double helix

Double Helix

by James D. Watson and Gunther S. Stent  · 1 Jan 1968  · 134pp  · 43,617 words

By James D. Watson THE DOUBLE HELIX 1968 THE MOLECULAR BIOLOGY OF THE GENE 1965 (Second Edition, 1970; Third Edition, 1976) SCRIBNER 1230 Avenue of the Americas New York, NY 10020 www.

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United States of America 7 9 10 8 6 The Library of Congress has cataloged the Atheneum edition as follows: Watson, James D. 1928- The double helix. 1. Deoxyribonucleic acid. I. Title. [DNLM: 1. DNA. 2. Biochemistry—History. QU58W339d 1968a] QD435.W37 1980 574.87′3282 80-13990 ISBN 0-684-85279

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. L. B. Sir Lawrence Bragg (b. 1890) was the director of the Cavendish Laboratory of Cambridge University at the time of the discovery of the Double Helix. He and his father, William Henry, the originators of X-ray crystallography, received the Nobel Prize in 1915. Preface HERE I relate my version of

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the structure was established. Nonetheless, I feel the story should be told, partly because many of my scientific friends have expressed curiosity about how the double helix was found, and to them an incomplete version is better than none. But even more important, I believe, there remains general ignorance about how science

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of ambition and the sense of fair play. The thought that I should write this book has been with me almost from the moment the double helix was found. Thus my memory of many of the significant events is much more complete than that of most other episodes in my life. I

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deduced the molecular structure of deoxyribonucleic acid, DNA. That structure, they reported in a short article in Nature just weeks later, was the beguilingly beautiful “double helix.” Noting that the helix could “unzip” and copy itself, Crick and Watson confirmed what had hitherto only been suspected: that DNA was the substance that

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. Watson tells how they pulled it off in this now-classic memoir. First published in 1968 and in print for more than three decades, The Double Helix remains unique in the annals of science writing. The discovery it describes was of a magnitude comparable, in terms of scientific and social significance, to

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is also a wonderfully readable human drama that lets nonscientists share some of the intellectual excitement, high emotion, and incredible suspense. Small wonder that The Double Helix became the inspiration for the whole genre of science best-sellers. Its enduring freshness owes much to Watson’s decision to write it from the

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the time of the book’s initial publication, of Watson’s candid and sometimes barbed sketches of scientists at work. Yes, the theme of The Double Helix is the unbridled lust for fame. (“It was certainly better to imagine myself becoming famous than maturing into a stifled academic who never risked a

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x-ray photographs of DNA and tragically died of cancer at thirty-seven in 1958 before reaping the rewards her critical experimental work deserved. The Double Helix is also an affectionate paean to a rare friendship, and, perhaps more surprisingly, a joyous celebration of the importance of being playful while pursuing a

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at the movies, or a bottle of burgundy, anything at all to avoid “narrow-mindedness and dullness.” Neither is dullness something that readers of The Double Helix run the slightest risk of encountering. Sylvia Nasar holds the Knight Chair in Journalism at Columbia University and is the author of A Beautiful Mind

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the Italim Alps, August 1952 Early ideas on the DNA-RNA-protein relation X-ray diffraction photograph of DNA, B form Original model of the double helix Watson and Crick in front of the model Photograph A. C. Barrington Brown Morning coffee in the Cavendish photograph A. C. Barrington Brown Letter to

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-with-like base pairs Base pairs for the like-with-like structure Tautomeric forms of guanine and thymine Base pairs for the double helix Schematic illustration of the double helix DNA replication THE DOUBLE HELIX IN THE summer of 1955, I arranged to join some friends who were going into the Alps. Alfred Tissieres, then a

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him whether this time he had any objection to my new base pairs. The adenine-thymine and guanine-cytosine base pairs used to construct the double helix (hydrogen bonds are dotted). The formation of a third hydrogen bond between guanine and cytosine was considered, but rejected because a crystallographic study of guanine

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with cytosine. Chargaff’s rules then suddenly stood out as a consequence of a double-helical structure for DNA. Even more exciting, this type of double helix suggested a replication scheme much more satisfactory than my briefly considered like-with-like pairing. Always pairing adenine with thymine and guanine with cytosine meant

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. It seemed almost unbelievable that the DNA structure was solved, that the answer was incredibly exciting, and that our names would be associated with the double helix as Pauling’s was with the alpha helix. When the Eagle opened at six, I went over with Francis to talk about what must be

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the possibility that he might stumble upon the base pairs before we told him the answer. That night, however, we could not firmly establish the double helix. Until the metal bases were on hand, any model building would be too sloppy to be convincing. I went back to Pop’s to tell

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nucleotide. Because of the helical symmetry, the locations of the atoms in one nucleotide would automatically generate the other positions. A schematic illustration of the double helix. The two sugar-phosphate backbones twist about on the outside with the flat hydrogen-bonded base pairs forming the core. Seen this way, the structure

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DNA. But with the sugar-phosphate backbone on the outside, it did not matter which salt was present. Either would fit perfectly well into the double helix. Bragg had his first look late that morning. For several days he had been home with the flu and was in bed when he heard

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tension now off, I went to play tennis with Bertrand, telling Francis that later in the afternoon I would write Luria and Delbrück about the double helix. It was also arranged that John Kendrew would call up Maurice to say that he should come out to see what Francis and I had

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he was now about to go full steam ahead on DNA and intended to place emphasis on model building. The original demonstration model of the double helix (the scale gives distances in Angstroms). 28 MAURICE needed but a minute’s look at the model to like it. He had been forewarned by

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sort of X-ray diagram the structure should produce, then becoming strangely noiseless when he perceived that Maurice’s wish was to look at the double helix, not to receive a lecture in crystallographic theory which he could work out by himself. There was no questioning of the decision to put guanine

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in London only two days before he rang up to say that both he and Rosy found that their X-ray data strongly supported the double helix. They were quickly writing up their results and wanted to publish simultaneously with our announcement of the base pairs. Nature was the place for rapid

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her sharp, stubborn mind, caught in her self-made antihelical trap, might dig up irrelevant results that would foster uncertainty about the correctness of the double helix. Nonetheless, like almost everyone else, she saw the appeal of the base pairs and accepted the fact that the structure was too pretty not to

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saw no reason to argue about. At the same time, her fierce annoyance with Francis and me collapsed. Initially we were hesitant to discuss the double helix with her, fearing the testiness of our previous encounters. But Francis noticed her changed attitude when he was in London to talk with Maurice about

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structure I had written Delbrück about. Reading his letter, I drew a deep breath, for I realized that Delbrück did not know of the complementary double helix at the time of Linus’ talk. Instead, he was referring to the like-with-like idea. Fortunately, by the time my letter reached Cal Tech

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to postpone a visit which now had the bonus of letting me be the first to tell Ephrussi’s and Lwoff’s labs about the double helix. Francis, however, was not happy, telling me that a week was far too long to abandon work of such extreme significance. A call for seriousness

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for information on what his scientific clowns were up to. Watson and Crick in front of the DNA model. 29 PAULING first heard about the double helix from Delbrück. At the bottom of the letter that broke the news of the complementary chains, I had asked that he not tell Linus. I

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phages contained a modified type of cytosine called 5-hydroxy-methyl cytosine. Most important, its amount equaled the amount of guanine. This beautifully supported the double helix, since 5-hydroxy-methyl cytosine should hydrogen-bond like cytosine. Also pleasing was the great accuracy of the data, which illustrated better than any previous

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and on Wednesday, April 2,went off to the editors of Nature. Morning coffee in the Cavendish just after publication of the manuscript on the double helix. Linus arrived in Cambridge on Friday night. On his way to Brussels for the Solvay meeting, he stopped off both to see Peter and to

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. Maurice Wilkins’ work remained centered on DNA for some years until he and his collaborators established beyond any doubt that the essential features of the double helix were correct. After then making an important contribution to the structure of ribonucleic acid, he has changed the direction of his research to the organization

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working on a high level until a few weeks before her death. On the six following pages: The letter written to Delbrück telling of the double helix. In Stockholm for their Nobel Prizes, December 1962: Maurice Wilkins, John Steinbeck, John Kendrew, Max Perutz, Francis Crick, and James D. Watson. JAMES D. WATSON

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of proteins. In 1962, together with Francis Crick and Maurice Wilkins, Dr. Watson was awarded the Nobel Prize for Medicine and Physiology. Prior to The Double Helix, he wrote The Molecular Biology of the Gene, which is now in a third edition. * For a clear description of X-ray diffraction technique, see

Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life

by J. Craig Venter  · 16 Oct 2013  · 285pp  · 78,180 words

continue to publish books for every reader. LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA Venter, J. Craig. Life at the speed of light : from the double helix to the dawn of digital life / J. Craig Venter. pages cm Includes bibliographical references and index. ISBN 978-1-101-63802-6 1. Science—Social

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code-script, which ultimately led them to DNA and to discover the most beautiful structure in all biology, the double helix, within whose turns lay the secrets of all inheritance. Each strand of the double helix is complementary to the other, and they therefore run in opposite (anti-parallel) directions. As a result the

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double helix can unzip down the middle, and each side can serve as a pattern or template for the other, so that the DNA’s information can

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allow of thirty different specifications.”23 Even though von Neumann conceived his self-replicating automaton some years before the actual hereditary code in the DNA double helix was discovered, he did lay stress on its ability to evolve. He told the audience at his Hixon lecture that each instruction that the machine

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crystal data obtained by Rosalind Franklin and Raymond Gosling at King’s College London. Watson and Crick described the elegantly functional molecular structure of the double helix, and how DNA is reproduced so its instructions can be passed down the generations. This is nature’s self-reproducing automaton. The onset of efforts

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May 1952, revealed a black cross of reflections and would prove the key to unlocking the molecular structure of DNA, revealing it to be a double helix, where the letters of the DNA code corresponded to the rungs.9 On April 25, 1953, Watson and Crick’s article “Molecular Structure of Nucleic

