The Hidden Power of Plants
Plants produce some of the world's most potent chemicals in the fight against disease. NOVA follows the urgent efforts to track down new medicines in nature.
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00:00Tonight on NOVA. Ten-month-old Laura has cancer, but this houseplant contains a chemical that may save her life.
00:10From everyday painkillers to prescription heart medications, modern pharmacies are stocked with powerful drugs that were first derived from plants.
00:19Scientists are searching for new medicines among the exotic plants of the tropical rainforest.
00:25But will they find tomorrow's wonder drugs before the forest disappears?
00:30Tonight on NOVA. The hidden power of plants.
00:41Major funding for NOVA is provided by this station and other public television stations nationwide.
00:48Additional funding was provided by the Johnson & Johnson family of companies, supplying health care products worldwide.
00:57And by Allied Signal, a technology leader in aerospace, electronics, automotive products, and engineered materials.
01:18NOVA is an international, independent, nonprofit organization based in Germany.
01:48By any measure, the plants of the tropical rainforest are beautiful and mysterious.
01:59In this profusion of leaves and blooms are thousands of plant species, many still undiscovered and unnamed.
02:10Plants that provide shelter and nourishment for the animals that live among them.
02:19Plants that help sustain the Earth's atmosphere, renewing the oxygen that makes life possible.
02:27And plants that provide medicine.
02:31Indeed, the history of medicine has been largely the story of plants and the potent chemicals they produce.
02:39Around the world, traditional healers using plant medications provide health care to 80% of the human population, over 4 billion people.
02:51Ayurveda, also called the science of life, developed in India more than 3,000 years ago,
02:57laying the foundations for one of history's most remarkable medical traditions.
03:04This system of herbal remedies and natural healing is still dominant in India.
03:14There are more than 8,000 prescriptions in this ancient system of medicine,
03:19and factories like this one process raw materials into preparations used by over half a billion people.
03:26From Ayurveda, the Western world learned about Rawulfia serpentina, or the snake root plant.
03:32Also known as racerpene, it is used to control hypertension and is a compound essential to modern cardiology.
03:46Like India, Chinese medicine is also used to treat heart disease.
03:52Like India, China is the home of an ancient and sophisticated natural medicine system.
04:04Over 4,000 years, the Chinese have discovered, developed and refined more than 11,000 medical prescriptions based on the natural chemistry of plants.
04:14These mixtures and compounds were based on centuries of empirical observation of their effects on the human body.
04:24Using ancient recipes, remedies are carefully weighed and measured in accordance with the physician's requests.
04:31While the final prescription may contain unusual-looking elements,
04:36the herbal drugstore is as common in China as the corner drugstore in the West.
04:44Even in parts of the world where vegetation is sparse, there is a legacy of medicinal plants.
04:51For centuries, the Bedouin have used Ami seeds, which contain Chromelin, as an effective asthma remedy.
04:58Even our own Western pharmacology, with its pills and other medicines,
05:02has been used to treat asthma.
05:10The Bedouin have used Ami seeds to treat asthma.
05:14Ami seeds are a type of herbal medicine that is used to treat asthma.
05:18Ami seeds are a type of herbal medicine that is used to treat asthma.
05:23Even our own Western pharmacology, with its pills and white crystalline powders,
05:28owes much of its potency to the plant kingdom.
05:33Many common medications were first derived from plants.
05:40More than 2,400 years ago, the Greeks used extracts of willow bark to treat pain.
05:46The active compound it contained is better known today as aspirin.
05:53The flowering foxglove was used to treat heart problems as far back as the 15th century.
06:00Today, digitalis from the foxglove is still an important component of heart medications.
06:08Aspirin, digitalis, and many other medicines are now synthetics, chemical versions of plant compounds.
06:14But not all modern medicines can be synthesized.
06:18Over 25% of the drugs prescribed in the U.S. still contain plant materials as their principal active ingredient.
06:27According to a recent study by a congressional group,
06:30the U.S. imported over $24 million a year of medicinal plants in 1974,
06:35and then turned these into $3 billion worth of medicines.
06:39So it is fairly a significant business.
06:43What is it about plants that gives them the power to heal or to harm?
06:48For in addition to their beneficial uses,
06:51some plants are well known to contain chemicals that are harmful to the human body.
06:57Rhubarb leaves, for instance, produce a deadly broth of chemicals that can cause diarrhea,
07:02vomiting, and can prevent the blood from clotting.
07:07Every part of the potato plant, except the fleshy tuber, can cause severe poisoning.
07:14What lies behind the mysterious chemistry of plants?
07:21Of all living things, only plants have the power to transform light energy into life energy.
07:29This precise chemical process is known as photosynthesis.
07:33These leaf cells under the microscope reveal a constant stream of green particles called chloroplasts.
07:45Magnified 40,000 times, the inside of the chloroplast is seen to be made up of tiny light collectors arranged in layers.
07:55There are thousands of chloroplasts in the world,
07:59There are thousands of such chloroplasts in each green leaf, performing the task of photosynthesis.
08:05Within the leaf, carbon dioxide absorbed from the atmosphere and water taken up by the root system
08:11undergo complex chemical reactions fueled by energy from sunlight.
08:16The result is the simple sugar glucose, which is stored in the leaf cells as food.
08:21The oxygen that is released back into the atmosphere is simply a byproduct of the process.
08:30The primary products of photosynthesis, carbohydrates and sugars, sustain the plant itself,
08:36and the plant can then in turn be consumed as part of the food chain.
