Ethics: January 2009 Archives
Bum-bum-bum, bum-ba-dum, bum-ba-dum.
Bum-bum-bum, bum-ba-dum, bum-ba-dum.
Sorry.
Nine FDA scientists who complained to the House Energy and Commerce Committee and Obama's transition team about lax medical-device reviews at the FDA's Center for Devices and Radiological Health (CDRH) are now targets of an internal criminal investigation, writes Gardiner Harris in today's NYT. The scientists reported this new development in their ongoing struggle with CDRH's management in a letter sent to President Obama on Monday and also provided to the paper.
Harris quotes the letter: "It has been brought to our attention that FDA management may have just recently ordered the FDA Office of Criminal Investigations to investigate us rather than the managers who have engaged in wrongdoing! It is an outrage that our own agency would step up the retaliation to such a level because we have reported their wrongdoing to the United States Congress."
Harris implies that the alleged criminal investigation may relate to the scientists' sharing of confidential CDRH documents, including e-mail messages, with the NYT. On January 12, Harris wrote that a CDRH supervisor overruled agency scientists and approved iCAD's SecondLook Digital Computer-Aided Detection System for Mammography, after receiving a phone call from former Connecticut congressman Christopher Shays. The device is used in conjunction with screening equipment made by Fujifilm Medical Systems, which is based in Stamford, CT, the center of Shay's former district. Harris's article was evidently prompted by FDA documents, which were given to the NYT by the dissident scientists.
Harris also wrote that a recent report from the Government Accountability Office largely validated the FDA scientists' claims of a broken approval process at CDRH.
Yesterday, Chinese courts handed down sentences in proceedings against 21 defendants who were charged with involvement in the country's recent scandal regarding melamine-tainted milk. Sentences ranged from execution to prison time, with the heaviest penalities for 3 men.
- Zhang Yujun, a Hebei province dairy farmer (described by the court as the single largest source of melamine in the country), received the death penalty for "producing and selling poisonous food" or "endangering public security." Zhang reportedly produced 776 metric tons of melamine, 600 of which were added to milk. The court charged that he made $1.26 million in the process.
- Geng Jinping, a small dairy operator in Zhengding County, Hebei province, received the death penalty for "producing and selling poisonous food" or "endangering public security." The court claimed that Jinping added melamine to raw milk and sold "hundreds of tons" of the product to Sanlu, the Chinese dairy-products company.
- Gao Junje, a small business operator, received the death penalty for "producing and selling poisonous food" or "endangering public security." Junje's death sentence was suspended for 2 years.
- Tian Wenhua, 66, former chairwoman of the now-bankrupt Sanlu, received life in prison for "producing and selling shoddy goods." Wenhua pleaded guilty to the charge and was also fined $4.5 million. Some affected parents are reportedly upset that Wenhua was not sentenced to death for her role in the scandal.
- Three former (unnamed) Sanlu executives received 5-15-year prison terms for "producing and selling shoddy goods."
The group of 22 implicated dairies is also offering 200,000 yuan (~$30,000 USD) to parents of a dead child, 30,000 yuan (~$4400) to children with severe kidney stones, and 2000 yuan (~$290) to less severe cases. Total compensation would run to 1.1 billion yuan (~$160 million). State-run television indicates that 90% of families have taken the time-limited and government-backed financial compensation. However, the Toronto Star reports that hundreds of affected parents have rejected the offers.
Melamine, a fake protein additive, in baby formula caused the deaths of at least 6 Chinese infants and sickened nearly 300,000 last year, according to various news sources. But lawyers for the affected families suggest that as many as 10 children died after consuming melamine-laced milk. The Chinese Health Ministry admits that more than 300 affected infants remain hospitalized.
Sources: Toronto Star; China Daily; AP
Depiction of melamine chemical structure from Wikipedia.
[W]e are here concerned with a preparation not standardized by any reliable agency, semisecret in composition and apparently hastily rushed into the market to meet an overenthusiastic reception of a new remedy.
———Journal of the American Medical Association, October 23, 1937
In June 1937, drug salesmen for the S. E. Massengill Co. of Bristol, Tennessee, reported demand for a liquid preparation of the new, wildly popular antibiotic sulfanilamide [1], which was currently sold in capsule and tablet forms by several US pharmaceutical interests, including the Massengill company.
Only 5 years earlier, a corporate chemist for the German conglomerate I. G. Farben, Gerhard Domagk (left), had demonstrated the life-saving properties of a related compound, an azo dye trade-named Prontosil, in streptococcal-infected mice [2]. One year later, a German physician reported dramatic recovery of an infant with staphylcoccal septicemia after receiving Prontosil [3], and Domagk successfully used the agent on his own daughter, who was near death with streptococcal septicemia [4].
Then in 1935, French investigators showed that the active metabolite of the patented Prontosil was actually sulfanilamide—a compound that had been synthesized by an Austrian chemist more than 25 years earlier [5,6]. Consequently sulfanilamide was in the public domain and available for general production. Quick, follow-up studies of Prontosil and sulfanilamide by physicians in London and at Johns Hopkins established the equivalence of the 2 agents in human streptococcal infections [7,8].
But the real enthusiasm for sulfanilamide would be generated by a high-profile case study. Shortly before the Hopkins work was printed in the medical literature, news reports were buzzing with the recuperation of the American President's son, Franklin D. Roosevelt, Jr., from a serious throat and sinus infection. While hospitalized at the Massachusetts General Hospital in December 1936, the junior Roosevelt was treated with sulfanilamide tablets (branded as Prontylin by the Winthrop Chemical Co., NY) in a near last-ditch effort. The dramatic recovery of the President's son after treatment with the antibiotic was chronicled faithfully by Associated Press reports in the country's newspapers, including the New York Times [9].
Scientific endorsement and the glowing anecdoctal publicity for sulfaniladmide fueled widespread zeal for the drug among physicians and the American public. And zeal gave way to near fanaticism when medical studies described sulfanilamide's efficacy in cases of gonorrhea. News reports, overstating the medical findings, startled some readers by broadcasting that the drug was "the best thing ever for gonorrhea" and cured the veneral disease in 48 hours [10].
Soon the American market was flooded with several competitive brands of the antibiotic, including Prontosil (the original Farben drug), sulfanilamide, and several brand names for identical preparations. In May 1937, the AMA's Council on Pharmacy and Chemistry attempted to avert confusion by adopting "sulfanilamide" as the preferred nonproprietary term for the drug and stated, "It is regretted that certain firms in America are using proprietary names [for sulfanilamide]" [11].
Established in 1905, the Council's job was to determine standards for pharmaceutical manufacturing and advertising and to eradicate quackery [12]. In the absence of any federal legislation that required proof of safety, efficacy, or advertising claims for pharmaceutical products, the Council, in 1937, was the leading authority that reviewed and endorsed or dismissed commercial medicines that were submitted for inclusion in its widely read pharmacopoeia, New and Nonofficial Remedies. In July 1937, the Council published its "Examination of Certain American Brands of Sulfanilamide," which included assessments of products from the major American pharmaceutical firms Eli Lilly, Merck, Parke Davis, and E. R. Squibb & Sons [13]. The preparations were in powder, tablet, and injectable forms; no orally administered solution existed. The Council advised that the drug "has the apparent disadvantage of being relatively insoluble" and has a tendency to crystallize out of solution [11].
