Testing the FDA: Pathway Genomics, a startup that sells a genetic testing kit to consumers over the Internet, garnered regulatory attention when it announced plans to sell the test at Walgreens.     Credit: Pathway Genomics


Questions arise over several companies’ plans for over-the-counter genetic tests

MIT Technology Review, May 26, 2010, by Arlene Weintraub  –  On May 19, the U.S. House of Representatives Committee on Energy and Commerce sent a toughly worded letter to three CEOs, including James Plante of San Diego-based Pathway Genomics. Pathway was preparing to sell an over-the-counter genetic-testing kit at Walgreens. The product, called Genetic Health Report, purported to test for more than 70 health issues, including predispositions to Alzheimer’s, breast cancer, and diabetes. But the committee’s questions prompted Walgreens to postpone its plans to sell Genetic Health Report.

The committee’s action could mark a crackdown on companies that sell genetic tests directly to consumers. The tests–which use saliva samples–have been sold, mostly over the Internet, with little interference from authorities, including the U.S. Food and Drug Administration. But some experts in law and genetics say Walgreens’s plan to stock the tests on shelves may have made enough of a splash to change all that. “We could see a demand for more transparency from these companies, so consumers can clearly see what they’re testing for, and what the evidence is” for the legitimacy of the results, says Daniel Vorhaus, attorney at Robinson, Bradshaw & Hinson in Charlotte, NC, and editor of the firm’s Genomics and Life Sciences blog.

The committee is demanding that consumer genetic-testing companies provide documents that describe the accuracy of the tests, and how the analysis of the results takes into account such factors as age, gender, and geographic location. Less than two weeks before the committee mailed its letters, the FDA sent a letter to Pathway requesting that Plante justify Genetic Health Report’s lack of FDA approval.

An FDA spokesman said in an e-mail that the other two companies that were contacted by the House committee–23andMe and Navigenics–had also been asked to defend their lack of FDA clearance: “This type of communication is often an initial step to open discussions with companies to clarify the FDA’s role in regulating their products and it’s also a step to gather more information about the products themselves.”

The three companies contacted by the House committee declined to comment for this story, though all released public statements expressing their willingness to cooperate with the investigations. “Pathway is in compliance with currently applicable regulations and guidelines for our laboratory and the services we offer to our customers,” said a company statement.

As it stands, the regulations governing genetic tests are a bit muddy. Pathway’s statement says the company has a certification known as Clinical Laboratory Improvement Amendments (CLIA), a federal certification that merely establishes quality standards for the laboratories that perform the tests.

But should the FDA be more vigilant? Most genetic tests–including those given by doctors–are subject to the FDA’s medical-device regulations. There are three classes of medical devices, each requiring an increasing degree of regulatory control. Depending on the nature of the test and what reagents are used to produce the results, the consumer genetic tests may or may not require premarket approval, though they must include a disclaimer stating that they have not been cleared by the FDA. The agency’s discussions with Pathway and its rivals may result in more such cautionary language being displayed prominently on packaging and consumer leaflets.

Some genetics experts believe consumers need even more comprehensive information about the limitations of genetic testing. They point out that scientists have not yet decoded the genetic causes of most diseases and many uncertainties surround genetic testing.Take BRCA1 and BRCA2, for example. While mutations in these genes have been linked to breast cancer, less than 10 percent of women who develop the disease actually test positive for the genes. For other diseases, such as Alzheimer’s, very few genes have been linked to the illnesses, and it’s unclear how important those genes are in the diseases. So genetic tests might create unwarranted fear in some patients, says Hope Northrup, director of the Division of Medical Genetics in the Department of Pediatrics at the University of Texas Medical School at Houston.

Edward McCabe, codirector of the Center for Society and Genetics at the University of California at Los Angeles, believes consumers who buy genetic tests–either online or on store shelves–should be instructed on exactly what each result can accurately predict and what it can’t. The FDA should have the authority to vet the tests, as well as the information that comes with them, he says. “Otherwise inappropriate health-care decisions could be made.”

The FDA and Congress are unlikely to outlaw the marketing of genetic tests to consumers altogether, most experts believe. But Vorhaus predicts they will put pressure on the U.S. Federal Trade Commission to monitor the messages that these companies are giving to consumers.

In any case, the fact that these agencies are paying attention to genetic testing could be enough to change how Pathway, Walgreens, and other companies communicate the value of their products to consumers. “Shine a bright light on the industry,” Vorhaus says, “and you’ll get the industry to monitor itself.”

By S. James Gates Jr.

“The reason we are doing this with urgency is because it’s connected to our country’s future economy.” John Consoli/University of Maryland

Is science education broken in the United States? And if so, how should the country fix it? A working group of the President’s Council of Advisors on Science and Technology (PCAST) has been investigating these long-standing questions and is expected to issue a report on its policy recommendations this month. Science News Contributing Editor Alexandra Witze spoke with the working group’s cochair, physicist S. James Gates Jr. of the University of Maryland in College Park. Gates also serves on the Board of Trustees of Society for Science & the Public, the parent organization of Science News.

What is the outlook for U.S. science education?

If you look at U.S. performance on various international metrics, depending on which one you use, we come out something like 24th or 25th in the world. A lot of people might argue: “Well, who cares? It’s just science.” The only problem with that theory is we’re moving into a time in the development of the world economy when innovation and the formation of novel approaches will clearly come from countries best situated to create a population that can innovate in science and technology.

