Pharmaceutical Development Resources

Introduction

The genetic diversity in the world’s plants, animals, and microbes can be a rich resource for potential medicines. Examples of drugs whose active ingredients were first isolated from environmental sources include penicillin, aspirin, and the anti-cancer drug taxol. There are probably many more potential drugs available in the biodiversity of rain forests, deep oceans, and other biomes. However, many countries where pharmaceutical development resources originate are now demanding that companies work out agreements that share profits equitably if a successful drug is developed from a nation’s genetic resources.

The pharmaceutical industry also consumes other natural resources, particularly water, and generates waste. To reduce the impact of pharmaceutical development on the environment, many in the industry are now adopting green chemistry. This involves introducing new chemical reactions that do not require organic solvents and produce fewer toxic by-products. There is also a new emphasis on reducing water and energy consumption, and waste generation in pharmaceutical development.

Historical Background and Scientific Foundations

Traditional systems of medicine rely on the use of extracts from plants and animals for therapeutic purposes. Developments in chemistry during the eighteenth century led to the more scientific application of these compounds, with an early example being the use of digitalis, extracted from the foxglove plant, for the treatment of heart failure. This was followed at the start of the twentieth century with the extraction of salicylic acid from willow bark. Salicylic acid and related compounds have an analgesic and anti-inflammatory effect. Salicylic acid was then chemically modified by chemists at the German company Bayer and the result, acetylsalicylic acid, which is better known as aspirin, went on to become one of the best known drugs of all time. Aspirin is still used to relieve pain and has found new applications in the prevention of heart disease, stroke, and maybe even cancer.

Another important drug derived from natural resources is penicillin, the first major antibiotic, which was isolated from the airborne mold Penicillium nota-tum by Scottish bacteriologist Alexander Fleming (1881–1955) in 1928. Antibiotics are compounds that kill or slow the growth of bacteria and fungi. They treat a wide range of infections including septicemia, pneumonia, and tuberculosis. Penicillin was the first effective antibiotic, and the advent of World War II (1939–1945), with the prospect of many lives lost to wound infections, drove its large-scale production. Penicillium notatum proved not to be the best species for this purpose. It was replaced by a strain of Penicillium chryosgenum isolated from a moldy melon found in a market stall in Peoria, Illinois.

The search for a mold that could produce a good yield of penicillin in the factories of a pharmaceutical company typifies the way natural resources can be turned into modern medicines. Pharmaceutical development resources are found all over the planet, including rain forest plants, soil microbes, and invertebrates and bacteria from the deep ocean. Around half of today’s top-selling drugs originally come from natural sources. For example, the immunosuppressant drug cyclosporin is extracted from a fungus and it has dramatically transformed the outlook for people having an organ transplant. Meanwhile, although many bacteria have developed resistance to penicillin, limiting its use, there are thousands of bacteria and fungi living in the soil that secrete other antibiotic compounds, like streptomycin and cephalosporin.

Plants are an important source of anti-cancer drugs. One of these is vincristine, used for treating leukemia, which is extracted from the rosy periwinkle found in the Madagascar rain forest. Another is taxol, which was originally obtained from the leaves of the Pacific yew tree. Meanwhile, both the deep ocean floor and the layers just beneath the surface of the water are a source of bacteria and invertebrates, such as sponges, which are being screened for their anti-bacterial and anti-cancer potential. New types of antimicrobial peptides are also being isolated from the skin of certain frogs and toads.

Pharmaceuticals are derived either from natural resources, as described earlier, or from synthetic chemistry. Some medicines are semi-synthetic, using a natural resource that is then modified by chemical reactions. Aspirin was, originally, one example of a semi-synthetic drug, although it is a simple enough molecule for total chemical synthesis and this is how it is now manufactured.

Besides its chemical raw material, whether it is natural or synthetic, pharmaceutical development also requires the use of water, energy, and other components in order to produce drugs. Industrial use of water accounts for 20% of global usage, varying from country to country from less than 5% to around 7%, depending on how industrialized the country is. The pharmaceutical industry uses water both in manufacturing processes and in cleaning equipment. The latter accounts for 60 to 80% of water usage in a pharmaceutical manufacturing plant.