In the wake of continued enthusiasm for the drug, an editorial in the October 2nd issue of the AMA's journal—while acknowledging that the drug was "truly remarkable"—warned against its indiscriminate use [14]. Toxic reactions, including dermatitits, photosensitization of the skin, and hemoglobin abnormalities, had been reported. Specifically some cases of self-medication for venereal disease were associated with severe drug reactions, which necessitated hospitalization. (Although sulfanilamide was largely dispensed by means of prescription in the United States, no federal law in 1937 prevented pharmacists from providing the drug directly to the patient, on request.) The editorial warned, "Responsibility lies considerably with pharmacists who are willing to sell dangerous drugs to anybody over the counter."
In 1937, the S. E. Massengill Company introduced its own versions of sulfanilamide tablets and capsules for human consumption to the US market [15]. Originally a small family operation, the Bristol-based company began manufacturing nonproprietary pharmaceuticals for regional distribution at the end of the 19th century. Since 1916, the company had been led by one of its founding brothers, president Samuel E. Massengill, a proud and locally respected descendant of East Tennessee's original Massengill settlers and a 1899 medical graduate of the University of Nashville.
Steady growth of Massengill's company during the early 20th century, from a 1-room laboratory to a 4-building plant on "spacious grounds" in the piedmont city of Bristol, eventually led to the establishment of a manufacturing and distribution branch in Kansas City, Missouri, and warehouses in New York City and San Francisco. Sales offices were also established in Hawaii and Puerto Rico. Massengill himself boasted that his company was "the largest pharmaceutical manufacturer for the entire South." At the end of 1936, net annual sales were recorded at more than $1.6 million (more than $24 million in 2007 USD) [16].
The firm's 1936 catalog, which offered hundreds of tablets, capsules, elixirs, or ointments, reads like a drug compendium on the cusp of modern medicine. Products like antimony wine, mercurial ointment, and rhubarb elixir share index space with aspirin, novocaine, and phenobarbital. The catalog promised," Every step in the manufacture of our general line of pharmaceuticals is under the supervision of skilled workmen and strict chemical control, and the physician may rely upon our products for prompt and full therapeutic effect" [17].
In fact, the FDA had brought charges against the S. E. Massengill Company on 3 previous occasions, all during the 1930s. The cases, however, were not unusual in character or frequency given the nature of the pharmaceutical industry at the time. In 1 case, the company's Fluidextract of Colchicum, a gout treatment, was found to be overstrength; in another, the strenth of its Tincture of Aconite was determined to be below its stated concentration. Fines of $250 and $150, respectively, were paid by the company for these 2 infractions. In the third instance, the seizure of Massengill's Elixir Terpin Hydrate and Codeine, a steadfast cough suppressant, was based on charges of adulturation and misbranding. The case was successfully prosecuted in court [18].
Despite the fact that sulfonilamide was relatively insoluble in the typical pharmaceutical solvents, Massengill's head chemist, Harold Cole Watkins, was not deterred [1]. The son of a Maine newspaper publisher, Watkins had graduated from the University of Michigan in 1900 with a degree in pharmaceutical chemistry and thereafter had led an itinerant career in the drug industry. He performed laboratory work for Merck and was employed briefly in "various wholesale and pharmaceutical houses" [19]. US census records show that Watkins worked as a chemist in Spokane, Washington, in 1910, and in Brooklyn, New York, in 1920 (where he lived with his Norweigian wife, Marie, and their 4-year-old son, who was born in California). Census records from 1930 suggest that Watkins may have tried his luck at farming in the town of Benton in northeastern Pennsylvania (with Marie and their 2 sons). This brief career change may have had something to do with the fact that Watkins (as Watkins Laboratories) had been cited by the Solicitor of the Post Office Department on charges of fraud the previous year. Records indicate that, on October 30, 1929, the chemist agreed to discontinue the promotion of a weight-loss medicine, which he had claimed produced a "perfect slenderness" and a "trim, youthful, athletic look" [1].
In any event, 5 years later, Watkins moved his family to the relatively cloistered city of Bristol to join the Massengill company as head chemist. He was 55. In the summer of 1937, he set out to find a liquid vehicle for sulfonilamide at the company and turned his attention to the glycols. He based this decision on their chemical similarity to glycerine, a commonly used solvent in liquid pharmaceuticals [19]. He soon discovered that he could dissolve as many as 75 grains of sulfanilamide in 1 fluid ounce of clear, odorless diethylene glycol. However, the resultant solution tended to separate on chilling, so he reduced the antibiotic concentration to 40 grains per fluid ounce and quickly settled on the following mass-quantity recipe for a stable product [1]:
Sulfanilamide, 58½ pounds
Elixir flavor, 1 gallon
Raspberry extract, 1 pint
Saccharine, soluble, 1 pound
Amaranth solution, 1-16, 1½ pints [a synethic, bright red, azo dye, which was presumably added to resemble the color of the patented Prontosil]
Caramel, 2 fluid ounces
Diethylene glycol, 60 gallons
Water q. s., 80 gallons
No animal or clinical tests were conducted by Watkins or the company at large to determine the toxicity of the individual ingredients or that of the combination. Any possible effects of diethylene glycol on sulfanilamide were also left to chance. The company's sole process for quality control consisted of checking the elixir for its appearance, flavor, and fragrance. The Acting Chief of FDA's Drug Division, Theodore Klumpp, bluntly described the company's elixir development: "[T]he only criteria of its safety and value as a medicine were that the ingredients were mixed, did not immediately explode, and the color, taste and smell of the product were satisfactory to their so-called control department" [20].
Watkins was evidently unaware that, for several years, the FDA had advised against the use of glycol solvents in foods, on the basis of limited safety data [21]. He was also presumably ignorant of 2 published reports, one in 1931 and one in early 1937, which described the lethality of diethylene glycol in experimental animals [22,23].
In late August, Watkins's formula for Massengill's Elixir Sulfanilamide was sent to the company's Kansas City branch in Missouri (208-214 W. 19th St.), where 40 gallons of the product were mixed in a large "stone jar" on September 20 [24,25]. Supplied instructions were remarkably simple: "Dissolve sulfanilamide in the diethylene glycol, add the other ingredients and mix" [25]. Sulfanilamide was obtained by the company from Ganes Chemical Works in New York, and diethylene glycol was purchased (at 23 cents per gallon) from Carbide & Chemical Corporation in West Virginia. No assay was made of the finished product, despite the fact that tests for sulfonilamide in blood and urine had been described several months earlier by pharmacologists at Johns Hopkins in the Journal of the AMA [18]. Another batch of 40 gallons was produced by Watkins himself at the company's Bristol plant, which began shipping the product to its San Francisco and New York branches on September 4 [1,26,27]. Two more batches of 80 gallons each were manufactured at Bristol; most of these batches also went into distribution.
