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[maywillow] 01/2/2005 20:41

Posted on Wed, Jan. 26, 2005





New Roche DNA chip could be boon

By JUDY SILBER

Contra Costa Times (Walnut Creek, Calif.)


WALNUT CREEK, Calif. - Ever since 2000, scientists have hyped personalized medicine as a natural outcome of the much-ballyhooed human genome project. They predicted that the new knowledge would soon be commonly used to improve patient care.

But five years later, the practice of personalized medicine - targeting drugs and dosages to specific patients - has been limited. When it comes to prescribing drugs, genetics and DNA are still mostly ignored.

Researchers say a DNA chip developed at Pleasanton, Calif.-based Roche Molecular Systems and approved by the U.S. Food and Drug Administration two weeks ago may help change that. They say Roche's DNA chip may usher in a new era, where genetics plays an increasingly important role in defining patient care.

"It's a very important milestone," said Jorge Leon, president of Leomics, a molecular diagnostics consulting firm. "Roche is taking a leadership position to pave the way."

Roche's test known as the AmpliChip CYP450 focuses on two enzymes that can strongly influence how the body responds to many drugs. The idea behind the chip is to determine whether a patient processes drugs at a normal, slow or fast rate. In this way, doctors can more easily prescribe appropriate medications and dosages.

For example, if someone processes drugs slowly, they will likely do better on a lower dosage. A higher dose may work better for a patient who processes drugs quickly.

This biology has been well understood for a while, but until now, there has been no simple way to screen for differences.

Instead, doctors have traditionally relied on trial and error. The majority of patients might respond well to the recommended dosage. However, a minority would not, experiencing bad side-effects, or not seeing any benefits.

Among Caucasians, about 8 percent process the affected drugs slower than normal. Roche has also found that about 4.5 percent of African-Americans and Latinos process the drugs much faster than the normal rate.

The size of a thumbnail, the AmpliChip contains 15,000 short stretches of DNA, representing 31 genetic variations in two enzymes that belong to a family of genes called cytochrome P450. According to Roche, the two enzymes affect 25 percent of commonly prescribed medications, including anti-depressants, anti-psychotics, beta-blockers, tamoxifen and benzodiazepines.

The wide applicability made the enzymes an obvious first choice for a genetic test, said Walter Koch, vice president and head of research for Roche Molecular Systems, a division of F. Hoffman-La Roche Ltd.

"We wanted to start with what made the most sense and impacted the largest number of drugs," Koch said.

Still, Roche has hard work ahead to gain acceptance. It must first prove that its test really can help patients. It must also demonstrate that the test can save money by avoiding costly and unpleasant side-effects. Roche has not yet set a U.S. price for the test. Roche charges 400 euros in Europe, or about $521.

The field of psychiatry is an obvious first marketing target. It can take weeks for patients to respond to many psychiatric drugs. So the sooner doctors can figure out the proper dose, the better. However, even among psychiatrists, Roche does not expect the AmpliChip to take off with a bang.

"We expect there to be slow adoption at first," said Tita Forrest, head of commercial marketing for genomics at Roche Molecular Systems. "Psychiatrists are still unaware of how this can help them in their every day practice."

In fact, while much basic research has been done on the cytochrome P450 enzymes, data are still scant on the AmpliChip.

"You have to know if it really works in clinical practice," said Peter Wedlund, an associate professor at the University of Kentucky's College of Pharmacy.

So far, the data look good for at least one drug. In a study with Roche, Wedlund looked at patients on the anti-psychotic risperidone. Using the AmpliChip, he found that patients who had experienced bad side-effects also carried predicted variations in DNA.

Now Wedlund is tackling the cost side. In a new study, he's looking to see whether it costs more to treat psychiatric patients who process drugs slower or faster than normal.

"If you're an HMO or running a hospital, you want to know the bottom line," Wedlund said. "It's nice to say you want this patient to do better. But you want to know if it's worth it financially to invest in a new technology."

The sentiment is echoed by Kaiser Permanente. Before it authorizes use of the chip, Kaiser needs evidence that it changes patient outcomes, said Doug Monroe, a drug information pharmacist for Kaiser Permanente.

"Obviously, there's a potential," Monroe said. "We just don't know what it is."

[ariane] 15/1/2005 07:09

Nano World: DNA meets nanotechnology
By Charles Q. Choi
UNITED PRESS INTERNATIONAL
Published January 14, 2005


NEW YORK -- DNA and related nucleic acids help assemble life as we know it, but now scientists hope to employ those same complex molecules in nanotechnology to assemble electronics and even microscopic robots -- in as soon as five years.