We’re not doing this because we want to make more scientists. The reason we are doing this with urgency is because it’s connected to our country’s future economy.

The Obama administration has announced a number of science education initiatives. Will they do enough?

I think the true test is yet to come. Does one put one’s money where one’s mouth is? To some substantial degree, this administration has stepped up to the plate with its increased support of science. On the other hand, we have heard concerns about sustainability of this commitment in light of current economic constraints.

How is PCAST approaching its deliberations about science education?

We’re trying to be mindful of the tremendous number of efforts that have gone before; there are at least 40 to 50 such reports that one could list. We have found discussions in the literature all the way back to the ’60s where people were raising issues of science and technology education.

When I look at the country’s current crisis with regard to STEM [science, technology, engineering and mathematics] education, this is in fact the third such crisis.

The first one was World War II in my opinion. If you look at the way this nation prosecuted the war successfully, it was because the United States innovated at a level far beyond its competition.

Crisis two in my opinion was the launch of Sputnik. Once again there was a public resolution. You create NASA, our space program, and we successfully get men on the moon by 1969.

In this third STEM crisis, what we really need to do is start thinking in light of our previous experience. What might be policy structures that could bring to bear the kind of transformational and long-term vision to allow our nation to progress to higher levels of performance?

How do we do that?

My [PCAST working group] cochair [Eric Lander of the Broad Institute of MIT and Harvard in Cambridge, Mass.,] says the problem is that we in this nation do not have the structures that have allowed us to get inside the innovation cycle in education in the way that we have in scientific research.

One way to look at this problem is to look at education as a system to be engineered and to ask how one might do this. What I’ve been looking for is maps between how research works in this country and how education works in this country. In particular I have been struck by the fact that there is nothing like DARPA [the Defense Advanced Research Projects Agency] for education. You need something like that in the system to drive innovation like we haven’t seen.

Previous education has been mostly about the delivery of facts; you wanted people to remember and manipulate facts. But one thing that’s different now is in a world that has a Web [and] access to information at your fingertips, the memory of facts won’t be that important. What’s going to be important is the capability of people to marshal those facts to solve the kinds of problems they’re engaged in.

Are you optimistic about the country’s future in science education?

I’m optimistic in the long term. There’s lots of evidence that this country solves difficult problems, especially if you give us enough time. In the short term, I’m afraid it’s going to be very painful. I fear that we may not be able to impress upon the larger society quickly enough that the issues around science, technology, engineering and mathematics are not tied to just those fields — that in fact this is the basis for our wealth formation. If we can’t get that message out quickly enough, the nation’s not going to respond quickly enough.

Human molar scaffolding from the lab of Dr. Jeremy Mao. (Credit: Image courtesy of Columbia University Medical Center)

New Technique Grows Dental Implants Right in Your Mouth

Columbia University Medical Center, May 25, 2010  —  A technique pioneered in the Tissue Engineering and Regenerative Medicine Laboratory of Dr. Jeremy Mao, the Edward V. Zegarelli Professor of Dental Medicine at Columbia University Medical Center, can orchestrate stem cells to migrate to a three-dimensional scaffold infused with growth factor, holding the translational potential to yield an anatomically correct tooth in as soon as nine weeks once implanted.

People who have lost some or all of their adult teeth typically look to dentures, or, more recently, dental implants to improve a toothless appearance that can have a host of unsettling psycho-social ramifications. Despite being the preferred (but generally painful and potentially protracted) treatment for missing teeth nowadays, dental implants can fail and are unable to “remodel” with surrounding jaw bone that undergoes necessary changes throughout a person’s life.

An animal-model study has shown that by homing stem cells to a scaffold made of natural materials and integrated in surrounding tissue, there is no need to use harvested stem cell lines, or create an environment outside of the body (e.g., a Petri dish) where the tooth is grown and then implanted once it has matured. The tooth instead can be grown “orthotopically,” or in the socket where the tooth will integrate with surrounding tissue in ways that are impossible with hard metals or other materials.

“These findings represent the first report of regeneration of anatomically shaped tooth-like structures in vivo, and by cell homing without cell delivery,” Dr. Mao and his colleagues say in the paper. “The potency of cell homing is substantiated not only by cell recruitment into scaffold microchannels, but also by the regeneration of periodontal ligaments and newly formed alveolar bone.”

This study is published in the most recent Journal of Dental Research, a peer-reviewed scientific journal dedicated to the dissemination of new knowledge and information on all sciences relevant to dentistry, the oral cavity and associated structures in health and disease.

Dental implants usually consist of a cone-shaped titanium screw with a roughened or smooth surface and are placed in the jaw bone. While implant surgery may be performed as an outpatient procedure, healing times vary widely and successful implantation is a result of multiple visits to different clinicians, including general dentists, oral surgeons, prosthodontists and periodontists. Implant patients must allow two to six months for healing and if the implant is installed too soon, it is possible that the implant may fail. The subsequent time to heal, graft and eventually put into place a new implant may take up to 18 months.

The work of Dr. Mao and his laboratory, however, holds manifold promise: a more natural process, faster recovery times and a harnessing of the body’s own potential to re-grow tissue that will not give out and could ultimately last the patient’s lifetime.