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Hochschule (ETH), in Zürich, where he was a professor until he moved to Freiburg, in 1926. It was only in 1953 (the year of the double-helix discovery) that Staudinger was eventually awarded the Nobel Prize for his important contribution. In recent years we have come to regard that basic unit of

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Overall, protein synthesis is extremely fast, requiring only seconds to make chains of one hundred or so amino acids. As was the case with the double helix, X-ray crystallography was needed to reveal the ribosome’s detailed structure. First, however, someone had to make the ribosomes crystallize—like salt in a

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reveal how the ribosome enforces the pairing of the first two letters of RNA code: molecules flip out to “feel” for a groove in the double helix of well-matched RNAs to ensure that the code is read with high fidelity. A “wobble” makes this mechanism less stringent in checking the third

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importance. According to the central dogma, RNA functioned as a mere middleman, carrying out the commands encoded in DNA. In that model the DNA’s double helix unwinds, and its genetic code is copied onto a single-stranded mRNA. In turn, the mRNA shuttles the code from the genome to ribosomes. It

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small enough to be jostled by the constant pounding of the surrounding sea of atoms and molecules. So while DNA is indeed shaped like a double helix, it is a writhing, twisting, spinning helix as a result of the forces of random Brownian motion. The protein robots of living cells are only

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in its DNA as its software. All the information needed to make a living, self-replicating cell is locked up within the spirals of its double helix. As we read and interpret that code, we should, in the fullness of time, be able to completely understand how cells work, then change and

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’s president, David Schlessinger, of Washington University, in St. Louis, announced what he described as an “historic event.” With Haemophilus influenzae we had transformed the double helix of biology into the digital world of the computer, but the fun was only now beginning. While we had used its genome to explore the

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DNA, Sinsheimer found that immediately after it had infected its host, enzymes present in the bacterium converted the circle of DNA to the familiar linear double helix. This discovery illuminated a problem encountered by Kornberg in his first efforts to make a copy of the virus genome: while DNA polymerase could copy

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, due to the chemical attraction of the complementary bases on each strand, à la Watson and Crick. To ensure that we ended up with complete double-helix strands, we then added DNA polymerase, as well as some free nucleotides, so that any place where the 3'-exonuclease chewed away too much of

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suggests, means wrapping up coils within coils. Most bacterial genomes are “negatively supercoiled,” meaning that the DNA is twisted in the opposite direction of the double helix. Some preliminary experiments had suggested that the precise state of the DNA was important, in that intact, circular chromosomes appeared to work best for transplantation

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, 177 Dirac, Paul, 163 Discourse on Method (Descartes), 10 DNA: and cells, 145 composition of, 28–9 digital, 163–4 digitized-life-sending-unit, 177 double helix structure of, 4, 21, 28–9, 45 electrical charge of, 104 forensic, 111 fragility of, 103 as genetic material, 4, 24, 26–31 half-life

The Gene: An Intimate History

by Siddhartha Mukherjee  · 16 May 2016  · 824pp  · 218,333 words

form and function. James Watson, Francis Crick, Maurice Wilkins, and Rosalind Franklin solve the three-dimensional structure of DNA, producing the iconic image of the double helix. The three-letter genetic code is deciphered. Two technologies transform genetics in the 1970s: gene sequencing and gene cloning—the “reading” and “writing” of

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tucked against each other. The zipper’s teeth had to intercalate. For A, T, G, and C to sit in the interior of the DNA double helix, they had to have some interaction, some relationship. But what did one base—A, say—have to do with another base? One lone chemist

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triangle, like the cave paintings at Lascaux, like the Pyramids in Giza, like the image of a fragile blue planet seen from outer space, the double helix of DNA is an iconic image, etched permanently into human history and memory. I rarely reproduce biological diagrams in text—the mind’s eye is

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. But sometimes one must break rules for exceptions: A schematic of the double-helical structure of DNA, showing a single helix (left) and its paired double helix (right). Note the complementarity of bases: A is paired with T, and G with C. The winding “backbone” of DNA is made of a

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One million helices stacked side by side would fit in this letter: o. The biologist John Sulston wrote, “We see it as a rather stubby double helix, for they seldom show its other striking feature: it is immensely long and thin. In every cell in your body, you have two meters of

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a yin-and-yang structure). Molecular forces between the A:T and G:C pairs lock the two strands together, as in a zipper. A double helix of DNA can thus be envisioned as a code written with four alphabets—ATGCCCTACGGGCCCATCG . . .—forever entwined with its mirror-image code. “To see,” the

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—I know I am right.’ ” He returned to London and confirmed that his most recent crystallographic data, as well as Franklin’s, clearly supported a double helix. “I think you’re a couple of old rogues, but you may well have something,” Wilkins wrote from London on March 18, 1953. “I

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living organism could be stored in such a regular structure had to be solved.” Old questions were replaced by new ones. What features of the double helix enabled it to bear the code of life? How did that code become transcribed and translated into actual form and function of an organism? Why

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acids—Methionine, Glycine, Leucine, and so forth—strung together in a chain. Unlike a chain of DNA, which exists primarily in the form of a double helix, a protein chain can twist and turn in space idiosyncratically, like a wire that has been sculpted into a unique shape. This shape-acquiring ability

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themselves: How are genes replicated when a cell divides into two cells, or when a sperm or egg is generated? To Watson and Crick, the double-helix model of DNA—with two complementary “yin-yang” strands counterposed against each other—instantly suggested a mechanism for replication. In the last sentence of the

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function. Watson and Crick proposed that each DNA strand was used to generate a copy of itself—thereby generating two double helices from the original double helix. During replication, the yin-yang strands of DNA were peeled apart. The yin was used as a template to create a yang, and the

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yang to make a yin—and this resulted in two yin-yang pairs. But a DNA double helix cannot autonomously make a copy of itself; otherwise, it might replicate without self-control. An enzyme was likely dedicated to copying DNA—a replicator

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Remarkably, the three R’s of gene physiology are acutely dependent on the molecular structure of DNA—on the Watson-Crick base pairing of the double helix. Gene regulation works through the transcription of DNA into RNA—which depends on base pairing. When a strand of DNA is used to build the

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DNA is, once again, copied using its image as a guide. Each strand is used to generate a complementary version of itself, resulting in one double helix that splits into two double helices. And during the recombination of DNA, the strategy of interposing base against base is deployed yet again to restore

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DNA. The damaged copy of a gene is reconstructed using the complementary strand, or the second copy of the gene, as its guide.V The double helix has solved all three of the major challenges of genetic physiology using ingenious variations on the same theme. Mirror-image chemicals are used to generate

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spread linearly along chromosomes. In the 1940s and 1950s, Avery, Watson, and Crick identified DNA as the gene molecule, and described its structure as a double helix—thereby bringing the anatomical conception of the gene to its natural culmination. Between the late 1950s and the 1970s, however, it was the physiology of

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development of an organism is addressed in a subsequent chapter. IV. DNA replication requires many more proteins than just DNA polymerase to unfold the twisted double helix and to ensure that the genetic information is copied accurately. And there are multiple DNA polymerases, with slightly different functions, found in cells. V.

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the Latin word ligare—“to tie together”), chemically stitches the two pieces of the broken backbone of DNA together, thus restoring the integrity of the double helix. Occasionally, the DNA-copying enzyme, “polymerase,” might also be recruited to fill in the gap and repair a broken gene. The cutting enzymes came

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proteins are called “restriction” enzymes because they restrict infections by certain viruses. Like molecular scissors, these enzymes recognize unique sequences in DNA and cut the double helix at very specific sites. The specificity is key: in the molecular world of DNA, a targeted gash at the jugular can be lethal. One microbe

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by identifying the chemical form of that material: genetic information was carried in DNA. Watson, Crick, Wilkins, and Franklin solved its molecular structure as a double helix, with two paired, complementary strands. In the 1930s, Beadle and Tatum solved the mechanism of gene action by discovering that a gene “worked” by specifying

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four quarters of the century.” “The first established the cellular basis of heredity: the chromosomes. The second defined the molecular basis of heredity: the DNA double helix. The third unlocked the informational basis of heredity [i.e., the genetic code], with the discovery of the biological mechanism by which cells read the

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to photograph and study the structure of DNA. Photograph 51 is the clearest of Franklin’s photographs of a DNA crystal. The photo suggested a double-helix structure, although the precise orientations of the bases A, C, T, and G were not clear from it. James Watson and Francis Crick demonstrate

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their model of DNA as a double helix in Cambridge in 1953. Watson and Crick solved the structure of DNA by realizing that the A in one strand was paired against the T

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.nlm.nih.gov/ps/retrieve/Narrative/CC/p-nid/35. No one knew or understood the chemical structure: Robert C. Olby, The Path to the Double Helix: The Discovery of DNA (New York: Dover Publications, 1994), 107. Swiss biochemist, Friedrich Miescher: George P. Sakalosky, Notio Nova: A New Idea (Pittsburgh, PA:

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Dorrance, 2014), 58. extremely “unsophisticated” structure: Olby, Path to the Double Helix, 89. “stupid molecule”: Garland Allen and Roy M. MacLeod, eds., Science, History and Social Activism: A Tribute to Everett Mendelsohn, vol. 228 (Dordrecht: Springer Science

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& Business Media, 2013), 92. “structure-determining, supporting substance”: Olby, Path to the Double Helix, 107. “primordial sea”: Richard Preston, Panic in Level 4: Cannibals, Killer Viruses, and Other Journies to the Edge of Science (New York: Random House, 2009

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perspective,” Zebrafish 5, no. 4 (2008): 243–45. “Important Biological Objects Come in Pairs” One could not be a successful scientist: James D. Watson, The Double Helix: A Personal Account of the Discovery of the Structure of DNA (London: Weidenfeld & Nicolson, 1981), 13. It is the molecule that has the glamour: Francis

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Research: A Risk Worth Taking (Hoboken, NJ: John Wiley & Sons, 2004), 85. Among the early converts: Maurice Wilkins, Maurice Wilkins: The Third Man of the Double Helix: An Autobiography (Oxford: Oxford University Press, 2003). Ernest Rutherford: Richard Reeves, A Force of Nature: The Frontier Genius of Ernest Rutherford (New York: W. W

