July 1999

J. Craig Venter is no stranger to contradiction and controversy. He seems to thrive on it. In 1991, when the National Institutes of Health was haggling over patenting expressed sequence tags (ESTs)--a shortcut to identifying protein-encoding genes--Venter the inventor accepted a private offer to found The Institute for Genomic Research (TIGR) in Rockville, Md. TIGR would discover ESTs and give most of them to a commercial sibling, Human Genome Sciences (HGS), to market. ESTs are now a standard

On Dec. 17, 1998, Iceland's parliament, the Althing, gave the go-ahead for a Delaware-based biotechnology company, deCODE Genetics Inc., to use existing health and genealogy records to establish a nationwide "health sector database ... with the aim of increasing knowledge in order to improve health and health services."1 The public's participation was presumed--citizens were given six months to "opt out" of the plan. By June 17, 1999, with only about 9,000 of the country's 270,000 residents of

SNP CENTRAL: A genetics researcher takes to the bench at the Wellcome Trust's Sanger Centre in Cambridge, England. The sequencing center and its London sponsor provided key leadership in the SNP Consortium, a public-private venture to find and map 300,000 single nucleotide polymorphisms. The Wellcome Trust helped entice 10 pharmaceutical firms to join the consortium by putting up $14 million of the project's estimated $45 million price tag. The Sanger Centre will provide much of the radiation h

Steps in positional cloning. Positioning of disease loci to chromosomal regions requires multidisciplinary collaborations. "You have a clinician out in Israel gathering patients, a medical geneticist doing genetic mapping, my lab doing physical mapping, and Washington University sequencing. All these things come together and, boom, in record time you have this gene," says Green. Green goes on to point out that this is a classic example of finding a gene from sequences the Human Genome P

Technological developments helped make single nucleotide polymorphism (SNP) databases possible. But further innovations will be necessary to make those records of thousands of genetic variations useful. Francis Collins, director of the National Human Genome Research Institute, remembers a swell of developments that crested in 1996. "The technology for finding SNPs seemed to be moving along pretty well," he recalls. "You could imagine getting a pretty good set." Enabling technologies included

The SNP Consortium collaboration of 10 pharmaceutical companies and the Wellcome Trust will spend $45 million over two years to identify and map about 300,000 randomly generated SNPs. The industry partners are AstraZeneca (London); Bayer (Pittsburgh, Pa.); Bristol-Myers Squibb Co. (New York); F. Hoffmann-LaRoche (Nutley, N.J.); Glaxo Wellcome (Research Triangle Park, N.C.); Hoechst Marion Roussel (Kansas City, Mo.); Novartis (Basel, Switzerland); Pfizer (New York); Searle (Skokie, Ill.); and S

1982 The Human Polymorphism Study Center, the first academic institution to propose the systematic study of polymorphisms, is founded in Paris. Its primary objective: to make an inventory of all possible polymorphisms in the human population and associate them with diseases. However, the technology to take on such a project would not be advanced enough for more than a decade. 1995 An initiative led by the Wellcome Trust, of Cambridge, England, to form a consortium of pharmaceutical companies,

The 1997 resurrection of a snippet of Neandertal mitochondrial DNA electrified human paleontology and attracted wide media attention.1 By comparing the number of base changes in that Neandertal sample to variability in modern humans, scientists concluded that a common African ancestor existed about 600,000 years ago, far earlier than the generally accepted origin of modern humans about 150,000 years ago. And while Neandertals were still around as late as 30,000 years ago, it's unlikely that mod

if (n == null) The Scientist - Are We There Yet? Researchers Differ on When a Genome Sequence Is 'Complete' The Scientist 13[15]:12, Jul. 19, 1999 News Are We There Yet? Researchers Differ on When a Genome Sequence Is Complete By: Karen Hopkin A great deal of fanfare and much celebration greeted the publication of the C. elegans sequence in Science this past December.1,2 "Caenorhabditis elegans made it big today as Human Genome Project researchers in

if (n == null) The Scientist - Promise and Problems Loom for Stem Cell Gene Therapy The Scientist 13[15]:0, Jul. 19, 1999 News Promise and Problems Loom for Stem Cell Gene Therapy By Paul Smaglik Photo courtesy of Harry Malech A network of gas-permeable plastic bags connected by tubing helps make ex vivo stem cell gene therapy more feasible. The insides of the bags are coated with recombinant human fibronectin fragments. That protein helps more r

If the size of a society provides a reading of the health of a field, gene therapy may be heading for a fruitful stretch. The American Society of Gene Therapy (ASGT) attracted 600 abstracts and 1,700 participants to its inaugural meeting in Seattle last year, compared to 1,000 abstracts and 2,100 participants to its second annual meeting in Washington, D.C., last month. In a conversation with News Editor Paul Smaglik, James Wilson, ASGT president and director of the University of Pennsylvania's

The Scientist 13[15]:2, Jul. 19, 1999

Edited by: Eugene Russo Reprinted with the permission of Nature and The Institute for Genomic Research Circular representation of the H. pylori chromosome. The outer concentric circle is the predicted coding region on the plus strnd; the second concentric circle is the predicted coding region on the minus strand. At the third and fourth concentric circles are insertion sequence (IS) elements (red) -- short DNA sequences in bacteria capable of transposing to a new genomic location -- and other

