Tuesday, December 23, 2014

In Search of True Energy Independence

Published on Huffington Post

Americans are thanking their lucky stars that gas prices are falling to levels not seensince July 2010.
The root causes of the fall in oil prices are many: increasing production from sources such as U.S. shale, and declining consumption, due to improved vehicle fuel economyhere at home and stagnating economies abroad. At the same time, OPEC nations have agreed -- for the time being at least -- to allow oil prices to fall in an effort to drive high-cost oil producers such as U.S. shale operations bankrupt.
At the moment, though, everything is coming up roses: consumers are happy, OPEC is nervous, and America is producing a greater share of the oil we consume than at any time in the last 30 years. Could it be that the United States is on the verge of energy independence?
Not hardly, and here's why: as long as the United States remains dependent on the global market for oil -- even if an increasing share of that oil is produced domestically -- we remain subject to wild swings in price for a fossil fuel that is becomingincreasingly expensive to produce.
Oil price volatility hurts the economy, lowering consumer confidence and making businesses less willing to invest. For fear of future price fluctuations, everyone slows their spending. That decreases consumer demand, which has ripples throughout the economy.
Increasing domestic oil production does not solve the problem. Oil produced in America does not necessarily stay in America; rather, oil is a globalized commodity, which is why revolution or war in far-off lands has a rapid impact on gas prices here at home. While increasing production at home adds to global supply, the effect on prices is no different than if production were to increase in Saudi Arabia or Venezuela.
And a "drill baby drill" approach to maximizing oil production brings its own risks, including that of environmental damage that threatens precious natural places and warms the planet. Oil booms also have the potential to create big economic problems when they go bust, as U.S. shale oil producers may find out soon and as world leaders such as Vladimir Putin are becoming keenly aware.
There is only one true path to energy independence, one that frees our economy of its ties to volatile world oil markets and our environment of the damage and risk that comes from oil production: cutting our dependence on oil entirely.
America is actually making good progress in cutting our reliance on oil. This stunningBloomberg News data visualization shows that the U.S. is "shaking off its addiction to oil," with America using about a third less oil per dollar of GDP than we did in the mid-1970s. Americans are driving less, and what driving we do is in cars that are more fuel-efficient than in the past. New technologies -- such as electric vehicles -- areshowing strong promise for displacing oil use in the transportation sector.
In the 1980s and 1990s, America responded to lower oil prices by slacking off on efforts to reduce our consumption of oil -- fuel economy standards for cars stagnated, SUVs proliferated, progress toward alternative-fuel vehicles stalled and auto-dependent sprawl spread across the land, leaving us all, and the American economy, to pay the piper in higher fuel prices over the last decade.
Let's not make the same mistake again. By using oil more efficiently and continuing progress toward electric vehicles, Americans can finally enjoy the lasting economic, environmental and health benefits of true energy independence.

Wednesday, August 13, 2014

The Challenger: Can Shenna Bellows ’97 stun the political establishment by upsetting an entrenched incumbent and winning a U.S. Senate seat in Maine?