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Physiology: A Biographical Dictionary (New York: Garland, 1990), 575. She “barks often, doesn’t succeed in biting me”: James D. Watson, The Annotated and Illustrated Double Helix, ed. Alexander Gann and J. A. Witkowski (New York: Simon & Schuster, 2012), letter to Crick, 151. “Now she’s trying to drown me”: Brenda

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Rosalind Franklin: The Dark Lady of DNA (New York: HarperCollins, 2002), 164. Franklin found most of her male colleagues “positively repulsive”: Watson, Annotated and Illustrated Double Helix, letter from Rosalind Franklin to Anne Sayre, March 1, 1952, 67. It was not just sexism: Crick never believed that Franklin was affected by sexism

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, if any, excitement: Watson Fuller, “For and against the helix,” Maurice Wilkins Papers, no. 00c0a9ed-e951-4761-955c-7490e0474575. “Before Maurice’s talk”: Watson, Double Helix, 23. “Maurice was English”: http://profiles.nlm.nih.gov/ps/access/SCBBKH.pdf. “nothing about the X-ray diffraction”: Watson

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, or TMV. But he was vastly more interested in DNA and soon abandoned all other projects to focus on DNA. Watson, Annotated and Illustrated Double Helix, 127. “A youthful arrogance”: Crick, What Mad Pursuit, 64. “The trouble is, you see, that there is”: Watson, Annotated and Illustrated

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of the polypeptide chain,” Proceedings of the National Academy of Sciences 37, no. 4 (1951): 205–11. “product of common sense”: Watson, Annotated and Illustrated Double Helix, 44. “like trying to determine the structure of a piano”: http://www.diracdelta.co.uk/science/source/c/r/crick%20francis/source.html#.Vh8XlaJeGKI. The

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British: A Genetic Journey (Edinburgh: Berlinn, 2014); and from Rosalind Franklin’s laboratory notebooks, dated 1951. “Superficially, the X-ray data”: Watson, Annotated and Illustrated Double Helix, 73. “check it with”: Ibid. Wilkins, Franklin, and her student, Ray Gosling: Bill Seeds and Bruce Fraser accompanied them on this visit. As Gosling recalled

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, “Rosalind let rip”: Watson, Annotated and Illustrated Double Helix, 91. “His mood”: Ibid., 92. In the first weeks of January 1953: Linus Pauling and Robert B. Corey, “A proposed structure for the nucleic

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, no. 2 (1953): 84–97. “V.Good. Wet Photo”: http://profiles.nlm.nih.gov/ps/access/KRBBJF.pdf. “important biological objects come in pairs”: Watson, Double Helix, 184. he would later write defensively: Anne Sayre, Rosalind Franklin & DNA (New York: W. W. Norton, 1975), 152. “Suddenly I became aware”: Watson, Annotated

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.2046%2C0.5569%2C0.3498. “I like the idea”: Fuller, “Who said helix?” with related papers. “The positioning of the backbone”: Watson, Annotated and Illustrated Double Helix, 222. On April 25, 1953: J. D. Watson and F. H. C. Crick, “Molecular structure of nucleic acids: A structure for deoxyribose nucleic acid,”

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and metabolism in Neurospora,” Physiological reviews 25, no. 4 (1945): 643–63. “For over a year”: James D. Watson, Genes, Girls, and Gamow: After the Double Helix (New York: Alfred A. Knopf, 2002), 31. “I am playing with complex organic”: http://scarc.library.oregonstate.edu/coll/pauling/dna/corr/sci9.001.43

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. Müller-Wille, Staffan, and Hans-Jörg Rheinberger. A Cultural History of Heredity. Chicago: University of Chicago Press, 2012. Olby, Robert C. The Path to the Double Helix: The Discovery of DNA. New York: Dover Publications, 1994. Paley, William. The Works of William Paley. Philadelphia: J. J. Woodward, 1836. Patterson, Paul H.

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Lee, eds. Genetics and the Unsettled Past: The Collision of DNA, Race, and History. New Brunswick, NJ: Rutgers University Press, 2012. Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. London: Weidenfeld & Nicolson, 1981. ———. Recombinant DNA: Genes and Genomes: A Short Course. New York

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. Mapping Fate: A Memoir of Family, Risk, and Genetic Research. Berkeley: University of California Press, 1995. Wilkins, Maurice. Maurice Wilkins: The Third Man of the Double Helix: An Autobiography. Oxford: Oxford University Press, 2003. Wright, William. Born That Way: Genes, Behavior, Personality. London: Routledge, 2013. Yi, Doogab. The Recombinant University: Genetic

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creativity bipolar disease and, 448–49, 453 gene variants linked to, 386, 450 Crick, Francis, 147 background and training of, 147 DNA replication and, 179 double-helix DNA model of, 13, 148–49, 150–52, 154–56, 158, 159, 160, 161, 179, 182, 314, 502 Franklin’s talk on DNA structure

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microbial defense system, 472, 477, 478, 489 Cro-Magnons, 332–33 crossing over, 96, 97, 182, 208, 334–35, 502 Crow, James, 274, 275 crystallography double-helix model using, 152, 158 three-dimensional structure of DNA on, 142, 143, 147 Culver, Kenneth, 424n Curie, Marie, 145 Cutshall, Cynthia, 426, 427–28, 429

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experiments to form, 411 recombinant. See recombinant DNA replication of, 179–80, 180n, 182, 288, 296 sequencing of. See gene sequencing Watson and Crick’s double-helix model of, 13, 150–51, 154–59, 160, 179, 182, 314, 502 Watson on Wilkin’s research on, 146 Wilkin on three-dimensional structure of

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, in humans, 451 Dolly (sheep cloning experiment), 397 dominant traits, Mendel’s plant-breeding experiments, 51–52 dopamine-receptor gene, 385 Doppler, Christian, 20, 52 double-helix model of DNA, 13, 150–51, 154–59, 160, 179, 182, 314, 502 Doudna, Jennifer, 470, 471–72, 474, 476 Down syndrome description of

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, 30 human origin and migration theory and, 336 Foucault, Michel, 462 Franklin, Rosalind background and training of, 143–44 criticism of Watson and Crick’s double-helix DNA model by, 151–52 imaging research on DNA structure by, 13, 144–45, 149–50, 153, 153n, 155, 158, 159, 314, 502 Watson’

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Celera’s genome sequencing and, 319 Crick’s relationship with, 147–48, 147n decision to work on DNA structure by, 146 DNA replication and, 179 double-helix DNA model of, 13, 150–51, 154–59, 160, 161, 179, 182, 314, 502 evaluation of genome sequencing by, 302, 303 Franklin’s research

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, 13 three-dimensional structure of DNA and, 13, 142–44, 145–46, 149, 153–54, 153n, 155, 158, 159, 314, 502 Watson and Crick’s double-helix DNA model and, 151, 158 Wilson, Allan, 333, 333n, 334–36, 438, 439 Wilson, Edmund, 358, 359 Wilson, James, 429–30, 431, 432, 434,

The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race

by Walter Isaacson  · 9 Mar 2021  · 700pp  · 160,604 words

. It was an echo of the work Rosalind Franklin had done with DNA, which was used by James Watson and Francis Crick to discover the double-helix structure of DNA in 1953. As it happens, Watson, a complex figure, would weave in and out of Doudna’s life. Doudna’s expertise in

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like I was the son that he wanted to have,” she says. “I was treated a bit differently than my sisters.” James Watson’s The Double Helix Doudna’s father was a voracious reader who would check out a stack of books from the local library each Saturday and finish them by

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from the library or the local secondhand bookstore, for her to read. And that is how a used paperback copy of James Watson’s The Double Helix ended up on her bed one day when she was in sixth grade, waiting for her when she got home from school. She put the

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the reasons why nature worked the way it did.” Doudna’s career would be shaped by the insight that is at the core of The Double Helix: the shape and structure of a chemical molecule determine what biological role it can play. It is an amazing revelation for those who are interested

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molecules—becomes biology. In a larger sense, her career would also be shaped by the realization that she was right when she first saw The Double Helix on her bed and thought that it was one of those detective mysteries that she loved. “I have always loved mystery stories,” she noted years

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make what Watson, with his typical grandiosity cloaked in the pretense of humility, would later tell her was the most important biological advance since the double helix. Darwin Mendel CHAPTER 2 The Gene Darwin The paths that led Watson and Crick to the discovery of DNA’s structure were pioneered a century

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unable to refrain from correcting his colleagues’ sloppy thinking and then crowing about it. As Watson memorably put it in the opening sentence of The Double Helix, “I have never seen Francis Crick in a modest mood.” It was a line that could likewise have been written of Watson, and they admired

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the atoms comported with the X-ray data and the laws of chemical bonds. In Watson’s memorable and only slightly hyperbolic phrase in The Double Helix, “Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life.” The solution was too beautiful not

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that science could be fun. All of the previous science books she read had “pictures of emotionless men wearing lab coats and glasses.” But The Double Helix painted a more vibrant picture. “It made me realize that science can be very exciting, like being on a trail of a cool mystery and

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sleeping grass that curled when you touched it, and the human cells that became cancerous: they were all connected to the detective story of the double helix. She decided that she wanted to study chemistry at college, but like many female scientists of the time, she met resistance. When she explained her

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of the many roots of the Human Genome Project involved Doudna’s childhood hero James Watson and his son Rufus. The provocative author of The Double Helix was the director of Cold Spring Harbor Laboratory, a haven for biomedical research and seminars on a 110-acre wooded campus on the north shore

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laugh. “That was his way. You know how it is.” Despite his frequent public comments about women’s looks, beginning with Rosalind Franklin in The Double Helix, he was a good mentor to women. “He was very supportive to a close woman friend of mine who was a postdoc,” Doudna says. “That

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molecules. Linus Pauling worked out the spiral structure of proteins in the early 1950s, which was followed by Watson and Crick’s paper on the double-helix structure of DNA. Doudna realized that she would need to learn more about structural biology if she wanted to truly understand how some RNA molecules

