A nurse administers a flu vaccine during a clinic at the Giant food market in Fairfax, Virginia in this October 13, 2004 file image.
GoogleNews.com, October 14, 2009, by Kate Kelland — LONDON (Reuters) – Shaping the future of personalized medicine is not all about developing expensive new drugs — it will also mean revisiting older, cheaper medicines armed with new genetic knowledge.
Recent discoveries of genetic clues as to why medicines work better in some patients than others suggests combining new tests with old drugs will be a cost-effective approach — attractive to governments and insurance companies, experts say.
“There are two sides to personalized medicine — there is work in looking for new gene clues for the design of new drugs, and we are also doing a lot of work on currently used medications,” said Colin Palmer of Dundee University, whose role as head of pharmacogenomics puts him at the heart of work to use genetic information to personalize medicine.
“We’re trying to get rid of the one-size fits all approach … and create more effective drugs tailored to the individual.”
Few believe it is possible to make all drugs work for all patients all the time, but experts say the current situation — where many patients do not get any benefit — demands action.
Its easy to see why. According to a report by PricewaterhouseCoopers earlier this year, patient response rates to medicines “can be very low — varying from 20 percent to 75 percent, depending on the drug.”
It is no surprise that industry is under pressure to improve efficacy and safety, thereby making drugs more cost-effective.
It is already the case that more and more new drugs, particularly for cancer, are coming to market with a so-called companion diagnostic — a test allowing doctors to determine if a patient has the right genetic makeup to respond to treatment.
In Europe, there are around a dozen drugs — including GlaxoSmithKline’s Ziagen for HIV and AstraZeneca’s lung drug Iressa — that require the use of companion diagnostics.
And in the United States, the Food and Drug Administration requires patients be tested for genetic variants before taking Pfizer’s HIV drug Selzentry, Eli Lilly and Bristol-Myers Squibb’s Erbitux for colorectal cancer and Roche’s Herceptin for breast cancer, among others.
GENETICS AND GENERICS
But these are new and highly pricey drugs — and experts say payers may be more encouraged by recent studies which show genetic clues being found for response rates in generic drugs.
“In the last year or so people have been beginning to find gene markers in much more common areas,” said Donald Singer, a professor of clinical pharmacology and therapeutics at the University of Warwick’s medical school. “We are really on the cusp at the moment in terms of the cost effectiveness.”
While pharmaceutical companies would rather promote new drugs, he believes a better approach for payers may be to revisit old drugs armed with greater genetic knowledge.
A study published last week showed that common asthma drugs — salbutamol, a popular inhaler medicine also known as Ventolin, and salmeterol, an ingredient in Glaxo’s Advair — do not work in patients with a particular genetic make-up and may make things worse.
Another study showed that about half of patients given the generic drug tamoxifen as a hormone therapy in breast cancer have a genetic variation which helps them metabolize the drug — meaning they are likely to respond well — but 8 percent have a gene type which means it will not work.
Palmer’s team is also investigating the genes involved in defining whether a patient can respond well to statins, a class of drugs used by millions of people to try to lower cholesterol.
In some of these areas, scientists say a relatively cheap and easy test, such as a cheek swab or blood test, could be carried out to see ahead of time whether a patient is likely to respond well to the medicine usually prescribed.
“From the point of view of governments, testing and then going for the older off-patent drugs could be more cost-effective, rather than plowing money into new ones,” Singer said.
Experts in this field point to rapid acceleration in genetic technology since 2003 when scientists completed the Human Genome Project — a decade-long race to sequence all the DNA in people.
Some companies already offer a “genotyping service,” where you can send in a DNA sample and, for a fee, they give you a typing for as many as a million genetic variants.
For now such information is not widely useful without the ability to act on it, but as studies on common medicines reveal more about how and when they work, clinical knowledge about how to exploit those genetic variations to best effect is growing.