Published in Middlebury Magazine

Shenna Bellows ’97 is cold. This is not the sort of brief chill that passes now and again: It’s the deep, bone-shaking kind that both racks her slight frame and causes others nearby to shiver in sympathy. I am surprised for two reasons: First, Shenna knows Maine weather well. She grew up here, in a house that didn’t get electricity or running water until she was in fifth grade. When she and her siblings got home from school, their chore was to relight the woodstove. As often as not, though, they would huddle under the bedclothes, doing their homework until their parents got home. It is also surprising because the feeling she usually exudes is not contagious cold but rather infectious, friendly warmth.
Right now, though, Shenna is freezing. We have just gotten in the car after an election-campaign visit to Mount Desert Island Biological Laboratory, right on the Maine coast. She didn’t check the weather this morning and didn’t bring a coat on this blustery, sprinkling spring day.
As the heat comes on in the car, she settles into the backseat; her staffer-driver and I ride up front to give her space to work. She stops shivering, takes off her shoes, tucks her feet under her, and resumes her most frequent activity: typing on her iPhone.
Sending texts and emails whooshing into the ether is key to Shenna winning what she admits is “an uphill battle” against United States Senator Susan
Collins, a three-term Republican incumbent with a big bankroll, who is widely expected to win handily. Even more crucial will be Shenna’s idea of what a candidate and a campaign can be.
Her vision has paid off before. While heading the American Civil Liberties Union of Maine, she co-led the 2012 statewide same-sex marriage referendum that made Maine the first state to approve marriage equality at the ballot box. (Maryland did the same that day.)
The ACLU of Maine lobbied for and won major legislative victories too: passing a first-in-the-nation law requiring police to get a warrant before tracking suspects with cell-phone data, defending transgender Mainers’ rights, limiting police use of drones, and protecting women’s reproductive health rights.
She is still campaigning—and gaining national media attention and donations—for civil-rights protections, economic opportunity and justice, constitutional freedoms, and environmental protection. She is bringing together what she calls “an unusual coalition” of people who, like her, hold positions that transcend stereotypical political divides.
On the left of most Democrats, she backs universal single-payer health care, legalizing marijuana, “bold, visionary action” on climate change, and student-loan debt reform as a means to boost the economic prospects of young college graduates, who face the toughest job market in decades.
In the middle, she supports Internet neutrality and equal pay for women.
And well to the right—at times on turf occupied only by the libertarian wing of the Republican Party—she insists on ending the National Security Agency’s domestic-spying program and repealing the USA PATRIOT Act.
We have been friends for years; when she asked me what I thought would be the hardest thing about her running, I told her she would have to ask people for money not to support a cause, but to back her.
***
As a Peace Corps volunteer in Panama from 1999 to 2001, Shenna helped give microloans to artisans in a remote community. And, more recently, as executive director of the ACLU of Maine for more than eight years, she was responsible for raising its annual budget of around $750,000, as well as for contributions to the various campaigns the group joined.
But even now, Shenna is not running for herself. She says that she wants her candidacy to be viewed as a revolutionary rethinking of how campaigning—and politics—can and should work. And her plan for victory is very much like her previous public-service efforts, most notably that 2012 same-sex marriage campaign.
Then, supporters had hundreds of thousands of individual conversations with their friends, neighbors, and communities, making personal connections to explain the importance of marriage equality. The strategy gave backers strong talking points they could repeat in their own words, multiplying the effectiveness of the campaign’s direct appeals to the broader public.
Shenna’s fundamental idea, one adopted by few on the left (though many on the far right), is that elections can be won by the power of human connection and fidelity to one’s ideals. (And integrity. Having spent years working for marriage equality, she refused to get married until all Maine couples could; her September 2013 emailed wedding announcement ended with a request: “And please… no gifts. For real,” with a link to the Federal Election Commission’s campaign-finance rules.)
And she believes that beyond being funded by small, individual donations for regular-person candidates (which Tea Party candidates espoused), campaigns should be staffed by actual humans, who have real lives and families amidst the fray.
Hearing Shenna talk about both unseating Maine’s senior senator and upending a broken electoral system is strange not because it’s so divergent from cynical national political punditry, nor because critics might call it naïve, but because it’s oddly empowering. It sounds rational, reasonable, possible. It’s an idea whose time, like Shenna’s, may at long last have come.
The execution of Shenna’s impossibly possible candidacy is being shepherded by campaign manager Katie Mae Simpson ’02, a native of rural Washington County, Maine. She’s the type of person for whom political science was too philosophical a major; religion was not.
A lifelong progressive activist and campaigner, Katie Mae was on maternity leave with her second child when Shenna came to her house to ask her to run the campaign. She declined; an all-consuming job running a campaign for U.S. Senate was not compatible with meeting the needs of her young family.
So Shenna went to work employing those skills of connection and persuasion that would go on to make her such an attractive candidate. She told Katie Mae that she wanted her to embody the campaign’s beliefs, to be the standard bearer for a candidacy based on fairness and equality and concern for the everyday Mainer. (To that end, all Shenna’s campaign workers are paid above minimum wage and have health-insurance benefits.)
“The pop culture picture you get of politics is not right for 99 percent of people,” Katie Mae says. So Shenna’s campaign manager (yes, she was quickly persuaded to join the campaign) has set out to reclaim it for the rest of us, which can include breastfeeding her son while conducting an interview. Two other campaign staffers are working mothers whose partners also work full time. Striking a balance is important—teammates who are exhausted from the spring’s battles are of little use come fall’s crunch time.
The same is true of the candidate herself. Her husband, Brandon Baldwin ’98, initially shielded himself from the campaign, hoping to create a refuge where Shenna could escape from the 12-plus-hour-days, seven-days-a-week effort. It wasn’t that he didn’t want Shenna to run— quite the opposite. He’s been supportive of her ambitions ever since she revealed on their fourth or fifth date in 2009 that she was going to run for U.S. Senate some day, possibly soon.
A watershed moment came in February 2012. With the announcement that Olympia Snowe would not run for a fourth Senate term that fall, Maine’s political circles went into a frenzy, handicapping potential successors to the state’s senior senator.
Shenna took a week of unpaid leave from the nonpartisan ACLU to explore her options. But then former independent governor Angus King joined the race (ultimately winning Snowe’s seat handily). Shenna went back to the ACLU, but with a new fire inside.
What surprised her husband about that week was how enthusiastic he felt about the prospect of her being a candidate. It was a powerful realization. “It didn’t feel like it was taking you away from me,” he tells her during a joint interview.
Though removed from the campaign at first, Brandon has slowly become more involved. “It’s tapped into everything that I hold to be important,” he says, admitting that her candidacy has awakened his “somewhat dormant love of politics.” He spoke on Shenna’s behalf at caucuses and house parties, where he would write “campaign spouse” on his nametag sticker. Crucially, he has found himself able to disengage, too. So has she.
“We take one day a month that is our day,” Shenna says. They hike, read, watch movies, sleep in, relax. It’s a private—and vital—aspect of the campaign they both say.
During this joint interview, Shenna suddenly stands up and walks to the fridge, retrieving a card that has been hanging there since she started campaigning. On the front is an inspirational quote: “Be the change you wish to see in the world.” It is a note from Shenna to herself.
Brandon is surprised: He has seen the card daily for months, without realizing there was a message inside. Shenna wrote herself resolutions as she began the campaign. Highlights include “have fun,” “be your authentic self,” and, finally, what Shenna declares as “the most important rule of this race: ‘Love matters most.’”