Commercial lots from 1 pint to 1 gallon were shipped from Massengill's Bristol and Kansas City plants, as well as from its New York and San Francisco sales branches. In all, 633 shipments were made. The product label (example below) failed to list the product's ingredients, other than sulfanilamide. In addition, a total of 671 physicians' or salesmen's samples were sent from Bristol or Kansas City.* In time with the mass distribution, a promotional brochure for physicians announced, "Our research department has just released an Elixir Sulfanilamide...It is ideal for your patients who can take liquids—but little else. Also, it is not unpleasant to take, so is suitable for children" [28].
Both commercial and sample lots were distributed nationwide through October 15, 1937—the same day that Tulsa physicians telegraphed the AMA to convey their autopsy findings from 5 children who had consumed the elixir.
* The company employed approximately 200 salesmen.
1. Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937.
2. Domagk G. Ein beitrag sur chemotherapie der bakteriellen infektionen. Deutsche Medizinische Wochenschraft. 1935;xx:250-253. Domagk's company, I. G. Farben, received a German patent for Prontosil on December 25, 1932. However, the patent was not published until January 1935, for reasons unclear. One month later, Domagk's landmark article was printed. The author offered clear credit to his company above the article's title ("Aus den Forschungslaboratorien der I. G. Fabenindustrie...") and little explanation for Prontosil's mechanism of antibacterial action, only writing that the agent possibly bolstered the immune system. For this work, Domagk would receive the Nobel Prize for Physiology or Medicine in 1939; however, he was prevented from accepting the prize at the time by the Nazi government.
3. Foerster R. Sepsis im anschluß an ausgedehnte periporitis: heilung durch streptozon. Zentralbl Haut Geschlechtskr Grenzgeb. 1933;45:549-550.
4. Dictionary of Scientific Biography. 1972:4:153-156.
5. Trefouel J, Trefouel J, Mitti F, Bovet D. Activite due p-aminophenylsulfamide sur les infections streptococciques expeimentales de la souris et du lapin. C R Seances Soc Biol Fil. 1935:120:756-760. English bacteriologist Ronald Hare—mistrusting German pharmaceutical development—argued that Domagk, in fact, knew in 1932 that the no-longer-patented sulfanilamide was the active ingredient in Prontosil. Hare further claimed that the intervening time between Domagk's initial experiments and his 1935 publication was sucked up by the creation and testing of a patentable analog of sulfanilamide (ie, Prontosil) for the interests of his company, I. G. Farben. (See Dowling HF. Fighting Infection: Conquests of the Twentieth Century. Cambridge, Mass.: Harvard University Press; 1977:108-124.)
6. Gelmo P. Uber sulfamide der p-amidobenzolsulfonsaure. J Praktische Chemie. 1908;77:369-382.
7. Colebrook L, Kenny M. Treatment of human peurperal infections, and of experimental infections in mice, with Prontosil. Lancet. 1936;June 6:1279-1286.
8. Long PH, Bliss EA. Para-amino-benzene-sulfonamide and its derivatives. J Am Med Assoc. 1937;108:32-37. For a contemporaneous history of the development of sulfanilamide and its introduction into the United States, see Long PH, Bliss EA. The historical aspects of sulfanilamide therapy. In: The Clinical and Experimental Use of Sulfanilamide, Sulfapyradine and Allied Compounds. New York, NY: MacMillan Company; 1939:1-13.
9. F D Roosevelt Jr is in
10. Drug and Cosmetic Industry. July 1937.
11. Council on Pharmacy and Chemistry. Sulfonilamide and related compounds. J Am Med Assoc. 1937;108:1888-1890.
12. Smith A. The Council on Pharmcy and Chemistry and the Chemical Laboratory. In: Fishbein M, ed. A History of the American Medical Association, 1847 to 1947. Philadelphia, Pa.: W. B. Saunders Co. 1947:865-886. Note that the federal Food and Drugs Act of 1906, still in effect in 1937, merely required manufacturers to accurately label and brand medicinal products that were intended for interstate commerce.
13. The Chemical Laboratory. Examination of certain American brands of sulfanilamide. J Am Med Assoc. 1937;109:353-359.
14. Sulfonilamide--a warning [editorial]. J Am Med Assoc. 1937;109:1128.
15. Masengill Brothers Company and the S. E. Massengill Company, 1897-1971. Knoxville, Tenn.: Tennessee Valley Publishing; 1996.
16. Massengill, Samuel Evans. In: National Cyclopaedia of American Biography. Vol 34. New York City, NY: James T. White and Company; 1948; FDA records. Company assessment by Dun & Bradstreet, Inc. November 8, 1937.
17. Complete Catalog of the Products of the Laboratories of the S. E. Massengill Company. Bristol, Tenn.: King Printing Co.; 1936.
18. Citations of Notices of Judgment Under the Food and Drugs Act (23228 [1935], 27136 [1937], 24029 [1935]) and FDA correspondence (George Larrick to Central District Chief, November 21, 1934). In: Parascandola J, Whorton JC, eds. Chemistry and Modern Society: Historical Essays in Honor of Aaron J. Inde. Washington, DC: American Chemical Society; 1983:105-125.
19. Citations of FDA reports in Young JH. Sulfanilamide and diethylene glycol. In: Parascandola J, Whorton JC, eds. Chemistry and Modern Society: Historical Essays in Honor of Aaron J. Inde. Washington, DC: American Chemical Society; 1983:105-125. Young writes, "During the depression, Watkins had been idle some of the time, before joining Massengill."
20. FDA correspondence. Theodore O. Klumpp to Perrin H. Long. November 1, 1937. Klumpp also wrote, "It is also a sad but true fact that the chemist told me that they could not assay the sulfanilamid because there were no assay methods known. This might lead Doctor Marshall to wonder what he has been doing with his time all these months." Presumably Klumpp is referring to pharmacologist Eli Kennerly Marshall, PhD, of Johns Hopkins, who was lead author of "Para-aminobenzenesulfonamide: absorption and excretion--method of determination in urine and blood." The article, describing assays for sulfonamide, was printed several months earlier, in the March 20 issue of the Journal of the AMA (1937;108:953-956).
21. FDA correspondence. July 26, 1938.
22. von Oettingen WF, Jirouch EA. Pharmacology of ethylene glycol and some of its derivatives. J Pharmacol Exp Ther. 1931;42:355-372.
23. Haag HB, Ambrose AM. Studies on the physiological effect of diethylene glycol. J Pharmacol Exp Ther. 1937;59:93-100.
24. FDA correspondence: October 18, 1937, and Leo J. Cramer to Baltimore Station Chief. October 20, 1937. According to an FDA investigative report of the distribution of sulfanilamide (from FDA inspector Hugh F. Smyser, November 11, 1937, re interview with Otto B. May), the antibiotic was manufactured by heating acetanilid with chlorsulphonic acid, drowning in flake ice, and filtering in crocks. "The resulting paste is charged with ammonia, neutralized with sulfuric acid, filtered and charged with hydrochloric acid and neutralized with sodium hydroxide and filtered. Instead of recrystallizing twice as a matter of routine, the product is recrystallized from hot water repeatedly until two successive recrystallizations give a constant melting point. Three recrystallizations are the usual number."
25. FDA correspondence. Letter from Leo J. Cramer to Chief, Baltimore Station. October 21, 1937. The letter provides an inventory of samples sent from Massengill's Kansas City branch to the FDA's Baltimore laboratory for testing.