Because pharmaceutical products are intended for human consumption, the regulatory authorities are very particular about the grade of water that is used. There are waters at various grades of purification that are required for specific operations in the plant. Water for injection (WFI) is the purest water used in manufacturing and should be fit for the purpose that the name implies. It is virtually sterile and has to be distilled as part of the purification process. The demand for WFI is increasing, not least because of the more stringent demands of the regulatory authorities for purity in the final pharmaceutical product. Since WFI is so costly to produce, manufacturers are looking increasingly at ways of optimizing its use in manufacture.

Impacts and Issues

Any species, anywhere on the planet, may contain genes that make it suitable as a pharmaceutical development resource. Traditionally, companies have regarded the sampling of soils and plants around the world for such genetic knowledge as being acceptable. However, a debate over who owns these genetic resources has arisen. There has been particular concern that the activities of the pharmaceutical companies amount to gene plunder, particularly where resources like rain forest plants are concerned. In other words, the companies exploit the genetic resources originating in a poor country and turn them into profits for rich countries.

WORDS TO KNOW

BIODIVERSITY: Literally, “life diversity”: the wide range of plants and animals that exist within any given geographical region.

BIOME: A well-defined terrestrial environment (e.g., desert, tundra, or tropical forest) and the complex of living organisms found in that region.

CARBON FOOTPRINT: The amount of carbon dioxide (or of any other greenhouse gas, counted in terms of the greenhouse-equivalent amount of CO2) emitted to supply the energy and materials consumed by a person, product, or event.

GENE PLUNDER: Exploiting genetic diversity without compensating the country of origin.

GREEN CHEMISTRY: An approach to chemical manufacturing that reduces its negative impact on the environment.

IMMUNOSUPPRESSANT: Something used to reduce the immune system’s ability to function, like certain drugs or radiation.

The United Nations Convention on Biodiversity attempts to stop gene plunder. Pharmaceutical companies are now expected to enter into research agreements with governments and scientists in places where they wish to exploit genetic resources. If a useful drug is developed, then the country of origin can expect to share in the profits. In one example, the pharmaceutical giant Merck Inc. has paid $1.35 million to Costa Rica for the right to genetic information in a local rain forest. Costa Rica has to dedicate this payment to preserving the rain forest habitat.

If biodiversity agreements can help preserve rain forests, then the pharmaceutical industry is benefiting the environment. However, there are other ways in which the industry can have a negative impact. Pharmaceutical manufacture often involves the use of organic solvents, which may be toxic and comprise a hazardous waste. The industry also generates large amounts of wastewater that require treatment and may have an adverse effect on local water supplies.

The pharmaceutical industry is working to reduce its negative impacts on the environment with a green chemistry approach, developed by scientists Paul Anastas of the U.S. Environmental Protection Agency (EPA) and John Warner of the University of Massachusetts. Green chemistry tries to devise new chemical syntheses that use less, or no, organic solvent, and that eliminate the formation of toxic by-products. It also involves the use of online real time analysis of processes to control the formation of hazardous substances. Reduction of energy use and waste are other goals of green chemistry. All the major pharmaceutical companies now have a green chemistry program and ambitious goals for reducing their carbon footprint.

See Also Hazardous Waste; Industrial Pollution; Industrial Water Use; Water Supply and Demand

BIBLIOGRAPHY

Books

Chivian, Eric, and Aaron Bernstein, eds. Sustaining Life: How Human Health Depends on Biodiversity. Cambridge, MA: Oxford, 2008.

Cunningham, W.P., and A. Cunningham. Environmental Science: A Global Concern. New York: McGraw-Hill International Edition, 2008.

Web Sites

American Institute of Biological Sciences. “Searching for Nature’s Medicines.” http://www.actionbioscienceorg/biodiversity/plotkin.html (accessed May 2, 2008).

Susan Aldridge