“A key consideration in tooth regeneration is finding a cost-effective approach that can translate into therapies for patients who cannot afford or who aren’t good candidates for dental implants,” Dr. Mao says. “Cell-homing-based tooth regeneration may provide a tangible pathway toward clinical translation.”

Dr. Ira B. Lamster, dean of the College of Dental Medicine, stated: “This research provides an example of what is achievable when today’s biology is applied to common clinical problems. Dr. Mao’s research is a look into the future of dental medicine.”

This research was supported by NIH ARRA Funding via 5RC2 DE020767 from the National Institute of Dental and Craniofacial Research. Columbia has filed patent applications relating to the engineered tooth and, through its technology transfer office, Columbia Technology Ventures, is actively seeking partners to help commercialize the technology.

Story Source:

Adapted from materials provided by Columbia University Medical Center.

Journal Reference:

  1. K. Kim, C. H. Lee, B. K. Kim, J. J. Mao. Anatomically Shaped Tooth and Periodontal Regeneration by Cell Homing. Journal of Dental Research, 2010; DOI: 10.1177/0022034510370803

The story of scientists who came up with ideas that recently convinced Pharma to give them millions of dollars.


The-Scientist.com, May 2010  –  After 2 decades doing industry science, Roger Tung decided to take a break. For a year and a half, he played the role of “Mr. Mom” and independent consultant by day, while contemplating what to do next between the hours of 10 P.M. and 3 A.M. He wanted to come up with something big—something that could reduce the risks and costs that are rampant in the “expensive and failure-prone” business of drug discovery and development, he says.

It was during one of these late-night brainstorming sessions in 2005 that Tung suddenly remembered deuterium—a heavier form of hydrogen he had learned about as a graduate student. Deuterium forms much stronger bonds with carbon than hydrogen does, which can impact a drug’s absorption, distribution, and metabolic properties. Replacing hydrogen atoms with deuterium in existing therapeutic compounds, he thought, might boost their safety or efficacy. And because the shape and size of deuterium is nearly identical to hydrogen, the drugs should still hold their same pharmacological properties, he reasoned.

After doing some background research, Tung convinced himself that his idea was a good one. He immediately started filing patent applications for various deuterium-based compounds and speaking with dozens of venture capital groups and hedge funds to raise the start-up money he needed. Finally, in 2006, with six figures out of his own pocket and $10 million from investors, Tung launched CoNCERT Pharmaceuticals, Inc—five employees (including Tung) on their cell phones in a one-room office in Burlington, Mass., with little more than an Internet connection and a potentially great idea.

Since that time, CoNCERT has raised more than $100 million in capital, filed more than 100 patent applications, grown to about 45 employees, and moved to a 4,200–square meter facility. Almost half of that is laboratory space, where its scientists synthesize, test, and even manufacture many deuterium-substituted compounds.

Last March, CoNCERT announced the Phase I results of a deuterium-modified analog of paroxetine—a serotonin reuptake inhibitor most commonly marketed as an antidepressant (e.g., Paxil, Seroxat), but also shown to reduce vasomotor symptoms (hot flashes) in menopausal women. A serious problem with this treatment, however, is that paroxetine inactivates a liver enzyme important for the metabolism of xenobiotics, which can lead to serious side effects such as cardiovascular toxicity when taken in combination with other drugs. In the CoNCERT clinical trial for hot flashes, however, the deuterium-based product retained the enzyme activity, suggesting that the drug could be used in a broader context than its hydrogen relative.

After nearly 6 months of “pinching ourselves,” deBethizy says, Targacept struck a deal worth $1.24 billion with AstraZeneca last December.

“It demonstrated that the theoretical efficiency of the platform was really playing out,” Tung recalls. Finding a suitable partner and striking a deal “didn’t happen overnight,” he says, but after several discussions with GlaxoSmithKline (GSK), which sells Paxil, Tung could finally “see the light bulbs going off” in the heads of GSK’s scientific advisory board. “They got very excited about [the technology],” Tung remembers, and the meeting, which was slated for just 1 hour, lasted more than two. Sure enough, just 3 months after releasing the results of the trial, CoNCERT struck a $1 billion partnership with GSK to develop three of CoNCERT’s deuterium-based drug candidates.

When it was all said and done, Tung felt “somewhere between incredible elation and exhaustion,” he admits. “That was a huge deal for us,” he says.

Last year, partnering deals between biotech and pharmaceutical companies totaled over $37 billion, nearly double the deals made in 2008, according to a report released by Burrill & Company this January. “When collaborations work, they’re really beautiful,” said Stuart Peltz, founder, president and CEO of PTC Therapeutics, which struck a nearly $2 billion deal with Roche last September—the largest deal on record for 2009.

Below are the tales of three more deals that made some scientists and business executives with a great idea rich in the last year.

Thank You for Smoking [$1.24 billion]

After 3 years as a subsidiary ofᅠR. J. Reynolds Tobacco Company (RJR), Targacept became an independent biotech company in August 2000, focused on studying neuronal nicotinic receptors (NNRs) and their role in the central nervous system.

Breaking away from RJR, “the social burden of being in a tobacco company was eliminated, [which was] very good and very energizing” to Targacept’s employees, says CEO Don deBethizy. They got to work applying their understanding of NNRs acquired at RJR to develop new therapies.

“We all know that people smoke [to relieve] stress,” says deBethizy—an effect largely driven by nicotine and its power to block NNRs in the brain. Mimicking that action with an antagonist, he reasoned, may serve as a possible therapy for certain depressive disorders, which are associated with an overstimulation of NNRs.

