Ethics: April 2009 Archives

Since 1937, there have been at least 8 episodes of fatal mass poisoning caused by the oral ingestion of diethylene glycol-tainted drug products; although none has occurred in the United States.

In the summer of 1969, 7 children (ages 6-31 months) died in the area of Cape Town, South Africa, after receiving one or both of 2 liquid sedatives (Pronap or Plaxim). The products were made by the same pharmaceutical firm, which had substituted diethylene glycol for propylene glycol (the latter being an FDA-approved solvent for drugs, cosmetics, and food). Attempted treatment included rehydration, correction of metabolic acidosis, peritoneal dialysis (in 2 cases), and life support.

In 1986, 14 inpatients in a Bombay (Mumbai) hospital died of acute renal failure after receiving in-house glycerin therapy. The glycerin—which contained 18.5% diethylene glycol, 51% polyethylene glycol, and 9% glycerin—was purchased by the hospital through intermediary brokers, who had bought the product on the cheap from an industrial producer in India. Treatment with sodium bicarbonate, various diuretics, and dialysis (in 12 cases) was unsuccessful.

Between June and September of 1990, 47 children died at a Nigerian teaching hospital after ingesting paracetamol syrup that was tainted with diethylene glycol. Treatment consisted of rehydration and correction of acidosis, but none underwent dialysis. All died within 2 weeks of admission. (In a related incident, 109 Nigerian children died the same year after consuming ethylene glycol-tainted cough syrup.)

Beginning in 1990, a significant rise in the incidence of unexplained renal failure in Bengalese children was believed to be due to the ingestion of various brands of paracetamol elixir that were tainted with diethylene glycol. At least 67, and as many as 272, children were affected. After the government banned the sale of paracetamol elixirs in December 1992, pediatric hospitalizations for unexplained renal failure dropped by 84%.

In 1992, 29 people in Argentina died of acute renal failure as a result of consuming diethylene glycol-tainted propolis syrup. A study of 15 adult victims revealed a "good correlation" between the amount of diethylene glycol ingested and the anion gap. Syrup samples contained 65% diethylene glycol (w/v), and victims took between 5 and 20 mL. Therefore, the lethal dose of diethylene glycol for adults was estimated at 0.014-0.170 mg/kg body weight.

An increase in the incidence of unexplained renal failure in Haiti led to the discovery of diethylene glycol-induced disease in 109 children (ages 1 month-13 years) from the fall of 1995 to July 1996. The ingestion of locally made acetaminophen syrups (Afebril and Valodon) was significantly associated with the condition. Analysis revealed that these formulations were made with diethylene glycol-contaminated glycerin, which had been imported from a Chinese manufacturer by way of Europe. The median concentration of diethylene glycol in the final products was 14.4% (range, 1.2%-19.6%). The median estimated dose of consumed diethylene glycol (n = 32) was 1.34 mL/kg (range, 0.22-4.42 mL/kg), but toxic doses were often less than 1 mL/kg. The death rate among the children who remained in Haiti was 98% (85 of 87*). Among the 11 children transported to the United States for treatment, 8 survived, and 7 recovered renal function.

In 1998, 36 Indian children developed acute renal failure after consuming a diethylene glycol-tainted cough syrup, which was produced by a company in Gurgaon; 33 of these children died despite undergoing peritoneal dialysis. How and when diethylene glycol entered the syrup was unknown at the time of the medical report.

In the fall of 2006, an investigation into cases of unexplained renal failure in Panama ultimately led to the discovery of more than 100 deaths due to the consumption of cough syrup made with Chinese-imported glycerin. The glycerin, which was sold to the Panamanian health service, was incorporated into 260,000 bottles of the medicine. In its investigation, the New York Times traced 46 barrels of imported glycerin stock, labeled as 99.5% pure but containing ~24% diethylene glycol, from a Panamanian port to the Taxing Glycerine Factory in the Yangtze Delta (by way of Barcelona). A Panamanian government report released last year concluded that at least 174 people were poisoned and 115 were killed (66% death rate) as a direct result of the contaminated syrup (Bogdanich W. Panama releases '06 report on poisoning. NYT, February 14, 2008).

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The toxicity of diethylene glycol is believed to be due to its metabolite, HEAA—which is produced by the enzymatic activity of ADH and ALDH. But how HEAA produces cellular dysfunction is unclear, according to Kraut et al. Like other alcohols, diethylene glycol is rapidly absorbed from the gut and has a low volume of distribution (0.5 L/kg). Animal studies indicate that 30%-50% of diethylene glycol is eliminated through the liver, and 50%-70% via the kidneys. Although toxic and lethal doses in humans have been estimated in some reports of mass poisoning, susceptibility to diethylene glycol appears to vary widely for reasons that remain unknown.

