Wednesday, March 19, 2014

Portland vs. Her People: Fighting over the possible futures of Maine's largest city

Published in the Portland Phoenix

Beneath the deep rifts of disagreement about how Portland should grow, change, and develop, there lies one underlying point of concord: The city is increasingly attractive to a wide range of people and businesses, and therefore is uniquely poised to have options about how its future will be built. And there’s another, related area of agreement: Nearly all the players in the ongoing land-use disputes in the city (including municipal leaders) share a list of goals, which include more housing that is more affordable, preservation of historic assets, celebration of unique attributes of the city’s landscape and architecture, and the pivotal importance of energizing the downtown — including but not just maximizing use of open space.
But when faced with choices about how to achieve those goals, Maine’s largest city has of late suffered a gigantic split, between City Hall and the people themselves. And most of these conflicts are similar in one root element: This city, which all agree is lucky to have so many options, has leaders who do not behave as if they have any choice at all. To the frustration of the citzenry, the City Council and the Planning Board often run off with the first partner who asks for a dance.
Sometimes there’s no real controversy, as with the new hotels sprouting around the downtown, the $60-million renovation of the Eastland Park Hotel, or the $110-million redevelopment of Thompson’s Point. But when there is disagreement, a pattern has emerged: citizen outcry builds, corporate interests flex their muscles, the city stands its ground, lawsuits swirl, and the future of Portland gets decided not through a participatory process ending with a majority vote, but in adversarial courtroom hearings before a judge who will make a decision alone.
The most notable issues exemplifying this pattern are the potential sale of Congress Square Plaza, the repurposing of the former Williston-West Church, and the massive Federated “Midtown” housing development in Bayside (see sidebar, “Timelines”). All three have been subjected to long, contentious hearings before the City Council and the Planning Board, as well as several lawsuits, which the city has a track record of losing (see “Legally Blind,” by Al Diamon, February 28).
The projects are different in their details, but looking at their processes is revealing, and worrying. There are interdependent problems, and even if they are solved, the three projects at the center of the current storms are likely lost to litigation forever. That said, a closer look at what ails Portland could help us avoid future maladies.
Diagnosis #1: Bad timingThe first, and perhaps truly the biggest, underlying problem is not a lack of citizen involvement. Ask anyone — board member, citizen, or reporter — who was at any of the multi-hour municipal meetings about these projects.
It’s that the involvement comes too late in the process to really make a big difference. Planning Board member Jack Soley puts it best: “At the eleventh hour it’s difficult to give public testimony as much weight as it is earlier in the project....Their voice will carry more weight at the early stages.”
Projects that come before the Planning Board have already been reviewed by city planning staff, and often outside experts, such as traffic engineers and stormwater engineers, but there’s still lots of time to make changes. Soley, a developer himself (the hotel on Fore Street is his) whose father is notorious Old Port landlord Joe Soley, says the Planning Board tries “to improve on what the developer has brought to us,” within the standards set by the City Council’s ordinances.
While citizen input is always welcome, earlier is better. Projects can take months to move through the Planning Board, during which time the board has typically requested — and received — many changes from the developer. By the end of the process, the members can find themselves in a bind if new public objections arise, or if citizens ask for additional changes to aspects of the project the board has already addressed.
“To a developer, it might cost a tremendous amount of time, money, and resources to make those changes,” after the company has typically invested a great deal already. The end is “a really difficult time to go backwards,” Soley says. “There’s a point at which it’s unfair.”
Which leaves one last option, where the Midtown project has ended up: “At the eleventh hour the only way to stop [a project] is litigation,” he says.
Mayor Michael Brennan agrees with Soley about getting citizens involved up front, and notes his surprise at the anti-Midtown outcry after more than a decade of discussions about Bayside. “If there were some type of opposition you would have expected it long before” the very end of the process, he says.
However, if the Planning Board’s attitude in this regard seems to favor developers over public concerns, that may be by design. Board members are appointed by the City Council, who are “very developer-friendly,” says Frank Turek, a leader of Friends of Congress Square Park, which leads him to ask (rhetorically) of the Planning Board “a basic philosophical question: What do you do that’s best for the people?”
Soley counters that the Planning Board works hard to fix, not kill, flawed projects, but ultimately when faced with imperfection, must “make our best judgement for what makes sense for the city of Portland.”
