Biological warfare Biological warfare is the intentional use of living microorganisms or their toxic products for the purpose of destroying or reducing the military effectiveness of man. It is the exploitation of the inherent potential of infectious disease agents by scientific research and development, resulting in the production of BW weapons systems. Man may also be injured secondarily by damage to his food crops or domestic animals. Biological warfare is considered to be primarily a strategic weapon. The major reason for this is that it has no quick-kill effect. The incubation period of infectious disease, plus a variable period of illness even before a lethal effect, render this weapon unsuitable for hand-to-hand encounter. A man can be an effective fighting machine throughout the incubation period of most infectious diseases. Thus, an enemy would probably use this weapon for attack on static population centers such as large cities. An important operational procedure in BW for an enemy would be to create an areosol or cloud of agent over the target area. This concept has stimulated much basic research concerning the behavior of particulate biological materials, the pathogenesis of respiratory infections, the medical management of such diseases and defense against their occurrence. The biological and physical properties of infectious particles have been studied intensively during the past fifteen years. Much new equipment and many unique techniques have been developed for the quantitative exposure of experimental animals to aerosols of infectious agents contained in particles of specified dimensional characteristics. Much information has been gathered relative to quantitative sampling and assesment techniques. Much of the older experimental work on respiratory infections was accomplished by very artificial procedures. The intranasal instillation of a fluid suspension of infectious agent in an anesthetized animal is far different from exposure, through natural respiration, to aerosolized organisms. The importance of particle size in such aerosols has been thoroughly demonstrated. The natural anatomical and physiological defensive features of the upper respiratory tract, such as the turbinates of the nose and the cilia of the trachea and larger bronchi, are capable of impinging out the larger particles to which we are ordinarily exposed in our daily existence. Very small particles, however, in a size range of 1 to 4 microns in diameter are capable of passing these impinging barriers and entering the alveolar bed of the lungs. This area is highly susceptible to infection. The entrance and retention of infectious particles in the alveoli amounts almost to an intratissue inoculation. The relationship between particle size and infectious dose is illustrated in Table 1. In considering BW defense, it must be recognized that a number of critical meterological parameters must be met for an aerosol to exhibit optimum effect. For example, bright sunlight is rapidly destructive for living microorganisms suspended in air. There are optimal humidity requirements for various agents when airborne. Neutral or inversion meteorological conditions are necessary for a cloud to travel along the surface. It will rise during lapse conditions. There are, of course, certain times during the 24-hour daily cycle when most of these conditions will be met. Certain other properties of small particles, in addition to those already mentioned in connection with penetration of the respiratory tract, are noteworthy in defense considerations. The smaller the particle the further it will travel downwind before settling out. An aerosol of such small particles, moreover, diffuses through structures in much the same manner as a gas. There may be a number of secondary effects resulting from diffusion through buildings such as widespread contamination of kitchens, restaurants, food stores, hospitals, etc. Depending on the organism, there may be multiplication in some food or beverage products, i.e., in milk for example. The secondary consequences from this could be very serious and must be taken into consideration in planning for defense. Something of the behavior of clouds of small particles can be illustrated by the following field trials: In the first trial an inert substance was disseminated from a boat travelling some ten miles off shore under appropriately selected meteorological conditions. Zinc cadmium sulfide in particles of 2 microns in size were disseminated. This material fluoresces under ultraviolet light which facilitates its sampling and assessment. Four hundred and fifty pounds was disseminated while the ship was traveling a distance of 156 miles. Figure 1 describes the results obtained in this trial. The particles traveled a maximum detected distance of some 450 miles. From these dosage isopleths it can be seen that an area of over 34,000 square miles was covered. These dosages could have been increased by increasing the source strength which was small in this case. The behavior of a biological aerosol, on a much smaller scale, is illustrated by a specific field trial conducted with a non-pathogenic organism. An aqueous suspension of the spores of B. subtilis, var. niger, generally known as Bacillus globigii, was aerosolized using commercially available nozzles. A satisfactory cloud was produced even though these nozzles were only about 5 per cent efficient in producing an initial cloud in the size range of 1 to 5 microns. In this test, 130 gallons of a suspension, having a count of Af organisms per ml, or a total of approximately Af spores, was aerosolized. The spraying operation was conducted from the rear deck of a small Naval vessel, cruising two miles off-shore and vertical to an on-sure breeze. Spraying continued along a two-mile course. This operation was started at 5:00 p.m. and lasted for 29 minutes. There was a slight lapse condition, a moderate fog, and 100 per cent relative humidity. A network of sampling stations had been set up on shore. These were located at the homes of Government employees, in Government Offices, buildings and reservations within the trial area. A rough attempt was made to characterize the vertical profile of the cloud by taking samples from outside the windows on the first, ninth, and fifteenth floors of a