Animal studies also indicate that the administration of ADH and ALDH inhibitors (eg, fomepizole) may prevent the production of HEAA, and dialysis (with or without fomepizole) has been used successfully in patients with diethylene glycol poisoning. Dialysis is not only instituted for renal failure, but may remove diethylene glycol and its toxic metabolite.

ADH = alcohol dehydrogenase; ADLH = aldehyde dehydrogenase; HEAA = 2-hydroxyethoxyacetic acid.

* Follow-up was unavailable for 11 children.

Depicted chemical structure of diethylene glycol from Wikipedia.

January 10, 1939

: Three months after Dr. Samuel E. Massengill pleaded guilty to 174 counts of adulterating and misbranding Elixir Sulfanilamide, he was elected president of the Bristol Chamber of Commerce in a show of municipal confidence [1].

January 17, 1939: Former Massengill chemist and creator of Elixir Sulfanilamide, Harold Cole Watkins, 58, shot himself in the heart with a .38 caliber automatic pistol at 7:30 am in the kitchen of his Bristol home. Watkins had "retired" from the Massengill company 6 months earlier; the circumstances of his departure from the firm, whether voluntary or by request, were not clear. Although the death was reported a suicide, Watkins's wife claimed that the self-inflicted gunshot was accidental. In addition to his widow, Watkins was survived by 2 sons [2-4].

January 19, 1939: Massengill sales manager Gordon Fletcher reported that the company had paid out more than $500,000 in injury claims regarding Elixir Sulfanilamide [4].

April 14, 1939: In the District Court for the Northeastern Division of the Eastern District of Tennessee (at Greeneville), judge George C. Taylor* ordered Massengill to pay $8500** and court costs for the wrongful death of Earl L. Beard, who had died in a Tulsa hospital on October 16, 1937, after consuming Elixir Sulfanilamide. The suit was brought by the deceased's mother, Mrs. Norris T. Beard of Oklahoma City [5]. (The plaintiff, represented by Swingle and Hardin of Greeneville, originally filed the suit in September 1938 and asked for $50,000.)

April 19, 1939: A civil suit brought by the widow and heirs of John W. Gibbons of Mt. Olive, Mississippi, against Massengill was dismissed without prejudice in the same federal court. Gibbons, 71, had died October 9, 1937, after consuming 2.5 ounces of a 4-ounce elixir prescription, which had been written by his physician, Archie Calhoun. (The civil complaint, originally filed on October 1, 1938, asked for a total of $45,000 in damages and a jury trial.) The plaintiffs moved for a voluntary nonsuit, most likely on the basis of deposition testimony. One of the deceased's physicians testified that Gibbons had died of coronary thrombosis, which was believed to be independent of diethylene glycol toxicity. A treating urologist also suspected prostate cancer. The plaintiffs were required to pay court costs [5].

April 20, 1939: A civil complaint was filed against Massengill in the same federal court by Claire B. Williams, widow of Fred L. Williams, a Florida resident who had died October 12, 1937, after consuming probably 6 ounces of Elixir Sulfanilamide. The plaintiff, represented by Caldwell, Brown, and O'Dell of Bristol, Tennessee, demanded $10,000 and court costs. Three months later, the case was settled out of court for an undisclosed amount [5].

November 3, 1939: A civil complaint was filed against Massengill in the same federal court by Sylvia Cauley, who alleged the wrongful death of her husband, Emanuel Cauley. Cauley, a Florida resident, had died October 16, 1937, after consuming 5 ounces of Elixir Sulfanilamide. The plaintiff, also represented by Caldwell, Brown, and O'Dell, demanded $10,000 and court costs. Massengill defended the suit by arguing that the 1-year Tennessee statute of limitations applied, not the 2-year limit in Florida. Judge Taylor agreed, and the suit was dismissed in March of 1940. The plaintiff was ordered to pay court costs [6].

Also in November, Theodore Klumpp, Chief Medical Officer of the FDA, and Herbert Calvery published their report on the Elixir Sulfanilamide deaths, which included information from 353 persons who consumed the drug. Data were "sufficient" to conclude that Elixir Sulfanilamide was the primary cause of 105 deaths; although in "several" cases, concomitant illness may have contributed to mortality. The drug was most often prescribed for the treatment of gonorrhea (39% of deaths) or sore throat (23% of deaths). The average time of survival from the first elixir dose to death was 9.4 days (range, 2-22 days) [7].

The most common, initial symptoms were nausea and vomiting—symptoms which may have been life saving for some by prompting discontinuation of the drug. Headache was also frequently experienced. These symptoms were followed by a progressive decrease in urine output, which was often associated with considerable back, flank, and/or abdominal pain. Signs of uremic encephalopathy then emerged, leading to coma, convulsions, and death. In only a few cases were laboratory studies performed (eg, South Carolina case report).

The average elixir dose taken by the deceased, both children and adults, was somewhat higher than that taken by the 248 survivors, although there was considerably overlap in the range of doses taken by the 2 groups.

