Fifty years ago this week, two brash young scientists in an obscure lab at the University of Cambridge in England unraveled the structure of DNA.
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Double helix unlocked key to life
By Steve Sternberg, USA TODAY
Fifty years ago this week, two brash young scientists in an obscure lab at the University of Cambridge in England unraveled the structure of DNA, the elegant living thread that is the genetic basis of inheritance and evolution.
The discovery of the double helix by James Watson, 25, and Francis Crick, 36, on Feb. 28, 1953, unveiled what Crick called "the secret of life."
DNA is the molecule that makes and maintains all life. It enables life to re-create itself. It contains the blueprints and the toolbox for understanding how humans work. Even now, researchers are exploiting these tools to turn medicine from an uncertain science in which they treat the symptoms of disease to one in which they attempt to find out and fix precisely what is wrong.
"What we're learning is totally redefining medicine as I learned it," says Donald Lindberg, director of the National Library of Medicine.
How much DNA does it take to make, operate and maintain a human? The human body has 10 trillion cells. Each one contains a strand of DNA that, uncoiled, is 2 yards long. If you were to place each of the 10 trillion strands end to end, they would span the solar system. "It's absolutely remarkable that humans get made," says Rick Young, a geneticist at MIT's Whitehead Institute.
Understanding DNA paved the way to gene therapy, DNA fingerprinting, a cloned sheep named Dolly, stem-cell research, genetically engineered crops, research into human origins and evolution and DNA-based medicines.
Understanding DNA also enabled scientists to decode the entire human genome, the genetic blueprint that distinguishes a man from a mouse. That milestone is scheduled to be announced in April, two years after President Clinton feted two groups of rival scientists — one funded by a consortium of governments, the other by Celera, a private company — who jointly announced in 2001 the completion of a rough draft.
If all goes as planned, researchers will announce the completion of the Human Genome Project on April 14, 11 days shy of the 50th anniversary of the publication of the DNA double helix in the British journal Nature, which noted that DNA "has novel features which are of considerable biologic interest."
For proof, Watson and Crick constructed a metal model of the now-famous double helix, showing its graceful intertwined spirals and the chemicals that hold them together. Tall as a man and jury-rigged from the precisely engineered lab equivalent of Tinker Toys, the model gracefully answers so many questions about how life re-creates itself that even rivals pronounced it beautiful.
"It was the most important scientific paper of the century," says Francis Collins, who replaced Watson as director of the National Human Genome Research Institute, which launched the $3 billion Human Genome Project.
Outside a narrow circle of geneticists, few took note of the historic discovery. No major newspaper or magazine in 1953 gave much space to the finding. Coverage would lag until 1962, when Nobel prizes were awarded to Watson, Crick and Maurice Wilkins, who refined a technique for X-raying DNA. Even then, the eminent scientist who presented the awards told reporters that the work had "no immediate practical application."
It would take half a century and a flurry of follow-up discoveries to lay the cornerstones of a new foundation for the practice of medicine.
As far as the science has come, it still has far to go. Scientists who have sequenced the human genome say 95% remains a scientific black hole. Only a handful of DNA-based medicines are on the market, and others are still in the early stages of research.
Fifty years after Watson and Crick, the work is just beginning.
"It has taken a long time for the pot to boil," says Anthony White, CEO of Applied Biosystems, the parent company that sponsored Celera's $100 million effort to sequence the human genome. "It's starting now."
Spellbinding story
On a Saturday morning recently in the village of Cold Spring Harbor on Long Island, N.Y., an aging but still brash James Watson began the first of three lectures he was to give that day on the race to solve the structure of DNA.
No longer a gangly youngster with a vertical nest of hair, Watson, 75, is balding, his hair and eyebrows wild as ever. Now director of the famed Cold Spring Harbor Laboratory, Watson is still untamed, the shock jock of world-class science who is known for sometimes outrageous assertions. But he has a spellbinding story to tell.
"I wanted to know where life came from," Watson says. "Francis and I were real soul mates, united in wanting to explain life by means of molecules."
The story is famous worldwide, partly through Watson's book about the discovery, The Double Helix, which was published in 1968 by Athenaeum after it was rejected as too controversial by Harvard University Press. A new book, DNA: Secret of Life, is due in the spring.
Michael Gilman, senior vice president of research at Biogen in Cambridge, Mass., one of the world's first biotech companies, worked under Watson at Cold Spring Harbor. In 1953, he notes, relatively few people were working seriously on DNA.
Now, from the window in his corner office, Gilman can point at half a dozen genetic research centers within walking distance of his office: MIT's Whitehead Institute, Whitehead's Human Genome Sequencing Center, the rival biotech firms Genzyme and Amgen. Harvard is almost next door.
The National Institutes of Health sponsors $1.5 billion in research in the area annually. The San Francisco Bay Area, the Washington, D.C., metro area, Atlanta and Research Triangle Park, N.C., also have biotech centers, as do Canada, England, Japan and China.
The biotech revolution stemmed from another set of discoveries in the '70s. Researchers found they could accurately snip out genes and slip them into the DNA of another organism so that it would make proteins Mother Nature never intended to make.
Untold applications await
Next to Gilman's office is a brick building housing five 2,000-liter tanks. Inside the tanks are billions of Chinese hamster ovary cells, reprogrammed to make therapeutic human proteins on an industrial scale. In Research Triangle Park, Biogen has six 15,000-liter tanks.
Biotechnology means that insulin no longer must be extracted from pigs or growth hormone from human cadavers, which were sometimes tainted with prions, the proteins that cause the dementia-causing disease Creutzfeldt-Jacob syndrome. Clotting factors used to treat hemophilia are no longer drawn from human plasma, and they no longer transmit HIV.
In the world of genetics, biotechnology is old news. What's new is the amount of data being mined from the human genome — and the computing revolution enables scientists to analyze it, figuring out the functions of crucial genes and their links to human illness. "It's beyond even the brightest scientist's ability to assimilate all this new information," MIT's Young says.
Gene sequencing has gone industrial. GenBank, the genome project's repository of genetic sequences, now has 30 billion units of genetic code. The total is doubling every 14 months.
"Who's responsible for this explosion of information?" asks Eric Lander, head of the Whitehead Institute's Human Genome Sequencing Center. "The DNA molecule itself, because it packs so much information that it unleashed all the forces of science, economics and competition" among researchers and drug firms seeking to mine DNA for scientific breakthroughs.
The genetic and computer revolutions have merged in even a more concrete way: the DNA microarray, a marriage of DNA with the silicon chip. Invented by a research team at Stanford University and brought to market by companies such as Affymetrix, DNA chips now may contain half a million synthetic pieces of DNA, adding up to 10,000 genes.
Using DNA chips, researchers can study which genes are turned on and which are turned off in normal and abnormal cells. Studying these patterns of gene expression, scientists can figure out where a tumor cell has gone wrong. Someday, doctors hope to use that information to diagnose illnesses before symptoms appear and treat them on a molecular level.
Even Watson marvels at how the double helix has changed the world. "We didn't envision any consequence," he says, "except knowledge." |
