Ethics: March 2009 Archives

Several weeks after Samuel E. Massengill pleaded not guilty to federal charges of adulteration and misbranding in the case of Elixir Sulfanilamide, the FDA received word of the company's possible defense [1]. A "confidential informant," who had obtained information from a pharmaceutical chemist and "close friend" of Dr. Massengill, told FDA Assistant Chief Paul B. Dunbar that the firm had acquired at least 660 affidavits from elixir customers who attested to their "entire satisfaction" with the product.

According to Dunbar's source, Massengill would contend that those who suffered elixir-related deaths used the medication "recklessly and in excess of the dosage recommended." When given under competent medical supervision in the advised amounts, the company would argue, the product caused no harm.

In addition, Massengill would attempt to show that sulfanilamide alone could have caused the deaths. A 15% mortality rate with the antibiotic, as quoted by the company, would compare favorably with the firm's calculated elixir-related death rate. The latter statistic would be acquired by dividing the estimated number of reported deaths, approximately 100, by the total number of cases of use per the company (660 + 100, or 760) for a death rate of 13%.

Dunbar also learned that Massengill was worth about $11 million (>$165 million in 2009) and had expended about 5% of his net worth (>$7 million) on the tragedy. Although Massengill regretted the deaths, he believed himself to be "blameless," the chemist reported. Moreover, Massengill and others in the Bristol area considered the doctor to be a public benefactor. Last, while admitting to be a friend of Massengill, the chemist had no respect for the elixir's creator, Harold Cole Watkins, who was described as "unreliable."

1. FDA correspondence. Letter from P. B. Dunbar to Drug Division. July 23, 1938.

At a closed federal hearing on January 12, 1938, in Cincinnati, attorneys for the S. E. Massengill Company denied that the firm's Elixir Sulfanilamide was adulterated or misbranded. Massengill's counsel Ruby D. Garrett of Kansas City and Robert Burrow of Bristol presented a written denial—which was forwarded to Washington, where a "prompt decision" was expected with respect to prosecution [1]. The federal hearing had been postponed twice to permit the company "to gather all the facts" before their presentation [2].

On February 17, the FDA's records concerning the interstate shipments of Elixir Sulfanilamide were forwarded to the Justice Department, along with recommendations for an expedited prosection [3,4]. FDA chief Walter G. Campbell wrote the following letter to then-Solicitor Mastin G. White, explaining the rationale for the charges against Samuel E. Massengill and his chief chemist, Harold Cole Watkins.

...The business of the firm is largely interstate so that Watkins had a responsibility in manufacturing the article to see that it complied with the Food and Drugs Act. The use of the article in various parts of the country resulted in the death of numerous patients because of the presence of a poisonous ingredient, diethylene glycol, used as a vehicle or solvent for the sulfanilamid[sic]. On the shipments from Kansas City, Samuel E. Massengill should be named as sole defendant. Although 5 of the 30 samples shipped from Kansas City bore code numbers of two batches made at Bristol, the remaining 25 samples were taken from Kansas City shipments representing a batch made at Kansas City with which Harold C. Watkins had no connection in the actual manufacture. It is accordingly felt that Watkins should not be included as a defendant on the Kansas City shipments.

[...]

The charges on which citation was issued are as follows:

Adulterated: Its purity falls below the professed standard or quality under which it was sold, namely, "Elixir Sulfanilamide", since the article is not an elixir of sulfanilamid but is a solution in a mixture of diethylene glycol and water.

Misbranded: (1) The statement on the label, "Elixir Sulfanilamide", is false and misleading as applied to an article containing sulfanilamid dissolved in diluted diethylene glycol.

(2) The statement on a sticker attached to the stopper of the bottle "Quality Pharmaceuticals" is false and misleading as applied to an article consisting of a solution of sulfanilamid in diluted diethylene glycol and labeled "Elixir Sulfanilamide."

To both the physician and pharmacist the term "elixir" when associated with the name of a drug means that the drug is dissolved in a palatable, aromatic, harmless solvent.

We will be in a position to adduce medical and pharmaceutical testimony to the effect that the term "Elixir Sulfanilamide" means a solution of the sulfanilamid, having the medicinal properties of sulfanilamid alone. We will be able to adduce clinical testimony that the principal effect of this product, "Elixir Sulfanilamide", when administered to patients, was due to the highly toxic ingredient, diethylene glycol; as a matter of fact, the use of this preparation resulted in nearly 100 deaths during the period in which the product was on the market. In other words, this article fell below the professed standard under which it was sold, that is, "Elixir Sulfanilamide", a solution having the therapeutic action of the drug sulfanilamide, in that its principal action was that of an acute poison.

The misbranding charges are practically restatements of the adulteration charge, and are based on the same considerations. We believe it highly important in presenting this case that the testimony of doctors whose patients actually died be introduced as conclusive evidence of the poisonous properties of the article. It is assumed that the allegations to be drawn on the basis of the charges of adulteration and misbranding mentioned will permit the introduction of evidence that the diethylene glycol present is a toxic ingredient and an acute poison. We suggest that the counts in the information be so framed as to permit the introduction of such evidence.

The large number of shipments involved in this case entailed numerous investigations to establish interstate shipment and identity of samples. Inevitable delays occurred, therefore, before citation[s] could be issued. Citation notices issued on December 8, 1937, setting December 20, 1937, as the date for the hearing. A postponement of the hearing was then requested by the defendant and granted by the Administration. Hearing was actually held on January 12, 1938, and since that time we have been actively engaged in preparing the case for transmission to you.

It is highly important that the further preparation of the case be expedited, first, because of the extensive public interest in this matter and, second, because of the gravity of the offense. In transmitting these records we wish to urge the importance of an early preparation of the information. The Food and Drug Administration is ready to cooperate with you to the fullest extent in expediting these cases.

Of note, the distributed elixir shipments from San Francisco (which resulted in one death, that of 5-year-old Orvin C. Kutz, Jr., of Fresno, California) and those from New York City were considered a continuation of the violations originating from the company's Bristol headquarters. Therefore, the FDA did not advise prosections against Massengill in these jurisdictions [5,6].

The compilation of witnesses for the prosecution would be assigned to Cincinnati-based FDA Inspector William T. Ford and the task of locating them to Inspector W. B. Simmons [7]. "Wherever possible," Campbell advised, "physicians who administered the Elixir and lost patients as a result will be used; first, as dealer witnesses; second, to testify to the medical concept of the term 'Elixir Sulfanilamide'; and third, as to the toxic character of the product." Campbell believed that most of these doctors would voluntarily testify on the basis of their duty as public servants. Those unwilling would be subpoenaed.

At least one former employee of the S. E. Massengill Company came forward to the FDA as a witness against the firm [8]. C. (possibly Clarence) Falstrom had worked from 1925 to 1933 in Massengill's Kansas City "laboratory," a word he placed in quotes in a letter to the FDA. Falstrom claimed that he "saw many abuses which were in violation of the laws." "They don't even have a registered pharmacist in Kansas City!" he declared and predicted, "You will see the day again when they violate the law." Falstrom went on to describe how the company prepared for on-site inspections:

When an inspector would call for samples they would have some all "fixed" for him so they passed OK. On one particular case they were told to discontinue selling a certain batch of Fl. Ext. Ergot. USP. This stock was hidden away for a time. When the inspector called for a sample of Ergot later they told him they were temporarily out of stock but this particular batch of Ergot was sold just the same. I would like to appear as a witness against them but I am afraid it would actually hurt me on future jobs.

Although intrigued by Falstrom's letter, Campbell believed that the former employee's testimony would not be particularly useful in the Elixir Sulfanilamide litigation, given that Falstrom had been terminated from the company at least 4 years before the incident. 

On March 11, The Kingsport Times reported that Massengill was preparing to contest a suit for more than $120,000 in a Greeneville, Tennessee, federal court regarding the death of Oklahoman Earl Lee Beard. Beard, 25, died 5 months earlier after consuming an unknown amount of an 8-ounce prescription for Elixir Sulfanilamide. The suit was brought by the victim's divorced mother, Mrs. Norris Beard [9].

On June 6 in Kansas City, a federal complaint by US District Attorney Maurice M. Milligan alleged that Massengill had violated the Pure Food and Drugs Act on 93 counts [10]. Five days later, US District Attorney James B. Frazier, Jr, confirmed to news sources that the government had instituted criminal charges against Massengill in the US Federal Court in Eastern District of Tennessee (Greenville). This complaint alleged violation of the Pure Food and Drugs Act on 166 counts, each relating to an interstate shipment of "mislabeled" and "misbranded" Elixir Sulfanilamide.* Frazier explained that the complaint, in this case, was equivalent to an indictment and had recommended that Massengill be placed under arrest, with a $25,000 bond.