Group	Mean Dose, cc	Minimum Dose, cc	Maximum Dose, cc
Deceased
7 months-16 years    (n = 34)	52.7 ± 32.8	5	120
17-78 years    (n = 71)	98.6 ± 37.9	20	240
Survivors
1-14 years    (n = 48)	44.2 ± 30.2	3	105
≥15 years    (n = 200)	83.7 ± 57.5	1	240

March 8, 1940: A civil complaint was filed against Massengill in the District Court for the Northeastern Division of the Eastern District of Tennessee (at Greeneville) by the administrator for Pearl Locklair. Locklair died October 4, 1937, in Charleston, SC, after consuming an unknown quantity of Elixir Sulfanilamide. The plaintiffs asked for $35,000 in total damages. Massengill defended the complaint by arguing that the 1-year Tennessee statute of limitations applied, not the 6-year limit in South Carolina. Judge Taylor agreed, and the suit was dismissed on August 7, 1940. The plaintiff appealed to the US Court of Appeals for the Sixth Circuit [5,8].

January 9, 1942: The US Court of Appeals for the Sixth Circuit reversed the lower court's decision, and the wrongful death suit for Pearl Locklair was remanded for trial [8]. 

May 25, 1942: Massengill's petition to the US Supreme Court in the wrongful death suit for Pearl Locklair was denied [9].

September 2, 1942: In a settlement with the administrator for Pearl Locklair, Massengill agreed to pay $1500, plus $150 in expenses and court costs [5].

* The same judge who presided over the government's adulteration and misbranding case against Massengill. The Beard judgment was the result of a non-jury decision.

** $7500 for loss of support and other pecuniary loss and $1000 for pain and suffering.

1. Massengill heads Bristol chamber. Bristol Herald Courier. January 11, 1939; p 5, cols 1-3.

2. H. C. Watkins victim wound. Bristol News Bulletin. January 17, 1939; p 1, col 6.

3. Harold Cole Watkins victim of gunshot. Bristol Herald Courier. January 18, 1939; p 2, col 2.

4. Maker sulfanilamide formula is suicide. Greeneville Sun. January 19, 1939; p 1, col 6.

5. Greeneville, TN, court records; obtained from NARA. 

6. Cauley v S. E. Massengill Co. 35 F 371 (TN Dist 1940).

7. Klumpp TG, Calvary HO. The toxicity for human beings of diethylene glycol with sulfanilamide. South Med J. 1939;32:1105-1109.

8. Wilson v Massengill. 124 F2nd 666 (US App 1942).

9. Massengill v Wilson. 316 US 686; 62 S Ct 1274; 86 L Ed (US SC 1942).

In a way that only grand tragedy can instigate reform, the rising number of deaths due to Massengill's Elixir Sulfanilamide mobilized a formerly apathic press and public to demand revision of the 30-year-old Wiley statute. The principal House opponent of Copeland's first S. 5 bill, B. Carroll Reece (R-TN), was particularly stung by the fact that Massengill's company resided in his district, and reformists were only too happy to point out this fact.

But passage of S. 5, while facilitating the FDA's ability to seize bottles of Elixir Sulfanilamide, would not have prevented the disaster. The bill, unlike the original Tugwell measure (S. 1944), had no licensing provisions for new drugs entering the market, as the League of Women Voters was quick to note. This fact was verified by Representative Lea with Paul Dunbar of the FDA, and the California legislator requested an appropriate amendment to rectify the omission.

Copeland was way ahead; on December 1, he introduced S. 3073, which stated that any manufacturer who sought to market a new drug must submit the drug's components, testing records, an explanation of the manufacturing processes, labeling examples, and drug samples (if requested) to the Secretary of Agriculture. Five months later, the Senate passed S. 3073 unanimously, after a few minutes of half-hearted objections.

However, the old sticking point of the government's advertising purview remained, manifest in the Wheeler-Lea bill (S. 1077)—which was intended to expand the FTC's control over food, drug, and cosmetic advertising. After heated debate, the House had passed the measure in January of 1938, and the Senate had followed 2 months later. The bill was signed into law on March 21. The FDA was "apoplectic," given that the act not only stripped the agency of any marketing control over drugs but required proof of fraudulent intent after the fact (like the 1912 Sherley amendment).*

By the spring of 1938, Lea, after increasing pressure, finally brought S. 5 no. 2 out of House committee, but not before he had slipped in a section that allowed for numerous appeal reviews for alleged violators in any one of the 85 federal district courts. Lea's rationale was to provide a check on the Secretary of Agriculture's regulatory power, but reformists were having none of it. Consumer and national women's organizations were outraged and bombarded the President with pleas to intervene. FDR did so, although somewhat cryptically. Publicly he gave no indication that he would sign the Copeland-Chapman bill if Lea's appeal section was included; privately he informed the House committee of a forthcoming veto.

