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Posted by on Feb 3, 2009 in Ethics, FDA, Pediatrics, Pharma

Massengill’s Elixir Sulfanilamide: Early Investigation and Recall

Massengill’s Elixir Sulfanilamide: Early Investigation and Recall

The bottle contained…a reddish, somewhat viscous liquid, having an aromatic odor resembling raspberry and anise, a sweet taste, and resembling glycerin in general physical character.

Journal of the American Medical Association, November 6, 1937

When the AMA learned of the Tulsa deaths and that diethylene glycol was a prominent ingredient in Massengill’s Elixir Sulfanilamide, the organization immediately sought out the product for testing. In addition to receiving a 50-mL bottle (~1.7 fluid ounces) of the elixir from Tulsa physician Darwin B. Childs (which his patient, Glen Entler, had purchased from the city’s Quaker Drug Company), the AMA obtained samples on the open market and a 1-gallon bottle directly from the Massengill company. Investigators at the AMA’s chemical laboratory found the product to be “a reddish, somewhat viscous liquid, having an aromatic odor resembling raspberry and anise, a sweet taste, and resembling glycerin in general physical character” [1]. Distillation experiments confirmed the elixir to be a solution of approximately 40 grains (~2.6 g) of sulfanilamide per fluid ounce in a “menstrum” of about 72% diethylene glycol and about 16% water [1,2].

Although diethylene glycol was suspected to be the kidney-damaging substance in the Tulsa cases, it was not known if the solvent had any effect on the toxicity of sulfanilamide or vice versa. It was also not known if there had been any errors in Massengill’s manufacturing process. The AMA’s Morris Fishbein advised, “Indeed the possibilities are unlimited, since we are here concerned with a preparation not standardized by any reliable agency, semisecret in composition, and apparently hastily rushed into the market to meet an overenthusiastic reception of a new remedy [2].” But when the AMA’s chemical laboratory tested the elixir’s solid residue, they found sulfanilamide to be chemically intactmeaning that the diethylene glycol solvent had not affected the antibiotic [1]. Further tests also failed to reveal other potentially toxic substances, like lead, mercury, or arsenic.

Immediate experiments on rats, rabbits, and dogs at the University of Chicago showed effects that were strikingly similar to those seen in the Tulsa victims: death, always preceded by anuria, was observed in 20%-30% of animals that received either diethylene glycol alone, Massengill’s elixir, or a synthetic version of the product (which had been mixed up by the AMA for experimental purposes). However, the authors noted the toxicity of the substance varied considerably among species and among individual animals. Most important, sulfanilamide, by itself, did not produce the same renal symptoms or death [3]. The experiments therefore confirmed the suspicion that chemically intact diethylene glycol in Massengill’s preparation was the lethal ingredient and had not affected the toxicity of the antibiotic.

In conjunction with the arrival of FDA inspectors William H. Hartigan and Walter E. Donaldson on October 15, 1937, the Tulsa County Medical Society launched its own investigation of the deceased children who “had a peculiar kidney ailment, following sore throats” [4]. Despite the fact that there were rumors of similar deaths in the St. Louis area, there remained confusion as to why “the particular treatment would affect children in Tulsa and not…children or patients in other places where it [presumably sulfanilamide generally] has been used to much greater extent.” To that end, cases of unexplained death in the area would be reexamined, and local tests of the elixir on guinea pigs were initiated [5].

Hartigan himself anticipated a cautious and perhaps protracted investigation in Tulsa, given his experience several years earlier with numerous cases of paralysis in Oklahoma City [5]. Consuming months, the investigation led to the discovery of Jamaica ginger, or “jake,” that was adulterated with a neuropathy-inducing organophosphate. The jake, sold legally as a medicinal compound, was consumed enthusiastically for its alcohol content during the era of prohibition [6]. Hartigan’s immediate job in Tulsa was to secure samples of Massengill’s elixir for testing at the FDA’s Baltimore laboratory. In the meantime, the president of the Tulsa Retail Druggists urged its members not to sell sulfanilamide without a prescription, and the sale of Massengill’s elixir was to be discontinued entirely [4,7].

