nd01.JPG (15136 bytes)The DNA double helix is now a model 50 years old
This year is the 50th anniversary of one of the most important breakthroughs in science – the discovery of the DNA double helix by James Watson and Francis Crick. Watson and Crick’s discovery marks the creation of the biotechnology industry.

     This photo, taken at Cambridge in May of 1953 by Antony Barrington Brown, has been made available by the Science Photo Gallery in London   together with its background story.

     Barrington Brown was living in Cambridge at the time, and received a tip that someone at the Cavendish Laboratory had made an important discovery. He went to take a picture to go with a freelancer’s story for Time magazine. Barrington Brown recalls, “I knocked at the door of one of dozens of similar rooms where research students worked and was affably greeted by a couple of chaps lounging at a desk by the window, drinking coffee. ‘What’s all this about?’ I asked. With an airy wave of the hand one of them, Crick I think, said ‘we’ve got this model’ indicating an array of retort stands holding thin brass rods and balls. It meant absolutely nothing to me, so I set up my lights and camera and said ‘you’d better stand by it and look portentous’ which they lamentably failed to do, treating my efforts as a bit of a joke.”

     The story and the photos were never published by Time but Watson and Crick were later awarded the Nobel prize, and Barrington Brown’s photo hangs in the National Portrait Gallery in London.

     Science Photo Gallery has produced limited edition prints of the portrait of Watson and Crick with their DNA model. One edition of 750 prints at 20×16-inch size is available for $475, and a second edition of 350 prints at 30×20-inch size is $650. The prints are signed and numbered by Barrington Brown. Further details are available at www.sciencephotogallery.com.

nd02.JPG (11491 bytes)UK Biobank project plans a national gene survey to aid health and disease research
Set to begin piloting in 2003 and recruitment in 2004, the UK Biobank project is planned as “the world’s biggest study of the role of nature and nurture in health and disease,” according to the Medical Research Council, the Wellcome Trust and the Department of Health, the public and independent charitable organizations working in partnership on the study. The Biobank project is a long-term research study aimed at establishing how genes, lifestyle and environmental factors interact to affect people’s health.

     The study is similar to the genetic study completed in Iceland, but with a much larger and more heterogenous population. The study will involve about 500,000 middle-aged participants, who will provide information about their lifestyle and diet, their medical history and a DNA sample. Participants will be followed for ten years through their National Health Service medical records.

     Like the Icelandic study, the information gathered from the study could lead to improved DNA-based diagnostics and therapies. The data from Iceland were unique in researchers’ ability to very carefully trace participants’ genealogy, while the British study would have the additional benefits of information from study participants who are unrelated and from diverse backgrounds, followed over time.

Roche and deCODE identify osteoporosis risk factors, anticipate DNA-based diagnostic test
Roche Diagnostics of Basel, Switzerland and deCODE Genetics of Reykjavik, Iceland announced that deCODE scientists have identified specific variations within a single gene that confer significantly increased risk of osteoporosis. Under their alliance to develop and bring to market DNA-based diagnostics, the companies are analyzing these and other markers to create a test that can identify individuals who are at a high risk of developing the disease. Such a test promises to enable effective prevention strategies for the disease itself and for complications such as bone fractures. deCODE receives milestone payments for these discoveries.

     In its population genetics research on osteoporosis in Iceland, deCODE has identified seven SNPs (single-base variations in DNA) within a gene on chromosome 20 which confer a several-fold increased risk of osteoporosis. These variations contribute to decreased bone mass density in later life – the hallmark of osteoporosis – as well as to an increased risk of bone fractures, one serious and frequent result of the disease. The deCODE team identified the gene through a population- and genome-wide linkage study involving more than 1,000 patients and unaffected relatives in 139 families.