***
Love is a strange value to want to bring to Washington, D.C. Congressman Mike Michaud, a Democrat now running to be Maine’s next governor, says that Shenna would do well in the nation’s capital, working hard to forge connections in spite of the heightened partisanship that has infected the city.
Shenna says that she’d bring activist organizing tactics to Congress, meeting with lawmakers as a colleague, while facilitating conversations between legislators and regular citizens. She wants other legislators to hear about the mother Shenna met who is a student and has a full-time job, but still can’t cover all of her bills. “She eats one meal a day so her son can eat three,” Shenna says, tearing up.
At a recent political rally, a woman told Shenna her house had just been foreclosed upon. And there she was, offering to volunteer for Shenna’s campaign, hoping for change. “There are people who are persevering in really horrible situations,” Shenna says. “That is humbling.”
Shenna’s personal touch goes a long way. On an evening in Lewiston, in a room full of Democratic supporters, Shenna makes sure to talk to each one, working the room with a smile, a ready hug for friends, and a laugh audible across the gathering. At one point she leaps with joy and shouts “Yay!” The next second, she regains composure and says soberly, “I’m sorry. That wasn’t very senatorial.” But she is beaming: She has just learned that she was endorsed by the Maine People’s Alliance, a statewide progressive grassroots organization.
Her support is broader, though. Chuck Quintero, the director of the Maine Democratic Party’s coordinated statewide campaign, says of Shenna’s appeal across the political spectrum: “She kind of puts a wrench in our partisan politics. . . .We have to reach out to lots of people we might not otherwise.”
Just hours before Quintero’s half-complaint, some party faithful were lamenting—to Shenna’s face—her insistence on meeting with people she often disagrees with. Shenna had begun the day sparring amiably with popular Maine conservative Ray Richardson on his talk-radio show. Long a fan of Shenna’s, particularly on privacy and limited-government issues, he has announced on the air that he is not voting for Collins. (Cagily, he hasn’t endorsed Shenna—yet.)
Alienation and division get in the way of the important work she wants to do, Shenna says. When she learned that independent U.S. Senator Angus King was about to endorse Collins, Shenna was gracious, but worked to defuse any partisan angst. Moving quickly, she set up interviews on early morning TV and radio programs, so viewers and listeners would hear the news from her. It defused a problem political commentators might have harped on for months.
While still firmly in underdog territory, Shenna’s campaign is on solid footing. She outraised Collins in the first quarter of the race and has already hit $1 million in total fundraising, with the vast majority of that money coming from Maine residents giving under $100.
It’s late May, and Shenna and I are heading south on I-295 when we spot a “Shenna Bellows – U.S. Senate” bumper sticker on a car ahead of us.  As we pass it, she looks carefully at the driver and exults, half-kidding: “And I don’t even know him!” The driver must be a big fan: Our rear-view mirror shows a Bellows sticker on the front bumper too.
***