So in June, a legislative compromise was hammered out in conference: industry's appeals would be restricted by circumstance and court venue. And in a conciliatory mood, the conferees also accepted stronger language on the subjects of label disclosure, standard variations, and seizures. The conference report was quickly passed by the Senate and House, and FDR signed the new Food, Drug and Cosmetic Act on June 25, 1938—12 days after Massengill pleaded not guilty to federal charges of mislabeling and misbranding Elixir Sulfanilamide and 8 days after an exhausted Royal Copeland collapsed on the Senate floor and died later that evening. He was 69.

The Act that Copeland championed would become effective 1 year later.

* Regulation of prescription-drug advertising was finally transferred to the FDA after passage of the Kefauver-Harris Drug Amendments in 1962.

Chief source: Jackson Co. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

In relentless pursuit of food and drug law reform, Copeland introduced a second version of S. 5 (S. 5 no. 2 or S. 5-1937) into the Senate in December 1936. A companion bill in the House, HR 300, was launched concurrently by Virgil Chapman. Important differences between the 2 bills rested in clauses defining seizure rules, drug-strength variations, and penalties for false advertising; but the main point of contention remained the FDA's proposed control over drug marketing. Industry—which was now becoming anxious for a federal law that would override the increasing tangle of state drug laws*—was evidently split on the point of advertising purview by the FDA and the FTC.

With the input of the FDA and the influence of the all-important women's groups (who had the backing of Eleanor Roosevelt), S. 5 no. 2 was strengthened in committee on the points of misbranding and seizures. The bill was passed by the upper chamber on March 9, 1937, and forwarded to the House, where the FTC had historically exerted its influence to retain advertising control.

The power struggle between the FDA and the FTC was further complicated by the simultaneous introduction of the Wheeler-Lea bill, which was drafted to expand the FTC's authority. The measure (S. 1077), spearheaded by Senator Burton Wheeler (D-MT) and Representative Clarence Lea (D-CA), was sent to the House after Senate passage on March 29, 1937. The timing meant that both the Copeland-Chapman bill and the Wheeler-Lea bill would be debated in House committee at the same time—in this case, mid-May of 1937. Political maneuvering between the Chapman and Lea camps would keep both measures in House limbo when Massengill's Elixir Sulfanilamide hit the market during the fall of 1937.

* From January 1935 to October 1936, 92 drug-related laws had passed in 39 states.

Chief source: Jackson Co. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

In the summer of 1935, the House conducted hearings on Copeland's latest food and drug bill, S. 5. Chairing the hearings was Representative Virgil Chapman (D-KY), a lawyer and newcomer to food and drug reform. Chapman, however, was quick on the uptake. He rapidly grasped the thorny issues that impeded the passage of effective reform—particularly the conflict between the FTC and the FDA for advertising control. S. 5's best chance for passage, he concluded at the end of the hearings, lay in a quiet education campaign, until sufficient House support was confirmed.

In the meantime, Chapman held the bill in committee, where efforts were made to strengthen the drug variation and seizure clauses. But the chief question remained: Who would control drug advertising, the FTC or the FDA? The President offered little in the way of decisive input, and after 9 months, Campbell's agency ultimately lost its fight for purview over advertising.

On May 22, 1936, the House version of S. 5 was finally reported out of committee, with a minority dissent (led by Virgil Chapman) on the advertising section. In mid-June, this version of the bill was passed in the House, after which time Senate and House conferees met to hammer out a compromise on the amendments—and specifically, on the issue of advertising oversight. After considerable wrangling, the final bill stipulated that all health-related advertising would be regulated by the FDA; the FTC would oversee the marketing of food and cosmetics.

Although the Senate accepted the compromise, fierce opposition to the advertising agreement was led in the House by lawyers B. Carroll Reece (R-TN) and Samuel D. McReynolds (D-TN). Both men represented districts in East Tennessee, the home of influential FTC member Ewin L. Davis. Reece's district was also the headquarters of the S. E. Massengill Company, in Bristol.* Their arguments, which drew on FTC loyalty and fears of Tugwell, were persuasive; in the summer of 1936, the House killed S. 5 in an overwhelming vote.

* In November 1937, Massengill would deny any attempted influence on Reece regarding passage of a food and drug law: "I have never, directly or indirectly, opposed any proposed Food and Drug law. I never spoke to Hon. Carroll Reece, my congressman, about the one now pending, nor, to my knowledge, did any of my friends do so."

Chief source: Jackson Co. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

Photograph of Virgil Chapman from the Biographical Directory of the US Congress.

Shortly after S. 2800 died in committee, Senator Copeland (newly reelected, no thanks to FDR) began drafting yet another food and drug bill, this time without the input of Tugwell or the FDA. In January 1935, Copeland introduced his new reform measure, S. 5, into the Senate. Concessions made to industry in this bill were even heavier than those in Copeland's previous drafts.