Diagnosis #2: InsecurityBut what city leaders think is best can differ significantly from what residents believe. Charles Remmel, one of the plaintiffs in the Williston-West case, and the first president of the Western Prom Neighborhood Association when it was founded in the 1970s, says city leaders should “have a little more faith in how the city will develop,” rather than thinking “if they don’t do [a proposed project] right now, it’s the end and we’ll never get another chance.”
“Portland has enough vibrancy” to attract good development, Remmel says, citing the city’s thriving food and entertainment scene, which he says has flourished “in spite of” city officials’ efforts.
When faced with these developers’ ideas, “Portland’s insecurities come into play,” Remmel says. City leaders often are “so insecure” that they approve the first thing that comes along. “They don’t have enough faith in themselves.”
Regarding Williston-West specifically, he says city officials were so worried about the future of the building if it lay dormant for too long that they eagerly embraced “the first guy who comes in,” even though that meant offices and a performance space in the middle of residences, and despite a lack of parking. (He says any parallels between fears for Williston-West and the St. Lawrence Church on Munjoy Hill, which did lay vacant and ultimately deteriorated until it needed to be demolished, are weak at best, because of different neighborhood environments.)
With Congress Square, he says, the city was afraid it would never have the money or the civic interest to improve it, so when a developer proposed the idea that involved selling off public land in the heart of the Arts District, officials leapt at the chance.
And with Midtown, the official thought line was, “We’re afraid if we don’t approve this, we’ll never get an opportunity like this ever again,” Remmel says. So the city raised the allowable building height in that area, and made other changes to accommodate the plan, rather than, for example, turning it down and waiting for one that made more sense for Portland.
Housing advocate and urban-issues blogger Christian MilNeil says the Congress Square situation and the Williston-West proposal are similar: “Those were really developer-driven. The developer came in with a proposal and that became the plan.”
(Former councilor John Anton, who was the only person to vote against both the Williston-West and Congress Square decisions, declined to comment for this story, saying he left public office “to get my life back” and didn’t want to get involved in current issues, nor revisit old ones.)
But MilNeil says the Midtown project was different, the result of a 15-year planning process. “You can’t really blame the developers for following the city’s plan,” he says. “The developers really were proposing something that was faithful to the city’s vision,” a development with an active street level, retail shops, and lots of housing.
Diagnosis #3: Resistance to changeBrennan says those are the city’s goals — his particular focus is “initiatives and proposals that are going to bring people to the downtown, galvanize the downtown, revitalize the downtown” — and says officials are balancing “a number of competing objectives,” including the city’s historic feel and overall aesthetics. 
Citizens who have risen up to oppose some of these developments have “different objectives,” he says.
When asked why some projects got a green light with barely a whisper, and others ignited firestorms, Brennan as much as throws up his hands.
“You get to a point where you’ve tried to compromise,” he says. “You just get to a point where you fundamentally have disagreements.”
Remmel agrees with that assessment: “Planning means to me you have a long-term idea” rather than being “focused on project approvals,” he says, arguing that city officials “are basically project-oriented. I don’t think they think in the same way the neighborhoods do.”
“A lot of these arguments are really about disruptive effects in a neighborhood,” Remmel notes. He admits, though, that what might count as disruption for him is fine for others, and vice-versa. He is confident, for example, that the Williston-West building could easily be converted into high-end residences by a developer who would protect the building’s historic facade. But Portland Landmarks, which protects the city’s architectural heritage, is against splitting up the beautiful interior of the sanctuary.
“It’s not a church anymore,” Remmel says. He’s right, but that statement alone doesn’t directly suggest any single course of action.
And that’s where MilNeil, a commissioner of the Portland Housing Authority, comes in. First, he observes, “cities change. It’s pretty much the definition of a city.” And second, he posits a clear dichotomy: “If the city doesn’t change architecturally, we’re going to change demographically.”
He’s speaking of the proposed Midtown towers, but the point is just as valid about putting a business in the residential West End: Either we have more and denser housing of all kinds, or the city prices out lower-income residents.
For his part, MilNeil puts social values over aesthetic ones. “I’d much rather preserve our city’s egalitarianism and embrace changes to our skyline,” he says.
Diagnosis #4: Class ConflictWhile on the one hand, MilNeil says, “it’s great that we’ve become such a successful city,” with merchants, restaurants, and a vibe that’s attractive to wealthy people; on the other hand he wonders, “Where are we going to put all the rich people who are going to move here?”
And with housing in short supply, and prices on the rise, where will the people the newcomers displace live?
“The rich people are just going to crowd out the working-class and middle-class people,” MilNeil predicts, unless the city undertakes major efforts to “make room for the people who want to live here and need to live here.”
