Meleney (1889-1963)in 1943;the cephalosporins,by Sardinian medical researcher Giuseppe Brotzu (1895-1976)in 1945:chloramphenicol,the fi rst broad-range antibiotic,by the research team of John Ehrlich,Paul Burkholder and David Gotlieb in 1947:chlortetracycline,by the American plant physiologist Benjamin Minge Duggar(1872-1956)in 1947;and neomycin by Waksman and his colleague Hubert Lechevalier in 1949. Today,scientists have a good understanding of the molecular mechanisms antibiotic compounds use to impair or kill these diseasecausing bacteria.In many instances,for example,an antibiotic molecule will bond with one of the enzymes responsible for the synthesis of a bacterial cell membrane.Openings develop in the cell membrane,water enters,and the cell bursts and dies.More than 150 different antibiotics are now available for treating a host of infectious diseases that had once been considered incurable,diseases such as plague,pneumonia,tuberculosis,typhus,typhoid fever scarlet fever,staphylococcus infections,gonorrhea,meningitis,pertussis(whooping cough),and urinary tract infections.These antibiotics exist because researchers came to understand how certain microorganisms live and grow. Marine Organisms as a Source of Drugs People have long used marine organisms as the source of a limited number of synthetic products used in everyday life.Perhaps the most famous of these organisms has been the mollusk Murex brandaris,from which a beautiful purple dye can be extracted.The dye is obtained from a small organ of the mollusk(the hypobranchial gland).and its preparation is so expensive that it was traditionally used as a dye only for clothing worn by the nobility.For that reason,the dye was called royal purple or, more commonly.Tyrian purple,after the region from which it is obtained. Traditionally,there has been almost no research into the use of marine organisms as a source of drugs.Beginning in the 1960s,however,that situation changed and
Meleney (1889–1963) in 1943; the cephalosporins, by Sardinian medical researcher Giuseppe Brotzu (1895–1976) in 1945; chloramphenicol, the fi rst broad–range antibiotic, by the research team of John Ehrlich, Paul Burkholder and David Gotlieb, in 1947; chlortetracycline, by the American plant physiologist Benjamin Minge Duggar (1872–1956) in 1947; and neomycin by Waksman and his colleague Hubert Lechevalier in 1949. Today, scientists have a good understanding of the molecular mechanisms antibiotic compounds use to impair or kill these diseasecausing bacteria. In many instances, for example, an antibiotic molecule will bond with one of the enzymes responsible for the synthesis of a bacterial cell membrane. Openings develop in the cell membrane, water enters, and the cell bursts and dies. More than 150 different antibiotics are now available for treating a host of infectious diseases that had once been considered incurable, diseases such as plague, pneumonia, tuberculosis, typhus, typhoid fever, scarlet fever, staphylococcus infections, gonorrhea, meningitis, pertussis (whooping cough), and urinary tract infections. These antibiotics exist because researchers came to understand how certain microorganisms live and grow. Marine Organisms as a Source of Drugs People have long used marine organisms as the source of a limited number of synthetic products used in everyday life. Perhaps the most famous of these organisms has been the mollusk Murex brandaris, from which a beautiful purple dye can be extracted. The dye is obtained from a small organ of the mollusk (the hypobranchial gland), and its preparation is so expensive that it was traditionally used as a dye only for clothing worn by the nobility. For that reason, the dye was called royal purple or, more commonly, Tyrian purple, after the region from which it is obtained. Traditionally, there has been almost no research into the use of marine organisms as a source of drugs. Beginning in the 1960s, however, that situation changed and
people began to seek out and identify marine organisms that could be used as the source of natural-productbased drugs.One problem that has hindered research in this area is the diffi culty of collecting and identifying marine organisms and of determining both the chemical products that can be extracted from them and the biological effects of those compounds.The 1990s saw a rapid growth of interest in this fi eld of research,however,with almost half as many patents for marine products being granted 1999 as had been granted in the preceding25 years At this point,only a handful of products derived from marine organisms have been approved by the FDA for sale to consumers.The majority of these products have been approved for nondrug use.For example,researchers at the University of California have extracted an anti-infl ammatory agent,which they named pseudopterosin,from a Caribbean sea whip called Pseudopterogorgia elisabethae. Pseudopterosin is currently used as an additive to a cosmetic skin cream called Resilience produced by Estee Lauder.Because the compound has undergone study only relatively recently,it is possible pseudopterosin will have important therapeutic applications,and researchers are exploring this possibility.For example,the compound is also being studied for possible use in the treatment of various infl ammatory disorders,such as rheumatoid arthritis,osteoarthritis,rheumatic carditis bronchial asthma,myasthenia gravis,and psoriasis.It is also being considered for use with insect bites and as additional treatment during organ and tissue transplants. The diagram above shows how a large number of similar compounds can be produced by making changes in a basic molecule.In this diagram,R1,R2,and R3 represent three positions in the basic pseudopterosin molecule where atoms or groups of atoms can be added.If a hydrogen atom is used as a substituent at all three positions,the compound formed is called pseudopterosin A.If an acetate group is used at position RI and hydrogen atoms at R2 and R3,the compound is pseudopterosin B,and so on.Each compound in this family has generally similar characteristics but differs from its cousins'efficacy,chemical and physical properties. safety,and other properties. Another commercially available product containing naturally occurring marine