Looking into this possibility further, deBethizy and his colleagues discovered an old drug already on the market—a noncompetitive antagonist known as mecamylamine. The compound was originally developed by Merck in the 1950s and marketed as a blood pressure lowering agent, and has more recently been used as an off-label treatment for Tourette syndrome and autism to manage anger, deBethizy says. Acquiring the rights to mecamylamine, Targacept decided to test the drug in the context of depression. Promising preliminary results—both from Targacept and a Yale clinical trial—revealed that mecamylamine could help alleviate depression symptoms in patients who did not respond to traditional antidepressants.

Further research revealed that the left-handed form of the molecule showed most of the antidepressant activity. Creating and testing a new drug with just the left-handed form, the researchers saw a “dramatic” result, deBethizy recalls—a positive outcome on every endpoint, with p-values of 0.0001 or lower for each.

“That was the moment,” he says, referring to how he felt when he first saw the results. He called a company-wide meeting to share the news, and with all employees gathered around, deBethizy lay down on the floor—as he often does when he’s excited, but never before in front of over 100 people. “Everybody stood up, hooting and hollering,” he recalls. “We were so excited about what [those results] meant. It is a potential paradigm-changing therapy for depression, which is a $20 billion market.”

After nearly 6 months of “pinching ourselves,” deBethizy says, Targacept struck a deal worth $1.24 billion with AstraZeneca last December for the purified version of mecamylamine, known as TC-5214. “Our market cap went from $45 million to $500 million,” he says. “We have now the potential to become a very successful biotech company.”

Playing with UTRs [$1.9 billion]

Stuart Peltz always “liked the idea of unknowns.” The regulation of gene expression via untranslated regions (UTRs) of mRNA transcripts was one such underexploited but important area of research. So shortly after leaving his professor position at the University of Medicine and Dentistry of New Jersey to launch PTC Therapeutics in 1998, he decided to set up a system to test how interactions between various compounds and UTRs affect protein expression. “We built a technology [to] look for small molecules that regulate the expression of a protein through targeting the UTR of the RNA,” Peltz says.

When it was all said and done, Tung felt “somewhere between incredible elation and exhaustion,” he admits.

The system involves taking the 5´ and 3´ UTRs of medically important genes, and attaching each to either end of a reporter that allows the scientists to track expression of that gene when exposed to various treatments—any of about 200,000 compounds in the company’s library. Expressing these reporter-UTR hybrids in stable cell lines, Peltz and his colleagues can identify which compounds enhance or inhibit gene expression, providing potential drug candidates of interest.

During one of the very first experiments using the technology, dubbed gene expression modulation by small molecules (GEMS), the researchers screened for factors that inhibit the production of vascular endothelial growth factor (VEGF), which stimulates the growth of new blood vessels, and found several compounds that were selectively targeting the endogenous protein. The researchers realized that “this is a technology we can use over and over again against many different targets,” Peltz says. “We were very excited” to see those results, he recalls.

To date, PTC has five deals with big pharma, and counting. So far the deals include drug candidates for oncology (a candidate that stemmed from the initial VEGF experiments), hepatitis C, and cardiovascular health. Most recently, PTC struck its largest deal to date—nearly $2 billion with Roche—to look for compounds that impact the central nervous system.

In total, the deals involving the GEMS technology total more than $2.5 billion plus royalties, and the company is “hoping to do another GEMS deal this year,” says senior vice president of Corporate Development Claudia Hirawat.

Breeding yeast [$1.05 billion]

Manufacturing biologics is difficult and expensive, which limits these drugs’ availability and affordability. “It costs us hundreds of dollars per gram to manufacture these [molecules], sometimes thousands,” says Randy Schatzman, co-founder and CEO of Alder Biopharmaceuticals.

Immunex’s Enbrow, for example, a tumor necrosis factor blocker used to treat a variety of immune diseases, including rheumatoid arthritis, became so popular in the early part of the new millennium that the company was unable to produce enough of it to meet the demand of the market. “There needed to be a better way to manufacture these complex biomolecules,” Schatzman says.

Schatzman and his colleagues identified one potential manufacturing problem they thought they could fix—the use of traditional mammalian cell lines, which are expensive to culture and only divide once every 24 to 36 hours. Yeast, on the other hand, are easy to grow, and can divide every 90 minutes or so, reducing the time it would take to fill a 2,000-liter tank from 2 to 4 weeks to just 90 hours. The problem: How does one “get a simple microorganism to express a complex molecule like an antibody?” Schatzman wondered.

The trick, it turns out, is to produce the separate parts of the molecule in different yeast lines, and then to mate the yeast together until you find the right combination of different protein components. “Low and behold there were colonies in there that were making lots of protein,” Schatzman recalls. “It almost seemed too simple, but it worked,” he adds, comparing the first time the experiment worked to having his first-born because of the pride he felt in the success of the program.

Alder just struck its first big pharma deal worth more than $1 billion—an agreement with Bristol-Myers Squibb for a humanized monoclonal antibody that blocks interleukin-6 (IL-6), involved in inflammation. When the contracts were finally signed late one night, Schatzman says he was “tired but thrilled.”