Massengill's General Counsel and son-in-law, Frank DeFriece, stated that if the government prevailed in its cases against his boss, the doctor could be fined a total of $261,000 and sentenced to 261 years in prison [11]. "This ridiculous situation," DeFriece explained, "is made possible in a simple misdemeanor offense because [the] alleged offense is the second one."** DeFriece went on to predict the fallout from the federal prosecution, which he likened to "simple persecution."

So far as Massengill is personally concerned perhaps the Department [of Agriculture] figures he hasn't suffered enough, but there is another angle. Continuous gouging at the business will, of course, eventually kill it. When that is done it may be that Massengill's financial ruin would be pleasing to some, but to do it destroys the source of living for 350 families all over this country, and also destroys a substantial business in Tennessee-Virginia, of which the entire South may be justly proud. Is such animus fair to these people, who had absolutely nothing to do with it, and who are paying for houses and subsistence, all of which may be suddently wiped out!

On June 13, Dr. Massengill pleaded not guilty after being arraigned and posting bond in Bristol for his appearance at the September 19 term of the federal court in Greeneville [12].

Twelve days later, FDR signed into law the newly passed Food, Drug, and Cosmetic Act—legislation that was largely forged through a historically gridlocked Congress at the urging of an enraged public. The law specifically required manufacturers, like Massengill, to demonstrate the safety of any new drug to the FDA before its sale.

* Specifically the charge stated that the drug was sold as being suitable for human consumption when it was not.

** The first being related to Massengill's sale of understrength Tincture of Aconite.

1. Associated Press. Denial is issued on adulteration. Kingsport Times. January 12, 1938; p 1, col 6.

2. Associated Press. Deny adulteration of fatal Elixir of Sulfanilamide. Times Recorder (Ohio). January 13, 1938; p 1, col 8.

3. FDA correspondence. Letter from P. B. Dunbar to J. O. Clarke. February 24, 1938.

4. FDA correspondence. Letter from W. G. Campbell to Solicitor. February 17, 1938.

5. FDA correspondence. P. B. Dunbar to Chief, Eastern District. February 11, 1938.

6. FDA correspondence. W. G. Campbell to Chief, Western District. February 19, 1938.

7. FDA correspondence. W. G. Campbell to Chief, Central District. February 4, 1938.

8. FDA correspondence. W. G. Campbell to Chief, Central District. January 31, 1938. 

9. Massengill will face damage suit. Kingsport Times. March 11, 1938; p 3, col 2.

10. International News Service. US accuses maker of sulfanilamide. El Paso Herald-Post. June 3, 1938; p 1, col 4. According to Massengill's General Counsel, Frank DeFriece, a capias was issued for Massengill in Kansas City on information charging 95 shipments, with 3 counts per shipment. DeFriece also claimed that, because Massengill was a resident of Tennessee, the Kansas City court could not serve process on the defendant. See Pully P. Masengill Brothers Company and the S. E. Massengill Company, 1807-1971. Knoxville, Tenn.: Tennessee Valley Publishers; 1996: Appendix 7.

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

12. Massengill enters plea of not guilty. Greeneville Sun. June 14, 1938; p 1, col 5.

In response to my concerns regarding the recently published (online) autism-biomarker study by Geier et al in the Journal of Neurological Sciences, editor-in-chief Robert Lisak asked 2 "distinguished scientists"* to review the article, as well as my letter to the editor and the response of Geier et al. While the new reviewers did not recommend that the paper be retracted (for some inexplicable reason), they did have "significant concerns with parts of the paper," the study's methods, and the authors' interpretation, wrote Dr. Lisak.

Neither reviewer addressed my concerns about the specific metabolite values of Geier et al nor the possibility of subject overlap in a similar Neurochemical Research article; however, Reviewer #1 chided the authors for not providing norms for laboratory values, if available. Reviewer #2 expressed concerns with the authors' lack of intra-assay standards when measuring urinary porphyrins, how these values compare with those from normal controls, and sample collection (both blood and urine). Information regarding control subjects—such as the exact number, gender breakdown, and reasons for testing—were also lacking. Both reviewers stated that Geier et al should have matched subjects and controls for age and sex, when analyzing their results.

Both reviewers also suggested that Geier et al were far too eager to ascribe their results (specifically the presence of urinary porphyrin metabolites) solely to mercury toxicity. They did not consider other possibilities, such as immune conditions, infection, or exposure to other heavy metals. Geier et al did not control for these factors, Reviewer #2 noted, and concluded, "The authors are clearly not objective. They continually refer to the results as indicative of exposure to mercury...not so."

* These unnamed scientists did not originally peer review the manuscript before publication.

In December 1937, while continuing to "deny all liability and responsibility for deaths of persons whose relatives claim they took the sulfanilamide compound," the S. E. Massengill company distributed a lengthy question-and-answer statement to their "friends and customers" regarding Elixir Sulfanilamide. The statement, the firm claimed, was intended "to correct the false statements that have been circulated" about the product, with the following qualification: "For legal reasons, we cannot at this time give some information that we would like to give" [1].

Among the 29 questions posed and answered by the company were several concerning the inclusion of diethylene glycol in Elixir Sulfanilamide. Massengill defended the use of the substance on the basis of its solvency and, perhaps unbelievably, its relative lack of toxicity when compared with the common anti-freeze ingredient, ethylene glycol. While attempting to dissociate diethylene glycol from ethylene glycol, the company indicated, nevertheless, that the former substance, if ever used as an anti-freeze, "should not reflect unfavorably upon it"; both alcohol and glycerin had been used for the same purpose. Moreover, ethylene glycol was a solvent in hypodermic injections that had been approved by the AMA, the firm argued.*

Massengill then endorsed its control department, claiming, "[W]e have six graduate pharmaceutical chemists in our employ who spend their entire time in the control and testing of our products before they are placed on sale," and denied that Elixir Sulfanilamide was rushed into the marketplace. When the company asked itself, "Why did your tests not show any bad results?" it replied, "At this time we cannot say, but undoubtedly we will have the answer when it can be shown why many using the identical lots sold had most excellent results." Massengill proceeded to indicate that the reason for elixir-related fatalities may never be known:

Is your company making an effort to ascertain what did happen to cause the ill effects?
Yes, our own chemists are continually working on the problem, and we also have independent sources doing similar work. After working on the problem for several weeks, one body of scientists makes the statement: "It is probable that no chemist or pharmacologist will ever be able to determine exactly what happened," and added, "Theory and guess work on the part of all who are working on this problem is all that has developed at the present time." The latest report of another one of our connections is as follows: "We are making an effort to determine the exact cause of the present trouble, and shall keep you advised of the progress of the work as soon as it has advanced to the stage where any reasonable interpretation of the results obtained can be made."

Last, the company floated the idea that deaths due to the consumption of its Elixir Sulfanilamide were actually the result of adverse drug-drug interactions. The only known drug that could be safely taken with the antibiotic was sodium bicarbonate, Massengill claimed, and a number of drugs—saline cathartics, sulfates, analgesic coal-tar derivatives, and many laxatives—were either probably or definitely contraindicated with sulfanilamide.

* The company cited the 1935 edition of the AMA's New and Nonofficial Remedies, page 132, and the 1937 edition, page 116.

1. Pully P. Masengill Brother Company and the S. E. Massengill Company, 1897-1971. Knoxville, Tenn.: Tennessee Valley Publishers; 1996; Appendix 6.

In an effort to initiate some kind of corrective, but arguably foolhardy, dialog with the editors of the Journal of the Neurological Sciences—who recently published an autism-biomarker study by Geier et al (see critical posts here and here, for example)—I submitted a Letter to the Editor that identified (what I believe to be) serious flaws in the published work. My letter was published online by the journal March 9 (DOI: 10.1016/j.jns.2009.02.309 [subscription required]). The response letter submitted by Geier et al was published online March 19 (DOI: 10.1016/j.jns.2009.02.305). 

Without reproducing the letters, which would violate copyright, I can describe my published criticisms of the JNS article by Geier et al and the authors' responses—which, in my opinion, are compelling only in their creativity.

Criticism 1: Geier et al presented a cherry-picked introduction of published information that causally connects environmental exposure to mercury with autism, while implying support for this link from the Centers for Disease Control and Prevention.

But in their introductory discussion, Geier et al neglected to acknowledge the known pharmacokinetic differences between environmental mercury (primarily methylmercury) and ethylmercury; the growing series of epidemiologic studies that have found no association between ethylmercury-containing vaccines and the risk of autism; and authoritative statements made by the CDC, the Institute of Medicine, and the World Health Organization that deny any persuasive evidence for an autism-mercury link.

Instead of acknowledging these facts, however, Geier et al respond that my comments imply "only isolated statements by researchers associating mercury poisoning with autism." This is a different argument altogether. I don't contend that there's limited published information associating mercury exposure with autism. There's a lot of published crap out there contending all sorts of unfounded nonsense. Certainly Geier et al themselves have contributed liberally to the medical literature that attempts to link mercury exposure with autism and, unfortunately, they have found sympathetic publishers.