Though Shenna is still a relative unknown, those who know her like her—indeed, many Mainers agree with her positions on key issues, and, perhaps more important, disagree with Collins. Tasked with becoming better known every day, she is giving a nod to a state political tradition of sorts: She has planned a month-long, 350-mile walk across Maine to draw media attention and connect more directly with all stripes of voters.
Being the underdog energizes her. “The only way to win is to outwork my opponent. The only way to do that is to organize and inspire,” she says.
Brandon chimes in: “Then if you win, it’s an endorsement” of that approach by the voters. “It’s the best possible way to win.”
It is a winning strategy, whether Shenna beats Collins or not, says Geoffrey Skelley, associate editor of Sabato’s Crystal Ball, an election analysis website at the University of Virginia’s Center for Politics that calls Collins’s seat safe.  Skelley points out in an email that though Maine leans Democratic at the federal level and despite Republicans’ national image problems, Collins’s reelection margins have been high. “In a midterm cycle with a Democrat in the White House, Republicans are naturally positioned to do better,” he says. “About the only way to change that would be for a scandal to develop that centrally involves Collins.”
Nevertheless, Skelley sees a silver lining for Shenna. “While she may deny this, a failed Senate run against a powerful politician like Collins may serve as a stepping stone for her political future,” he says. “If Bellows acquits herself well enough in a difficult race where she stands little chance to win, she might get another electoral shot in the future in more favorable circumstances.”
For the long term, Shenna believes her campaign is on “the right side of history” on the crucial issues facing the nation and the world. But the short term is here. And she is hoping two parallels in Maine’s political history are on her side. In 1964, the unsinkable Republican senator Margaret Chase Smith was beaten by Democrat Bill Hathaway. And more recently, Angus King entered the governor’s race as a relative unknown, and beat, yes, Susan Collins.
“A lot can happen between June and November,” Shenna says.

Wednesday, April 9, 2014

Making clinical trials more diverse

Published in Drug Discovery News

WASHINGTON, D.C.—Hoping to expand both statistical validity of clinical trials and access to experimental therapies beyond their current confines, major medical-industry players have united to launch a campaign called “I’m In,” encouraging minorities and their doctors to find out about, and participate in, clinical medical-research trials.
 
While encouraging African Americans, Asian Americans, Hispanics and members of other ethnic groups to join medical research, speakers at a March 12 press event announcing the initiative were cognizant of the shadow of the Tuskegee syphilis experiments, an unethical and long-condemned study of the spread of untreated syphilis in African-American men that ran from the 1930s to the 1970s.
 
While Dr. Carlos Cardenas, board chairman of Doctors Hospital at Renaissance in Edinburg, Texas, alluded more vaguely to the idea of “removing any and all stigma that is associated with being part of a clinical trial,” another speaker, Averl Anderson, a breast-cancer survivor and participant in clinical trials, mentioned Tuskegee by name as a reason “people have a lot of mistrust in medical research”—particularly in the African-American community, she said.
 
But they and others representing a range of partners in the new campaign stressed the importance of broadening participation.
 