26. FDA correspondence. W. G. Campbell to Central District Chief. November 12, 1937.
27. FDA memorandum. Charles Hyak. October 21, 1937.
28. Citation of Massengill brochure in Young JH. Sulfanilamide and diethylene glycol. In: Parascandola J, Whorton JC, eds. Chemistry and Modern Society: Historical Essays in Honor of Aaron J. Inde. Washington, DC: American Chemical Society; 1983:105-125. For Massengill's salesmen's talking points, see FDA correspondence. J. F. Earnshaw to Baltimore Station Chief. October 19, 1937.
Photo of Gerhard Domagk from nobelprize.org.
On Saturday, October 9, 1937, the following telegram was sent from the Springer Clinic in Tulsa, Oklahoma, to Dr. Morris Fishbein, editor of the Journal of the American Medical Association in Chicago [1].
ATTENTION IS CALLED TO AT LEAST SIX DEATHS IN TULSA FOLLOWING ADMINISTRATION OF ELIXIR OF SULFANILAMIDE SYMPTOMS OF ANURIA AND TOXIC DEGENERATION OF LIVER AND KIDNEYS
The necessary brevity of the clinic's wire understated the tragedy of the deaths. Five days earlier, a 5-year-old boy, Millard Wesley Wakeford, died in a Tulsa hospital (possibly Morningside Hospital or St. Joseph's), after receiving a 4-ounce prescription for the elixir [1,2]. Then the following night, a 6-year-old girl, Joan Marlar, died in hospital. She had received a 3-ounce prescription [1,3].
The deaths continued. Michael S. Sheehan, a 6-year-old boy, died October 6, and 8-year-old Kathleen E. Hobson died October 9. Both had received 4-ounce prescriptions for the elixir. Then a young man died Saturday, after taking Massengill's concoction: 19-year-old Glen F. Entler of Tuscola, Illinois, who had been visiting his aunt and uncle in the city [1,4].*
The deaths were not peaceful. Twenty-four hours after Entler had taken approximately 9 ounces of the elixir (about 260 cc), he developed symptoms of acute nephritis—nausea, vomiting, and intense flank pain. A day later he stopped producing urine altogether. (Dialysis for acute renal failure wouldn't be available for at least another decade.) He died 4 days after taking the last dose of medication [1]. Joan Marlar's mother described her daughter's anguish during the 9-day illness before her death. "[W]e 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"[5].
A pathologist in Tulsa, Dr. Ivo A. Nelson, had noticed the cluster of unusual nephritis cases and quickly suspected poisoning [6]. After dismissing the possibility of mercuric chloride toxicity, he interviewed the families and doctors of the victims and discovered, in all cases, that Massengill's elixir had been prescribed. In some cases, it was the only medication consumed by the deceased.
After performing autopsies on 4 of the victims, Dr. Nelson "took his findings to his horrified associates in the Tulsa County Medical society, some of whom had prescribed the solution—notably child specialists" [6]. (Presumably Nelson presented his medical findings to the society on the evening of October 10, 1937, per Dr. James Stephenson's telegram to the AMA.)
On October 12, the AMA determined by telegraph that Massengill's product contained a substantial amount of diethylene glycol, a known toxin. However, this information was too late for the parents of 4-year-old Charlene Canady of Tulsa, who had received the elixir for a sore throat. The girl died that day [1].
On Friday, October 15, Dr. Homer Ruprecht and Dr. Nelson telegraphed their autopsy findings on the Tulsa victims to the AMA. Eight out of 10 were now dead, and one was in critical condition. Astonishingly one patient had recovered. Urine production typically stopped within 2 days after patients received variable amounts (as little as one-half ounce) of the antibiotic elixir. Death occurred within 2-7 days after the onset of anuria. Gross postmortem findings revealed cortical necrosis of the kidneys, and microscopic examination showed a "consistent hydropic tubular nephrosis." No oxalate crystals were observed in the kidneys (as suggested by data conveyed by the AMA's Paul Leech). The telegram ended with, "Federal inspectors arrived today"[7].
In fact, the first word of the Tulsa deaths only came to the Food and Drug Administration the previous day. A New York physician "associated with a large drug manufacturing concern" had evidently telephoned the agency and repeated rumors, "presumably through professional or trade contacts, that fatalities had occurred at Tulsa" [5,8]. Immediately the agency telegraphed its Kansas City Office, and 2 agents, district chief William H. Hartigan and Walter E. Donaldson, "jumped into a motor car." They arrived in Tulsa, 250 miles away, the following morning and wired their findings to the FDA's Chicago office, which, in turn, wired Washington, DC [6,9].
TULSA COUNTY MEDICAL SOCIETY SUSPECTS DEATHS EIGHT CHILD STREPTOCOCCIC THROAT CASES ONE ADULT GONORRHEAL DUE ALIXIR[sic] SULFANILAMIDE MASSENGILLS SYMPTOMS ACUTE ANURIA STOP MEDICAL SOCIETY SUBMITTED SAMPLE TO AMERICAN MEDICAL ASSOCIATION STOP THREE SAMPLES ELIXIR COLLECTED TODAY FROM RETAIL DRUGGISTS WHO WITHHELD STOCKS FROM SALE ON REQUEST MEDICAL SOCIETY AIR EXPRESS-ED BALTIMORE STOP STLOUIS NOTIFIED VIA WESTERNUNION RUMOR HERE SIMILAR CIRCUMSTANCES STLOUIS WILL CONTINUE INVESTIGATION INCLUDING CLINICAL RECORDS UNTIL FURTHER NOTICE...MEDICAL ASSOCIATION REPORTS DIETHYLENE GLYCOL FOUND IN THEIR SAMPLE STOP CINCINNATI INSPECTOR WITH KLUMPP PROCEEDING BRISTOL FOR INVESTIGATION MASSENGILL STOP WILL FORWARD SAMPLES FINISHED PRODUCT AND ALL RAW MATERIAL BALTIMORE STOP HARTIGAN INSTRUCTED EMBARGO ALL WHOLESALE AND RETAIL LOTS IN TULSA STOP CINCINNATI TO REPORT ALL DISTRIBUTIONS THIS AND OTHER CODES PROBABLY CONTAINING DEITHYLENEGLYCOL AND ALL LOTS WILL BE EMBARGOED PENDING COMPLETE INVESTIGATION STOP BALTIMORE BEING ADVISED.
Most concerning was a rumor that similar cases had been observed in St. Louis, Missouri. Indeed, a pathologist in East St. Louis, Illinois, who was unaware of the Tulsa deaths, was preparing his necropsy report of 4 patients who had consumed the new antibiotic elixir [10]. And in addition to notifying its St. Louis office, the FDA was sending investigators (ie, Cincinnati inspector William T. Ford and the FDA's Acting Chief of its Drug Division, Theodore G. Klumpp, MD) to the Massengill company in Bristol, Tennessee.
For his part, Massengill was engaged in shrouded damage control. (The company had also learned of the Tulsa deaths in a complaint from the city's Getman Drug Store, which had dispensed several prescriptions for the elixir, including those to the deceased.) The day that FDA agents arrived in Tulsa, the Massengill company sent out more than 1000 telegrams nationwide [5]:
To its customers: DO NOT USE ELIXIR SULFANILAMIDE SHIPPED. RETURN OUR EXPENSE.
