The Lost Correspondence of Francis Crick

New twists in double helix discovery story are uncovered. Two Watson School professors find unread correspondence of Francis Crick
Thursday, 30 September 2010

The story of the double helix's discovery has a few new twists. Two professors at the Watson School of Biological Sciences at Cold Spring Harbor Laboratory (CSHL) have uncovered a new primary source – a never-before-read stack of letters to and from Francis Crick, and other historical materials dating from the years 1950-76.

The letters both confirm and extend current knowledge of the circumstances surrounding the epoch-making discovery of DNA's elegant double-helical structure, for which Crick, James D. Watson (now CSHL's chancellor emeritus) and Maurice Wilkins were awarded the 1962 Nobel Prize in Medicine and Physiology. Unlike the structure itself, which amazed even its discoverers in its simplicity, the story of the discovery has revealed a complex tangle of people, ambitions and institutional politics behind the process of scientific investigation.

"It's primarily the insights these new letters provide about the personalities of the discoverers that people will find most fascinating," says Alex Gann, Ph.D., who along with Jan Witkowski, Ph.D., uncovered the new Crick materials and co-authored a paper on them that appears in the journal Nature Sept. 30.

Following the publication of landmark works including Watson's confessional ‘The Double Helix’ in 1968 and Horace Freeland Judson's ‘The Eighth Day of Creation’ 11 years later, most historians have been content to believe that the archives had been fully explored and would not reveal much more about the double helix story. But 34 of the newfound letters are between Crick and Wilkins and draw attention to what Gann and Witkowski have described as Wilkins' "tortured soul" during the critical period 1951-53, when Watson and Crick were alternately put on, taken off and then restored to an effort to discover DNA's structure.

"We are really between forces which may grind all of us into little pieces," Wilkins wrote to Crick in one letter.

As Witkowski explains, "Maurice Wilkins on the one hand wanted to be open – he believed science should be open and was all in favour of cooperation, the exchange of ideas and data; but on the other hand, he was also mindful of his own career: he knew he had to get results and publish papers."

As the upstarts Watson and Crick, then unknowns, jockeyed for permission at Cambridge to explore the DNA structure problem, Wilkins, at King's College, was already well engaged in experimentation that would prove vital in determination of the solution. Wilkins' boss at King's, John Randall, hired Rosalind Franklin and had, unknown to Wilkins, assured her that she was in "sole charge" of the DNA work at King's. This led to conflicts between Franklin and Wilkins, who assumed he and Franklin would be partners.

This was but the beginning of a series of now historic misunderstandings. Between the lines of the newly discovered Crick letters with Wilkins, one grasps, on Wilkins' end, the anguish, and on Crick's, what at times comes across as the self-assurance and jocularity of the player possessing superior position.

This is but a fraction of the newly found letters, which were uncovered unexpectedly in the midst of an archival collection of materials donated to Cold Spring Harbor by Sydney Brenner, the distinguished molecular biologist and Nobel laureate, who worked alongside Crick following discovery of the double helix. The two shared an office at Cambridge from 1956 to 1977. Coincidentally, the CSHL Press has just released a new biography of Brenner by Errol Friedberg.

Among the new letters, there are some 30 between Crick and George Gamow, dating to 1953-64. Other of his correspondents included Leo Szilard, C. P. Snow, and J. Robert Oppenheimer, among many others. The most important of the new letters, cited in the Gann-Witkowski paper, are now in the process of being digitized at the CSHL Archives to facilitate public access.

Mila Pollock, Executive Director of the CSHL Library and Archives, says it is her hope that digitization will proceed so that the Crick correspondence in its entirety will be accessible to all via the Internet. The greater part of the collection resides at the Wellcome Library.

Source: Cold Spring Harbor Laboratory
Contact: Peter Tarr

Reference:
The Lost Correspondence of Francis Crick
Alexander Gann and Jan A. Witkowski
Nature 467, 519-524 (30 September 2010), doi:10.1038/467519a
.........


ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at
http://cellnews-blog.blogspot.com/

---

Low Price Mapping of DNA

Low Price Mapping of DNA Monday, 06 October 2008 The company Complete Genomics in Mountain View, CA, will offer complete human DNA sequence for US$ 5.000:- next year. The company is set to announce its plans on Monday, according to Andrew Pollack of The New York Times. The company was started two years ago, and have developed a unique, miniaturized sequencing process that will permit the low price. The first human genome sequence, completed by the federally financed Human Genome Project in 2003, is estimated to have cost a few hundred million dollars. Last year, the genome sequence of James D. Watson, a discoverer of the structure of DNA, was completed at a cost of about $1 million. Today, the cost to obtain a complete human DNA sequence is about $100,000. See further: Dawn of Low-Price Mapping Could Broaden DNA Uses NY Times - October 6, 2008 See also at CellNEWS: Sequencing 15 Human Genomes Each Week Wednesday, 02 July 2008 First Human Female DNA Sequenced Monday, 26 May 2008 Large-scale Genetic Differences in Humans II Thursday, 01 May 2008 Large-scale Genetic Differences in Humans I Thursday, 01 May 2008 James Watson's DNA sequenced... II Wednesday, 16 April 2008 Future of personal genomics Friday, 21 September 2007 James Watson's DNA sequenced Monday, April 02, 2007 ......... ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

---

EuroDYNA Takes Lid Off the Genome

EuroDYNA Takes Lid Off the Genome Saturday, 14 June 2008 European researchers have made significant progress unravelling how genes are governed and why this sometimes goes wrong in disease. The key lies in the dynamic ever-changing structure of the chromatin, which is the underlying complex of protein and DNA making up the chromosomes in which almost all genes are housed within the genome. The way this structure changes and responds to external signalling molecules within the cell determines how and when genes are expressed and also the mechanisms used to repair DNA damaged by a variety of internal and external insults, such as ultra violet radiation and free radical by-products of metabolism. Understanding the structure of chromatin and its interactions with proteins and RNA within the cell was the goal of the European Science Foundation 's (ESF) EuroDYNA programme, which held its last conference at the Wellcome Trust Conference Centre near Cambridge in May 2008. The study of genome structure involves interaction between various disciplines including cell biology, molecular physics, biomechanics and bioinformatics, as well as access to a wide range of expensive equipment such as electron microscopes, supercomputers, and scanners for simultaneous profiling of RNA expression across the whole genome. EuroDYNA helped broker these collaborations and enable projects to develop the critical mass needed to make real progress. The expression of genes involves an apparatus comprised mostly of proteins for reading the DNA, leading to production of RNA. This RNA in turn is either transported within the cell to the protein factory called the ribosome, where the code is translated into proteins, or else it interacts with other genes to control their expression in turn. These processes are intimately related to the constantly changing physical and chemical structure of the chromatin. Furthermore the overall state of the genome evolves during the life cycle of the cell, leading to its duplication if and when the cell eventually divides. All these inter-related processes need to be understood in order to unravel the complex network of mechanisms controlling gene expression. One of the big fundamental questions tackled within EuroDYNA concerned the detailed structure of how the DNA double helix is folded in the nucleus of higher organisms. Although the double helix structure was discovered by Crick and Watson in 1953, the way it folds and stretches such that it fits in the cell nucleus is only now becoming clear, as is its relevance both for cell replication and gene expression. At the EuroDYNA conference, John van Noort from Leiden University in the Netherlands reported that the DNA molecule, which in humans and most mammals is about two metres in length but only 2 nanometres in diameter, is coiled up like a spring in a solenoid structure. In such a folded structure it behaves according to the well known Hooke's law, stating that up to a certain point the extension is proportional to the force applied. It turns out chromatin is a very elastic molecular complex, capable of stretching to three times its normal rest length without breaking, according to van Noort. Even more remarkably – and here it differs from a familiar metal spring - even if stretched beyond three times its rest length, the chromatin solenoid is capable of repairing itself and regaining its former shape and elasticity. Indeed the ability of DNA to repair itself is essential for the long term survival of the cell and ultimately of the whole organism. DNA damage occurs not just from factors outside the cell nucleus, but also during the process of cell division (mitosis). The overall objective is to hand down the correct genetic code to the daughter cells during mitosis, a process so important that a number of surveillance and repair systems have been put in place to ensure its completion. One of those systems is called PRR (Post Replicative Repair) and it is highly conserved among all organisms, from bacteria to eukaryotes. PRR was discovered in the 1970s, but here again the detailed mechanisms are only now being elicited. At the EuroDYNA conference, Simone Sabbioneda from the University of Sussex presented new findings about one of the key PRR mechanisms called Translesion DNA Synthesis (TLS). This project, like some of the others, involved direct observation of processes as they take place in living cells, in this case using a technique called Fluorescence Recovery after Photobleaching. This comprises an optical microscope combined with a probe to observe the radiation emitted (the fluorescence) by molecules within a cell in response to a laser source. Such work is yielding important clues on how the PRR pathways work, hoping to help in the long term campaign to find novel, more specific, treatments for cancer, without the side effects of current therapies based on surgery, radiotherapy, or chemotherapy. One EuroDYNA project however yielded a more immediate insight into a treatment already used to alleviate the symptoms of another important disease, MS (multiple sclerosis). Pavel Kovarik from the University of Vienna's Department of Microbiology and Immunology noted that the only compound capable of alleviating MS symptoms was the protein interferon beta. This resembles the interferon produced naturally by the body in response to infection, but until now it has not been known how it relieves symptoms for MS sufferers. However Kovarik and colleagues have shown that interferon works by up-regulating (increasing production of) members of the protein family Tristetraprolin (TTP), which have an anti-inflammatory affect by in turn inhibiting production of pro-inflammatory agents. "We have demonstrated a novel function for interferon," said Kovarik. By understanding how it works, there is the potential for delivering interferon beta more effectively for treating MS. There were other projects within EuroDYNA with great therapeutic potential, many of which will continue, but which would benefit greatly from an extension to this highly successful programme. ......... ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