“These breakthroughs do not happen on their own,” said John Castellani, president and CEO of Pharmaceutical Research and Manufacturers of America, but rather rely “very heavily on volunteer participation in clinical trials.”
 
Years of work by the pharmaceutical industry to increase diversity in trials have not borne the hoped-for fruit: “African Americans, Asian Americans, and Hispanics are still dramatically underrepresented in clinical trials,” he said.
 
As Castellani said, “the future of medicines is going to be aimed more and more at genetically homogeneous populations,” which means drawing more from minority populations to properly test drugs—especially those aimed at diseases those populations suffer from disproportionately.
 
For example, prostate cancer is twice as fatal for African Americans as Caucasians, according to material distributed in advance of the campaign kickoff—and yet only 4 percent of prostate-cancer clinical trial participants are African American. Cancer is the top cause of death for Asian Americans, but just 2.8 percent of cancer trials patients are Asian American. And despite the higher prevalence of diabetes in the Hispanic population, only 1 percent of all trial members are Hispanic.
 
Based on early glimpses, the campaign is centering on personal connections to family members and the wider community of each minority group. A video promoting the effort included lines like “It’s not enough to wait for someone else to act” and “We all have a responsibility to each other and future generations.”
 
Gary Puckrein, president and CEO of the National Minority Quality Forum, noted that by 2020, more than half of Americans will be members of groups now called “minorities,” leading him to argue that “underrepresentation of minorities affects everyone.”
 
He said this is a campaign to help test “medicines for a biodiverse America.”
 
Cardenas offered an example: When he started practicing medicine, there was just one medication for hypertension; he noticed, though, that it didn’t work the same in people with Hispanic backgrounds as it did in those with non-Hispanic heritage.
 
“How are we to know how our patients will respond to these medications?” he asked. “It’s something we should not leave to chance.”
 
Anderson, for her part, said she is a five-year breast-cancer survivor. She was diagnosed in 2009 with stage three, triple-negative cancer, “a very aggressive form of breast cancer that’s common in African-American women.” Her doctor suggested she participate in a trial, which she credits with her survival.
 
That’s another key element beyond encouraging individuals to participate, said Dr. Ho Luong Tran, founding president and CEO of the National Council of Asian Pacific Islander Physicians.
 
“As physicians we must recognize our role as trusted healthcare providers,” she said. Doctors “owe it” to their patients to “share all possibilities” for treatment, including clinical trials. She said more than two-thirds of Americans report being likely to join a clinical trial if their doctor suggests it, but only 22 percent of people say they have had such a conversation.
 
Citing statistics that 38 percent of Hispanics, 36 percent of Asian Americans, 33 percent of African Americans and 42 percent of non-Hispanic whites say doctors have the greatest impact and the greatest responsibility to talk about trials and research, Tran called on her fellow doctors to learn about, support and encourage their patients to join trials. “If we don’t talk to them about clinical research, few others will,” she said.
 
Puckrein said the website for I’m In, at www.JoinImIn.org has options to register as a member of the public, an interested doctor, and even as a trial researcher, to allow all three groups to connect with each other more efficiently.

Merck HIV therapies make big news at CROI

Published in Drug Discovery News

NEW YORK—Two separate HIV therapies manufactured by Merck, one new and the other a groundbreaking favorite from the past, had big announcements at the 21st Conference on Retroviruses and Opportunistic Infections in early March.
 
It was just a peek at the newcomer, doravirine (MK-1439), looking at data from the first 24 weeks of the first part of a two-segment 96-week trial comparing doravirine to the current standard of care, efavirenz (Bristol-Myers Squibb’s Sustiva).
 
“This study is really the first data we have,” apart from a very small, very short monotherapy study, said Dr. Hedy Teppler, executive director, infectious diseases at Merck Clinical Research, who was also an investigator on the trial.
 
This was a Phase 2 trial (Phase 3 will come later in 2014), in which a range of once-daily doses, 25 milligrams, 50 mg, 100 mg and 200 mg, were used in combination with once-daily doses of emtricitabine/tenofovir disoproxil fumarate, Gilead Sciences’ Truvada.
 