Government office building. All samplers were operated for a period of two hours except one, which was operated for four hours. In this instance, there was a dosage of 562 during the first two hours and a total dosage of 1980 for the four-hour period, a four-fold increase. This suggests that the sampling period, particularly at the more distant locations, should have been increased. As can be seen from Figure 2, an extensive area was covered by this aerosol. The maximum distance sampled was 23 miles from the source. As can be seen from these dosage isopleths, approximately 100 square miles was covered within the area sampled. It is quite likely that an even greater area was covered, particularly downwind. The dosages in the three levels of the vertical profile were: Af . This was not, of course, enough sampling to give a satisfactory description of the vertical diffusion of the aerosol. A number of unique medical problems might be created when man is exposed to an infectious agent through the respiratory route rather than by natural portal of entry. Some agents have been shown to be much more toxic or infectious to experimental animals when exposed to aerosols of optimum particle size than by the natural portal. Botulinal toxin, for example, is several thousand-fold more toxic by this route than when given per os. In some instances a different clinical disease picture may result from this route of exposure, making diagnosis difficult. In tularemia produced by aerosol exposure, one would not expect to find the classical ulcer of "rabbit fever" on a finger. An enemy would obviously choose an agent that is believed to be highly infectious. Agents that are known to cause frequent infections among laboratory workers such as those causing Q fever, tularemia, brucellosis, glanders, coccidioidomycosis, etc., belong in this category. An agent would likely be selected which would possess sufficient viability and virulence stability to meet realistic minimal logistic requirements. It is, obviously, a proper goal of research to improve on this property. In this connection it should be capable of being disseminated without excessive destruction. Moreover, it should not be so fastidious in its growth requirements as to make production on a militarily significant scale improbable. An aggressor would use an agent against which there was a minimal naturally acquired or artificially induced immunity in a target population. A solid immunity is the one effective circumstance whereby attack by a specific agent can be neutralized. It must be remembered, however, that there are many agents for which there is no solid immunity and a partial or low-grade immunity may be broken by an appropriate dose of agent. There is a broad spectrum of organisms from which selection for a specified military purpose might be made. An enemy might choose an acutely debilitating microorganism, a chronic disease producer or one causing a high rate of lethality. It is possible that certain mutational forms may be produced such as antibiotic resistant strains. Mutants may also be developed with changes in biochemical properties that are of importance in identification. All of these considerations are of critical importance in considering defense and medical management. Biological agents are, of course, highly host-specific. They do not destroy physical structures as is true of high explosives. This may be of overriding importance in considering military objectives. The question of epidemic disease merits some discussion. Only a limited effort has been devoted to this problem. Some of those who question the value of BW have assumed that the only potential would be in the establishment of epidemics. They then point out that with our present lack of knowledge of all the factors concerned in the rise and fall of epidemics, it is unlikely that a planned episode could be initiated. They argue further (and somewhat contradictorily) that our knowledge and resources in preventive medicine would make it possible to control such an outbreak of disease. This is why this approach to BW defense has not been given major attention. Our major problem is what an enemy might accomplish in an initial attack on a target. This, of course, does not eliminate from consideration for this purpose agents that are associated naturally with epidemic disease. A hypothetical example will illustrate this point. Let us assume that it would be possible for an enemy to create an aerosol of the causative agent of epidemic typhus (Rickettsia prowazwki) over City A and that a large number of cases of typhus fever resulted therefrom. No epidemic was initiated nor was one expected because the population in City A was not lousy. Lousiness is a prerequisite for epidemic typhus. In this case, then, the military objective was accomplished with an epidemic agent solely through the results secured in the initial attack. This was done with full knowledge that there would be no epidemic. On the other hand, a similar attack might have been made on City B whose population was known to be lousy. One might expect some spread of the disease in this case resulting in increased effectiveness of the attack. The major defensive problems are concerned with the possibility of overt military delivery of biological agents from appropriate disseminating devices. It should be no more difficult to deliver such devices than other weapons. The same delivery vehicles -- whether they be airplanes, submarines or guided missiles -- should be usable. If it is possible for an enemy to put an atomic bomb on a city, it should be equally possible to put a cloud of biological agent over that city. Biological agents are, moreover, suitable for delivery through enemy sabotage which imposes many problems in defense. A few obvious target areas of great importance might be mentioned. The air conditioning and ventilating systems of large buildings are subject to attack. America is rapidly becoming a nation that uses processed, precooked and even predigested foods. This is an enormous industry that is subject to sabotage. One must include the preparation of soft drinks and the processing of milk and milk products. Huge industries are involved also in the production of biological products, drugs and cosmetics which are liable to this type of attack.