Personalized Medicine

This DNA sequencing machine from Illumina is capable of reading over five billion bases per day.  Credit: Illumina

DATA SHOT

3,669

The number of genes currently known to be associated with diseases, out of an estimated total of 20,000 to 25,000.

MIT Technology Review, March/April 2010, by Emily Singer  —  The majority of genetic diagnostic testing is done with sequencing, which identifies each base, or “letter,” in a string of DNA. Sequencing can be used to identify all of the roughly three billion base pairs in a human genome, but most clinical testing is limited to sequencing single genes, which can reveal the presence of a mutation that could result in a disease or other disorder. In research, scientists use newer techniques that can scan millions of strands of DNA in parallel–a faster, cheaper process that provides vast amounts of genetic data. But these advanced sequencing tests have yet to be approved or optimized for the practice of medicine.

Most of the fast new sequencing technologies, developed by Illumina, Applied Biosystems, Complete Genomics, and others, use a camera to record fluorescently labeled bases as they bind to bits of a target sample of DNA. Watching a series of these reactions enables software to piece together the DNA sequence. Each company has developed novel ways to densely pack short strands of DNA onto a chip or slide, allowing millions of reactions to be recorded at once (see “Complete Genomics“). Most techniques require DNA molecules to be amplified, or copied many times before sequencing, but even newer methods such as those being developed by Pacific Biosciences and Oxford Nanopore can read the sequence of a single molecule, making it simpler to prepare samples and piece together the sequence.

Another way to scrutinize DNA uses microarrays, chiplike devices that, instead of reading the DNA sequence letter by letter, spot genetic variants known as single-nucleotide polymorphisms (SNPs). Microarrays provide a fast and effective way of screening for a particular variant or pattern of SNPs. Microarray studies have identified hundreds of SNPs that are linked to common diseases. But for the most part, the results have yet to translate into clinical practice. Because such mutations account for only a small percentage of an individual’s overall risk of disease, scientists haven’t yet figured out how to use this information to improve health (see “Drowning in Data“). Researchers are also developing tests for proteins and other biomarkers that reflect how an individuals’ genes interact with the environment.

To date, most advances in personalized medicine have occurred in cancer. For example, genetic screens that sequence portions of genes linked to breast cancer have been available to women with a family history of the disease for over a decade, so that those who carry high-risk variants can be monitored aggressively. Drug makers and scientists have also found genetic markers that predict whether a patient will respond to a given cancer drug, and a few new drugs require accompanying diagnostic tests that use sequencing or microarray technology to profile these markers (see “FDA Takes On Personalized Medicine“).

But so-called pharmacogenetic testing is still limited, especially beyond cancer drugs, not least because most genetic testing must be done in specialized labs and can take weeks. In order to personalize a prescription for someone who has suffered a heart attack, a physician needs information while the patient is still in the hospital. A number of companies are developing desktop devices for use in hospitals, using microarrays that can determine from a drop of blood whether a patient is likely to respond well to a drug. But to truly fulfill the promise of personalized medicine, the advanced sequencing methods in development will need to extend further into clinical practice, making it as easy to read patients’ DNA as it is to send them for x-rays or cholesterol tests.

Personalized Medicine

Illustration by David Simonds

 

A machine that prints organs is coming to market

 

TheEconomist.com, March 1, 2010  —  The great hope of transplant surgeons is that they will, one day, be able to order replacement body parts on demand. At the moment, a patient may wait months, sometimes years, for an organ from a suitable donor. During that time his condition may worsen. He may even die. The ability to make organs as they are needed would not only relieve suffering but also save lives. And that possibility may be closer with the arrival of the first commercial 3D bio-printer for manufacturing human tissue and organs.

The new machine, which costs around $200,000, has been developed by Organovo, a company in San Diego that specialises in regenerative medicine, and Invetech, an engineering and automation firm in Melbourne, Australia. One of Organovo’s founders, Gabor Forgacs of the University of Missouri, developed the prototype on which the new 3D bio-printer is based. The first production models will soon be delivered to research groups which, like Dr Forgacs’s, are studying ways to produce tissue and organs for repair and replacement. At present much of this work is done by hand or by adapting existing instruments and devices.