To its salesmen: ELIXIR SULFANILAMIDE DISCONTINUED. PICK UP AS RAPIDLY AS POSSIBLE ALL SOLD IN YOUR TERRITORY.
To "jobbers" (presumably wholesalers), druggists, and doctors who had received the product: HAVE WITHDRAWN PRODUCT ELIXIR SULFANILAMIDE. PLEASE RETURN UNUSED STOCKS IMMEDIATELY.
But within 24 hours, Massengill's elixir claimed its ninth Tulsa victim, Earl L. Beard, 26 years. He had received an 8-ounce prescription for the product and was ill for 2 days before requiring hospitalization [11,12,13,14].
* The sixth death at this time has not been deduced by this blog writer. It was likely one of 3 children: John "Jack" King; Robert "Bobby" Sumner; or 10-month-old Mary Earline Watters (or Waters). Each had received either a 3- or 4-ounce prescription for Massengill's Elixir Sulfanilamide.
1. FDA records. Correspondence from AMA Council, October 13, 1937.
2. Tulsa Daily World. October 6, 1937.
3. Tulsa Daily World. October 7, 1937.
4. Tulsa Daily World. October 10, 1937.
5. Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937. The AMA also reported that it telegraphed the FDA on October 14, 1937, regarding the presence of diethylene glycol in Massengill's product. See footnote in Deaths due to Elixir of Sulfanilamide-Massengill. J Am Med Assoc. 1937;109:1985-1987.
6. Frantic fight on death is heart-breaking job. Kansas City J. October 31, 1937. According to the article, "precious days, hours, minutes were saved by" the work of Dr. Nelson.
7. Ruprecht HA, Nelson IA. Elixir of Sulfanilamide-Massengill: clinical and pathologic observations. J Am Med Assoc. 1937;109:1537.
8. FDA records. Letter from Perrin H. Long to FDA, October 15, 1937. The letter conveys information that rumors regarding the Elixir-Sulfanilamide deaths began spreading in the Tulsa community on October 7, 1937. A representative from Squibb and Sons and a representative from Winthrop Chemical Company reportedly called on several hospitals in the Tulsa area to obtain additional information. The reps discovered that all patients who were dead at the time, 5 children, were attended by the same pediatricians and were prescribed Massengill's product.
9. FDA records. Record of telegraph correspondence, October 16, 1937.
10. Hagebusch OE. Elixir of Sulfanilamide-Massengill: necropsies of four patients following administration of Elixir of Sulfanilamide-Massengill. J Am Med Assoc. 1937;109:1537-1539.
11. Tulsa Daily World. October 17, 1937.
12. Tulsa Tribune. October 17, 1937.
13. FDA records. November 20, 1937, correspondence.
14. Tulsa Tribune. October 17, 1937.
Picture of bottle of DEG-tainted Elixir Sulfanilamide from the FDA.
In 1937, more than 100 US citizens—many children—died after consuming Elixir Sulfanilamide, a raspberry-flavored antibiotic syrup manufactured by the S. E. Massengill Pharmaceutical Company of Bristol, Tennessee. The difficult-to-dissolve antibiotic was mixed with diethylene glycol (DEG), a known toxin, by the company's uninformed head chemist, Harold Cole Watkins. Watkins reportedly tested the elixir only for its appearance and palatability before its nationwide distribution. The catastrophic event led to the passage of the 1938 Federal Food, Drug, and Cosmetic Act.
In a series of posts (and perhaps what may be a very lengthy series), the Pathophilia blog will attempt to provide a chronology of this US pharmaceutical disaster, drawing on primary sources when available. The effort is intended to be a kind of memorial to those who died as a result of the catastrophe and an homage to those who attempted to avert further disaster. However, the reader's indulgence is requested for what may frequently resemble a patchwork construction: Because the series is a work in progress, newly discovered and rediscovered information, as it emerges, may need to be incorporated into existing posts for clarity, accuracy, and completeness. For those individuals whose family, friends, or colleagues were directly affected by the event, your input and corrections are urged.
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In the fall of 1937, the first reports of deaths that were suspected to be related to the S. E. Massengill Company's "Elixir Sulfanilamide" came from Homer A. Ruprecht, MD, of the Springer Clinic of Tulsa, Oklahoma, and James Stephenson, MD, president of the Tulsa County Medical Society. Their correspondence, by telegraph and letter, to the American Medical Association indicates the historical importance of the national association and its journal editor, Morris Fishbein, MD, as primary sources of medical and pharmaceutical guidance for physicians in the country (in contradistinction to the Food and Drug Administration or any other government agency, at the time). Specifically the AMA had formed the Council on Pharmacy and Chemistry in 1905, an organization created to examine the composition of industry-submitted pharmaceutical products for sale in the United States.
On Saturday, October 9, 1937, the following telegram was sent from the Springer Clinic in Tulsa to Dr. Fishbein in Chicago.
ATTENTION IS CALLED TO AT LEAST SIX DEATHS IN TULSA FOLLOWING ADMINISTRATION OF ELIXIR OF SULFANILAMIDE SYMPTOMS OF ANURIA AND TOXIC DEGENERATION OF LIVER AND KIDNEYS
In Dr. Fishbein's absence, Paul Nicholas Leech, PhD, Secretary of the AMA's Council on Pharmacy and Chemistry responded:
YOUR TELEGRAM WILL BE BROUGHT TO DR FISHBEINS ATTENTION ON HIS RETURN THURSDAY STOP IN MEANTIME WOULD APPRECIATE RECEIVING FULL DETAILS CONCERNING DEATHS IF THIS OFFICE CAN AID YOU FURTHER PLEASE ADVISE
The following day, Sunday, Dr. Stephenson telegraphed the AMA with a brief description of the deaths and asked for information regarding the contents of the elixir:
ELIXIR SULFANILAMIDE MASSENGILL THERAPY MANY CASES COMPLETE ANURIA WITH UREMIA TULSA COUNTY MEDICAL SOCIETY MEETS SUNDAY NIGHT DESIRE ALL POSSIBLE INFORMATION AT ONCE WIRE OR PHONE ME MY EXPENSE
Leech responded, indicating that the Council had not examined any such elixir:
NO PRODUCT MASSENGILL COMPANY ACCEPTED BY COUNCIL ON PHARMACY AND CHEMISTRY STOP SULFANILAMIDE IN ELIXIRS NOT RECOMMENDED STOP PHYSICIANS WOULD DO WELL TO USE ONLY ACCEPTED BRANDS AND DOSAGE FORMS STOP SEE EDITORIAL IN JOURNAL OCTOBER SECOND COMMA TEN ARTICLES IN JOURNAL SEPTEMBER TWENTY FIFTH AND COUNCIL REPORTS IN JOURNAL MAY TWENTY NINTH AND JULY THIRTY FIRST
The October 2nd editorial, referred to by Leech (Sulfanilamide—a warning. J Am Med Assoc. 1937;109:1128), advised of the potential toxicities of the wildly popular antibiotic—namely, dermatitis, photosensitization, granulocytopenia, and sulfhemoglobinemia—and the indiscriminate use of the product and its unvetted derivatives. These warnings were initially provided in reports to the journal and published in its September 25th issue. The Council on Pharmacy and Chemistry also submitted its review of the antibiotic, related compounds, and proprietary US formulations in the May and July issues of the journal (Sulfanilamide. J Am Med Assoc. 1937;108:1888-1890; New and nonofficial remedies: sulfanilamide. J Am Med Assoc. 1937;109:358-359).