“In real life what you really want is to be able to go to your doctor, get a blood test which could lay out a genetic map, and then they prescribe based on the test results,” said Singer.
Fractal genome: Researchers theorize that DNA molecules inside the cell nucleus are packed into a compact, unknotted structure called a fractal globule (shown above), making it easy to pack and unpack. Adjacent regions in the linear chain of DNA are indicated using similar colors. Credit: Leonid A. Mirny and Maxim Imakaev
New technology reveals how DNA molecules pack themselves inside a cell nucleus
MIT Technology Review, October 14, 2009, by Emily Singer — Unfurled, the human genome would contain approximately six feet of DNA. Amazingly, all of that length is packed into a cell nucleus about three micrometers in diameter–roughly one-tenth the width of a human hair.
New technology that makes it possible to assess the three-dimensional interactions among different parts of the genome has revealed how these molecules are packed into such a tiny space. The findings could also yield new clues to genome regulation–how specific genes are turned on and off.
While scientists have previously been able to resolve the three-dimensional structure of parts of the genome, a new study is the first to do so on a genome-wide scale. “Our technology is kind of like MRI for genomes,” says Erez Lieberman-Aiden, a researcher in the Harvard-MIT Division of Health Sciences and Technology and one of the authors of a new paper detailing the work. (Lieberman was named to Technology Review‘s TR35 list young innovators this year).
DNA has multiple levels of organization–the linear sequence of bases, its famous helical structure, and higher-order formations that wrap it around proteins and coil it to form chromosomes. But identifying how DNA is organized at these higher levels across the genome has been difficult. “We have the entire linear sequence of the genome, but no one knows even the principles of how DNA is organized in higher-order space,” says Tom Misteli, a scientist at the National Cancer Institute, in Bethesda, MD, who was not involved in the study.
A growing pool of research also shows that this organization is crucial for regulating gene activity. For example, genes must be unwound before they can be transcribed into proteins. And some genes are turned on only when bound to DNA sequences on entirely different chromosomes, says Misteli. “That means they have to come together in three-dimensional space.”
In a new method, dubbed Hi-C, scientists first use a preservative such as formaldehyde to fix the three-dimensional structure of a folded DNA molecule in place. This way, gene sequences that are close together in the three-dimensional structure but not necessarily adjacent in the linear sequence become bonded together. The fixed genome is then broken into a million pieces using a DNA-cutting enzyme. But the DNA segments that were stuck together during the fixation process remain bonded together.
Researchers then add a marker called biotin to the ends of the bonded genome fragments and use another enzyme to glue the ends of each fragment together, making a circle of DNA. The biotin-marked pieces are then sequenced, revealing which pieces of DNA were physically close together in the three-dimensional conformation.
While scientists have been working on some aspects of the Hi-C technology for several years, the rapidly declining cost of gene sequencing has just recently made it possible to tackle the whole genome. “Only now, with the development of novel sequencing technologies, can we pull this off,” says Job Dekker, a biologist at the University of Massachusetts Medical School, in Amherst, and senior author of the paper. The findings are published today in the journal Science.
Using this new technology, the researchers identified two organizing principles in DNA. Chromosomes appear to be folded in such a way that active genes–those that are being made into proteins–are close together, and inactive genes are also close together, properties that had previously only been observed on a smaller scale. “The active stuff tends to be in one compartment that is not so densely packed,” says Lieberman. “The second compartment is like a storage compartment–it’s a bit denser and holds most of the genome.” Adds Dekker: “We think this is an efficient way for cells to organize chromatin within the nucleus.”
The researchers also developed a model for how they think DNA is organized within these active and inactive compartments. DNA molecules appear to form a polymer structure known as a fractal globule, in which segments that are close to each other in the linear sequence are also close in the three-dimensional globule. Lieberman likens the structure to a fresh packet of ramen noodles, before they are stirred into a tangled glob. “It suggests there is a kind of beautiful un-entangled structure that the genome folds into,” says Lieberman. “It has no knots, and a very simple physical process can be used to pull out a piece of fractal globule and then put it back.”