To start with, only simple tissues, such as skin, muscle and short stretches of blood vessels, will be made, says Keith Murphy, Organovo’s chief executive, and these will be for research purposes. Mr Murphy says, however, that the company expects that within five years, once clinical trials are complete, the printers will produce blood vessels for use as grafts in bypass surgery. With more research it should be possible to produce bigger, more complex body parts. Because the machines have the ability to make branched tubes, the technology could, for example, be used to create the networks of blood vessels needed to sustain larger printed organs, like kidneys, livers and hearts.

Printing history

Organovo’s 3D bio-printer works in a similar way to some rapid-prototyping machines used in industry to make parts and mechanically functioning models. These work like inkjet printers, but with a third dimension. Such printers deposit droplets of polymer which fuse together to form a structure. With each pass of the printing heads, the base on which the object is being made moves down a notch. In this way, little by little, the object takes shape. Voids in the structure and complex shapes are supported by printing a “scaffold” of water-soluble material. Once the object is complete, the scaffold is washed away.

Researchers have found that something similar can be done with biological materials. When small clusters of cells are placed next to each other they flow together, fuse and organise themselves. Various techniques are being explored to condition the cells to mature into functioning body parts—for example, “exercising” incipient muscles using small machines.

Though printing organs is new, growing them from scratch on scaffolds has already been done successfully. In 2006 Anthony Atala and his colleagues at the Wake Forest Institute for Regenerative Medicine in North Carolina made new bladders for seven patients. These are still working.

Dr Atala’s process starts by taking a tiny sample of tissue from the patient’s own bladder (so that the organ that is grown from it will not be rejected by his immune system). From this he extracts precursor cells that can go on to form the muscle on the outside of the bladder and the specialised cells within it. When more of these cells have been cultured in the laboratory, they are painted onto a biodegradable bladder-shaped scaffold which is warmed to body temperature. The cells then mature and multiply. Six to eight weeks later, the bladder is ready to be put into the patient.

The advantage of using a bioprinter is that it eliminates the need for a scaffold, so Dr Atala, too, is experimenting with inkjet technology. The Organovo machine uses stem cells extracted from adult bone marrow and fat as the precursors. These cells can be coaxed into differentiating into many other types of cells by the application of appropriate growth factors. The cells are formed into droplets 100-500 microns in diameter and containing 10,000-30,000 cells each. The droplets retain their shape well and pass easily through the inkjet printing process.

A second printing head is used to deposit scaffolding—a sugar-based hydrogel. This does not interfere with the cells or stick to them. Once the printing is complete, the structure is left for a day or two, to allow the droplets to fuse together. For tubular structures, such as blood vessels, the hydrogel is printed in the centre and around the outside of the ring of each cross-section before the cells are added. When the part has matured, the hydrogel is peeled away from the outside and pulled from the centre like a piece of string.

The bio-printers are also capable of using other types of cells and support materials. They could be employed, Mr Murphy suggests, to place liver cells on a pre-built, liver-shaped scaffold or to form layers of lining and connective tissue that would grow into a tooth. The printer fits inside a standard laboratory biosafety cabinet, for sterile operation. Invetech has developed a laser-based calibration system to ensure that both print heads deposit their materials accurately, and a computer-graphics system allows cross-sections of body parts to be designed.

Some researchers think machines like this may one day be capable of printing tissues and organs directly into the body. Indeed, Dr Atala is working on one that would scan the contours of the part of a body where a skin graft was needed and then print skin onto it. As for bigger body parts, Dr Forgacs thinks they may take many different forms, at least initially. A man-made biological substitute for a kidney, for instance, need not look like a real one or contain all its features in order to clean waste products from the bloodstream. Those waiting for transplants are unlikely to worry too much about what replacement body parts look like, so long as they work and make them better.

Investmentu.com, March 1, 2010, by Louis Basenese  —  In terms of innovation, I’m not exaggerating when I say that this one ranks right up there with other life-changers like the personal computer, mobile phones, e-mail, DNA testing and sequencing, even the Internet.

It will conceivably alter how every last penny is spent on healthcare. And that’s a lot of darn pennies. In the United States alone, we spent $2.4 trillion on healthcare in 2009 – roughly 17% of GDP.

If you have any doubt that sniffing out these opportunities early represents one of the most profitable strategies, consider Intuitive Surgical (Nasdaq: ISRG).

When the firm went public in 2000, investors were clueless about robotic surgery, let alone the company’s market-leading position in the space. In fact, Intuitive had to cut its IPO price by 30% just to attract enough interest and raise a measly $47 million.