My point is that Geier et al refuse to acknowledge the facts raised and, specifically, the series of epidemiologic studies that negates an association between mercury exposure (whether by methylmercury or ethylmercury) and autism. Geier et al completely sidestep this criticism; but moreover, they go on to make a flabbergasting analogy between a mercury-autism relationship and a smoking-lung cancer relationship.

Criticism 2: Metabolite data (specifically for plasma cysteine, plasma oxidized glutathione [GSSG], and plasma total sulfate) of Geier et al are substantially different from values in the literature, including articles cited by the authors themselves.

In their response, Geier et al note that their values for plasma reduced glutathione (GSH) were consistent with those in the published literature. So their initial defense boils down to, "We got 1 out of 4 right." Next Geier et al note that they measured circulating free cysteine, not total cysteine—despite the fact that they cited Han et al as their assay reference, a study providing plasma cysteine values approximately one order of magnitude higher (160-360 µmol/L) than their values (eg, 17.8 µmol/L).* Geier et al go on to cite Mansoor et al (an article not mentioned in their JNS study) as a reference for their cysteine values. In this case, Mansoor et al found a mean plasma reduced cysteine value in their male controls of 14.5 µmol/L, which, in fact, is closer to the cysteine values of Geier et al.

However, Mansoor et al imply that free (ie, non-protein-bound) cysteine exists in both reduced and oxidized forms. So in this case, their mean control value for free cysteine in men would be 14.5 + 88.2, or 102.7 µmol/L. This summed value is consistent with values in other studies, which indicate that the free cysteine level in human plasma is approximately 50% of the total cysteine value and therefore remains substantially higher than the values obtained by Geier et al—for example, 112 µmol/L ± 15.2 in 13 volunteers aged 24-29 years (Guttormsen et al) and 140 µmol/L ± 21 in 10 healthy fasting subjects aged 31-52 years (Suliman et al).

Geier et al then thank me for "raising a question about the units for our [GSSG] measurement." But they claim they had prior knowledge (before submission of my letter to the JNS editor) of a typographical error and state that the units should have been µmol/L, not nmol/L.

Let me just say that this claim is—How can I put it?—very interesting. As documented at this blog, I e-mailed Henry Sershen, associate editor of Neurochemical Research on October 14, alerting him to the discrepant metabolite values of Geier et al, including those for plasma GSSG (which were similarly published in JNS—see Criticism 3):

The associate editor of Neurochemical Research, Henry Sershen, forwarded my e-mail to Mark Geier (anchor author), who reviewed the information and responded to Dr. Sershen that the published values for GSSG were consistent with those of James et al in a 2004 study (which was also cited by Geier et al). In fact, a review of this study reveals that the printed mean value for plasma GSSG in control children, 0.32 nmol/L ± 0.1 (range, 0.11-0.43 nmol/L), is very similar to the control value of Geier et al (0.35 nmol/L ± 0.05). But it is also very different from the control value published by James et al in their 2006 study, 0.24 µmol/L ± 0.1, or 240 nmol/L ± 100.

To that end, I e-mailed Dr. James asking for clarification of the plasma GSSG values in her articles, and she responded that the units in the 2004 article were incorrect and should have been µmol/L, not nmol/L. Consequently this correction negates Dr. Geier's rebuttal that his values for plasma GSSG are consistent with those of James et al.

So after defending his original GSSG units and citing James et al as a confirmatory reference (which was acknowledged to be incorrect by the lead author), Dr. Geier (as the anchor author of Geier et al) now claims that the GSSG unit notation—made in both the Neurochemical Research and JNS articles—was a typographical error.

Last, it should be noted that Geier et al, in their letter response, do not address their discrepant values for total plasma sulfate.

Criticism 3: The possibility of significant overlap between subjects in the JNS study and those in a nearly simultaneously published study by Geier et al in Neurochemical Research is raised. If overlap existed in the 2 study populations, it should have been acknowledged by the authors.

To this point, Geier et al flat out deny that their JNS data were previously published (although, they do not specifically address any overlap of subjects between the 2 studies). This claim is made despite the fact that their control metabolite values (including standard deviations) are identical between the 2 publications, and the fact that their metabolite values in Neurochemical Research (n = 38) and JNS (n = 28) are very similar.

Plasma Measurement	Mean ± SD
	ASD Subjects of Geier et al (n = 28)	ASD Subjects of Geier et al (n = 38)	Control Values of Geier et al
Cysteine, µmol/L	17.8 ± 9.5	17.8 ± 8.3	23.2 ± 4.2
GSSG, nmol/L	0.46 ± 0.16	0.48 ± 0.16	0.35 ± 0.05
Total sulfate, µmol/g protein	924 ± 245	934 ± 252	1930 ± 184

Criticism 4: Geier et al failed to control for age-related differences in urinary porphyrin excretion, given that their subjects ranged in age from 2 to 16 years (for a rationale, see Minder and Schneider-Yin).

Geier et al rebut that I did not read "Table 1" from their study, which compared urinary porphyrins with similar mean and age ranges. They claim, therefore, that subject age should not have affected their results to any significant extent. However, Geier et al fail to note that the age ranges of these groups were still very wide—eg, 3-13 years. 

Geier et al then write that 3 "independent" studies from 3 continents "have now demonstrated that porphyrinuria is concomitant with [autism spectrum disorder]." One of these studies is, not surprisingly, from Mark and David Geier, who obtained their porphyrin data from the Laboratoire Philippe Auguste. The author of another autism-porphyrin study is, in fact, at this very laboratory. 

* In a previous post at this blog, the possible distinction between total cysteine values and free cysteine in the work of Geier et al was addressed.

By mid-December 1937, the S. E. Massengill Company had made out-of-court settlements in "about a dozen" cases of elixir-related deaths. Massengill's Kansas City attorney, Ruby D. Garrett, reported that the company intended to dispose of all claims that it regarded as justified before they could make it to court. He added that the company, which was solely owned by Dr. Massengill, had no insurance to cover death claims resulting from the use of its products. The firm's assets consisted solely of its drugs, some real estate, and its income-raising sales force, the attorney stated [1].

Garrett stressed that settlements would continue "purely on a basis of good faith," but that "we will continue to deny all liability and responsibility for deaths of persons whose relatives claim they took the sulfanilamide compound" [2]. However, he also stated that "a number" of claims were unjustified: some were presented by survivors whose relatives did not even consume Elixir Sulfanilamide; in other cases, the decedent would have died anyway, he proposed. Garrett provided an anecdotal example to the Tulsa Daily World:

Several doctors told me and my investigators that deaths had been attributed to sulfanilamide erroneously, due to the widespread publicity regarding the fatal cases...One woman took an elixir which she thought was sulfanilamide because she developed all the symptoms of sulfanilamide poisoning. Later it was found that she had taken a harmless cough medicine and she had recovered.

In no case, Garrett publicly declared, could Massengill's product be conclusively proved as the cause of death. Claimants would probably receive greater financial compensation by settling, he argued. Bad publicity from the elixir-related deaths would result in reduced income for the company, which would limit the firm's ability to pay off high-dollar court rulings.

The following elixir-related settlements were publicized in contemporary news reports:

Matilda Schroeder, widow of William M. Schroeder of St. Louis, received $2000 [3].

Thomas M. Hobson, father of 8-year-old Kathleen Hobson of Tulsa, received $1000 [4].

Mrs. Maise Nidiffer, mother of 6-year-old Joan Marlar of Tulsa, received $1250 [4].

The parents of 5-year-old George Nixon, of East St. Louis, received $1000 [1].

The parents of 4-year-old Maurice Slaughter, of East St. Louis, received $1000 [1].

The family of Alexander A. Brooks, 70, of East St. Louis, received $1000 [1].

Ellis Black, the husband of Gertrude L. Black, 38, of East St. Louis, received $1500 [1].

The family of Joseph L. Henry, 60, of East St. Louis, received $1500 [1].

In 2 unidentified cases in Mississippi, settlements were made for less than $300 each [5].

Addie Kyte, widow of 38-year-old William A. Kyte, of Knoxville, Tennessee, settled for an unknown amount [6].

Other claims against Massengill, which may or may not have been settled, are listed:

Mayme Welch Miller, wife of Charles W. Miller, 25, of Memphis, TN, asked for $50,000 in damages [7].

As a prelude to lawsuits, a Tulsa court appointed administrators in the cases of Millard O. Wakeford, father of 5-year-old Millard Wesley Wakeford ($6000 claim); George P. Sheehan, father of 6-year-old Michael S. Sheehan ($6000 claim); J. M. Sumner (of Leonard, OK), father of 2-year-old Robert "Bobby" Sumner ($6000 claim); and Mrs. Norris T. Beard (of Oklahoma City), mother of Earl L. Beard, 25 (undesignated amount) [8,9].

