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OCR for page 210
210 THE LIFE SCIENCES
edge and understanding in sound management programs can man expect
to conserve the natural resources that are his great heritage.
INDUSTRIAL TECHNOLOGY
Biological science finds application in many aspects of the economy. There
is no precise biology-related equivalent of the chemical or electronics in-
dustries, which bear one-to-one relationships with specific areas of science.
As we have seen, agriculture, medicine, protection of the public health, and
conservation of renewable resources all directly apply increments in bio-
logical understanding. Here we shall indicate briefly a few additional in-
dustries whose capabilities, scale, and quality rest on applied biology.
Pharmaceuticals
Reference has repeatedly been made to the role of the pharmaceutical
industry; suffice it to note, then, the magnitude of this industrial endeavor.
In 1967 the industry had gross sales of about $4.2 billion. Of this, 10.5
percent was allocated to its own research and development programs-
about one fifth of the nation's entire biomedical research enterprise in
which just under 20,000 scientists and supporting personnel were employed.
Table 5 summarizes the categories of drugs sold in 1967. The magnitude
of the research task is shown by the number of animals required (Table 61.
By now, the general pattern of pharmaceutical research is somewhat
standardized. Research directors, aware of the Ileeds of human and veteri-
nary medicine, monitor the output of worldwide fundamental biomedical
research for clues to potential new drugs. Chemists then either purify some
TABLE 5 1967 U.S. Drug Shipments in Major Categories (In $ Millions
TOTAL HUMAN AND VETERINARY DRUGS
Drugs for treatment of cancer, endocrine and metabolic diseases
Hormones
Corticoids
Oral Contraceptives
Other
Other
4,143.0
439.6
413.5
141.7
103.5
168.3
26.1
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BIOLOGY IN THE SERVICE OF MAN 211
TABLE 5 continued
Drugs acting on the central nervous system and sense organs
Internal Non-Narcotic Analgesics
Internal Narcotic Analgesics
Tranquilizers
Antidepressants
Central Nervous System Stimulants
Barbiturate Hypnotics
Nonbarbiturate Hypnotics
General and Local Anesthetics
Other
Drugs acting on the cardiovascular system
Drugs acting on the respiratory system
Drugs acting on digestive or genito-urinary system
Antacids
Antidiarrheal Drugs
Laxatives
Antiulcer Drugs
Motion-Sickness Remedies
Urinary Antibacterials and Antiseptics
Diuretics
Other
Dermatological preparations
Hemorrhoidal Drugs
Other Dermatological Drugs
Nutrients
Vitamins
Hematinics
Other
Drugs affecting parasitic and infective disease
Antibiotics
Sulfonamides
Antifungal agents
Antibacterials and antiseptics
Other
Pharmaceutical preparations for veterinary use
Pharmaceutical preparations not specified by kind
1,130.1
448.4
40.3
321.4
45.0
80.5
25.4
35.4
47.4
86.3
204.0
366.6
552.4
137.3
41.4
79.0
73.5
24.6
28.7
94.8
73.1
236.9
27.6
209.3
168.5
204.1
58.5
145.6
698.8
468.3
32.5
28.7
133.1
36.2
140.4
1.6
t' Data from U.S. Department of Commerce, Bureau of the Census, Current Industrial Reports,
"Pharmaceutical Preparations, Except Biologicals-1967," December 4, 1968.
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212 THE LIFE SCIENCES
TABLE 6 Animal Usage in the Pharmaceutical Industry in 1965 a
Mice
Rats
Hamsters
Guinea Pigs
Rabbits
Dogs
Monkeys
Cats
23,200,000
9,900,000
900,000
350,000
250,000
93,000
60,000
33,000
a Data from a survey made by the Institute of Laboratory Animal Resources, Division of Biology
and Agriculture, National Research Council.
