorities might have been less confident of conviction on thi s charge because of an earlier Federal court ruling that clouded the issue.(24)

Gross and Reisman eventually pleaded guilty to the charges, but apparently convinced the court that the real culprits were some New York bootleggers from whom they had obtained their Jake. The judge imposed a fine of $1,000 on the Hub Products Company and sentenced each man to two years in prison. However, the prison sentences were suspended and the men placed on two years probation instead. As part of the conditions of their probation, the defendants agreed to assist the government in efforts to locate and prosecute the parties whom they claimed were actually responsible for the adulterated product.(25)

The FDA was very unhappy with the results of the conviction and began to conduct further investigations of its own.(26) The agency soon acquired evidence that cast serious doubts on the existence of a New York supplier and pointed to Hub Products as the manufacturer of the poisoned Jake. In 1932, Gross was charged with violation of his probation. Evidence was presented at a hearing to show that Gross himself mixed the poisonous Jake. On the basis of this new evidence, he was ordered to serve his two-year prison term. The judge in the case refused, however, to hear the government's case for revocation of the probation of Reisman.(27)

The other major federal case involving Jake resulted in a trial held in Brooklyn, New York, in December 1932. This case resulted largely from a second, smaller epidemic of Jake poisoning that occurred in southern California at the end of 1930 and the beginning of 1931. About 125 cases were reported in Los Angeles and nearby areas. Maurice Smith traveled to California and assisted in confirming that the problem was indeed ginger paralysis due to Jake containing tri-ortho cresyl phosphate.(28)

A group of Jake dealers in Brooklyn had obtained a shipment of the adulterated ginger extract from Hub Products in February 1930. They still had this material on hand at the end of the year, and apparently mixed it with some of their own product (which was adulterated with castor oil). Most of this batch of Jake seems to have been shipped to southern California, although at least some of it was sent to Kansas City. A grand jury brought indictments against five men, but the charges against one of them were later dropped. The other four men were tried for conspiracy to violate the food and drug law. Maurice Smith testified at the trial as a witness on behalf of the government. Three of the defendants were found guilty and received jail sentences of from 15 to 20 months. Two of the men were fined $2,500 as well. The verdicts were appealed, but the judgements were affirmed.(29)

CONCLUSION

The poisoned Jake incident affected enough individuals that the victims actually founded the "United Victims of Ginger Paralysis Association," an organization that claimed 35,000 members. The organization's leader hoped to be able to obtain compensation for its members from the federal government, but he was destined to be disappointed in this regard.(30)

Not surprisingly, some victims of ginger paralysis were desperate enough to try anything that promised to cure their illness. The FDA's Food and Drug Review reported that in Kansas stories of "cures effected by the victims wading in oil slush ponds caused many to hobble painfully to such ponds in the vicinity of refineries at Wichita." Unscrupulous entrepreneurs are always ready to capitalize on the plight of the sick, and the Jake situation was no exception. The Food and Drug Review also noted that a "doctor" in Wichita claimed to be able to cure paralysis victims by electrical treatment, but his career was cut short when he was arrested for practicing without a license.(31)

The ginger paralysis incident also made its way into some of the popular songs of the day. Morgan and Tulloss have identified a dozen songs recorded by rural southern artists that mention Jake. Most of these songs, with titles such as "Jake Leg Blues" and "Jake Walk Papa," refer specifically to the poisonous effects of the adulterated Jake and were presumably inspired by the tragedy.(32)

In many ways this incident was a forerunner of the more famous Elixir Sulfanilamide tragedy of 1937, helping to point out the need for more effective food and drug legislation. Over one hundred individuals, many of them children, died in the Elixir Sulfanilamide incident.(33) Although there were very few fatalities that could even conceivably be attributed to the consumption of the poisoned Jake, thousands suffered long-term, sometimes permanent, damage to the nervous system. Like the Elixir Sulfanilamide disaster, the problem was not the active ingredient itself, but an additive. In the case of Elixir Sulfanilamide, however, the effort was not to adulterate the product but to find a suitable solvent. The solvent chosen, diethylene glycol, was unfortunately toxic, as was the adulterant chosen in the Jake incident. In an effort to find an adulterant to dilute the ginger taste of an extract designed for consumption as an alcoholic beverage rather than a medicine, one manufacturer selected tri-cresyl phosphate because it was soluble in alcohol, miscible with the oleoresin of ginger, and cheap.

