Historic breakthroughs are rare in science, particularly in biology. Knowledge grows by bits and pieces, accretions and deletions. Often, the work of hundreds of scientists must come together before it is obvious that substantive progress has been achieved.
But on April 25, 1953, American biochemist James D. Watson and British biophysicist Francis H.C. Crick, working at Cambridge University, published a paper in Nature that is considered a masterpiece of understatement. They began: "We wish to suggest a structure for the salt of deoxyribose nucleic acid (DNA). The structure has novel features which are of biological interest."
That publication was a true watershed in biology, forevermore changing the face of research on genetic inheritance. Although 20 more years would pass before scientists had acquired all the tools necessary to work effectively with DNA, it set the stage for a massive change in the practice of medicine and the art of agriculture.
Gene therapy, genetically engineered drugs, monoclonal antibodies, transgenic animals and genetically modified foods are among the results.
Given today's impressive accomplishments, it is difficult to imagine how little we actually knew before Watson and Crick's breakthrough.
Historically, scientists and farmers had the idea that traits were passed down from parent to offspring, a knowledge that was used in domesticating corn, wheat, dogs and a host of other plants and animals by selective breeding. How this happened, however, was a complete mystery.
The first insight came from an obscure 19th century Austrian monk named Gregor Johann Mendel, who performed precisely designed, carefully controlled breeding experiments with peas. He concluded that every trait of the plants--and by extension, all living things--was controlled by two "factors," one inherited from each parent, and demonstrated how these factors interacted with each other. The factors later came to be known as genes.
Shortly after the beginning of this century, it became clear that genes resided in DNA. Over the next 40 years, biologists learned that DNA contained only four principle chemicals, called bases: adenine, thymine, cytosine and guanine. They also knew that the amounts of adenine and thymine were identical, as were the amounts of cytosine and guanine. Not an impressive amount of information to explain how such complex genetic traits as vision or thinking ability could be passed along.
Watson and Crick changed that. Using X-ray images taken by Maurice H.F. Wilkins, they concluded that DNA formed the now famous double-stranded double helix. The key feature was that the two strands were mirror images, with adenine always pairing with thymine and cytosine pairing with guanine. This allowed genetic information to be retained when the new strands separated during replication.
The pair published a second paper in Nature on May 30 pointing out another key feature of their model. "Any sequence of the pairs of bases can fit into the structure. . . . It therefore seems likely that the precise sequence of the bases is the code which carries the genetical information."
Their achievement won them the 1962 Nobel Prize for physiology or medicine.
Biologists now routinely put genes into bacteria to make proteins for medical uses. They insert genes into viruses to use for gene therapy in humans. They add genes to plants to introduce desirable new characteristics, such as the ability to resist pesticides used on weeds in fields or the production of amino acids needed in the human diet. They add genes to animal embryos or subtract them to produce animal models of human disease, to make food animals that are leaner and more healthy for human consumption, or even to make animal tissues more like those of humans so that they can be safely transplanted.
Meanwhile, the quest for understanding DNA continues. Researchers throughout the country are now racing to sequence the entire 3 billion bases that make up the complete human genetic blueprint and have found a broad variety of genes that represent tempting targets for new therapies in treating diseases ranging from cancer to mental illness.
Progress, however, always brings fears. Europeans, for example, have recently been up in arms about the supposed dangers of genetically modified foods. Animal rights proponents object to any genetic engineering experiments in animals. Less extreme opponents fear that the use of transgenic animals for human transplants may introduce dangerous new viruses into the human population. Gene therapy opponents decry the possibility of modifying humans to give them desired traits such as increased intelligence or athletic abilities.