From Nothing, to Thing, to Something

Almost 55 years have passed since the publication in Nature of Francis Crick and James Watson’s description of the structure of DNA. It was on February 28, 1953, that the two Cambridge colleagues actually pulled together the crystallographic and chemical data to form the original model of the double helix. They shared the 1962 Nobel Prize with King’s College physicist Maurice Wilkins for their innovative discovery.

Research crystallographer Rosalind Franklin, who had made the key reports and x-ray images from which Watson and Crick gleaned their data, died in 1958 and thus was not included in the Nobel Prize.

In retrospect, the discovery of the structure of the gene was a landmark event. But at the time, it was met with skepticism and doubt. The new era of biotechnology that sprang from that initial discovery could have followed the same track as the space program. Man’s first step on the moon was hailed as a fantastic moment in the history of technology and exploration in 1969, yet a coherent follow-up remains illusive and piecemeal.

As Watson reminisced at a 2005 Technology, Education, Design (TED) conference presentation, the next few years after their initial discovery remained scientifically lean. Most biologists did not immediately buy the “twisted ladder” as the reality of the gene. But Watson and Crick were confident that they had solved the most basic secret of life: how life begets life.

We knew we were right,” Watson says in his presentation, and adds that they went “from nothing to thing” in about two hours.

While they believed that the structure they proposed also solved the multiple riddles of replication, inheritance and evolutionary variability and mutability, Watson recalls that there were only five references to their work over the next few years. The run-up to today’s world of burgeoning gene-centric potentials was at first slow.

We were left by ourselves trying to do the last part of the trio,” Watson continues. That trio—the three-step process the cell uses to translate the DNA information into a molecule called RNA and then into working proteins that drive all biochemistry—is the focus of new research into disease and diagnosis.

This is particularly a focus of cancer research. Finding ways to block gene function, to literally interfere with the faulty protein-making process that seems to control cancer cells, would be an ideal way to attack these cells. Rather than blanketing the body with generic therapies such as radiation or toxic chemicals, RNA-based therapies would target the errant cells precisely.

According to a Cold Spring Harbor Laboratory press release concerning recent research published in Science, “These [RNA molecules] can target a specific gene and stop it from being expressed. If the cancerous cells die off, and the same short-hairpin RNA doesn’t kill off healthy cells, then the gene it targets is a cancer proliferation and survival gene.”

The work has led Gregory Hannon, Ph.D. CSHL professor, Howard Hughes Medical Institute investigator and his coauthors to propose a “Genetic Cancer Genome Project” in which geneticists will identify and catalogue cancer type-specific genes with the goal of revealing potential drug targets. The press release continues: “This could mean that the next generation of cancer treatments will include fewer side effects, and be tailored to target certain types of cancer, such as breast or colon cancer, specifically.

“‘This means that we can investigate thousands of genes at a time which will allow us to comb through the human genome with previously unattainable efficiency,’ said Dr. Hannon. ‘We have already identified several genes that appear to be selectively required by certain breast cancer cells but not by normal cells.’” The press release concludes that as this new technique is used to discover increasing numbers of cancer proliferation and survival genes associated with different kinds of cancer, it could introduce a new era in cancer treatment. “We have opened a door into a whole new world of cancer treatment possibilities,” Dr. Hannon said.

It is certainly something to imagine a world of personalized medicine where the very chemical core of our maladies could be repaired, patched or blocked. While it will certainly be quite some time before these possibilities ever reach the clinic, the process had to begin with understanding DNA. For that we can be thankful for the work and sacrifice of Rosalind Franklin and for those who used her work to lay the foundation of our genetic century.