naturally occurring material or synthesize a desired chemical entity and a
series of variations on this theme. The potential drug is then put through a
"screen," an increasingly large and diverse battery of biochemical and
physiological tests. If the material still appears to have the desired activity,
it is tested in animal models of the human disorder, where such exist, and
then screened for short-term and long-term toxicity in a variety of animal
species. If all appears to be in order, permission is requested of the Food
and Drug Administration to test the drug in man. After a tolerable dosage
level is established in a few subjects, a much wider group of patients is
treated with the drug for its specific use, while also being observed for any
signs of toxicity. When a sufficient series has been tested, if the drug has
proved efficacious for its intended purpose and if undesirable side reactions
are minimal, permission is sought for free marketing. Finally, the Food
and Drug Administration must balance hazard against benefit as it comes
to a decision. No foreign compound is totally devoid of untoward effects.
Indeed, were aspirin invented tomorrow, the Food and Drug Administra-
tion would have a difficult time in deciding whether to issue a license. If
the benefits warrant and the hazards are tolerable- particularly if the drug
offers decided advantages over existing drugs or is truly lifesaving the
Food and Drug Administration will issue the desired license, about 5 to 10
years and $5 million to $10 million after the start of the project.
The overall results are evident in the facts that no more than 10 percent
of drug sales represent entities available before 1940, that mortality from
all infectious diseases fell from 88,000 deaths in 1941 to 17,000 in 1961,
that tuberculosis sanitariums are closed, tranquilizers have emptied thou-
sands of sanitarium beds, and few of us any longer are asked to bear extreme
pain, thanks to nonaddicting, powerful analgesics.
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BIOLOGY IN THE SERVICE OF MAN 213
Food
Once harvested or slaughtered, the products of agricultural practice must
be "brought to the table." This is accomplished by the many components
of the food industry, employing 14 percent of the working population in
an endeavor aggregating $90 billion in 1966. Through the combined efforts
of applied biologists, chemists, and engineers, the housewife may now
choose among 8,000 items in the supermarket. This team has solved the
problems of raw storage; out-of-season processing; long-term storage; min-
imization of contamination by agricultural chemicals, bacteria, yeast, and
molds; maintenance of moisture and nutritional content. It has upgraded
the nutritional value of various native foods; monitored all stages of the
preparative and marketing process; established the optimal conditions for
transport and storage; devised such preservative mechanisms as ethylene
oxide, sulfur dioxide, and nitrogen gas atmospheres, as well as procedures
such as vacuum-, spray-, drum-, and freeze-drying, while monitoring such
processes as fermentation of sauerkraut, cheese, or buttermilk and sterile
filtration of beer, wine, and fruit juices. It has devised the wide variety of
food additives now available and has developed specialized foods for dia-
betics, phenylketonurics, and galactosemics, as well as for those with heart
or kidney disease or gastrointestinal limitations.
Pesticides
As noted earlier, the properties of DDT and 2,4-D inaugurated a new era
in management of our living resources and gave rise to a new industry.
Each touched off a wave of research that continues to the present, seeking
newer compounds that are species-specific, safe, and degradable. For the
moment, the use of such compounds is indispensable; until superior means
and materials are found, these compounds are essential to the success of
our agriculture, while assisting in maintenance of our woodlands and pro-
tection of our health. It is the scale of this use, rather than their intrinsic
toxicity, that has properly generated public concern over the effects of
these chemicals on the public health. In 1966, total production of all
pesticides in the United States was 1,012,598,000 pounds.
The rapid increase in use occurred because new pesticides have been
developed that control hitherto uncontrolled pests, and broader use of
pesticides in large-scale agriculture has increased crop yields significantly.
Current trends in crop production involving large acreages, greater use of
fertilizers, and intensive mechanized cultivation and harvesting offer par-
ticularly favorable opportunities for insect pests and would result in large
crop losses to these pests unless control measures were applied.