people began to seek out and identify marine organisms that could be used as the source of natural-productbased drugs. One problem that has hindered research in this area is the diffi culty of collecting and identifying marine organisms and of determining both the chemical products that can be extracted from them and the biological effects of those compounds. The 1990s saw a rapid growth of interest in this fi eld of research, however, with almost half as many patents for marine products being granted from 1996 to 1999 as had been granted in the preceding 25 years. At this point, only a handful of products derived from marine organisms have been approved by the FDA for sale to consumers. The majority of these products have been approved for nondrug use. For example, researchers at the University of California have extracted an anti-infl ammatory agent, which they named pseudopterosin, from a Caribbean sea whip called Pseudopterogorgia elisabethae. Pseudopterosin is currently used as an additive to a cosmetic skin cream called Resilience® produced by Estée Lauder. Because the compound has undergone study only relatively recently, it is possible pseudopterosin will have important therapeutic applications, and researchers are exploring this possibility. For example, the compound is also being studied for possible use in the treatment of various infl ammatory disorders, such as rheumatoid arthritis, osteoarthritis, rheumatic carditis, bronchial asthma, myasthenia gravis, and psoriasis. It is also being considered for use with insect bites and as additional treatment during organ and tissue transplants. The diagram above shows how a large number of similar compounds can be produced by making changes in a basic molecule. In this diagram, R1, R2, and R3 represent three positions in the basic pseudopterosin molecule where atoms or groups of atoms can be added. If a hydrogen atom is used as a substituent at all three positions, the compound formed is called pseudopterosin A. If an acetate group is used at position R1 and hydrogen atoms at R2 and R3, the compound is pseudopterosin B, and so on. Each compound in this family has generally similar characteristics but differs from its cousins’ efficacy, chemical and physical properties, safety, and other properties. Another commercially available product containing naturally occurring marine
products is Formulaid produced by Martek Biosciences as a nutritional supplement for infant formulas.Formulaid contains two fatty acids,arachidonic acid(ARA)and docosahexaenoic acid(DHA),extracted from a variety of marine microalgae.ARA and DHA are the most abundant polyunsaturated fatty acids found in breast milk,and they are the most important fatty acids used in the development of brain gray matter. They are especially desirable for use in infant formulas because they come from nonmeat sources and can be advertised as vegetarian additives to the product An especially intriguing pair of products obtained from marine organisms in recent years are Vent and Deep Vent DNA polymerase.These products are used in DNA research studies.Their special feature is that they are at least 10 times as effi cient as other similar products in polymerase chain reactions because they can tolerate temperatures just below the boiling point of water,a characteristic that comparable research tools lack.Vent and Deep Vent DNA polymerases are obtained from the bacterium Thermococcus litoralis,which is found around deep-sea hydrothermal vents at the bottom of the ocean. A number of other products obtained from marine organisms are used in research also.Among the best known of these is green fluorescent protein(GFP),a compound that fl uoresces(gives off light when exposed to radiation)bright green when exposed to blue or ultraviolet light.When GFP is attached to a compound being studied in an experiment,the compound's movement can be followed visually because of the very noticeable green light produced by the GFP.Green fl uorescent protein is obtained from a bioluminescent jellyfish,Aequora victoria.Some scientists who study marine organisms believe that they may be at the threshold of an exciting new era in which extracts from such organisms can provide a host of new therapeutic drugs for use against some of the most intransigent diseases known to humans,including cancer and malaria.Two of the most promising of these products were discovered in the early 1950s by W.Bergmann,R.J.Feeney,and D.C.Burke.The products were modifi ed forms of familiar nitrogen bases(aromatic carbon compounds that contain nitrogen)given the names of spongothymidine and spongouridine that demonstrated strong antitumor and antiviral properties.A synthetic analog of these natural products
