Tech Forecast Digest
Updated: Nov 24, 2019
Sometimes technology is lost. Sometimes it is rediscovered.
“In most cases, we don’t know what causes asthma, and we don’t know how to cure it”
- Centers for Disease Control and Prevention (CDC)
Every day in the U .S. 44,000 people have an asthma attack. There are more than 3,300 deaths due to asthma each year and asthma is indicated as “contributing factor” for nearly 7,000 other deaths.
In the 1950’s Dr. Elmer D. Gay treated thousands of asthma sufferers with a solution that included arsenic. For over 2,400 years, arsenic has been used as a therapeutic agent. Arsenic and its derivatives have been found to be useful in treating diseases including forms of cancer.
My life had been threatened by severe attacks of asthma that would last up to two weeks. After starting treatments with Dr. Gay (the treatments lasted for two years), I never again experienced an asthma attack. I have been asthma free for more than 60 years.
In 1967, Harvard University researchers Drs. John Nader and Mark Novitch reported the results of a controlled trial of Gay's solution in patients whose asthma was intractable to treatment with either bronchodilators alone or bronchodilators plus corticosteroids. The Harvard researchers observed the following in their research paper: An evaluation of Gay’s solution in the treatment of asthma - John G. Nader, M.D., and A. Mark Novitch, M.D., Boston, Mass., December, 1967 concluded that “Gay’s solution is effective in the treatment of severe asthma and that this effectiveness is dependent on the presence of arsenic in the mixture. Because of the high incidence of side effects we recommend that it be tried only in refractory cases and that they be followed carefully.”
According to the Asthma and Allergy Foundation of America:
Asthma is characterized by inflammation of the air passages resulting in the temporary narrowing of the airways that transport air from the nose and mouth to the lungs. Asthma symptoms can be caused by allergens or irritants that are inhaled into the lungs, resulting in inflamed, clogged and constricted airways. Symptoms include difficulty breathing, wheezing, coughing, tightness in the chest. In severe cases, asthma can be deadly.
Asthma has a genetic component. If only one parent has asthma, chances are 1 in 3 that each child will have asthma. If both parents have asthma, it is much more likely (7 in 10) that their children will have asthma.
More Americans than ever before say they are suffering from asthma. It is one of this country's most common and costly diseases.
Every day in America:
44,000 people have an asthma attack.
36,000 kids miss school due to asthma.
27,000 adults miss work due to asthma.
4,700 people visit the emergency room due to asthma.
1,200 people are admitted to the hospital due to asthma.
9 people die from asthma.
Nearly 25 million Americans suffer from asthma (over 8% of adults, over 9% of children), and 60% of asthma cases are “allergic-asthma.” The prevalence of asthma has been increasing since the early 1980s across all age, sex and racial groups.
Asthma is the most common chronic condition among children.
Asthma is more common among children (7 to 10%) than adults (3 to 5%).
Nearly 5 million asthma sufferers are under age 18. It is the most common chronic childhood disease, affecting more than one child in 20.
Asthma is slightly more prevalent among African Americans than Caucasians.
Ethnic differences in asthma prevalence, morbidity and mortality are highly correlated with poverty, urban air quality, indoor allergens, and lack of patient education and inadequate medical care.
Morbidity and Mortality
Asthma accounts for one-quarter of all emergency room visits in the U.S. each year, with 1.75 million emergency room visits.
Each year, asthma accounts for more than 10 million outpatient visits and 479,000 hospitalizations.
The average length of stay (LOS) for asthma hospitalizations is 4.3 days.
Nearly half (44%) of all asthma hospitalizations are for children.
Asthma is the third-ranking cause of hospitalization for children.
Asthma is the #1 chronic cause of school absenteeism among children each year accounting for more than 13 million total missed days of school.
African Americans are three times more likely to be hospitalized from asthma.
Each day 9 Americans die from asthma. There are more than 3,300 deaths due to asthma each year, many of which are avoidable with proper treatment and care. In addition, asthma is indicated as “contributing factor” for nearly 7,000 other deaths each year.
Since 1980 asthma death rates overall have increased more than 50% among all genders, age groups and ethnic groups. The death rate for children under 19 years old has increased by nearly 80% percent since 1980.
More females die of asthma than males, and women account for nearly 65% of asthma deaths overall.
The death rate for children under 19 years old has increased by nearly 80% percent since 1980.