The technology makes it possible to tackle a number of questions, such as how the three-dimensional structure of the genome varies among cell types, among organisms, and between normal and cancerous cells. “Maybe this could help explain why cancer genomes are so misregulated,” says Dekker.
But it’s not yet clear how quickly the technology will catch on. While fast, cheap sequencing has made such experiments possible, “it is still a major undertaking,” says Misteli. That may change as prices continue to fall.
The researchers now hope to improve the resolution of the technology. Currently, they can examine the three-dimensional structure of the genome on a megabase scale–in units of a million DNA letters–but they are ultimately aiming for a kilobase resolution. “I think there are more structural features we haven’t discovered,” says Dekker. Increasing the resolution by a factor of 10 will require a hundredfold more sequencing, he says.
Scientists also want to explore exactly how the three-dimensional structure of the genome affects regulation. “What happens when you move a gene artificially from an inactive to an active area?” asks Dekker. “People have started to develop methods to move genes around in the nucleus, but the results are generally mixed.”
GoogleNews.com, October 14, 2009 — (Media-Newswire.com) – Researchers at Columbia University have developed a statistical method that accurately predicts how an organism will respond to dozens of commonly used drugs. This clinical and conceptual advance moves medical science a step closer to an era of personalized medicine-one where doctors could prescribe treatments based on an individual patient’s genome.
“Our study shows proof of concept and suggests how we should go about developing personalized medicine,” said Dana Pe’er, an assistant professor in the department of biological sciences and head of Columbia’s Computational Systems Biology Lab. “The hope is that one day you’ll go to the doctor, and for every disease you might have, they’ll say, ‘Here’s the medicine for you and the dose for you, and you won’t have side effects.'”
Professor Dana Pe’er and her co-authors, including doctoral student Bo-Juen Chen, worked with yeast as a model system. Their findings appear in the current issue of Molecular Systems Biology.
Unlike many other genomic-medicine studies that focus solely on DNA, Pe’er’s study relied on a combination of DNA and RNA data to predict drug resistance in yeast and identify the genes that cause it. RNA, which is synthesized from DNA, reflects which genes in a cell are turned off and on-information known as gene expression.
“RNA gives us a much more sophisticated measure than DNA of what’s going on in the cell,” said Pe’er.
She and Chen started with a set of data containing information on how well or how poorly 104 strains of yeast grew in the presence of 94 chemicals, or drugs. Each strain came with a genomic sequence and a gene expression profile. After identifying the genes responsible for variation among the strains, the team designed a computer function to determine, for each drug, which genetic features correlated with resistance. Pe’er and her coworkers then took previously untested strains of yeast and asked the computer to predict their level of resistance based on genomic and RNA data.
Their program, called Camelot, accurately predicted how well or how poorly the yeast grew in the presence of 87 out of 94 drugs. To test these results, they went back into the lab and genetically modified the yeast, deleting the genes they had identified as causing drug resistance. When they retested the modified yeast, exposing them to the drugs once more, they saw that the strains were no longer resistant, just as their model had predicted.
“To our knowledge, our approach is the first to systematically predict drug resistance and identify the genes that cause it,” said Pe’er.
The Institute for Palliative Medicine in San Diego officially launches PAL-MED CONNECT
California‘s first statewide consultative service for palliative care
GoogleNews.com, October 14, 2009 — SAN DIEGO, Oct. 13 /PRNewswire-USNewswire/ — Health care professionals in California communities lacking palliative medicine resources can now access top quality palliative care consultative and educational support through a new hotline provided by The Institute for Palliative Medicine.
Palliative care provides advanced pain and symptom management to those
suffering from complex chronic or life-limiting illnesses. Now physicians,
physician assistants, nurse practitioners and clinical pharmacists anywhere in
the state can call and get help providing the best possible care for those
suffering and in need of palliative care.
