CONTRIBUTIONS TO BETTER LIVING FROM CHEMICAL CORPS RESEARCH CARL B. MARQUAND Army Chemical Center, Maryland
IRRESPECT~VE
of the fact that the primary purpose of research and development conducted by the Chemical Corps is the successful production of implements of war, it produces a succession of incidental hyproducts wvhich become significant contributions to the arts and sciences as well as to the general welfare and better living. There are few branches of the Army whose military activities are more readily reflected in peacetime benefits than those of the Chemical Corps. I n the period following World War I the Chemical Warfare Service evolved a safe method for the fumigation of ships, exploited the technique of spraying crops by airplane, discovered a toxic agent for protecting sea piling from the Marine Borer, and developed special masks to guard against dangerous industrial fumes. Mechanical smoke generators originally developed by the Service and used effectively for screening combat areas have also been used very successfully for disseminating agricultural chemicals. Thesei'smoke ginnies" have frequently demonstrated their usefulness in putting out fogs of insecticides, fungicides, and plant growth regulators. Growth regulators are particularly useful in the prevention of premature apple drop in orchards. The efficacy of sprayed material is a function of droplet size: The fine size obtainable with smoke generators, therefore, make them excellent equipment for orchardists. Even the chemical agents developed in the effort
to keep us fully prepared for gaq ww-arfare have had co11siderable peacetime importance. These include chloropicrin, hydrogen cyanide, nitrogen mustards, and others. The war gas, chloropicrin, is xidely used in greenhouse and field work for the control of nematodes, soil-borne fungi, and bacteria, and more recently, weeds. It has also been used as a fumigant in mills. warehouses, and ships where inserts and rodents are a nuisance, and as a fumigant for insects infesting granaries, cereal bins, and other grain storage facilities. RODENTICIDE DEVELOPMENT
The discovery of 1080 (sodium fluoroa,cetate) is one of the outstanding examples of the effectiveness of cooperation in research activities. Spurred by a wartime shortage of the then-standard rodenticides, the Wildlife Research Laboratory of the Fish and Wildlife Service began a systematic searrh for effective substitutes. The importance of this work r a r dramatically emphasized when our Armed Forces operating in the Pacific islands encountered rat-borne diseases. The Office of Scientific Research and Development provided additional funds, and a close cooperation mas set up among various research groups, including the Medical Division of the Chemical Warfare Service. From this coordinated activity, sodium fluoroacetate
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was developed and its pharmacology studied. Today it is one of the most potent rodenticides available. By interfering with acetate utilization in the carbohydrate metabolism of susceptible species, 1080 produces severe disturbances in the central nervous system and in the heart. FUNGICIDES AND MILDEW-PROOFING AGENTS
During World War I1 in the tropical areas of the Pacific it soon became evident that improved methods of t r ~ a t i n g and packing material were necessary. Due to the excessive humidity and extremely high temperatures of these regions, corrosion and rot caused by fungus or bacterial action rendered large quantities of equipment defective even before it could be used. The demands by all services for fungicides quickly created shortages. To overcome these shortages, research was initiated to discover new fungicides and to develop more efficient methods of application. More than 2000 organic compounds were evaluated as fungicides, an appreciable number of which have been found to offer promise as substitutes for copper naphthenatc and dichlorod~hydroxydiphenylmethane,the two fungicides which XTere then standard for military use. PROTECTION AGAINST INDUSTRIAL GASES AND VAPORS