---

First Human Female DNA Sequenced

First Human Female DNA Sequenced Monday, 26 May 2008 Geneticists of Leiden University Medical Centre (LUMC) are the first to determine the DNA sequence of a woman. She is also the first European whose DNA sequence has been determined. Following in-depth analysis, the sequence will be made public, except incidental privacy-sensitive findings. The results will contribute to insights into human genetic diversity. DNA of geneticist Marjolein Kriek The first woman in the world to have her complete DNA sequenced is described as a red-haired, 34-year-old Dutch woman. The DNA is that of Dr. Marjolein Kriek, a clinical geneticist at LUMC, scientists at Leiden University Medical Centre announced on Monday. “If anyone could properly consider the ramifications of knowing his or her sequence, it is a clinical geneticist,” says professor Gert-Jan B van Ommen, leader of the LUMC team and director of the Center for Medical Systems Biology (CMSB), a center of the Netherlands Genomics Initiative. Van Ommen continues: “Moreover, while women don’t have a Y-chromosome, they have two X-chromosomes. As the X-chromosome is present as a single copy in half the population, the males, it has undergone a harsher selection in human evolution. This has made it less variable. We considered that sequencing only males, for ‘completeness’, slows insight into X-chromosome variability. So it was time, after sequencing four males, to balance the genders a bit”. He smiled: “And after Watson we also felt that it was okay to do Kriek”. Eight times coverage The DNA sequencing was done with the Illumina 1G equipment. This was installed in January 2007 in the Leiden Genome Technology Center, the genomics facility of LUMC and CMSB. In total, approx. 22 billion base pairs (the ‘letters’ of the DNA language) were read. That is almost eight times the size of the human genome. Dr. Johan den Dunnen, project leader at the Leiden Genome Technology Center: “This high coverage is needed to prevent mistakes, connect the separate reads and reduces the chance of occasional uncovered gaps.” “The sequencing itself took about six months. Partly since it was run as a ‘side operation’ filling the empty positions on the machine while running other projects. Would such a job be done in one go, it would take just ten weeks”. The cost of the project was approximately €40.000. This does not include further in-depth bioinformatics analysis. This is estimated to take another six months. History of human DNA sequencing In 2001, the DNA sequence was published of a combination of persons. The DNA sequences of Jim Watson, discoverer of the DNA’s double helix structure, followed in 2007, and later the DNA of gene hunter Craig Venter. Recently the completion of the sequences of one Han Chinese individual and two Yoruba-Africans was announced. Bessensap The researchers announced their news at the yearly ‘Bessensap’ meeting, bringing together the Dutch scientists and the press. The Netherlands Organization for Scientific Research NWO organizes this event jointly with the Association of Science Writers VWN and Science Center NEMO. In its eight years of existence, Bessensap has had several high-profile news items. It has had a debate with Italian ‘clonedoctor’ Severino Antinori and hosted dino-hunter Jack Horner, who was key in the Jurassic-Park modelling. During Bessensap also the yearly Eureka prize is awarded for the best popular-scientific book and media production. Leiden University Medical Center Leiden University Medical Center (LUMC) is strongly committed to ongoing improvement in health care quality and intends to play a leading role in this field at both national and international level. Its core activities are research, patient care, education and post graduate training. LUMC is part of the Dutch Federation of University Medical Centers (NFU), which promotes the shared interests of the eight University Medical Centers in the Netherlands. See also: The human genome; you gain some, you lose some Kriek, Marjolein 6-Dec-2007 International Human Genome Project Launched CellNEWS - Wednesday, 23 January 2008 ......... ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html

