From the archives: The discovery of DNA’s structure explained how life ‘knows’ what to do

To mark our 150th year, we’re revisiting the Popular Science stories (both hits and misses) that helped define scientific progress, understanding, and innovation—with an added hint of modern context. Explore the entire From the Archives series and check out all our anniversary coverage here.

When Popular Science editor Wallace Cloud covered the 1962 Nobel Prize honoring the discovery of DNA, James Watson, one of the winners, told Cloud that “the discovery was not the work of an institute full of technicians, but the product of four minds.” But the Nobel Foundation only awarded three scientists for the discovery of DNA’s structure: James Watson, Francis Crick, and Maurice Wilkins. 

Since 1869, scientists had known about DNA, but its structure remained elusive until 1953. Understanding its shape would help explain how the life-generating molecule worked. It was Rosalind Franklin, working with Maurice Wilkins at King’s College, who would capture the first X-ray images of the molecules Watson and Crick would later decode and describe in their Nobel-winning paper. Watson told Cloud in an interview for his May 1963 Popular Science story that Franklin “should have shared” the Nobel Prize. 

In DNA discovery lore, it was Photograph 51—taken in May 1952—that revealed so much about DNA’s helical structure. Four decades later, award-winning writer and biographer Brenda Maddox detailed Franklin’s astonishing contributions to DNA research in Rosalind Franklin: The Dark Lady of DNA. And American playwright, Anna Ziegler, wrote Photograph 51, a play first performed in London’s West End in 2015, to chronicle the gender-bias exposed by Franklin’s Nobel Prize case.

Of the 975 laureates selected since 1895, when Alfred Nobel—a Swedish chemist best known for making dynamite—willed most of his fortune to an annual prize in the fields of physics, chemistry, medicine, literature, and peace (economics was added in 1968), only 58 have been women. It doesn’t take a Nobel Prize to see that the stats don’t add up. In Franklin’s case, the Nobel Foundation says they no longer award prizes posthumously (Franklin died in 1958). It’s been nearly seven decades since DNA’s double helix was decoded, and six decades since the Nobel Foundation awarded three scientists for the work of four. The stats still don’t add up.

“DNA–It calls the signals for life” (Wallace Cloud, May 1963)

How three men got the Nobel Prize for solving a jigsaw puzzle: assembling the pieces of a molecule that made you what you are—and keeps you ticking

Last December an American biologist and two English physicists received formal recognition, in the shape of a Nobel Prize, for a discovery made 10 years ago—a discovery that started a chain reaction in biology.

They determined the structure of a molecule that provides answers to questions scientists have been asking for over a century:

• How does a heart muscle “know” how to beat?
• How does a brain cell “know” how to play its role in thinking and feeling?
• How do the cells of the body “know” how to grow, to reproduce, to heal wounds, to fight off disease?
• How do infectious bacteria “know” what diseases to cause?
• How do single fertilized egg cells, from which most of nature’s creatures begin, “know” how to become Plants, animals, people?
• If one such cell is to multiply and form a human being, how does it “know” how to produce a potential Einstein or a Marilyn Monroe?

The stuff that genes are made of

Sounds like a lot to expect of a molecule—even one with a jaw-breaking name like deoxyribonucleic acid (known more familiarly as DNA). But it’s scientific fact that DNA is what genes are made of. DNA molecules supply the basic instructions that direct the life processes of all living things (except a few viruses). The DNA molecule contains information in a chemical code—the code of life.

The effects of discovery of the structure of DNA have been called “a revolution far greater in its potential significance than the atomic or hydrogen bomb.” Professor Arne Tiselius, President of the Nobel Foundation, has said that it “will lead to methods of tampering with life, of creating new diseases, of controlling minds, of influencing heredity—even, perhaps, in certain desired directions.”

I asked the American member of the Nobel Prize trio, Dr. James D. Watson, about these speculations in his laboratory at Harvard. It was a few weeks before he flew to Stockholm to receive the award along with Dr. Francis H. C. Crick of Cambridge University and Dr. Maurice H. F. Wilkins of King’s College, London.

The boyish 34-year-old Nobelman, who did the prize-winning research in England when he was only 25 (he entered college at 15, had been a Quiz Kid before that, in the days of radio), refused to endorse the wilder predictions about the future of DNA research. He said, “The average scientist busy with research looks ahead anywhere from an hour to two years, not more.”

Conceding that discovery of the structure of DNA was as important as the working out of atomic structure that led to the atom bomb, he added, “It will have a very profound effect, slowly, on medicine. Doctors will stop doing silly things. Our knowledge of DNA won’t cure disease, but it gives you a new approach—tells you how to look at a disease.”

Dr. Watson went on to explain just what he and his co-workers discovered during those days of inspired brainwork in England, back in 1953, and how they did it.

The discovery was not the work of an institute full of technicians, he said, but the product of four minds: He and Crick did the theoretical work, interpreting cryptic X-ray diffraction photos made by Wilkins, who had as collaborator an English woman scientist, Dr. Rosalind Franklin. She died in 1958. She “should have shared” the Nobel Prize, said Dr. Watson.

Picking up the thread

DNA was not a newly discovered substance. It had been isolated in 1869, and by 1944 geneticists were sure it was the substance of the genes—the sites of hereditary information in the chromosomes. Then they started asking, “How does it work?” That’s the question Watson and his co-Nobelists answered.

They knew DNA as one of the most complex of the “giant molecules” known to man. It was believed to have a long, chainlike structure consisting of repeating groups of atoms, with side groups sticking out at regular intervals.