"Imagine having a cathedral with all its pieces on the floor, and having all those bricks assemble into a defined structure -- this is the kind of idea we can truly foresee with nucleic acids, to assemble these complex structures with molecules," said biochemist and biophysicist Luc Jaeger at the University of California, Santa Barbara.

DNA molecules are best known for carrying the genetic instructions for all organisms, but 25 years ago nucleic-acid-nanotechnology pioneer Ned Seeman of New York University began envisioning another realm of applications for them -- as construction blocks, perhaps even in machines.

The result: "DNA machines have been built, as a route to nanorobotics," Seeman told UPI's Nano World. "Nanofacturing of new and revolutionary materials is going to result from some of these devices."

At times, a normally double-stranded DNA molecule can unzip a bit and form a branched version of itself. Seeman foresaw it was possible to weave these branches into three-dimensional structures capable of self-assembly.

To explain, a strand of DNA is made of four bases known, respectively, as A, T, C or G. Each base pairs up with another in a very specific way -- A only pairs up with T, and C only pairs up with G, for example. This means any sequence of bases -- say ATCG -- will only pair up with its complementary sequence -- in this case, TAGC.

By synthesizing a double-stranded DNA molecule and unzipping it partially, its branches will stick automatically with complementary sequences on other branched DNA -- like a molecular jigsaw puzzle. Mix DNA molecules together the right way and they should assemble into useful structures.

Modern technology allows laboratories to synthesize long strands of DNA at will in any sequence. This means nucleic acids potentially can hold a tremendous amount of information. In turn, scientists in theory can weave extraordinarily complex structures from DNA.

"We can basically create matter that is intimately programmable," Jaeger said.

In addition, nucleic acids "are a really nice material to connect molecules onto, metallic nanoparticles, carbon nanotubes," said chemist Hao Yan of Arizona State University in Tempe.

"Imagine 100 different molecules able to assemble into these intricate architectures, each positioned in an exquisite fashion, each able to be functionalized a different way. You can have this intricate control of the arrangement of matter," Jaeger said.

"If you try to build, say, a box from inorganic stuff, its corners are going to be basically identical. But with DNA, you can have goody type one in corner one, and goody type two in corner two," Seeman said. "You can have all these different functions together."

Nucleic-acid nanotechnology could help organize electronics components together in as soon as "maybe five years," Seeman predicted. "Molecular electronics should be smaller and faster as a consequence of nucleic-acid nanotech."

In time, the hope is to improve nucleic-acid nanotechnology to arrange organic molecules as well. Crystals of DNA could cage molecules that normally do not form into crystals on their own, allowing, for example, X-ray techniques to image their molecular structures -- something of critical importance in drug design and other research.

Yan's team is working on a self-assembled DNA array for extraordinarily rapid gene sequencing.

"Imagine having a 1-centimeter array having 1 billion sequencers," he said.

Creating scaffolds for inorganic electronic components or organic molecules comprise in principle the same process, but Seeman cautioned although electronics components such as metal nanoparticles could be 2 nanometers or 3 nanometers wide -- or billionths of a meter -- the organic molecules researchers would like to encase in DNA crystals are roughly one-tenth of that size.

"The criteria there are more stringent," he said.

Scientists already are creating devices from nucleic acids. In the Dec. 17 issue of the journal Science, Seeman and colleagues revealed they created a device from DNA that mimics the ribosome -- the protein factory of the cell -- for potential use in developing new synthetic fibers. In the future, they foresee nucleic-acid devices with DNA strands that move in space working as nanorobots.

"Imagine if you have self-assembled arrays from DNA and incorporate robots into them, you can have them all working together, for instance, in a device that could control medical reactions in the body," Yan told Nano World.

"You wouldn't have these DNA robots just running around, but rather as components in nanofactories the same way that on a larger scale you (use) robots to make cars," Seeman clarified.

"Of course, you still need to figure out how to incorporate these self-assembled arrays and nanorobots together," Yan added. "That's a challenging problem."

Nucleic-acid nanotechnology faces a number of other challenges. Scientists largely have conquered the problem of organizing DNA in two dimensions, but moving up to three dimensions remains difficult. DNA also possesses an electrical charge, which can be troublesome when attempting to build nano-sized scaffolds for electronics.

Aside from DNA, scientists are investigating other nucleic acids for use in nanotechnology. For instance, PNA, or peptide nucleic acids, which are designed to mimic DNA, could prove more chemically robust. They also do not possess that troubling charge DNA does. Other nucleic acids include TNA, which uses the sugar threose instead of DNA's deoxyribose.

Jaeger is experimenting with RNA, which in cells helps create proteins. RNA in certain ways is less chemically stable than DNA, but "it has a natural characteristic to be much richer in diversity of these exquisite structures," Jaeger said.