Requirements for drug labeling were considerably more lenient; formulas merely had to be filed with the Secretary of Agriculture, which would avert label disclosure. The list of diseases prohibited from advertising was shortened, and FDA seizures for misbranding were limited to 3 actions on a single product. Products that varied from the recognized Pharmacopeia standard were also permissible.

Once again, FDA leadership recognized Copeland's new draft as a general improvement on the 1906 law and a realistic compromise. S. 5, like its predecessors, also had the reluctant support of the all-important women's organizations and professional pharmaceutical groups. However, the AMA found the bill too weak. The more militant consumer groups were also unhappy with S. 5, as were proprietary drug manufacturers—whose Congressional lobbyists would become instrumental in the new bill's fate.

Public hearings in March of 1935 portended the early passage of S. 5, and the bill was reported out of committee on the 22nd, despite opposition efforts from Senators Josiah Bailey (D-NC) and Joel Bennett Clark (D-MO). The 2 senators' obstructive efforts were probably informed by their respective state's interests. North Carolina was the home of the Vick Chemical Company, maker of VapoRub; the Lambert Pharmaceutical Company, of Listerine fame, was located in Missouri.

On April 1, S. 5 came up for Senate debate, and Copeland expected a speedy vote. However, Bailey and Clark had other ideas. In an attempt to gain opposition support, the 2 senators extended the debate for 8 days, arguing for 1) modified definitions of "misbranding" and "adulteration" that would significantly undermine the FDA's right to seize products and 2) the FTC's continued control over advertising. The former argument was carried in a bill amendment that, to Copeland's frustration, was passed by the Senate on April 8.

The 2 sides now viewed this juncture of S. 5's journey through the Senate as a legislative flash point. To avoid further compromise on the bill, Copeland was ready to call for a vote; Bailey and Clark wanted to return the bill to committee to attack the advertising issue. To the relief of reformists, the tension was defused by procedural maneuvering on an unrelated bill, and S. 5 was placed in limbo back on the senatorial calendar—but at least it was safely out of the hands of a dickering committee.

A compromise on the Bailey amendment—instigated by FDR with Tugwell's influence—would be reached between Copeland and the opposition the following month. Multiple seizures of a product by the FDA would by allowed if there was "probable cause" that the product was "imminently dangerous." But the FDA and women's groups remained disheartened by the compromise, because the existing 1906 law stipulated no such restrictions. Nevertheless, these proponents of reform continued to support the passage of S. 5, while hoping to strengthen the seizure language before the bill became law.

On May 28, 1935, Copeland's S. 5 was brought to a vote and passed by the Senate. The bill was now at the mercy of the House.

Chief source: Jackson CO. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

Photograph of Royal S. Copeland from the Biographical Directory of the US Congress.

Toward the end of 1933, Senator Royal Copeland realized that, if a new food and drug bill had any chance of passage, revisions would have to be made in response to the powerful opposition from trade groups. In February of 1934, Copeland introduced his second rewrite of S. 1944 (the notorious "Tugwell bill"), now called S. 2800, into the Senate.

This "sane, sensible, workable bill," as Copeland described it, provided 4 major concessions to industry, 3 of which directly affected drug manufacturers. First, full disclosure of ingredients would no longer be required on proprietary drug labels; instead, the manufacturer need list only specified components of his product. Second, publishers of false advertising would not be held legally liable; however, they would be required to identify those who produced the false copy to the Department of Agriculture. And in response to concerns that previous bills gave unrestricted regulatory power to the government, the revised bill also allowed for the creation of advisory boards to appeal alleged violations.

But as is the case with most compromises, no one was particularly happy with S. 2800. Trade groups, while appeased, to some extent, on the issue of advertising, predicted continued economic gloom with so much regulation of their business in the midst of the Great Depression. Tugwell himself, despite the fact that the revised bill still carried his name, was also unhappy with the concessions—to the point of publicly calling the bill "very disappointing" and losing interest altogether in its passage. This opinion was echoed by proponents of the original Tugwell bill, consumer lobbyists, who described the new measure as "emasculated" and a godsend to quacks.

The FDA's leadership, while harboring reservations about concessions in S. 2800, was still in favor of its passage. Chief Campbell was sufficiently pragmatic to understand that potentially unpleasant compromises would have to be made if food and drug reform were ever to become reality. The sentiment was generally shared by the AMA, which urged its members to support the bill's passage by contacting their congressmen. Influential women's groups also backed S. 2800, while continuing to lobby for the restoration of original components of the Tugwell bill.

Unfortunately Tugwell's sour opinion of S. 2800 would inform the President's apathy for its passage. And without FDR's leadership to champion the bill through Congress, S. 2800 died a death of indifference at the end of the 1934 Congressional session. FDR's coolness toward S. 2800 was likely political, given the ongoing friction between Senator Copeland and the Administration's New Dealers. And the President's ambivalence toward the bill probably had something to do with the FTC's struggle with the FDA over the control of advertising. In the President, the FTC found a sympathetic ear to its concerns for retaining its purview over advertising. In the coming years, contention between the 2 government groups over advertising control would become a major obstacle to legislative reform.