08:41Yet only a few of the many chemicals produced by plants are primary compounds.
08:49Another group of chemicals called secondary compounds are unusual substances
08:54that do not seem essential to the plant's basic life cycle.
09:00The plant's primary compounds are the carbohydrates,
09:04and the secondary compounds are unusual substances that do not seem essential to the plant's basic life cycle.
09:15For the most part, the functions served by these secondary compounds are still unknown.
09:24Why does Oleander manufacture cardioactive glycosides that can paralyze the lungs, cause bleeding and even death?
09:34What is the role of calcium oxalate in household chalidions?
09:38In humans, it irritates the throat and can lead to asphyxiation.
09:45And why does Belladonna produce hallucinogenic compounds?
09:51One view is that the plants need these substances for protection and defense.
09:57It comes back to the competition between living organisms for nutrients.
10:03And for example, if you look at the tropical areas, you have a tremendous variety of plants
10:08and all of them have everything they need to grow very, very prolifically.
10:13They have oxygen, they have light, they have soil, warm temperature, everything except space.
10:20And the limitations of living space force these plants to prepare and to secrete
10:28different sorts of protective substances which enhance their ability to survive
10:34either by preventing predation or preventing attack by insects
10:39or by enhancing the destruction or limiting the ability of other plants to grow around them.
10:49But scientists are not in complete agreement about the role of secondary compounds.
10:55For some, they remain mysterious entities.
10:59We don't know what their function is in plants. We have absolutely no idea.
11:05And a lot of people are inclined to dismiss this as being idle metabolic chatter on the part of the plant, for example.
11:11Some useless chemical the plant doesn't know what it's doing, so it spends a lot of its time dreaming up some scheme
11:18for making weird molecules which people like myself might be interested in, you know.
11:27Whatever purpose they may serve in the plant, these secondary compounds are the critical components of plant medicines for human use.
11:34And the search for hidden power in plants has often revolutionized medicine.
11:40In 1803, a young German pharmacist, Friedrich Sutterner, was looking for the active substance contained in opium from the poppy,
11:48whose good and evil influence had been known for centuries.
11:55He was the first to identify an alkaloid, a secondary plant product characterized by its molecular structure,
12:01which includes at least one nitrogen atom, and by its ability to affect the human body.
12:07Once the alkaloid had been isolated, Sutterner could refine the opium into a more powerful drug, with more precise action in the body.
12:16After testing the new drug on himself and his colleagues, he named it morphine, for Morpheus, the Greek god of sleep,
12:23and its pain-killing properties remain unsurpassed.
12:29Alkaloids are the active component of opium.
12:33Alkaloids are the active compounds in such familiar drugs as nicotine, caffeine, and cocaine.
12:44They have also accounted for modern-day medical breakthroughs.
12:49The Madagascar periwinkle has a long history as a traditional remedy, used to treat everything from sore throats to diabetes.
12:58In the 1950s, scientists discovered that an alkaloid called vincristine, produced by the periwinkle,
13:04had a new application in treating childhood leukemia and other cancers.
13:11Ten-month-old Laura is receiving vincristine as part of a program of therapy to stop the growth of a malignant tumor.
13:18Her physician, Dr. Mark Greenberg, describes how vincristine works.
13:22Vincristine is a mitotic spindle poison.
13:26What the drug actually does is to arrest the division of cells.
13:32When a cell of any sort divides, its chromosomes split into two and then attach themselves to what's called a mitotic spindle.
13:41The mitotic spindle helps to pull the two halves of the chromosomes apart.
13:46What vincristine actually does biologically is to poison that spindle, or the tubules that form that spindle.
13:53It does this preferentially with malignant cells.
13:57So what it's doing is really attaching to any tubules, any mitotic tubules, in malignant cells that are in the process of dividing.
14:07The use of vincristine is just one part of an aggressive medical approach to childhood cancer.
14:13We almost never use drugs by themselves.
14:16We use a combination of drugs that act at various points in the cell cycle.
14:21So vincristine, used in combination with many other drugs, is enormously effective in this sort of range of malignant disease in childhood.
14:29Between the new drugs and the new methods of chemotherapy,
14:33we've gone from what was perhaps 10 or 15 percent five-year survival in childhood leukemias
14:41now up above 85 or 90 percent.
14:48Other life-saving medical breakthroughs have recently come from the natural world.
14:54A vacation stroll in Norway 15 years ago led to a discovery that revolutionized the science of organ transplantation.
15:03An employee of a Swiss drug company looking for dirt collected a few spoonfuls of mud from a murky swamp.
15:13He brought the mud back to the lab here in Basel, Switzerland.
15:20Because many antibiotics have been discovered in soil,
15:23drug companies routinely check soil samples from all over the world to see what they contain.
15:29Among the several microbes which grew from the Norwegian mud was a fungus that had never been seen before.
15:43This new fungus produced a chemical that had an unexpected benefit.
15:47It could counteract organ rejection.
15:50Although the surgical techniques that allowed transplants have been in use since the first kidney transplant in 1954,
15:56the transplants themselves were only moderately successful.
16:03In order for transplants to work, a significant problem must be overcome.
16:10A transplant is a process in which the organ is removed from the body.
16:14To work, a significant problem must be overcome.
16:20A transplanted organ is perceived as a foreign invader by the body's white blood cells,
16:24which then attack the new organ, in this case a kidney.