Another potential molecule of interest is LNA, or locked nucleic acids, which mimic RNA instead of DNA.

A critical factor in developing killer applications for nucleic-acid nanotechnology is a method to correct for assembly errors.

"So far, self-assembly happens in the tube, and there are defects in the superstructure when making them. If we move to replicating in large quantities, we have to have error correction, just as in cells in the body," Yan said.

Nano World is a series examining the exploding field of nanotechnology, by Charles Choi, who covers technology for UPI Science News. E-mail: [e-mail]

[grupo] 12/1/2005 07:18

ZURICH (AFX) - Roche Holding AG confirmed that the US Food and Drug
Administration (FDA) has approved its microarray-based test, the AmpliChip
CYP450 Test, for diagnostic use in the US.
The test analyses a patient's DNA and helps doctors in choosing medication
for a wide variety of common conditions such as cardiac diseases, pain and
cancer, the Swiss drugs and diagnostics group said in a statement.
The test was launched in Europe in autumn 2004.
scs/jfr

[waldron] 05/1/2005 21:04

Maclyn McCarty, put DNA in the map

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BY DELTHIA RICKS
STAFF WRITER

January 5, 2005

Dr. Maclyn McCarty, the last surviving member of the Manhattan team who provided the world's first convincing evidence that genes are made of DNA, died Sunday in Manhattan of congestive heart failure. He was 93.

As a professor at Rockefeller University and as a former physician-in-chief at Rockefeller University Hospital, McCarty brought an unmatched level of creativity and inquisitiveness to some of the more profound questions in mid-20th century science, fellow researchers say.











The DNA discovery was so important that scientists remain surprised that McCarty and his colleagues, Dr. Oswald T. Avery and Colin MacLeod, did not win the Nobel Prize for their groundbreaking work in 1944.

Avery, who led the group, had been attempting to unravel the mysteries of the spiraling molecule since 1928. When McCarty joined the project in 1941, bringing his strong skills in biochemistry to the task, the answer began to quickly unfold.

Nobel Prize winner Dr. Joshua Lederberg, Rockefeller's president emeritus, a longtime colleague and friend, wondered why the pioneering team was overlooked for the top honor in science.

"Many Nobelists have said this was the biggest mistake the Nobel committee ever made, by not awarding the prize to Avery and his group," Lederberg said yesterday.

"This was the pivotal discovery in biology in the 20th century because it really put DNA on the map. Once that work was done you really couldn't think much about genetics without thinking about DNA," Lederberg said. "Genes were no longer mysterious and inscrutable. Mac helped give [genes] personality as well as importance."

Without the 1944 discovery, it would have taken years for scientists such as James Watson, Francis Crick and Maurice Wilkins to determine DNA's structure, as they were able to do in 1953. Watson, Crick and Wilkins were awarded a Nobel Prize for their work.

Despite having been passed over for the Nobel, McCarty won dozens of scientific honors, including in 1994 the prestigious Albert Lasker Award for Special Achievement in Medical Science. Rockefeller University honored McCarty in 2001 with the Centennial David Rockefeller Award for Extraordinary Service to The Rockefeller University.

McCarty was born in South Bend, Ind., on June 9, 1911, and graduated from Stanford University in 1933. In 1937 he received a medical degree from Johns Hopkins University and specialized in pediatrics.

He achieved world reknown for his work with streptoccocal bacteria, the cause of rheumatic fever and once a formidable killer of children. He made inroads in the early 1940s in studies of sulfonamide medications, forerunners to modern antibiotics.

Twenty years ago McCarty authored the book, "The Transforming Principle," his recollection of the events leading to the discovery that DNA was indeed the hereditary material and the basic blueprint of life. Until last year he served as the editor of the Journal of Experimental Medicine.

"He was the most genial, generous, thoughtful, considerate, insightful and compassionate person you'd ever want to meet. We all admired what he had done," Lederberg said, adding McCarty helped pave the way for modern molecular biology.

McCarty is survived by his wife, Marjorie of Manhattan; two sons, Richard E., and Colin Avery McCarty; a daughter Dale Dinunzio; eight grandchildren and five great-grandchildren. Funeral plans are pending.

[grupo guitarlumber] 15/11/2004 13:12

Forensic science degrees queried

Students hoping to be the next Sam Ryan may be disappointed
Concerns have been raised about the content of forensic science courses, following a surge in their popularity.
Television dramas like Silent Witness and Waking the Dead have led many students to apply for such courses.

But the Science, Engineering and Manufacturing Technologies Alliance (Semta) says the content is often not sufficiently rigorous.

Semta warns many courses are hybrids, which do not offer the pure science degrees most police forces prefer.

The report calls for better quality controls to be brought in to monitor the quality of the 350 forensic science courses on offer.