Chief source: Jackson CO. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

Photograph of Royal S. Copeland from the Biographical Directory of the US Congress.

By 1933, serious shortcomings in the US Pure Food and Drug Act of 1906 (the so-called Wiley statute) were evident. First, the old law did not provide for the government regulation of cosmetics (relevant language was dropped from the proposed law in 1900). Second, the law did not adequately cover the regulation of patent medicines. Specifically the definition of dangerous drugs was outdated, given the pharmaceutical innovations of the early 20th century, such as the introduction of barbiturates. Third, language concerning the definition of food adulteration was vague and ambiguous; and fourth, the law provided no control over false advertising.**

Amendments to the 1906 act, such as the 1912 Sherley Amendment, attempted to rectify some of these shortcomings. Congress specifically enacted the amendment to supersede the 1911 Supreme Court decision in US v Johnson, which determined that drug "misbranding" only applied to statements regarding the product's identity and related properties (eg, its strength, purity, etc) and not to statements regarding the product's proposed curative powers (even claims as outrageous as curing cancer). The Sherley Amendment characterized the misbranding of drugs as statements that were both false and fraudulent. However, the wording of the law was unfortunate. The amendment required that the government prove fraudulent intent on the part of the manufacturer—a nearly impossible standard.

Public outcry, from both disinterested parties and dubiously motivated commercial sources*** (as well as muckraking journalists), against the inadequate oversight of food, drugs, and cosmetics led, in 1933, to Congressional hearings and an internal investigation of the Food and Drug Administration. And the FDA, headed by Kentucky lawyer Walter G. Campbell, was only too happy to concede deficiencies in the 1906 law. Perhaps the most important outcome of these events was the spark of interest created in Senator Royal S. Copeland (D-NY), a physician and former New York City health commissioner, to reform the old statute.

In the Spring of 1933, Senator Copeland became the Congressional backer of the so-called Tugwell bill, a measure initially drafted by Rexford G. Tugwell, then Assistant Secretary of Agriculture, with considerable input from the FDA's Campbell. Senate Bill 1944, as it was labeled, would no longer place the burden of proving the manufacturer's fraudulent intent on the government, and misbranding would be defined as any therapeutic claim on the label that was "contrary to general medical opinion." Palliative claims would be distinguished from those that promised cure, and drug manufacturers would have to disclose the ingredients of their products. The charge of adulteration would be applied to any product that was dangerous to health, when used according to the manufacturers directions. Last, provisions relating to drugs would also encompass medical devices.

Support for S. 1944 was mixed. Not surprisingly, most of the drug industry wanted the bill defeated and argued that the measure gave far too much discretionary power to the government. The response from the American Medical Association was curiously lukewarm and the influential Consumers' Research (a frequent critic of the FDA) labeled the bill as too weak. Support for the Tugwell bill was to be found, however, among women's groups—particularly the difficult-to-ignore League of Women Voters.

The FDA engaged in a concerted publicity campaign to promote S. 1944—through favorable press coverage, speaking engagements, the Department of Agricultures' "National Farm and Home Hour," posters, and the agency's notorious "Chamber of Horrors" exhibit. The exhibit was a popular, traveling display of the most worthless, fraudulent, and dangerous drug products on the US market, like Crazy Crystals, Koremlu (a thallium-containing depilatory cream), Marmola, and radioactive Radithor. However, these government-back efforts were ultimately stifled by charges that the FDA was violating the 1919 Deficiency Appropriation Act. The act prevented government agencies from lobbying their causes to Congress. Consequently organized opposition to S. 1944 gained steam, after the FDA's publicity campaign for reform was silenced. Toward the end of 1933, FDA Chief Campbell became convinced that Congressional compromise of the bill was inevitable.

* Not as boring as you think.

** And the Federal Trade Commission was hamstrung in its power to prosecute false advertising given the 1931 Supreme Court decision in the case of the FTC v Raladam Co.

*** Specifically chemist and crude-ergot peddler Howard Ambruster.

Chief source: Jackson, Charles O. Food and Drug Legislation in the New Deal. Princeton, NJ: Princeton University Press; 1970.

On October 3, 1938, Dr. Samuel E. Massengill, head of the S. E. Massengill Company of Bristol, Tennessee-Virginia, pleaded guilty in a federal court to 112 counts of adulteration or misbranding of Elixir Sulfanilamide [1]. The US District Attorney, James B. Frazier, recommended that the defendant be fined $150 for each count—a recommendation that the federal judge, George C. Taylor, accepted. Massengill was consequently fined a total of $16,800 (~$252,826 in 2009), the largest fine posed to date under the 1906 Pure Food and Drugs Act. No jail time was handed down.*

According to news reports, the doctor was required to pay one third of the fine immediately and the remainder within 30 days [2]. Judge Taylor also announced that Massengill would plead guilty to 62 counts of adulteration or misbranding that were pending in a Kansas City, Missouri, federal court [1]. The fine stemming from these charges would total $9300 [3].