The wife of Willie Badger (25?) of Scotia, SC, was represented by a Hampton attorney, according to FDA letters [10,11].

The father of Edward (B. E.) Walker, Charles D. Walker of Enterprise, AL, was represented by a Montgomery attorney, according to FDA correspondence [12]. 

On December 15, 1937, simultaneous citations were issued in Kansas City, KS, Cincinnati, OH, and New York City for Massengill to appear before FDA officials on Monday, December 20, and show why the agency's information on the elixir-related deaths should not be turned over to the Justice Department. The citations covered 32, 52, and 4 instances of interstate shipments of Elixir Sulfanilamide in the respective cities [13].

N.B.: According to an online inflation calculator, $1000 in 1937 = $14,735.63.

1. FDA newspaper clippings. Five elixir death claims settled here. St. Louis Post-Dispatch. December 28, 1937.

2. FDA newspaper clippings. US agents push new drug inquiry. Tulsa Daily World. December 16, 1937.

3. FDA newspaper clippings. Drug firm paying on sulfanilamide elixir claims. St. Louis Post-Dispatch. December 10, 1937.

4. FDA newspaper clippings. Sulfanilamide maker pays. Kansas City Times. December 22, 1937.

5. FDA newspaper clippings. $2000 claim paid for elixir death of St. Louis man. Star-Times. December 10, 1937.

6. FDA correspondence. Letter from G. P. Larrick to Lindsay, Young & Atkins. March 4, 1938.

7. Associated Press. $50,000 is asked in 'elixir' death. Atlanta Constitution. November 13, 1937; p 9. Miller's widow filed suit against Massengill and the Memphis drug store that sold the elixir over the counter.

8. Two new moves in elixir suits. Tulsa Daily World. November 4, 1937.

9. Associated Press. Claims damages from medicine co. Ada Weekly News. November 2, 1937.

10. FDA correspondence. Letter from W. G. Campbell to Armstrong, Cranford, Barker and Bedford. December 14, 1937.

11. FDA correspondence. Letter from W. G. Campbell to George Warren. December 4, 1937.

12. FDA correspondence. Letter from P. B. Dunbar to Hill, Hill, Whiting & Rives. May 2, 1938.

13. FDA newspaper clippings. US agents push new drug inquiry. Tulsa Daily World. December 16, 1937.

Massengill's chief chemist and the creator of Elixir Sulfanilamide, Harold Cole Watkins, maintained (and perhaps informed) the defense of the product, a defense that was gaining at least local steam in November 1937. Writing to the publication Drug Trade News, Watkins claimed that his company had performed its own animal experiments after news of the first elixir-related deaths [1]. "We gave forty times the human dose of the elixir to pigs and they liked it," he wrote to the journal, "They had not, of course, been taking other medicines with it."

In addition to suggesting that the deaths were somehow due to adverse drug-drug combinations, Watkins floated the idea that some of the casualties were actually caused by sulfanilamide itself and not diethylene glycol. Patients may have overdosed on the elixir, or the product was taken in combination with epsom salts or other sulfates, he proposed. Watkins went on to conclude that "[t]he solvent itself [diethylene glycol] had nothing to do with the deaths," despite very recent experimental evidence (performed at the University of Chicago), which indicated the contrary.

Watkins also boasted that he had taken the elixir himself, without consequence, after the first public warning from the AMA: "On Monday [probably October 18] I started taking the elixir, one ounce a day, in two doses, and am still here and writing to you, though I have taken four ounces in four days. Federal men and our men saw me take it." (According to Theodore G. Klumpp, the FDA's chief medical officer, Watkins claimed that he had taken a large swig of diethylene glycol, when Klumpp and inspector Ford first arrived at the company's headquarters in Bristol, Tennessee. Klumpp wrote later that he doubted Watkins's claim [2].)

Stunningly enough, Watkins also cited the study by Haag and Ambrose, "Studies on the physiological effect of diethylene glycol," which was published earlier that year in the Journal of Pharmacology and Experimental Therapeutics [3]. Although the solvent was determined by the authors to be less deadly than ethylene glycol in rats, they nevertheless observed the lethality of the substance, when given intramuscularly, intravenously, or orally to experimental animals.

Watkins further attempted to bolster whatever specious argument he was weaving by noting that the AMA reported no apparent chemical reaction between diethylene glycol and sulfanilamide in its recent distillation experiments of the company's elixir. This finding was raised by the chemist, despite the fact that the AMA found pure diethylene glycol and Massengill's product to be equally deadly in animals, and that pure sulfanilamide in proportional doses was not.

Last, Watkins noted that the use of diethylene glycol—which was "manufactured exclusively by the Carbon and Carbide Chemicals corporation"—in consumer products was not without precedent. The substance had been advertised as preventing throat irritation in a "widely known brand of cigarettes."*

* The use of diethylene glycol as a humectant in cigarettes was promoted by a number of manufacturers, including Philip Morris, in the 1930s and later. For a discussion of cigarette-related health claims in marketing, see Garner MN, Brandt AM. The physician in US cigarette advertisements, 1930-1953. Am J Public Health. 2006;96:222-232. 

1. Details of deadliness of sulfanilamide revealed in comprehensive news story. The Amarillo Globe. November 17, 1937; p 7 cols 2-5.

2. Klumpp TG. FDA report on Massengill Co. October 18, 1937. Cited in Young JH. Sulfanilamide and diethylene glycol. In: Parascandola J, Whorton JC, eds. Chemistry and Modern Society: Historical Essays in Honor of Aaron J. Ihde. Washington, DC: American Chemical Society; 1983:105-125.

3. Haag HB, Ambrose AM. Studies on the physiological effect of diethylene glycol. J Pharmacol Exp Ther. 1937;59:93-100.

The day after the Secretary of Agriculture, Henry A. Wallace, gave his report to the Senate on the Elixir Sulfanilamide deaths, Dr. Massengill claimed that the casualties attributed to his product were being exploited by the FDA in an effort to widen its powers [1,2]. On Saturday, November 27, both the Bristol Herald Courier and the Bristol News Bulletin printed Massengill's statement in full—a scattershot and head-spinning response that defended, among several things, the "elixir" label, the use of diethylene glycol, the "unpredictable effect" of his product, and his support of more stringent food and drug regulation.

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.[*] This proposed bill is not supposed to be aimed to any great extent at manufacturers of drugs for prescription use, but, chiefly, at the advertising of drugs sold to the public. It is to my personal interest that the laws governing the manufacture of drugs be made stringent. I has been evident from the first interview given out by the Food and Drug Administration that they hoped to use this deplorable occurrence to stampede Congress into giving them power they had, heretofore, refused.

The preparation we marketed was just as properly labeled "elixir" as many others of this class on the market and to which no objection has, heretofore, been made. There is no requirement that an "elixir" contain alcohol. The current National Formulary, a government standard, and one of the authorities under which we work, contains two formulas that do not contain alcohol as a part of the menstrum. One of them does not even contain aromatics.

The Elixir Sulfanilamide was not rushed on the market by us before it was tested. I am not defending the preparation, but the several hundred patients who took it with good result is evidence of the unpredictable effect. We had precedent for using a glycol as a solvent. We used the diethylene glycol, which is much less toxic than the ethylene glycol which is used as an anti-freeze mixture. The American Medication Association approved and published in their New and Nonofficial Remedies two formulas for intramuscular injection which contained ethylene glycol as the solvent. The doses recommended are 1-2 teaspoonful.

I am heartily in favor of the passage of the Food and Drug Act now pending in Congress.

One week later, the Sullivan-Johnson County Medical Society, representing 2 East Tennessee counties (which included the city of Bristol), adopted a resolution expressing its "sincere confidence in the integrity of Dr. S. E. Massengill and the products of The S. E. Massengill Company" [3]. The resolution stressed that Massengill's products were only supplied to the professions and not advertised to the "laity." The members of the medical society, which included Dr. Massengill, "deeply regret[ted] the unfortunate occurrence and the unfavorable publicity to which the S. E. Massengill Company has recently been subjected." The sympathetic paper concluded its front page coverage of the medical society's endorsement with the sentence, "Seventy-three 'known' deaths have been attributed to the preparation," placing "known" in quotation marks.

* Likely refers to Senate bill 5-1937, which was foundering in the House in the fall of 1937.

1. Massengill avers false statements made about elixir. Bristol Herald Courier. November 27, 1937; p 1.

2. Dr. Massengill in defense of sulfanilamide. Bristol News Bulletin. November 27, 1937; p 7 col 1.

3. Massengill and firm endorsed by doctors. Bristol Herald Courier. November 2, 1937; p 1.

In mid-November of 1937, the US Senate and House adopted resolutions* asking then Secretary of Agriculture Henry A. Wallace to report on the Elixir Sulfanilamide deaths [1]. Wallace's report, the content of which became widely publicized, was submitted to the Secretary of the Senate, Edwin A. Halsey, on November 25, Thanksgiving morning [2,3].