Fast-forward to today, though. The robotic surgery trend has exploded and ISRG is up 1,558%.

I don’t think the robotic surgery trend has peaked just yet. But I wouldn’t recommend buying into it this late in the game. Not when another, more powerful mega-trend is unfolding…

Imagine… a pill with a tiny radio implanted inside it. Once digested, the radio powers up by using electrolytes in your stomach acid and lets your doctor know immediately that you took the medicine.

Imagine… a band-aid sized monitor that tracks seven heart functions and can wirelessly alert your doctor – or call 911 – if a heart attack is imminent.

Imagine… a wireless stethoscope that can be mailed to patients who face a long commute to reach a doctor’s office, or require an exam by a specialist located thousands of miles away.

Okay, stop imagining. These breakthrough technologies actually exist. And they’re just the start…

“There are hundreds of devices [like these] out there waiting in the queue,” says Dr. Eric Topol, Director of the Scripps Institute.

And thanks to the convergence of healthcare and low-cost, ubiquitous wireless technologies, they represent a sea change in the way medicine will be practiced.

From “Doctors Without Borders” to “Wireless Medicine “

He’s particularly keen on “ingenious sensors” – non-invasive, disposable devices that can track heart rhythm, blood pressure, respiratory rate, oxygen saturation, blood glucose, brain waves and many more physiological metrics.

And it doesn’t take much imagination to know that this trend – affectionately dubbed “Wireless Medicine” – isn’t just big. It’s colossal.

For example, the top 10 diseases that would benefit from wireless monitoring affect a massive 252 million Americans alone and account for hundreds of billions of dollars in annual costs. We’re talking about diseases like Alzheimer’s, asthma, breast cancer, depression, diabetes and heart failure. On a global scale, the market potential would reach billions of people.

So it’s no wonder insiders dub this the most important medical trend for the next 20 years. And why countless technology companies – Verizon (NYSE: VZ), Qualcomm (Nasdaq: QCOM), Microsoft (Nasdaq: MFST), IBM (NYSE: IBM), Intel (Nasdaq: INTC) and AT&T (NYSE: T) – are jockeying to get a piece of this healthcare revolution.

Here’s how you can, too…

Wireless Medicine… Getting a Piece of The Healthcare Revolution

Let’s start with what not to do: Don’t try to play the wireless medicine revolution by buying mega-cap stocks (like the ones I mentioned above). They won’t hand us mega profits because they’re already too big.

But that’s not the case with small-cap companies. A trend like wireless medicine can catapult them from $100 million market cap unknowns into multi-billion dollar household names.

Need an example? Consider Intuitive Surgical again. When it went public, it sported a market cap of less than $200 million. Today, it tips the skills at a hefty $13.3 billion.

I’m convinced that the explosion of wireless medicine could easily create similar results for the leading players in the space. And that’s why I’m tracking promising privately held companies.

My shortlist includes…

  • HQ, Inc., which has developed a patented thermometer pill for NASA.
  • Epocrates, which turns a doctor’s cell phone into a real-time medical library.
  • Zeo, Inc. – a company started by a group of sleep-deprived students at Brown University and now markets a technology that helps you monitor and improve your sleep.

Want another medicine mega-trend? Take a look at genomics – a science that studies the genetic makeup of organisms and their DNA

A flexible electricity-producing sheet of rubber that can be implanted in the body.

 

 

The New York Times, March 1, 2010, by Henry Fountain  —  It may not seem like it, but even the laziest of couch potatoes is a human dynamo. The act of breathing — of moving the ribs to draw air into the lungs and expel it — can generate about a watt of power. And if the potato actually gets up off the couch and walks briskly across the room, each heel strike can produce even more power, about 70 watts’ worth.

That energy could be put to work, charging a cellphone, say, or a medical sensor inside the body. The problem is how to harvest it.

Michael C. McAlpine of Princeton and colleagues have developed a promising approach for converting body movements into electricity. They have printed piezoelectric crystals onto flexible, biocompatible rubberlike material.

Piezoelectric crystals produce an electric current when bent and have many uses — the igniter on a gas barbecue grill being one of them. But highly efficient crystals of the kind that might be useful in the body are made at high temperatures that would destroy most plastics or rubbers.

