Growing proteins in space

Published in Drug Discovery News

BOSTON—Taking protein-growing to high altitude and low gravity, Emerald Bio has joined an arrangement led by the Center for the Advancement of Science in Space (CASIS) and catalyzed by the Broad Institute of MIT and Harvard to send labs on chips to the International Space Station to study growth of proteins that may help develop treatments for cholesterol and cancer back here on Earth.

 

Though Melbourne, Fla.-based CASIS has offices in Cambridge, Mass., this is the first time the NASA-selected manager of the International Space Station U.S. National Laboratory has collaborated with the Cambridge-based Broad, according to Brian Hubbard, director of the Broad’s Therapeutics Project Group.

 

The Broad does work frequently with Emerald Bio, though, and when Hubbard heard last summer that CASIS was interested in growing proteins in space (which had been done before, but not with current technology), he thought of Emerald. “It came together very quickly,” Hubbard tells DDNews, crediting the Broad’s “open collaborative model” with the efficiency. “You don’t need to form a team. The team is already there.”

 

And it’s a diverse but focused team. In addition to CASIS, Emerald and the Broad, the crew also has NanoRacks of Houston (which has scientific hardware on the ISS) and Protein BioSolutions of Gaithersburg, Md., which recently purchased from Emerald the microfluidic technology that will enable more than 7,000 separate protein-growth experiments to fit in the space allotted on the space station.

 

“We were actually approached by CASIS … through the Broad,” George Abe, president of Emerald Bio, says. With available time and energy, CASIS was interested in new reasons for growing proteins in microgravity. And CASIS wanted something of real therapeutic value.

 

Emerald suggested two possibilities: proprotein convertase subtilisin/kexin type 9 (PCSK9), a gene that raises LDL (low-density lipoprotein) cholesterol, and myeloid leukemia cell differentiation protein 1 (MCL1), a key gene in cancer treatments.

 

Neither structure has “been solved in its empty state before,” Abe said. Protein structures are “extremely sensitive to a lot of environmental factors,” Abe said. “A protein structure will grow or evolve differently in a microgravity environment than on planet Earth.” How they grow when freed from Earth’s gravity could provide new information that will lead to approaches to inhibit relevant genes.

 

That direct approach is typical of the Broad, Hubbard said. “We’re looking to have real impact on patients but we’re also looking to . . . disruptive technologies” with prospects not today but five to 10 years out, he said. Often, if things aren’t druggable directly, researchers work to find the relevant genes, then proteins and then follow the thread back through gene regulators, eventually finding something that is druggable, he said. But at the Broad, they go for the target itself, even if that means inventing new technology, Hubbard said.

 

And while the technology itself already existed, the method had to be created to allow this research to proceed. Originally, Emerald had thought it might send the equipment to grow proteins up to the ISS, but that was too big to fit, and too complex to ask astronauts to handle in addition to their other duties.

 

Instead, Emerald will express and purify the proteins, and then ship them to Protein BioSolutions with protocols for building 36 identical pairs of labs on chips, with each chip holding 200 different configurations of pH, salinity and other environmental factors. The chips will be immediately frozen, with one of each pair sent to the ISS and the other 36 sent to Emerald as controls. (The launch was slated for April as of the writing of this article.)

 

The chips will be thawed and the astronauts—as well as scientists on Earth—will observe what happens. After about six months in space, the samples will be returned to Earth.

 

“For any structures that actually grow in space, we will be performing X-ray diffraction on those,” Abe said. And then chemists associated with the Broad will work to identify potential therapeutics that could bind with those proteins, either to prevent their formation, or block or otherwise modify them.

 

This does not mean that protein production or other aspects of drug development will have to occur in space; rather, it will allow people to discover important information they can use in terrestrial study and production. Nevertheless, this experiment will be a test in another way: of how valuable “a potential market demand for doing early-stage drug discovery work in a microgravity environment” might be, Abe said, noting that this new opportunity could help the ISS remain scientifically and budgetarily viable.

Bringing FDA-approved NGS tests to the masses

Published in Drug Discovery News

SAN DIEGO—Expanding applications of its recently FDA-approved MiSeqDx in-vitrodiagnostic next-generation sequencing (NGS) system, Illumina has agreed to help develop a multigene, NGS-based test to identify prospective patients for Vectibix (panitumumab), an anti-EGFR monoclonal antibody drug developed by Amgen, a drug company based in Thousand Oaks, Calif.

 

“This collaboration is consistent with our strategy to bring the power of NGS to clinical diagnostics,” said Nick Naclerio, senior vice president of corporate and venture development and general manager of Illumina's Enterprise Informatics business. “With three FDA-cleared NGS products in our portfolio, we intend to complement internal development programs by taking products developed with external partners through the FDA submission process. Amgen is a key partner given their leadership in therapeutic development and strong track record in commercializing novel products.”

 

“NGS provides an advantage over traditional technologies that typically detect only one or a few variants,” added Dr. Rick Klausner, chief medical officer and acting general manager of Illumina’s oncology business. “Multigene NGS panels provide a more complete genetic picture of each patient's tumor, which can better inform critical treatment decisions. We see the development of multigene diagnostic tests as a natural evolution to improve cancer care and outcomes.”

