Chapter 12: NATURAL PRODUCTS |
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Natural
Products |
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Registered UCI
students: view the slide
show for this chapter or download it:
http://darwin.bio.uci.edu:80/~sustain/protected/chap12slides.ppt |
Pesticides. Many tropical plants produce chemicals
that deter herbivores. Tropical indigenous people have discovered many of these
plants, and use them as poisons or medicines:
i.Calabar bean was
traditionally used as a poison in West Africa. Chemical studies of this plant
led to the development of methyl carbamate insecticides.
ii. Daisy plants
(Chrysanthemum cinerariaefolium) were first used centuries ago as a lice remedy
in the Middle East, and this led to the discovery of pyrethrum insecticides. The
seeds contain a natural insecticide called pyrethrin, a generic name for six
related active compounds. It is one of the safer insecticides for several
reasons: it decomposes rapidly in sunlight; it has few known effects on mammals;
and insects do not develop resistance to it. It is used on foodstuffs, in head
lice shampoos, and in many indoor insect sprays. 100,000 tons of mosquito coils
made from pyrethrum are sold each year. Scientists have synthesized similar
compounds called pyrethroids, but the chemical synthesis produces all geometric
isomers of the compounds, many of which are ineffective and are difficult to
separate from the active forms. The plant material contains only the active
isomers.
iii. In South America, the natives use an extract of a forest vine
to stun fish; this led to the discovery of rotenone, a biodegradable
insecticide.
iv. The bacterium Bacillus thuringiensis produces toxic proteins
that kill certain insects but are apparently harmless to humans. These are being
produced and marketed as biopesticides. And Monsanto has engineered cotton
plants that produce their own protein insecticide.
v. The Neem tree, in India, has been found to be a source of the insecticide azadirachtin, as well as fungicides, spermicide, and agents potentially valuable in birth control such as materials that prevent implantation or cause abortion. The tree has been used in traditional agriculture, medicine and cosmetics for centuries. However, recently companies from industrialized countries have been seeking patent protection, and 90 patents have been granted worldwide for "inventions" of products from Neem. A coalition or organizations has been fighting patenting of materials already in traditional use (biopiracy), and in 2000 they achieved their first victory in persuading the European Patent Office to revoke a patent from USDA and W.R. Grace on Neem tree fungicide on the basis that the product was already being used traditionally (in India) before the Company patented it.
Other tropical plants have been found to be toxic to leafcutter ants, mosquitoes, and other insects, and could lead to the discovery of other pesticides.
Medicines. The potential for discovering medicinal compounds in wild organisms is enormous, and provides one of the most powerful arguments for conservation of biological diversity. This is especially true of tropical forests.
The pharmaceutical industry is much
more dependent on natural products than is generally realized. About a quarter
of all prescription drugs are taken directly from plants or are chemically
modified versions of plant substances, and more than half of them are modeled on
natural compounds. About 121 prescription drugs are derived from higher
plants. These include morphine, codeine, quinine, atropine, and digitalis. Yet
fewer than 1% of rainforest plants have been tested.
MEDICINES
FROM WILDLIFE
(from a list of 117) | |||
|
Purpose |
Drug |
Source |
Traditional
use
|
|
Immunosuppressant |
Fungus,
Tolypocladium inflatum |
| |
|
Contraceptives
|
Steroids |
Fungus, Rhizopus
nigricans |
|
|
Anti-inflammatory
|
Cortisone and
prednisone |
Fungus, Rhizopus
nigricans |
|
|
Cholesterol lowering
|
Lovastatin
|
Fungus, Aspergillus
terreus |
|
|
Painkillers
|
Aspirin |
Willow |
+ |
|
Antimalarial
|
Quinine
|
Cinchona
(coffee |
+ (Indian fever
bark) |
|
Amebicide |
Emetine
|
Cephaelis |
+ |
|
Heart stimulants
|
Digitalis |
Foxglove |
+ |
|
Pupil dilator
|
Atropine
|
Nightshade
|
|
|
Antispasmodics for
intestinal disorders |
Scopolamine,
Hyoscyamine |
Nightshade
|
|
|
Muscle relaxant
|
Tubocurarine
|
Chondrodendron |
+ (arrow poison)
|
|
High
Blood pressure |
Reserpine
|
Rauwolfia |
+ |
|
Glaucoma |
Pilocarpine
|
Pilocarpus |
+ |
Why should plants make medicines?