The government had prepared for the testimony of "numerous world famous experts in physiology and toxicology" at the trial, but these witnesses were told not to appear, given Massengill's change in plea [1]. According to Massengill's General Counsel, Frank DeFriece, Massengill initially offered $100 per shipment, or $9000, in plea negotiations with the government [4]. DeFriece rationalized any plea bargaining and the avoidance of further litigation on the basis of "the welfare and best interests of the company."

Invoking the government's slim chances of conviction, additional negative publicity for the company, and the expense of continued litigation, DeFriece further defended his boss's decision—that is, as long as the government's fine wasn't too hefty.

Massengill and his advisors feel that in view of the very narrow grounds upon which the government has based its case its chances of conviction, or even of sustaining its indictment, are very slim, and about all that the government would get out of it would be the satisfaction of further advertising the calamity of Elixir Sulfanilamide to the nation. Even in this event it would be expensive litigation. And if the government obtains a compromise judgement and fixes a reasonable fine, it certainly wins its point, and the amount of the fine ought not to be a matter of so great importance. It is felt that, in view of the immense amount of money which has been expended in the adjustment of claims both valid and invalid which have been made against the Massengill Company on account of Elixir Sulfanilamide, the payment of any large fine would seriously cripple the future business of the Company, and unless it is the purpose of the government to make an effort to wipe out the Company entirely, it is impossible to find the reason for the infliction of so great a sum as a penalty.

Following the plea, Time magazine reported that the S. E. Massengill Company had expended more than $150,000 in the settlement of damage suits brought by survivors of elixir victims [5]. (By mid-1938, the company maintained that all claims, except for two, had been negotiated out of court and that only 2 civil suits had been filed. One of these had been settled [4].) 

Also according to company accounts, Frank DeFriece, Massengill's General Counsel and son-in-law, personally visited the close relatives of elixir victims and, often, their physicians in an effort to negotiate out-of-court settlements. During these extended road trips, DeFriece frequently avoided claimant's lawyers and county officials who had issued arrest warrants for Massengill and his top executives. DeFriece claimed to have made friends with most of the bereaved and relayed a story (as told by his son) of the welcome he received in the "deep South" from the brother, a gas station attendant, of one of the elixir victims [6].

A young man came out to serve them and, immediately upon seeing his customer, said something like, "By golly, it's you, Mr. DeFriece. I'm glad to see you." After introducing his wife, Frank DeFriece asked about the man's wife (by name!) and his children. In answering, the man gave some details on them and several other relatives and invited both of them to "come over for supper tonight—nothing special, you know. My wife will be glad to have you and meet the missus."

DeFriece reportedly declined the invitation.

* It's not clear that jail time was or could be considered in this case.

1. Bristol man submits to charge violating Pure Drug Law. Greeneville Sun. October 3, 1938; p 1, cols 6-8; p 6, cols 5,6.

2. Associated Press. Massengill fined total of $16,800. Bristol Herald Courier. October 4, 1938; p 9, col 6.

3. FDA correspondence. Letter from Theodore G. Klumpp to Mr. H. H. Smith. November 29, 1938.

4. Pully P. Masengill Brother Company and the S. E. Massengill Company, 1807-1971. Knoxville, Tenn.: Tennessee Valley Publishers; 1996. Appendix 7.

5. Massengill pays. Time. October 17, 1938.

6. Pully P. Masengill Brother Company and the S. E. Massengill Company, 1807-1971. Knoxville, Tenn.: Tennessee Valley Publishers; 1996. Appendix 5.

On September 7, 1938, attorneys for Samuel E. Massengill filed a demurrer, or formal objection, to each of the 166 charges of adulteration or misbranding of Elixir Sulfanilamide, which were filed in the Greeneville, Tennessee, federal court. The demurrer overtly capitalized on the inadequacies of the Pure Food and Drugs Act of 1906.

With respect to charges of adulteration, the government contended that the "purity" of Elixir Sulfanilamide "fell below the professed standard or quality under which it was sold." Specifically the product's name indicated that the antibiotic was dissolved in a nonpoisonous solvent, which was, in reality, poisonous. Massengill responded that the charges did not violate the Pure Food and Drugs Act, because "adulteration...is not anywhere so defined under said Act, nor by any interpretation thereof..." The doctor was evidently drawing on the Act's nonspecific definition of drug adulteration, which was described as differing "from the standard of strength, quality, or purity as determined by the test laid down in the United States Pharmacopoeia or National Formulary official at the time of investigation."