 

Vectibix has regulatory clearance in the United States and the European Union for targeting metastatic colorectal cancer that has not responded to chemotherapy.

 

At present, Illumina has just three tests available for the MiSeqDx instrument, which uses the sequencing-by-synthesis method of assaying. There is a universal kit allowing researchers to make their own tests, and two tests for assaying genes connected with cystic fibrosis. MiSeqDx’s November 2013 FDA approval makes it the first NGS platform with that imprimatur. To build on that achievement, market analysts report that the company has eagerly sought partnerships like the new one with Amgen.

 

Using the Illumina platform, the test to be developed could solve a key problem Amgen has with Vectibix: the drug is aimed at less-aggressive forms of the cancer and is restricted for patients who have, or do not know whether they have, KRAS mutations, which are associated with more aggressive cancers and lower survivability. But there is not yet an FDA-approved test to determine KRAS mutation status for potential Vectibix patients.

 

According to a report on GenomeWeb.com, Amgen is also working with Dutch-headquartered QIAGEN to develop a polymerase chain reaction kit to detect KRAS mutations that might affect Vectibix’s usefulness. The financial details of that deal are not being made public.

 

The Illumina test would not only use NGS technology, but would also detect RAS oncogene mutations beyond just those in KRAS.

 

“We believe the NGS platform offers great market potential,” reads a report from Zacks Investment Research, which also says the analysis firm is “optimistic about management’s expansion strategy,” which involves working with diagnostic and therapeutic developers and providers. In January alone, the company announced agreements with both Quest Diagnostics and LabCorp, with Illumina providing equipment and supplies for its partners to develop new lab tests.

 

Under the terms of the Vectibix deal, Illumina will develop the test, which will be validated by Amgen. Then both companies will work to get FDA and European approval, before Illumina commercializes the test.

Absorbing more ‘bad’ cholesterol

Published in Drug Discovery News

THOUSAND OAKS, Calif.—Completing a key step toward filing for regulatory approval of a broadly applicable cholesterol-reducing drug, Amgen has announced promising results from its fifth Phase 3 trial—the RUTHERFORD-2 trial—of evolocumab, a fully human monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver’s ability to remove low-density lipoprotein cholesterol (LDL-C) from the blood.

 

LDL-C is a major risk factor for cardiovascular disease, and more than 71 million Americans have high LDL-C, according to the U.S. Centers for Disease Control and Prevention. Patients who have both high cholesterol and high cardiovascular risk are key target markets for evolocumab.

 

While the trial’s full results will be announced in Washington, D.C., at the American College of Cardiology’s 63rd Annual Scientific Session in late March, Amgen has said that the drug successfully combined with statins and other lipid-lowering drugs to reduce LDL-C, also called “bad” cholesterol, for patients with heterozygous familial hypercholesterolemia.

 

Previous trials have found evolocumab useful for patients with high cholesterol who were not previously getting anti-lipid treatment, as well as those already on statin drugs, and those who cannot tolerate statins, the most common type of anti-cholesterol drug.

 

While statins inhibit an enzyme that controls production of cholesterol in the liver, evolocumab binds to PCSK9, blocking it from binding to LDL receptors on the surface of the liver, according to the company’s description of the drug. That frees up more LDL receptors to remove LDL-C from the blood.

 

According to the company, a total of 13 trials are slated, including testing varying methods of injecting the drug and different frequencies of administration. About 30,000 patients will be involved, including those with cardiovascular disease, hyperlipidemia, coronary atherosclerosis and familial hypercholesterolemia (whether heterozygous or homozygous).

 

Those latter conditions, which are genetic, cause high levels of LDL-C starting at birth, and place patients at high risk for cardiovascular problems early in life. Heterozygous familial hypercholesterolemia affects about one in every 300 to 500 people worldwide, according toWorld Health Organization data.

 

The results so far will be shared with regulators, in hopes of securing approvals in 2014, the company said in a statement to DDNews. The exact timeline depends on results of ongoing trials.

 

Since Jan. 23, Amgen has touted positive top-line results for evolocumab from the Phase 3 GAUSS-2 trial in statin-intolerant patients with high cholesterol, the Phase 3 LAPLACE-2 trial in combination with statins in patients with high cholesterol and the Phase 3 RUTHERFORD-2 trial in patients with heterozygous familial hypercholesterolemia.

 

Of the most recently announced top-line results, Dr. Sean E. Harper, executive vice president of research and development at Amgen, said, “Data from the RUTHERFORD-2 study suggest that evolocumab, when used as an add-on therapy to existing lipid-lowering medications, may offer a new treatment option for patients with heterozygous familial hypercholesterolemia. The RUTHERFORD-2 study is the fifth pivotal LDL-C lowering study in our Phase 3 program. The robust data from these five studies will form the basis of our global filing plan, and we look forward to discussions with regulatory agencies.”