16:29This immune response overwhelms the organ and leads to rejection,
16:33unless the recipient is given immunosuppressant drugs.
16:39These drugs kill the white cells that cause rejection,
16:42but they also kill all the other cells that protect the body from intruders,
16:46leaving the patient vulnerable to serious infection.
16:53More than ever before, cyclosporine solved the problem.
16:57When the white blood cells start to attack a new organ, cyclosporine calls them off.
17:04But unlike the other anti-rejection drugs, it doesn't kill them.
17:08It just stops their assault.
17:11So the organ is protected, but the white blood cells can still patrol the body
17:16and keep it free from infection.
17:21Over 7,000 transplants are performed in the U.S. each year.
17:25Since cyclosporine was first made available in 1983,
17:29the success rate of certain transplants has grown to nearly 80%.
17:34The recent discovery of such drugs as cyclosporine and vincristine
17:38suggests that there is still untapped potential in nature's chemistry
17:42and has inspired the search for new medical products from plants.
17:47When you consider that all the drugs that come from plants in the world
17:52come from about 90 species, and there are 250,000 leaf species in the world,
17:57then common sense tells you there have to be more drugs.
18:01It tells you there have to be more drugs in plants if we rely on only 90 of them
18:07to provide 25% of the medication in the United States.
18:15Dr. Richard Schultes of Harvard University has spent more than 40 years
18:19searching for plants that might help realize this potential.
18:24There are a half a million species of plants in the world.
18:28My interest is purely medicinal, but I hope one day at least
18:32one of the plants that I have brought to the attention of science
18:37may give us a new medicine.
18:42An ethnobotanist, Schultes specializes in the medical uses of plants
18:46in traditional cultures.
18:50His work has focused on the rainforests of the Amazon
18:53and in teaching others the ways of the jungle.
18:56The blowgun among the peoples who use it is extremely accurate.
19:02Blowguns and poison arrows have played a significant role in Schultes' research,
19:07and he enjoys showing off his prowess with them.
19:11Of course, I'm in a building here, and I can't shoot very high,
19:17but we're going to try to see if we can hit that target up there.
19:27When I got my Ph.D. at Harvard in 1941,
19:32I had a grant to go down to work on arrow poisons
19:37in the headwaters of the Amazon.
19:41Arrow poisons, which the natives used to kill animals,
19:45were becoming very important in medicine.
19:49The best known of those arrow poisons, curare,
19:52has become indispensable as a muscle relaxant during surgery.
19:56To Schultes, the Amazon was an obvious starting place
19:59for botanical research.
20:02When you look at any flora,
20:04even our own deep-harbored flora here in New England and Canada,
20:10it's a veritable chemical factory.
20:15Multiply our 1,800, 1,900, 1,000,
20:201,800, 1,900 species,
20:23multiply that to 80,000,
20:26and you can see what an emporium of chemical wealth the Amazon is.
20:35Schultes himself has collected over 24,000 plant specimens,
20:39many of them previously unknown.
20:42With such plant riches available for study,
20:44botanists must find a way to focus their research
20:47on the plants most likely to have medicinal value.
20:51If chemists are going to have to get material of
20:56and analyze 80,000 species, they'll never finish the job.
21:00One shortcut is to concentrate on those plants
21:05that the natives have found to have some activity on the human body.
21:13Schultes found the local medicine men
21:15to be his most valuable tutors in plant medicines.
21:18He even participated in their rituals.
21:21He's the tall one on the right.
21:25Mark Plotkin, an ethnobotanist who was trained by Schultes,
21:29also works in the Amazon using the same methods.
21:33Well, according to Professor Schultes,
21:35the oldest profession in the world is actually that of a shaman or witch doctor.
21:40Through the course of human history,
21:41most of the world's medicines have come from plants.
21:44It's only relatively recently with the advent of modern technology
21:47that we've been able to reduce our dependence on medicinal plants
21:51as a source of medicines.
21:52The medicine man or shaman or witch doctor or brujo or curandero
21:56is the person who knows the most about these plants.
22:00Now, if you look in Western literature and movies and films and books,
22:04he's often been derided as somebody who runs around with rubber snakes
22:07screaming gibberish and mumbo-jumbo.
22:09But the people who've had the real pleasure
22:11and the opportunity to work with these people
22:13has found out quite the opposite,
22:15that this is a very serious profession.
22:17This is the predecessor of modern doctors,
22:20and we have a lot to learn from these people.
22:28This is Dionisio Aguinda.
22:31He is a brujo or medicine man of the Ecuadoran Amazon.
22:35He is searching for plant remedies he can use in treating his patients.
22:43For Aguinda, a Kichwa Indian, the rainforest is a living pharmacy,
22:48a potent, varied and infinitely renewable source of plant medicines.
22:54Aguinda uses this bark as a treatment for pain.
22:58as a source of plant medicines.
23:17Aginda uses this bark as a treatment for pain.
23:24He draws on an extensive but unwritten body of knowledge
23:27about plant medicines and their preparation.
23:31For today's treatment, the bark is prepared according to a formula
23:35that calls for it to be boiled, along with several other ingredients.
23:39The formula, along with countless others,
23:42was passed down to him from his father and grandfather,
23:45who were also medicine men.
23:50His patients often journey for days through the jungle to seek his help.
23:54This woman has a persistent stomach pain.
24:01Because of the bark's unpleasant taste,
24:04the medication was prepared in a weak broth.
24:09Like many plant medicines,
24:11it must be taken several times to reach its full effect.