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to create its three-dimensional shape. A cluster of metal ions in that domain formed a core around which the structure folded. Just as the double-helix structure of DNA revealed how it could store and transmit genetic information, the structure discovered by Doudna and her team explained how the RNA could

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, Doudna’s thesis advisor, discovered in the 1980s one of the keys to editing a gene: causing a break in both strands of the DNA double helix, known as a double-strand break. When this happens, neither strand can serve as a template to repair the other. So the genome repairs itself

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appear ambitious, but she knew how to balance this by being collegial and forthright. She had learned about the importance of competition from reading The Double Helix, which describes how the perceived footsteps of Linus Pauling were a catalyst for James Watson and Francis Crick. “Healthy rivalries,” she later wrote, “have fueled

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we could genetically engineer height or eye color? What about intelligence? Would we do that? Should we? Francis Crick, the co-discoverer of DNA’s double-helix structure, was there, but he stayed silent as he sipped his beer.6 The discussions led Berg to convene a group of biologists in January

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first arose.” Her parents, she recalls, were shocked when the first test-tube baby was born in 1978. She was fourteen, had just read The Double Helix, and remembers discussing with them why they thought creating babies by in vitro fertilization was unnatural and felt wrong. “But then it came to be

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, it’s genetic.” Later, there was a moment of self-awareness. “It should be no surprise that someone who won the race to find the double helix should think that genes are important.” The documentary aired the first week of January 2019, and Amy Harmon of the New York Times wrote a

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with their greatness. But Watson is an important part of the story I am writing—this book begins with Doudna picking up his seminal The Double Helix and deciding to become a biochemist—and his views on genetics and human enhancement are an undercurrent of the policy debates over gene editing. So

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is the most important discovery since DNA’s structure,” he tells Doudna, “is that it not only describes the world, as we did with the double helix, but makes it easy to change the world.” He and Doudna discuss the Watsons’ other son, Duncan, who lives in Berkeley near Doudna. “We were

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’s home, I ask Doudna her thoughts. “I was thinking back to when I was twelve and began reading the dog-eared copy of The Double Helix,” she says. “It would have been wild to know that years later I would be visiting with him in his home having that conversation.” She

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says. “He has said some really bad things, but every time I see him, I am brought back to that day when I read The Double Helix and first started thinking, ‘Gee, I wonder if I could do that kind of science someday.’ ”2 PART NINE Coronavirus I have no idea what

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him to give me and our daughter who lives in Paris a Zoom lecture on the book.”2 Like Doudna, Urnov read Watson’s The Double Helix when he was about thirteen and decided to become a biologist. “Jennifer and I joke about the fact that we both read The

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Double Helix at about the same age,” he says. “For all of Watson’s shortcomings as a human being, which are substantial, he produced a ripping good

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. It celebrated the hundredth anniversary of the birth of Rosalind Franklin, whose pioneering work on the structure of DNA inspired Doudna, when she read The Double Helix as a young girl, to believe that women could do science. The cover of the meeting’s program featured a colorized photograph of Franklin peering

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the Plague made me realize that I was understating the case. A few weeks ago, I found my old copy of James Watson’s The Double Helix. Like Doudna, I got the book as a gift from my father when I was in school. It’s a first edition with the pale

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section draws from my multiple interviews with James Watson over a period of years and from his book The Double Helix, originally published by Atheneum in 1968. I used The Annotated and Illustrated Double Helix, compiled by Alexander Gann and Jan Witkowski (Simon & Schuster, 2012), which includes the letters describing the DNA model and

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’s interviews with George Church, Eric Lander, and James Watson. 6. Frederic Golden and Michael D. Lemonick, “The Race Is Over,” and James Watson, “The Double Helix Revisited,” Time, July 3, 2000; author’s conversations with Al Gore, Craig Venter, James Watson, George Church, and Francis Collins. 7. Author’s own notes

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–46 cowpox, 436 Crichton, Michael, 271 Crick, Francis, 20–28, 47, 166, 389, 475 at Asilomar, 269 on central dogma of biology, 44 in DNA double-helix structure discovery, xviii, 7, 11, 26–28, 29–31, 46, 51, 58, 159, 423, 470 with DNA model, 16 Franklin’s work and, 25, 26

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biology, 44, 47, 270 cloning, 34–35, 98, 153, 280, 313, 415–16 CRISPR sequences of, see CRISPR crystallography and, 19–23, 51 discovery of double-helix structure of, xviii, 7, 11, 26–28, 29–31, 46, 51, 58, 159, 386, 390, 395, 397, 423, 470 editing of, see gene editing Franklin

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, 74, 79, 80, 83, 172 vaccines, 439–41, 444–45, 456 in viruses, 65 in yeast, 35, 45 Dolly the sheep, 280, 313, 415–16 Double Helix, The (Watson), xix, 6–8, 9, 20, 21, 27, 29–31, 50, 157, 328, 391, 397, 398, 414, 459, 477–78 Doudna, Dorothy (mother), 2

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), 215 Zhang’s emails and, 200–201, 207 see also CRISPR-Cas9 gene editing curiosity of, xix, 4, 5, 8, 31, 46, 51, 479 The Double Helix read by, xix, 6–8, 29–31, 157, 328, 391, 397, 398, 414, 459, 477 first marriage of, 54–56, 63 Genentech and, 97–102

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Doudna, Martin (father), 2, 3–8, 32, 34, 58–60, 397–98, 472–73 cancer of, 58–59 death of, 59–60 Watson’s The Double Helix given to Jennifer by, xix, 6–8, 477 Doudna, Sarah (sister), 2, 3, 472–73 Down’s syndrome, 337 Doxzen, Kevin, 255 dragonflies, 170 Dr

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, 18 as Cold Spring Harbor director, 37 Cold Spring Harbor’s cutting of ties with, 386, 387, 390 Crick’s meeting of, 20 in DNA double-helix structure discovery, xviii, 7, 11, 26–28, 29–31, 46, 51, 58, 159, 386, 390, 395, 397, 423, 470 with DNA model, 16 The

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Double Helix, xix, 6–8, 9, 20, 21, 27, 29–31, 50, 157, 328, 391, 397, 398, 414, 459, 477–78 Doudna and, xviii, 8, 29, 48–

Editing Humanity: The CRISPR Revolution and the New Era of Genome Editing

by Kevin Davies  · 5 Oct 2020  · 741pp  · 164,057 words

have even expanded the original four-letter genetic alphabet by synthesizing novel chemical building blocks that can substitute for the naturally occurring ones in the double helix. This paves the way for designing synthetic proteins containing novel building blocks.20 Advances in reading and writing are very important. But if I could

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applications. According to the doyen of DNA, Jim Watson, what Doudna and Charpentier did was “the biggest advance in science since the discovery of the double helix.” But it’s important to use it so that it’s equitable. “If it’s only used to solve the problems and desires of the

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torn or out of order—was a monumental achievement. This was the moonshot of biology, arguably the biggest event since Crick and Watson assembled the double helix in 1953. We had become the first species to translate the instruction manual, even if we couldn’t describe how much of it works. Textbook

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.15 One of the simplest arrangements—Type II—features an enzyme called Cas9. This nuclease makes a clean break on both strands of the DNA double helix like a pair of nail clippers, but not indiscriminately. It grabs an RNA tag, holding it like a mugshot, searching the incoming DNA for a

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cue to briefly caress the DNA. “That ephemeral interaction results in a distortion of the DNA,” explains Wiedenheft. By bending the DNA, Cas9 unzips the double helix to allow the guide RNA to slip into the resulting crevice (forming a so-called R-loop).18 The guide conducts a quick sequence check

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, each Cas9 molecule scours the densely packed coils of DNA to identify PAM sites, which occur on average once every full 360° rotation of the double helix. In principle, the enzyme has to interrogate 300–400 million bases to identify its precise target. Johan Elf, a biophysicist at Uppsala University in Sweden

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hours to search through every PAM sequence in the bacterial genome, pausing at each prospective site for a mere twenty milliseconds to peer into the double helix to see if it has found the correct target.21 But the packaging of DNA in a eukaryotic cell nucleus is far more complex than

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of a PAM sequence, which is the cue to check for a sequence match. 2. Locking In: Cas9 binds to the DNA and unzips the double helix, allowing the crRNA to align to the single-stranded DNA. 3. Cutting: If there is a perfect DNA:RNA match, Cas9 undergoes a conformational change

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can be any of the four bases. IV. Cas9 actually has two active sites, providing two separate cutting actions, one for each strand of the double helix. V. ZFN, zinc finger nuclease; TALEN, transcription activator-like effector nuclease (see chapter 8). VI. It will never catch on, but Patrick Harrison, a geneticist

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and ponder their evolution. When she was about twelve, Doudna’s father left a book on her bed—a dog-eared paperback copy of The Double Helix, Jim Watson’s riveting personal tale of the discovery of the structure of DNA. She ignored it at first, assuming it was a detective novel

…

—which, in a sense, it was. The Double Helix remains an astonishing story of naked scientific ambition and fierce rivalries. Watson was widely criticized for the sexist manner in which he portrayed Rosalind Franklin

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and thus was denied a share of the Nobel Prize, which was awarded to Crick, Watson, and her former colleague, Maurice Wilkins, in 1962. The Double Helix captured Doudna’s imagination, as it has countless young scientists, revealing how biologists could solve the secrets of life by probing the atomic structure of

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Crick—DNA >>> RNA >>> protein—RNA was sometimes overlooked. It was considered by some a disposable copy of the genome, lacking the majestic symmetry of the double helix or the exquisite three-dimensional complexity and diversity of proteins, which carry out the essential functions in life. In 1960, Crick and Sydney Brenner postulated

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Research Council report containing Rosalind Franklin’s unpublished DNA crystallography data with Crick and Watson. That sneak peak proved critical in the assembly of the double helix. CHAPTER 5 DNA SURGERY In March 2011, Doudna and Charpentier met for the first time at a small conference at the InterContinental San Juan in

