The origin of the FDA and the Elixir Sulfanilamide disaster of 1937

Safe and effective means just that to the Food and Drug Administration

A bottle of the Elixir of Sulfanilamide

The Pure Food and Drug Act of 1906

The early 1990’s was the age of the Progressive Era, and one key piece of legislation at that time that we benefit from today is the Pure Food and Drug Act of 1906. A result of 27 years of public awareness of manifold problems with food and medicines in the United States, such as syrups for infants with opium derivatives, nostrums and panaceas were widely advertised to cure a manifold of ills. As an example, Benjamin Brandreth became wealthy in 1862 widely advertising the ‘Vegetable Universal Pill’, a ‘household word in the United States’ for 50 years, even warranting mention in the Herman Melville classic novel Moby Dick.

In 1902 a government chemist named Dr. Harvey Washington Wiley played a key role in the passage of the 1906 act, commencing a widely-followed study of the effects (on human volunteers) of a controlled diet supplemented with various preservatives in wide use at that time. Called the “Poison Squad”, a group of eight young men were allowed to eat dinner with him, and afterwards would take capsules of different preservatives in use at that time, beginning with boric acid, then copper sulfate, salicylic acid (aspirin), and formaldehyde.

Needless to say this public demonstration of the dangers of food additives led Dr. Wiley as well as the work of Alice Lakey to spur one million American women to write to the White House to support the 1906 Act. The jurisdiction for the enforcement of the 1906 Act went to the Bureau of Chemistry under Dr. Wiley’s leadership, and the FDA was then eventually created years later. The 1906 Pure Food and Drug Act was initially concerned with proper labelling of products, later expanded to require certain drugs to accurately indicate dosage including alcohol, cocaine, morphine and cannabis.

The uses of sulfanilamide

By the 1930’s the 1906 Pure Food and Drug Act was in need of revision, and languished in congressional committee as disagreements arose over its replacement. And in the 1930’s sulfanilamide (in a class of drugs called sulfonamides or sulfa drugs) was recognized for killing streptococcus bacteria. A pair of Nobel Prizes were awarded to their discovery (by a German pathologist Gerhard Domagk in 1932 and by a Swiss pharmacologist Daniel Bovet in 1936), and were first seeing wide use in the United States in 1936 when President Franklin Roosevelt’s son recovered from a nearly-fatal severe sinus infection.

Sold in powdered format, a chemist Harold Watkins at a pharmaceutical manufacturer called S.E. Massengill Co. (headquartered in Bristol TN) discovered he could use diethylene glycol (DEG) to dissolve sulfanilamide, and added raspberry flavoring and red coloring to the product to make it appealing to children. This medication was called Elixir Sulfanilamide.

At that time there was no regard for testing for safety or toxicity, and over 600 bottles were distributed to pharmacies and physicians throughout the southeast mainly in Oklahoma and Mississippi, although another 700 bottles were distributed to physician offices and Massengill sales representatives as samples.

Devastation and impact

The lethal dose of DEG is only 2 ounces (here’s an MSDS for the details). Abdominal pain, nausea, vomiting, leading to blindness, comatose it was said “thrash about on the bed for days on end… The lucky ones were the ones that lasted three or four days. The typical time of death would be about nine days. It was a extremely painful, excruciating death.” The first telegram to the manufacturer was sent Saturday October 9, 1937 from the American Medical Association office in Tulsa Oklahoma, reporting the first six deaths with similar symptoms of low respiration, loss of kidney function, and lower-than-normal temperatures.

By the following Monday the death toll reached 11, the two others were being treated with the Elixir of Sulfanilamide for gonorrhea. The Tulsa AMA learned the solvent used to formulate the elixir was 60 gallons of DEG, with no known antidote or treatment at that time for DEG poisoning. The FDA was alerted at that time, but was powerless to do anything about it. The FDA, empowered over the labelling of foodstuffs and drugs, exercised its enforcement where it could. First the usage of the term ‘elixir’, which implied containing alchohol (which the product did not), second the label said the bottles contained ‘Quality Pharmaceuticals’ which it clearly did not, and third Massengill listed their address in Bristol TN (where their headquarters were) instead of Kansas City MO where the product was manufactured.

The following is a quote from Dr. Archie Calhoun of Mt. Olive MS, who was so distraught over this tragedy that he personally visited every one of his patients that he prescribed this medicine to. From this account:

Nobody but Almighty God and I can know what I have been through in these past few days. But to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that the medicine that I have used for years in such cases suddenly had become a deadly poison in its newest and most modern form, as recommended by a great and reputable pharmaceutical firm in Tennessee; well, that realization has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive. I have spent hours on my knees, once I had done all any physician could do for his patients. I have known many hours when death for me would be a welcome relief from this agony.

Dr. Archie Calhoun, shown examining a bottle of Elixir of Sulfanilamide

The company sends a ‘recall notice’

A week after that first initial report, on Friday October 15 1937 shipments stopped and the company sent 1,100 recall telegrams. To the salesmen (and at that time it was all men), “Elixir sulfanilamide discontinued. Pick up as rapidly as possible all sold in your territory.”; to the customers the telegram read “Do not use elixir sulfanilamide shipped. Return our expense.” Afterward a federal inspector demanded a more urgent message be sent, which read: ““Imperative you take up immediately all elixir sulfanilamide you may have dispensed. Product may be dangerous to life. Return our expense.”

By Friday October 22, 1937 the death toll rose to 22, and the FDA sent out their entire staff of 239 field inspectors to search for every ounce of unaccounted-for elixir. At that time in 1937 there was still little electrification in the Southern US and many people did not own radios; the only method of mass communication was newspapers, and the story was buried inside.

On Monday October 25 the death toll rose to 41, and an announcement was made that almost all the bottles shipped had been collected. Of 240 gallons manufactured, 95% was either recovered or otherwise accounted for; however there were a total of 105 confirmed or probable deaths due to this tragedy, with 37 of these victims being children. The youngest victim was only 6 months old.

(photo, credit and Dr. Achie Calhoun examining a bottle of Exlixir Sulanilamide, from Nov 2 1937 issue of the Danville Morning News PA)

Samuel Evans Massengill, founder and president, was arrested and eventually pled guilty to 112 counts of violation against the 1906 Pure Food and Drugs Act in TN, followed by a similar plea to 62 counts in Kansas City MO. He served no jail time, and was fined for a total of $26,100 (or about $500,000 today). He was a multimillionaire in 1937, thus this financial penalty was not significant.

The Federal Food, Drug and Cosmetic Act of 1938

The Federal Food, Drug and Cosmetic Act of 1938 was a direct result of this tragedy. By replacing the Pure Food and Drug Act of 1906 and giving the FDA considerably more powers and authority, this Act would be amended in 1976 to include regulation for medical devices. This is where we find the Section 510(k) for the 90 day notification of intention to market a medical device, the different Classes (I, II or II) that devices are approved under, and details the Premarket approval (PMA) process.

The FDA had its beginnings with both outrageous claims and a medical tragedy. This history is important to keep in mind when thinking of the FDA’s mandate for ‘safety and efficacy’ of all medical devices, including in vitro diagnostics.