The solution developed by Dr. McAlpine and colleagues, which is described in the journal Nano Letters, is to first make the crystals, in a series of narrow ribbons, on a rigid substrate of magnesium oxide. Then, after the substrate is etched away from the crystals, they are transfer-printed on a flexible biocompatible polymer, called PDMS.

Dr. McAlpine said his team had started building prototypes, in which tiny wires are deposited on the crystals so that the electricity can be harvested. The crystals are also covered with another layer of PDMS to protect them, and to safeguard the body since the crystals contain lead.

A first application might be in shoes, to produce enough power to keep a music player or phone charged. But the eventual goal would be to make a flexible power generator that could be implanted in the chest or elsewhere.

ScienceDirect.com

Johanna Parker, Omar Hashmi, David Dutton, Angelique Mavrodaris,

Saverio Stranges, Ngianga-Bakwin Kandala, Aileen Clarke and Oscar H. Franco

Health Sciences Research Institute, Warwick Medical School, University of Warwick,

Coventry CV4 7AL, United Kingdom

Clinical Sciences Research Institute, Clifford Bridge Road, Coventry CV2 2DX, United Kingdom

Abstract

Cardiometabolic disorders and vitamin D deficiency are becoming increasingly more prevalent across multiple populations. Different studies have suggested a potential association between abnormal vitamin D levels and multiple pathological conditions including cardiovascular diseases and diabetes.

We aimed to evaluate the association between vitamin D levels, using 25-hydroxy vitamin D (25OHD) as an indicator of vitamin D status, and the presence of cardiometabolic disorders including cardiovascular disease, diabetes and metabolic syndrome.

We performed a systematic review of the current literature on vitamin D and cardiometabolic disorders using the PubMed and Web of Knowledge databases in September 2009. Studies in adults looking at the effect of vitamin D levels on outcomes relating to cardiometabolic disorders were selected. We performed a meta-analysis to assess the risk of developing cardiometabolic disorders comparing the highest and lowest groups of serum 25OHD.

From 6130 references we identified 28 studies that met our inclusion criteria, including 99,745 participants. There was moderate variation between the studies in their grouping of 25OHD levels, design and analytical approach. We found that the highest levels of serum 25OHD were associated with a 43% reduction in cardiometabolic disorders [OR 0.57, 95% (CI 0.48–0.68)]. Similar levels were observed, irrespective of the individual cardiometabolic outcome evaluated or study design. High levels of vitamin D among middle-age and elderly populations are associated with a substantial decrease in cardiovascular disease, type 2 diabetes and metabolic syndrome. If the relationship proves to be causal, interventions targeting vitamin D deficiency in adult populations could potentially slow the current epidemics of cardiometabolic disorders.

Previous studies have suggested a potential association between abnormal vitamin D levels and cardiometabolic disorders including heart disease, diabetes, and metabolic syndrome. Johanna Parker, from University of Warwick (United Kingdom), and colleagues conducted a systematic literature review of studies examining vitamin D (25-hydroxy vitamin D [25OHD] as an indicator of vitamin D status) and cardiometabolic disorders.  The team reviewed 28 studies involving a total of 99,745 subjects across a variety of ethnic groups and including both men and women. The studies revealed a significant association between high levels of vitamin D and a decreased risk of developing cardiovascular disease (33% compared to low levels of vitamin D), type 2 diabetes (55% reduction) and metabolic syndrome (51% reduction).  Writing that: “High levels of vitamin D among middle-age and elderly populations are associated with a substantial decrease in cardiovascular disease, type 2 diabetes and metabolic syndrome,” the researchers posit that: “If the relationship proves to be causal, interventions targeting vitamin D deficiency in adult populations could potentially slow the current epidemics of cardiometabolic disorders.”

WorldHealth.net

For the first time, a team of scientists has identified definitive genetic variants associated with biological aging in humans. Tim Spector, from King’s College London (United Kingdom), and colleagues from the University of Leicester (United Kingdom) and University of Groningen (The Netherlands) studied telomeres, the endcaps on chromosomes and the shortening of which is considered a marker of biological aging.  The researchers found that those individuals carrying a particular genetic variant had shorter telomeres – they looked biologically older. The variants identified lies near a gene called TERC, which has been previously posited as a contributor in the maintenance of telomere length. The team postulates that some people are genetically programmed to age at a faster rate. They noted the effect to be quite considerable in those with the variant, equivalent to between 3-4 years of ‘biological aging” as measured by telomere length loss. Alternatively, the researchers speculate that genetically susceptible people may age even faster when exposed to proven ‘bad’ environments for telomeres like smoking, obesity or lack of exercise – and end up several years biologically older or succumbing to more age-related diseases.