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of a eukaryote cell nucleus? Human DNA might have the same four-letter alphabet as bacterial or viral DNA, but in its natural habitat, the double helix in eukaryotic cells is wrapped, bundled, and looped like a garden hose around protein cores in a material called chromatin. Nobody knew for sure how

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good collaborate [sic] on in the future! Very best wishes, Feng The Boston bombshell came from Feng Zhang at the Broad Institute. Just like the double helix, the story of CRISPR genome editing has a complementary strand, the twists and turns of which are still being unraveled. I. Cool’s scope of

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scientific household, Urnov’s father was friends with the family of the great Russian molecular biologist Vladimir Engelhardt, who lent him a copy of The Double Helix. Watson’s book had a profound effect on the fourteen-year-old Urnov, especially the “incomparable taste of having discovered a secret.” After one reading

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CXCR4 co-receptor. CHAPTER 9 DELIVERANCE OR DISASTER The conceptual seeds of genetic engineering date back deep into the 20th century, two decades before the double helix and more than a decade before the demonstration that DNA, not protein, was the genetic material. In 1932, some five hundred scientists traveled to Ithaca

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the banks of time with the dinosaurs and trilobites—if he will only accept the new science of genetic engineering. Written two years before the double helix, Williamson understandably took some pleasure in his foresight—only to learn that the Oxford English Dictionary had unearthed a previous use of the phrase in

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I have made the most remarkable discovery. We have solved the structure of deoxyribosenucleic acid (D.N.A.)…” On the next page, Crick sketched the double helix, showing the pairing of the four bases—C with G, A with T. After several more pages of near textbook detail, Crick invited his son

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his twenty-fifth birthday. A few weeks later, on April 25, 1953, the world—or at least Nature subscribers—got their first glimpse of the double helix. It was a family affair: the eight-hundred-word report was typed up by Watson’s sister Elizabeth, while the

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traveled slowly in those days. It took the New York Times six weeks before it saw fit to print a front-page story on the double helix. Watson and Crick published a follow-up paper in which they proposed that “the precise sequence of the bases is the code which carries the

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diseases. Only then could they contemplate how to fix it. Watson has been justifiably criticized for his sexist portrayal of Franklin (“terrible Rosie”) in The Double Helix, which was published over Crick’s objections in 1968. In subsequent editions and other venues, he has acknowledged the importance of her scientific contributions. But

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1977. Along the way, Sinsheimer demonstrated that the viral genome was merely a single strand of DNA, a stunning result that overturned six years of double helix dogma, like “finding a unicorn in the ruminant section of the zoo,” Sinsheimer said. He followed that with another heretical result: the ΦX174 DNA wasn

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event. * * * Sinsheimer’s vision of “genetic change, specifically of mankind,” was fueled by the successful elucidation of the universal genetic code. The beauty of the double helix had immediately suggested how DNA could replicate itself, each strand unzipped becoming the template for a new daughter strand. Kornberg won the Nobel Prize for

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summit he had wanted to conquer since his audacious manifesto was dismissed by the medical establishment two decades earlier. As a student, inspired by the double helix and Roger Bannister’s four-minute mile, Anderson had two goals in life: “I was going to be in the Olympics and I was going

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Tokyo by showing a picture of the serpent-entwined Rod of Asclepius, the ancient Greek symbol of medicine. Next he substituted the snake with the double helix—the repository of all genetic information. “We would like to think that knowledge of this molecule is going to markedly change the way we understand

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acid to valine) in the beta globin chain. Ingram made his breakthrough at the Cavendish Laboratory in Cambridge, where Crick and Watson had assembled the double helix four years earlier, although Ingram’s lab was a converted bicycle shed.18 A decade later, Makio Murayama showed how the appearance of that rogue

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joking with colleagues, and proudly displaying an encyclopedia of books he had published containing a complete human genome sequence, dozens of volumes stacked in a double helix tower configuration. There were also scenes of him enthusiastically playing five-a-side soccer as his wife and baby look on.34 Early in 2018

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six months later. It was logical that JK would select Nature as the prize venue for his CRISPR babies report. The journal had published the double helix of course, but also the seminal IVF papers of JK’s idol Robert Edwards, as well as the first (and only) two human embryo editing

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Halcyon that could read gene sequences by stretching a DNA molecule like a piece of bubble gum, allowing scientists to visualize the rungs of the double helix under an electron microscope. He also founded Knome,I the first company to offer personal genome sequencing years before the $1,000 genome became a

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in the 20th century, the new century will be driven by the parts list of biology—the seminal discoveries of molecular biology spinning off the double helix and the genomic revolution. In the first two decades of the 21st century, we advanced from a White House celebration of the first human genome

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off. “Single-stranded DNA is a lot more reactive than when it is double-stranded,” Komor says. When Cas9 binds to DNA, it unzips the double helix to expose a stretch of about five bases of single-stranded DNA. Here, then, was a window to perform some cool chemistry. Komor began with

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that cleaves DNA. By replacing a single amino acid in the enzyme, Komor could restore a “nickase” function that would clip one strand of the double helix. By nicking the G-containing strand (leaving the U intact) she could trigger the cell’s DNA repair machinery to fix the G rather than

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pegRNA and RT enzyme to copy the pegRNA strand into DNA. This results in a flap of DNA that needs to be stitched into the double helix. (Helpfully, cells have enzymes called “flap nucleases” that help in this process.) Finally, the method introduces a nick into the complementary strand, which is then

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induced “a kind of moral vertigo.”49 That unease has been triggered numerous times before and after the genetic engineering revolution—the structure of the double helix, the solution of the genetic code, the recombinant DNA revolution, prenatal genetic diagnosis, embryonic stem cells, and the cloning of Dolly. “Test tube baby” was

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supported. I believe that day will come eventually. Perhaps by 2032, the centennial of Brave New World. Or 2053, the one hundredth anniversary of the double helix. Or 2078, when Louise Brown turns one hundred. Or 2100, a century since we first cracked the sequence of the human genome. No drug comes

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have made over the past fifty to seventy-five years, unraveling the secrets of the gene and the genome like the Cas enzyme unzipping the double helix. Francis Crick and Jim Watson’s classic 1953 letter to Nature consisted of eight hundred words and one diagram—a beautiful, elegant pencil drawing of

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the double helix courtesy of Crick’s wife Odile. CRISPR has given us the means to modify the DNA code as easily (almost) as a deft flick of

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Odile’s pencil eraser. Odile Crick was a professional painter with a penchant for nudes. She wasn’t as enamored with the double helix breakthrough as her husband. “You were always coming home and saying things like that, so naturally I thought nothing of it,” she recalled. Nevertheless, her

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double helix became not only the most famous scientific drawing of the 20th century but also the universal symbol of humankind’s quest to understand, repair, manipulate,

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Body. New York: Simon & Schuster, 1994. Luke Timmerman. Hood: Trailblazer of the Genomics Age. Seattle: Bandera Press, 2016. James D. Watson. The Annotated and Illustrated Double Helix. New York: Simon & Schuster, 2012. James D. Watson, Andrew Berry, and Kevin Davies. DNA: The Story of the Genetic Revolution. New York: Knopf, 2017. Timothy

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Delbruck, March 12, 1953, http://scarc.library.oregonstate.edu/coll/pauling/dna/corr/corr432.1-watson-delbruck-19530312-transcript.html. 7. Brenda Maddox, “DNA’s double helix: 60 years since life’s deep molecular secret was discovered,” Guardian, February 22, 2013, https://www.theguardian.com/science/2013/feb/22/watson-crick-dna

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-60th-anniversary-double-helix. 8. J. D. Watson and F. H. C. Crick, “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid,” Nature 171, (1953):737–738

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, http://dosequis.colorado.edu/Courses/MethodsLogic/papers/WatsonCrick1953.pdf. 9. Brenda Maddox, “DNA’s double helix: 60 years since life’s deep molecular secret was discovered,” Guardian, February 22, 2013, https://www.theguardian.com/science/2013/feb/22/watson-crick-dna

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-60th-anniversary-double-helix. 10. Symposium held at Ohio Wesleyan University, Delaware, on April 6, 1963. The proceedings were published in The Control of Human Heredity and Evolution (1965

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, 182–186, 322, 327–328 cutting, xii, 7, 20–21, 24, 26–29, 28, 45, 55, 65, 69, 99–100, 112–113, 180, 296, 324 double helix, xvi, 7, 18, 26–28, 47–48, 60, 68, 100, 123–130, 154–155, 227, 280, 327–328, 333–334, 355, 362, 367 editing, xii

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–354 sponsored sequencing, 281 views on, xiv–xv DNA surgery, 63–75 Dobbs, David, 147 “Don’t Edit the Human Germline,” 197 Doomsday Clock, 5 Double helix. See also DNA anniversary of, 362 assembly of, 18, 60, 123–125, 154–155 description of, 68 discovery of, 7, 18, 123–130 glimpse of

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–28, 28, 47–48, 100, 124–130, 227, 327–328, 333–334, 355 symmetry of, 47–48 unzipping, 26–28, 28, 130, 327–328, 367 Double Helix, The, 47–48, 108, 126 Doudna, Andrew, 10 Doudna, Jennifer, x–xii, xvi, 7–10, 13, 21, 29, 46–67, 70–74, 84, 87–106

A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution

by Jennifer A. Doudna and Samuel H. Sternberg  · 15 Mar 2017

four compounds. The letters of these molecules are connected in long single strands. Two of these strands come together to form the famous double-helix structure of DNA. The double helix is a bit like a ladder twisted into a long, spiraling coil. Two strands of DNA wrap around each other along a central

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A from one strand always pairs with T on the other strand, and G always pairs with C. These are known as base pairs. The double helix beautifully reveals the molecular basis of heredity; this is how a relatively simple chemical like DNA can transmit genetic information to two daughter cells upon

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strand acts as a perfect template for its matching pair. Shortly before cell reproduction, the two strands are separated by an enzyme that “unzips” the double helix right down the middle. After that, other enzymes build a new partner strand for each single strand simply by using the same base-pairing rules

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, resulting in two exact copies of the original double helix. My own introduction to the DNA double helix coincided with my discovery that scientists could learn about molecules that were too tiny to see with even the most powerful light