Another contribution of the Chemical Corps has been the development of various masks as protection against the deadly gases employed in many industries and thedetailed study of methods to prevent other forms of poison. Since all of these poisons have at one time or another been ?,onsidered as possible chemical warfare a.gents, the Chemical Corps necessarily made close studies of them and of methods for protecting a,gainst them The knowledge thus gained was freely offered to industry. Due to its prevalence, insidious properties, and the difficulty of protecting against it, carbon monoxide is one of the most dangerous industrial poisons. It cannot be used in warfare directly as a gas due to its physical properties, hut it enters into the manufacture of some gases like phosgene (COCI?), and it was often encountered in wartime whenever explosives were detonated in enclosed spaces. Carbon monoxide is difficult to remove from the air. Due to its high volatility it is difficult to absorb. I t is chemically inert--does not readily react with other rhemicals and has very low solubility insolventstwo factors which increase the difficulty of protection. Since the inhaled air in a mask is only in contact with the absorbent for a short time, the absorbent must react very quickly vith the carbon monoxide under a11 possible conditions of temperature and pressure. The Chemical Corps devised a mask to meet these rigid requirements, and it was adopted hy the Navy for submarine crews and by many industrial firms. Most of the commercial carbon monoxide masks can trace their lineage hack to this model. Ammonia fumes are encountered most frequently in ice plants, in handling cylinders, also in fire fighting and in miscellaneous chemical plant work. Inasmuch as the war gas mask canister did not afford satisfactory protection against ammonia, it was necessary to develop VOLUME 34, NO. 11, NOVEMBER. 1957
a special canister to meet this requirement, and the Chemical Corps set out to do so. A new absorhent for ammonia (silica gel) was found which completely eliminated these disadvantages and has twice the adsorptive capacity for ammonia as the old absorbent. A poisonous gas (hydrocyanic acid) and a tear gas (cyanogen chloride) were the two gases for which a third type of mask was to he used. It therefore had to have a high capacity for adsorbing them; and as a result of a thorough study of absorbents for these two gases, two chemical compounds were found particularly effective. The absorbents (whetlerite and soda lime) were placed in a modified war canister. By an ingenious proportioning arrangement, when the canister was exhausted, tear gas rather than poison gas penetrated and gave warning to the wearer. The amount of tear gas which penetrated was extremely small for some time so that a workman could finish his work in an emergency without danger from the hydrocyanic acid in the air. After exhaustion of the canister, it could easily be replaced. AEROSOLS
The aerosol industry owes its initial design and development to research carried out during World War I1 in the production of aerosol insecticides for the Armed Forces. The insecticide aerosol made it possible for our Armed Forces to campaign and live in insect infested areas. Spray dispensers which were first used to spread insect killer in jungle fighting have developed into a major U. S. business. About 185 million units were filled in 1955 by 105 firms for a 190 million dollar husiness. More than 300 products, from shave lather to paint remover, are now packaged in spray cans under 500 brands. While the insecticide aerosol still heads the list, room deodorants, hair lacquers, shave creams, and other production items are growing by leaps and bounds. PEACETIME APPLICATIONS OF NERVE GAS DEFENSE
While scientists are busy at Army Chemical Center developing weapons to keep the United States ahead of the rest of the world in chemical warfare, they are just as busy developing defensive measures, some of which have important peacetime applications. The Center's Medical Laboratories have shown that investigations into nerve gas defense may contribute to the treatment of agricultural and chemical industry workers exposed to accidental lethal doses of some of the newer types of insecticides, and on several occasions members of the Medical Laboratories have been called into consultation on groups of patients exposed to commercial insecticides. Scientists found that both the insecticides and the gas can cause chemical reactions in the body which paralyze nerve centers, among- them the centers which control breathing. The Chemical Corps studies revealed, however, that even lethal dosaees are not necessarilv fatal when artificial respiration and an antidote such as atropine are promptly given as soon as the symptoms of nausea are noted.