     “We are delighted to see our partnership with deCODE yielding results in such an important disease area”, said Heino von Prondzynski, Head of Roche Diagnostics. “As part of the expansion of our molecular diagnostics business into genomics and women’s health, we will focus our efforts on development of a diagnostic test and will be evaluating opportunities to license this marker to laboratory service providers. We believe this test will provide actionable health information that allows individuals to better understand their risk for osteoporosis and thereby obtain early treatment to help prevent the disease.” The two companies cite the anticipated test as a concrete example of how our breakthroughs in genetics are going to contribute to better healthcare in the very near future.

Study identifies CRP as an underlying cause of blood clot formation, with added links to diabetes and metabolic syndrome
In a study published in the January 25, 2002 edition of the American Heart Association publication Circulation, UC Davis physicians link CRP to the formation of blood clots. According to Ishwarlal Jialal, professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at UC Davis School of Medicine and Medical Center, “The study provides further conclusive evidence that CRP, until now viewed as an ‘innocent bystander’ in the formation of heart disease, is in fact a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes.”

     According to the authors, in addition to being a risk marker for cardiovascular disease, much recent data suggest that CRP promotes atherogenesis via effects on monocytes and human aortic endothelial cells (HAECs). HAECs are a major source of plasminogen activator inhibitor-1 (PAI-1), an enzyme that inhibits the breakdown of clots, and is used as a marker of atherothrombosis. This study concludes that CRP induces PAI-1 expression and activity in endothelial cells, causing lesions in the arteries that ultimately lead to the formation of plaque and blood clots.

     “Based on these findings, if a patient has normal cholesterol but high levels of CRP, an aggressive course of treatment is recommended to help the patient reduce the risk of heart attack, stroke and other heart diseases,” said Jialal. “By relying on cholesterol alone, a physician could significantly underestimate a patient’s risk level.”

     High CRP levels can occur in otherwise healthy individuals, according to the study. Patients with high levels of CRP can reduce risk by losing weight, exercising on a regular basis, stopping cigarette smoking, or taking statin drugs, Jialal added.

     The study also closely links CRP and PAI-1 to diabetes and metabolic syndrome, a disorder characterized by a disproportionate amount of abdominal fat, elevated blood pressure, blood sugar and triglycerides and low levels of HDL, the “good” kind of cholesterol.

     “In another important discovery, this study shows that in the presence of high blood-glucose levels, CRP is especially active in the stimulation of PAI-1. As a result, the effect of CRP is especially acute for patients with diabetes and metabolic syndrome,” said Sridevi Devaraj, a co-investigator and assistant professor of pathology at UC Davis. “Given the current pandemic of obesity which increases one’s risk of diabetes, the study’s insights about the active role of CRP and PAI-1 in heart disease are especially valuable.”

     The new study adds to the findings of another landmark study on CRP by Jialal’s team at UC Davis that showed CRP actually damages the blood vessel wall by blocking a critical “protector” protein and inhibiting nitric oxide.

     “Interestingly, the new study indicates that activation of PAI-1 was unrelated to the nitric oxide inhibition identified in the earlier study,” said Jialal. “This indicates that CRP has multiple, independent effects that cause heart disease.”

nd03.JPG (18328 bytes)FDA issues final guidance on donor deferral for smallpox vaccine recipients
The FDA has issued a document on “Recommendations for Deferral of Donors and Quarantine and Retrieval of Blood and Blood Products in Recent Recipients of Smallpox Vaccine (Vaccinia Virus) and Certain Contacts of Smallpox Vaccine Recipients,” available on the FDA Web site at http://www.fda.gov/cber/gdlns/smpoxdefquar.pdf. The AABB has also issued a bulletin addressing various blood banking related issues regarding the revival of an inoculation program for smallpox. These recommendations are applicable to pre-event, non-emergency smallpox vaccination and may need to be modified in the event of widespread emergency vaccination or due to an impending smallpox outbreak.