Peter Monro, a landscape architect who is a leader of Keep Portland Livable, the group leading the opposition to Midtown (and suing to block it), says the city has it backwards. Rather than building downtown housing and an industrial park on the outskirts of the city, he says the city should have “good paying jobs at the heart of it,” which will in turn encourage spin-off developments to house those workers and cater to their shopping needs and desires.
His perspective is, he readily admits, that of an urban designer who lives in a historic-landmark home in a historic neighborhood district in the West End. He has a specific vision for how development should occur in Portland, and says the city does too, in its zoning and planning ordinances.
MilNeil, though, says Monro is looking at the wrong problem. Observing Monro’s West End residence and the fact that other plaintiffs in the anti-Midtown suit live in upscale housing too, he is blunt: “They’re homeowners so they’re not really aware of Portland’s housing shortage . . . and they don’t see it in their neighborhoods.”
As a result, he says, their opposition rises from a lack of an appropriate sense of urgency about an issue the city has been working on for more than a decade. “In their privilege they think they have the right to overturn 15 years of neighborhood-planning efforts,” he says.
Now, he says, because of Monro and his allies — and their lawyers — “this whole Bayside Vision is on hold.”
Diagnosis #5: Too many lawyersPart of the conflict does boil down to lawyers, of course. “If you can hire enough lawyers and kill any project you want,” which makes it harder for all developers, MilNeil says — including the Portland Housing Authority and Avesta, a non-profit developing affordable housing.
In fact, MilNeil questions Monro’s claims of pure motives. “I don’t think they’re out to win the lawsuit, actually,” MilNeil says, citing a Press Herald opinion column from November 2013, in which Monro was quoted saying it didn’t matter if he won the case in the end.
“We think the delay may be a deal breaker (for the developer),” the paper quoted Monro saying. “The power to delay is the power to destroy.”
Monro vigorously denies the charge, saying “we’re in it to change that project,” and rattling off several very specific changes he would like to see in the Midtown project (a lower parking garage allowing a wider, lower residential tower, for example). “This is not about delay.”
Ensuring the city followed the proper legal process is indeed important; Monro observes that the recent court rulings suggest that’s not a strength at City Hall. Noting that the courts must weigh heavily the fact that the city has the right to govern itself, Monro sees Portland’s recent losses as evidence something is very wrong: “Even with a bias in their favor they can’t win.”
What some — including Monro and Brennan — see as part of the checks-and-balances system, others, such as MilNeil, see as elitist. “As a city we should not be resolving all these contentious debates by lawsuit,” he says. “It’s not democratic.”
The only people who get to sue if they see an outcome they don’t like are rich people who can afford to hire lawyers, he says. “A courtroom is not a public process. It’s rich people fighting against each other.”
In the balance hang more than a few important questions.
For MilNeil, the key is renters’ futures. If Midtown’s developers have to modify their project to make it smaller or shorter, those changes will cost money, MilNeil says, on top of the relatively fixed
remediation costs for cleaning up the former railyard. With fewer tenants available to cover those costs, rents go higher — which is the opposite of MilNeil’s goal.
For Brennan, the suits boil down to the city’s sovereignty. Particularly with regard to the Congress Square petition and upcoming vote, he asks, “Is everything that the City Council does subject to a petition drive or a referendum?”
For Turek, it’s about taking on problems head-on. “All over the country cities are realizing that if we invest directly in public parks, we’ll get a lot more economic benefit” than selling the space and hoping development spreads, he says.
And for Monro, the effort is about holding back City Hall’s eagerness to grow. “They want population and tax base,” he says. “They’re looking for as many Empire State Buildings as they can get.”
Diagnosis #6: Being overwhelmedIt is possible that at least some of the popular resistance is because many areas of Portland are changing rapidly at the same time.
Brennan calls this period in Portland’s history one of “unprecedented development and development opportunities in the city,” saying there is “a lot of pent-up demand due to the recession” that started in 2008 and kept bankers and builders laying low, waiting for better times. Now, he observes, projects are being proposed throughout the city, including on High Street and India Street, as well as the working waterfront.
“There seems to be development every place we turn,” he says.
Listing off nearly a dozen active projects, Soley echoes that sentiment: “If you look at almost every corner of the city, there is substantial development going on.” With a tone of wonder audible in his voice, he says, “this is one of the most spectacular periods of development in the history of Portland.”
And that era is only continuing. The redevelopment of Franklin Street could open many acres of developable land in the heart of the city, which could be worth as much as $1 million per acre, a real-estate analyst told the Portland Press Herald.
As we plot that area’s future, we hope these lessons help Portlanders — both in and out of City Hall — reflect on one question, as Brennan posed it: “Is this development reflective of where we want to go as a city?”

