Episode 1: The Secret of Life
The discovery of the double helix structure of DNA is to science what the Mona Lisa is to painting. It's been called the single biggest discovery of all time. But it wasn't just stumbled upon - it was a race. Specifically, it was a race between two teams of young scientists working in Britain, as well as the esteemed chemist Linus Pauling, based in California. Already a Nobel laureate, Pauling may have been the favorite, but the discovery would ultimately be made by his British counterparts. Rosalind Franklin and Maurice Wilkins were trying to identify the structure by studying X-ray diffractions of the DNA molecule. But Jim Watson and Francis Crick studied a little bit of everything -- including, to the consternation of some, the work of their competitors. A few have gone so far as to accuse Watson of stealing Franklin's X-ray work. In any case, Waston and Crick's inquisitive working style ultimately allowed them to determine the DNA structure first, in 1953 -- an achievement that led to their Nobel Prize in 1962. Meanwhile, Franklin passed away in 1958 from cancer.
Produced/directed by David Glover and edited by Joe Bini.
DNA: The Ugly Duckling of Genetics, by Magdalena Eriksson
We probably don't have a gene for curiosity, but our inquisitive nature still seems encoded in the combined messages of our genes. The progress of man and our intellectual history -- from painting on cave walls to travels in space -- are all spurred by our irresistible desire to understand the unknown. And for many of today's researchers, the great scientific frontier involves the mining of the codes of genomes.
When James Watson and Francis Crick took up the quest of determining the three-dimensional structure of DNA in the early 1950s, they sat down as uninvited guests at a set table. The two, at the time junior, scientists did not hesitate to grasp for data already obtained by other scientists -- sometimes even picking from their plates. Studying Rosalind Franklin's x-ray crystallography of the DNA molecule without her knowledge, for instance, was a vital step toward their discovery. What Watson and Crick brought to the table was primarily their strong conviction that the DNA structure would be of great importance. And so they succeeded in connecting pieces, old and new, from friend and from foe, and in 1953 delivered the structure of a double helix DNA molecule.
Watson and Crick's accomplishment was in some measure built on the work of their contemporary DNA researchers, but it was also a coalescence of years of work in a number of scientific fields. In 1926, the theoretical physicist Erwin Schrödinger had introduced an equation that describes the behavior of matter, which in practice only works for only very small systems, an isolated atom or molecule at a time. In the 1940s, Schrödinger's interests had expanded to include biology. He proclaimed that living and non-living matter all obey the same laws of physics and chemistry, and proposed that living organisms should be treated in terms of molecular and atomic structure. In 1944, he challenged the biological-science community by postulating the existence of a similar description, a "hereditary code-script," in his book WHAT IS LIFE.
Long before anyone attempted to describe life in terms of chemistry and physics, biology was developing from the observation of animals and plants in nature. The work of two early pioneers had made the existence of a hereditary code-script logical.
In 1859, Charles Darwin had proposed his principles of evolution and in 1865 Gregor Mendel had discovered the basic laws of heredity, but neither of them addressed what actually directed the systems they studied. The actual carrier of the rules of evolution and heredity, which must be contained somewhere, in animals as well as in plants, were never found by these early pioneers.
By 1869, an important clue leading to the location of these carriers was in the making, as the Swiss scientist Friedrich Miescher isolated what he termed "nuclein" while working at a local hospital in Tübingen, Germany. There, he found the mysterious substance in pus-soaked bandages, rich in white blood cells. Miescher learned that the only source for nuclein was chromosomes, which he realized was a significant discovery. Hence he supported the "chemical heredity theory," which contends that our basic biological information is passed from generation to generation and is stored in chemical substances in our cells.
Meischer made his discovery at a time when medicine was undergoing a revolution. Theories about the four humors -- a balance among four supposedly elemental fluids, including blood, yellow bile, phlegm, and black bile -- were under scrutiny. For thousands of years, the medical field had relied upon the practice of bloodletting, the intentional bleeding of patients, to restore a balance of the humors. Bloodletting was gradually losing popularity among physicians. Still, few scientists were prepared to subscribe to the hereditary importance of nuclein.
Thomas Hunt Morgan, a Kentucky-born biologist active at Columbia University in the early 20th century, picked up where others left off. He localized genes to specific locations on chromosomes. Morgan also concluded that gene s were the hereditary unit Mendel had described, and the key element in Darwinian evolution.
Morgan's specific mapping of genes onto chromosomes made biology accessible for experiments. Many new questions could be addressed. The basic structure and chemical properties of genes were still unknown, and their function was far from understood. How do genes function and duplicate? What is the basis of genetic disease and the role of mutations? But perhaps the most thrilling problems were: how do genes contain and forward hereditary information, and how do they direct the development of entire organisms?
Another clue came from Great Britain, where Fred Griffith at the Ministry of Health studied different strains of pneumococci, the bacteria that can cause pneumonia. One strain, the S-form, has a capsule. To Griffith, it looked smooth under the microscope, whereas the R-form doesn't have a capsule and therefore appeared rough. The S-form was virulent and killed infected mice, while the R-form had no serious effect. Griffith concluded that the immune system failed to break through the cell wall of the smooth bacterium, but destroyed the rough one and rendered it harmless.
Griffith experimented with mixtures of the two forms, and injected mice with heat-killed S, and normal R bacteria. He expected the mixture to be harmless since the dangerous S-form bacteria had been killed. But the mice died, and Griffith found living S bacteria in their dead bodies. He concluded that something had been transferred between the two types of bacteria -- a genetic change had occurred in the R-form.
Like Miescher's work, Griffith's discovery drew little attention from his contemporaries. He didn't realize the full implications of his result and failed to convince his colleagues of its importance before he died in a London bomb raid in 1941. Fifteen years later, however, Griffith's pneumococcus experiment was repeated at Rockefeller Institute for Medical Research in New York City by Oswald Avery, who for years had focused his research on bacteria from pneumonia patients.
Avery and his colleagues, Colin MacLeod and Maclyn McCarty, went about their quest for the transforming principle in a systematic manner. They showed that proteases, enzymes that degrade proteins, had no effect on the heat-treated S pneumococci. Only when the bacteria were treated with the enzyme DNase, which degrades DNA, could the S-form no longer induce its virulence on the R-form. They had made it clear that DNA is the transforming principle.
Yet even this discovery was received with skepticism. To many, DNA seemed too simple for the task of holding such vast amounts of biological information. Proteins, with their 20 different amino acids, had for so long been favored as the most likely carrier of genetic information. And for years there was a looming suspicion that the DNA that Avery had claimed as the transforming principle had been contaminated by proteins that might have carried the genetic information. It wasn't until 1952, when another team independently showed that DNA, safely separated from proteins, brought genes into bacteria, that the last skeptics were persuaded. DNA won general acceptance as the carrier of genes and the race for the structure was on. The rocket into modern biology was launched.