Veryan Codd, Massimo Mangino, Pim van der Harst, Peter S Braund, Michael Kaiser, Alan J Beveridge, Suzanne Rafelt, Jasbir Moore, Chris Nelson, Nicole Soranzo, et al. “Common variants near TERC are associated with mean telomere length.”  Nature Genetics, 7 February 2010; doi:10.1038/ng.532.

http://www.defense.gov/news/newsarticle.aspx?id=58088
American Forces Press Service

US Department of Defense, March 1, 2010, by Donna Miles  —  FORT DETRICK, Md. – Movie-goers have seen the concept play out time and time again on the big screen. Sinister Borg drones reconstitute missing digits and limbs before their eyes in the “Star Trek” series. Alien Jack Jeebs in “Men in Black” regrows his head after it’s damaged or blown off.

The military is working to bring some of that science-fiction capability to wounded warriors so they can harness their own body’s power to regenerate itself and repair disabling and disfiguring battlefield injuries.

The Armed Forces Institute of Regenerative Medicine is leading the charge with an ambitious program that aims to help soldiers with burn and blast injuries regrow muscle, skin, tendons, nerves and even bone, said Army Col. (Dr.) Robert Vandre, the project director, based at this western Maryland Army post

“Ultimately, we will be able to grow limbs,” Vandre said. “But in the next decade, we should be able to reduce the number of limbs that have to be amputated, just because we will have new ways to fix things that can’t be fixed now.”

A dentist with a background in combat casualty care research, Vandre said he’s been impressed by the way the military has saved warfighters’ lives, even those who in past wars would have died from their combat wounds.

“They are alive, but a lot of them still have deformities, or things that are wrong,” he said. “What we want to do is to put wounded warriors back together, and restore them to how they were before their injury.”

Think of a salamander that’s able to regenerate a lost tail, and apply that same amphibian technology to humans, Army Surgeon General Lt. Gen. (Dr.) Eric Schoomaker said last spring as he unveiled the five-year, $250 million initiative.

The effort has attracted some of the best minds in regenerative medicine, working together through consortiums at Wake Forest and Rutgers universities, and in cooperation with the Army Institute of Surgical Research. Funding comes from the Defense Department, the National Institutes of Health and a broad range of public and private organizations.

But unlike other regenerative medicine programs, which focus primarily on basic research or commercial enterprises, the AFIRM effort is dedicated to “translational research” – which Vandre defines as putting research into practice.

“We are aimed completely toward the clinic,” he said. “Our goal is to take research being done, get a clinical trial and get it into military patients.”

Over the course of the program, AFIRM plans to develop clinical therapies to repair burns; reconstruct the head, skull and face; reconstruct, regenerate or transplant limbs; eliminate scarring as wounds heal; and reduce inflammation around wounds that can damage nerves and kill muscle cells.

The work already is paying off, Vandre said, with three clinical trials under way, and five more to start within the next year.

And it’s already showing promise.

Former Marine Josh Maloney, 24, who lost his right hand in a training accident at Marine Corps Base Quantico, Va., was among the first troops to benefit from the effort. When he received a hand transplant last March at the University of Pittsburgh Medical Center, his doctors introduced a new protocol that combines cell therapy and a bone marrow transplant.

The goal, Vandre explained, was to get Maloney’s body to accept the new hand while reducing the risk associated with toxic anti-rejection drugs. Just 10 days after his transplant, he had some movement in his fingers.

In another trial, researchers used regenerative medicine to get a soldier whose entire thigh muscle had been blown away a roadside bomb to generate new tissue. They applied “extracellular matrix” material – a mix of growth factors, protein and connective tissue taken from a pig’s bladder – to the wound. This, Vandre explained, signaled the body to start the tissue regrowth process.

So far, AFIRM researchers have used the procedure on two patients, and they plan to conduct 15 more surgeries as part of their trial.

In other trials, researchers are constructing “scaffolding” in the exact shape of a nose or other missing or damaged body part, then applying cells on it to grow new tissue. After the new growth is completed, the biodegradable scaffolding material dissolves.