Press Releases: Beyond politics

Published in the Portland Phoenix

Today’s US media environment might well seem extremely gay-friendly. American mainstream media consumers saw a fair amount of coverage of anti-gay discrimination in Russia in the lead-up to, and during, the Winter Olympics in that country (read more on this topic on page 10); there was relatively little outcry when President Barack Obama selected several gay former Olympians to represent the United States in the audience. Johnny Weir both dressed and behaved flamboyantly on NBC’s nightly figure-skating broadcasts. Heck, even marriage equality gets little more than ho-hum headlines these days as this vital civil-rights issue continues its progress around the country.

But there is still much more to be done, and last weekend, a one-day conference at Colby College in Waterville sought to explore what, and how.

Called “Queering the Media,” the event, put together by members of Colby’s all-inclusive LBGTQ-plus-allies support group The Bridge, appeared to be less about news-media coverage and more about modern culture, as described by organizers Andy Kang and Sonja Hagemeier.

The intent was that “‘queering’ would be a relatively broad and very widely interpreted term,” Kang says. Looking at “how the media portrays or represents, or tries to represent, or fails to represent, people who don’t fit into mainstream culture” is important, he says, because it can help remind consumers of that information that other viewpoints and experiences exist.

This is important in Maine particularly, says Hagemeier, because “a lot of people think of Maine as really isolating, especially for queer people.” She spoke in almost mystical tones about Portland, a place she has heard is “very very queer friendly,” while observing that it is only slowly that “people are getting used to the idea” in other parts of Maine.

Their conversations at the conference, including presentations by students and current and former Colby faculty, as well as noted queer scholar Jack Halberstam, covered athletic environments, video games, and churches’ roles in social-justice efforts. That’s certainly a departure from most coverage of LGBTQ issues in Maine’s mainstream media. In those outlets, Kang says, queerness is not treated culturally. Instead, “all these topics seem much more politically charged.”

That’s a lesson many Maine journalists could take to heart regarding not only gay culture but other aspects of Maine’s shifting demographics. Somali immigrants, for example, are interesting at times other than just when they’re running for political office or being attacked by anti-immigration activists. The same goes for people of other cultures and backgrounds.

>> Farewell This will be my last Press Releases column; managing editor Deirdre Fulton will take over starting next month. I’ll leave you with a few goals to hold the Maine media to in the coming year:

1) Ask candidates for electoral office (at all levels) hard questions about specific issues, rather than allowing the candidates themselves to set the discussion agenda — thereby neatly avoiding any controversial issues or having to actually take positions on important questions of the day.

2) Allow politicians to change their minds. But don’t let them pretend they didn’t, nor that their new position is functionally the same as the old one. People grow, learn, and change. Expecting people to hold the exact same positions and beliefs forever in effect demands that people remain as misguided and unenlightened tomorrow as they were yesterday. But, when public figures change their minds, they should be able to, and asked to, explain why and how that happened.

3) Lastly — and this is to everyone, whether you work in the media or not — remember that government works for us. We own the desks and filing cabinets in City Hall and the State House, and the documents stored in them. We own the computers and the servers in government offices, and the information stored on them. If a government official wishes to keep something secret, she must prove that she is legally allowed to do so. The burden is not on us as the public to force openness on government, but on government — and its (our) workers — to lay themselves and their records open in exchange for the privilege of serving with the public trust.

Never Again Dept.: Learning from FairPoint's disasters

Published in the Portland Phoenix

Two bills before the Maine legislature seek to pry lessons from the hard time FairPoint has had taking over the former Verizon landline operations in Maine since 2009. Both step up government oversight, in hopes of preventing future debacles.

The first, LD 1761, could in fact be called the “FairPoint: Never Again” bill. It reads like an admission that the Public Utilities Commission’s process around the FairPoint-Verizon takeover was a disaster.

It would require state regulators to review all mergers and sales of companies earning more than $50 million a year not just to the standard of “doing no harm” to Maine consumers (incidentally, a standard current PUC chairman Tom Welch admits the FairPoint deal did not meet — a pity he wasn’t on the PUC when the deal was being considered) but rather such a deal must offer a “net benefit” to Mainers.

It would also specifically require regulators to consider any proposed deal’s impact not just on consumers and ratepayers, but also on workers at the company involved, as well as the state’s overall economic-development goals.

The move specifically anticipates the possibility that FairPoint might be looking for a buyer. “The hedge funds that own FairPoint are looking for an exit strategy,” says Matt Schlobohm, executive director of the Maine AFL-CIO. Unions are key proponents of this bill because of its enhanced consideration of the labor force in deals involving utility companies, which are often unionized, as FairPoint is.

If FairPoint does plan to sell — and there is a handful of potential buyers, mainly regional landline companies — “we’re not well prepared to get a good outcome” for Maine, Schlobohm says.

He fears a repeat of the FairPoint deal, in which regulators approved a deal that was questionable at best (see “A Bad Idea Triumphs,” by Jeff Inglis, February 29, 2008), with certain conditions imposed, but then over time waived many of those conditions one by one (such as benchmarks for rolling out higher-speed Internet service to more customers in Maine). 