Other recent $1B+ pharma deals

Date Biotech Company Pharma Company Primary Therapy/Disease Target Total (up to)
January 12, 2009 Zymogenetics Bristol-Myers Squibb Hepatitis C $1.107 billion
May 28, 2009 Exelixis Sanofi-Aventis Cancer $1 billion
September 21, 2009 Nektar AstraZeneca Pain and opioid-induced constipation $1.5 billion
November 2, 2009 Amylin Takeda Obesity $1.075 billion
November 25, 2009 Incyte Novartis Myelofibrosis $1.1 billion
February 16, 2010 Rigel AstraZeneca Rheumatoid arthritis $1.245 billion
March 31, 2010 Isis GlaxoSmithKline Rare diseases $1.5 billion


Read more: Billion-Dollar Babies – The Scientist – Magazine of the Life Sciences http://www.the-scientist.com/article/display/57364/#ixzz0ot6kHDMH

Shock treatment: These images show blood flow in the left ventricle of a 62-year-old patient’s heart (red indicates blood flow). The images on the left show the ventricle before acoustic shockwave treatment; the ones on the right show it after treatment.   Credit: R. Erbel, Essen University, Germany


A device sends shockwaves to prompt blood vessel growth


MIT Technology Review, May 2010, by Lauren Gravitz  –  Cardiac patients are living longer and longer–up to 20 years after receiving stents, a heart bypass, or heart-valve replacements. But extended lifespan is often accompanied by other complications, as a repaired heart can still have difficulty getting enough oxygen. The accompanying pain, a squeezing pressure in the chest called angina, can plague patients for years, and there are some for whom no surgery can provide relief. But a noninvasive shockwave machine could help prompt the growth of new blood vessels, restoring the heart’s oxygen supply and alleviating the pain.

In a clinical trial at three centers across the United States, cardiologists are testing the safety of the shockwave device, developed by Maryland-based Medispec. The “Cardiospec” machine is based on the same sound-wave technology used to break up kidney stones, but it requires only about one-tenth the energy. “Shock waves are acoustic waves that create pressure that can be focused,” says Medispec’s Gil Hakim, the company’s director of new product development. Direct that pressure toward the heart muscle with just the right intensity, and it causes the body to produce new blood vessels.

Researchers aren’t sure precisely why shockwaves have this effect–they believe that the pressure may induce a cascade of events that mimic wound-healing, recruiting undifferentiated cells to the area to build blood vessels. Preliminary studies show that about 70 percent of the patients who undergo the shockwave procedure experience somewhere between a 60 to 70 percent improvement in blood flow to their hearts.

“Patients with [recurring] angina consume a lot of medical care because they have multiple emergency visits, they have multiple angiograms, and their quality of life is extremely low,” says Amir Lerman, a cardiovascular specialist at the Mayo Clinic in Rochester, MN, who’s heading up the Cardiospec trial. And, he notes, the treatments available to these patients to date are short-term therapies that address the symptoms rather than the cause. “These patients currently don’t have any alternative solution. And we need to find one because they live a long time.”

The trial will recruit 15 patients–five each at the Mayo Clinic, the University of California at San Diego, and Albert Einstein Medical Center in Philadelphia–and it will consist of nine treatments applied over a nine-week period (three treatments per week during weeks one, five, and nine).

The Cardiospec technology has already been used to treat about 1,000 patients worldwide, in Europe, Canada, and other regions around the globe. And so far, it seems that about two to three years after the original treatment, patients can experience a relapse. Many patients who undergo treatment don’t change their exercise habits or diets, their blood vessels begin to narrow, and once again their hearts can’t get enough oxygen. “It’s like when patients have undergone a stenting procedure,” Hakim says. “That won’t necessarily be the only stent, because they develop another problem in another area in the heart.”

It’s not that the shockwave treatment has failed. Rather, a patient ends up with the same problem in a different region of his heart. “It’s like maintenance–after a few years, patients can be evaluated, checked again, and then retreated,” Hakim says.

The options available for so-called “refractory angina” patients, who have pain after surgery or aren’t candidates for surgery in the first place, are quite limited, says Timothy Henry, an interventional cardiologist at the Minneapolis Heart Institute who’s not involved in the trial. “We definitely need new options, and this is an interesting one. The preliminary data looks very good, it’s low risk. I think this is a really good option, but it needs to be tested,” Henry says.

Lerman and his collaborators hope to complete the safety trial in a few months, and Medispec is aiming for U.S. Food and Drug Administration approval by 2012. Hakim is hopeful that the technology can provide relief for patients who are now completely dependent on oral medications to stem the tide of their angina attacks. “On average, before starting the treatment, the patients took their medication around three times a day. After the therapy, they’re taking it around three times a week. It’s a marked improvement in their quality of life,” he says. “It’s not a cure, but it’s an improvement.”

Stuart Isett for The New York Times

Shawn Verrall waters his upside-down tomato plants with his daughter, Megan, in their Richmond, Wash., garden.


Published: May 19, 2010

IF pests and blight are wrecking your plants, it might be time to turn your garden on its head.

Erich Schlegel for The New York Times, Donald Rutledge, in New Braunfels,

Tex.,  put his buckets on pulleys to protect his plants from deer.

The Topsy Turvy Garden

Mark McAlpine made his own containers for his Ontario garden.

Growing crops that dangle upside down from homemade or commercially available planters is growing more popular, and its adherents swear they’ll never come back down to earth.