The hotline, formally called the “California Palliative Care Consultation
Center Hotline,” is better known as PAL- MED CONNECT. Launched in the San
Diego region in July, it is now available across California and can be
accessed by calling (toll free) 1-877-PAL-MED4. There is also a companion web
site at www.palmedconnect.org.
“The need for access to consultative resources in palliative care is great,”
noted Dr. Charles von Gunten, Provost of The Institute for Palliative
Medicine. “Yet there are only 273 board-certified palliative care physicians
in California and many smaller communities and rural areas don’t have any to
serve their residents. As our population ages, the need will only increase. We
want this hotline to become the lifeline that helps caring professionals bring
Californians relief from suffering.”
PAL-MED CONNECT is made possible through a grant from UnitedHealth Group.
“Thanks to the grant from UnitedHealth Group, we can share everything we’ve
learned from our research and our clinical practice at The Institute by phone
and online with physicians, nurse practitioners, and clinical pharmacists
caring for seriously ill patients,” said Helen McNeal, Executive Director of
The Institute for Palliative Medicine. “We expect this resource to make a
significant difference in the lives of many patients and their families by
connecting their healthcare professionals with specialized information,
advice, and resources.”
To date, the most popular topics among callers accessing PAL-MED CONNECT have
been on safely prescribing opioids, converting between different therapies,
pain management and having difficult family conversations. Despite formally
operating only in San Diego until today, calls have come from as far away as
Oklahoma and New York, demonstrating the critical need for this resource.
The experts at The Institute for Palliative Medicine have been providing
outstanding education and research for 20 years since its founding as the
Center for Palliative Studies in 1989. The Institute for Palliative Medicine
has achieved international recognition for its innovative education programs,
patient/family-centered research and evidence-based advocacy. In 2006, The
Institute for Palliative Medicine helped pioneer the palliative medicine
subspecialty approved by the American Board of Medical Specialties.
About The Institute for Palliative Medicine
The Institute for Palliative Medicine is internationally recognized for its
excellence in palliative care education and research. Located on the campus of
San Diego Hospice in San Diego, CA, The Institute for Palliative is the home
of the PAL-MED CONNECT Hotline and is dedicated to the relief of suffering
through the transformation of health care. It focuses on discovering,
demonstrating and disseminating strategies for palliative care in existing
health care systems whether here in San Diego or throughout the world.
Physicians and healthcare professionals from around the globe come to The
Institute for Palliative Medicine to study. Home to the country’s largest
palliative medicine physician fellowship program, the Institute also provides
education to more than 1700 health care students and professionals each year.
For more information, visit online at www.sdhospice.org
CONTACT: Melissa DelaCalzada, The Institute for Palliative Medicine,
SOURCE San Diego Hospice and The Institute for Palliative Medicine
Melissa DelaCalzada, The Institute for Palliative Medicine, +1-619-278-6139;
Flying wing: The Boeing X-48B, an unmanned prototype with a 6.4-meter wingspan, has a blended-wing design that could one day replace that of today’s commercial planes. Credit: NASA
Advanced technology won’t be enough for the industry to meet its own greenhouse-gas targets
MIT Technology Review, October 14, 2009, by Kevin Bullis — Last week the global aviation industry called on the United Nations to establish a single, worldwide policy for reducing aviation greenhouse-gas emissions, in an attempt to avoid a costly network of regional regulations. The industry proposed two primary goals–that by 2020 it should stop increasing its greenhouse emissions, and that by 2050 it should cut its emissions by 50 percent compared to 2005 levels.
These goals, while less stringent than the 80 percent reductions proposed for the rest of the world’s economy, may nevertheless prove too ambitious, some experts say. Furthermore, an array of potential technologies that could significantly reduce emissions will be difficult to deploy quickly in an industry that is reluctant to take on the cost and risk of radical innovation and that can take decades to replace old airplanes.