“Why would the state not want to have more leverage” when dealing with big companies that have outsize impacts on Maine, both as utilities providers and major employers, Schlobohm asks.

The second bill is even more directly aimed at FairPoint itself. This one, LD 1479, could be called the “Oh No You Don’t, FairPoint” bill. It secures legislative oversight, review, and approval of any PUC ruling in response to FairPoint’s recent request for $67 million in support from Maine telecom consumers to subsidize its service to rural Mainers with no other options for phone connectivity. That amount would be paid by raising the Maine Universal Service Fund surcharge on all telecommunications bills (including Mainers who do not use FairPoint’s services) by as much as $5 per line per month. (See “FairPoint Wants Bigger Subsidies, From All Mainers,” by Jeff Inglis, January 3.)

And it comes at a time when FairPoint’s stock price is recovering — largely because of the prospect it may resume issuing dividends. Investors are certainly clamoring for that to happen; dividends were curtailed in the original deal by order of state regulators, and ultimately done away with because the company couldn’t afford them.

“There’s a pattern here,” says Schlobohm. “The company seeks resources . . . they figure out where to get them . . . they’re sent very quickly to Wall Street.”

While he admits this may not be the case now, he observes that “there’s not much trust built” between FairPoint and Mainers.

The union does support the idea of having phone service available to every Maine home, but is not sure that FairPoint’s request is the best or most efficient way to achieve that.

The online chef: Hungry for restaurant-quality scallops at home, one writer turns to YouTube

Published in the Portland Phoenix

A couple years back, I decided I wanted a new challenge in the kitchen. I love eating scallops at restaurants, and wanted to learn to make them myself. It turns out that home-cooked scallops are crazy-easy, super-delicious, and far cheaper than if you get them when you’re dining out.

But they’re intimidating: How do you get that crispy crust without burning the delicate mollusks? And how do you get them done just medium-rare in the middle, so they’re moist and flavorful, not rubbery and bland?

Recalling a previous year’s cooking lesson from Gordon Ramsay (he taught me how to cook delicious, tender scrambled eggs), I went to the same place I’d found Gordon: YouTube.

It’s truly surprising how much teaching is available on YouTube — and cooking lessons are no exception. I searched for scallops and came up right away with a 2008 video made by Bill King, who was then the executive chef at McCormick and Schmick’s seafood restaurants. (Searching for clams, mussels, oysters, or any other shellfish is similarly rewarding.)

King had a mouthwatering recipe for pan-seared scallops with sweet Thai chili and udon noodles. The video’s production value wasn’t that great, but I wasn’t there for a visual spectacle. The images and audio were clear, the instructions simple and basic, and the demonstration smooth.

I watched it, took notes, and watched it again. Then I went out and bought the ingredients: sweet Thai chili sauce, sesame oil, fresh sea scallops, and a couple packages of precooked udon noodles. (You can also get uncooked ones and make them yourself, just like pasta. I went for the easier option.)

It didn’t cost much; in fact, the scallops, which are so often expensive in restaurants, were under $7 for a solid handful that would serve two. (King’s example included three large scallops; I sometimes opt for four if they’re smaller.) The udon-noodle packets were a dollar apiece. The bottles of chili sauce and the oil were a few dollars each, but they’d keep and be available when I made more scallops later. Sure, it was more expensive than a couple of hamburgers, but not far off the price of steak, and much cheaper than lobster for two (even at today’s sea-bottom prices).

All that remained was to emulate a chef with formal training and decades of experience, in my own kitchen.

It didn’t quite work out the first time. Heeding King’s suggestion to have a very hot skillet, I ended up giving everything a nice layer of carbon. But I was learning, and I could see where I had gone wrong by comparing what happened in my pan with what happened in the video. I knew where I’d gone astray; in fact, I had indeed feared I was burning the noodles and the scallops while they were cooking. I hadn’t jumped in to lower the heat or stop the cooking earlier because I was on my first trial run and taking the directions very seriously.

I would not make that mistake again. It turns out — shocker! — that getting the cooking temperature right is crucial to preparing seafood properly (and, yes, other food too). My pan had been too hot, and I had left the noodles and scallops in the too-hot pan for a bit too long.

Still, I enjoyed the flavors, and was able to craft a plan for improving my performance next time.

And that’s perhaps the crucial rule of taking cooking lessons from YouTube: Test it out before you’re on the spot. If you’re cooking for a family gathering, or even just a hot date, don’t have that be the first time you’re trying to follow a video. Do it a couple times, even several, until you get it right.

Sure enough, a few days later, I was back at the seafood counter, buying more scallops, and then into the Asian section to grab some udon.

That time, I got the noodles right, but undercooked the scallops — I was too afraid of burning them and took them off the heat early. But I rescued them by returning them to the heat. (The removal-and-return to the pan meant the golden-brown crust wasn’t perfect, but I was making progress.)

It took a few more times — and a bad experiment cooking on a different stove at a friend’s house — before I felt confident in being able to make this dish reliably. And even now, I occasionally let them cook too long or too short, and have to make do with a substandard dish.