Timelines
*Williston-West Church*
Summer 2011
 Williston-West Church merges with Immanuel Baptist Church and moves worship to High Street. The beautiful, historic Williston-West Church is sold to Frank Monsour, an Australian businessman who proposes converting the parish house into residential space and office space for up to 14 of his employees; a future concept is to convert the sanctuary into either a community hall or a performing-arts venue.
May 2012 The Planning Board hears nine hours of public testimony, and entered into the record 97 letters and a 140-signature petition opposing the idea, according to the Forecaster’s report of that meeting. Objections relate to the city’s comprehensive plan, which protects the residential character of the West End neighborhood (and other parts of the city). Putting a business in the middle of an upscale residential area seems to run counter to the overall plan.
June 2012 Fifty people, about half in favor and half opposed, speak to the City Council during a two-and-a-half-hour public hearing, the Portland Press Herald reports. The council votes 6-3 to approve the plan, which involves a zoning change to allow the business (opposing were John Anton, John Coyne, and Cheryl Leeman).
July 2012 Twelve neighbors sue Monsour and the city, asking a Superior Court judge if the city went too far in changing the property’s zoning.
December 2013 The ruling is that the rezoning did violate the comprehensive plan, and that the building did not need a specially brokered deal to protect it, given the city’s strong historic-preservation ordinance. The city is planning to appeal that ruling to the Maine Supreme Court.
*Federated’s Midtown project*
2000
 The city issues the Bayside Vision, calling for more housing and larger, taller buildings in the area, including the former railyard in the center of the neighborhood. The plan also recognizes a related need for a city-funded parking garage.
July 2011 The city agrees to sell 3.25 acres, the former railyard, to the Federated Companies for $2.3 million, with an agreement that any development would include a parking garage paid for in part with $9 million in federal money passed through the city.
Fall 2012 Federated unveils a $150-million plan to build 675 apartments in four 15-story towers, plus two parking garages with more than 1000 spaces, and more than 90,000 square feet of retail space.
Fall 2013 After nearly a year of hearings before the Planning Board and City Council, including ordinance changes allowing buildings to be as tall as 165 feet throughout the parcel, public opposition arose (see “Curb Appeal,” by Deirdre Fulton, November 22, 2013).
January 2014  The Planning Board approves the project. Two members of the board, Jack Soley and Bill Hall, say they don’t like aspects of it, but vote in favor because it meets the city’s ordinance requirements.
February 2014 Keep Portland Livable sues the city, saying the process did not properly respect the city’s own planning documents.
*Congress Square Plaza*
2008
 City Council creates the Congress Square Redesign Study Group. After about three years of meetings, the 15-member body was no closer to an idea than they had been at the start.
November 2011 RockBridge Capital, the new owner of the Eastland Park Hotel (now renovated and reopened as the Westin Portland Harborview) proposes buying the plaza to erect an event center (see, among other coverage, “Congress Square’s Controversial Facelift,” by Deirdre Fulton, May 24, 2013).
May 2013 The city Parks Commission says the council should consider not just the status quo and the frequently revised RockBridge proposal but other ideas “such as a re-designed park in the same space, a fully designed smaller plaza, and other building or architecture options.” (See “Getting (Congress) Square to Work,” by Jeff Inglis, August 16, 2013, and “Reimagining Portland,” by Calvin Dunwoody, August 24, 2012.)
September 6, 2013 Friends of Congress Square, which had objected to the proposed sale for months, asks the city to allow the circulation of a petition for a citizen initiative to amend the city’s land bank, making protected land harder to sell, and adding 35 parcels to the Land Bank list, including Congress Square.
September 13, 2013 The city refused to issue petitions, arguing that the ordinance it proposed conflicted with city ordinance and state law barring initiatives and referenda on administrative and financial issues.
September 16, 2013 The City Council votes 6-3 (John Anton, Kevin Donoghue, and David Marshall opposed) to sell 9500 square feet, about two-thirds of Congress Square Plaza, to RockBridge Capital for $524,000.
September 25, 2013 Friends of Congress Square Park sues the city to force it to issue the petitions.
November 2013 A judge orders the city to issue petitions, which were finally released for circulation the day before Election Day. While the city planned to appeal, the Friends collected signatures at the polls, ultimately turning in 4250, far more than the required 1500.
March 2014 The City Council approved the petition’s question for the June ballot, but also moved to enact a slightly different ordinance that would add almost exactly the same properties to the protected Land Bank (with the notable exception of Congress Square), but with more modest protections against their potential sale.
April 2014 The Maine Supreme Court will hear the city’s petition-issuing appeal in early April, and is expected to rule shortly thereafter, in time to allow or block the June election.