In his plain-speaking "Letter of Transmittal," Wallace revealed not only the extent of known elixir-related casualties in the United States (93 at the time), but unpacked, for the first time, the chronology of events that led to them. Details included the elixir recipe, the lack of testing before marketing, the wide distribution of elixir shipments, the evasive words of Massengill's first recall telegrams, and the FDA's yeoman efforts to confiscate the poisonous medicine—often in the face of considerable obstruction. And if this information did not sufficiently convey the impact of the tragedy, the full content of a letter written by the mother of elixir victim Joan Marlar to President Roosevelt was added:

Tulsa, Okla., November 8, 1937.

President Roosevelt:

Dear Sir: Two months ago I was happy and working taking care of my two little girls, Joan age 6 and Jean age 9. Our byword through the depression was that we had good health and each other. Joan thought her mother was right in everything, and it would have made your heart feed good last November to have seen her jumping and shouting as we listened to your re-election over the radio.

Tonight, Mr. Roosevelt, that little voice is stilled. The first time I ever had occasion to call in a doctor for her and she was given the Elixir of Sulfanilamide. Tonight our little home is bleak and full of despair. All that is left to us is the caring for of that little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. During her 9 days of illness as we sat by her bed only once did those little eyes lose their dull and unknowing look. Jean and I begged her to look and know us. A smile broke over her face and she laughed aloud with us and as quickly it vanished, never to smile and know us again.

Tonight, President Roosevelt, as you enjoy your little grandchildren of whom we read about, it is my plea that you will take steps to prevent such sales of drugs that will take little lives and leave such suffering behind and such a bleak outlook on the future as I have tonight.

Surely we can have laws governing doctors also who will give such a medicine, not knowing to what extent its danger, and then lying and stealing the prescription they wrote supposedly from a reliable drug store. I don't believe such a doctor has taken his oath in all sincerity. Our lives are not safe entrusted in the hands of such a doctor, for that was my experience to my sorrow.[**]

In my confidence in you I am writing you and hope that you can realize a little of what I am suffering and that you will take steps to prevent such in the future for I realize also there are other homes where hearts are broken such as mine.

It is easy for people to say "Try to think that she died that others might live." It is easier to say when it doesn't strike in your own home.

Enclosed is a picture of the baby I grieve for day and night.

Thanking you and
   Sincerely,

(Mrs.) Maise Nidiffer

Wallace further revealed that 25 seizures of the elixir had been made by federal agents on the basis of misbranding during interstate commerce. Many other lots were confiscated by state agents under state or municipal laws. (For instance, in New York City, a patent medicine could not be sold until the manufacturer had registered the product with the health department and gave details of its ingredients and indications [4].) Wallace assured the Congress (and the public), "Citations are already in preparation for issuance to the manufacturer, in accordance with established procedure, calling on him to show cause why the cases should not be referred to the Federal courts for criminal prosecution."***

The Secretary concluded by recommending the following measures to improve existing drug legislation:

1. License control of new drugs to insure that they will not be generally distributed until experimental and clinical tests have shown them to be safe for use.
2. Prohibition of drugs which are dangerous to health when administered in accordance with the manufacturer's directions for use.
3. Requirement that drug labels bear appropriate directions for use and warning against probable misuse.
4. Prohibition of secret remedies by requiring that labels disclose fully the composition of drugs. [Notably labels of exported US drugs provided this information, owing to foreign laws that required disclosure.]

Congress and the public now informed, the job of replying to Mrs. Nidiffer was left to FDA Chief Walter G. Campbell [5].

My dear Mrs. Nidiffer:

Your letter of November 8 was received and read at the White House and immediately referred to the Food and Drug Administration, which was even then trying by all means in its power to trace down every possible ounce of the poisonous Elixir Sulfanilamide. In sending your letter to me there was transmitted the President's request that your letter be answered.

Believe me when I say, Mrs. Nidiffer, that in the course of my thirty years in the Government service I have never had a more difficult assignment than the President's request to reply to you. Your letter was laid before me during the weeks that we were desperately following up outstanding lots of the Elixir. I have looked at the lovely smiling face of your little girl and I think I realize in some measure your unending sorrow at a needless sacrifice.

The President and the Department of Agriculture, and many enlightened legislators as well as representatives of the public, have been urging with the utmost earnestness for the past four years the passage of a food and drug law which will give more ample protection than our present statute. One of the first actions of both the House and the Senate when they convened for the present special session was to pass resolutions calling upon the Secretary of Agriculture for a report on the Elixir Sulfanilamide tragedy, together with recommendations for legislation which would prevent such catastrophies[sic] in the future. The Secretary's report was delivered to both Houses of Congress on Thanksgiving morning. Your letter was included as a part of the report in the belief that it would impress upon our national legislators, more forcibly than an official recital, the horror of this tragedy and the absolute necessity for national legislation which will make its repetition impossible.

I agree with you it should not have been necessary for your baby to die to arouse public sentiment to the point that proper legislation will be enacted. If it is enacted—and I sincerely believe that there are strong and good men in both the House and Senate who have resolved that laws will be passed which will make a repetition of this tragedy impossible—it may be of some small comfort to you to know that your letter has had a real influence in bringing about this result.

With the most sincere sympathy, I am

Sincerely yours,

W. G. Campbell 

* Senate resolution 194 of November 16, 1937, and House resolution 352 of November 18, 1937.

** According to FDA records, both the druggist at Tulsa's Getman Drug Store and the prescribing doctor, Logan A. Spann, attempted to obstruct the FDA's investigation in this case.

*** A particularly interesting notation made by the Secretary was that the fact that some drug manufacturers had considered making a solution of sulfanilamide in diethylene glycol but had abandoned the idea after learning of the solvent's potential toxicity.

1. The day in Washington. The New York Times. November 19, 1937; p 7.

2. Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937.

3. 'Death drug' hunt covered 15 states. The New York Times. November 26, 1937; p 42.

4. FDA newspaper clippings. City has its own restrictions on sale of medical remedies. Herald Tribune. October 31, 1937.

5. FDA correspondence. Letter from W. G. Campbell to Mrs. Maise Nidiffer. November 30, 1937.

Photo of elixir victim Joan Marlar from Ballentine C. Taste of raspberries, taste of death: the 1937 Elixir Sulfanilamide incident. FDA Consumer. 1981;June:18-21.

As FDA inspectors continued to collect outstanding bottles of Massengill's Elixir Sulfanilamide throughout the country, calls for legislation to ensure the safety of marketed drugs filled the nation's newspapers. Particularly troubling was the fact that the elixir could only be seized legally on the tenuous basis of misbranding—given that an "elixir" technically should include an alcohol solvent. If Massengill's product had been labeled a "solution," no seizure could have been effected by the federal agency.

In the press, the League of Women Voters specifically was highly critical of existing laws and chastised legislators for their historical ineptitude and disregard for public safety [1]:

For four years the league has been vainly urging on Congress adequate regulation of food, drug and cosmetic products. In the face of opposition of special interests, one measure of protection after another has been whittled away from pending bills. The bill that passed the Senate at its last session and was pending in the House had been shorn long since of original provisions that would have protected the public against the tragedies of this elixir.

The women's group referred to Senate bill 5 no. 2, a highly watered-down version of the originally proposed "Tugwell bill" and a revision of the original 1906 Pure Food and Drugs Act. In a November 7 editorial, Washington, DC, journalist Rodney Dutcher concurred that the original revisionist bill, introduced in 1933, had "long since been pulverized by lobbyists and congressional sympathizers." Those called out by Dutcher for the "final emasculation of such shreds of the Tugwell bill" were Senators Josiah Bailey (D-NC), Joel Clark (D-MO), and Arthur Vandenberg (R-MI) [2].

Morris Fishbein, Editor-in-Chief of the AMA's journal, described the series of missteps that led to the scores of elixir-related deaths. He extended blame from the Massengill Company to blindly prescribing physicians [3]:

Who should have made certain of the safety of the preparation if not the purveyor? In the cycle comes first the manufacturer who launched the preparation without proper precaution; second, the detail man who importuned physicians to use the product; third, the pharmacist who was willing to sell across the counter, either on request from the public or on physicians' prescriptions, toxic preparations of secret character, yet whose training is vaunted as a protection to the public. But most serious perhaps after the manufacturer are those physicians who will not heed the warnings concerning the use of proprietary, unstandardized, semisecret remedies.

Fishbein described the ambiguity of the term "elixir," the definition of which "has undergone some changes in the practice of pharmacy" through the use of solvents like glycerin, instead of alcohol. Furthermore, he claimed no legal definition of the term (probably to the FDA's consternation) and urged the US Pharmacopeial Revision Committee or "some group with legal power" to define the word in practice. Last Fishbein acknowledged, "Surely there has been no blacker picture of the inadequacy of our present food and drug laws or the lack of common scientific decency in drug manufacture than that illustrated by this tragic disaster" and likened the current FDA to a hunter stalking a tiger with a fly swatter.