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Work in the laboratories of the Chemical Corps and in universities has led to the use of DFP, a compound similar to nerve gas, in relieving the pressure that occurs in the eye balls of people with glaucoma, a serious disease often leading to blindness. This and similar compounds known to the Chemical Corps are additional weapons useful to the eye specialists in combating this disease. DFP has proved itself to be effective also in overcoming partial paralysis of the urinary bladder and the intestines that may occur in patients after operations and following - debilitating - diseases that confine people to bed. A chronic, fatal disease, myasthenia gravis, that is characterized by weakness of the muscles, has frequently been benefited by the use of TEPP (tetraethylpyrophosphate) and OMPA (octamethylpyrophosphoramid) and related materials by strengthening some victims of this disease over longer periods than was possible with the previously used, short-time acting drugs. They can be used in combination with older drugs, often to the advantage of the patient. The advantages gained by medicine, through direct application in disease, from research carried out under the auspices of the Chemical Corps, are based on fundamental studies having wide horizons. Work with these materials has facilitated research designed to understand the way in which the nervous system operates in health and disease. Controlled experimental inhibition of the cholinesterase enzymes with these compounds has provided scientists with an important tool with which to study the nervous system. In connection with the study of the basic functions of newe tissues, DFP was found to be one of the compounds which could inhibit these enzymes. It had for some time been postulated that they played an essential role in the transmission of nerve impulses, but proof was lacking due to the absence of a drng which could inactivate such enzymes. Demonstration of this property of DFP by Chemical Corps scientists and their subsequent nerve studies have excited worldwide interest. The interest of the Chemical Corps in controlling convulsions that may result from nerve gas poisoning has resulted in screening a large nnmher of drugs, old and new, which may also prove effective in alleviating epileptic convulsions. Brain seizures, including the grand ma1 effect, have been artificially induced in various animals. Control and prevention of these seizures with various drugs have been studied. Mode of action studies with the nitrogen mustards proved that these compounds possess a marked leucopenic action when injected intravenously. These observations stimulated the use of nitrogen mustards in the treatment of the leukemias, Hodgkin's Disease, and lymphosarcoma. All are fatal forms of cancer. The nitrogen mustards were also tested clinically in various types of cancer of the lungs. The nitrogen mustards probably do not cure any form of cancer, hut they do prolong life in many instances, and bring about remarkable remissions in others. TREATMENT OF HEAVY METAL POISONING
Early in World War I1 intensive investigations were undertaken both in the United States and the United
Kingdom to find antidotes to the toxic action of Lewisite, a potent vesicant compound containing arsenic. Widespread clinical studies based on the experimental work at Army Chemical Center have shown that BAL (2,3-dimercaptopropanol) is effective in the treatment of human poisonings by antimony, arsenic, bismuth, cadmium, chromium, cobalt, gold, mercury, and nickel. It is ineffectivein poisonings with lead, selenium, silver, tellurium, thallium, and uranium. BAL is also effective as a prophylactic in poisonings by metals of the first group, except cadmium. The end result is that research started in connection with Chemical Corps problems has supplied a treatment agent of great value in preventing death from metals like arsenic and mercury, which have been employed fairly widely for homicidal and suicidal purposes, and from other metals like antimony, cadmium, and chromium which may be causative of industrial poisoning. CONTROL OF ANIMAL DISEASES
Rinderpest is a serious cattle disease with a fairly high mortality. It has played a disastrous role in the economy of many countries, particularly in the Orient and in Africa. A joint American-Canadian mission was estabIished for the purpose of studying rinderpest of cattle. Shortly after the end of the war this information was declassified and made available t o all countries. Also, much rinderpest vaccine (11/2 million doses) was supplied through UNRA to the Orient (China) for treatment of the animal population. Anthrax is a disease of domestic animals of major economic importance. It occasionally affects man. especially those exposed to certain occupational hazards such as in the wool and tanning industry Heretofore the only vaccine of reasonable value for use in animals has been a live spore vaccine developed by Louis Pasteur. There has been considerable justifiable resistance to the use of this material since it consists of live but presumably attenuated spores which use is not without some danger. It cannot be used in man. During and after the war, scientists a t Fort Detrick and colleagues in England developed an entirely new vaccine. It is a soluble antigen containing no live material and can be produced by cultivation in a protein-free medium. For this vaccine, Dr. George G. Wright of the Army Biological Laboratories a t Fort Detrick received the Army's highest award t o civilians, "The Exceptional Civilian Service Award." The examples which have been cited are but a few of the many contributions t o the general welfare and better living resulting from the Chemical Corps research and development program. Significant contributions to scientific knowledge cover a large and varied area including the fields of bacteriology, embryology, epidemiology, pathology, botany, chemistry, biochemistry, physiology, immunology, entomology, animal and poultry husbandry, and other sciences. Additional studies have been made in decontamination, protection, prophylaxis, and treatment. Perhaps one can best emphasize these contributions by pointing out that more than 600 scientific publications have JOURNAL OF CHEMICAL EDUCATION
been made by the Chemical Corps in the year 1955. These are publications in the various scientific journals and provide information of a general scientific nature to all who care to use it. The benefits of research and development conducted by the Chemical C o r p ~ o n l ya few of which have been cited-have produced a succession of incidental by-
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products which have become outstanding contributions to arts and sciences as well as to the general welfare and better living. While an accurate dollar value of such contributions is impossible, a reasonable estimate by conservative personnel within the Corps places the estimate well above the total cost of the program.