24:24The Western reaction to some of these medical practices
24:28is often a skeptical one.
24:30One of the things you learn in working with these different cultures
24:33is these people have a different approach, in many cases,
24:36to curing and healing.
24:38And in the case of some Indian societies in South America,
24:41the medicine man, or curandero, actually takes the medicine,
24:45which in this case is a hallucinogen,
24:47and defines the cause of the illness
24:49and attempts to cure it through contact with the spirit world.
24:51There's a wonderful quote where it said
24:53the white man goes into his church and talks about Jesus,
24:56and the Indian goes into his tipi and talks to Jesus.
25:00In ceremonies like this one,
25:02the patients entrust their health and their lives
25:04to an ancient alliance between the natural and the supernatural.
25:12There will often be further treatment with herbal medicines,
25:15and some of the hallucinogens themselves
25:17may prove to have important medical applications.
25:21In the 1940s, Professor Schultes was working with Indians
25:24in the Northwest Amazon,
25:26and he found them using the sap of the tree of the nutmeg family
25:29for two purposes.
25:31One is as a hallucinogenic snuff,
25:33and the second to paint on fungal infections of the skin.
25:35Forty years later, I was working on the Suriname-Brazil border,
25:38and I found the Indians using this for the same purpose,
25:41that is, to paint on fungal infections of the skin.
25:43Now, modern medicine cannot cure serious fungal infections of the skin.
25:47If you get a bad case of athlete's feet, for example,
25:49you have to suffer from it.
25:51We can only suppress it, we can't cure it.
25:53A real problem with cancer patients
25:55is because of the problems with their immune systems
25:57resulting from the disease or the medication,
25:59is they have problems with fungal infections of the skin.
26:03Now, a Brazilian plant chemist
26:05looked at fresh material of this family
26:07and found three new compounds
26:09previously unknown to science,
26:11two of which have antifungal properties.
26:13It's my belief that focusing on plants,
26:15which are used for the same purpose by different peoples,
26:16are where we're going to find
26:18new and important medicines for the future.
26:39This remote part of Ecuador
26:41has recently become the focus of intensive scientific study.
26:44Part of a systematic effort
26:46to document the elaborate medical tradition
26:48of the Kichwa Indians.
26:54In a collaborative venture,
26:56ethnobotanists Robin Marles of the University of Illinois
26:59and David Neal of the Missouri Botanical Gardens
27:02head off on a collecting trip.
27:06Our project is involved
27:08in basic biological inventory
27:10of the Amazon rainforest.
27:11To find out just what's here,
27:13what plants are here.
27:15Because although this region,
27:17the upper Napa,
27:19is one of the richest areas biologically in the world,
27:22it's very poorly known.
27:27Today, the Inisio Aguinda
27:29allows the scientists to accompany him
27:31as he sets out on one of his routine trips
27:33to collect medicinal plants.
27:42This fieldwork is part of a massive effort
27:45to identify and investigate
27:47nearly 2,000 therapeutic plants
27:49used in the Northwest Amazon.
28:00Even to experienced naturalists,
28:02the sheer diversity of the Amazon
28:04with its more than 80,000 plant species
28:07is overwhelming.
28:08Without Aguinda's guidance,
28:10their chances of discovering
28:12useful medicinal plants are remote.
28:28Aguinda's intimate knowledge
28:30of the jungle and its healing plants
28:32has been a family legacy for generations.
28:38But around the world,
28:40the knowledge of such natural healers
28:42is on the verge of disappearing.
28:45Aguinda's son, Enrico,
28:47represents the end of the family tradition.
28:50Instead of training as a medicine man
28:52like his father,
28:54Enrico has become a guide and translator
28:56for the growing traffic of prospectors,
28:58oil men, and even tourists
29:00who now filter into the heart of the forest.
29:05When Aguinda dies,
29:06his family legacy will pass
29:08from the human record,
29:10and science will lose a vital link
29:12to the mysterious plant kingdom.
29:14What we're looking at
29:16is a culture that's standing
29:18on the edge of a precipice.
29:20And this culture and this knowledge
29:22is going to disappear
29:24over the edge of that precipice
29:26unless we work to document that knowledge
29:28in the next generation.
29:30Every time one of these old medicine men dies,
29:32it's as if a library has burned down.
29:34In fact, it's worse than that.
29:36That knowledge is found
29:38in other libraries as well.
29:40When these old medicine men die,
29:42that knowledge is lost forever.
29:47With an increasing sense of urgency,
29:49the research team will attempt
29:51to make a permanent record
29:53of Aguinda's medical knowledge.
29:57Following his leads,
29:59they continue their search
30:01for samples of the plants Aguinda uses
30:03which might have further medical potential.
30:06This is a species of Sloania.
30:08S-L-O-A-N-I-A.
30:10This field work in Ecuador
30:12resulted in the collection
30:14of over 200 species.
30:16Before the scientists leave the jungle,
30:18they must prepare the plant specimens
30:20to be shipped back to the U.S.
30:28Through the ages,
30:30botanists have used similar methods
30:32to organize and preserve their findings.
30:34Samples of each plant,
30:36called voucher specimens,
30:38are first sorted according
30:40to common characteristics,
30:42such as leaf shape and structure
30:44or presence of flowers.
30:46The voucher specimens
30:48are then pressed between layers
30:50of newspaper to dry.
30:54Known species are identified on site.
30:57For other species,
30:59any special characteristics
31:01that might aid in identification
31:04of a particular species.