On Monday, October 18, 1937, Fishbein publicized the dangers of Massengill’s elixir in an editorial released to the nation’s newspapers and radio stations. Specifically he identified the death-causing ingredient: “It would appear that diethylene glycol rather than sulfanilamide was responsible since one of the patients [Glen Entler] had received [sulfanilamide] tablets over a period of two weeks without any bad effects and then developed the typical train of symptoms after taking the elixir…This tragic experience should be a final warning to physicians relative to the prescribing and administration of semi-secret, unstandardized preparations” [8]. Despite the understandable speed with which Fishbein acted to warn a vulnerable public, the finality of his report (and probably its chastising tone toward those who prescribed the elixir) was resented by Tulsa physicians. They still were waiting for an official AMA report on the analysis of local samples and, perhaps taking a cue from Hartigan, believed that a more complete investigation was necessary before judgment could be pronounced [9,10].

At present, Hartigan’s boss, FDA Commissioner Walter G. Campbell was less emphatic than Fishbein about the cause of the Tulsa deaths. “We do not know as yet the explanation of the fatalities,” he told the Associated Press. “It has been reported that the solvent, diethylene glycol, is probably the responsible agent. We know that there is something radically wrong” [11].

To initiate an investigation of all liquid sulfanilamide preparations on the US market, Campbell air-mailed the following letter to the agency’s District Chiefs on October 18 [12].

The tragic results at Tulsa, Oklahoma, following the administration of sulfanilamide elixir made with diethylene glycol, indicate the necessity of immediate investigation of preparations of sulfanilamide already placed on the market by numerous pharmaceutical houses and coming into existence in new form almost daily.

For the present, it is suggested that this investigation be restricted to liquid preparations since these are more likely to undergo change than are the tablet and other solid preparations.

Because of the fact that Baltimore Station has already inaugurated a study of sulfanilamide preparations, such samples as are collected in the immediate future, may, if desired, be sent to that laboratory for examination. Each District, however, should promptly arrange for examinations of sulfanilamide preparations in one or more of its own laboratories.

Regardless of whether competing liquid products (if they existed*) posed the same risk as Massengill’s product, an urgent and complete withdrawal of the proprietary elixir was imperative. Although the company had initiated its own recall by telegraph, Campbell initiated the FDA’s oversight of what would become a massive and far-reaching process, ultimately drawing on nearly all of the agency’s field force [13]. Federal seizure of the poisonous product, Campbell argued, would have to be rationalized on the basis of a “technical and trivial charge of misbranding,” given the “present inadequate Federal law” [14]. Technically an elixir should contain alcohol, the FDA claimed; Massengill’s product did not.

The FDA first targeted Massengill’s distribution branches. On October 19, Campbell telegraphed San Francisco’s FDA chief [13]:


Meanwhile, in Bristol, FDA agents Klumpp and Ford pushed Massengill to issue more explicit telegrams to all elixir consignees, given that the company’s previous wires conveyed no sense of the product’s toxicity or the emergency of situation. The follow-up telegrams, which were sent to all those listed as having received shipments from the company’s headquarters or 1 of its 3 branches, now included the warning, “PRODUCT MAY BE DANGEROUS TO LIFE” [15].

The large job of taking Massengill’s elixir out of the hands of consumers was forecasted by a quick inventory of product remaining at the company’s Kansas City distribution center (which was the source of the elixir in Tulsa). FDA inspector Leo J. Cramer found a little more than 4 gallons left of the 40 gallons made there. In addition, the company’s initial telegrams resulted in the return of 27 unopened pint bottles; 21 opened pint bottles, some of which contained as little as 4 ounces; and a 1-gallon bottle that was about 5/6 full. Optimistically the tally left approximately 30 gallons unaccounted for. After this disheartening inventory, the local production manager told the inspector “that if harmful effects had resulted from the use of Elixir Sulfanilamide…they were due either to improper dispensing or from the use of other drugs in connection with this product” [16].