products is Formulaid®, produced by Martek Biosciences as a nutritional supplement for infant formulas. Formulaid® contains two fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), extracted from a variety of marine microalgae. ARA and DHA are the most abundant polyunsaturated fatty acids found in breast milk, and they are the most important fatty acids used in the development of brain gray matter. They are especially desirable for use in infant formulas because they come from nonmeat sources and can be advertised as vegetarian additives to the product. An especially intriguing pair of products obtained from marine organisms in recent years are Vent® and Deep Vent® DNA polymerase. These products are used in DNA research studies. Their special feature is that they are at least 10 times as effi cient as other similar products in polymerase chain reactions because they can tolerate temperatures just below the boiling point of water, a characteristic that comparable research tools lack. Vent® and Deep Vent® DNA polymerases are obtained from the bacterium Thermococcus litoralis, which is found around deep-sea hydrothermal vents at the bottom of the ocean. A number of other products obtained from marine organisms are used in research also. Among the best known of these is green fluorescent protein (GFP), a compound that fl uoresces (gives off light when exposed to radiation) bright green when exposed to blue or ultraviolet light. When GFP is attached to a compound being studied in an experiment, the compound’s movement can be followed visually because of the very noticeable green light produced by the GFP. Green fl uorescent protein is obtained from a bioluminescent jellyfish, Aequora victoria. Some scientists who study marine organisms believe that they may be at the threshold of an exciting new era in which extracts from such organisms can provide a host of new therapeutic drugs for use against some of the most intransigent diseases known to humans, including cancer and malaria. Two of the most promising of these products were discovered in the early 1950s by W. Bergmann, R. J. Feeney, and D. C. Burke. The products were modifi ed forms of familiar nitrogen bases (aromatic carbon compounds that contain nitrogen) given the names of spongothymidine and spongouridine that demonstrated strong antitumor and antiviral properties. A synthetic analog of these natural products
arabinosyl cytosine,is now available commercially from the Pharmacia&Upjohn Company under the brand name of Cytosar-U.As of this writing.it is the only marine-derived anticancer agent available for clinical use A number of other marine-derived products are waiting in the wings,however. Among the many compounds that have shown promise and are undergoing further testing for anticancer properties are halichondrin B.isolated from four marine sponge genera,Halichondria.Axinella.Phakellia.and Lissodendoryx:halomon,from the red alga Portieria hornemannii:dolastatin 10,from the sea slug (sea hare)Dolabella auricularia;and ecteinascidin 743,from the Caribbean sea squirt Ecteinashidia rbinata.One of the compounds furthest along in development is bryostatin-1. derived from the marine bryozoan Bugula neritina.In 2001,the FDA granted "orphan drug"status to bryostatin-1,reserving marketing rights for the product to the German-based fi rm GPC Biotech AG.The compound has showed great promise for the treatment of esophageal cancer,especially when used in conjunction with another anticancer agent,Taxo It also appears to have potential value in the treatment of melanoma,ovarian cancer,and non-Hodgkin's lymphoma. Drug researchers now hold high hopes for the promise of marine organisms as the source of new drugs.More than 80 percent of all life-forms on Earth exist only in the oceans.so a vast supply of organisms is available for study.Some authorities have stated that the chances of finding new drugs in marine organisms may be 300 to 400 times that of finding drugs in terrestrial organisms Plant Products as the Source of New Drugs Despite all the contributions that microorganisms have made to the development of new drugs and all the promise held by marine organisms for such purposes,many researchers still count primarily on plants as the most likely source for the discovery of new drugs.In some areas,that hope has already been realized.In 2002,authorities estimated that anywhere between one third and one-half of the best-selling prescription drugs used around the world were derived from natural products In recent years,however,some of the greatest emphasis has been placed on the
arabinosyl cytosine, is now available commercially from the Pharmacia & Upjohn Company under the brand name of Cytosar-U®. As of this writing, it is the only marine-derived anticancer agent available for clinical use. A number of other marine-derived products are waiting in the wings, however. Among the many compounds that have shown promise and are undergoing further testing for anticancer properties are halichondrin B, isolated from four marine sponge genera, Halichondria, Axinella, Phakellia, and Lissodendoryx; halomon, from the red alga Portieria hornemannii; dolastatin 10, from the sea slug (sea hare) Dolabella auricularia; and ecteinascidin 743, from the Caribbean sea squirt Ecteinashidia turbinata. One of the compounds furthest along in development is bryostatin-1, derived from the marine bryozoan Bugula neritina. In 2001, the FDA granted “orphan drug” status to bryostatin-1, reserving marketing rights for the product to the German-based fi rm GPC Biotech AG. The compound has showed great promise for the treatment of esophageal cancer, especially when used in conjunction with another anticancer agent, Taxol®. It also appears to have potential value in the treatment of melanoma, ovarian cancer, and non-Hodgkin’s lymphoma. Drug researchers now hold high