“I’m totally converted,” said Mark McAlpine, a body piercer in Guelph, Ontario, who began growing tomatoes upside down two years ago because cutworms were ravaging the ones he planted in the ground. He made six planters out of five-gallon plastic buckets, some bought at the Home Depot and some salvaged from the trash of a local winemaker. He cut a two-inch hole in the bottom of each bucket and threaded a tomato seedling down through the opening, packing strips of newspaper around the root ball to keep it in place and to prevent dirt from falling out.

He then filled the buckets with soil mixed with compost and hung them on sturdy steel hooks bolted to the railing of his backyard deck. “Last summer was really hot so it wasn’t the best crop, but I still was able to jar enough whole tomatoes, half tomatoes, salsa and tomato sauce to last me through the winter,” said Mr. McAlpine, who plans an additional six upside-down planters this year.

Upside-down gardening, primarily of leggy crops like tomatoes, cucumbers and peppers, is more common partly because of the ubiquity of Topsy Turvy planters, which are breathlessly advertised on television and have prominent placement at retailers like Wal-Mart, Walgreens and Bed Bath & Beyond. According to the company that licenses the product, Allstar Products Group in Hawthorne, N.Y., sales this year are twice last year’s, with 20 million sold since the planter’s invention in 2005. Not to be outdone, Gardener’s Supply and Plow & Hearth recently began selling rival upside-down planters. “Upside-down gardening is definitely a phenomenon,” said Steve Wagner, senior product manager for Plow & Hearth.

The advantages of upside-down gardening are many: it saves space; there is no need for stakes or cages; it foils pests and fungus; there are fewer, if any, weeds; there is efficient delivery of water and nutrients thanks to gravity; and it allows for greater air circulation and sunlight exposure.

While there are skeptics, proponents say the proof is in the produce.

Tomato and jalapeño seedlings sprout from upside-down planters fashioned out of milk jugs and soda bottles that hang from the fence surrounding the Redmond, Wash., yard of Shawn Verrall, a Microsoft software tester who blogs about gardening at Cheapvegetablegardener.com. Mr. Verrall turned to upside-down gardening last summer as an experiment.

“I put one tomato plant in the ground and one upside down, and the one in the ground died,” he said. The other tomato did so well, he planted a jalapeño upside down, too, and it was more prolific than the one he had in the ground. “The plants seem to stay healthier upside down if you water them enough, and it’s a great way to go if you have limited space,” he said.

While horticulturists, agronomists and plant scientists agree that pests and blight are less likely to damage crops suspended in the air, they said they are unsure whether growing them upside down rather than right-side up will yield better results.

“Growing things upside down seems like a fad to me, but I’m glad people are fooling around with it and hope they will let us traditionalist gardening snobs know what we’ve been missing,” said Hans Christian Wien, a horticulture professor at Cornell University in Ithaca, N.Y.

Judging from gardening blogs and Web sites, those fooling around with upside-down gardening are generally enthusiastic, particularly if they have planted smaller varieties of tomatoes.

“Bigger tomatoes are too heavy and put too much stress on the vine, causing it to twist and break,” said Michael Nolan, an avid gardener in Atlanta and a writer for Urbangardencasual.com, who has four upside-down planters also made out of five-gallon buckets in which he grows bushels of cherry and patio varieties of tomatoes as well as small pickling cucumbers.

Tomato varieties are labeled as either indeterminate or determinate, and horticulture experts recommend choosing indeterminate ones for upside-down gardens. Determinate tomato plants are stubbier, with somewhat rigid stalks that issue all their fruit at once, which could weigh down and break the stems if hanging upside down. Indeterminate types, by contrast, have more flexible, sprawling stems that produce fruit throughout the season and are less likely to be harmed by gravity.

When Mr. Nolan first tried upside-down gardening, he used the Topsy Turvy planters, which are made of polyethylene bags and look like Chinese lanterns gone wrong. But he was disappointed in the yield. “I far prefer using buckets,” he said, which hang from tall metal shepherd hooks bolted to the posts supporting his backyard deck. He paints his buckets bright colors, and plants herbs and marigolds in the top to help retain moisture.

Another, less decorative solution for preventing evaporation is to top the planters with mulch or simply cover them with a lid. Regardless, Mr. Nolan said, “The upside-down planters tend to dry out really fast, so I have to water a lot — probably once a day in the heat of the summer.”

Many gardeners reported that the thinner, breathable plastic Topsy Turvy planters ($19.98) dried out so quickly that watering even once a day was not enough to prevent desiccated plants. There were similar comments about the Plow & Hearth version ($12.95) and while the Gardener’s Supply upside-down planter ($19.95) has a built-in watering system, online reviewers said it is difficult to assemble.

In addition to plastic soda bottles, milk jugs and five-gallon buckets, upside-down planters can be made out of thick heavy-duty plastic trash bags, plastic reusable shopping totes, kitty litter containers, laundry hampers and even used tires. Web sites like Instructables.com and UpsideDownTomatoPlant.com show how it can be done, and YouTube has several how-to videos. Variations include building a water reservoir either at the top or bottom of planters for irrigation, cutting several openings in the bottom and sides for planting several seedlings and lining the interior with landscape fabric or coconut fiber to help retain moisture.