Reality check: Could MH370 have hidden from radar next to another plane?

Published on GlobalPost

Yes, says an MIT aeronautics professor. With caveats.

BOSTON — It’s the Malaysia Airlines missing jet theory that has taken the internet by storm.
Ohio aviation hobbyist and IT professional Keith Ledgerwood dug deep into the data and emerged with the idea that — after making the sharp left everyone seems to now agree on — flight MH370 appears to have piggybacked on another aircraft, Singapore Airlines Flight 68, which also departed Kuala Lumpur around the same time.
In doing so, the theory goes, it could have evaded radar detection. Unlike MH370, which was heading for Beijing, SIA68’s destination was Madrid. Its flight path passed over parts of IndiaPakistan, and Afghanistan, after which the Malaysian Boeing 777 could have peeled off and landed in the desert or in Central Asia.
The hypothesis, replete with charts and technical details, is compelling. But is it feasible?
Yes it is, according to Massachusetts Institute of Technology professor of aeronautics and astronautics R. John Hansman Jr.
But it’s not very likely.
An airplane as big as a Boeing 777 can effectively hide from radar systems, Hansman says, if it gets close enough to another plane of similar size. Hansman is also the director of MIT’s International Center for Air Transportation.
Speaking to GlobalPost Tuesday, he said he was familiar with Ledgerwood’s idea, and termed it “technically possible but operationally very difficult.”
Hansman said with planes of that size, “you don’t have to get that close — within a half-mile or a quarter-mile” to appear on radar screens as, effectively, part of the same plane, even on military radar.
“It would be a slightly larger radar blip, but not enough to get anybody’s attention,” Hansman said. Since radar operators would be expecting to see a contact at that speed and on that flight path — they would be assuming it was only SIA68 — they would not see anything worrying.
However, maneuvering two massive aircraft that close together in flight at high altitude is extremely hard, he said.
First, while the flights departed from the same airport, “it’s hard to catch up with the other airplane.” Big airliners don’t have much of a range of possible speeds, especially when flying at cruising altitudes, so it’s not like the Malaysia Airlines pilot could have done the airplane equivalent of stepping on the gas pedal — it would have already been quite near the floor.
If it was possible to catch up with speed, the Malaysian pilots would have had a challenge locating the Singapore Airlines plane — having turned off their transponder and anti-collision signaling systems, that equipment would have been useless to provide other planes’ whereabouts.
Transponder silence also would have prevented the Singapore Airlines plane from noticing it had a shadower, Hansman said, as airplanes’ on-board primary radar is designed to detect weather, not other aircraft.
Even assuming MH370 could catch up to, find, close in with, and shadow SIA68 in the middle of the night over the ocean, “at some point you’re going to have to separate” and fly elsewhere, Hansman said. “Then you have to land it somewhere.”
As suggested by another aviation expert speaking to GlobalPost, being certain of escaping radar detection all the way to landing at a remote airstrip would mean discovering and evading secret military radar capabilities, or at least being absolutely sure that the nations in question would not want to expose their technological expertise by sharing information those systems might have detected.
Hansman discounts the possibility of a thief having run off with the plane because “it’s easier to just go out on the ramp and steal an airplane” than to gain enough expertise to accomplish what Ledgerwood’s hypothesis suggests, and then to go and actually execute it.
He is more persuaded by an idea he and others have been discussing for several days: The possibility of some sort of onboard emergency, an electrical malfunction or a fire, like that described in a Wired post earlier Tuesday.
“The original turnback” — the one Ledgerwood thinks was to chase SIA68 — “was in a direction toward an appropriate emergency-diversion field,” Hansman said.
But even that change raises questions for him: In an emergency, pilots wouldn’t likely have taken the time to use the flight computer, but would instead have changed the plane’s heading manually. And if there was time to use the computer, he said, there would have probably been time to make a radio call announcing the problem.
But Hansman said the basic assumption of Ledgerwood’s idea is true: Only very high-tech radars can tell the difference between two planes traveling close together at altitude, and many countries in South Asia may not have that equipment. In fact, “we hope not,” Hansman said.