African Americans are three times more likely to die from asthma. African American Women have the highest asthma mortality rate of all groups, more than 2.5 times higher than Caucasian women.
Social and Economic Costs
The annual cost of asthma is estimated to be nearly $18 billion.
Direct costs accounted for nearly $10 billion (hospitalizations the single largest portion of direct cost) and indirect costs of $8 billion (lost earnings due to illness or death).
For adults, asthma is the fourth leading cause of work absenteeism and “presenteeism,” resulting in nearly 15 million missed or lost ("less productive") workdays each year (this accounts for nearly $3 billion of the "indirect costs" shown above).
Asthma accounts for more than 10 million total missed days of work for adults each year.
Among children ages 5 to 17, asthma is the leading cause of school absences from a chronic illness. It accounts for an annual loss of more than 14 million school days per year (approximately 8 days for each student with asthma) and more hospitalizations than any other childhood disease. It is estimated that children with asthma spend an nearly 8 million days per year restricted to bed.
Senior citizens in the U.S. account for nearly 2,400 of the annual deaths due to asthma.
From: HemOnc Today, November 10, 2008
Despite its proven therapeutic benefits, concerns of toxicity and carcinogenicity caused a decline in the medicinal use of arsenic.
For over 2,400 years, arsenic — from the Greek word arsenikon, meaning “potent” — has been used as both a therapeutic agent and a poison. During their time, Hippocrates used the arsenic sulfides realgar and orpiment to treat ulcers, and Dioscorides used orpiment as a depilatory. Since then, arsenic and its derivatives have been found to be useful in treating diseases such as cancer and syphilis.
In the 19th century, arsenides and arsenic salts were used in the form of external pastes to treat ulcers and cancer. They were also prescribed as antiperiodics, antipyretics, antiseptics, antispasmodics, caustics, cholagogues, depilatories, hemantinics, sedatives and tonics. The drugs were used to treat systemic illnesses and could be prescribed in liquid or solid form, could be inhaled as vapor, injected, administered intravenously or given as enemas.
In the 1700s, English inventor Thomas Fowler developed a solution of arsenic trioxide in potassium bicarbonate (1% w/v) that was used to treat asthma, chorea, eczema, pemphigus, psoriasis, anemia, Hodgkin’s lymphoma and leukemia.
In 1878, the compound, aptly named “Fowler’s solution,” was discovered to lower white blood cell counts in normal individuals, with a more significant decrease occurring in those with chronic myelogenous leukemia treated for 10 weeks. After this finding, Fowler’s solution was used as a mainstay in the treatment of leukemia until it was succeeded by radiation in the 20th century.
Application and Research
In the 1950’s Dr. Elmer D. Gay treated thousands of asthma sufferers with a solution that included arsenic.
Letters written to the Journal of the American Medical Association (JAMA) in the early 1950’s were critical of Dr. Gay’s methods. Dr. Gay responded in a letter published in December 1954:
ASTHMA AND ARSENIC
To the Editor:- During the past few years there have appeared in medical publications several articles pertaining to the use and dangers of arsenic in the treatment of bronchial asthma. Although the subject matter merits constructive criticism, in several instances alleged prescription of the “Gay treatment” were published that were false, dangerous, and misleading. It is apparent that the authors of these articles failed to validate their factual material. In THE JOURNAL of March 1, 1952, page 734, there was published an article entitled “Cutaneous Sequelae Following Treatment of Bronchial Asthma with Inorganic Arsenic.” In the description of case 2 a prescription was quoted in such a way as to imply that the said prescription was essentially the Gay formula. This prescription called for three times the amount of potassium arsenite (Fowler’s) solution ever recommended by me or any of the physicians trained by me. In The Journal of Aug. 29, 1953, page 1711, and article was published entitled “Hemorrhagic Encephalopathy During Arsenic Therapy for Asthma.”
Although it was not specifically stated that this patient was treated by me or one of my former associates, there was an obvious inference to that effect. In this article it was stated categorically that analysis of the medicament at a well-known clinic revealed concentrations equivalent to 5 gm. of arsenic per liter. I wish to state emphatically that this represents over 11 times the amount of arsenic ever used or advocated by me. It is obvious that this is a dangerous mixture, and it was evidently prepared by someone completely ignorant of the danger of arsenic therapy or by someone attempting to discredit the form of treatment by misrepresentation.