hopes for the promise of marine organisms as the source of new drugs. More than 80 percent of all life-forms on Earth exist only in the oceans, so a vast supply of organisms is available for study. Some authorities have stated that the chances of finding new drugs in marine organisms may be 300 to 400 times that of finding drugs in terrestrial organisms. Plant Products as the Source of New Drugs Despite all the contributions that microorganisms have made to the development of new drugs and all the promise held by marine organisms for such purposes, many researchers still count primarily on plants as the most likely source for the discovery of new drugs. In some areas, that hope has already been realized. In 2002, authorities estimated that anywhere between one third and one-half of the best-selling prescription drugs used around the world were derived from natural products. In recent years, however, some of the greatest emphasis has been placed on the
search for anticancer and antiviral agents derived from natural products.Success in that area has not been as great as that achieved in other fi elds.Since 1960,only seven plant-derived drugs have been approved by the FDA for use as anticancer agents Four of those drugs,vinblastine,vincristine,etoposide,and teniposide.were discovered in the 1950s.The last three-Taxol,topotecan,and irinotecan-were discovered and approved much more recently.The discovery of vinblastine and vincristine is one of the most intriguing examples of serendipity in scientificresearch in recent years.In 1952,the Canadian medical researcher Robert Laing Noble (1910-90)received a package from his brother,Dr.Clark Noble,containing 25 leaves from the Madagascar periwinkle plant,Vinca rosea.Clark had received the leaves from one of his patients in Jamaica,who said that natives on the island often used the plant to control their diabetes when insulin was not available.Clark,who was retired, suggested that his brother study the plant for possible use as a drug for the treatment of diabetes When Robert Noble carried out his studies on the periwinkle leaves,he found that they had no effect on blood sugar levels.However,they did appear to significantly reduce a subject's white blood cell count.Perhaps,Dr.Noble reasoned,the product could be used to treat diseases characterized by abnormally high white blood cell counts,such as leukemia.He was successful in isolating two chemicals from the periwinkle leaves,which he named vinblastine and vincristine,that markedly decreased white blood cell counts in patients with certain forms of cancer.The two chemicals were the first anticancer agents derived from natural sources to be approved for use with human patients. Perhaps the most exciting story about an anticancer agent derived from a natural product is that of Taxol.That story begins in 1958.when the National Cancer Institute began a program to screen natural products for substances that might have anticancer activity.The plan was to examine more than 35,000 species in the research. Five years later,scientists at the Research Triangle Institute in North Carolina Monroe Wall and M.C.Wani,found that the bark of the Pacific yew tree (Tax brevifolia)demonstrated tumor-suppressing qualities.In 1971,those same scientists
search for anticancer and antiviral agents derived from natural products. Success in that area has not been as great as that achieved in other fi elds. Since 1960, only seven plant-derived drugs have been approved by the FDA for use as anticancer agents. Four of those drugs, vinblastine, vincristine, etoposide, and teniposide, were discovered in the 1950s. The last three—Taxol®, topotecan, and irinotecan—were discovered and approved much more recently. The discovery of vinblastine and vincristine is one of the most intriguing examples of serendipity in scientifi c research in recent years. In 1952, the Canadian medical researcher Robert Laing Noble (1910–90) received a package from his brother, Dr. Clark Noble, containing 25 leaves from the Madagascar periwinkle plant, Vinca rosea. Clark had received the leaves from one of his patients in Jamaica, who said that natives on the island often used the plant to control their diabetes when insulin was not available. Clark, who was retired, suggested that his brother study the plant for possible use as a drug for the treatment of diabetes. When Robert Noble carried out his studies on the periwinkle leaves, he found that they had no effect on blood sugar levels. However, they did appear to significantly reduce a subject’s white blood cell count. Perhaps, Dr. Noble reasoned, the product could be used to treat diseases characterized by abnormally high white blood cell counts, such as leukemia. He was successful in isolating two chemicals from the periwinkle leaves, which he named vinblastine and vincristine, that markedly decreased white blood cell counts in patients with certain forms of cancer. The two chemicals were the first anticancer agents derived from natural sources to be approved for use with human patients. Perhaps the most exciting story about an anticancer agent derived from a natural product is that of Taxol®. That story begins in 1958, when the National Cancer Institute began a program to screen natural products for substances that might have anticancer activity. The plan was to examine more than 35,000 species in the research. Five years later, scientists at the Research Triangle Institute in North Carolina, Monroe Wall and M. C. Wani, found that the bark of the Pacifi c yew tree (Taxux brevifolia) demonstrated tumor-suppressing qualities. In 1971, those same scientists