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THE LIFE SCIENCES
The increased number of new pesticides in part resects a second gen-
eration of pesticides with more appropriate persistence for economic con-
trol of specific pests, more complete control of the pest, less hazard for the
applicator, or less hazardous residues on the crop. An additional impetus
to the development of new pesticides comes from the fact that many insect
pests have developed resistance to the older pesticides. The development
of pest resistance does not necessarily entail the development of more dan-
gerous pesticides; the new agent need only be chemically different to over-
come resistance. The continuing search for new, more nearly ideal pesti-
cides requires the joint effort of research teams composed of organic
chemists, biochemists, pharmacologists, physiologists, entomologists, and
botanists. The effort is managed much like the development of new drugs,
each chemical entity being tested in a "screen" of a variety of insects.
About 73 percent of the total insecticide usage is in agriculture, and
about 25 percent is used in urban areas by homeowners, industry, the
military, and municipal authorities. The remaining 2 percent is applied to
forest lands, grassland pasture, and on salt and fresh water for mosquito
control. Over 50 percent of the insecticide used in agriculture is applied
to cotton acreage alone.
When insect-control measures are not used in agriculture, insect pests
take 10 to 50 percent of the crop, depending on local conditions. Losses
of this magnitude are not readily tolerated in the United States in the face
of a rapidly increasing population and a concomitant decrease in agricul-
tural acreage. In this sense, the use of insecticides might be deemed essen-
tial at this time for the production and protection of an adequate food supply
and an adequate supply of staple fiber. While alternative methods of pest
control are under investigation and development, they are not yet ready to
displace completely the chemical pesticides, and it appears that a pesticide
industry will be required for some years to come.
Pesticides have been tremendously effective, but individual pesticides,
like sulfa drugs and antibiotics, tend to lose their effectiveness as species
resistance to them develops. Hence, there will be a continuing search for
new pesticides as long as pesticides are considered to be required for the
economy or the public health. This search will require the continuing par-
ticipation of able biologists. As with drugs, new pesticides, optimally, should
be selectively toxic for specific pests, rather than broadly toxic against a
wide variety of pests with serious side-effects on nonpest species. Broad-
spectrum pesticides affect an essential enzyme or system common to a wide
variety of pests. A selective pesticide, on the other hand, either should
affect an essential enzyme or system peculiar to a particular pest or should
be applied in such a way that only the particular pest gains access to it.
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BIOLOGY IN THE SERVICE OF MAN 215
An interesting example of a selective pesticide is the rodenticide norbor-
mide, which is highly toxic for rats, particularly for the Norway rat. By
contrast, the acute oral toxicity of norbormide for other species is much
lower, the lethal dose for a great variety of birds and mammals, per kilo-
gram of body weight, being more than 100 times greater. The mechanism
of the selective toxic action of norbormide for rats is not yet elucidated.
Achievement of target specificity requires a sophisticated knowledge of the
anatomical, physiological, or biochemical peculiarities of the target pest as
compared with other pests or vulnerable nonpests; a pesticide may then be
developed that takes advantage of these peculiarities. This is obviously not
easy to accomplish, and norbormide may prove to be unique for many
years. An alternative is the introduction of a systemic pesticide into the
host or preferred food of the target pest. Other pests or nonpests would
not contact the pesticide unless they shared the same host or food supply.
As an example, a suitable pesticide may be applied to the soil and imbibed
by the root system of a plant on which the pest feeds. The pest feeding on
the plant then receives a toxic dose. The application of attractants or re-
pellents (for nontarget species) would increase the selectivity of the sys-
temic pesticide. The use of systemic pesticides on plants used for food by
humans or domestic animals poses an obvious residue problem.
There has been a strong public reaction against the continued use of
pesticides on the grounds that such use poses a potential threat to the
public health as well as being a hazard to wildlife. Careful investigations
have so far failed to establish the magnitude of the threat to the public
health; i.e., there are as yet few if any clear-cut instances of humans who
have suffered injury clearly related to exposure to pesticides that have been
used in the prescribed manner. Report No. 1379 of the 89th Congress
(July 21, 1966 ~ * concluded:
The testimony balanced the great benefits of disease control and food production
against the risks of acute poisoning to applicators, occasional accidental food con-
tamination, and disruption of fish and wildlife.... The fact that no significant hazard
has bee'' detected to date does not constitute adequate proof that hazards will not
be encountered in tile future. No final answer is possible now, but we must proceed
to get tlze answer. (Italics ours)
Failure to establish such hazard does not mean that it does not exist.