It is in the public interest to have all controversial data carefully checked before publication. This holds true particularly in scientific articles in which the use or abuse of potentially toxic drugs is discussed. Although I have had excellent results in following the Gay treatment, others who have not had extensive experience may run into apparently insurmountable difficulties. Although I have encountered an occasional arsenical reaction, it has not constituted a serious threat to the merit of the treatment because of its early recognition and resultant modification of procedure. Since a positive approach to the matter is required, I am preparing a detailed account to the procedures involved in the Gay treatment and making a statistical survey of 1,000 cases that may be of considerable interest to all physicians engaged in this work.
ELMER D. GAY, M.D.
From The National Acadamies Press (http://www.nap.edu/openbook.php?record_id=6444&page=258 )
In the 1950s, the chronic, often unsupervised use of [ Dr.] Gay's solution containing potassium arsenite, digitalis, potassium iodide, and phenobarbital for asthma created controversy when reports of success were countered by reports of overt arsenic toxicity (Silver and Wainman 1952; Pascher and Wolf 1952; Gay 1954).
In 1967, Harvard investigators Harter and Novitch reported the results of a controlled trial of Gay's solution in patients whose asthma was "intractable" to treatment with either bronchodilators alone or bronchodilators plus corticosteroids. The patients' pre-enrollment regimen was supplemented, in a double-blind manner, with variants of Gay's solution containing or lacking inorganic arsenic.
"Definite" clinical improvement was found within 10 days in 7 of 18 patient trials that included arsenic administration (5-6.7 mg of arsenite per day) compared with only 1 of 11 patient trials lacking arsenic (p = 0.007). Approximately one-fourth of the patients receiving arsenic manifested gastrointestinal toxicity.
The precise mechanisms by which inorganic arsenic exerted salutary effects in treatment have not been elucidated, but it is of interest that its reported benefit in psoriasis, eczema, and bronchial asthma and its antipyretic effect in certain febrile diseases suggest that it might have exerted suppressive effects on immune-mediated inflammation.
From the Harvard University Research
The Harvard researchers observed the following in their research paper: An evaluation of Gay’s solution in the treatment of asthma - John G. Nader, M.D., and A. Mark Novitch, M.D., Boston, Mass., December, 1967.
Forty-three patients with severe asthma were treated with Gay’s solution (Fowler’s solution). which contains potassium arsenite, tincture of digitalis, sodium phenobarbital, and potassium iodide). Eight of 25 patients in a pilot uncontrolled study and 13 out of 18 patients on arsenic double-blind study were improved. The results of the double blind study were statistically significant at a p < 0.01 level.
It is concluded that Gay’s solution is effective in the treatment of severe asthma and that this effectiveness is dependent on the presence of arsenic in the mixture. Because of the high incidence of side effects we recommend that it be tried only in refractory cases and that they be followed carefully.
Although good results have been reported in treating asthma with a mixture of Fowler’s solution, tincture of digitalis, sodium phenobarbital, and potassium iodide (Gay’s solution), this treatment has not been widely used or accepted. It has been generally assumed that the efficacy and toxicity of the mixture is largely due to the potassium arsenite in the Fowler’s solution.
The present study was undertaken because of the dramatic improvement of a patient after a trip to Gulfport, Mississippi, where he received Gay’s solution with no other change in his management as far as we could see. The study was conducted in two phases. The first phase involved the use of Gay’s solution in 25 patients to familiarize ourselves with its administration and side effects. The second phase involved a double-blind study in 28 patients of mixtures with and without Fowler’s solution and with and without the potassium iodide.
Based on our own experience reported here, as well as that, reported in the literature, we would make the following recommendations for the use of Gay’s solution in patients with asthma until further information becomes available:
(1) Gay’s solution should be reserved for trial in those patients with asthma which cannot be well controlled by conventional treatment, short of corticosteroids.
(2) The physician should discuss with the druggist the importance of careful compounding and the advisability of making up small batches so that it is less than 90 days old when dispensed. The physician should follow the patient carefully for signs and symptoms of efficacy and toxicity. If there is doubt about the efficacy, the mixture should not be continued. If toxicity occurs, the dosage should be decreased or the mixture stopped, depending on the circumstances.
Used in this way, Gay’s solution may be the treatment of choice in approximately one third of the patients with difficult-to-manage, intractable asthma.