At Massengill’s San Francisco branch, the FDA’s local chief inspector found that, of the nearly 30 gallons shipped from Bristol (in pints, gallons, or samples), more than 4 gallons of the elixir, mostly in pint containers, had been distributed regionally between September 23 to October 13. These were shipped to a dozen pharmacies, several physicians offices, and one hospital. Some shipments went to nearby Oakland, but most were dispersed to small towns scattered throughout the middle of California. Two pints each were shipped to Meeker, Colorado, and Eugene, Oregon. On the morning of October 19, only 2 1-pint bottles had been returned from drug stores [17,18].

Massengill’s New York branch in Greenwich Village had sent out 21 pints of the approximately 8 1/2 gallons it received from Bristol. From September 19 to October 11, these pint bottles were shipped throughout New York, Connecticut, and Pennsylvania to a handful of physicians or druggists and 1 hospital.** In addition, several bottles were sent to a Massengill distributor in Puerto Rico, and 30 salesman samples had also been shipped. Although Massengill’s branch manager, Athel W. Price, knew of the elixir recall, he claimed that did not know the reason until he was told by the visiting FDA inspectors [19].

When the FDA showed up on the afternoon of October 18 to the New York office, Price was initially cooperative; however, the following day, he put up considerable resistance to an on-site inspection for the remaining elixir. His stubbornness could only be broken by a telegram (GIVE GOVERNMENT AGENTS FULL INFORMATION DO NOT CONCEAL ANY FACT) and a phone call from the home office, but not before he tried the limited patience of New York City health inspectorswho, by this time, were also on the scene. As payback, the city agents confiscated, not only Price’s remaining lots of elixir, but all of his other sulfanilamide products (tablets, capsules, and ampules). When Price asked the FDA inspector to intervene, the on-site agent declared that he could only honor the independence of the 2 regulatory bodies [19].

Back in Tulsa, physicians witnessed a small medical victory. Eight-year-old John T. “Jack” Voorhees was recovering after receiving a total of 2 ounces of Massengill’s elixir for a sore throat. Like the other Tulsa victims, Voorhees experienced symptoms of nephritis but “did not pass into complete anuria.” In news reports, doctors attributed his recovery to aggressive oral hydrationnamely the consumption of 1 gallon of water and 2 quarts of fruit juice daily. Local reports also indicated that Tulsa’s experimental guinea pigs were now “near death” after receiving the elixir [20].

And papers finally confirmed rumors of elixir-related deaths in the St. Louis area, after Fishbein officially announced the news. Without knowledge of the Tulsa deaths, a pathologist had sent the following case report to the AMA journal on October 19, with the “thought that this information should be in the hands of as many physicians as possible, and The Journal was the best means of accomplishing this end” [21].

In the last several days I have seen four deaths in patients using a product called “Elixir of Sulfanilamide” and sold by Massengill & Company.

These patients, all Negroes, were treated by a Dr. [H. H.] Weathers of East St. Louis, Ill. In all he has given the drug to about thirty people, but of the six people treated recently four are dead and have come to autopsy. One is expected to die at any time, and one may recover.

All have had similar symptoms: vomiting and diarrhea, subnormal temperatures, slow respiration, anuria, edema of the face, hands and feet, a progressive anemia and then death.

All four autopsies have shown the same findings; pulmonary edema, marked nephritis with hemorrhage into the cortex of the kidney, marked hemorrhage into the pericardium, mucosa of the stomach and duodenum and into the serous surfaces of lung and liver. The liver is pale, edematous and enlarged. Microscopic sections have not as yet been completed.

* Reports circulated that an identical product was being marketing by the Merrill Company of Cincinnati. (FDA correspondence. John L. Harvey to Western District Stations. October 20, 1937.)