But it’s in my own home, with friends and family, and vastly cheaper than dining out. So I eat with relish! 

Make them yourselfHere’s the recipe; watch the video at: tinyurl.com/learntocookscallops.

Ingredients

>>Three to four sea scallops per person
>>One packet of pre-cooked udon noodles per person
>>Thai sweet chili sauce
>>Sesame oil

Procedure

>>Pat the scallops dry with a paper towel and then put them in a bowl with a small amount of Thai chili sauce atop each scallop, and a thimble-full or two of sesame oil apiece. Gently mix them with tongs or a spoon, to coat evenly. Set aside.
>>Heat a skillet on medium heat (ignore the video’s recommendation to have it very hot!), and lighly coat the pan with vegetable oil.
>>Put the udon noodle cakes in — only as many as will fit comfortably. Don’t pack them too close together. Now, don’t move them.
>>Cook them for 3-5 minutes, until you can see a golden-brown crust forming on the underside. You can peek carefully if you want to, or just flip them over and cook on the other side as well.
>>While they’re cooking on the second side, put a dab of the chili sauce on top, as well as a drop or two of sesame oil.
>>When they’re cooked through (they become more translucent and flexible), remove them from the heat and set them aside.
>>Wipe the pan with a dry paper towel, just to remove any debris or residue from the noodles.
>>Now return the pan to the heat (still medium) and put the scallops in.
>>Here’s the trick to getting the right crust on the scallops: Don’t touch them once they’re in the pan. Let them sit right where they are, sizzling, for about 2 minutes. (Three minutes if they’re much thicker than an inch.)
>>Then flip them over, revealing the very nice crust, and cook them for another two minutes on the other side.
>>Remove from the pan, and serve immediately.

Physicians now taking payment by bitcoin: Lower transaction costs, increased privacy protections lead some practices to accept controversial e-currency

Published in Healthcare IT News, Healthcare Finance News, and Medical Practice Insider

Whether looking to draw attention to their practices, experiment with new technology or simply have a bit of fun with their otherwise dreary financial operations, several American medical professionals are now accepting bitcoins, the Web-based virtual currency, in addition to dollars.

Bitcoin, a peer-to-peer, open-source digital currency network that was first launched five years ago, has been getting a lot of media attention lately – sometimes for dark stories such as those spotlighting its role as the currency of choice for Silk Road, an online black market for illegal drugs that was shut down by the FBI this past October.

But it's also getting strong positive attention, especially from Internet thought leaders, because the Bitcoin system, which depends on no centralized authority but rather a loosely affiliated community of techies, offers some key breakthroughs in the areas of information exchange – particularly between parties unknown to each other – and digital cryptography.

The legal status of this so-called cryptocurrency is in flux worldwide, as various policymakers, monetary bodies and tax agencies get up to speed on its true ramifications.

In the meantime, curious people can still educate themselves and explore this new payment alternative without fear and in relative safety.

Doctors who have taken bitcoins have found that doing so is both simple and relatively "unmagical," as San Francisco physician Paul Abramson, MD, put it.

Abramson, founder of My Doctor Medical Group, is a former software programmer and trained electrical engineer with a significant personal interest in privacy.

It was privacy that drew him to learn more about bitcoins. Early assessments of the technology suggested the bitcoin exchange system had significant anonymity protections that could augment existing medical privacy laws and allow patients who sought the ultimate discretion a nearly invisible form of payment.

"It's important for people to be able to maintain their privacy" about all things, but particularly medical issues, Abramson said.

However, as bitcoin use has expanded, further exploration of its privacy protections has shown that, while it does take some effort to uncover a bitcoin user's identity, it is possible.

"As I've learned more about it," said Abramson, "I'm less excited about the anonymous possibility."

In any case, patients in his office seeking medical attention can't very well protect their identity from him – which removes one possible benefit of using bitcoins: the anonymity between buyer and seller.

Despite the media hype and controversy surrounding this new currency, Abramson is almost blasé about the fact that he accepts bitcoins.

"It's actually not that big a deal," he said.

But the benefits do exist. For instance, taking transactions out of the hands of credit card companies can preserve patient privacy, as those organizations can legally access certain protected health information for the purposes of verifying the transactions.

And, as a business practice, accepting bitcoins has real potential to save Abramson money.

He uses a fairly simple setup, where he has a merchant account with a company that handles bitcoins; when he receives bitcoins, that company handles converting them into U.S. dollars. The company charges a 1 percent fee – which is less than the typical 2 or 3 percent transaction processing fee charged by credit card companies.

This method is in fact in common use throughout the bitcoin community: People contemplating a purchase buy bitcoins with dollars, and then, in exchange for goods or services, send them to a vendor, which then immediately converts the bitcoins back into dollars.

But it's only in the conversions where fees arise.

As John Gomez, MD, owner and medical director of RapidMed Urgent Care Center in Lewisville, Texas, points out, to transfer bitcoins from one person to another, there are "zero transaction fees. Zero. It's beautiful."