31:06Unfamiliar specimens
31:08may also be recorded
31:10by a botanical illustrator.
31:13In some cases,
31:15a plant will warrant
31:17more than a single specimen.
31:19If it seems particularly interesting,
31:21for example,
31:23something that's used
31:25to treat intestinal parasites
31:27or something that's used
31:29to treat sores
31:31which don't heal for a long time,
31:33it's important to collect
31:35about five kilos dry weight
31:37of the plant
31:39to bring back to Chicago
31:41for a chemical
31:43and biological analysis.
31:45Plant chemist,
31:47Dr. Bryce Douglas,
31:49is familiar with the obstacles
31:51faced by collectors
31:53when large amounts
31:55of plant materials are required.
31:57That is when it is
31:59extremely difficult,
32:01keeping in mind
32:03it's 100% humidity,
32:05try to dry natural materials,
32:07try to get the water out of them.
32:09Under those conditions,
32:11it's very difficult.
32:13And if you don't,
32:15you simply rot.
32:17So there are a lot of logistics
32:19of that sort
32:21that have made
32:23the chances of success
32:25just a little bit tougher.
32:27Once the samples
32:29are back in the lab
32:31in Chicago,
32:33it may be months
32:35or even years
32:37before they know
32:39if they've discovered anything.
32:41You're only going to find activity
32:43in a few percent
32:45of all the plant extracts
32:47that you test.
32:49Then from there,
32:51you've only got the initial stage
32:53which is some sort
32:55of a crude extract
32:57or gum or goo
32:59that has the biological
33:01activity you're after.
33:03So it takes an awful lot
33:05of time and work.
33:07And at each stage,
33:09you've got to follow it
33:11by biological assays
33:13looking for the same activity
33:15that's desired in the end
33:17so as to make sure
33:19that you're on the track
33:21of the active substance.
33:23One active substance
33:25of potential pharmacological value
33:27has recently been detected
33:29at the University
33:31of British Columbia.
33:33It's a variety
33:35of garden marigold.
33:37The marigolds contain compounds
33:39called polyacetylenes
33:41which seem to be
33:43showing some promise
33:45in lab experiments
33:47as anti-tumor agents.
33:49In this demonstration,
33:51an extract from the marigold
33:53is added in equal parts
33:55to two dishes
33:57containing mosquito larvae.
33:59The larvae absorb
34:01the polyacetylene molecules
34:03from the dish.
34:05These molecules are unusual
34:07because they are photosensitive,
34:09becoming active only
34:11in the presence of sunlight.
34:13The specimens are placed
34:15in an ultraviolet light chamber.
34:17One dish is covered
34:19so that its contents are shielded.
34:21The combination of polyacetylenes
34:23and ultraviolet light
34:25causes a violent reaction
34:27that destroys the cells of larvae
34:29in the unshielded dish.
34:31Those in the covered dish
34:33are exposed to light.
34:35Researchers are hopeful
34:37that such light-activated toxins
34:39could be modified
34:41for use in the human body
34:43where they would be targeted
34:45to destroy particular cancer cells
34:47while leaving the body's
34:49normal cells intact.
34:51Extensive research
34:53into anti-cancer drugs
34:55that could be derived from plants
34:57is now being sponsored
34:59by the National Cancer Institute.
35:01It's the largest program
35:03with something over
35:0535,000 plants,
35:07different plants,
35:09different species,
35:11over 120,000 extracts,
35:13and when you're looking at
35:15a large variety of substances
35:17with biological activities,
35:19you're going to find some
35:21that have good medicinal activity.
35:24Thanks to the development
35:26of new technologies,
35:28the NCI scientists
35:30have become increasingly sophisticated
35:31when it comes to screening
35:33for anti-cancer agents in plants.
35:35After perhaps 25 to 30 years
35:37of testing,
35:39we've now realized
35:41that we're not apt to find
35:43a kind of magic bullet,
35:45as it were, for cancer
35:47because cancer is so many
35:49different diseases
35:51and each cancer
35:53in each different organ
35:55is different to the others
35:57and doesn't respond
35:59to the same sorts of drugs.
36:01So we're screening for agents
36:03against lung cancer,
36:05colon cancer,
36:07breast cancer,
36:09and looking for agents
36:11which affect those specific
36:13types of cells
36:15and not other cells in the body.
36:17The Natural Products Division
36:19of the NCI
36:21is extending its search
36:23for new anti-cancer agents
36:25beyond the plant kingdom.
36:27Recently,
36:29they've carried their exploration
36:31to the sea.
36:33One promising discovery
36:35comes not from a plant
36:37but from a marine animal
36:39called a tunicate or sea squirt.
36:41Dr. Kenneth Reinhart.
36:43The sea is really
36:45a rather harsh environment
36:47in the sense that
36:49everything grows on everything else
36:51and everything eats everything else
36:53so that something
36:55that's just sitting there
36:57like sponges or tunicates
36:59really have to have
37:01to defend themselves.
37:03They are just sitting there
37:05and they are invertebrates
37:07like sponges.
37:09They don't have the shells
37:11that mollusks have
37:13and they don't have the spines
37:15that sea urchins have
37:17so they have to defend
37:19themselves chemically.
37:21This chemical defense system
37:23is proving to be a rich source
37:25of potential new medicines.
37:27Among the several hundred species
37:29so far discovered,
37:31there are no known diseases
37:33or tumors
37:35and the research
37:37is only just beginning.