---

James Watson's DNA sequenced... II

James Watson's DNA sequence published Wednesday, 16 April 2008 James Watson's DNA sequence, the first full genome to be sequenced using next-generation rapid-sequencing technology, is published today in Nature. See: The complete genome of an individual by massively parallel DNA sequencing Nature 452, 872-876 17 April 2008, doi:10.1038/nature06884 Comments: James Watson's genome sequenced at high speed Nature 16 April 2008, doi:10.1038/452788b ......... ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at http://www.geocities.com/giantfideli/index.html

---

Future of personal genomics

As personal genomics stands poised to go mainstream, researchers urge caution Friday, 21 September 2007 Giving Nobel Laureate James Watson his personal genome and Craig Venter publishing his own complete genome was just the beginning. In a future that promises similar information to much of the population, ethicists, scientists and physicians are only beginning to understand and consider the possibilities. In a commentary in today’s issue of the journal Science, four experts ponder the implications of this new technology and information and ask the crucial questions that should be answered before the era of personal genomics comes to pass. They combined their different perspectives to consider what is possible now and in the future. Along with that, they look at the ethical and legal issues that will inevitably arise with such technology. Imagine this: you visit your clinician, undergo genetic testing, and then you are handed a miniature hard drive containing your personal genome sequence, which is subsequently uploaded onto publicly accessible databases. This may sound like science fiction, but it is scientific fact, and it is already happening. University of Alberta researcher Tim Caulfield and co-authors highlight the need to proceed with caution when it comes to personal genomics projects that represent research milestones but are also fraught with ethical, social and clinical implications. Caulfield, who is the Canada Research Chair in Health Law at the U of A and professor and research director in public health sciences, is recognized as one of the foremost experts in health law research in Canada. Scientists predict that within five years DNA sequencing technologies will be affordable enough that personal genomics will be integrated into routine clinical care. Companies are responding by offering their services for ancestry tracing, forensics, nutritional advice and reproductive assistance. It won’t be long before companies are able to offer Facebook-like social networking services centred around our genomes.

• Once we have our personal genomic information, what will we do with it and how might this information be used outside the medical context?
• How will physicians educate patients about the significance of genetic risk information?
• Will already-strained health-care systems be able to cope with the inevitable influx of “worried well” patients seeking follow-up investigations for genetic risks that are not clinically meaningful?

Caulfield and his colleagues pose these questions and warn that the routine generation of individual genome sequences will pose challenges to our health-care system. They argue that only clinically meaningful genomic test results should be integrated into medical decision-making — however, this will require clear standards, multidisciplinary collaboration and careful consideration of the ethical, social and clinical implications. Drs. Amy L. McGuire of Baylor College of Medicine, Mildred K. Cho of Stanford University in Palo Alto, California; Sean E. McGuire of The University of Texas M.D. Anderson Cancer Center and Timothy Caulfield of the University of Alberta in Edmonton, Canada, participated in this study. ......... ZenMaster

---

For more on stem cells and cloning, go to CellNEWS at http://www.geocities.com/giantfideli/index.html

---

James Watson's DNA sequenced

"James Watson's DNA Secrets Revealed ... or Not" Monday, April 02, 2007 The codiscoverer of the double helix has had his whole genome sequenced, and he realizes that he may not want to reveal all after all. ZenMaster