Ironically, diethylene glycol was one of the chemicals tried as an adulterant by Gross before he settled on tri-ortho-cresyl phosphate, but it proved to be too volatile for his purposes. It is reasonable to ask whether the adulterated Jake would have led to large numbers of fatalities, as in the Elixir Sulfanilamide case, if Gross had indeed used diethylene glycol. John Morgan has calculated, however, that the dosage that Gross would likely have used for the adulteration would have been much too low to be lethal. The Jake drinker would have had to consume many bottles of the product, presumably within a relatively short period, to suffer the renal failure that was the chief cause of death in the Elixir Sulfanilamide tragedy.(34)

The manufacturer of Elixir Sulfanilamide could readily have discovered that diethylene glycol was toxic if he had simply checked the literature. In the case of Jake, however, the fact that tri-ortho-cresyl phosphate was toxic was not so well known. As noted above, chemist Peter Valaer of the Bureau of Industrial Alcohol indicated that tri-cresyl phosphate was not identified as the toxic agent more quickly because it was not listed as a poison in medical reference works.

In fact, Gross actually did inquire about the toxicity of the cresyl phosphate. When diethylene glycol failed to satisfy Gross, he asked his supplier, Raffi and Swanson, for something less volatile, and lindol (a trade name for cresyl phosphate) was suggested. Benjamin Werby, a chemist working for Gross, asked John Swanson about the toxicity of lindol. When Swanson contacted a manufacturer of the substance, the Celluloid Corporation of Newark, New Jersey, he was informed that lindol was not toxic. An FDA employee later contacted Celluloid and confirmed that the company had indeed not considered the product to be toxic. The production manager claimed that the company had at one time arranged for a pharmacologist (said to be a professor at Columbia University) to test lindol, and that he had reported no toxic effects. Assuming that the story is true, the toxicity may have failed to show up because of the experimental animals, doses, or modes of administration used. As we have seen , Smith and Elvove had themselves encountered difficulty in producing toxic effects in all cases.(35)

Creosote phosphate, which was used to treat tuberculosis around the turn of the twentieth century, had been reported to cause paralysis in some cases. Creosote is a mixture of phenol and phenol derivatives obtained from the distillation of coal tar or wood tar. Improper distillation can lead to the presence of ortho-cresyl phosphate, which is responsible for the paralysis, but this was not known at the time.(36) There have been several incidents of cresyl phosphate poisoning since the Jake incident, including paralysis induced in several hundred European women in the early 1930s who had taken apiol (an alcoholic extract derived from parsley seeds) as an abortifacient. The apiol was adulterated with cresyl phosphate.(37)

There were no requirements in the 1906 food and drug act for premarket testing and approval of drug products, and so neither Hub Products nor the manufacturer of Elixir Sulfanilamide broke the law simply by putting their products on the market without testing them for safety. Gross and Reisman violated the food and drug law for selling a product that was supposedly fluid extract of ginger U.S.P., but which differed from the standards of strength, quality, and purity of fluid extract of ginger as set down in the U.S.P. They were also in this particular case liable for prosecution under the Prohibition act. Likewise, the manufacturer of Elixir Sulfanilamide was prosecuted for misbranding and adulteration, not directly for the toxic results, and he escaped with just a fine and no jail sentence.

As the 1930s progressed, pressure for reform of food and drug legislation increased. In 1937, the Elixir Sulfanilamide tragedy created enough of a public outrage to lead to the passage of the 1938 Food, Drug, and Cosmetic Act. This act did finally prohibit the marketing of new drugs in interstate commerce until their manufacturers provided FDA with satisfactory evidence of their safety.(38)

Acknowledgements

Appreciation is expressed to Dr. John Morgan of the Sophie Davis School of Biomedical Education, City University of New York, and to the FDA History Office for assistance in locating materials that were useful in the preparation of this paper. I also wish to thank Dr. James Harvey Young for his helpful comments on the original draft of the paper.

Notes and References:

(1.) For a general historical overview of the incident, see John P. Morgan, "The Jamaica Ginger Paralysis," JAMA, 248 (1982): 1864-1867. A useful contemporary review is John G. Kidd and Orthello R. Langworthy, "Jake Paralysis: Paralysis Following the Ingestion of Jamaica Ginger Extract Adulterated with Tri-Ortho-Cresyl Phosphate," Bull. Johns Hopkins Hosp., 52 (1933): 39-60. Early reports in the medical literature include E. Goldfain, "Jamaica Ginger Multiple Neuritis," J. Oklahoma State Med. Assoc., 23 (1930): 191-192; Benjamin Burley, "The 1930 Type of Polyneuritis," New England J. Med., 202 (1930): 1139-1142; and Scale Harris, "Jamaica Ginger Paralysis," Southern Med. J., 23 (1930): 375-380.

(2.) Goldfain, "Jamaica Ginger"; David T. Bowden, L. A. Turley, and H.A. Shoemaker, "The Incidence of `Jake Paralysis' in Oklahoma," Amer. J. Pub. Health, 20 (1930): 1179-1186.