37:39Marine animals
37:41have really been
37:43very, very little investigated
37:45as potential sources
37:47of pharmaceuticals.
37:49This area has really
37:51expanded tremendously
37:53in the past five to ten years
37:55and there are many
37:57chemists and biologists
37:59around the world
38:01who are looking
38:03for new drugs.
38:05We're really very excited
38:07about the prospects
38:09for marine natural products.
38:11We've only been looking
38:13for new drugs
38:15from the marine area
38:17in the last ten years
38:19so in that time
38:21we're really very pleased
38:23that out of our efforts
38:25that one drug is actually
38:27in clinical trials now,
38:28Didemnon B was the first
38:30cancer drug in the NCI program
38:32obtained from a marine organism.
38:34Didemnon destroys tumor cells
38:36by inhibiting protein synthesis.
38:38In laboratory tests,
38:40mice with leukemia
38:42that were given Didemnon B
38:44lived twice as long
38:46as those that were not treated.
38:48The drug is now
38:50in human toxicity trials.
38:52Didemnon B was first
38:54discovered in 1978.
38:56A complex series of steps
38:58were required to transform
39:00the natural chemical
39:02found in a marine animal
39:04to a refined substance
39:06that may someday save lives.
39:08The substances that we get
39:10from nature are very often
39:12not the optimal substance
39:14which is going to be
39:16the final drug.
39:18But what we are looking for
39:20is all these wild leaves,
39:22these unusual wonderful compounds
39:24that we would never
39:26dream up ourselves.
39:28And to take that compound
39:30and then either modify it synthetically
39:32or make related sorts of compounds
39:34by synthesis.
39:37Many promising drugs
39:39must first be chemically altered
39:41to reduce their toxic side effects.
39:43This long, expensive
39:45and painstaking process
39:47has been considered routine
39:49when working with substances
39:51from nature.
39:53But recent breakthroughs
39:55in computer technology
39:56speed up this work.
40:01The process is called
40:03molecular modeling.
40:05Using this powerful computer system,
40:07scientists can simulate
40:09the interaction of a natural drug
40:11with human biology.
40:13By studying how molecules
40:15fit together,
40:17the scientists have a front row view
40:19of organic chemistry
40:21that can never otherwise be seen,
40:23even with the most
40:25advanced technology.
40:27The researchers use
40:29electronic puppet strings
40:31to simulate chemical experiments
40:33and can quickly determine
40:35which parts of a natural substance
40:37might cause toxic reactions.
40:39Their ability to visualize
40:41these experiments
40:43represents a dramatic advance.
40:45The process was pioneered
40:47by Richard Feldman.
40:49On the one hand,
40:51it provides scientists
40:52with the tools they need
40:54and from this they can
40:56understand how the drugs
40:58relate to those things.
41:00But on the other hand,
41:02we can also do modeling
41:04by ourselves
41:06and then go to the scientists
41:08and say,
41:10look, this is interesting,
41:12this is important.
41:14Why don't you start thinking
41:16about these sorts of problems?
41:18Using this technique,
41:20the molecules can be
41:22synthesized into a drug.
41:24The resulting molecule
41:26becomes a template
41:28that the scientists can use
41:30to design a safe
41:32and effective drug.
41:34The combination of
41:36molecular modeling
41:38and new bioengineering
41:40techniques suggests
41:42a promising future
41:44for drugs from natural sources.
41:46But today,
41:48the major research thrust
41:50into natural medicines
41:52is the United States
41:54that have research programs
41:56designed to look for
41:58new drugs and plants.
42:00It's a mystery as to
42:02why this is true
42:04because in 1981,
42:06the American public
42:08paid $8 billion
42:10for prescriptions
42:12dispensed from
42:14community drug stores
42:16that have as their
42:18active ingredients
42:20drugs that are
42:21a lot of new drugs
42:23to come from plants
42:25with this small emphasis
42:27on the discovery aspect.
42:29One explanation for this
42:31might be found in the
42:33experiences of the
42:35pharmaceutical company
42:37Smith, Kline & French.
42:39During the mid-1950s,
42:41the company began
42:43an extensive plant
42:45screening program.
42:47Its director was
42:49Dr. Bryce Douglas.
42:51We realized,
42:53because we were aware
42:55of history,
42:57that so many of the
42:59then used drugs,
43:01this is some 20 years ago,
43:03the drugs then used
43:05had come from natural
43:07products and particularly
43:09from a class of
43:11substances called
43:13alkaloids.
43:15So we systematically
43:17started looking at
43:19plants from their
43:21alkaloids.
43:23Using the techniques
43:25available at the time,
43:27the SKF team mounted
43:29the most extensive
43:31plant medicine research
43:33program ever undertaken,
43:35collecting and screening
43:37over 30,000 plants
43:39from all over the world.
43:41The Smith, Kline & French
43:43program was a very
43:45systematic one in
43:47which as much science
43:49as was available on
43:51determining its pharmacology.
43:53What we found
43:55after looking at so many
43:57plants was that there
43:59was a uniformity of
44:01action in many of
44:03these alkaloids,
44:05unfortunately.
44:07In other words,
44:09there was not enough
44:11new activity in these
44:13results to justify
44:15continuing a large-scale
44:17survey of plant materials.
44:19The logistics of
44:21the research were
44:23very limited.
44:25There was something
44:27else happening at
44:29this time.
44:31The science of
44:33chemistry, the
44:35science of
44:36chromatography, the
44:38science of separation
44:40of natural materials
44:42always coming along.