     According to the AABB, blood collection centers should work carefully to disseminate information to existing and potential donors so that they are aware of the deferral criteria for vaccination. In order to maintain an adequate supply, blood centers may wish to encourage potential vaccinees to donate prior to receiving the vaccination.

     The complete text of the AABB Bulletin (Association Bulletin #02-11) can be found at [removed]http://www.aabb.org/Pressroom/In_the_News/ab02-11.pdf[/removed].

nd04.JPG (10402 bytes)DHHS issues new regulations for select agents and toxins
On December 13, 2002, the Department of Health and Human Services (DHHS)/Centers for Disease Control and Prevention (CDC) and the U.S. Department of Agriculture (USDA) published the interim final rules which establish

new stricter regulations for the possession, use and transfer of select biological agents and toxins that could pose a threat to human, animal and plant health and safety. According to the American Society for Microbiology(ASM), the new regulations have important implications for microbiology laboratories and research with select agents and toxins and require careful attention.

The new rules will take effect on February 7, 2003. They established a registration process for facilities possessing select agents and toxins, and timeline dates for compliance, including access restrictions in accordance with the restricted preson prohibition of the USA Patriot Act. Phase-in dates are provided, but all facilities possessing, using and transferring select agents and toxins must be in full compliance with the new regulations by November 12, 2003. Given the potential value of microbial cultures for future biomedical research and biodefense efforts, the ASM has stated that it would be prudent for some institutions to transfer rather than destroy select agents. As indicated in a New York Times article that appeared on December 17, 2002, the Office of Science and Technology Policy (OSTP) has requested the assistance of the ASM in notifying the research community of its interest in attempting to preserve the biodiversity of select agents either by the lawful retention in accordance with the regulations by those possessing such agents or through the lawful transfer in accordance with the regulation of those agents to registered facilities. The requirements for retention and/or transfer of select agents are available from the CDC.

nd05.JPG (9449 bytes)Lack of awareness and control of risk factors contribute to preventable strokes in high-risk African American population
The African American Antiplatelet Stroke Prevention Study (AAASPS) is a clinical trial comparing the effectiveness of ticlopidine hydrochloride (an anti-clotting agent) with aspirin in preventing recurrent stroke, heart attack and other vascular-related death. Its participants are African Americans who have suffered a stroke. In a study that appears in the January 14, 2002 issue of Neurology, investigators found low rates of awareness, treatment and control of major risk factors among study participants. The investigators performed baseline assessments with 1,086 patients, including medical and neurologic history, physical exam, CBC, metabolic profile, lipid profile and urinalysis.

     Nearly nine in ten patients had a history of hypertension, though one-fourth of those individuals took no medication for it. At the time of assessment, elevated blood pressure was found in more than half of those with a positive history of hypertension and no use of medication, and in more than two thirds of those who were taking antihypertensive medication. Approximately forty percent of patients also had known diabetes and/or high cholesterol. One-third of those with known diabetes demonstrated inadequate control of the disease.

     According to study author Sean Ruland, DO, of Rush University in Chicago, although study participants had already suffered a stroke, they controlled their risk factors at rates no better than the community at-large. Ruland concluded, “We must identify and address the underlying reasons why the African American population appears to be less aware of and/or less likely to control the risk factors contributing to our nation’s number one and number three killers.”

BD Biosciences licenses Stanford technology for proteomics and cell research
BD Biosciences has licensed technology and intellectual property developed by two researchers at Stanford University. The Methods and Composition for Detecting the Activation State of Multiple Proteins in Single Cells. Th technology is anticipated to enable scientists to use flow cytometry to detect the modified state of proteins within a signal transduction pathway. These signal transduction, or cellular, pathways are involved in a variety of metabolic functions and diseases.

     Using this technology, BD Biosciences will attempt to develop and commercialize tools to study the interaction of proteins within a given pathway. Insight into these pathways could lead to a more complete understanding of their effect on a variety of disease states such as cancer, AIDS, and other immune system disorders.