Dr. Gay’s solution, as noted in the Harvard study, consists of the following components:
“Fowler's solution” is a solution containing 1% potassium arsenite (KH2AsO3).
A copy of the Harvard researchers’ complete paper can be downloaded from: http://www.sciencedirect.com/science/article/pii/0021870767900226
Other research on animals indicated that arsenic could alleviate the adverse effects of asthma.
The evaluation of arsenic as an antiasthmatic. Effect on experimental asthma of guinea pigs
Journal of the American Pharmaceutical Association
Volume 45, Issue 1, pages 1–5, January 1956
Duane G. Wenzel, Philip Rosenberg
Copyright © 1956 Wiley-Liss, Inc., A Wiley Company
(from the Abstract)
Arsenic, administered as a single dose of potassium arsenite or oxophenarsine, was found to prolong significantly the response time of guinea pigs to aerosolized histamine.
More recently, researchers have rediscovered the potential beneficial effects of Arsenic for human asthma.
Arsenic trioxide, a potent inhibitor of NF-κB, abrogates allergen-induced airway hyperresponsiveness and inflammation
Lin-Fu Zhou, et al
“Clinically, low dosage of As2O3 may have a potential benefit in treating patients with asthma, especially in those with steroid-dependent and -resistant asthma.”
Arsenic trioxide alleviates airway hyperresponsiveness and eosinophilia in a murine model of asthma
Kuan-Hua Chu, et al. 2010
“As2O3 might therefore have therapeutic potential in treating allergic airway inflammatory diseases.”
Effects and Mechanism of Arsenic Trioxide on Reversing the Asthma Pathologies
Li Zhang, et al. 2012
Department of Respiratory Medicine, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China
“Our study suggested that Arsenic Trioxide had potential medical value for the treatment of human asthma.”
Effects of arsenic trioxide (As2O3) on airway remodeling in a murine model of bronchial asthma
Zi-ping Xu,et al. 2012
Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, No.155 Nanjing Street, Heping District, Shenyang, Liaoning Province, China
“Our results suggest that steroids and As2O3 can inhibit airway remodeling in chronic asthma by mechanisms related to inhibiting the expression of the 3 aforementioned mediators.”
University of Maine
Department of Molecular and Biomedical Sciences
Professor Julie Gosse envisions a safe medical alternative that would mimic arsenic’s valuable suppressive effects for disorders such as asthma or autoimmune disorders, without undermining overall immune response — and without arsenic’s potentially lethal risks.
In 1998, the Food and Drug Administration (FDA) removed Fowler’s solution – the essential component of Dr. Gay’s solution – from “the Market for Reasons of Safety or Effectiveness”.
[Federal Register: October 8, 1998 (Volume 63, Number 195)]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 216
[Docket No. 98N-0655]
List of Drug Products That Have Been Withdrawn or Removed From
the Market for Reasons of Safety or Effectiveness
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
its regulations to include a list of drug products that may not be used
for pharmacy compounding pursuant to the exemptions under section 503A
of the Federal Food, Drug, and Cosmetic Act (the act) because they have
had their approval withdrawn or were removed from the market because
the drug product or its components have been found to be unsafe or not
effective. The list has been compiled under the new statutory
requirements of the Food and Drug Administration Modernization Act of
1997 (Modernization Act).
DATES: Comments must be received on or before November 23, 1998.
ADDRESSES: Submit written comments to the Dockets Management Branch
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061,
Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-2041.
Potassium arsenite: All drug products containing potassium arsenite. Potassium arsenite, formerly marketed as Fowler's Solution (oral), was toxic and highly carcinogenic. FDA determined Fowler's Solution was a new drug in April 1980, and the manufacturers removed the drug product from the market.
In spite of the action by the FDA in 1980 as noted above, a current approved arsenic-based treatment of humans is in use. The FDA approved Arsenic trioxide (Trisenox), in September of 2000 to treat patients with acute promyelocytic leukemia.
APPENDIX: Dr. Elmer D. Gay
Elmer D Gay was born on 12/15/1906 and died on 09/09/1980 at the age of 73. Dr. Gay is buried in the Biloxi National Cemetery.
Dr. Gay served in the U.S. Army during World War II .
Dr. Gay's work during the war is cited by the cardiac surgeon Dr. Michael E. DeBakey and Dr. B. Noland Carter.