Wednesday, March 12, 2014

Five Prime steps up search for monoclonal antibodies

Published in Drug Discovery News

SOUTH SAN FRANCISCO, Calif.—Seeking to continue, and accelerate, its work developing new protein therapeutics for cancer and inflammatory diseases, Five Prime Therapeuticshas made an agreement with Adimab of Lebanon, N.H., that will help discover monoclonal antibodies for cancer immunotherapy. Five Prime also recently closed its initial public offering, raising $43 million.
 
Under the terms of the Adimab deal, which marks the first time the companies have worked together, Five Prime will identify potential targets for development as therapeutic candidates and send them to Adimab for discovering and optimizing the corresponding fully human antibodies.
 
Five Prime will then develop and commercialize those antibodies, with Adimab receiving not only payment for each target campaign, but also potential milestone payments and royalties, according to a news release from the company. Specific financial details were not disclosed.
 
“Working with Adimab, we will be generating antibody products to targets of our choosing, and these could become clinical candidates for Five Prime’s proprietary pipeline,” Five Prime Chief Business Officer Aron Knickerbocker told DDNews in an email.
 
Five Prime has “a library of over 5,700 extracellular proteins (ligands and receptors),” Knickerbocker wrote. “We believe these include substantially all medically important protein drug targets, including many proteins not in public domain.”
 
Five Prime can produce “thousands of proteins weekly,” from which it screens “novel protein therapeutics and antibody targets,” Knickerbocker wrote.
 
From there, Adimab will use its library of fully human whole immunoglobulin-G molecules (IgCs), and its technology that rapidly identifies appropriate matches, returning results to Five Prime. While Knickerbocker declined to talk about project timelines, Adimab’s website says its usual turnaround from target receipt to return of purified, whole IgGs is eight weeks.
 
That includes screening more than 10 billion IgGs from its various libraries; past results have “generated large numbers of fully human IgGs (100s up to 1000s) to all targets screened to date,” Adimab’s website says.
 
“Working with Adimab will allow us to generate fully human monoclonal antibodies to our targets of interest,” said Knickerbocker.
 
The advantages of being able to test with full antibodies are significant. Unlike the more commonly used antigen fragments, whole IgGs are capable of cross-linking receptors, as well as sterically blocking interactions.
 
Less than a month after announcing that agreement, and highlighting its progressing collaboration with British pharma giant GlaxoSmithKline developing FP-1039 (GSK3052230), a fibroblast growth factor ligand trap targeting multiple solid tumors, Five Prime also grossed $43,125,000 in its initial public offering of 3.4 million shares of common stock. The company trades on the NASDAQ exchange, with symbol FPRX.