Wild plants have been evolving chemical defense mechanisms for millions of
years. The chemicals that have evolved are highly specific toxins that attack
herbivores at various different points in biochemical pathways. Although the
chemicals are often toxic, sometimes if they are delivered in the right way or
in the right dose, or altered chemically, they can be used to attack
disease-causing agents or even cancer cells.
Many of these chemicals are derived from plants that had been used in traditional medicine. For example, Peruvian Indians had a cure for malaria; they used an extract of the bark of the Cinchona tree, and this led to the discovery and use of quinine as an antimalarial treatment. Many plants have been used traditionally because they are psychoactive. Of the 121 drugs mentioned earlier, 74% were identified through native folklore.
A Japanese company was recently awarded a patent on a chemical derived from the Congorosa bush, a plant that is native to Uruguay. The native people have known for centuries that the plant can be used to combat inflammation and as a stomach and liver analgesic, so they are very much opposed to paying a fee to a Japanese company for the right to continue these uses.
Natural products isolated from higher plants and microorganisms
Even compounds produced by insects and other invertebrates may be useful. Recently a protein isolated from the salivary gland of a biting sandfly was shown to have a very powerful vasodilation effect (this facilitates blood feeding by the insect when it is injected into the host).
i. Anti-cancer
drugs. The rosy periwinkle
was used in Cuba, the Philippines, and South Africa for the treatment of
inflammation, rheumatism, and diabetes. In the late 1950s, vincristine and
vinblastine were isolated from the periwinkle plant by Eli Lilly scientists and
these chemicals were shown to have anti-cancer effects. Treatment with these
drugs has increased the chances of remission to 99% in childhood leukemia and to
70% in Hodgkin's disease. Global sales of vincristine and vinblastine earn the
Eli Lilly Company about $100 million each year.
|
ANTI-CANCER DRUGS | ||
Drug |
Source |
Traditional use |
|
Cantharidin
|
Chinese
Blister beetle |
+ (abortifacient)
|
|
Etoposide, |
Podophyllum peltatum
|
+ (snake
bites, weakness, condyloma, |
|
Monocrotaline
|
Crotalaria spectabilis
|
+ (skin cancer)
|
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Vincristine, |
Rosy periwinkle
|
+ (diabetes)
|
|
Taxol |
Yew
(Taxus brevifolia) |
_ |
In 1986, the National Cancer Institute started a new, extensive plant collection and screening program and has tested (on cultured cells) 35,000 species of higher plants as well as other organisms for anti-AIDS and anti-cancer activity. As of 1991, over 800 had shown some anti-HIV activity and 60 had shown anti-cancer activity (the HIV screens have been given higher priority). Plants used as medicines or toxins by forest people were 2-5x more likely to be active in these assays as other plants. This is a very preliminary result, and many more tests have to be done before any of these compounds will go into clinical trials. NCI estimates that of every 10,000 extracts tested, fewer than 10 will reach clinical trials. NCI is also supporting botanical exploration, research and training to increase the number of species to be tested. The collections have identified more than 40 new species of plants. NCI requires that if a pharmaceutical company receives a patent license, they have to share a percentage of the royalties with the country where the sample originated.
Chemists have devised ways of synthesizing many of the medicinal compounds found in plants. But it is usually (in about 90% of cases) cheaper to extract the natural product. In spite of this, pharmaceutical firms in the U.S. are doing very little to discover new drugs from higher plants. They are concentrating on other approaches; for example, using supercomputers to design new molecules.