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microscopes. I came home from school one day when I was about twelve or so to find a tattered copy of James Watson’s The Double Helix lying on my bed. (My dad would occasionally pick up books for me at used bookstores to see if they sparked any interest.) Thinking this

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microscopes. I came home from school one day when I was about twelve or so to find a tattered copy of James Watson’s The Double Helix lying on my bed. (My dad would occasionally pick up books for me at used bookstores to see if they sparked any interest.) Thinking this

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-start my own scientific career by determining some of the first three-dimensional structures of far more complex RNA molecules.) The structure of the DNA double helix In the years that followed Watson and Crick’s discovery, scientists sought to understand how this molecule’s structure and rather simple chemical ingredients could

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had culminated in the fantastically exciting discovery that RNA can fold up into three-dimensional structures that are very different from the elegantly simple DNA double helix. But my joy in determining the ribozyme structure, work I did with graduate student Jamie Cate, was accompanied by personal tragedy. That fall, my father

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exciting potential. Comparisons with known genes suggested that cas genes coded for specialized enzymes whose functions might include unzipping the two strands of the DNA double helix or slicing up RNA or DNA molecules, just like the DNA-cutting function of restriction endonucleases. Given how useful the discovery of restriction endonucleases had

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RNA is chemically so similar to DNA, it can create double helixes of its own by using base-pairing interactions, the same process that forms the famous double helix of DNA. Matching RNA strands can pair with each other, forming an RNA-RNA double helix, but a single strand of RNA can also pair with a

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matching single strand of DNA, forming an RNA-DNA double helix. This versatility, and the variety of different sequences found in CRISPR RNA, gave scientists an intriguing idea. It seemed possible that these CRISPR RNA molecules

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been posited in that paper that lured me into CRISPR research in the first place! In RNA interference, animal and plant cells form RNA-RNA double helixes to destroy invading viruses. In much the same way, CRISPR RNA molecules might target phage RNA during an immune response by using RNA-RNA

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double helixes. I was fascinated by the added possibility that, unlike in RNA interference, CRISPR RNAs might be able to recognize matching DNA too—a power that

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CRISPR RNA, meaning that the CRISPR RNA and one of the two DNA strands should be able to form their own double helix through complementary base pairing. Such an RNA-DNA double helix could be the key to the specificity of Cas9’s DNA-cutting activity. Cas9 cuts DNA using two RNA molecules Monitoring

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test tube required a sensitive detection method, since there was no way to directly visualize the DNA being cut. At fifty letters long, the DNA double helix would be just seventeen nanometers, or seventeen-billionths of a meter, long, roughly one-thousandth the width of a human hair. Not even the most

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and Krzysztof labored tirelessly to answer these questions, and, quickly, an incredible picture began to emerge. They found that Cas9 could latch onto a DNA double helix, pry open the two strands to form a new helix between the CRISPR RNA and one strand of DNA, and then use two nuclease modules

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, and his graduate student Terry Orr-Weaver. At the time, many scientists were puzzled by their model describing how cells repaired damage to the DNA double helix, and they were even more flummoxed by the idea, advanced by Memorial Sloan Kettering’s Maria Jasin and others, that researchers could harness this mode

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of designer molecular scissors because of its core function: to home in on specific twenty-letter DNA sequences and cut apart both strands of the double helix. Yet the types of gene-editing outcomes that scientists can achieve with this technology are remarkably diverse. For this reason, it might be better to

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first characterizing Cas9’s biochemical function, he demonstrated exactly which amino acids of the enzyme chemically cleaved, or sliced apart, each strand of the DNA double helix. By mutating those amino acids, he created a version of Cas9 that had completely lost the ability to cut DNA but, remarkably, could still interact

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recessive, 169 diseases, mitochondrial, 196 diversity, 233 DMD (Duchenne muscular dystrophy), 169–70 DMD gene, 169 DNA, 8, 9–15, 104–8 base pairs, 9 double helix, 9–11, 10 editing source code of, 22–26 mutations, 223 repair process, 92–93, 104–8 repeating sequences, 41–42, 43. See also CRISPR

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DNA, lab-made, 22 DNA, recombinant, 19, 201, 205, 207 DNA repair, 104–8 dogs, 143–44 Dolly (sheep), 191 double helix, 9–11, 10 double helix, DNA-RNA, 58, 79 double helix, RNA-RNA, 58 Double Helix, The (Watson), 10 double muscling, 130–32, 132, 133, 143 double-strand-break model, 27–29 Doudna, Jennifer American Society

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on animal models, 139–40 Caribou Biosciences, 66 Cas9. See Cas9 as classroom guest, 101–2 CRISPR, introduction to, 39–45 CRISPR article (Science), 85 Double Helix, The (Watson), 10–11 dream of, xi–xii education, 21, 25, 27 on ethics of germline editing, 225–30, 234–35 father’s death, 37

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defense, 57–58 DNA cutting and, 81, 83 targeting of DNA, 59, 61, 62 RNA interference, 39–40, 44, 45, 58 RNA-DNA double helix, 58, 79 RNA-RNA double helix, 58 Rogers, Stanfield, 16–17 Rothstein, Rodney, 27 Royal Society, 220 S Sabatini, David, 174 Sabine, Charles, 234 safety, of germline editing, 160

Life's Greatest Secret: The Race to Crack the Genetic Code

by Matthew Cobb  · 6 Jul 2015  · 608pp  · 150,324 words

the deepest level. It’s a bloody brilliant book.’ Professor Brian Cox ‘Life’s Greatest Secret is the logical sequel to Jim Watson’s The Double Helix. While Watson and Crick deserve their plaudits for discovering the structure of DNA, that was only part of the story. Beginning to understand how

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(1944–2014) – historian, colleague, friend. CONTENTS Foreword 1Genes before DNA 2Information is everywhere 3The transformation of genes 4A slow revolution 5The age of control 6The double helix 7Genetic information 8The central dogma 9Enzyme cybernetics 10Enter the outsiders 11The race Update 12Surprises and sequences 13The central dogma revisited 14Brave new world 15Origins and

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the mitochondria that are found in our cells – see Chapter 12. An outline of how the genetic code works during protein synthesis. A DNA double helix in the cell nucleus is partially unravelled and one strand is transcribed into RNA (mRNA). In organisms with a cell nucleus, this mRNA often contains

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protein chain. AUG FOREWORD In April 1953, Jim Watson and Francis Crick published a scientific paper in the journal Nature in which they described the double helix structure of DNA, the stuff that genes are made of. In a second article that appeared six weeks later, Watson and Crick put forward

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variation that might explain the many functions of genes.22 However perceptive this idea might look in the light of what we now know – the double helix structure of DNA and the fact that genes are composed of molecular sequences – Koltsov’s argument was purely theoretical. Furthermore, it was not unique –

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infected cell. And when he made his first public presentation of the results, at the June 1953 Cold Spring Harbor meeting, speaking after the double helix structure of DNA had been described, Hershey was still sure that DNA could not be the sole carrier of hereditary specificity. He addressed this issue

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J. ‘The birth of information in the brain: Edgar Adrian and the vacuum tube’, Science in Context, vol. 27, 2015, pp. 31–52. –SIX– THE DOUBLE HELIX On 6 August 1945, when the atomic bomb destroyed Hiroshima, Maurice Wilkins was a 28-year-old British physicist working on the Manhattan Project. Like

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between Wilkins and Crick led to what is probably the most intensely studied moment in the history of twentieth century science: the discovery of the double helix structure of DNA. The events surrounding this event have been described in memoirs, biographies, exhibitions, TV programmes, countless academic articles, many inaccurate blog posts

…

Watson and Crick had already crossed the finishing line. By the end of February 1953, Watson and Crick had agreed the basic outline of the double helix model, but this was merely a seductive concept. It needed to be turned into precise numbers, spatial relationships and chemical bonds, in the shape

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of a physical model. It took a week of calculation and intense work before the double helix, with complementary base pairing between A and T and between C and G, finally emerged from a tangle of precise metal templates held together by

…

four years before the Nobel Prize was awarded to Watson, Crick and Wilkins for their work on DNA structure. In 1968 Jim Watson published The Double Helix, in which he gave a gripping but partial account of events and a frank description of his own bad behaviour, particularly with regard to Franklin

…

. The epilogue to the book contains a generous and fair description of Franklin’s vital contribution and a recognition of his own failures. The Double Helix also suggested that Max Perutz had given Watson and Crick a confidential document when he handed over the MRC report containing those vital paragraphs by

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rap contest can be seen at http://www.youtube.com/watch?v=35FwmiPE9tI. –SEVEN– GENETIC INFORMATION On 19 March 1953, about two weeks after the double helix model had been completed, Francis Crick wrote a letter to his 12-year-old son, Michael, who was at boarding school. Crick told Michael

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our notice …’. Much of Watson and Crick’s second article was devoted to expanding on that cheeky insight. They described how, during gene duplication, the double helix could unwind, with each chain forming the template for the construction of a new molecule, leading to the creation of two identical daughter double helices

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was Wilkins himself.6 Despite these doubts, the advantage of Crick’s approach was that it explicitly set out the two revolutionary implications of the double helix: complementary base pairing explained gene duplication, while the sequence of bases explained genetic specificity. Here were two hypotheses that would revolutionise biology, if they

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were true. Crick recognised the links between the discovery of the double helix and Schrödinger’s ideas from a decade earlier. On 12 August 1953, he sent copies of the two Nature articles to Schrödinger, accompanied by a

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much about the relationship between a base sequence in DNA and the amino acid sequence – they were more focused on the problem of how the double helix might unwind during gene replication. They suggested that the sequence was ‘the code that carries the genetical information’, but they had not thought beyond

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sequence of amino acids.39 This pointed question went to the heart of everything that had been done since Watson and Crick had discovered the double helix – they had been avoiding the central issues of what the sequence of bases did, or to put it another way, what information they contained.