And there were no startup costs, because his office already had an iPad for other purposes. (One possible problem may arise there, as Apple has recently been removing bitcoin-related programs from its app store.)

Gomez's office manager, Barbie Fiorendino, says no patients have yet used bitcoins to pay for service, but customers are expressing curiosity and interest in the prospect – especially since a local television station did a story about the clinic and bitcoins in January. The clinic distributes printed literature with explanations, and also has a bitcoin section on its website.

Unlike Abramson, Gomez is not planning to convert his payments out of bitcoins. His accountant, who was "very open-minded" about him accepting bitcoins, said he should book his revenue as dollars according to the bitcoin exchange rate at the time of the transaction – and keep records for future years, when he might convert the bitcoins he received back into dollars.

At that time, he would have to calculate capital gains or losses for tax purposes.

His decision to keep his holdings in bitcoins is "a personal belief," he added. "I consider myself a future rich man" because of bitcoins' value prospects, he said.

"There will be ups and downs and there will be potential manipulations," said Gomez, but "in the long run, I think that it's a smart play."

Gomez is more enthusiastic about bitcoins than Abramson – perhaps even qualifying as somewhat of an evangelist.

"I am, generally speaking, an early adopter of technology," Gomez said. Beyond that, "I have certain, I guess you would say politically libertarian leanings," he said.

He is among the many bitcoin enthusiasts who are particularly excited about the existence of a relatively secure currency that is not controlled by a government or other central authority.

Rather, the Bitcoin system is managed by software and mathematical principles, and is made possible by a peer-to-peer network that shares the burden of tracking bitcoins to ensure nobody counterfeits any, or spends the same bitcoin twice.

"It is an abstract concept at first," Gomez admitted – but said that's really no less foreign than the idea that swiping a credit card is a functional stand-in for exchanging dollar bills.

Meanwhile, government regulators are paying close attention, with several countries, the U.S. included, studying how to track – and tax – bitcoin transactions. How those regulations shape up will likely determine the degree to which bitcoins become more widespread, Abramson said.

It's not always easy to use bitcoins, as Wall Street Journal writer Anne Kadet found when visiting various New York City businesses that take them.

"This took some doing," she wrote in January. At one point, using bitcoins was so technologically "cumbersome" that it was "looking like the worst currency ever."

But Gregory Levitin, MD, a Manhattan physician and assistant clinical professor of otolaryngology at the New York Eye and Ear Infirmary, believes bitcoins can help people improve access to medical care.

Levitin, who has patients around the world, was in India and not available for an interview. But in a December press release announcing his acceptance of bitcoins, he said he hoped the move "will open doors to treatment options and follow up care for patients the world over," by allowing them to use "a universal or virtual currency."

One area where Gomez and Abramson agree is the fact that bitcoins are not particularly useful when it comes to their business operations.


Gomez said he wishes more vendors and suppliers took bitcoins. (He has convinced the person who cuts his hair to accept them in payment, however, and he's also ordered items from Tiger Direct, an online retailer that accepts bitcoins.)

Likewise, Abramson says he has nobody with whom he can really do business in bitcoins. His landlord won't take them, and he has asked his employees if they want to be paid in bitcoins, but they have all declined.

There is, however, a cupcake store near his office that accepts them.

Further thoughts on bitcoin

Dos and don'ts

If you're not sure about setting up your practice to accept bitcoins, consider the following suggestions:

"If you don't believe in bitcoin, don't bother," Gomez said. Abramson echoes this, suggesting people not accept bitcoins "unless you understand the potential ramifications," including keeping your bitcoin account information secure (if it's lost, your bitcoins are gone forever, with no way to recover them), as well as exchange-rate fluctuations and government regulatory moves. And it's important to follow new developments in this rapidly changing community.

If you do accept them, Gomez suggested holding them, reflecting his belief that bitcoins will appreciate in value over time. Abramson said just the opposite, calling people who hang onto bitcoins "gamblers" playing a market that has fluctuated wildly, hitting highs of over $1200 per bitcoin in early December to around $600 right now.

That said, "it's easy to take bitcoin," Abramson said. "As a technology I think it's very interesting." He suggests accepting bitcoin "for amusement value," or perhaps as "a marketing move."

Changing behavior

Paul Abramson, MD, of My Doctor Medical Group in San Francisco offers addiction treatment as one of his services, and has found that accepting bitcoins brought him some unexpected business.

"I had some patients who had been buying drugs with bitcoins on Silk Road," an illegal-drug marketplace website that only handled transactions in bitcoins, but was shut down by the FBI in October 2013. "They had been buying heroin with bitcoins."

When they were no longer able to buy high-quality heroin, they decided to seek help from him instead.

As he observed, "you could buy both drugs or drug treatment with bitcoins." But then, "the same is true of hundred-dollar bills, so it's really not that novel."

Bad advice?

CoinMD, a website where users can ask medical questions from a group of anonymous people who claim to be doctors – paying for their advice in bitcoins, has been called "the absolute worst place on Earth to spend your bitcoins," by Wired.

