The case for serendipity

Gary Kuhlmann
Published: January, 2009

Progress in biomedical science owes much to serendipity. Basic research, or the simple curiosity about how things work, has led to many of the discoveries that have transformed health, medicine, and our understanding of human disease. Here is Lens magazine’s list of the “top 10” discoveries in biomedical science in the 20th century.

Genetics, 1910.

Experimenting with the common fruit fly, Drosophila melanogaster, Columbia University embryologist Thomas Hunt Morgan demonstrates that genes are the mechanical basis of heredity, thereby launching the modern science of genetics.

Morgan reportedly tells colleagues about experiments that lead to unexpected results: “They (the flies) will fool you every time.” His first attempts to find tractable mutations fail, but Morgan perseveres and discovers the white-eyed fly, which leads to his discovery of sex-linked inheritance.

Cholesterol, 1913.

A Russian finding -- that cholesterol is the main dietary culprit in atherosclerosis -- languishes for decades until researchers at the University of California, Berkeley, establish in a landmark 1950 paper the role of lipoproteins in the disease.

A 3-year-old boy before, and several weeks after receiving insulin in 1922.
Photos courtesy of Eli Lilly and Company Archives.
In the early 1970s, Michael Brown and Joseph Goldstein at the University of Texas Southwestern Medical School in Dallas discover cholesterol receptors and the mechanism by which blood cholesterol is regulated. After a National Institutes of Health study establishes that lowering cholesterol lowers the risk of heart attack, the stage is set for the introduction of the first cholesterol-lowering statin drugs in 1987.

Insulin, 1921.  

When Canadian surgeon Frederick Banting gives up his struggling practice, he goes into the research laboratory to follow a nagging hunch about a cure for diabetes. In 1921, he and his assistant Charles Best reverse diabetes in a dog by injecting a concoction of pancreatic extracts.

John J.R. McLeod and James Collip at the University of Toronto help them purify the extract, and in 1922, insulin saves the life of 14-year-old Leonard Thompson. Within a year, the manufactured protein becomes available worldwide.

Penicillium mold in a Petri dish.
Image provided by Visuals Unlimited.
Penicillin, 1928.

Scottish bacteriologist Alexander Fleming accidentally grows a culture of penicillin in a dirty Petri dish. At the outbreak of World War II, scientists at Oxford University, working with scant wartime resources, show penicillin can clear a range of infections without the toxic effects of sulfa drugs.

To keep the precious culture out of the hands of Nazis, it’s smuggled into the United States, and the mold thrives in the corn steep liquor (the syrupy byproduct of corn starch production) in a federal fermentation research lab in Peoria, Ill. By 1943, penicillin makes it to the battlefields, where it saves the lives of thousands of wounded Allied soldiers.

Double helix, 1953.

The discovery of the double helix, the twisted-ladder structure of deoxyribonucleic acid (DNA), by American James Watson and his British colleague Francis Crick gives rise to modern molecular biology.

Watson and Crick come to their pursuit with complimentary backgrounds in physics and X-ray crystallography (Crick) and viral and bacterial genetics (Watson), but they act on the advice of Caltech chemist Jerry Donahue – and the first X-ray pictures of DNA taken by British chemist Rosalind Franklin -- to arrive at a correct DNA model.

In short order, their discovery yields groundbreaking insights into the genetic code and protein synthesis, and a few decades later, helps produce new and powerful scientific techniques, specifically recombinant DNA research, genetic engineering, rapid gene sequencing, and monoclonal antibodies.

Psychotropic drugs, 1950s

An observation by French naval surgeon Henri Laborit that the antihistamine promethazine promotes “euphoric quietude” in patients being treated for shock leads to development of one of the first psychotropic drugs, chlorpromazine. By the early 1950s, the drug, marketed in the United States under the trade name Thorazine, has become a mainstay in the treatment of schizophrenia.

Jonas Salk, M.D., inoculates a child against polio in 1954.
Courtesy of the March of Dimes Foundation
About the same time, two doctors in Staten Island, N.Y., Irving Selikoff and Edward Robitzek, observe that new anti-tuberculosis drugs appear to lift patients’ moods. One of the drugs, iproniazid, is found to block the enzyme monamine oxidase, thereby increasing brain levels of neurotransmitters, and is championed by flamboyant New York psychiatrist Nathan Kline for the treatment of depression.

Thus begins what has been called the “pharmacologic revolution of psychiatry.”

Polio vaccine, 1954.

U.S. physician Jonas Salk defies conventional wisdom to develop the vaccine that helps eradicate polio. Contrary to the widely held view at the time that immunity develops only after the body survives infection by live virus, Salk observes that the body can acquire immunity through contact with inactivated (killed) virus.

Salk tests injections of inactivated polio virus on himself and his family. Within two years of its widespread introduction in 1954, Salk’s vaccine nearly eliminates polio in the United States, but a live oral vaccine developed by another American physician, Albert Sabin, later becomes the preferred alternative.

Reverse transcriptase, 1970.

Working independently, David Baltimore of MIT and Howard Temin of the University of Wisconsin-Madison discover an enzyme used by certain tumor viruses to “transform” the cells they infect into cancer cells.

The enzyme, called reverse transcriptase, allows these viruses to convert their RNA into DNA copies that can slip into – and alter -- the cell’s genetic instructions. This finding leads, in 1984, to the discovery of the human immunodeficiency virus (HIV).

In recognition of their discovery, Baltimore and Temin share the 1975 Nobel Prize in medicine with Renato Dulbecco.

Gene splicing and sequencing, 1970.

John Hopkins University microbiologist Hamilton Smith sparks a revolution in genetic research when he discovers the first restriction enzyme that cuts DNA. After this comes a flurry of follow-up discoveries: the first recombinant DNA molecule in 1972; DNA cloning in 1973; rapid DNA sequencing in 1977; DNA copying in 1983; and the first automated gene sequencing machine in 1986.

Neurons derived from human embryonic stem cells project from a neurosphere in this confocal microscopy image taken by Sharona Even-Ram, Ph.D., of Hadassah University Hospital’s Goldyne Savad Institute of Gene Therapy in Jerusalem.
Understanding DNA has paved the way to gene therapy, DNA fingerprinting, a cloned sheep named Dolly, genetically engineered crops, and efforts to sequence the human genome -- a feat accomplished in 2000 by Celera Genomics and the federally funded Human Genome Project.

Embryonic stem cells, 1981.

Researchers in Britain and the United States, working independently, isolate cell lines from mouse blastocysts that are pluripotent. These so-called embryonic stem cells can be grown into all types of cells in tissue culture.

In 1988, James Thomson and coworkers at the University of Wisconsin-Madison extract the first human embryonic stem cell line -- and in 2007, the same team, simultaneously with an independent team in Japan, reports that they have successfully restored pluripotency in human connective tissues cells.

The newly induced pluripotent stem (iPS) cells, as they’re dubbed, reproduce steadily, meaning scientists should be able to produce an unlimited supply, and with the same chameleon-like characteristics as embryonic stem cells. The discovery gives new hope to medical scientists who have been investigating how stem cells might help treat age-related diseases such as Parkinson’s and Alzheimer’s, as well as stroke and diabetes.

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