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Friday, March 15, 2013

THE MEDICINE SOIL



Medicine

  • Soil is commonly used in antibiotics. Microbes created in the soil are harmful to bacteria, which is why soil is used in medicine. Medicines created by soil include skin ointments, tuberculosis drugs and anti-tumor drugs.





    While many people recognize the important duties that soil performs in our everyday lives—nourishing plants, filtering ground and surface water and providing a foundation for our homes and offices—most do not realize that soil has also served as an important source of commonly used antibiotics.
    Soil is indeed almost a perfect laboratory for the creation of natural medicines. Soil contains a wide array of tiny microhabitats that creates an enormous variation in the appearance and survival strategies of soil microbes. This diverse group of microbes, of which there are billions in an average teaspoon of soil, must then compete with one another for every available nourishing piece of organic matter. Through the lens of a microscope, scientists have observed this fracas and realized that the methods microbes use to subdue other microbes in the soil can be adapted to fight infections in the human body.
    The pioneering work behind the discovery of soil-derived antibiotics was performed by Dr. Selman Waksman. In fact, it was Dr. Waksman who coined the term antibiotic to describe the focus of his research. Dr. Waksman was a Russian immigrant who came to the United States in 1911 to study agriculture at Rutgers University. After receiving a Ph.D. in biochemistry from the University of California and becoming a naturalized citizen, he returned to Rutgers to become a lecturer of soil microbiology and a microbiologist at the New Jersey Agricultural Experiment Station. He later became a full professor and used his position to study an order of soil bacteria called the actinomycetes. Actinomycetes seemed to compete for food in the soil by secreting compounds that were harmful to rival bacteria, thus keeping them away. Dr. Waksman realized that if he could identify and isolate these compounds, he might be able to use them to combat human infections. 

    Indeed, starting with the discovery of actinomycin in 1940 until his retirement in 1958, Dr. Waksman and his students derived 22 different antibiotic compounds from actinomycetes. Three of the antibiotics — actinomycin, neomycin and streptomycin — became commonly used. 

    Actinomycin, the first antibiotic isolated by Dr. Waksman, is used sparingly as an anti-tumor drug (it is highly toxic) and frequently as an investigative tool for cell biologists. Neomycin is an extremely common antibiotic that is found in many skin ointments such as Neosporin®, as well as numerous treatments for eye and ear infections. Streptomycin was the first practical treatment for tuberculosis. 

    While working at Rutgers, Dr. Waksman was also hired as a consultant to the Merck pharmaceutical company. A share of the royalties from patents held by Merck on Waksman’s antibiotics and other medicines went back to Rutgers University and helped to establish a fellowship in the Department of Soils. Dr. Waksman convinced Merck to license out streptomycin to other manufacturers and used the profits to found the Institute of Microbiology at Rutgers, which was renamed the Waksman Institute of Microbiology after his death. As a result of his work and charity, Dr. Waksman was awarded the Nobel Prize in 1952. He is the only soil scientist ever to have received that honor. 

    Looking to the soil for antibiotics did not stop with Dr. Waksman’s retirement. Vancomycin, an antibiotic isolated in 1956 from a species of actinomycete found in Indian and Indonesian soils, is extremely powerful and the current last line of defense for the treatment of bacterial infections. However, as with all other antibiotics, strains of bacteria resistant to vancomycin recently have been discovered. This means that some bacteria are now impervious to all known treatments. This is a scary reality, but rest assured that scientists are already at work in the soil, trying to find the microbe that will provide the next miracle medicine.


    Erythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often prescribed for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including Mycoplasma and legionellosis. It was first marketed by Eli Lilly and Company, and it is today commonly known as EES (erythromycin ethylsuccinate, an ester prodrug that is commonly administered). It is also occasionally used as a prokinetic agent.

    In structure, this macrocyclic compound contains a 14-membered lactone ring with ten asymmetric centers and two sugars (L-cladinose and D-desosamine), making it a compound very difficult to produce via synthetic methods.

    Erythromycin is produced from a strain of the actinomycete Saccharopolyspora erythraea.


    Abelardo Aguilar, a Filipino scientist, sent some soil samples to his employer Eli Lilly in 1949. Eli Lilly’s research team, led by J. M. McGuire, managed to isolate erythromycin from the metabolic products of a strain of Streptomyces erythreus (designation changed to "Saccharopolyspora erythraea") found in the samples.

    Lilly filed for patent protection of the compound and U.S. patent 2,653,899 was granted in 1953. The product was launched commercially in 1952 under the brand name Ilosone (after the Philippine region of Iloilo where it was originally collected). Erythromycin was formerly also called Ilotycin.

    In 1981, Nobel laureate (1965 in chemistry) and professor of chemistry at Harvard University (Cambridge, MA) Robert B. Woodward (posthumously), along with a large number of members from his research group, reported the first stereocontrolled asymmetric chemical synthesis of erythromycin.

    The antibiotic clarithromycin was invented by scientists at the Japanese drug company Taisho Pharmaceutical in the 1970s as a result of their efforts to overcome the acid instability of erythromycin.
    Scientists at Chugai Pharmaceuticals discovered an erythromycin-derived motilin agonist called mitemcinal that is believed to have strong prokinetic properties (similar to erythromycin) but lacking antibiotic properties. At the present time, erythromycin is commonly used off-label for gastric motility indications such as gastroparesis. If mitemcinal can be shown to be an effective a prokinetic agent, it would represent a significant advance in the GI field as treatment with this drug would not carry the risk of unintentional selection for antibiotic-resistant bacteria.

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