Edited by: Eugene Russo F.R. Blattner, G. Plunkett, C.A. Bloch, N.T. Perna, V. Burland, M. Riley, J. Collado-Vides, J.D. Glasner, C.K. Rode, G.F. Mayhew, J. Gregor, N.W. Davis, H.A. Kirkpatrick, M.A. Goeden, D.J. Rose, B. Mau, Y. Shao, "The complete genome sequence of Escherichia coli K-12," Science, 277:1453, 1997. (Cited in more than 490 papers since publication) Comments by Fred R. Blattner, professor of genetics, University of Wisconsin, Madison The utility of obtaining the whole genome s

if (n == null) The Scientist - Commentary: Even in Prosperity, Long-Term Investments Are Key The Scientist 13[15]:18, Jul. 19, 1999 Opinion Even in Prosperity, Long-Term Investments Are Key By: Gerald Dinnen Suddenly many of the old threats to the U.S. economy do not seem very threatening. Inflation is nonexistent. The federal deficit has been eliminated. And--at a time when our gross domestic product, productivity, and disposable income are reaching n

In a news article in The Scientist titled "Managers on a Mission,"1 I learned that my long-time fear had come to pass: Mr. Chips is really dead. Although his illness, initiated in part by managed care and declining availability of National Institutes of Health research dollars need not have been terminal, the adoption of mission-based management by university medical schools across this nation promoted his demise. In this article, Robert Jones, executive director of the American Association of

While some institutional administrators may view scientists as merely sources of revenue, basic research cannot be fundamentally described as a "business,"1 since it can flourish in the absence of commodities, transactions, and markets. Given the tremendous research advances during the past century, it is curious that academic scientists (and the government that supports them) would permit a business management regime to replace the academic freedom and intellectual independence that have serve

Kudos for exposing the power of industry to make a mockery of true science.1 "He who hath the gold, makes the rules" has no place in the realm of science. Breast implant science is 30 years behind itself because of unfavorable studies such as those described in this phenomenal exposé, which were hidden. To date, doctors still describe silicone as being safe and inert and state that it doesn't migrate throughout the body. Let's keep examining these and other serious conflicts of interest

if (n == null) The Scientist - Trickle-Down Genomics: Reforming ""Small Science"" As We Know It The Scientist 13[15]:19, Jul. 19, 1999 Opinion Trickle-Down Genomics: Reforming "Small Science" As We Know It By Edward J. Smith Each generation attempts to develop programs and activities that help it fulfill the ancient Chinese wish "May you live in interesting times." These are indeed interesting times from the perspective of the biologist: The complete geno

Kelly Taylor Not long ago, a young couple entered Deborah Lochner Doyle's office with a dilemma that most people, thankfully, never have to face. Their 6-year-old child had been born with cystic fibrosis (CF), a common genetic disease that results in chronic lung infections and usually kills by the age of 30. The couple had become pregnant again and had come in to have the fetus tested. Though neither parent had CF, both carried one flawed copy of the cystic fibrosis transmembrane receptor

In the rush to sequence every gene in existence researchers need to increase their capacity and throughput. However, the ability to sequence samples quickly is fruitless if the quality of the DNA is poor. Sequencing of double-stranded DNA can complicate the process because it may produce a less clean read-through of the gene fragment of interest than a single-stranded starting template would. On the other hand, manual preparation of single-stranded DNA can be time consuming and result in decrea

CLONTECH's SMART RACE cDNA amplification process diagram On your mark, get set, go! And the RACE is on to obtain that potentially elusive full-length cDNA for characterizing the best gene ever. In the molecular biology arena, RACE refers to rapid amplification of cDNA ends, a PCR-based cloning strategy used to obtain clones representing transcripts of the int-2 gene, expressed at low abundance in the early mouse embryo.1 Traditional methods of cDNA production, such as constructing and screenin

Table of Carbohydrate Products Model of glycoprotein supplied by Seikagaku America Glycobiology. It has been called the "last frontier of pharmaceutical discovery." Hampered by a lack of economical and convenient tools, however, advances in glycobiology have been largely overshadowed by the rush to exploit PCR and the ready availability and comparative simplicity of the tools and enzymes for molecular biology. But that is changing. By all reports, the field of glycoprotein and carbo

Date: July 19, 1999Mutation Detection Systems and Methods Affymetrix's p53 chip Researchers leading the Human Genome Project (HGP) originally envisioned completion of the entire genome sequence (approximately 3 billion base pairs) by the year 2005. Recently the arena of human genome sequencing has seen a lot of heat generated by the entry of both commercial entrepreneurs and public consortia. Celera, a company formed by highly skilled and competent commercial organizations (TIGR and Perkin-Elm

ALZHEIMER'S VACCINE It's the classic vaccine approach: Get protection against a disease by training the body's immune system, using a bit of the disease itself, to respond to infection in force. Typically applied to infectious diseases such as smallpox or polio, immune system-boosting treatments have more recently been aimed at cancerous tumors. Now a recent paper suggests that Alzheimer's disease (AD) might be effectively treated by priming the immune system with a form of the damaging, neuro