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this time it was generally accepted as a working hypothesis that all genes in all organisms were made of DNA and that the Watson–Crick double helix structure was also correct. Joshua Lederberg, a stickler for terminology, declared audaciously that ‘“gene” is no longer a useful term in exact discourse’.33

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Frank Stahl, who carried out what has been described as ‘the most beautiful experiment in biology’.39 One of the problems raised by the double helix structure was how the DNA molecule copied itself. The complementarity of the base pairs on the two strands suggested that the cell used each strand

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At the same 1956 Johns Hopkins meeting at which Benzer spoke, Max Delbrück outlined three models for DNA replication – ‘conservative’, in which the original DNA double helix remained intact and was entirely copied into a completely new molecule; ‘semi-conservative’, in which one strand of each molecule was copied, producing two daughter

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Stahl’s interpretation. In each round of reproduction the bacterial DNA was copied, using nitrogen from the 14N medium. After one generation, each DNA double helix was composed of a new 14N strand and an old 15N DNA strand. At the second generation, some molecules were composed entirely of 14N-rich

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. By resolving the thorny problem of DNA replication, Meselson and Stahl’s elegant and precise experiment represented the final confirmation of the significance of the double helix structure of DNA. As it closed one phase of the history of molecular biology, it opened another, showing that DNA molecules – and hence the

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significance of their approach.48 Together, these three papers have been cited more than 5,500 times – more than Watson and Crick on the double helix structure of DNA. In their 1961 review article, Jacob and Monod brought together the ideas that they had been developing in a series of unnoticed

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and algae) that indicated that the genetic code was universal; they outlined the growing conviction that only one of the two strands in the DNA double helix was used to make protein via RNA; and they described the recent discovery that non-U-containing polynucleotides could code for amino acids. But

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only was Nirenberg allowed to attend, he had pride of place on the programme. In the ten years since gangly Jim Watson had presented the double helix structure of DNA in a stifling Cold Spring Harbor lecture theatre, the field of molecular biology had been utterly transformed – this was the largest

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microbial genetics, which had transformed the way that genes were understood and could be studied, and Watson, Crick and Wilkins won in 1962 for the double helix structure of DNA. In 1965, Jacob, Monod and Lwoff were awarded the prize for their work on the repressor and the genetic regulation of

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human nuclear genome contains about 3 billion base pairs). (Genes and genomes are measured in ‘base pairs’ because of the two strands of the DNA double helix – for each base there is a complementary base on the other strand, forming a base pair.) It appears that all mitochondria, in all the

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gene expression.82 These RNA sequences bind to the DNA of the structural gene and are often produced by the complementary DNA strand in the double helix – this is called anti-sense RNA.83 A large proportion of RNA transcripts produced by mammalian genomes have an anti-sense counterpart that seems

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tape, but it can be safely stored for thousands of years if kept in the right conditions. One joker has facetiously suggested that the double helix would be particularly useful for storing the wave of genetic sequence data that is being generated at an exponential rate in laboratories all over the

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breakthrough brings the development of organic sensors, for both environmental and medical uses, much closer. * Although we generally describe the structure of DNA as a double helix, it is in fact a bit more complicated than this. Unlike a screw thread, which has a constant pitch or interval between each turn, the

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direction – anticlockwise as seen from the top, or right-handed, like a normal screw. It is easy to get confused about which way the double helix should spiral, and in many representations of DNA the molecule spirals the wrong way. In 1996 Tom Schneider began posting images of leftward spiralling double

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structures have some functional role, probably in regulating transcription, the evidence is still unclear.21 DNA is not the only molecule that can form a double helix. In 1961, Watson and Crick, together with Alexander Rich and David Davies, suggested that in certain circumstances, RNA, which is normally single-stranded, could

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crystallise double stranded RNA and to describe its structure. It, too, has a right-handed spiral.23 There is no evidence that the RNA double helix has any biological function in normal cells, but it may be possible that biotechnology will be able to employ this novel molecular structure. Although RNA

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performs essential functions within the cell, even if it has lost its role as the embodiment of genetic information, replaced by the semi-inert double helix of DNA. The double helix – iconic, rigid and fixed – contrasts with the many physical forms that RNA can take, enabling it to carry out such a wide

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The adoption of DNA as the genetic material, with its built-in error-correction mechanism in the shape of the two complementary strands in the double helix, and the use of thymine in the sequence, provided a more reliable information store and slowed the rate of potentially damaging mutations. These kind

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, vol. 13, 2012, pp. 153–62. Debré, P., Jacques Monod, Paris, Flammarion, 1996. De Chadarevian, S., ‘Portrait of a discovery: Watson, Crick, and the Double Helix’, Isis, vol. 94, 2003, pp. 90–105. Deichmann, U., ‘Early responses to Avery et al.’s paper on DNA as hereditary material’, Historical Studies in

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Witkowski, J., ‘The lost correspondence of Francis Crick’, Nature, vol. 467, 2010, pp. 519–24. Gann, A. and Witkowski, J. (eds), The Annotated and Illustrated Double Helix, London, Simon & Schuster, 2012. García-Sancho, M., ‘The rise and fall of the idea of genetic information (1948- 2006)’, Genomics, Society and Policy, vol. 2

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1986, p. 618. Gilbert, W., ‘Towards a paradigm shift in biology’, Nature, vol. 349, 1991, p. 99. Gingras, Y., ‘Revisiting the ‘quiet debut’ of the double helix: a bibliometric and methodological note on the ‘impact’ of scientific publications’, Journal of the History of Biology, vol. 43, 2010, pp. 159–81. Glass, B

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and Biomedical Sciences, vol. 42, 2011, pp. 119–28. Hall, K., The Man in the Monkeynut Coat: William Astbury and the Forgotten Road to the Double Helix, Oxford, Oxford University Press, 2014. Halloran, S. M., ‘The birth of molecular biology: An essay in the rhetorical criticism of scientific discourse’, in R.

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encoded at least 10 kb upstream from their main coding regions’, Cell, vol. 12, 1977, pp. 9–21. Klug, A., ‘The discovery of the DNA double helix’, Journal of Molecular Biology, vol. 335, 2004, pp. 3–26. Kogge, W., ‘Script, code, information: How to differentiate analogies in the ‘prehistory’ of molecular

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Cell Host Microbe, vol. 15, 2014, pp. 692–705. Watson, J. D., Molecular Biology of the Gene, New York, Benjamin, 1965. Watson, J. D., The Double Helix: A Personal Account of the Discovery of the Structure of DNA, London, Weidenfeld & Nicolson, 1968. Watson, J. D., Genes, Girls and Gamow, Oxford, Oxford University

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: Nobel Lecture, December 11, 1962’, in Nobel Lectures Physiology or Medicine 1942–1962, Elsevier Publishing Company, Amsterdam, 1964. Wilkins, M., The Third Man of the Double Helix: An Autobiography, Oxford, Oxford University Press, 2003. Wilkins, M. H. F., Gosling, R. G. and Seeds, W. E., ‘Physical studies of nucleic acid: an

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(1994, 2009), Ridley (2006), Sayre (1975), Watson (1968, 2001), Wilkins (2003). The most potent account, which has framed all others, is Jim Watson’s The Double Helix (Watson 1968, Gann and Witkowski 2012). For a collection of articles covering this period and afterwards, see Witkowski (2005). 3.Daly et al. (1950), p

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genome sequencing Dobzhansky, Theodosius 38–9 Dochez, Alphonse 36 dodder 271 dogs, relatedness 239, 239n domains of life 238–9 Donohue, Jerry 106, 109 double helix A, B, C and Z forms 98–101, 103–6, 273–4 discovery, representations of 90 error-correction mechanisms 290 gene duplication via 111–12

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containing Franklin’s data 105, 122 human genome project and 233 joined by Watson 97 at the Moscow Biochemistry Congress 185–6 reaction to The Double Helix 108 reaction to What is life? 17 rhino 239 whale 239, 239n phages defined 317 DNA amplification using 230 genome sequencing 229 Hershey and

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243 involvement in protein synthesis 58, 71–2, 116, 184 numbering of sugars and strands 212 presence in tobacco mosaic virus 64 as single or double helix 118, 274 synthetic versions 174–7, 208–10 transgenerational epigenetic factors 258–9 uracil replacing thymine in 123 variety of forms and roles 243,

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congress 186–7 attendance at Naples symposium 97 banned from further DNA work 100, 105 book, Molecular Biology of the Gene 140, 251 book, The Double Helix 105, 108 discovery of ‘split genes’ 221 failure to take notes 99–100, 109 first meeting with Crick 97 International Human Genome Sequencing Consortium

As Gods: A Moral History of the Genetic Age

by Matthew Cobb  · 15 Nov 2022  · 772pp  · 150,109 words

need to begin (there is also a glossary at the back). Our genes are made of DNA, a molecule that has two strands – the famous double helix. Each strand carries a sequence of four chemical structures called bases, which are known by their initials, A, C, G and T. The shape of

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– in particular they can be structural (for example, hair) or they can alter physiology (for example, enzymes or hormones). When a gene is activated, the double helix is unravelled by enzymes in the cell and the gene is transcribed: the DNA on the strand that carries the gene is used to produce

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little over five years after Jim Watson and Francis Crick, using data from Rosalind Franklin and from Maurice Wilkins, had proposed that DNA has a double-helix structure. At this time the role of DNA as the hereditary material in all life was still no more than a working hypothesis. It had

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nestled on young scientists’ shelves next to Jim Watson’s recent best-selling novelised account of the race to discover the structure of DNA, The Double Helix.i Watson’s book described events that occurred fifteen years previously but the breakthrough was only now bearing fruit. Furthermore, his lively first-hand descriptions

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of the young generation: although Watson’s scornful treatment of women, in particular his depiction of Rosalind Franklin, was straight out of the 1950s, The Double Helix made molecular biology seem modern, attractive, rule-breaking and sexy. These complex and contradictory cultural, political and psychological changes that were shaking the world had

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solve the problem of getting two pieces of DNA to fuse together, using what were called ‘sticky ends’. Phage DNA is composed of the usual double helix, but at either end one of the strands sticks out an extra twelve bases.iii These twelve-base sequences at each end are complementary, meaning