An exception is Shaman Pharmaceuticals, a company set up specifically to identify and obtain medicinal compounds from tropical plants. Their program involves a serious effort to obtain not only materials but also knowledge from the people of the rain forest; they spend a lot of time interviewing forest people about medicinal uses of plants, then give much higher priority to testing those that have folk uses. They are screening for antiviral, antifungal, and sedative/analgesic activity. Out of the first 58 species screened, they found that 60% had activity in one of their screens, and 74% of their active samples correlated with the original ethnobotanical use. This is a much higher "hit" rate than then NCI rate, perhaps because of the different activities being screened for, and perhaps because they make greater use of ethnobotanical knowledge. This company is also dedicated to developing nondestructive harvesting methods and in providing benefits from any discoveries to the indigenous people who are the primary sources of the inventions. Merck & Co. have also set up an agreement with a research institute in Costa Rica to screen samples from micro-organisms, plants and insects from that country's forests. The institute will earn a share of any royalties on the sale of products derived from the project.
In 1982, the TRAMIL (Traditional
Medicine for the Islands) research network was launched in the
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Commercial overharvesting of some medicinal plants including goldenseal root, American ginseng, and Echinacea, may be endangering the survival of these species.? American Indians have developed ways of using these plants more sustainably. Recommended book: |
In 1998, the Indian Council of Scientific and Industrial Research successfully challenged six patent applications on the medicinal properties of turmeric. The U.S. patent office ruled that turmeric's medicinal properties were part of the traditional Indian knowledge base and were therefore not patentable.
The Pacific Yew tree, a rare and slow-growing tree in the Pacific Northwest, is the only source of a drug called taxol, which appears to be very effective in treating ovarian cancer and has great promise for treating breast cancer as well. Each year, about 20,500 women are diagnosed with ovarian cancer and about half that number die from it. But it takes six Pacific yew trees to extract enough taxol to treat one patient. The National Cancer Institute has enough available to treat about 300 patients-not even enough to complete clinical trials. The yew tree is found only in old-growth forests, so it has now become a potential problem, along with the spotted owl, in trying to save these forests. Recently, chemists found ways of synthesizing taxol, but it is a very complicated process. Another more feasible solution is to chemically modify related compounds that are found in the English Yew, which is a widely planted ornamental plant and could produce a sustainable supply so that the Pacific Yew will not have to be harvested.
The taxol story will hopefully have a happy ending, and it teaches us that the forest (and other natural habitats) should be considered a source of knowledge about medicines, rather than a source of the medicines themselves.
ii. Antibiotics. Antibiotics are generally isolated from
fungi (e.g. penicillin) or bacteria (e.g. erythromycin). However, a small group
of antibiotics comes from marine animals- mimosamycin, that comes from a
nudibranch (sea slug) and a sponge.
ANTIBIOTICS
(about 1,000 now known) |
| |
|
Antibiotic
|
Source |
|
|
Penicillin |
Penicillium
chrysogenum |
|
Fertilizers. Recent research has led to the identification of species of bacteria from the deep ocean that are capable of fixing nitrogen, converting into a form that can be used as a fertilizer for crops.
Materials. Many organisms have evolved materials whose unusual physical properties may make them useful. They may be obtained from the wild or, better, copied by biochemists. In many cases, finding one useful material may lead to the discovery of many more, with subtle differences in physical properties, from related organisms.
i. Fibers. Silkworm silk has been used for hundreds of years in production of fabrics. Spider silk, which is chemically very similar to silkworm silk, comes in many different varieties (some species make seven different kinds - see slide) and has 5-10x the tensile strength of steel and some very unusual elastic properties. It has been used on a limited basis for fishing nets and for wound dressings, and for cross hairs in optical instruments. However, for other applications it cannot be obtained in large enough quantities from spiders. Therefore, the genes for spider silk have been placed in bacteria or animal cells, which then make the silk protein. However, they make it in a solution, and this has to be extruded (forced through a small orifice at high pressure) to force the protein molecules to line up into a fiber. Nexia Biotechnologies is now producing transgenic goats in which a gene for spider silk is expressed in large quantities in the mammary glands. They are now working on ways to spin it into fiber. The artificial silk has the potential to be strong enough to make bullet-proof vests, surgical sutures and artificial tendons.
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ii. Coatings. Shellac, a wax produced by insects that is harvested by hand from trees in India. 4 million pounds/year are harvested and used in varnishes, paints, stiffeners and other uses. Some related species of insects in the southwestern U.S. make colored waxes that were used by the Indians to waterproof and decorate baskets and to repair pottery.