The shape of the DNA molecule was important. In the cell, many of the larger molecules work together like machine parts, and their mechanical properties are as important as their chemical activity. However, even the electron microscope, through which it is possible to see some of the biggest giant molecules, shows DNA only as a thread, without detail.

One way of “looking” at molecules is to take them apart by chemical treatments that make small molecules out of big ones. In the case of DNA, the pieces—six kinds of submolecular units—had been identified. Now it was necessary to figure out how the jigsaw puzzle fitted together.

Another way is to use X rays, but in a special manner. A technique called X-ray diffraction lets physicists take a peculiar kind of look inside certain kinds of molecules—those that form crystals.

DNA extracted from cells and purified is a jelly-like material. Not much resemblance to a crystal, you might think. But when ifs pulled like taffy and dried under the right tension, it forms fibers that do have a complicated crystalline structure.

One of the Nobel Prize Winners, Dr. Wilkins, is a physicist who worked in this country on the Manhattan Project. After World War H, back in England, he got interested in biological problems and became a biophysicist. During the early 19505 he perfected a method of making X-ray diffraction photos of DNA fibers.

Such photos are taken by shooting a very narrow beam of X rays through the sample. Some of the X rays are bent by interaction with atoms. The emerging X-ray waves interfere with each other to form a pattern that registers on the film.

X-ray diffraction photos do not show the outlines of the molecules they represent. They are in “reciprocal space”-small distances on a photograph stand for large spaces in the molecule, and vice versa. The pictures must be interpreted by mathematical analysis; and the more complex the molecule, the more difficult that is.

Drs. Crick and Watson began to work on methods of interpreting the X-ray diffraction photos of DNA. They met at Cambridge, where Watson had gone to do research a couple of years after getting a Ph. D. from Indiana University.

Working backwards

Crick had worked out a theory for predicting what X-ray pictures of various molecular models would look like. That is, the pictures were so hard to interpret they had to work backwards: devise a model, then determine mathematically what its X-ray diffraction equivalent should be. Then the prediction was compared with actual distances and angles on the X-ray photos.

The two experimenters shared with Wilkins the idea that a twisted, helical molecular structure might fit the X-ray data (it had been discovered that such twists exist in other molecules produced by the cell). They built a model of rods, clamps, and sheet-metal cutouts (representing the various known pieces of the jigsaw puzzle), and evaluated it mathematically.

This first model didn’t prove out, and they temporarily dropped the problem, going on to other research. Some months later, in February, 1953, they learned of a structure proposed for DNA by Linus Pauling, Caltech’s Nobel-Prize-winning chemist. From their previous work, they knew that Pauling had to be wrong. This stimulated them to try another model, incorporating new information about the exact shapes of some of the subunits of DNA.

A month later they had a model that fitted the X-ray data closely. From it, they worked out the profound “Watson-Crick hypothesis,” which explains how the DNA molecule does its work in the cell. That hypothesis has been tested through ingenious experiments in numerous laboratories, and is accepted as gospel in the new world of molecular biology.

The key to life

The DNA molecule stands revealed as a double helix shaped roughly like a twisted ladder. 

The two legs of the ladder are identical, but the rungs are not, and this is the key to the molecule’s ability to store information. The order of the four different subunits that make up the rungs is the code of life.

The way the subunits link across the rungs is the key to DNA’s ability to transmit information. Each rung actually consists of two units, but the pairing of the units follows definite rules; the molecule can “unzip,” and each half serves as a template for rebuilding the missing half, producing two new molecules identical to the original one.

The Watson-Crick hypothesis has made possible a new view of the “molecular basis of life”: In the cell—really a miniature chemical factory-—DNA molecules contain the instructions that tell the molecular machinery of the factory what new molecules to build. The product molecules in turn determine the function of the cell whether it’s a blood cell, a nerve cell, a sperm cell, or (if not part of a many-celled organism) perhaps a harmful bacterium.

In this way, the information stored in DNA molecules specifies an entire community of cells, such as those that add up to a human being—the color of his hair and eyes, his basic aptitudes, his built-in sensitivity or resistance to disease.

Programing a man

An individual DNA molecule is about 10,000 subunits long (that is, there are that many rungs on the ladder), and the list of instructions necessary to specify a human being is about 10 billion DNA units long. If the DNA molecules containing that message were placed end to end, they would make a strand 10 feet long, but only one twelve-millionth of an inch thick. Actually the strands are bundled in the microscopic bodies called chromosomes, in the nucleus of each cell, which hold the machinery of heredity.

The specifications must be passed on from generation to generation. This takes place during the cell division, when the chromosomes divide. Preparatory to cell division, the DNA molecules in the chromosomes have unzipped and have been copied by the machinery of the cell.

Work in the cell, controlled by DNA, is important not only to healthy life, but also to disease. Viruses, for example, take over cells and turn them into virus factories by interfering with the normal flow of instructions and substituting new instructions. Hereditary diseases are the result of “errors” that have crept into the coded instructions during copying of DNA molecules. Such changes also transform normal cells into cancer cells, which have “forgotten” their usual roles and “learned” new functions.

Those facts explain why DNA has created such excitement among biologists. If a way can be found to send man-made chemical messages into cells and alter the instructions stored there by DNA molecules, almost anything is possible.

But that isn’t likely to come about this year or next. First the code must be deciphered. That’s where most of the research on DNA is concentrated today.

Another unsolved problem, perhaps even more mysterious, is how cells “decide” to use particular instructions stored in their DNA archives. Discoveries on this frontier will explain how cells respond to outside stimuli—-and how a single fertilized cell can multiply selectively to produce the many different kinds of specialized cells that make up a human being.

Some text has been edited to match contemporary standards and style.