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the DNA molecule means that A can only bind with T and C can only bind with G. The result is a chain of viral double helixes, or even a circular molecule. These sticky ends would be used as pieces of molecular Velcro that would allow larger molecules to be assembled. David

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organism). This had recently been isolated by Herb Boyer’s group at the University of California San Francisco (UCSF). When this enzyme cut the SV40 double helix, it left short sticky ends which Mertz and Davis used to fuse two different lengths of DNA.29 Instead of employing six enzymes with a

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biologist Sydney Brenner wrote a think-piece in Nature, ‘New Directions in Molecular Biology’, to mark the twenty-first anniversary of the publication of the double-helix structure of DNA.47 Looking back, the article seems uncharacteristically out of touch. The new directions Brenner described were the basic academic problems of how

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the numbers, talent, resources or perhaps simply the drugs that were available at Stanford. iii The cohesive sequences at either end of the phage lambda double helix were GGGCGGCGACCT and AGGTCGCCGCCC. The two strands of a DNA molecule point in different directions; you can see how the last T of the first

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he had done in his life – far more significant than his co-discovery of the structure of DNA. He explained that the discovery of the double helix was inevitable and would eventually have been found by somebody, but his arguments had been pivotal in NIH deciding not to patent human genes. When

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its report, the Commission dismissed fears that scientists ‘might remake human beings, like Dr Frankenstein’s monster’ as ‘exaggerated’ (despite this, the cover showed joyous double-helix humans emerging from a test tube). US Presidential report on genetic engineering in humans, 1982. However, the Commission also warned that ‘if beneficial rather than

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are today. At the heart of this radical change has been the discovery of what happens in cells when the DNA double helix is broken. Damage to a single strand of the double helix is easy for the cell to repair – the sequence on the intact strand is used as a way of synthesising

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mammalian stem cells and had a very low level of efficacy. The ideal way of changing genes precisely and effectively would be to cut the double helix at a desired point in the genome, in a cell that was in an appropriate physiological state to use homologous recombination to alter the damaged

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finger recognises three base pairs, so by stringing together a number of these molecules a high degree of sequence specificity can be achieved), cutting the double helix at that point.5 These artificial zinc finger nucleases were described as chimeric, after the chimera, a hybrid animal in Greek mythology. In 1999, Chandrasegaran

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involved in CRISPR, vast. The CRISPR components have to rapidly find the chromosomes, get access to the bases which are on the inside of the double helix and then screen billions of base pairs to find their unique target. And they have to do this twice, once for each chromosome that contains

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challenge for our ingenuity. And as that broader focus implies, heritable human gene editing is not the only worrying application of our understanding of the double helix – scientists also have their eyes on nature itself. Footnotes i In 2022, Rebrikov revealed that as soon as he could find a willing deaf couple

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. As long ago as 1990, Steven Benner – one of the founding figures of synthetic biology – created two new complementary bases that could slot into the double helix, extending the genetic code from sixty-four possible combinations to 216.86 Since then, many other researchers have introduced yet more bases, and have altered

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by the past decades is utterly different and would bewilder the French philosopher. In 1953 Watson and Crick published a paper in Nature (not the double helix article but another one, which appeared six weeks later) outlining this new view. They claimed that in the DNA molecule ‘the precise sequence of the

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given allele will not be dominant against all others) and in many cases both alleles are expressed. DNA. Deoxyribonucleic acid, a molecule formed of a double helix that is composed of a sugar/phosphate backbone and four bases: adenine, cytosine, guanine and thymine (A, C, G and T). The genetic material in

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. Non-homologous end-joining. DNA repair mechanism in response to a double strand break, in which the cell fuses the two cut ends of the double helix. Different cells at different points in their cycle and in different organisms tend to preferentially use either homologous recombination or non-homologous end-joining. Non

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, S. (1974), Nature 248:785–7. The next article in the issue described, in great detail, Rosalind Franklin’s contribution to the discovery of the double helix: Klug, A. (1974), Nature 248:785–8. 48 Morange, The Black Box of Biology, p. 197. The same was true of Brenner’s friend and

Life on the Edge: The Coming of Age of Quantum Biology

by Johnjoe McFadden and Jim Al-Khalili  · 14 Oct 2014  · 476pp  · 120,892 words

in the Cavendish Laboratory in Cambridge, managed to fit a remarkable structure to the experimental data obtained from DNA by their colleague Rosalind Franklin: the double helix. Each DNA strand was found to be a kind of molecular string made up of atoms of phosphorus, oxygen and a sugar called deoxyribose, with

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DNA provided a mechanistic key that unlocked the mystery of genes. Genes are chemicals and chemistry is just thermodynamics; so did the discovery of the double helix finally bring life entirely into the realm of classical science? Life’s curious grin In Lewis Carroll’s Alice’s Adventures in Wonderland, the Cheshire

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to life’s deepest mysteries was and continues to be so revolutionary we need to return to the beginning of the twentieth century, before the double helix had been discovered, when the world of physics was being turned upside down. The quantum revolution The explosion of scientific knowledge during the Enlightenment of

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in the soil or, indeed, reading this book. The estrangement The years following the publication of Schrödinger’s book saw the discovery of the DNA double helix and the meteoric rise of molecular biology, a discipline that developed largely without reference to quantum phenomena. Gene cloning, genetic engineering, genome fingerprinting and genome

…

of DNA has rightly become one of the most iconic images in science, reproduced on T-shirts and websites and even in architecture. But the double helix is essentially just a scaffold. The real secret of DNA lies in what the helix supports. As we outlined briefly in chapter 2, the helical

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we have postulated immediately suggests a possible copying mechanism for the genetic material.” What hadn’t escaped their notice was a crucial feature of the double helix, that the information on one of its strands—its sequence of bases—is also present as an inverse copy on the other strand: an A

…

make two copies of the original double-strand. This is precisely what happens when genes are copied during cell division. The two strands of the double helix with their complementary information are pulled apart to allow an enzyme called DNA polymerase access to each separated strand. The enzyme then attaches to a

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same process is repeated on the other strand, giving rise to two copies of the original double helix: one for each daughter cell. Figure 7.1: The structure of DNA: (a) shows Watson and Crick’s double helix; (b) shows a close-up of the paired genetic letters A and T; (c) shows a

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a message or the plot of a book is written into the position of letters on a page, so the positions of protons on the double helix determine the story of life. The Swedish physicist Per-Olov Löwdin was the first to point out what seems obvious in hindsight: that the protons

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physical mechanisms were that were responsible for generating mutations—changing one marble into another. That all changed in 1953 when Watson and Crick unveiled the double helix. The gene marbles were shown to be made of DNA. The principle that mutations were random then made perfect sense, since well-established causes of

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7.2: (a) A standard A–T base pair with the protons in their normal positions; (b) here the paired protons have jumped across the double helix to form the tautomeric form of both A and T. Let’s consider one possible base pair, such as A–T, with the A on

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tautomers (figure 7.2b). Each of the DNA bases can therefore exist both in its common canonical form, as seen in Watson and Crick’s double helix structure, and in the rarer tautomer, with its coding protons shifted across to new positions. But remember that the protons forming the hydrogen bonds in

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rate than the one in a billion or so rate of mutation we find in nature, so if tautomeric bases are indeed present in the double helix then most of the resulting errors must be removed by the various error correction (“proofreading”) processes that help to ensure the high fidelity of DNA

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affect many other biomolecular processes without recourse to any quantum mechanical explanation. Jim has focused on investigating whether quantum tunneling of protons in the DNA double helix is feasible on theoretical grounds. When a theoretical physicist tackles a complex problem such as this, he or she tries to create a simplified model

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it. Biologists cannot even agree on a unique definition of life itself; but that hasn’t stopped them from unraveling aspects of the cell, the double helix, photosynthesis, enzymes and a host of other living phenomena, including many driven by quantum mechanics, that have now revealed a great deal about what it

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it is and what it does. RNA is DNA’s simpler chemical cousin, and it comes as a single-stranded helix compared with DNA’s double helix. Despite this difference, RNA has more or less the same genetic information coding capacity as its more famous cousin—it just doesn’t have the

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chromosome, 2.1, 2.2, 7.1, 9.1 copying errors (mutations), 7.1, 7.2, 7.3 discovery of structure, 2.1, 2.2 double helix, 2.1, 2.2, 7.1, 9.1 emergence genetic engineering genetic information, 2.1, 7.1, 9.1 magnetoreception mitochondrial quantum mechanics, 1.1

The Year's Best Science Fiction: Twenty-Sixth Annual Collection

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wanted to hold time back to the twentieth century, but the Adareans had advanced far beyond that. “What? You mean like the discovery of the double helix, the first genome projects?” “More than that,” the Adarean said. “It’s the great century of political change, of people like Mahatma Gandhi and Martin

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Conflicted: How Productive Disagreements Lead to Better Outcomes

by Ian Leslie  · 23 Feb 2021  · 280pp  · 82,393 words

Navel Gazing: True Tales of Bodies, Mostly Mine (But Also My Mom's, Which I Know Sounds Weird)

by Michael Ian Black  · 5 Jan 2016  · 171pp  · 57,379 words

The Great Derangement: Climate Change and the Unthinkable

by Amitav Ghosh  · 16 Jan 2018

A Thousand Brains: A New Theory of Intelligence

by Jeff Hawkins  · 15 Nov 2021  · 253pp  · 84,238 words

Power Systems: Conversations on Global Democratic Uprisings and the New Challenges to U.S. Empire

by Noam Chomsky and David Barsamian  · 1 Nov 2012

Einstein's Dice and Schrödinger's Cat: How Two Great Minds Battled Quantum Randomness to Create a Unified Theory of Physics

by Paul Halpern  · 13 Apr 2015  · 282pp  · 89,436 words

To Explain the World: The Discovery of Modern Science

by Steven Weinberg  · 17 Feb 2015  · 532pp  · 133,143 words

Mind Wide Open: Your Brain and the Neuroscience of Everyday Life

by Steven Johnson  · 2 Jan 1999  · 294pp  · 86,601 words