Even industry groups recognized the need for a revision of law in the wake of so many deaths. Editors of the trade journal The Drug and Cosmetic Industry wondered, "Why a comparatively small manufacturer should, in ignorance or carelessness, believe that he alone had suddently discovered a proper answer to a problem which the entire industry was trying to solve is beyond comprehension," and concluded, "The only way in which the industry can properly protect itself against another accident of the same type is for [an] outside agency, such as the government, to have proper control over manufacturers and their products." [4].

Likewise, the Oil Paint and Drug Reporter found the sale of Massengill's Elixir Sulfanilamide "appalling for its evidence of ignorance or greed on the part of some who seek to be entrusted with ministration to the needs of the sick...Why a pharmaceutical manufacturer would use an industrial solvent of unknown pharmacologic activity in the making of a medicine for internal use is beyond comprehension." For the drug industry, the editors advised [5]:

Experimentation is as desirable in pharmacy as it is in medicine. Improved or more acceptable dosage forms of valuable drugs are helpful to the medical profession. It is an important function of [pharmaceutical] manufacturing to provide these. But experimentation with drugs in every connection should be scientific. Empirical trial and error is dangerous, especially when concerned with potent drugs of complex chemical composition and inestimable potential chemical reactivity.

And predictions were made [5]:

Juridical awards of damages for the losses of life will not satisfy the needs for protection of the public...It is inevitable that the "poison elixir" calamity will arouse public sentiment for speedy and closely tightening revision of the Food and Drugs Act [of 1906]. There will be no great difficulty in calling up a pending bill in the special session of Congress. It cannot be denied that revision of the law has been too long deferred. It must be realized that the delay had to be attended with the possibility of increasing demand for still more rigorous prohibitions.

It is to be expected that the public demand for protection will not be satisfied with making it possible to catch a poisonously adulterated drug in commerce, or with classifying the undisclosed presence of a dangerous ingredient as misbranding. The cry will be for formula disclosure and for factory inspection. The drug industry must expect attacks more severe than any it has known.

In its coverage of the national tragedy, Time also noted that the original, revised food and drug bill that had been up before Congress in its last session would have made Massengill liable to federal prosection. The magazine described Dr. Samuel Massengill, the company's chief, as a compounder of "veterinary medicines in a good-sized factory at Bristol, Tenn.," and cited an FDA source for the company's "total lack of testing facilities" [6].

Massengill's local paper, the Bristol Herald Courier took umbrage with the news magazine's critical, and very national, coverage of the recent events. In a pseudonymous opinion piece, the paper—while giving a passing nod to the tragedy of the deaths—defended the scope of Massengill's company and its reputable history [7]. The writer's tone forecasted the level of insular, public defense to be employed by Massengill.

It is deplorable, of course, that any deaths have occurred. But had there been many more deaths, and could they have been traced to the sulfanilamide elixir, the fact would not have warranted Time in publishing an article containing an intimation that the Massengill Drug Company is a small and irresponsible firm. The company is domiciled in a large group of modern buildings, it employs an army of men and women, and it has branch houses in New York, Kansas City, and San Francisco. And thousands of physicians and druggists all over the country will bear testimony to its responsibility.

The article in Time quoted a Federal agent as saying the Massengill Company lacks testing facilities and is careless in the manufacture of drugs. Not by practices of that kind did Dr. Massengill, who holds the degree of M. D., become one of the leading manufacturing pharmacists of the country. He has built up an enviable reputation over a period of forty years, by patient and persevering effort, by sound business judgment and capable management, by close personal attention to the affairs of his company, and by turning out honest products.

The Time article stated that Federal men "confiscated every last flask of the Massengill 'elixir' upon which they could lay their hands." That publication may not have known that with the first report of a death from sulfanilamide, which came from Oklahoma, Dr. Massengill deluged the Western Union office in Bristol with telegrams to his salesmen and others to take every ounce of the elixir off the market. Probably there were few flasks left for Federal men to confiscate.

This column has no means of knowing what constituted the lethal quality of elixir sulfanilamide. But six registered chemical pharmacists are employed in the Massengill laboratories here, and one is loath to believe that mistake has been made in the preparation of a formula or in the manufacture of a medicine by that company. All the evidence seems to be that the fatalities caused by sulfanilamide were due to the use of other medicine in connection with the elixir.

The article in Time did a grave injustice to Dr. Massengill. So far as known, the quality of a product manufactured by his company has now been called in question for the first time in the forty years of its existence. And our information is that if this product has been fatal in a few cases, it has been beneficial in many—though the fatal results are not, of course, offset by the beneficial effects. One unacquainted with Dr. Massengill and unfamiliar with the history of his company would gain a false impression of both from the Time publication. We say what we have said with a view to correcting, as far as possible, in injustice and the false impression.

1. Sulfanilamide elixir deaths bring demand for US curb. St. Louis Post-Dispatch. November 2, 1937.

2. Dutcher R. Sulfanilamide Elixir deaths. Anniston Star. November 7, 1937; p 4 cols 3, 4.

3. Fishbein M. Deaths following Elixir of Sulfanilamide-Massengill: III. J Am Med Assoc. 1937;109:1544-1545.

4. The deadly "elixir." Drug Cosmet Ind. 1937; 41:611, 614,  615, 619. In an interesting aside, the editors criticized the AMA for "throwing out its chest and trying to impress everone with a desirability of the association having full power over all drugs and how they shall be marketed. This is so despite the fact that the association has been unable to control its own members as is evidenced by the fact that physicians failed to follow the Council of the association and prescribed or dispensed this 'Elixir' even though it had not been accepted by the Council."

5. Pharmaceutical Tragedy. St. Louis Post-Dispatch. November 11, 1397; p 2C. (Editorial reprinted from the Oil, Paint and Drug Reporter.)

6. Fatal remedy. Time. November 1, 1937.

7. Old Timer. "Time" article is unfair to Massengill Company, one of leading drug manufacturers. Bristol Herald Courier. November 21, 1937; p 1 col 1.

Image of commemorative stamp honoring the 1906 Pure Food and Drugs Act from the FDA.

A page providing the names and some details of all known (confirmed or possible) victims of Massengill's Elixir Sulfanilamide is now a permanent feature* of this blog (link in left-hand bar on main page). Any corrections, clarifications, or additions are urged and can be made by contacting barbara dot martin at bmartinmd dot com.

* Insofar as anything can be permanent on the web.

In all, 31 states and Puerto Rico received a total of 633 shipments of Elixir Sulfanilamide, the majority of which were in pint bottles. The elixir was distributed coast to coast within the (then) 48 states and as far north as Harvey, North Dakota, and the upper peninsula of Michigan and as far south as San Juan, Puerto Rico (map). Shipment endpoints were frequently tiny settlements, far from any remotely beaten path—like Wink, Texas, Wedowee, Alabama, and Doe Hill, Virginia (the last of which doesn't even have a Wikipedia entry). During the last 2 weeks of October 1937, nearly all FDA inspectors in the field (239) had picked up, destroyed, or otherwise accounted for 228 gallons and 2 pints of elixir of the 240 gallons produced, including hundreds of salesmen's and physicians' samples [1].

Along the way, the FDA uncovered scores of deaths, many of which would otherwise have been misattributed to other causes or remained deliberately concealed, as demonstrated by numerous field reports. Deaths roughly paralleled the volume of elixir shipments to a geographic region. But deaths were also a function of the willingness of local physicians* to prescribe the new product and chance—given that the likelihood of death after diethylene glycol consumption proved to be about 25%.

A total of 11 gallons and 6 pints of elixir were dispensed on prescription or over the counter (OTC) throughout the United States. Approximately half of this volume was consumed, and the remainder was literally (not just figuratively) taken out of the hands of patients by FDA inspectors, when possible. The first death occurred as early as September 24, and the last victim died October 31.** At least 97 deaths were believed to be due to elixir ingestion; approximately 30% of these victims were children or infants. Another 10 deaths were associated with and possibly due to elixir consumption.

If the entire 240 gallons of distributed Elixir Sulfanilamide had been dispensed and consumed, an estimated 4000 people would have died.

