Medical Miracles

Early medicines were the product of a fortuitous discovery of a plant or microbial extract and hit-or-miss testing of similar compounds to find the most effective version. Insight into how these drugs worked was limited. Today, we come full circle to focus anew on natural substances. Using the tools of modern chemistry, scientists map their structure, mimic their functions, and tailor drugs to individual needs — making medical miracles everyday events.

First antibiotic discovered in a dish
Penicillin, the first effective antibiotic, was discovered in 1928 almost by accident. Alexander Fleming, a professor of bacteriology at St. Mary's Hospital in London, was growing colonies of bacteria in petri dishes when he noticed that the area surrounding a gray-green mold was clear. Further testing revealed that the mold, Penicillium, killed most varieties of bacteria.
At first, the mold was a laboratory curiosity, its potential as an antibiotic all but ignored. Then, in 1939, a team of Oxford University researchers led by Howard Florey purified and produced the large amounts needed to test and confirm the mold's therapeutic potential. Research conducted by the U.S. Department of Agriculture laid the foundation for large-scale production by American pharmaceutical companies during World War II. By the mid-1940s, penicillin was widely used to treat infectious diseases ranging from pneumonia to rheumatic fever. (Read more)

Born in Alabama in 1899, Julian was barred from the local public school's college preparatory program because of his race. Nonetheless, he excelled academically and gained admittance to DePauw University in Indiana. As he departed for college, his grandfather, a former slave, waved goodbye with a three-fingered hand — the missing fingers had been severed as punishment for learning to read.

After earning his doctorate at the University of Vienna in Austria, Julian returned to DePauw. In 1935, he synthesized physostigmine, a natural substance used to reduce pressure in the eyeball caused by glaucoma, which can lead to blindness. The feat cut the cost of the drug from hundreds of dollars per drop to a few cents per gram, making treatment widely available and earning Julian worldwide acclaim.

When DePauw declined to appoint him to its faculty, Julian left academia and joined the Glidden Company. There, he used his knowledge of chemistry to make a variety of products from soybeans, including the hormone progesterone and fire-fighting foams used during World War II. In 1948, he developed a new way to synthesize hydrocortisone, still used to treat rheumatoid arthritis. (Read more)

Synthetic hormone research leads to birth control
Music, poetry, and romance aside, sex is basically a matter of chemistry — a complicated matter as Pennsylvania State University professor Russell Marker found out in 1938 when he set out to synthesize progesterone, a hormone critical to female reproduction.

Working with a steroid from the sarsaparilla plant, Marker deciphered and duplicated the hormone's chemical structure. After an exhaustive search, he located an economical source for manufacturing large amounts of the hormone: a plant growing in a remote area of Mexico.

Marker left Penn State to form Syntex, the first Mexican company to mass produce low-cost progesterone, then left Syntex to start another company, Botanica-mex. Soon, more than half the sex hormones sold in the United States were produced in Mexico. In 1951, Syntex introduced the first birth control pill, widely credited with starting the sexual revolution of the 1960s. (Read more).

Ulcer treatment breaks new ground in drug development
Cimetidine, better known as Tagamet®, opened a new chapter in drug development. Introduced in 1976 as a treatment for stomach ulcers — then a potentially life-threatening condition — cimetidine was the product of a logical and methodical search.

Researchers at SmithKline Beecham Pharmaceuticals identified the molecule that triggers the release of gastric acid when it binds to a receptor in the lining of the stomach. They reasoned that ulcers could be treated with a molecule that combined with the same receptor, but blocked rather than stimulated the release of gastric acid — much as a defensive player in a football game intercepts a pass.

After a decade-long search, the researchers achieved their goal with cimetidine. It represented a new class of drugs and a new approach to developing them. (Read more).

Natural products research leads to development of life-saving anticancer drugs

Thousands of lives have been saved by new chemotherapy drugs derived from natural products. Two of these natural products, camptothecin and Taxol®, were first isolated by Monroe Wall and Mansukh Wani at the Research Triangle Institute in North Carolina.

In the 1960s and 1970s, Wall and Wani led a team of scientists exploring the anticancer properties of natural products. Their first success came when they showed that an extract from a Chinese tree, Camptotheca acuminata, was active against a type of leukemia. A little later, Wall and Wani discovered that extracts from the bark of the Pacific yew, Taxus brevifolia, killed some cancer cells.

The successful introduction of the active compounds, camptothecin and Taxol®, as chemotherapy drugs came many years after the work of Wall and Wani. The delay was due in part to solubility problems, which meant that there was no way to deliver the substances intravenously. In addition, the supply of Taxol® was limited since the compound comes from the bark of a tree that is not prevalent and which grows slowly. The later discovery of a semi-synthetic version of Taxol® solved the supply problem.

Eventually Taxol® and analogs of camptothecin were approved for the treatment of ovarian, breast, lung and colon cancers and Kaposi's sarcoma. (Read more).

Carl and Gerty Cori and Carbohydrate Metabolism

Carl and Gerty Cori explored how the human body metabolizes glucose. In what beame known as the "Cori cyle," the Coris described the interplay between glucose and glycogen, the storage form of glucose. The Coris also elucidated the mechanisms behind glycogen breakdown in animal cells and the enzymatic basis of glucose metabolism. Building on their seminal research, other scientists developed new techniques to control diabetes. Their path-breaking research resulted in their winning the Nobel Prize in Physiology or Medicine in 1947 "for their discovery of the course of the catalytic conversion of glycogen." (Read more).

Selman Waksman and Antibiotics

Selman Waksman and his students at Rutgers University developed a series of antibiotics from actinomycetes, a group of soil microbes similar to bacteria. The Waksman team isolated about twenty antibiotics, the most prominent of which was streptomycin, the first effective pharmaceutical treatment for tuberculosis. Unlike the chance discovery of penicillin, streptomycin was isolated in 1943 by Albert Schatz using screening protocols developed by Waksman. Also unlike penicillin, which attacked only certain types of pathogenic bacteria, streptomycin was effective against a broad spectrum of bacteria. Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952. (Read more).