Sunday, March 9, 2014

We have a problem: The science behind rising seas

Published on GlobalPost

A hundred years after it spawned the iceberg that sank the Titanic in the North Atlantic, the Jakobshavn Glacier is now a major contributor to global sea-level rise, this time threatening the homes and lives not of 2,200 passengers and crew but of a billion people across the world.
As climate-watchers and coastal-dwellers keep a weather eye out for signals of irreversible changes in the environment, the world’s fastest-moving glacier has already begun self-destruction. 
Jakobshavn is now shedding ice nearly three times as quickly as it was 20 years ago, dumping enormous and growing quantities into the ocean. It's contributed 0.1 millimeters per year to worldwide sea-level rise — more than 3 percent of the 3 mm produced globally — for the past decade.
The glacier “has been retreating for the last 100 years,” according to Ian Joughin, senior principal engineer at the Polar Science Center, part of the University of Washington's Applied Physics Laboratory. “Retreat” means a glacier is shrinking in length, losing more ice from its face that meets the water than accumulates from higher up.
But it was only in recent decades that the retreat reached extreme levels.
Jakobshavn’s story isn’t unique. For decades now, more ice has been melting into the ocean than is falling from the sky in the world’s mountain and polar regions, where ice sheets store two-thirds of the planet’s fresh water — and the science shows us the situation won’t reverse any time soon.
To understand exactly what’s happened and what's likely to come, it’s critical to understand the topography underneath each glacier.
First, a note on how to think about glacial ice: it's not as simple as frozen water. Scientists consider glaciers to be "nonlinear viscous fluids," which behave like both solids and liquids. Think of a glacier as a frozen river, always flowing at some speed from source to outlet, but growing and receding with the seasons. Because ice is heavy and not a perfect solid like rock, it flows under gravitational pull and pressure from above. Sometimes big chunks become unstable and fall into the sea. When Earth’s climate is in balance, about the same amount of water flows into the oceans from glaciers as is evaporated and then precipitated as snow onto ice sheets from which those glaciers are made.
The Jakobshavn Glacier, known in Danish as Jakobshavn Isbræ, has its origins in large areas of land well above sea level, from which it flows down toward the ocean (in this case, Ilulissat Icefjord), where it calves icebergs into the water.
As physicist Joughin describes it, Jakobshavn Glacier flows off the land and into the 1,600-meter-deep fjord, filling it entirely with ice for a distance of about 50 kilometers, ultimately climbing up a slope in the sea floor that peaks at about 600 meters of depth. The narrow sheet of ice coming off the edge of the glacier at that peak — called a “glacier tongue” — once served as a sort of “cork” for the glacier, holding it back significantly and preventing quicker loss of ice.
You can see the rise in sea-bed elevation just to the left of center in this graphic.
In 1992, Jakobshavn was melting at a rate of about 6 kilometers a year. It was “about in balance” with the natural rhythm — gaining and losing roughly the same amount of ice over the course of a year’s winter accumulation and summer melting, Joughin said.
But in the late 1990s, the glacier’s tongue broke off, and the “uncorked” Jakobshavn began to calve and lose mass in ever-deeper water.
By 2000, the glacier was losing 11 kilometers in length every year, nearly twice the stable speed. As of last summer, according to a paper Joughin and others published recently in academic journal The Cryosphere, it was losing nearly 17 kilometers a year, retreating up the fjord into increasingly deep water that could cause it to melt even faster in the coming decades.
Jakobshavn’s dramatic change was recorded in the 2012 film "Chasing Ice," in a compelling scene that captured the calving of a kilometer of ice in a single event. That happens throughout the summer, Joughin said, though not always in such significant individual moments. (When it does, though, global seismic monitors have been known to register them as 4 or 5 on the Richter scale, he said.)
Eventually — perhaps in about 100 years — the glacier will have retreated far enough that it will no longer feed directly into the fjord. At that point, essentially landlocked, the glacier will only shrink through melting, which happens much slower than calving. With that slowing will come more stability in terms of the glacier’s size. “The next stable condition could be a regionally smaller ice sheet,” Joughin said.
Jakobshavn would still contribute a significant amount of global sea-level rise before then. But the real danger lies at the other end of the Earth, in the West Antarctic Ice Sheet (WAIS), which holds enough water to raise the ocean between three and six meters.
The WAIS is also meltingbut it’s doing it in open water; once the process starts, the sheet will never stop calving.
“The [WAIS] glaciers are going to keep retreating. At this point there is nothing we can do but watch,” said Eric Rignot, a glaciologist at the University of California Irvine who published his latest paper about the WAIS in December’s Geophysical Research Letters. “Just how fast they can flow, we don’t know,” he said.
It could take hundreds or thousands of years, but as Joughin puts it, the next stable point for WAIS is “no ice sheet.” By then huge areas of land, home to massive proportions of the world’s population, would be under water.
The question facing scientists and coastal dwellers is akin to the one facing the Titanic’s passengers: The water is rising, and we don’t quite know how fast it’s coming, or how quickly it will accelerate. But we need to plan, move, and adapt if we are to survive. There’s no way to stop the water, and no time to waste.