A degree in chemistry or some other pure science to be preferable to a degree in forensic science

Semta report
Semta's director of science and technology, Richard Smith, said: "Forensic science in its own right has been a success story, in that it has attracted young people to study science, perhaps when they would not have done so before."

And he praised universities for having seen an opening for science.

"What universities have done in their own right is quite remarkable, in that they've seized a marketing opportunity.

"And they've done an extremely good job in being able to promote science, which is great."

Pure science

But the major concern was that graduates from these courses did not have the detailed grasp of chemistry required by employers.

"Both forensic science and other science employers consider a degree in chemistry or some other pure science to be preferable to a degree in forensic science," the Semta report warns.

"The few science employers who had knowledge about forensic science degrees criticised the course content for lack of clarity and consistency."

Richard Smith said action must be taken for the future: "If we don't get science right now, there is likely to be a paucity in the future and that is not going to address the real skills issues of 2014."

A range of groups, including university course lecturers, students, police forces, drugs companies and other science employers were questioned for the report.

[ariane] 12/11/2004 07:04

Test could spot Alzheimer's early
By Paul Rincon
BBC News science reporter



A clinical assay could be ready within two years
A new nanotechnology-based technique could lead to a test for diagnosing the early signs of Alzheimer's disease.
The Bio-Barcode-Assay can recognise ADDL, a protein that accumulates in the brains of sufferers.

It is a million times more sensitive than conventional tests and could revolutionise disease detection.

In future, it might form the basis not only of a test for Alzheimer's but also for types of cancer, the human form of mad cow disease and HIV.

The next exciting step would be to move to blood. If you detect it in blood, you have a huge win

Professor Chad Mirkin
Details of the technique have been outlined at a one-day conference in London.

Until now, doctors had no way of diagnosing Alzheimer's disease in their patients. The disease could only be confirmed after death, by studying brain tissue.

"Diagnosis [of Alzheimer's] is 100% accurate post-mortem. What you want is the ability to detect the marker so you can begin to think about new types of therapies," said Professor Chad Mirkin, of Northwestern University in Evanston, US.

Professor Mirkin and his research group at Northwestern developed the highly sensitive test by manipulating molecules at the nanometre scale (one billionth of a metre).

"We have done the first set of experiments that quantify the number of ADDLs in cerebrospinal fluid," Professor Mirkin said.

'Exciting step'

ADDLs are protein bundles which attack nerve synapses in the brains of people with Alzheimer's.

"Nobody is able to study this with the existing tools. A nanotechnology-enabled tool is allowing us to study these kinds of markers and link them to disease.

"The next exciting step would be to move to blood. If you detect it in blood, you have a huge win."

To perform a Bio-Barcode-Assay, researchers select antibodies on the basis of the biomarker they need to detect in a solution.

Some antibodies are fixed to magnetic particles while others are attached to spherical gold particles just 30 nanometres in diameter. Strands of DNA are fixed to the gold nanoparticle.

When antibodies bind to a target biomarker, it becomes sandwiched between a magnetic particle on one side, and a gold particle and its strands of DNA on the other.

Applying a magnetic field brings this entire "complex" out of solution. Researchers then release the DNA strands and use a DNA detection device to recognise their signature sequences.

A research assay could be available to scientists within a year, Professor Mirkin said. A clinical assay could be commercialised within two, he added.

Professor Mirkin said it could also lead to a test to diagnose breast cancer by detecting the faint presence of a protein called PSA, normally associated with prostate cancer in men.

It could also form the basis of a new test for HIV and other diseases in blood screening.

The test could be used in GPs' surgeries as well as hospitals, or even by members of the public at home.






OTHER LINKS

[jl202] 09/1/2003 14:45

I was talking about .. not the sheep!

[jl202] 09/1/2003 14:42

balto, its been playing on my mind,,
Its the spiky red hair, terrier like eyes and small ears -- call me a cynic, but I bet he used blusher to cover up his freckles at Eton. Also, he hangs around in pubs and smokes joints - clearly (edit: allegedly) a commoner :)

[m.t.glass] 09/1/2003 14:22

What? Incest?
That sounds even worse.
Go wash your mouth out!

[execline] 09/1/2003 14:16

Charles Spencer

[m.t.glass] 09/1/2003 14:08

......... M.J.Hewitt.............................. Harry Hewitt? Surely not.


I mean... - if there were any truth in it, surely MJH would put the millions he's about to make from selling Diana's letters towards the upkeep of his child wouldn't he? (Harry was apparently already a toddler when Hewitt first met Diana)(Anyway the ears are wrong)

[balto] 09/1/2003 13:55

Then we have ADVFN filling my screen with green, orange, blue.........actually......well done advfn.