Whichever new technologies do get implemented may not be enough to keep up with the industry’s growth. Each year the industry reduces fuel consumption by improving efficiency by 1.5 percent to 2 percent. But each year people fly more–the industry is expected to grow by 4 percent to 5 percent–overwhelming fuel savings from efficiency.
Part of the problem is that it takes the industry as long as 20 to 30 years to replace planes. This means that the efficiency improvements of planes introduced in 2010 won’t be seen throughout the fleet until 2025 or later. If things continue as they have been in recent years, by 2050 the industry will have to fly “three times as many airplanes with only half as many emissions,” says Ian Waitz, a professor of aeronautics and astronautics at MIT and director of the Partnership for Air Transportation Noise and Emissions Reduction. “It’s a tremendous challenge,” he says. The challenge is so great that climate-change policies may force a tradeoff–requirements to cut emissions may increase prices and slow the growth of the industry.
The aviation industry can limit its emissions in three basic ways–making airplanes more efficient, improving logistics to waste less fuel, and replacing fossil fuels with biofuels. But some potential technical improvements are limited because of the engineering requirements of airplanes. For example, it’s conceivable that batteries and electric motors could one day replace internal combustion engines in cars. But batteries don’t store enough energy to transport a commercial airliner across the Pacific.
With these limitations in mind, by 2020, new technologies could make aircraft about 20 percent to 35 percent more efficient, on average, than planes today. Fuselage coatings and adjustable wings, among other things, could reduce drag. Engines that run hotter and at higher pressures would use less fuel, as would engines that use gears to optimize the speeds of different parts of a turbine, and open-rotor designs that resemble and have some of the efficiency advantages of turboprops.
The weight of airplanes could be decreased by using composite materials, for example, or replacing heavy wiring with lighter fiber optics. Some of these advances have already been incorporated into new airplanes. Airbus’s A380 and Boeing’s 787, for example, are expected to reduce fuel consumption by something like 17 percent to 20 percent. Beyond 2020, the industry could employ more radical designs. It could abandon the ubiquitous tube-and-wing design of airplanes, for example, in favor of something called the blended wing. The entire airplane would essentially be a wing, increasing the amount of lift it generates and reducing fuel consumption by perhaps 25 percent. Such a design has been considered for many decades but has yet to be used for commercial aircraft, although a variant was used for the military’s B-2 bomber.
Improving flight logistics could shave another 8 percent off fuel consumption by 2020. With cooperation from governments, it may be possible for planes to fly more direct routes. Better air traffic control technologies could also reduce the amount of fuel planes waste idling on the runway or waiting to land.
Finally, advanced biofuels could decrease carbon emissions by about 5 percent by 2020, according to aviation industry estimates. The contribution from biofuels is highly uncertain, however, and existing biofuels–ethanol and biodiesel–won’t work in today’s airplanes for a variety of reasons. Ethanol simply doesn’t store enough energy, and it introduces safety concerns because it’s much easier to ignite than jet fuel. Biodiesel would require heating at cold temperatures, and, more important, it breaks down at high temperatures, says James Hileman, associate director of the Partnership for Air Transportation Noise and Emissions Reduction. That leaves only advanced biofuels, such as hydrocarbons that are almost identical to jet fuel and can be made by refining oils produced by algae. But so far these are very expensive and available only in small quantities. In the distant future, alternative fuels such as liquefied hydrogen might help, but large obstacles remain, including the difficulty of storing liquid hydrogen on an airplane.
There are many possibilities for reducing emissions, but even the aviation industry acknowledges they won’t be adequate to meet its goals. The industry will likely exceed its emissions cap by 90 million tons of carbon dioxide in 2025, says Quentin Browell, assistant director for environmental issues in aviation at the International Air Transport Association, the group that announced the emissions goals. To make up for this, it will have to purchase offsets–essentially paying other industries to reduce emissions.