44:44Advances in science
44:46always seem to
44:48happen in spurts.
44:49We used crystallographic
44:51analysis to obtain
44:53the chemical structure
44:55of a complex substance
44:57in a reasonably short time.
44:59That helped a great deal
45:01in fact to move natural
45:03products along,
45:05but it also helped
45:07to move us away
45:09from the natural
45:11products method of
45:13screening and collection
45:15because now you had
45:17a chemical structure
45:19or a very intensive
45:21effort to modify a
45:22structure to produce
45:23the medicine. So
45:24natural products are
45:25really always with us,
45:26but in the formal sense
45:27of collecting, the
45:28logistics became
45:29burdensome for
45:31SmithKline by about
45:331966.
45:35The program was
45:36formally ended, and
45:37SmithKline, like other
45:38pharmaceutical companies,
45:40began to direct its
45:41energies toward the
45:42chemical synthesis of
45:43new drugs.
45:45But now, 20 years
45:46later, the research
45:47emphasis may be
45:48shifting back again.
45:50I think we're seeing
45:51a change in attitudes,
45:52and we're going to see
45:53much more of this type
45:54of sponsorship in the
45:55future with modern
45:56technology and the
45:57ability to analyze
45:58plants in a much more
46:00rapid manner than we
46:01were in the past. I
46:02think this is the wave
46:03of the future.
46:04Pharmaceutical companies
46:05in Western Europe and
46:06in the third world in
46:07particular are very
46:08interested in plant
46:09medicines.
46:10It has been said
46:11that there is a
46:13preference by
46:14pharmaceutical companies
46:15for a purely synthetic
46:16approach to discovering
46:17new drugs over the
46:18natural products.
46:20In fact, these two
46:21worlds are not
46:22separate, and they
46:23link very much
46:24together. I think no
46:25matter how brilliant
46:26the chemists are,
46:28synthetic chemists,
46:30we're all dependent
46:32on the natural ideas.
46:35So I don't think it's
46:36one or the other.
46:38Each area takes its
46:40predominance based on
46:42the point of evolution
46:43of the sciences.
46:45Today, in fact, we're
46:46much more deeply back
46:47in natural products than
46:48we ever were with
46:49genetic engineering.
46:51Because now you can
46:52in fact obtain a useful
46:53result with a small
46:54amount of a natural
46:55material, and instead
46:56of heading back to the
46:57jungle to collect it
46:58in large amounts, you
46:59now head to the
47:01molecular biologist
47:02laboratory, and he
47:03will probably produce
47:04it in a yeast for you,
47:06an uncommon host for
47:07that kind of material.
47:08So in fact, we're
47:09back more deeply in
47:11natural products than
47:12ever, and all the
47:13pharmaceutical companies
47:14obviously are, many
47:15institutions are.
47:16The medicines of the
47:17future are likely to
47:18come from the chemical
47:19modifications to nature
47:21made possible by new
47:22bioengineering techniques.
47:24But the most important
47:25idea from nature, the
47:27plant gene itself, can't
47:28be synthesized.
47:31I have a real problem
47:32with the fact that most
47:34of the general public
47:35thinks that genetic
47:36engineering is going to
47:37save the world. They
47:38think that with genetic
47:39engineering, we can
47:41invent everything in the
47:42laboratory. Nothing
47:43could be further from
47:44the truth. What genetic
47:45engineering allows us
47:46to do is combine
47:48different genes in the
47:49laboratory. This will
47:51have great use in the
47:53future if we preserve
47:54many of these genes,
47:56which are in great
47:57danger in the tropical
47:58countries.
48:07The tropical rain
48:08forest, nature's great
48:10storehouse of plant
48:11material, is under
48:12threat.
48:15Each year, over 28
48:16million acres of rain
48:17forest, an area about
48:18the size of West
48:19Virginia, are destroyed
48:20in lumber and land
48:21development projects.
48:32In the Amazon basin
48:33alone, over 40 million
48:34acres of rainforest are
48:35destroyed every year.
48:37In the Amazon basin
48:38alone, over 40 million
48:39acres of rainforest are
48:40destroyed every year.
48:41In the Amazon basin
48:42alone, over 40 million
48:43acres of forest have
48:44been cleared. But the
48:45thin soils that underlie
48:46these Amazon forests can
48:47sustain crops or cattle
48:48for no more than eight
48:49years. Roughly half of
48:50this area is now
48:51abandoned, and the soil
48:52and plant life it once
48:53supported cannot
48:54recover.
49:04It's been estimated
49:05that about 10 percent of
49:06all plant species on the
49:07face of the earth will
49:08become extinct.
49:12Per year.
49:15For every plant,
49:16therefore, that goes
49:17extinct, you have to
49:18consider it also as a
49:20potential source of a
49:21new cure for something.
49:24And so it has terrible
49:25implications.
49:26If we don't increase
49:27our commitment to
49:28conservation, we're
49:29going to see the rate
49:30of species extinction
49:31increase rapidly.
49:33Species are going
49:34extinct. Each time one
49:35of these species goes
49:36extinct, we're losing
49:37something. In most
49:38cases, we know not
49:39what. Who knows if
49:40it's a cure for AIDS?
49:41Who knows if it's a
49:42cure for cancer? Who
49:43knows if it's a cure for
49:44other afflictions that
49:45will develop in the
49:46future? When we lose
49:47these things, they're
49:48lost forever.