While many of the site's advice givers may be well-intentioned and knowledgeable, and its convenience when it comes to diagnosing minor ailments may seem obvious, Wired points out that "no legitimate licensed physician" would take part in a project like this because they "they would risk losing their license." CoinMD doesn't define how it tracks its contributors or vets their credentials.

So while the idea behind the site might be great in theory, as Iltifat Husain, MD, a practicing emergency physician the editor-in-chief of iMedicalApps, explained to Wired, there's a "tremendous" risk of getting poor advice or a wrong diagnosis. "I would never recommend this site to a patient," he said.

Downsizing has major benefits

Published in Drug Discovery News

BRISBANE, Australia—After a decades-long search for a so-called “holy grail” of biochemistry, Australian researchers have announced they have found a way to significantly reduce the size of molecules that have similar bioactivity to large proteins, preserving the proteins’ functions while also making the new molecules far more stable in the body.

 

Scientists at the Institute for Molecular Bioscience at the University of Queensland have proved the concept and method of growing small, stable molecules around key amino acids in complement protein C3a, which helps reduce inflammation and fight disease. By focusing tightly on the bioactive area of the protein, they have reduced the size of the molecule from 77 amino acids to just three, making the product much more suitable for inclusion in medications.

 

C3a, like many proteins, is large and expensive to make, as well as quick to degrade once introduced into the body. But this technique not only makes the molecules cheaper and smaller, it also makes them far less susceptible than the full protein to enzyme breakdown or immunogenicity once in the bloodstream.

 

Prof. David Fairlie, who co-led the research group with Dr. Robert Reid, said the method should be generalizable to other proteins with very different functions. “This technique is not specific to C3a. It relies only on knowing the location of a single amino acid of a binding protein within its receptor protein,” he says. “The trick … is of course to first know the location of an amino acid within the biologically active region of that protein, and then to know what amino acids in the target protein that you wish to bind to.”

 

Making that connection possible involves a very complicated multistep process, which is laid out in an appendix to the journal article announcing the discovery, published in Nature Communications in November under the title “Downsizing a human inflammatory protein to a small molecule with equal potency and functionality.” Involving multiple chemicals, heat, stirring and other techniques to build up and rearrange the amino acids so they will fit with the target protein, the process must not only preserve the amino acids themselves, but also build up a molecular scaffold that mimics the shape of the original protein, to ensure proper binding. The method took about 20 years to perfect, including the last 10 years focusing specifically on C3a as an example, Fairlie notes.

 

The breakthrough makes possible new and more effective medications more specifically targeting proteins in the body. Because the method of making smaller molecules is not specific to C3a, “it is potentially applicable to any protein involved in any disease, and most diseases involve proteins interacting with other proteins or macromolecules,” Fairlie says.

 

The lab will continue to work to improve “small-molecule drugs that target the human complement C3a receptor for use in treating inflammatory and metabolic diseases,” Fairlie says. And the researchers will use the now-proven approach to work with other types of proteins, targeting “a wide range of diseases like viral and parasitic infections, inflammatory diseases such as arthritis, metabolic diseases such as obesity, type 2 diabetes and cardiovascular disease and cancers,” according to Fairlie.

 

Beyond protecting the intellectual property with patent applications, the lab is “interested in discussing license agreements with pharmaceutical and biotechnology companies,” says Mark Ashton, manager for innovation and commercial development at Uniquest, the University of Queensland’s main commercialization company.

 

To that end, the lab has established a partnership with Pfizer, including $2.2 million in funding from the Australian Research Council and another $2.1 million from Pfizer itself, to develop specific new medicines with this technique. This may result in some medications that can be delivered orally using smaller drugs, where “currently there are only large peptide drugs available that need to be administered intravenously,” Ashton said.

Jazz Pharmaceuticals is jamming

Published in Drug Discovery News

DUBLIN—Rapidly expanding its orphan-drug portfolio and planning for $1 billion in revenue in 2014, Irish company Jazz Pharmaceuticals is in the process of acquiring Italian drug firmGentium, and has acquired anti-narcolepsy drug ADX-N05 from Aerial BioPharma, based in North Carolina.

The Gentium acquisition, announced in mid-December, is worth roughly $1 billion, with Jazz making a tender offer of $57 per share to Gentium holders (a 26-percent premium on the volume-weighted average share price over the previous 60 days). Jazz will pay for the deal with a combination of cash on hand, a $500 million incremental term loan from Barclays and the remainder under its existing senior secured credit agreement with Barclays. The company estimates its borrowing costs at 3 to 3.5 percent interest.

The deal will bring into Jazz’s stable a promising drug, Defitelio (defibrotide), which treats severe hepatic veno-occlusive disease (VOD) in children and adults receiving hematopoietic stem cell transplants. In October, Defitelio was approved by European regulators for sale in the European Union, and is protected under orphan-drug exclusivity laws there through 2023.

Hematopoietic stem cell transplantation (HSCT) is more common in Europe than the United States, with 35,200 EU patients in 2013, compared with 19,500 U.S. patients, and 7,600 in the rest of the world. About 10 percent of HSCT patients develop severe VOD, which can involve multiple organ failure; untreated, it has an 80-percent mortality rate within 100 days.