The AFIRM initiative to begin next month shows particular promise for burn patients, whose treatment often requires multiple painful, invasive skin grafts. Researchers will begin “cell spraying,” taking a postage stamp-size piece of a burn victim’s healthy skin, exposing it to an enzyme that separates the cells from each other, then immediately spraying them onto the damaged skin.

“There’s much less pain and cost, and the results look way better,” Vandre said of results seen in a previous clinical trial conducted in Australia. “The results are pretty incredible.”

Meanwhile, researchers also are looking into ways to reduce the scarring associated with burns. Not only is it unsightly, but it also limits movement and flexibility after patients have healed.

One trial soon to be introduced will involve injecting fat cells under the burn scars – a procedure Vandre said dermatologists and plastic surgeons do all the time, with good results.

Vandre gets downright giddy talking about the developments already being seen, and the potential they hold for wounded warriors. It’s the ultimate reward for an effort he took on with crusade-like enthusiasm, pitching the concept for an armed forces regenerative medicine program, identifying the government and private-sector funding sources and helping attract what he calls “the Einsteins” in the regenerative medicine field.

“I’m just thrilled that I have been able to have the chance to do something like this, that can mean so much to so many people, and that it’s gotten this level of support,” he said. Chuckling, he added, “I just think I have the greatest job in the whole world.”

ScienceDaily.com, March 1, 2010  —  An international research team led by Columbia University Medical Center successfully used mouse embryonic stem cells to replace diseased retinal cells and restore sight in a mouse model of retinitis pigmentosa. This strategy could potentially become a new treatment for retinitis pigmentosa, a leading cause of blindness that affects approximately one in 3,000 to 4,000 people, or 1.5 million people worldwide.

The study appears online ahead of print in the journal Transplantation (March 27, 2010 print issue).

Specialized retinal cells called the retinal pigment epithelium maintain vision. Retinitis pigmentosa results from the death of retinal cells on the periphery of the retina, leading to “tunnel vision,” where the field of vision is narrowed considerably and everything outside the “tunnel” appears blurred or wavy.

“This research is promising because we successfully turned stem cells into retinal cells, and these retinal cells restored vision in a mouse model of retinitis pigmentosa,” said Stephen Tsang, M.D., Ph.D., assistant professor of ophthalmology, pathology and cell biology, Columbia University Medical Center, and lead author of the paper. “The transplanted cells not only looked like retinal cells, but they functioned like them, too.”

In Dr. Tsang’s study, sight was restored in one-fourth of the mice that received the stem cells. However, complications of benign tumors and retinal detachments were seen in some of the mice, so Dr. Tsang and colleagues will optimize techniques to decrease the incidence of these complications in human embryonic stem cells before testing in human patients can begin.

“Once the complication issues are addressed, we believe this technique could become a new therapeutic approach for not only retinitis pigmentosa, but age-related macular degeneration, Stargardt disease, and other forms of retinal disease that also feature loss of retinal cells,” said Dr. Tsang.

In age-related macular degeneration, retinal cells in the center of the retina degenerate and cause the center part of vision to become blurry or wavy. In 2010, macular degeneration is prevalent in nine million Americans and its incidence is expected to double by 2020. It is estimated that 30 percent of the population will have some form of macular degeneration by the time they reach the age of 75.

Replacement of damaged retinal cells in patients with macular degeneration is currently offered in some hospitals, but the therapy is limited by a shortage of donor retinal pigment epithelium cells. By using stem cells and turning them into retinal pigment epithelium cells, the supply is virtually unlimited.

Similar approaches to macular degeneration have demonstrated efficacy in other rodent models, but since these models are of rare, unique pathophysiologies of retinal degeneration, they may not be generalizable to most human forms of retinal degeneration, e.g., age-related macular degeneration, retinitis pigmentosa or Stargardt disease.

“It’s a good thing that more models are being tried, as this shows there may be real potential for stem cells to treat different causes of the loss of retinal pigment epithelium in humans,” said Dr. Tsang.