49:51Awareness of what
49:52depletion of the world's
49:53biological diversity
49:54would mean has
49:55inspired some strategies
49:56for preservation.
50:04These exotic plants have
50:05survived from
50:06prehistoric origins in
50:07southern Africa.
50:11Today, like many
50:12plants in the Amazon,
50:13they are on the brink
50:14of extinction.
50:18But these species may
50:19still be saved.
50:25At the University of
50:26California's Arboretum,
50:28these plants and other
50:29rare and endangered
50:30species are protected.
50:33Under the direction of
50:34Dr. Harold Kupowicz,
50:36the Arboretum is a
50:37botanical ark and is
50:38may represent the last
50:39chance at survival for
50:40many plants.
50:44An authority on plant
50:45extinction, Dr. Kupowicz
50:46is committed to
50:47preserving endangered
50:48species, their seeds,
50:49and their pollen.
50:59According to Kupowicz,
51:00the loss of 10 percent
51:01of the world's plants,
51:02as many as 70,000
51:03species, would threaten
51:04the survival of the
51:05world.
51:08It could threaten a
51:09whole range of wildlife,
51:10from insects to songbirds,
51:12and be an unimaginable
51:13loss to modern medicine.
51:19We don't know what
51:21good genes there are
51:23in particular plants,
51:24and we can't foretell
51:26when we're going to
51:27need them.
51:28But if we don't do
51:29something to save as
51:30many as possible,
51:31we're potentially
51:32impoverishing ourselves
51:34and the future society
51:36as well.
51:38At the Arboretum,
51:39each species is viewed
51:40as a precious record
51:41of genetic information
51:43passed along in the
51:44seeds of the plant.
51:49For each plant here,
51:50a makeshift gene bank
51:52contains their genetic
51:53records.
51:55What I've done here
51:56is taken out two
51:57samples of seeds.
51:59Each tube has
52:01about 50 seeds in it,
52:03and they're sealed
52:04in a glass test tube.
52:05If a plant becomes
52:06extinct,
52:07as some here
52:08already have,
52:09these fragile records
52:10may well be
52:11all that remain.
52:14Once it's frozen,
52:15the seed can stay
52:17in a state of
52:18suspended animation
52:19literally for centuries.
52:21It can be retrieved
52:22in the future
52:23by anybody else
52:24who wants to see
52:25what that plant was like
52:26or to investigate
52:27any of its properties.
52:30The gene bank,
52:31although an important
52:32effort,
52:33cannot be used
52:34as a substitute
52:35for genetic diversity
52:36in the wild.
52:38These technological
52:39solutions,
52:40like cryogenic
52:41gene banks,
52:42should not be
52:43thought of
52:44as alternatives
52:45to conservation.
52:47We really do need
52:48to conserve
52:49the forest
52:50and the environment.
52:51But we should think
52:52of the gene banks
52:53as fail-safe devices
52:55so that we can
52:56retrieve
52:57plants from them
52:59if the plants
53:00we need
53:01are lost
53:02and do go
53:03extinct in the wild.
53:05Because of the
53:06realization that
53:07conservation is
53:08about protecting
53:09life on earth
53:10and protecting
53:11many of the
53:12plants and animals
53:13that we depend on,
53:14people are seeking
53:15new and innovative
53:16means of protecting
53:17biological diversity.
53:18For example,
53:19in a type of
53:20approach being
53:21pioneered by
53:22organizations
53:23like the
53:24World Wildlife Fund
53:25or Conservation
53:26International
53:27is the so-called
53:28debt trading approach.
53:29Buying up third
53:30world debt
53:31and allowing them
53:32to take
53:33new
53:34approaches
53:35in their own country.
53:36In just such
53:37a debt for nature
53:38program,
53:39Conservation
53:40International
53:41has recently
53:42bought up
53:43$650,000
53:44of Bolivia's
53:45massive foreign
53:46debt
53:47in exchange
53:48for setting aside
53:493.7 million acres
53:50of protected
53:51rainforest.
53:54Other economic
53:55incentives for
53:56conservation
53:57have also had
53:58some success.
53:59Carefully managed
54:00forest areas
54:01in Nepal
54:02currently account
54:03for over $1 million
54:04a year in medicinal
54:05plants and related
54:06product exports.
54:12But given
54:13current projections,
54:14it is unrealistic
54:15to expect that
54:16rainforest destruction
54:17will cease
54:18or that the
54:19plant kingdom
54:20can be entirely
54:21preserved.
54:27In a race to
54:28discover and
54:29understand what
54:30exists,
54:31scientists in the
54:32field continue
54:33their search for
54:34the hidden power
54:35of plants.
54:39In his office at
54:40Harvard,
54:41Dr. Richard Schultes
54:42pursues his lifelong
54:43quest for new
54:44medicines from
54:45among the thousands
54:46of specimens in
54:47his collection.
54:49And if there is
54:50a wonder drug
54:51in these dried
54:52leaves,
54:53we can only hope
54:54that the plant it
54:55came from can
54:56still be found.
54:58I think we have
54:59to understand how
55:00little we really know
55:01about creating
55:02certain chemicals.
55:03I think it would be
55:04arrogant of us to
55:05feel that we can do
55:06and invent and
55:07synthesize everything
55:08in the laboratory.
55:09And we have to
55:10remember that not
55:11only has Mother
55:12Nature synthesized
55:13many more chemicals
55:14than we have,
55:15Mother Nature
55:16synthesized us as well.
55:59© BF-WATCH TV 2021
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