Donald Rutledge, a construction project designer and manager in New Braunfels, Tex., devised a triple-pulley system so he could easily hoist his nine upside-down planters 16 feet above the ground, away from ravenous deer. He made his planters out of five-gallon buckets four years ago, following instructions on the Internet. “The tomatoes and basil worked real well upside down, but the lettuce, peas and carrots weren’t so successful,” he said. “It’s been trial and error.”

This year, he put his plantings right-side up in the buckets to see if it makes any difference. He said his suspended garden started as an entertaining summer project for him and his three children but has become more of a scientific pursuit: “Is upside down better than right-side up? I’m guess I’m going to find out.”

Neuron transform: An astroglial cell from a mouse’s brain has been transformed into a type of neuron called an excitatory neuron. The green color marks a molecule specific to excitatory neurons, and the white indicates a molecule critical for synaptic plasticity, a key function in communication between neurons.     Credit: Christophe Heinrich



Transforming support cells in the brain into neurons might one day help repair damage from stroke or injury



MIT Technology Review, May 2010, by Courtney Humphries  –  Support cells in the brain called astroglia can be turned into functioning neurons, according to a study in this week’s Public Library of Science Biology. Researchers found that they could transform the cells into two different classes of neurons, and that the neurons could form connections with one another in a dish. Although the research is at an early stage, the finding suggests that scientists could someday recruit existing cells in the brain to repair the brain and spinal cord after a stroke, injury, or neurodegenerative disease.

The research team, from the Helmholtz Center and Ludwig-Maximilians University in Munich, had previously shown that it was possible to turn astroglia–star-shaped cells that provide structural support in the brain–into neurons by introducing genes called transcription factors into the cells using a virus. In that study, however, the neurons did not form functioning connections, or synapses. Now the researchers have demonstrated that astroglial cells taken from young mice can be transformed into synapse-forming neurons, and can be directed into two different major classes of neurons.

The addition of one specific genegenerated excitatory neurons, which promote activity in other cells. By adding a different gene, they generated inhibitory neurons, which dampen cell activity. In principle, “you could generate other types of neurons if you choose the appropriate factors,” says study coauthor Benedickt Berninger. For instance, he said, researchers could generate the dopamine-releasing neurons that are destroyed by Parkinson’s disease.

The study adds to growing evidence that certain cell types can be transformed directly into other cell types without first being converted into stem cells. Researchers have previously transformed skin cells into neurons, and one type of pancreatic cell into another. Marius Wernig, a coauthor of the skin cell study and a stem cell biologist at Stanford University, says there’s a growing awareness that it may not be necessary to erase a cell’s existing identity before giving it a new one.

Wernig says that the PLOS Biology paper offers a new strategy for creating neurons that complements the approach of using skin cells. Skin cells, he says, would be more useful for generating a patient’s own cells in a petri dish for transplantation, because a skin sample is easy to obtain. In contrast, this latest study “means that these astroglial cells could be converted in the brain” without the need for a transplant. Berninger says that one of the next challenges is to determine whether these reprogrammed neurons can survive and function in a living brain.

Fortunately, the brain seems to have a ready source of astroglia. When the brain is injured, these cells proliferate, similar to the way the skin repairs itself after a wound. The researchers found they could also derive neurons from injury-induced astroglia taken from the brains of adult mice.

Sweet power: Scientists implanted a glucose-powered device into the abdominal cavity of a rat and measured its performance for three months. The glucose device consists of electrodes made of compressed graphite discs containing enzymes that catalyze the oxidation of glucose. The electrodes sit inside a dialysis bag that keeps enzymes inside but lets glucose and oxygen flow through.    Credit: Joseph Fourier University, National Center for Scientific Research

An implanted biofuel cell may someday power medical devices

MIT Technology Review, May 2010, by Janelle Weaver  –  Scientists have implanted the first functional glucose biofuel cell in a living animal. Unlike batteries that supply power to implants, a power-generating device may not have to be surgically removed and replaced, because glucose is a potentially limitless source of energy.

The device uses enzymes to harvest energy from glucose and oxygen found naturally in the body. Past attempts at using such a device in animals have failed because the enzymes have required acidic conditions or were inhibited by charged particles in the fluid surrounding cells. But Philippe Cinquin and his team from Joseph Fourier University in Grenoble, France, overcame these obstacles by confining selected enzymes inside graphite discs that were placed into dialysis bags. Glucose and oxygen flowed into the device, but enzymes stayed in place and catalyzed the oxidation of glucose to generate electrical energy.

The team surgically implanted the device in the abdominal cavity of two rats. The maximum power of the device was 6.5 microwatts, which approaches the 10 microwatts required by pacemakers. The power remained around two microwatts for 11 days in one rat, and the other rat showed byproducts of glucose oxidation in its urine for three months, indicating that the device lasts at least that long. “This is a big breakthrough for the field of implantable biofuel cells,” says Shelley Minteer, an electrochemist at Saint Louis University.

“It’s quite an interesting paper that demonstrates for the first time that one can generate electrical power from body fluids,” says Itamar Willner, a biomolecular chemist at the Hebrew University of Jerusalem.

The technology could be used for a range of applications, such as neural and bone-growth stimulators, drug delivery devices, insulin pumps, and biosensors, says Eileen Yu, a chemical engineer at Newcastle University. But whether enzymes remain stable for a long period of time is a concern, she says. And the efficiency of transfer of electrons between enzymes and electrodes should be improved, she says.

Cinquin believes his team can improve its efficiency. “I’m optimistic that we will get tens of milliwatts in future versions,” he says.