In a letter to the AMA, dated Monday, October 11, Dr. Ruprecht of the Springer Clinic further described the affected Tulsa patients and their symptoms:
Received your telegram in response to our wire regarding elixir of sulfanilamide. The details are as follows:
We have a list of ten patients who have received an elixir of sulfanilamide, all of which, so far as we have been able to determine, has been manufactured by the S. E. Massengill Company. Of these ten patients, four are living, two of whom have definitely recovered, and the other two will probably die. Eight of these patients were children and the drug was given because of an upper respiratory infection. The other two patients were young men and the drug was used for a gonorrheal infection. One of the latter two patients had received tablets of sulfanilamide over a period of two weeks without any bad effects and then changed doctors and the second doctor put him on the elixir of sulfanilamide and the typical train of symptoms followed shortly afterwards.
The onset is usually with nausea, vomiting, malaise, sometimes diarrhea, and then complete anuria. The N.P.N. [nonprotein nitrogen] urea nitrogen and creatinine rise rapidly. A fixed acid acidosis develops and death follows. Autopsy shows a marked accumulation of fluid in all the serous cavities and intense hydropic degeneration of the kidney tubules and a marked periferal[sic] type of liver necrosis.
We have asked Getman Drug Company of Tulsa to forward a sample of the material for analysis. Would appreciate any information which you can give me at the earliest opportunity.
In a separate letter, Dr. Darwin B. Childs of Tulsa indicated that he was providing a bottle of elixir to the AMA:
Under separate cover I am sending you a sample in the originally dispensed bottle, of "Elixir of Sulfanilamide".
This medicine was purchased by my patient, from the Quaker Drug Store of this City, and was sold from a stock bottle manufactured by the S. E. Massengill Company of Bristol, Tenn.-Va.
At least six deaths have been reported in this city during the last ten days as a result of so-called streptococcic throat. Each and every one of these patients had various amounts of the above drug. All of them took medicine manufactured by S. E. Massengill and Company. These patients developed, after about three days, an acute nephritis, with total anuria.
My patient, a 20 year old adult, who had an acute gonorrhea, took a total of 220 grains, as represented by 55 teaspoonfuls of the elixir of sulfanilamide. Twenty-four hours after the ingestion of this amount, he began to have symptoms of an acute nephritis, and forty-eight hours later he was totally anuric. He died four days after receiving the last dose. The clinical picture and autopsy reports of this case closely resemble each of the other cases.
It is my opinion, and the opinion of the other physicians here who have had such cases, and that probably your chemistry department will be able to give us some light on this matter. We have asked Massengill's representative to discontinue the sale of this product until we have a report from you.
On Monday, Leech telegraphed the Massengill company, requesting the composition of the elixir, and on the following day, October 12, the company wired its response—collect:
ACCEPT CONFIDENTIALLY ELIXIR SULFANILAMIDE CONTAINS SULFANILAMIDE FORTY GRAINS TO EACH FLUIDOUNCE DISSOLVED IN A MIXTURE OF TWENTY FIVE PERCENT WATER AND SEVENTY FIVE PERCENT DIETHYLENE GLYCOL WITH MINUTE QUANTITIES OF FLAVOR AND COLOR STOP WAS GIVEN CLINICAL TESTS AND WIDELY USED IN PRACTICE WITHOUT UNTOWARD RESULTS EXCEPT YESTERDAY SPRINGER CLINIC TULSA OKLAHOMA MADE COMPLAINT STOP WILL APPRECIATE ALL INFORMATION YOU MAY HAVE OR ACCUMULATE STOP
WIRE COLLECT BY WESTERNUNION
Leech then wired Dr. Ruprecht that day, warning him of the elixir's contents:
THANKS FOR YOUR LETTER OCTOBER ELEVENTH WOULD APPRECIATE FURTHER DETAILS WHEN AVAILABLE PARTICULARLY DOSAGE OF ELIXIR AND POSTMORTEN[sic] FINDINGS STOP PRODUCT CONTAINS MUCH DIETHYLENE GLYCOL AS SOLVENT THIS IS TOXIC AND REPORTED TO CAUSE NEPHROSIS POSSIBLY MAY BE OXIDIZED TO OXALIC ACID SEE JOURNAL PHARMACOLOGY AND EXPERIMENTAL THERAPEUTIC VOLUME FORTY TWO PAGE THREE FIVE FIVE COMMA NINETEEN THIRTY ONE STOP SUGGEST PATHOLOGISTS DETERMINE IF OXALATE POISONING IS INDICATED STOP WILL MAKE CHEMICAL EXAMINATION OF YOUR PRODUCT WHEN RECEIVED
Leech was referring Ruprecht to, "The pharmacology of ethylene glycol and some of its derivatives in relation to their chemical constitution and physical chemical properties" (J Pharmacol Exp Ther. 1931;42:355), in which investigators reported the minimum lethal dose of a 50% diethylene glycol solution in mice (5 mL/kg). Another study, published in early 1937, had also examined the lethality of diethylene glycol in animals: these investigators found that a 3% solution was rapidly fatal in rats (Haag HB, Ambrose AM. Studies on the physiological effect of diethylene glycol. J Pharmacol Exp Ther. 1937;59:93-100).
As would soon become apparent, the Massengill Company had manufactured 240 gallons of its DEG-loaded Elixir Sulfanilamide and had begun distributing the product nationwide on September 4, 1937.
Primary sources:
AMA correspondence. October 13, 1937. Food and Drug Administration Records. Record Group 88. National Archives; College Park, MD.
Wallace HA. Report of the Secretary of Agriculture on the deaths due to Elixir-Sulfanilamide-Massengill. November 16, 1937.
Picture of bottle of DEG-tainted Elixir Sulfanilamide from the FDA.
Yesterday, 9 FDA scientists sent a letter to Obama's transition team, pleading with the President-Elect to restructure the "fundamentally broken" agency, reports today's WSJ. The scientists allege that FDA managers "ordered, intimidated and coerced" the scientists to manipulate data during product reviews, particularly within the Center for Devices and Radiological Health (CDRH). The letter's authors were not reported.
A similar letter was sent in October to the House Energy and Commerce Committee, but yesterday's correspondence is more detailed, writes the WSJ, describing allegations like the "threat of disciplinary action against scientists who dissent from management." The letter also specifies that past CDRH approvals of certain computer-aided detection devices for mammography were not supported by scientific evidence, writes the WSJ.
The following excerpts from the scientists' October letter likely indicate the nature of their complaints in yesterday's correspondence:
Managers at CDRH have failed to follow the laws, rules, regulations and Agency Guidance to ensure the safety and effectiveness of medical devices and consequently, they have corrupted the scientific review of medical devices. This misconduct reaches the highest levels of CDRH management including the Center Director and Director of the Office of Device Evaluation (ODE).