The cuticles and eggshells of insects, crustaceans, and many other animals, and the seed coats and other protective layers on plants may have useful properties as waterproof coatings for other materials. Chitin (the carbohydrate part of cuticle, extracted from shrimp shells) is already used to make wool shrink-resistant.
Keratins (the protein of feathers and hair) is used as a coating for pills so that they survive the acid stomach but then release their contents in the alkaline intestine.
iii. Adhesives. Casein, a protein from milk, is already used extensively in glue manufacture as well as in plastics and paints.
At least two companies are now marketing a glue based on the adhesive used by marine mussels to hold themselves on rocks. This kind of glue will stick to animal tissue as well as to metals and other materials. It might be useful in surgery and in other places where glue needs to function in a wet environment or needs to join dissimilar materials like metal and bone. One company is extracting the glue directly from a gland in the mussel, the other is synthesizing a glue based on the composition of the natural adhesive. Unfortunately, the natural material is not well understood. However, there are hundreds of different kinds of mussel, and there may be many different versions of the glue to investigate.
iv. Biopolymers, especially moldable polymers, similar to plastics made chemically, have been produced in bacteria and theoretically could be produced in plants, so that the material could be grown as a crop.
v. Oils. About 20% of the petroleum used in this country is used for non-fuel purposes such as plastics, fertilizers, lubricants, and adhesives. The majority of these substances can now be synthesized from plant products. In fact, about 3 million tons of vegetable fats and oils are already used in these processes annually. Further development of these industries could help in reducing our dependence on non-renewable fossil fuels.
There are several promising
tropical oil plants in South America, including:
|
|
Patuፊ palm. The fruit
produces an oil that is almost identical to olive oil, and is rich in
protein as well. |
|
|
Babass?palm. Produces
a coconut-like fruit rich in oil and protein. The tree grows well in
deforested areas. |
|
|
Fevillea vine. Seeds
have an extremely high oil content. |
Another very important plant is Jojoba, a desert plant of the southwestern United States and northern Mexico that produces a "liquid wax" (chemically different from an oil) that is almost identical to sperm whale oil, is very useful as a heat-resistant lubricant and has many other potential uses. Another desert plant, guayule, has a very high content of natural rubber and could help to relieve the dependence of this country on rubber grown in Southeast Asia.
Oil from the seed of India's Pongamia pinnata tree is being used as a substitute for diesel in electricity generation in rural areas of the country.
vi. Enzymes. Some of the bacteria-like organisms found near submarine hot vents (Archaea) can live at temperatures as high as 113oC and may be useful in the production of enzymes that are stable at high temperatures (for use in washing machines, for example).
Biomimetic materials science
is the name given to
attempts to mimic the materials found in nature. Much of it is funded by the
Navy and the Air Force, because of the potential importance of lightweight but
strong materials in aerospace engineering, and of underwater glues and coatings
in marine engineering. It is necessary to understand not only the chemical
makeup of the biological materials, but also the organization of different
components within the material (e.g. calcite and proteins in sea urchin
skeleton, or carbohydrate and protein in cuticle), which in nature is controlled
by the cells producing the material.
Wild organisms carry out many functions in the environment that are vital to us, and that would be very difficult to do ourselves. Bees pollinate about a trillion apple blossoms each year in New York State.
Carpenter bees pollinate Brazil-nut trees. Bats pollinate wild bananas (not the cultivated ones that are parthenocarpic), breadfruit, guava and durian (Malaysian fruit). Wild micro-organisms biodegrade much of our garbage as well as fallen leaves and other dead animal and plant matter. Earthworms turn over soil and keep it aerated. Soil bacteria turn nitrogen into nitrate fertilizer. Plants use up carbon dioxide and produce oxygen, thereby slowing global warming due to CO2.
A few decades ago, the water in the Chesapeake Bay was clear because oysters were filtering out particles at a rate estimated to be the equivalent of the entire volume of the bay every three days. Because the oysters have been overharvested (99% gone) they are no longer able to keep up with the accumulation of silt and other particulates.