** One shipment, to the Ira Shapiro Co. in New York City, was made on behalf of the Winthrop Chemical Co. Winthrop then sent Massengill’s product to its Albany laboratories for analysis [19].

1. Schoeffel EW, Kreider HR, Peterson JB. Chemical examination of Elixir of Sulfanilamide-Massengill. J Am Med Assoc. 1937;109:1367.

2. Deaths following Elixir of Sulfanilamide-Massengill. J Am Med Assoc. 1937;109:1367.

3. Geiling EMK, Coon JM, Schoeffel EW. Preliminary report of toxicity studies on rats, rabbits, and dogs. J Am Med Assoc. 1937;109:1532-1536. These data were consistent with concurrent experiments conducted by the FDA’s chief pharmacologist, Herbert O. Calvery. See also a final, follow-up report from the University of Chicago investigators: Geiling EMK, Cannon PR. Pathologic effects of Elixir of Sulfanilamide (diethylene glycol) poisoning: a clinical and experimental correlation–final report. J Am Med Assoc. 1938;111:919-926.

4. Probe started in deaths of Tulsa children. Tulsa Tribune. October 15, 1937; p 1 col 6.

5. Death answer may be late: Tulsa investigators are to be thorough. Tulsa Tribune. October 16, 1937; p 1 col 5.

6. Parascandola J. The Public Health Service and Jamaica ginger paralysis in the 1930s. Public Health Rep. 1995;110:361-363.

7. Manufacturers seek to recall drug shipments: Tulsa deaths bring editorial comment in medical men’s journal. Tulsa Tribune. October 18, 1937; p 1 col 4, p 3 col 1.

8. Associated Press. Drug preparation blamed in deaths. New York Times. October 19, 1937; p 27.

9. Finality of AMA report resented: doctors here continue laboratory work with drug. Tulsa Daily World. October 19, 37.

10. Associated Press. Tulsa medical group acts. New York Times. October 19, 1937; p 27.

11. Associated Press. Shipments of fatal drug are seized by federal food body. Daily Capital News (Jefferson, Missouri). October 20, 1937; p 10 col 6.

12. FDA correspondence. Letter from W. G Campbell to Chiefs of Districts. October 18, 1937.

13. FDA correspondence. Telegram from W. G. Campbell to FDA, San Francisco, California. October 18, 1937.

14. Associated Press. Drug fatality case is traced to elixir. New York Times. October 20, 1937.

15. Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937. The exact text of the telegram sent to all consignees listed as having received shipments of the elixir from the company’s Kansas City, New York, and San Francisco branches: IMPERATIVE YOU TAKE UP IMMEDIATELY ALL ELIXIR SULFANILAMIDE YOU MAY HAVE DISPENSED. PRODUCT MAY BE DANGEROUS TO LIFE. RETURN OUR EXPENSE.

16. FDA correspondence. Letter from Leo J. Cramer to Central District Chief. October 18, 1937.

17. FDA correpondence. Telegram from W. G. Campbell to FDA, San Francisco. October 20, 1927.

18. FDA correspondence. Letter from R. B. Bork to San Francisco Chief. October 19, 1937.

19. FDA memorandum. Charles Hyak. October 21, 1937.

20. New deaths spur inquiry: four die in Illinois; Tulsa boy recovering. Tulsa Tribune. October 19, 1937; p 1 col 2, p 4 col 7.

21. Hagebusch GE. Necropsies of four patients following administration of Elixir of Sulfanilamide-Massengill. J Am Med Assoc. 1937;109:1537-1539.

bmartin (80 Posts)

A native East Tennessean, Barbara Martin is a formerly practicing, board-certified neurologist who received her BS (psychology, summa cum laude) and MD from Duke University before completing her postgraduate training (internship, residency, fellowship) at the Hospital of the University of Pennsylvania in Philadelphia. She has worked in academia, private practice, medical publishing, drug market research, and continuing medical education (CME). For the last 3 years, she has worked in a freelance capacity as a medical writer, analyst, and consultant. Follow Dr. Barbara Martin on and Twitter.