Managers at CDRH with no scientific or medical expertise [redacted] devices, or any clinical experience in the practice of medicine [redacted] have ignored serious safety and effectiveness concerns of FDA experts and have ignored scientific regulatory requirements. To avoid accountability, these managers at CDRH have ordered, intimidated and coerced FDA experts to modify their scientific reviews, conclusions and recommendations in violation of the law. Furthermore, these managers have also ordered, intimidated and coerced FDA experts to make safety and effectiveness determinations that are not in accordance with scientific regulatory requirements, to use unsound evaluation methods, and accept clinical and technical data that is not scientifically valid nor obtained in accordance with legal requirements, such as obtaining proper informed consent from human subjects. These same managers have knowingly avoided and failed to properly document the basis of their decisions in official Agency records.
Under the banner of regulatory "precedent," managers at CDRH have demanded that physicians and scientists review regulatory submissions employing methods, and accepting evidence and conclusions, that are not scientifically proven and clinically validated.
The letter goes on to describe the scientists' complaint to FDA Commissioner Andrew von Eschenbach in May 2008, which led to an investigation with William McConagha, Assistant Commissioner for Integrity and Accountability. The investigation culminated in a September meeting among FDA scientists, representatives from the Commissioner's office, and the CDRH Director, Daniel Schultz.
The meeting prompted Schultz to conduct his own investigation of CDRH. But Schultz concluded, according to the letter, that the "FDA physicians and scientists need to 'move forward,' thus allowing managers to avoid and evade any accountability and without taking any curative or disciplinary actions whatsoever." Schultz is also alleged to have allowed the continuation of management reprisals against FDA reviewers, including threats of job loss and "illegal and improper employee performance evaluations."
Schultz, a medical doctor, is a career FDA officer who was appointed CDRH Director in 2004. Donna-Bea Tillman, PhD, is Director of the ODE.
01/13/09 update: In yesterday's NYT, Gardiner Harris reveals that an FDA supervisor overruled FDA scientists and approved iCAD's SecondLook Digital Computer-Aided Detection System for Mammography, after receiving a phone call from former Connecticut congressman Christopher Shays. (FDA approval info here.) The device is used in conjunction with screening equipment made by Fujifilm Medical Systems, which is based in Stamford, CT, the center of Shay's former district.
Harris's article was evidently prompted by FDA documents, which were recently provided to the NYT. In e-mails, FDA scientists claimed that a supervisor forced them to change their reviews of iCAD's breast-imaging device, despite the fact that "iCAD never tested the device by the intended users (ie, radiologists) under the intended conditions of use." An FDA review indicated that the iCAD device was associated with unacceptable false-negative and false-positive rates, which resulted in missed cancers or unnecessary surgery and even radiation therapy. In response, iCAD's CEO told the paper, "We have done all the appropriate testing to get the product approved."
For his part, Shay claimed that he called an FDA supervisor 1 year ago "only to demand that the agency make a final decision, not that it approve the product." A spokesperson for Fujifilm admitted to the NYT that the company requested local congressional support to "get clarification on the FDA process."
In his article, Harris also cites the arguably inappropriate, abbreviated FDA review of complex, novel devices at the behest of FDA managers. One such example is the FDA review of AngioCT from Shina Systems.
In a country checked by stratospheric inflation and political corruption, a persistent cholera epidemic in landlocked Zimbabwe has now taken more than 1700 lives and sickened 35,330, according to the latest report from the World Health Organisation.
Since August 2008, the epidemic has affected all provinces in the country, reveals WHO; however, a large percentage of cases have been documented in Budiriro, a congested suburb of Harare, and in Beitbridge, a border town with South Africa. The overall fatality rate of disease is reported at 4%, but death rates have escalated to 20%-30% in remote areas.
The organization Medecins Sans Frontieres (Doctors Without Borders) reports a "clear shift" in cholera cases from Zimbabwe's urban areas to suburban and rural towns, which logistically confounds disease management. Nevertheless, unlike WHO, MSF reports an overall decrease in the number of cholera cases in Zimbabwe. MSF suggests that tally differences between the 2 organizations may be a function of the spread of disease and disease-reporting capabilities. Sources cited at Wikipedia indicate that the cholera epidemic has spread to neighboring countries Botswana, Mozambique, South Africa, and Zambia.
Cholera, caused by the bacterium Vibrio cholerae, is primarily transmitted through contaminated food or water. The characteristic symptom of copious, watery diarrhea, caused by the bacterial enterotoxin, can lead to death through dehydration. The collapse of clean water supplies, sanitation measures, and garbage collection in Zimbabwe are aggravating factors of the epidemic. Professional medical care in Zimbabwe has also been stymied by the country's economic crisis. To top it off, the rainy season began in November.
WHO currently urges proper food safety and personal hygiene, as well as the use of oral rehydration salts to reduce the mortality risk associated with cholera. Prophylactic antibiotics are discouraged, and once an outbreak has begun, the "internationally available WHO prequalified oral cholera vaccine" is not recommended. (The parenteral cholera vaccine was never recommended by WHO because of its low efficacy and risk of adverse events.)
Map showing spread of cholera in Zimbabwe as of December 6, 2008, from Wikipedia.
On the morning of November 30, 1982, Nancy Haigwood walked out of her Gaithersburg, MD, townhome to find "KKG" carefully spray painted on her fence, sidewalk, and the rear window of her fiancé's car. Haigwood, a member of the sorority Kappa Kappa Gamma, had moved in only a few months earlier. Her address, she claimed, had not been published.
At the time, Bruce Ivins, a USAMRIID scientist, lived just a block away. Haigwood had known Ivins, an acquaintance, through their recent postgraduate studies at the University of North Carolina. He was an unusual, officious kind of guy who, according to Haigwood, had shown a specific interest in her ΚΚΓ membership. She was sure that Ivins was the vandal and confronted him during a chance encounter soon afterward. He denied it.
Months later, a "Nancy L. Haigwood" wrote the following letter to the editor of The Frederick News-Post. The letter, published May 9, 1983, was in response to a buried AP story in the paper about a University of Montana frat member* who had floated a dead kitten in a block of ice in a punch bowl. Despite the fact that the article did not mention fraternity hazing, the letter defended the practice.
It seems that every time I read an article in the News-Post about college fraternities or sororities, the tone of the article is decidedly negative. "Frat member floats kitten in punch" (April 15, 1983) continues that unfortunate tradition.
As a member of Kappa Kappa Gamma, one of our nation's oldest and most prestigious college sororities, I am continually dismayed by attempts of the media and other outsiders to disparage the Greek System. I am especially incensed at vitriolic attacks on our practices of "hazing," which non-Greeks fail to realize serve numerous valuable functions that I would like to briefly enumerate.
First of all, hazing strengthens the mettle of pledges by preparing them for the many trials they will surely face in later life. Secondly, hazing builds loyalty to the pledge class and to the overall organization. Last but not least, hazing is the final stage of the all-important weeding-out process.
Charges that actives are to blame for accidental injuries which sometimes occur during pledge hazing are totally without foundation. No active ever forces any pledge or initiate to do anything in a sorority or fraternity—an individual is free to depledge at any time.
Charges that hazing and other related activities are detrimental to the academic performance of pledges obviously come from individuals who don't realize that the primary education in a college or university environment doesn't come from reading a book or sitting in a classroom, but rather from dynamically interacting with one's peers.