There are no living animals, including those in the Antarctic, that do not
* U.S. Congress. Senate. Committee on Government Operations. Interagency
Environmental Hazards Coordination, Pesticides and Public Policy (Senate Report
1379). Report of the Subcommittee on Reorganization and International Organiza-
tions (pursuant to S.R. 27, 88th Cong., as amended and extended by S.R. 288), 89th
Cong., 2d sees., Washington, D.C., U.S. Government Printing Once, 1966.
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216
THE LIFE SCIENCES
bear a body burden of some DDT. Large fish kills and severe effects on
bird populations have been demonstrated. The large-scale use of these
agents has been practiced for less than two decades, and use has increased
annually until this year ( 1969 ~ . Whereas the anticholinesterase compounds,
which have high acute toxicity (and hence are highly hazardous to the
applicator), are readily and rapidly degraded in nature, the halogenated
hydrocarbons are not. With time, their concentration in the soil and in
drainage basins, lakes, ponds, and even the oceans must continue to increase,
thereby assuring their buildup in plant and animal tissues. Over a sufficient
time period, this is potentially disastrous. And should such a period pass
without relief, the situation could not be reversed in less than a century.
Because of the large economic benefit to the farmer, it is pointless to adjure
him to be sparing; unless restrained by law, he will make his judgment in
purely personal economic terms. But mankind badly needs the incremental
food made possible by use of effective pesticides, and the enormous benefit
to public health of greatly reducing the population of insects that are disease
vectors is a self-evident boon to humanity. Thus it is imperative that
alternative approaches to pest control be developed with all possible dis-
patch, while we learn to use available pesticides only where they are clearly
necessary and desirable and to apply them in the minimal amounts adequate
to the purpose.
A recent development in insect-pest control has been the possible use of
juvenile hormone. This hormone, normally produced by insects and
essential for their progress through the larval stages, must be absent from
the insect eggs if the eggs are to undergo normal maturation. If juvenile
hormone is applied to the eggs, it can either prevent hatching or result in
the birth of immature and sterile offspring. There is evidence to suggest
that juvenile hormone is much the same in different species of insects, and
analogs have been prepared that are effective in killing many species of
insects, both beneficial and destructive. There would, therefore, be great
danger of upsetting the ecological balance if juvenile hormone were applied
on a large scale.
What is needed, then, is development of chemical modifications of
juvenile hormone that would act like juvenile hormone for specific pests
but not for other insects. For example, a preparation from balsam fir, which
appears to be such an analog, has been identified and is effective against a
family of bugs that attack the cotton plant, but not against other species.
If it proves possible to synthesize similar analogs specific for other pests, a
new type of pesticide may emerge. If this happens, it will be extremely
important to explore possible side-effects on other insect species and on
warm-blooded animals before introduction of yet a new hazard into the
biosphere.
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BIOLOGY IN THE SERVICE OF MAN
We cannot rest with existing pesticides, both because of evolving pest
resistance to specific compounds and because of the serious long-term
threat posed by the halogenated hydrocarbons. While the search for new,
reasonably safe pesticides continues, it is imperative that other avenues
be explored. It is apparent that this exploration will be effective only if
there is, simultaneously, ever-increasing understanding of the metabolism,
physiology, and behavior of the unwanted organisms and of their roles in the
precious ecosystems in which they and we dwell.
Fermentation Industry
Wine and leavened bread date back to antiquity, but the fermentation
industry is a product of modern biological science. In sum, the disparate
fermentation industry constitutes a major national resource. Each of the
major companies in that industry retains a staff of microbiologists, bio-
chemists, chemists, and engineers. Together, they are responsible for the
continuing monitoring control of the fermentations with which they are
concerned. The microbiologists constantly search, by the conventional
techniques of bacterial genetics, for new strains of micro-organisms that
will more efficiently or more rapidly conduct the fermentation in question.