State	Shipments	Prescription or OTC Consumed	Confirmed Deaths
Alabama	80	38	10
Arkansas	3	3	1
California	16	?	1
Colorado	1	0	0
Connecticut	1	?	0
Florida	18	5	2
Georgia	83	26	10
Illinois	38	68	7
Indiana	25	9	0
Iowa	2	0	0
Kansas	2	0	0
Kentucky	14	1	0
Louisiana	13	4	0
Maryland	3	1	0
Michigan	17	0	0
Minnesota	3	0	0
Mississippi	43	70	27
Missouri	17	1	1
New York	2	?	0
North Carolina	24	16	2
North Dakota	2	1	0
Ohio	15	3	1
Oklahoma	18	38	11
Oregon	1	0	0
Pennsylvania	7	?	0
Puerto Rico	1	0	0
South Carolina	12	19	9
Tennessee	45	23	4
Texas	106	33	7
Virginia	12	11	2
West Virginia	14	7	2
Wisconsin	2	0	0
Total	640	377	97

* For example, high-volume prescribers Dr. Archie Calhoun of Mt. Olive, MS, or Dr. Henry Weathers of East St. Louis, IL.

** John (Johney) C. Holloway of Clayton, AL, and John Thomas Tanner of Rocky Mount, NC, respectively. "Baby" Singleton of Eufaula died sometime in September; however, the date of death is currently unknown.

N.B.: Prescription data for CA, CT, NY, and PA are not presently complete. The total number of shipments exceeds 633, owing to occasional interstate shipping of stocks of elixir from pharmacy to pharmacy.

Primary source: Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937.

California

The FDA's San Francisco station oversaw the confiscation of elixir that was distributed from the Massengill Company's branch, located at 240 Fourth Street. Of the nearly 30 gallons shipped from Bristol, more than 4 gallons, mostly in pint containers, had been distributed between September 23 to October 13 to a dozen pharmacies, several physicians offices, and one hospital. A few shipments went to nearby Oakland but most were dispersed to small towns scattered throughout the middle of the state. Two pints each were also sent to Meeker, Colorado, and Eugene, Oregon, thereby establishing interstate commerce of the product from Massengill's San Francisco warehouse. An initial inventory by the FDA revealed that only 2 pints had been returned as a result of the company's recall telegrams [1].

At the Livermore General Hospital, which had received 1 pint of elixir, only 1 patient had been given the medicine—the son of staff physician, Dr. William E. Judson. What follows is probably one of the most complete case reports by the FDA of the effects of Massengill's product and that of contemporary medical treatment [2].

This son, a student in the University of California and member of the football squad, came home from school on the ninth of October with a sore throat that was diagnosed by his father as of streptococcic origin. In order to be positive a smear was made of the throat on Sunday morning, the 10th, and analyses run for the elimination of diphtheria, which was found to be negative.

Upon diagnosis of a streptococcic throat condition Dr. Judson, who had had some previous experience with the Massengill Sulphanilamide ampules [intended for intramuscular administration] and with negative results, decided to administer the Elixir Sulphanilamide orally and a course of three teaspoons at 12:00, 4:00, and 8:00 P.M. in treatment was started at noon on October 10th. The midnight dosage was reduced to 2 teaspoonsful and on Monday a full course of treatment of two teaspoonsful each was inaugurated. On Monday night early the stomach rebelled and throughout Tuesday the patient was nauseated but did not vomit. He complained of his head, stating that it did not feel right and that his mind was not clear. The urine on Tuesday was quite scanty.

On Wednesday morning the patient was in an almost comatose condition and Dr. Judson became greatly alarmed because he could not account for these symptoms. He ordered a continuing treatment of hot packs with frequent hot drinks, continuing this treatment throughout Wednesday afternoon and Wednesday night. On Thursday the treatment began to yield satisfactory results and the alarming symptoms cleared up but even up to the time of my interview with Dr. Judson on October 22nd he states that the boy was still in a very weak condition, showing a continued lassitude and dullness. It was also stated that he had lost about 20-lbs. weight and because of the weakened condition was still out of school. Dr. Judson stated that the feeling of nausea continued for approximately one weeks time and that at times the son complained of severe pains in the joints.

Insofar as other medication was concerned Dr. Judson stated that on Thursday the patient was thoroughly purged with Pluto water and that for several days beginning about Thursday the 14th, administration of salicylates was made for the joint pains. No other medication was used. Dr. Judson states that he feels the son is now out of danger and on the road to recovery but he is still naturally somewhat worried because of the publicity that the Elixir has received in connection with the deaths of certain patients having been treated with it. Dr. Judson is firmly convinced in his own mind that the alarming symptoms developed by his son after the administration of this drug were directly brought on and caused by the treatment.

The only death due to Elixir Sulfanilamide in California occurred in Fresno. Five-year-old Orvin Kutz, Jr, (son of Orvin, Sr, and Cecilia) consumed a total of 1 ounce from a 2-ounce prescription. Initially Orvin's clinical condition, characterized by a streptococcal sore throat and high fever, improved rapidly with treatment, but within 12 hours, he repeatedly vomited and became listless. Ten days later he developed anuria with uremic encephalopathy and died October 20 [3,4]. On November 30, Orvin would have celebrated his sixth birthday. 

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

2. FDA correspondence. Letter from R. B. Bork to Chief, San Francisco Station. October 26, 1937.

3. FDA correspondence. Letter from J. O. Clarke to P. B. Dunbar. November 20, 1937.

4. FDA correspondence. Letter from W. G. Campbell to Mrs. O. C. Kutz. May 25, 1938.

Photograph "Windmills and Golden Hills 2016" outside of Livermore, CA, by "CatDancing" at Flickr.

The FDA's St. Louis station oversaw confiscation of Massengill's Elixir Sulfanilamide in Arkansas, Illinois, and Missouri.

Arkansas

One pint each of Elixir Sulfanilamide was sent from Massengill's branch in Kansas City, Missouri, to 1 drug store each in the rural communities of Blevins, Ola, and Taylor. Only 3 prescriptions were written in the state, all of which were dispensed from the Blevins Drug Company [1].

When approached by the FDA inspector, the prescribing physician James E. Gentry (of McCaskill) identified one of his patients as "Jewell Long," an itinerant "negro" with gonorrhea. "Diligent investigation," however, revealed that Dr. Gentry's patient was, in fact, a young white girl, Ruth Jeanell Long, who was the daughter of a local farmer. Two ounces of the elixir had been prescribed for a streptococcal infection. Ruth Jeanell had last taken the medicine on October 16 and died October 24, 21 days after her seventh birthday.* The FDA concluded that Dr. Gentry probably tried to mislead the federal investigator [1,2].

In Arkansas, 3 wholly or partially consumed elixir prescriptions resulted in 1 death.

Illinois

A cumulative total of 7.5 gallons of Massengill's elixir, most of it sent from the company's Kansas City branch, were distributed in Illinois. Recipients included 16 physicians' offices and 22 drug vendors in 12 communities, the overwhelming majority of which which were in or clustered around East St. Louis. A total of 68 prescriptions were either wholly or partially consumed. The bulk of these prescriptions, 47 (or 70%), were dispensed by the Walter J. Daut Pharmacy (47) and the Lincoln Pharmacy (20), both in East St. Louis [1].

Except for 1 victim, Hazel Fea of Granite City, all the deceased were residents of East St. Louis and patients of Dr. Henry H. Weathers. The first of the 7 confirmed elixir-related deaths** occurred on October 10; the last, October 24 (38-year-old Gertrude L. Black). Among the elixir survivors in this region, a relatively high percentage complained of nausea, vomiting, or back pain during their treatment—which often prompted the discontinuation of the medication. This observation may explain the low fatality rate in Illinois, 10% (7 deaths among 68 prescriptions).

Missouri

A relatively small volume of elixir, 3.75 gallons, was distributed to 5 physicians and 12 drug vendors in 8 different communities, including St. Louis, where approximately 75% of the state's elixir stocks were shipped [1]. Only 1 prescription was dispensed.

Six ounces of elixir were given to William M. Schroeder, 50, of St. Louis, on October 14 by his physician, Dr. L. F. Murray, for an "infection." The physician had purchased 1 gallon of the product from the company's Kansas City branch the previous day. On October 16, Schroeder, a brewery employee, complained of nausea and pain, after taking a total of about 5 ounces. Dr. Murray advised his patient to stop the medication and proceed to the hospital, but Schroeder refused. During the FDA's statewide investigation, an inspector found the patient, ill at home on October 21, and attempted to confiscate the remaining ounce, but Schroeder refused to turn over the product, which he wanted for legal proceedings. Schroeder was taken to Barnes Hospital the following day, where he died on October 24. Schroeder's widow, Matilda, retained the remaining elixir. The couple had been married 4 months [1,4-7].  

* Findings consistent with diethylene glycol poisoning were confirmed by autopsy, after the body was exhumed for examination.

** Another elixir patient of Dr. Weathers, Bessie Lee Bosley, 53, died October 10 of "septicemia" and "infection of the neck" [1,3]. According to the FDA report, "Inspector visited the patient's sister who informed him that patient had infected teeth and her jaw was swollen and in very bad condition at time of death. The sister thought she died from the infection" [1].