Defitelio is also designated as an orphan drug by the U.S. Food and Drug Administration (FDA); it is not approved yet, but is in Phase 3 clinical trials and has fast-track status for FDA approval pending the results of those trials. There are no other drugs approved in the United States for VOD, according to Jazz disclosure materials.

In addition, Defitelio is being studied to treat graft vs. host disease, which could boost its sales potential significantly, the company anticipates.

Defitelio joins a handful of other orphan drugs in Jazz’s portfolio, addressing hematology and oncology, pain, psychiatric needs and sleep disorders. The company’s major earner in that last category was Xyrem (sodium oxybate), which brought in $154 million of the $230 million the company grossed in the third quarter of 2013. While the results of previous acquisitions and expansions mean Xyrem’s share of overall company revenue is dropping, the drug’s earning power remains on the rise. The Q3 total was 15 percent higher than the previous quarter, and 150 percent higher than the same quarter a year earlier.

In the wake of the deal, Bloomberg News reported that Jazz could be a very attractive acquisition target, with high growth and expanding potential. An advisory from Leerink Swann Research analyst Jason Gerberry said the opportunity “appears reasonably attractive, and potentially durable,” with an initial market size of up to $100 million.

A mid-January acquisition, ADX-N05, will expand Jazz’s presence in the sleep sector. Carrying worldwide development rights (except certain parts of Asia) and patent protection through 2027, the deal cost $125 million in cash, plus up to $272 million in future milestone payments, as well as ongoing royalties to both drug creator Aerial BioPharma and New Jersey-based SK Biopharmaceuticals, which holds the remaining Asian development rights.

The drug treats narcolepsy, which has in the United States about 25,000 patients with inadequate control of their condition; a major growth opportunity will come if ADX-N05 is also approved to treat obstructive sleep apnea, which offers a potential U.S. market of between 150,000 and 275,000. 

At a Jan. 13 presentation at the JP Morgan Healthcare Conference in San Francisco, Jazz chairman and CEO Bruce Cozadd presented slides saying the company expects between $867 million and $877 million in total revenue for 2013, but projects surpassing $1 billion in 2014.

Labor Relations: Blacklisting companies that ship work overseas

Published in the Portland Phoenix

Seeking to protect nearly 20,000 Maine jobs from being sent overseas, labor and union activists lobbied the state legislature last Thursday, with solid support and some modest, but expected, opposition. The bill they supported, LD 1710, would pressure companies that have customer-service call centers in Maine to keep their work in the United States.

Sponsored by Troy Jackson, a Democratic senator from Allagash who is running to replace Congressman Mike Michaud (who is himself running to replace Republican Governor Paul LePage), the bill would require call-center companies to notify the state before relocating call centers from Maine to foreign countries. (It does not require notification if a company moves elsewhere in the US.) And it would require all state-agency call centers to be in Maine.

Notification would have negative effects beyond bad publicity. The bill declares all companies that send Maine call-center jobs overseas ineligible for any “direct or indirect state grant, state guaranteed loan or tax benefit” for a period of five years after
the relocation.

Companies that, at the time of relocation, were receiving state benefits would have to repay to state coffers the unused amounts.

A recent union-conducted tally found 19,470 call-center jobs in Maine, with an average annual wage of $31,500, according to Jenn Nappi, assistant business manager of the International Brotherhood of Electrical Workers Local 2327, which represents most FairPoint employees in Maine.

FairPoint, which has about 900 unionized call-center workers in Bangor, Portland, and South China, is not the largest such company in Maine. That firm is LL Bean, which has about 2000 call-center staffers in Portland, Bangor, and Lewiston. Other major call-center players, according to the union research, are Bank of America with nearly 1000 people between Belfast and Brunswick, T-Mobile with 520 people in Oakland, and TD Bank with 500 in Auburn.

Companies often move call centers in search of low-cost labor: In 2009, the Baldacci administration’s economic commissioner John Richardson said Maine’s low wage levels should be considered by call-center firms (see “Maine — the India of the United States?” by Jeff Inglis, at thePhoenix.com/AboutTown).

In 2011, Carbonite, a Boston-based data-storage company, brought 150 call-center jobs from India to Lewiston. But other companies have gone the opposite direction: In February 2012, Bank of America closed a call center in Orono, laying off 200 people. Nappi and the IBEW say those jobs likely went to other Bank of America call centers in the Philippines.

And in September 2013, Sykes Enterprises, a Florida-based helpdesk company, closed a Wilton call center, laying off 150 people. The company has nearly 60 call centers in 25 countries, the IBEW says.

Some of these companies, including T-Mobile, have received tax incentives and other state support in exchange for promises of increased hiring.

“We’re constantly allowing all these companies to have all these great breaks, but we don’t require anything of them,” Nappi says.

There is, however, a possible loophole in the draft law, which allows state aid to go to a company that offshores work if not doing so “would result in substantial job loss in the State or harm the environment.”