On the counts of misbranding, specifically with respect to the use of the name "Elixir Sulfanilamide," the government charged that Massengill had used the term "elixir" in a misleading fashion by failing to dissolve sulfanilamide in a nonpoisonous solvent. The doctor, however, rebutted that the Pure Food and Drugs Act did not specify such a definition for misbranding—an argument that could be floated with some merit. The Act defined a misbranded drug as one that was "an imitation of or offered for sale under the name of another article," or if the contents of an original package were replaced by other contents. The government, however, could cling to legislative wording that also defined misbranding as failing to label a product with "the quantity or proportion of any alcohol, cocaine, heroin, alpha or beta eucaine, chloroform, cannabis indica, chloral hydrate, or acetanilide, or any derivative or preparation of any such substances contained therein." Diethylene glycol could be loosely construed as an alcohol derivative (although this rebuttal was contrary to the basis for the FDA's seizure of Elixir Sulfanilamide).

Last, Massengill countered the government's charges of misbranding on the basis of the sticker pasted to the elixir bottle's stopper, which read "Quality Pharmaceuticals." Massengill argued that the words have "no reference to the contents of the bottle to which it was attached," and added, "It referred solely and alone to the S. E. Massengill Company as pharmacists, and is a sort of slogan."

The federal judge, George Caldwell Taylor, evidently agreed with Massengill's third argument and, on September 30, dismissed all of the government's charges, 54 in total, relating to the doctor's use of the "Quality Pharmaceuticals" sticker. The decision left 112 counts of adulteration or misbranding, concerning 56 interstate shipments of Elixir Sulfanilamide, for Massengill to defend at trial.

Massengill's partial victory in federal court was dampened by civil action brought in a Fresno, California, superior court on September 19. A $25,000 damages complaint was filed by Mr. and Mrs. Orvin C. Kutz, parents of the deceased 5-year-old Orvin Kutz, Jr., against Samuel E. Massengill, the manager of Massengill's San Francisco branch, the Fresno druggist who sold the elixir, and 2 drug wholesalers. Counsel for the Kutz parents included California Congressman Bertrand W. Gearhart.

Sources:

United States v Massengill (ED TN 1938).

Death elixir is basis for big damage action. Fresno Bee. September 20, 1938; p 1, col 8.

In late October 1937, gossip columnist Louella Parsons revealed that both Warner Brothers and film executive B. P. Schulberg were in preproduction stages for 2 separate films that would dramatize the "shocking elixir deaths" [1].

Warner Brothers had bought the rights to the muckracking novel of investigative journalist Samuel Hopkins Adams, The Clarion. The book, published in 1914, was an expose of the fraudulent advertising of patent medicines. Screenwriters would incorporate the recent elixir-related deaths into the film, Parsons reported, which was to star Dick Foran (The Petrified Forest) and newcomer Ann Sheridan as the "romantic leads." The working title for Schulberg's production was Permit to Kill, with Edward Arnold (Diamond Jim) in a starring role.

Although the New York Times reported later that the Warner Brothers film title was changed to One Hundred Million Suckers, with a screenplay by Larry Kimble and Ring Lardner, Jr., neither film appears to have made it to production [2].

The elixir-related deaths were conveyed in nonprint media through NBC's radio broadcast of The National Farm and Home Hour, which was produced by the US Department of Agriculture, and William Randolph Hearst's "News of the Day"* newsreel, which was shown contemporaneously in movie theaters [3,4]. While attending the cinema in Flushing, New York, a pleasantly surprised FDA chemist praised the well-conceived "dramatic presentation" and the "clear and distinct voice" of FDA chief Walter G. Campbell in a letter to the FDA's New York station. The chemist described the production's scenes from memory:

I. S. E. Massengill's plant.

II. Dr. Calhoun [of Mt. Olive, Mississippi] (?) one of the physicians that had prescribed the Elixir, and a nurse who had taken some of the Elixir but was still alive.

III. The laboratory of the American Medical Association at Chicago, showing a chemist working on a distillation apparatus and then holding in a graduate some of the distillate which was described as being the deadly ingredient.

IV. The same A.M.A. laboratory protraying[sic] a chemist using a Spectrographic apparatus.

V. Mr. Campbell's office door.

VI. Scene showing Mr. Campbell picking up a phone, and instructing all agents to immediately stop all other work and to concentrate on location the Elixir, to be seized wherever found. In this scene Mr. Campbell did the talking rather than the commentator.

* Released by Metro-Goldwyn-Mayer.

1. Parsons L. Ford will direct Haycox in new film for Sam Goldwyn. Modesto Bee and News-Herald. October 31, 1937.

2. Screen news here and in Hollywood. New York Times. March 18, 1938; p 23.

3. FDA correspondence. Letter from W. G. Campbell to Chief, Central District. January 31, 1938.

4. FDA correspondence. Letter from D. M. Walsh to Chief, New York Station. October 29, 1937.

Public domain screenshot of Ann Sheridan from Wikipedia.