No one ever hears non-Greeks laud the accomplishments of those within the ranks, yet the proud Halls of American History are lined with men and women who were members of college fraternities and sororities. No matter what the press may say about us, I'm still proud to be in a sorority, proud to be counted among our country's very best.
NANCY L. HAIGWOOD
10265 Ridgeline Drive, Gaithersburg
Haigwood maintains that she never wrote the letter and believes that Ivins did. If true, the letter's author would have been a 37-year-old, male, USAMRIID scientist who had just published data about plasmid-mediated toxin production in Bacillus anthracis and the enhanced culture of the bacterium.
During the last few years, as jimmyflathead at Wikipedia, Ivins showed an interest in ΚΚΓ hazing by attempting to contribute information about the subject (see previous post here).
* God only knows where that creep is now.
Primary source: Microbiologist says she was stalked by Ivins. See also the FBI's Amerithrax search warrants for more information about Ivins's alleged online activity.
Public domain photograph of Daschle "anthrax" letter from Wikipedia.
Whether you believe that Bruce Ivins perpetrated the 2001 "anthrax letter attacks," one assertion is difficult to refute: The guy was more than just an affable oddball; he was chronically and seriously disturbed.
In yesterday's NYT, Scott Shane profiles the USAMRIID microbiologist, who is alleged to have mailed spores of Bacillus anthracis, the cause of anthrax, in block-letter-addressed envelopes to news organizations and congressmen shortly after 9/11. Shane's profile is not so much an examination of the scientific evidence against Ivins but a character portrait derived from, in part, interviews with family and friends and Ivins's own e-mails.
One notable feature of the NYT piece is the observation that Ivins led a highly compartmentalized life, in which he kept his long-time obsession with sororities in general and Kappa Kappa Gamma in particular from his family. His consuming thoughts about the sorority are germane to a behavioral study of the anthrax-letter perpetrator, because the Princeton, NJ, mailbox, from which all of the letters were posted, is 60 feet from a ΚΚΓ office.
Ivins's obsession materialized most disturbingly and concretely in his fixation on microbiologist and ΚΚΓ member Nancy Haigwood, a fixation that manifested in criminal activity according to Haigwood—namely, the vandalism of personal property and the usurpation of Haigwood's identity in the early 1980s. This information has been previously reported by other news sources (for instance, here). Also, like reporters before him, Shane reveals that Ivins spent an inordinate amount of time posting online about sororities by using the names kingbadger, jimmyflathead, and goldenphoenix.
Notably jimmyflathead's contributions to Wikipedia* include mention of Haigwood as an eminent ΚΚΓ member. Below are excerpts (not mentioned in the NYT article) that contribute to Bruce Ivins's very sad, strange, and enduring legacy:
Eelmonkey, I'm not a member of KKG, but at one time I had a copy of the Book Of Ritual. I'm familiar with their secrets and rituals, but I don't think that the organization would want them revealed. I would respectfully suggest you ask the opinions of some of the Kappas who have posted here. jimmyflathead 19:40, 7 July 2007 (UTC)
Eelmonkey, I also want to add that unless you have a copy of the KKG Cipher (decoder), or you have a decoded copy of the Book of Ritual, simply having the Book of Ritual won't do you any good...unless you got the information from the Fraternitysecrets.com message board which has now been down for quite some time. For example, do you know about the ***** room and *** room services? Do you know the secret names of the chapter officers? Do you know the terms for voting "yes" and "no?" Do you know what the Three Ideals of KKG are and what the Spirit is? Do you know what the ΚΚΓ Greek letters stand for? (It's NOT Key to the Kingdom of God, by the way.) The ritual book without the cipher is useless to you.jimmyflathead 19:19, 8 July 2007 (UTC)
Also, I'd like to see some Kappas put down for their scientific achievments[sic]. It's not my job to do it, but I can think of Dr. Nancy Haigwood and Dr. Gail Williams Wertz immediately as alumae who have distinguished themselves. It would look good, but I'm not about to go create a Wikipedia page for them just so they can be on the Kappa page. I just get tired of seeing lots of TV and moviestars, but scientists get short shrift. jimmyflathead 03:14, 15 August 2007 (UTC)
Last, I created a stub for Nancy Logan Haigwood, but she does not currently meet the criteria of having a wiki page. If we are going to keep her on the list, I think it at least makes sense for a page to be created. I don't know enough to make one - but jimmyflathead
I'm not in favor of removing Dr. Haigwood's name from the list of notable Kappas. I believe that her accomplishments warrant her inclusion and I know for certain that she is not only a KKG member, she was the chapter adviser (University of North Carolina at Chapel Hill) while in graduate school. I don't believe that fame or renown must derive from an individual's GLO membership and, as such, we may barely see a reference to it when describing the chief of neurosurgery at Johns Hopkins, or a Nobel lauriate[sic] in one of the scientific fields. There is certainly sufficient knowledge that the public can obtain (such as college yearbooks and the student newspaper, "The Daily Tarheel," to verify membership. jimmyflathead 00:25, 17 September 2007 (UTC)
* After Haigwood reluctantly struck up an e-mail correspondence with Ivins in 2006 at the behest of the FBI.
N.B. The NYT reveals that Ivins had stolen the KKG ritual book and cipher device during one of his 3 uninvited, post-college visits to a university chapter house. It is not known by me how or if Ivins ever knew Gail Wertz, PhD. Update: According to Wikipedia, there was no known relationship between Wertz and Ivins.
Public domain photograph of Daschle "anthrax" letter from Wikipedia.
Addendum: More about Ivins's activity as jimmyflathead at Wikipedia can be found here. His edits at the online encyclopedia almost exclusively concerned ΚΚΓ and escalated into an editing war, in which Ivins threatened to post derogatory or confidential information about the sorority if his additions were deleted or edited by another contributor. In at least one instance, Ivins attempted to add (and possibly re-add) information about hazing incidents.
The subject is important vis-a-vis Ivins, because a 1983 letter to the Frederick News-Post, signed by "Nancy L. Haigwood" defended the practice of hazing; however, Haigwood recently claimed to news sources that she never wrote the letter and suspects that Ivins did—several months after he allegedly spray painted "KKG" on property at her Gaithersburg, MD, home.
Pathophilia's Top 10 Medical Stories of 2008: A Recap
10. Gunvalson v. PTC Therapeutics
9. California v. Roozrokh and Cardiac-Death Organ Donation
8. Hand, Foot, and Mouth Disease in China
7. Continuing Backlash Against Pharma
6. Media Obsession With Delayed Results of ENHANCE Trial
5. Investigational Drugs for Alzheimer's Disease Disappoint
4. Milder Rotavirus Season Coincides With Vaccine Uptake
3. USAMRIID Scientist Identified as Sole Perpetrator of "Anthrax Letter Attacks"
1. Intentional Drug and Food Tampering in China
Other notable stories of 2008 that didn't make Pathophilia's totally arbitrary list:
- More cases of progressive multifocal leukoencephalopathy (PML) with Tysabri (natalizumab) use
- Pig-slaughter neuropathy
- US government compensates Poling family for vaccine-related autism
- Ted Kennedy diagnosed with glioblastoma multiforme