(3.) See, e.g., Hugh J. Morgan, "Comments on the Epidemic of Symmetrical Peripheral Neuritis in Tennessee," J. Tennessee State Med. Assoc., 23 (1930): 175-176, and the articles cited in note I for early reports of poisoning linked to Jake. For examples of patients who denied having used Jake but were later found to have lied, see Bowden, Turley, and Shoemaker, "The Incidence," pp. 1180-1181, and "Ginger Extract and Paralysis," Food, Drug, Insect. Rev., 14 (1930): 223-226.

(4.) Morgan, "Jamaica Ginger," pp. 1864-1865, and Kidd and Langworthy, "Jake Paralysis," p. 42.

(5.) Peter Valaer, "The Examination of the Cresyl-Bearing Extracts of Ginger," Amer. J. Pharm., 102 (1930): 571-74.

(6.) Ibid., p. 572.

(7.) Ibid., p. 573; René Lefaux, Practical Toxicology of Plastics, translated by Scripta Technica Ltd., English edition edited by Peter P. Hopf (London: Iliffe Books, 1968), pp. 128-129.

(8.) On the Hygienic Laboratory and the establishment of NIH, see Victoria A. Harden, Inventing the NIH: Federal Biomedical Research Policy, 1937-1987 (Baltimore: Johns Hopkins University Press, 1986).

(9.) Parascandola, John. "The Beginnings of Pharmacology in the Federal Government." Pharm. Hist., 30 (1988): 179-187.

(10.) Biographical data on Smith is taken from an obituary by George W. McCoy in Journal of the Washington Academy of Sciences, 42 (1952): 136, and from documents in his official personnel folder, Federal Records Center, National Archives and Records Administration, St. Louis. The quotation concerning Smith's reasons for leaving the Hygienic Laboratory is taken from a letter from Smith to the Director of the Laboratory, December 28, 1925, in the personnel folder.

(11.) Smith, Maurice I., and E. Elvove, with the cooperation of P. J. Valaer, Jr., William H. Frazier, and G. E. Mallory, "Pharmacological and Chemical Studies of the Cause of So-Called Ginger Paralysis: A Preliminary Report," Pub. Health Rep., 45 (1930): 1703-1716 (especially p. 17O4).

(12.) Ibid., pp. 1707-1708; Ralph Chester Williams, The United States Public Health Service, 1798-1950 (Washington, D.C.: Commissioned Officers Association of the United States Public Health Service, 1951), p. 220. In a report of one incident in Maine involving 19 people, the FDA inspector noted that none of the victims had any of the ginger extract left and that not "even an empty bottle could be found." J. W. Burke, "Investigation of Fluid Extract Ginger Paralysis at Caribou. Maine," records from FDA Boston Station, FDA History Office, Rockville, Maryland.

(13.) Smith and Elvove, "Pharmacological and Chemical Studies," pp. 1707-1710.

(14.) Ibid., pp. 1710-1713.

(15.) Ibid., p. 1714.

(16.) Ibid., pp. 1715-1716 (the quotation is from p. 1715).

(17.) Valaer, "The Examination," p. 572.

(18.) Smith, Maurice I., with the cooperation of E. Elvove and W.H. Frazier, "The Pharmacological Action of Certain Phenol Esters, with Special Reference to the Etiology of So-Called Ginger Paralysis," Pub. Health Rep., 45 (1930): 2509-2524.

(19.) Ibid., p. 2521.

(20.) Smith, Maurice I., E. W. Engel, and E. F. Stohlman, "Further Studies on the Pharmacology of Certain Phenol Esters with Special Reference to the Relation of Chemical Constitution and Physiologic Action," Nat. Inst. Health Bull., No. 160 (1932): 1-53; Maurice I. Smith and R. D. Lillie, "The Histopathology of Some Neurotoxic Phenol Esters," ibid., pp. 54-69; Maurice I. Smith and E. E Stohlman, "The Hydrolysis of the Phenyl and Cresyl Phosphoric and Phosphorous Acid Esters in Alcoholic and Aqueous Systems," Pub. Health Rep., 48 (1933): 734-739; Maurice I. Smith, "The Estimation of Tissue Phenols," ibid., pp. 1487-1496.

(21.) Morgan, "Jamaica Ginger," p. 1865.

(22.) See Notices of Judgment Under the Food and Drug Act (Food and Drug Administration, United States Department of Agriculture) in the early 1930s. Some of the judgments involving the toxic Jake are 17452, 17605, 17773, 19505, 20746, and 25057.

(23.) Morgan, "Jamaica Ginger," p. 1865.