All of these services, and many
more besides, are provided free of charge and usually taken for granted until
they stop.
|
ENVIRONMENTAL
SERVICES |
| |
|
Service |
Organism |
|
|
Pollination |
bees,
bats |
|
Bioremediation (=phytoremediation if it is done by plants) refers to the use of organisms to clean up toxic wastes. Some plant species that live naturally on soils that are rich in heavy metals have evolved biochemical mechanisms for extracting those metals from the soil and accumulating them to very high levels in their tissues. They are called hyperaccumulators. Plants in the mustard family are especially promising. Some of them accumulate so much metal that it makes up 5% of their weight. This makes them toxic to insects, so it has probably evolved as a defense mechanism. The accumulated metals also makes them harmful or lethal to grazing animals including cattle and horses. Read how "locoism" may have played a part in General Custer's defeat at the battle of Little Big Horn. Plants have been found that hyperaccumulate copper, nickel, lead, cadmium, chromium, zinc, cobalt, mercury and selenium, so they are being planted on toxic waste sites where they remove the toxic metals from the soil. They can be burned in order to recover the metal in cases (copper and nickel) where the metal is valuable. With less valuable metals such as lead, the hyperaccumulating plants are much easier to dispose of than contaminated soil.
A simple use of phytoremediation has been used in California's San Joaquin Valley, where there is a problem with high levels of selenium in the soil. Growing mustard plants on the contaminated soil reduced selenium levels by 50% at depths down to 1m.
Other sites where this technique is being used include abandoned mines (zinc and lead); military sites (lead and cadmium); municipal waste dumps (copper, mercury, lead); and sewage dumps (all of these metals). Phytoremediation is potentially much more effective and less expensive than current methods which consist mainly of excavation and reburial.
Some of the metals that are toxic at high levels (e.g., selenium) are actually required by the body at low levels. So hyperaccumulating plants may also be useful in providing essential metals in the diet at the appropriate levels.
Some of the hyperaccumulating plants are difficult to grow and do not produce much biomass. Scientists are therefore identifying and cloning the genes responsible for hyperaccumulation and exploring ways of transferring them into common crop plants that would not have these drawbacks.
In a paper published in Nature in
May 1997, a group of 13 ecologists, geographers and economists estimated the
economic value of these environmental services at between $16 and $54 trillion
per year. This estimate is based on the cost of artificially providing the same
services. The services they evaluated included food production, raw materials,
recreation and water supply, regulation of climate and atmospheric gases, water
cycling, erosion control, soil formation, nutrient cycling and the purification
of wastes. Also read the discussion of this paper.
Ecosystem Services: Benefits Supplied to
Human Societies by Natural Ecosystems
"Miners use canaries to warn them of deadly gases. It might not be a bad idea if we took the same warning from the dead birds in our countryside" (H.R.H. the Duke of Edinburgh at the Wild Life Fund dinner, about 1963 in reference to DDT). Today, we might take the same warning from the forest dieback, the dead sea lions and dolphins on our beaches, and the missing amphibians. (See Lecture 14 for examples of the effects of chemical pollutants on wildlife.) If the environment is killing animals and plants, it might eventually kill us too. Pesticide levels in human milk are enormous. If we were egg-laying mammals we might be suffering from eggshell thinning caused by DDT by now.
The necessity of looking to
wildlife species for warning signs becomes more evident when one considers that
for 71 percent of the 3,000 highest-volume chemicals in the U.S. economy no
human health-effect screening has ever been conducted. A 1984 report
released by the National Academy of Sciences' National Research Council
documented a lack of "even minimal" health screening tests for 78 percent of
high-production-volume chemicals in the U.S. In July of 1997, the
Environmental Defense Fund released a study entitled "Toxic Ignorance" that
pointed to the lack of improvement in screening over the last 13 years. In
conjunction with the report's release, the EDF called for commitments from the
chief executive officers of the 100 top chemical manufacturers in the U.S. to
complete preliminary health screening tests on each company's top-selling
chemicals before the year 2000, and disclose the results to the public.
According to the EDF study, the testing requested would cost between 1/10 of a
cent to 2/3 of a cent per dollar of profit for the top 100 US companies, which
made profits of $29.4 billion last year on $230.5 billion of chemical
sales. In the meantime, the effects of these chemicals on wildlife, and on
humans, remain unknown.