Rarely do these groups, as such, discover new fermentations yielding new
products of value. Most have been encountered earlier in the course of
systematic microbiology, and the industrial research team develops the
procedures whereby a laboratory observation is scaled up to the requisite
industrial magnitude. An important exception has been the systematic
hunt for new antibiotics by the drug companies.
Bakers', food, and fodder yeasts were produced in excess of 180,000
tons in 1967. Alcohol fermentation amounting to 685 million gallons in
1945 has largely been replaced by a process starting with petroleum-
cracking fractions, as has the fermentative production of acetone and
butanol. But 5 billion pounds of raw grains were used to produce 110
million barrels of beer and ale, while 235 million gallons of wine and 185
million gallons of distilled spirits were also produced by fermentation. Other
fermentation procedures produce lactic acid, vinegar, dextrans for drilling
muds and as a plasma substitute, verbose, and glutamic acid. Bacteria are
grown as legume inoculants and as bioinsecticides. Molds and streptomyces
are grown as a source of at least 30 distinct antibiotics in general use, as
well as of citric acid and a variety of other organic acids. One mold is now
used to make giberellin, which stimulates seed germination, improves
growth of young trees, increases the flowering of plants, "sets" tomato
fruit clusters, and breaks the dormancy of potatoes.
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218
THE LIFE SCIENCES
Allied to these processes is the use of molds, streptomyces, and bacteria
in synthetic chemistry to accomplish specific reactions not readily feasible by
chemical means. At least 25 such procedures are in current use in steroid
synthesis in pharmaceutical laboratories. Related, also, is a relatively new
industry, the manufacture of enzymes on a substantial scale. At least 20
enzymes are now articles of commerce. Thus, amylases from pancreas.
barley malt, or fungi are used to de-size textiles, start brewing fermentation,
precook baby foods, or cold-swell laundry starch. Papain from papaya,
bromelin from pineapple, and subtilisin from B. subtilis are used as meat
tenderizers, to stabilize chill-proof beer, and most recently as adjuncts to
laundry detergents. Still other enzymes are used in candy manufacture,
in clinical diagnostic procedures, to clarify wine and beer, to tan leather,
and for debridement of wounds. The list of enzymes and their uses is
growing, limited only by imagination.
No estimate of the magnitude of these diverse biological industries is
available, but clearly in sum they represent several billion dollars of the
gross national product. In every instance, biological understanding under-
lay the original industrial concept, guided the necessary research and de-
velopment, gave direction to the industrial installation, and is required for
continuing monitoring of the process.
instrumentation
The scale and sophistication of modern biological research and its appli-
cations have necessitated birth of a new industry the manufacture of
biological instruments. The need for and use of most instruments usually
arises in a research laboratory. But, thereafter, if it is to be more generally
available, conveniently packaged, simple and reliable in performance, and
readily serviced, its production must be taken over by a commercial manu-
facturer. Competition among manufacturers is the stimulus that has pro-
vided a stream of increasingly useful, sensitive, and reliable instruments,
annual sales of which now approximate $1 billion. Appreciation of the
diversity of such instruments may be gained from the data concerning use
and need presented in Chapters 3 and 4.
When established, such instruments are modified to monitor and con-
trol industrial biological processes and for diagnostic and therapeutic use
in hospital practice. An excellent example is the development of an auto-
mated apparatus that can accept an unmeasured small volume of blood,
perform about 15 different analytical procedures thereon, calculate the
results in conventional units, and record them on the patient's record. These
data are decidedly more reliable than are individual determinations per
OCR for page 219
BIOLOGY IN THE SERVICE OF MAN
formed manually by technicians, and the cost is comparable to that of a
single such manual procedure. In consequence, the physician's armamen-
tarium is markedly expanded, at no additional cost to the patient or to
society.
From this brief summary it will be evident that the skills and understanding
of the modern biologist find their way into a remarkable variety of human
endeavors, rendering life more secure, healthier, longer, more comfortable,
and more pleasant, while giving employment to millions.
Representative terms from entire chapter:
insect pests