The authors would next like to test the device for longer periods of time in larger animals, improve its design, and incorporate biocompatible materials. “If industry finds a willingness to enter into the technological development of biofuel cells, I’m sure the use of biofuel cells to power medical implants will materialize in a very short period of time,” Willner says.

Making Medicine Personal

MIT Technology Review, May 24, 2010  –  A number of scientists bared their genetic souls recently as part of the Personal Genome Project, a study at Harvard University Medical School. They were among the first of the eventually 100,000 volunteers who will agree to place their genetic profiles on the Internet.

Genetic profiling can provide information on what diseases may befall us. And knowledge of an individual’s genetic makeup may also help scientists figure out how to treat diseases—part of an emerging field known as personalized medicine.

As many doctors freely admit, says Julie Johnson, director of the Center of Phamacogenomics at the University of Florida (UF), prescribing medicine is “more of an art than a science.” Approved drugs work—but not 100 percent of the time, and not for 100 percent of the population. Some people have no response to certain drugs, and others experience severe side effects.

What determines whether a particular treatment is effective or leads to severe side effects is our genes, scientists believe. Personalized medicine holds the promise of tailored medical treatments based on genetic information, rather than a one-size-fits-all approach.

The UF center participated in studies on warfarin, a blood thinner prescribed for millions of Americans to prevent heart attack or clotting after a heart attack. Too little of the drug causes a risk of clotting, and too much can cause excessive bleeding. “There’s a very narrow window, and there’s a great deal of variability among patients,” says Johnson. “A lot of work in the past decade has uncovered several genes that help explain a great deal of that variability.” In 2007, the FDA cleared a genetic test for sensitivity to warfarin to help doctors prescribe the correct dosage, although the tests are not yet widely implemented.

The UF center is also focusing research on drugs prescribed for hypertension, in an attempt to find the genes that “will predict how much a person’s blood pressure will go down if they’re administered certain medicines,” says Johnson.

Speeding the Process

Part of what has contributed to the increasing interest in personalized medicine is the speed and cost of sequencing genomes. The first human genome took many years and millions of dollars to sequence. The price has already dropped into the thousands instead of millions of dollars, and it’s expected to continue to fall. The journal Science listed “faster, cheaper genome sequencing” as one of the top scientific advances in 2008.

These advances have increased the speed of research in the field. John Reed, the president and CEO of Burnham Institute for Medical Research, a center with campuses in San Diego, CA, and Orlando, FL, says that the Florida campus has engaged in major initiatives related to personalized medicine. While Burnham’s research has traditionally focused on cancer and on neurodegenerative and inflammatory diseases, the scientific team is expanding into obesity, diabetes, and metabolism research.

“We all have friends who can eat french fries every day and never gain weight, while the rest of us will have a hard time getting the belt to fit,” says Reed. “There are genetic differences in how we metabolize food—individual metabolic rates, hormone signaling—that’s all just being worked out.” Burnham is partnering with the clinical research institute at Florida Hospital, particularly the diabetes center, to engage in research on the metabolic systems of the patients there.

A related field of research involves investigating which chemicals can affect the actions of proteins, encoded by specific genes. This is a natural path to drug discovery, but it can also aid in genomic research. “A chemical probe can be used in basic research to help identify the role of a protein or a pathway, aiding in understanding the biology of a particular gene,” says Patrick Griffin, chair of Molecular Therapeutics at Scripps Florida, a campus of Scripps Research Institute headquartered in California.

The National Institutes of Health (NIH) funds four molecule-screening centers in the United States to rapidly test a library of chemicals against specific proteins. Scripps Florida operates one of the four centers.

Burnham operates a second of those NIH molecule-screening centers at both its California and Florida research centers. Currently, its screening output can tackle half a million chemicals in one day, but the new system being developed in Orlando will be able to handle as many as 2.2 million chemicals a day.

The fields of genome research and rapid drug discovery are coming together to enhance each other, says Reed. “We’ll be able to, with far more accuracy, define for whom a drug is really going to work, and to avoid a lot of trial and error that we experience when we’re confronted with a health issue.” He and other researchers in the field see a time not too far in the future when understanding individual genomes will lead to better, more effective medical treatments for everyone.

Target Health at DIA (Washington, DC) and BioMed (Israel)

June will be a busy month for Target Health. We will again have a booth at DIA (June 14-16) and will be sharing our paperless eClinical trial suite of software products as well as our full service CRO capabilities. We anticipate 2 FDA approvals this year as well as an eCTD submission. We will feature Target e*CRF® fully integrated with Target Encoder®, Target e*Pharmacovigilance™ and batch edit checks; Target Document® and Target e*CTMS™. For Pharma companies, we will share our eSource software which will revolutionize the monitoring of clinical trial data. Please contact Warren Pearlson (212-681-2100 ext 104) if you will be attending and would like to see any demos.

During the same week of DIA, Dr. Jules T. Mitchel will be attending BioMed (June 14-16) in Israel. BioMed highlights the biotech industry in Israel and gives us a chance to meet our colleagues in Israel. Let us know if you will be attending so we can plan a get-together. 

For more information about Target Health contact Warren Pearlson (212-681-2100 ext 104). For additional information about software tools for paperless clinical trials, please feel free to also contact Dr. Jules T. Mitchel or Ms. Joyce Hays. Target Health’s software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health website: www.targethealth.com

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