Wild species provide
raw material for basic research. The object of basic research is simply to
understand the natural world. Even though it often leads to material benefits,
and is justified that way, the motivation is simply the challenge to know as
much as possible about the natural world, and to understand how both living and
non-living things work.
Wildlife is worth conserving because it is interesting, beautiful, spectacular, or contributes to landscapes that are interesting, beautiful, or spectacular. Wild animals and plants provide inspiration not only to biologists but also to millions of naturalists, explorers, painters, photographers, writers, poets and musicians. After Aldous Huxley read Rachel Carson's Silent Spring (about the loss of songbirds due to DDT), his comment was that "we are losing half the subject-matter of English poetry".
Enjoying wildlife is far from being restricted to poets, however. According to a survey conducted for the U.S. Fish and Wildlife Service, 77 million Americans participated in wildlife-related recreation in 1996. During that time, they spent $108 billion compared to only $81 billion on cars. Preserving the environment is healthy for the economy as well as for the soul.
John Muir, one of the founders of the Sierra Club, valued wilderness and wild creatures for their aesthetic qualities. He managed to convince President Theodore Roosevelt, the hunter, that our most beautiful areas should be protected, simply for aesthetic reasons. His work led to the establishment of Yosemite National Park and many other protected areas.
These arguments justify saving
subspecies as well as species. Some of them justify preserving abundance as well
as existence of a species. Of course, ecosystems are interesting too, and
according to this view they should also be conserved. Some of the most
interesting aspects of animal life (social behavior, migration, etc.) occur only
in the wild, not in zoos. So this argument favors conservation in the
wild.
We do not know what our value systems will be in the future, or what the value systems of our successors will be. Perhaps they will need vast quantities of some species that we now consider insignificant or even harmful. Many of the natural sources of medicines are, in fact, poisonous. Nobody could have predicted that bread mold would be the source of one of the most useful antibiotics; that armadillos would have been useful in medical research because they are the only experimental animal that can be infected with leprosy; or that the Madagascar periwinkle would be a source of an antileukemic drug, or that a heat-loving microbe living in a hot spring at Yellowstone National Park would provide a key ingredient in the DNA fingerprinting work was so important in the O.J. Simpson trial.
The main reason for preserving not only species but also genetic variability of not only wild species but also domesticated ones (and humans!) is so that we, and the other animals and plants on the planet, can adapt to unforeseen changing circumstances.
A relevant question that is now being asked is whether we should destroy the last remaining stocks of the smallpox virus. They are being kept in a freezer pending review of a decision made to destroy them in 1999.
In the future we may find new reasons for keeping ecosystems, not just species, alive. We could not learn about medicinal plants from chimpanzees if they are in a zoo - they have to be in an intact environment in the wild.
By allowing species to become extinct and by destroying ecosystems we cut off options that we are not capable of imagining; the responsible course is to keep as many options open as possible.
For additional reading, see "Do We
Still Need Nature? The Importance of Biological Diversity".
INTERNATIONAL SOCIETY FOR ECOLOGICAL
ECONOMICS
The search for
agricultural and medicinal uses for the world's biodiversity can be
controversial. Legal and ethical issues surrounding the sharing of genetic
resources and the profits realized from them remain unresolved. The United Nations Convention on
Biodiversity addresses
many of these issues and has been ratified by 170 countries. Some countries,
including the United
States, still refuse to sign the agreement, primarily because it contains
clauses requiring profits from biodiversity be shared with the species' country
of origin.
Finding useful drugs in
wild plants and animals can be a mixed blessing. According to the World Health Organization the global trade was worth about
$500 million a year in 1980, but by 2000, the European market alone was
predicted to reach $500 billion. A 1998 study by TRAFFIC, the wildlife
trade monitoring program of World Wildlife Fund and
the World Conservation Union, identified 102 medicinal plant species (including
the frankincense tree) and 29 medicinal animal species (including the green
turtle, African rock python, and black rhinoceros) as priorities for early
conservation and management action.
|
Chapter
13: ENDANGERED SPECIES CONSERVATION Feedback
form for questions, comments and suggestions | |
|
Copyright ?2005 Peter J.
Bryant (pjbryant@uci.edu), Phone (949)
824-4714 A Project of the Interdisciplinary
Minor in Global Sustainability | |