Methods

The research methods used in this study were developed by Columbia researchers, past and present, including:

  • Dr. Peter Gouras (ophthalmology) pioneered retinal cell transplantation where stem cells are placed underneath the retina. Co-authors on this paper, Drs. Nan-Kai Wang (a former retinal fellow now at the Chang Gung Memorial Hospital, the Chang Gung University College of Medicine and National Taiwan University in Taiwan) and Joaquin Tosi (ophthalmology) used this technique to place transplanted stem cells underneath the retina.
  • Dr. Gouras also developed many of the non-invasive methods used to assess neuronal function in mouse visual system, such as electroretinography, which measures the retina’s response to light.
  • The strategies for embryonic stem cell use were developed at Columbia by Dr. Elizabeth J. Robertson (now at Oxford). In collaboration with Dr. Pamela L. Schwartzberg (now at the National Institutes of Health), and Dr. Stephen P. Goff (biochemistry, molecular biophysics and microbiology), Dr. Robertson combined embryonic stem cells with homologous recombination to achieve gene targeting, producing the first gene-targeted mice.
  • The techniques employed to engineer stem cells were developed at Columbia by Drs. Goff and Virginia E. Papaioannou (genetics).
  • Co-author Dr. Victor Chyuan-Sheng Lin (pathology) tapped Dr. Martin Chalfie’s (biological sciences) Nobel Prize winning work on green fluorescent protein, to turn the stem cells used in this research yellow, enabling the team to use imaging to see them non-invasively in the mice.
  • Dr. Takayuki Nagasaki (ophthalmology) developed an advanced imaging technique, known as fundus autofluorescence imaging, which enabled the researchers to examine the mouse eye using non-invasive methods.

“I am fortunate that this diverse expertise exists at the same university — Columbia is one of the few places in the world where this research could be conducted,” said Dr. Tsang. “And our multidisciplinary approach to basic science research is unique.”

This research was supported by grants from the National Institutes of Health, Research to Prevent Blindness, New York, NY, the Foundation Fighting Blindness, the Dennis W. Jahnigen Career Development Scholars Award Program of American Geriatics Society, the Schneeweiss Stargardt Fund, and Professor Gertrude Neumark Rothschild.

by Gabe Mirkin MD, March 1, 2010  —  Researchers from the University of California at Berkeley show that an hour’s nap makes you smarter. Four hours after a 90-minute nap, students performed much better on memory and reasoning tests (reported at the annual meeting of the American Association of the Advancement of Science, San Diego, February 21, 2010). The same author reported these results more than eight years ago (Neuron, July 3, 2002). Another study showed that a 60-minute nap helps you learn better than one of 30 minutes (Nature Neuroscience, July 2002). I learned to nap when I was in the 7th grade, and started a life-time habit of sleeping every afternoon. The benefit of sleeping before learning increases with aging. A regular afternoon nap can help older people remain awake afternoon and evenings (Sleep, June 2001). Napping does not interfere with sleeping at night.

Tiredness is a signal that your brain needs a rest. Exercise does not perk you up when you are tired. Eating does not prevent afternoon tiredness that causes a drop in mental and physical performance. The only effective treatment for tiredness is rest. Set a radio to wake you to music, rather than a harsh sound that will jolt you, and expect to be far more productive than you were when you struggled to get through afternoons and evenings without napping.

Thyme growing. Researchers have found that six essential oils -from thyme, clove, rose, eucalyptus, fennel and bergamot — can suppress the inflammatory COX-2 enzyme, in a manner similar to resveratrol, the chemical linked with the health benefits of red wine. (Credit: iStockphoto)

ScienceDaily.com  —  For those who do not drink, researchers have found that six essential oils -from thyme, clove, rose, eucalyptus, fennel and bergamot — can suppress the inflammatory COX-2 enzyme, in a manner similar to resveratrol, the chemical linked with the health benefits of red wine. They also identified that the chemical carvacrol was primarily responsible for this suppressive activity.

These findings, appearing in the January issue of Journal of Lipid Research, provide more understanding of the health benefits of many botanical oils and provide a new avenue for anti-inflammatory drugs.

Essential oils from plants have long been a component of home remedies, and even today are used for their aromatherapy, analgesic (e.g. cough drops), or antibacterial properties. Of course, the exact way they work is not completely understood. However, Hiroyasu Inoue and colleagues in Japan believed that many essential oils might target COX-2 much like compounds in wine and tea.

So, they screened a wide range of commercially available oils and identified six (thyme, clove, rose, eucalyptus, fennel and bergamot) that reduced COX-2 expression in cells by at least 25%. Of these, thyme oil proved the most active, reducing COX-2 levels by almost 75%.

When Inoue and colleagues analyzed thyme oil, they found that the major component -carvacrol- was the primary active agent; in fact when they use pure carvacrol extracts in their tests COX-2 levels decreased by over 80%.