1. FDA correspondence. Report from J. O. Clarke to P. B. Dunbar. November 17, 1937.

2. M'Caskill child is first reported victim in state. Hope Star. October 27, 1937; p 1 col 8, p 3 col 5.

3. Illinois death certificate 771.

4. Missouri death certificate 9912.

5. Most sulfanilamide elixir is recovered. St. Louis Post-Dispatch. October 26, 1937; p 10A, col 1.

6. Two more deaths here from Elixir of Sulfanilamide. St. Louis Post-Dispatch. October 25, 1937; p 3A, col 1.

7. FDA newspaper clippings. Elixir widow gets settlement. St. Louis Post-Dispatch. December 10, 1937. 

Photo of Eads Bridge connecting East St. Louis, IL, and St. Louis, MO, by "ca newsom" at Flickr.

Alabama

A total of 16 gallons of Elixir Sulfanilamide, nearly all of which were shipped from Bristol in pint bottles, found their way to 9 physicians' offices and 70 drug stores in 57 communities dispersed throughout the state. Before stocks could be confiscated by federal authorities, 37 prescriptions (including 2 for 1 individual) were either wholly or partially consumed. The consequences of 2 additional prescriptions dispensed in Eufaula could not be determined, despite local radio broadcasts that warned of the elixir's dangers and urged the return of prescriptions. Two over-the-counter purchases were also made in the state.

In addition to the 4 known Alabama deaths in Eufaula and Headland, which were reported nationally on October 23,* FDA officials discovered the following elixir-related casualties:

• In Clayton, 2 prescriptions (one for 6 ounces and another for 4 ounces) resulted in the death of John (or Johney) C. Holloway, age unknown, on September 24.
• In Clio, a 2-ounce prescription to Ewell Daughtrey, age unknown, resulted in her death on September 26 in Waycross, Georgia.
• In Ariton, Ethel Colston ("adult") drank about 8 tablespoons of her elixir prescription. She died sometime in October (exact date currently unknown). In this case, the FDA reported the "complication of possible cerebral hemorrhage."
• Martin Smith, age unknown, of Pisgah also died sometime in October after receiving a 3-ounce prescription; however, the FDA couldn't "prove" that his death was elixir induced.
• In Mobile, a partially consumed 3-ounce prescription resulted in the death of "baby" Glendyne Mallon on October 10.
• Another 3-ounce prescription was dispensed in Demopolis to Ed Scott, age unknown, who died October 14. The FDA did not recover any remaining elixir, because Scott's prescription bottle was placed in his casket.
• Two-year-old Betty Joe Story, of Arab, died October 16 after drinking some portion of a 6-ounce prescription for Elixir Sulfanilamide.

During the course of the investigation in Alabama, a "vicious deliberate lie" (as the FDA's J. O. Clarke characterized it) was discovered in Enterprise, where a local druggist reported selling 8 ounces of elixir over the counter to a "stranger." Persistent investigation by state and federal officials "failed to shake the story of this consignee," to determine the identity of the purchaser. Only later did the FDA discover that two 4-ounce bottles of elixir had been sold by the druggist for the treatment of Edward Walker. The boy died of acute nephritis on October 3 in a Dothan hospital, about 30 miles away. After his son's death, Charles Walker wrote the state's Public Health Service, stating that he suspected his son died of elixir poisoning. Mr. Walker submitted a portion of the elixir, which had, in fact, been purchased from the Enterprise druggist, to the FDA's New Orleans Station.

SENDING YOU PORTION DRUG I WANT ANALYZED. IT WAS PRESCRIBED FOR MY BOY. HE WAS TAKEN ACUTELY ILL AND DIED OF DISEASE DOCTORS DIAGNOSED ACUTE BRIGHTS.

A small sample of a reddish liquid was forwarded to the FDA's Baltimore laboratory for confirmatory analysis [1-4].

In Alabama, 37 elixir prescriptions (including 2 for 1 individual) and 1 over-the-counter purchase were associated with the deaths of 12 people (fatality rate, 32%).

Mississippi

Nearly 13 gallons of Massengill's elixir were distributed to 6 physicians' offices, 36 drug vendors, and 1 hospital in 36 communities [1]. A total of 70 prescriptions were written in the state. In 2 cases, 2 prescriptions (an original and a refill) were written for each of 2 patients, and 3 related children shared 1 prescription.

In addition to the publicized deaths in Mt. Olive (5), nearby Magee (2), Laurel/Ellisville (5), and Philadelphia (1),** the following elixir-related casualties were discovered in Mississippi during the course of the FDA's investigation and seizure. 

Also in Mt. Olive, the Calhoun Drug Company, which was run by the brother of the town's prescribing physician, Archie Calhoun, dispensed a total of 13 elixir prescriptions. Seven recipients died. Like Dr. Calhoun's previously named elixir victims, 2 individuals succumbed. John W. Gibbons, 71, died October 9, and Mrs. Katie Stuckey, 38(?), died sometime between October 5 and October 24. Both had consumed a little more than half of their 4-ounce prescriptions.

In Magee, 2 prescriptions were given to Julia Brown, age unknown, who died (like fellow residents Edie Sullivan and Hettie Young) as a consequence of diethylene glycol poisoning. The date of Brown's death is currently unknown.

In Itta Bena, 4 ounces of elixir were prescribed for Mrs. Robert (Elnore) Perkins, who died October 1 after consuming a portion of the medicine.

In New Albany, consumption of 3 ounces of a 4-ounce prescription resulted in the death of "negro" William Corneel Howell, age unknown, on October 14.

Six ounces of elixir, dispensed on prescription, to "negro" Columbus Bryant, 34, in Cary resulted in his death on October 17 at the John Gaston Hospital in Memphis, Tennessee [5]. Causes of death were "essential hypertension," "multiple cortical hemorrhage of both kidneys" (determined by autopsy), and "uremia."

In Corinth, 4 ounces of elixir were dispensed on prescription to 3-year-old Jerry Strickland on October 11. He drank a total of 1.75 ounces and died October 22.

Several communities in the state's delta county of Yazoo were affected by deaths due to Elixir Sulfanilamide.

In Yazoo City, a 2-ounce prescription was written for Sallie Louise Brown, age unknown, on October 13. She died 11 days later, after drinking less than 1 ounce of the elixir. 

Dr. Homer E. Frizell, who practiced in Deasonville and Vaughan, reported to the FDA inspector that he had dispensed 2-ounce prescriptions to "each of 3 or 4 colored patients." According to Dr. Frizell, the patients claimed that the medicine "made them sick," at which point he emptied out his elixir stock sometime before receiving Massengill's recall wire. The doctor also claimed that he did not know the names of his patients. Further investigation, however, revealed that Walter Bell, age unknown, of Benton was one recipient. He died October 11 after consuming nearly all of his prescription. Another patient was Joe Hewitt, 31(?), of Deasonville, who died of elixir poisoning on October 4. The amount of elixir that Hewitt had consumed was not determined. The FDA also discovered that Dr. Frizell had poured out the unused portion of Massengill's product "so as to refill [the bottle] with another medicine after ill effects began to show up."

In Bentonia, 9 prescriptions (for a total of 44 ounces) resulted in 5 deaths, the dates of which are currently unknown.

• Essie Davis: An unknown amount of a 6-ounce prescription was consumed.
• Henry G. Taylor: 4.75 ounces of a 6-ounce prescription were consumed.
• Franklin Jones: 2.75 ounces of a 4-ounce prescription were consumed.
• Little Martin Shelby: 2.75 ounces of an 8-ounce prescription were consumed.
• Steve Demus: An unknown amount of a 4-ounce prescription was consumed.

In Mississippi, 70 prescriptions for Elixir Sulfanilamide resulted in the deaths of 28 residents (fatality rate, 40%).  

* The previously reported deaths in Eufaula: a baby (possibly Syble G. Singleton), died in September (date unknown); Fannie Zeanah (age unknown), died October 13; and Alfred "Alf" McDade (age unknown), died October 17. In nearby Headland, Anderson Crews (or Cruce), 63, died September 25.

** In Philadelphia, the Davis Drug Company, which had received 1 pint of elixir from Bristol, returned a full 16 ounces to Massengill headquarters during the recall. Analysis, however, revealed that the returned product had been diluted with water. Investigation revealed that two 4-ounce prescriptions had been dispensed. One resulted in the death of Lorene Lewis.

1. FDA correspondence. Report from J. O. Clarke to P. B. Dunbar. November 17, 1937.

2. FDA correspondence. Telegram from G. P. Larrick to FDA, New Orleans Station. December 1, 1937.

3. FDA correspondence. Telegram from J. O. Clarke to FDA, Washington, DC. December 3, 1937.

4. FDA. Part III. Elixir Sulfanilamide Investigation.

5. Tennessee death certificate 3614.

Photo of warehouse in Eufaula, AL, by "Frankie 117" at Flickr.

"Somewhere in Yazoo County" by NatalieMaynor at Flickr.