Friday, March 7, 2014

GSK, Roche go head-to-head to fight melanoma

Published in Drug Discovery News

LONDON—Taking a lead in the tight race to develop and release melanoma medications,GlaxoSmithKline plc (GSK) has received accelerated approval from the U.S. Food and Drug Administration for its combination of Mekinist (trametinib) and Tafinlar (dabrafenib) for treatment of melanoma with BRAF mutations V600E and V600K. Roche, which is also a big player in this market, is now behind, said Aine Slowey, senior analyst for London-based analysis firm Datamonitor Healthcare. While both GSK drugs had been approved as monotherapies in 2013, the combined results “were very positive and significantly better than the BRAF monotherapy,” Slowey said.
 
The Swiss giant has a monotherapy in Zelboraf (vemurafenib) but does not yet have a combination therapy targeting BRAF mutations. In fact, “the combination of  Zelboraf and Yervoy has already crashed and burned,” she said. While Zelboraf is less toxic than Bristol-Myers Squibb’s (BMS) Yervoy (ipilimumab) and therefore may be used first, with Yervoy going only to those who see no improvement, a combination of the two drugs was hoped to be a powerful one-two punch. But the trial combining them was halted last year because of toxicity.
 
In the wake of that failure, Roche may be looking to “leapfrog” GSK, to combine dual therapy with additional PD-1 inhibitors, she said.
 
Both GSK’s approved dual treatment and the failed combination from Roche and BMS inhibit MEK as well as BRAF, delaying medication resistance that arose when inhibiting just BRAF. But it’s only a delay, Slowey said; eventually resistance does develop. Adding immunotherapy, such as PD-1 inhibition, may help, Slowey said.
 
Melanoma medications are a small, and relatively new, market. The disease is easily detected in its early stages, and surgery is usually both quick and effective, particularly when compared to surgery for other types of cancer. But basic research uncovered the fact that BRAF mutations are a “convenient biomarker that patients are going to respond well to this kind of targeted therapy,” Slowey said, so companies started exploring commercialization.
 
For those patients who do develop metastatic melanoma, about half have a BRAF V600 mutation; of those, 90 percent have the V600E variant, Slowey said. (The other half, who have what is called “wild-type” metastatic melanoma, get Yervoy and immunotherapy, Slowey said.)
 
While Datamonitor projects patient numbers will grow about 3.5 percent a year through 2021, the market numbers are still low: Seven years from now, there will only be 170,000 patients in the U.S., Japanese and European markets combined, the company projects, with sales totaling $459 million then.
 
Nevertheless, “it’s probably one of the fastest-moving oncology markets at the minute,” Slowey said.
 
Prior to 2011, only standard cytotoxic chemotherapies were available. But then Yervoy was approved for metastatic melanoma patients. Already there are four approved drugs, with more on the way.
 
BMS has entered the fray, winning fast-track designation for nivolumab, which is now in Phase 1 trials, as well as combination testing.
 
And Merck’s PD-1 inhibitor, MK3754, has breakthrough designation for treating melanoma; the company recently signed a deal with Amgen to see if MK3754 would work well in combination with Amgen’s oncolytic virus Talimogene laherparepvec.

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.”

Thursday, March 6, 2014

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.