Photo Credit: http://www.flickr.com/photos/jllbms/4921271681/
Building that housed Dr. Gay’s asthma clinic in the 1950’s. Downtown Gulfport, MS
I suffered from severe asthma when I was pre-school and in the first grade. I would lie propped up in bed for days struggling to breathe. I missed several weeks of school.
My parents were at a loss for how to treat the illness. Them they heard from a relative about a doctor in Gulfport, Mississippi who had success in treating asthma.
My father took me to Gulfport and to the clinic of Dr. Elmer D. Gay. Dr. Gay treated me for two years with a red colored solution that included arsenic. With my mother’s oversight, I followed Dr. Gay’s treatment regimen rigorously and precisely during the two years.
After the visit to Dr. Gay I never again had an attack of asthma. Coincidence?
I have lived an active life including competitive aerobic varsity high school sports (basketball and track) and serving as an officer in the U.S Army infantry in environments ranging from near the arctic circle to the jungle. The army tenure included intensive aerobic physical training in the Infantry Officer, Ranger and Airborne programs. Subsequently, I have continued with a variety of often strenuous aerobic activities into my sixties. I have resided in several geographic areas of the U.S. including Alabama, Florida, Georgia, Oklahoma, North Carolina, Connecticut, Chicago, San Francisco and Dallas.
Had my asthma persisted, I would have had a very different life.
Six decades later, I came across a story of asthma similar to mine.
In his book:” Persuasion of My Days, An Anecdotal Memoir”, the late professional sports mental skills coach Harvey A. Dorfman (he earned World Series rings from the Oakland A’s and the Florida Marlins for his work), who grew up in the Bronx, remembered his life with asthma and his relationship with Dr. Gay.
“Minutes later Dr. Gay opened the door and entered. I saw first a head of hair as silver as the Lone Ranger’s bullets. His face had lines of kindness and concern - and age. He wore a brown cardigan sweater over his white shirt and faded blue/purple/gray tie. He belonged on the cover of the Saturday Evening Post, I thought.
At that time, my attitude toward any particular doctor and his potential to be effective ranged from tolerance accompanied by low expectations, to distrust with no expectation.
The truth of the matter is that I was most often cynical, as well, about my future prospects, so long as doctors were responsible for orchestrating them. Those who did nothing to change my condition would request that I have return visits. Again-and again. For what? I’ll allow the question to be rhetorical.
So, despite Dr. Gay’s pleasing physical presence, my first word after he has said, ‘Hello, young man, I’m Doctor Gay’, were: ‘Tell me what I can’t do.’ I must have sounded like a disillusioned sixty-five-year-old.
Dr. Gay gave me his cover-boy smile and said, ‘you can do whatever you want to do, young man.’ To be surprised is to begin to understand, someone once said.”
“My parents found out that a surprising number of people who had come to visit Dr. Gay never left him. They moved to Biloxi or Gulfport, the next town. When told of this, I asked my father for the reason. After all, the bottled medicine could be sent to them. He told me they wanted to be near him. They had improved so much, they didn’t want to take the chance of having their condition get worse.”
“What I have just now finished reading – with interest – is a letter sent to my mother in 1951. I took it from a folder of personal papers. It read as follows:
Dear Mrs. Dorfman,
Thank you for your letter of January 2nd.
We are mailing two bottles of red medicine for Harvey today. It is perfectly all right if you notice a variation in coloring in the medicine. This often happens. Sometimes it fades out and leaves the medicine an Amber color. The essential ingredients are still present.
Elmer D. Gay, M.D.
Well beyond two years, I was still ingesting those ingredients into my system. Essential ingredients? ‘Anything you want …’ ‘As much as you’re able to manage …’ Those were the essential ingredients – the ‘real ingredients’ – and they weren’t to be found in the red potion, or the amber. Not long ago I was told that medical people believed a touch of arsenic to have been an ‘essential ingredient.’ ”
Harvey Dorfman’s asthma improved to the level that he played on his college’s soccer team which won a national championship, and he served for eight years in the U.S. Naval Reserve.
Mr. Dorfman contracted Bowen’s disease which has been associated with the prolonged intake of arsenic.
“In my sixties, I developed Bowen’s disease, a skin cancer caused by the ingestion, during one’s early years, of arsenic. My recent treatment has been successful. I have no regrets; I’d ‘swallow’ Dr. Gay’s ‘treatment’ again.”
Image of Dr. Gay’s letter to The Journal of the American Medical Association, December 1954