24. In June 1930, a Federal judge in New York had refused to extradite two Brooklyn men to Kentucky to face trial after a grand jury indictment under the Prohibition act. The defense lawyers successfully argued that the product was not labeled or sold by the manufacturer as an alcoholic beverage, and therefore the manufacturer should not be held liable under a law designed for deliberate bootlegging, even if some purchasers "misused" the product. See Morgan, "Jamaica Ginger," pp. 1865-1866. Another commentator has indicated that prosecutions involving the sale of liquor were often brought under revenue or conspiracy laws because it was easier to secure convictions under these statutes than under the National Prohibition Act in many jurisdictions. See Edward B. Dunford, "Legal Aspects of Prohibition," in Alcohol, Science and Society (New Haven, CT: Quarterly Journal of Studies on Alcohol, 1945), pp. 321-348 (especially p. 342). An FDA official also indicated that a stronger case could be brought against the manufacturer of adulterated Jake under Prohibition legislation than under the Federal Food and Drugs Act. Letter from P. B. Dunbar to the Solicitor, February 23, 1932, records from FDA Boston Station, FDA History Office.

25. Report from George H. Adams to Chief, Eastern District, April 7, 1932, pp. 9-12, records from FDA Boston Station, FDA History Office.

26. See, for example, letter from George H. Adams to W. R. M. Wharton, October 21, 1931, records from FDA Boston Station, FDA History Office.

27. Campbell, Walter, "1932 Report of Food and Drug Administration," in Federal Food, Drug and Cosmetic Law: Administrative Reports, 1907-1949 (Chicago: Commerce Clearing House, 1951), p. 771 (p. 3 of original report); "‘Ginger Jake’ Adulterator Goes to Jail," Food Drug Rev., 16 (1932): 137; Harold Hopkins, "Blues Language and the Jakewalk Blues," FDA Consumer, 14[5] (June, 1980): 6-11; Morgan, "Jamaica Ginger," p. 1866; report of George H. Adams to Chief, Eastern District, April 7, 1932, pp. 12-15, records from FDA Boston Station, FDA History Office.

28. Smith, Maurice I., and E. Elvove, "The Epidemic of So-Called Ginger Paralysis in Southern California in 1930-31," Pub. Health Rep., 46 (1931): 1227-1235.

29. Notice of Judgment 20554, Notices of Judgment Under the Food and Drug Act (Food and Drug Administration, United States Department of Agriculture); "Los Angeles Station Investigates Ginger Jake Paralysis Outbreak," Food Drug Rev., 15 (1931): 108; Morgan, "Jamaica Ginger," 1867.

30. "Editorial Comments on Claims of Jamaica Ginger Victims," Food Drug Rev., 16 (1932): 15.

31. "Fakes Follow in the Footsteps of ‘Jake’ Paralysis," Food Drug Rev., 14 (1930): 226.

32. Morgan, John P. and Thomas C. Tulloss, "The Jake Walk Blues: A Toxicologic Tragedy Mirrored in American Popular Music," Ann. Int. Med., 85 (1976): 804-808.

33. On this incident, see James Harvey Young, "Sulfanilamide and Diethylene Glycol," in John Parascandola and James C. Whorton, Chemistry and Modern Society: Historical Essays in Honor of Aaron J. Ihde (Washington, D.C.: American Chemical Society, 1983), pp. 105-125.

34. Morgan, "Jamaica Ginger," p. 1866.

35. Letter from Cyril C. Sullivan to Haven Parker, March 30, 1932, and report from George H. Adams to Chief, Eastern District, FDA, April 7, 1932, p. 6. Harvard pharmacologist Reid Hunt was also apparently unable to reproduce the ginger paralysis when he tested suspected samples of adulterated Jake on experimental animals. Record of conversation of Reid Hunt with J. J. Durrett, April 29, 1930. All of these documents may be found in records from the FDA Boston Station, FDA History Office.

36. Zinn, W.M., "Introduction: Survey of Earlier Triaryl-Phosphate Intoxications," in A. V. Albertini, D. Gross, and W.M. Zinn, Triaryl-Phosphate Poisoning in Morocco 1959: Experiences and Findings (Stuttgart: Georg Thieme Verlag, 1968), pp. 1-5 (especially p. 2); National Institute for Occupational Safety and Health, Criteria for a Recommended Standard....Occupational Exposure to Cresol (Washington, D.C.: Government Printing Office, 1978), p. 2; Tricresyl Phosphate, Environmental Health Criteria 110 (Geneva: World Health Organization, 1990), pp. 71-72.

37. On later examples of cresyl phosphate poisoning, including the apiol case, see Zinn, "Introduction," pp. 3-4 and Tricresyl Phosphate, pp. 72-73.

38. On the passage of the 1938 Act, see Charles O. Jackson, Food and Drug Legislation in the New Deal (Princeton, NJ: Princeton University Press, 1970).