“It certainly performed at least as well as efavirenz,” she tells DDNews. Merck is hoping doravirine will be better in terms of both tolerability and potency that existing drugs, and with less central nervous system toxicity.
 
“Each dose compared well,” according to Teppler—in fact, the data didn’t distinguish one dosage as being more effective than the others. Additional information, though, led to the choice of 100 milligrams to be the dose for the remainder of the 96-week trial and other further studies.
 
Teppler says those factors included providing a reasonable dosage level to discover potential negative drug interactions, and to explore the drug’s overall usefulness.
 
“Choosing the 100-milligram dose should protect against needing to do any dosage adjustment,” Teppler says.
 
For those not candidates for efavirenz (such as women of child-bearing age or people with central nervous system issues), another study offers hope. Merck’s drug Isentress (raltegravir), the first integrase inhibitor approved by the FDA (in 2007), featured in a new study by the AIDS Clinical Trials Group. It compared Isentress given twice daily against atazanavir (Bristol-Myers Squibb’s Reyataz) and darunavir (Tibotec’s Prezista), both given once daily. (All patients also got Truvada daily.)
 
While Merck itself had looked at Isentress versus efavirenz, and found positive results, the ACTG “felt there was a need to look at options in patients who were not candidates for efavarinz,” said Randi Leavitt, senior director, clinical research, global clinical development—infectious disease at Merck, such as women of childbearing age or people with central nervous system issues.
 
The 96-week ACTG study (ACTG 5257) looked at 1,800 treatment-naive patients, a quarter of whom were women, 34 percent non-Hispanic white, 42 percent non-Hispanic black and 22 percent Hispanic.
 
The study found encouraging news for Merck, Leavitt tells DDNews. First, “all three regimens were basically equivalent with regard to efficacy.” But when combining that result with tolerability, “raltegravir was superior to the other two regimens.”
 
And while Isentress has been criticized for being a twice-daily medicine up against once-daily competitors, the results showed that “if the drugs are well tolerated, people will be compliant with a twice-a-day regimen,” Leavitt said.
 
Nevertheless, the company is working on a reformulation to make a once-daily 1,200-mg dose available. That follows on the 2011 report of the failure of tests of an 800-mg daily dose; Leavitt said those results “provided a lot of information” that have improved expectations for the new formulation.

Smash and grab

Published in Drug Discovery News

LA JOLLA, Calif.—Scripps Research Institute scientists have devised two highly specific methods to create new drugs, one that flings a single atom as a wrecking ball and another that can find therapy targets in tiny folds of microRNA.
 
A paper published in Nature in March describes research by Scripps chemistry professor Jin-Quan Yu that builds on his earlier groundbreaking development of using a weak chemical bond in molecule frameworks previously thought to be an obstacle, instead turning it into a powerful advantage when building drug compounds.
 
To attach function groups to chemical frameworks, a C-H bond must be broken—and it must be a specific, and possibly different, one for each potential intended attachment option.
 
“The best way to make a molecule is to replace a C-H bond directly,” Yu tells DDNews.
 
Some C-H bonds, though, don’t react, and are far away from attachment points of potential catalysts, rendering them difficult to break. With previous methods, “you cannot make certain types of molecules,” Yu says.
 
Yu’s insight, which he has been developing since 2002 at the University of Cambridge, was that he could install nitrile groups—weak connections that were dismissed in the past as hurting the structure of a framework—and use that weakness to facilitate the swinging of a catalyst across the molecular distance to a remote C-H bond, allowing it to be broken.
 
At that point, just as with other broken C-H bonds, functional groups that are building blocks for drugs can be attached, Yu said.
 
He originally published about the technique for what is called “meta” C-H activation inNature in 2012; the most recent paper has both simplified the process and allowed it to be applied more specifically to targeted C-H bonds.
 
“The key is to tune the shape of the template to create a subtle bias towards the targeted carbon hydrogen bond,” Yu said in Scripps’s announcement of the paper. “At the same time the template’s movement towards the target site has to be exploited effectively by a super-reactive catalyst.”
 
The chemical reagent involved will be available through Bristol-Myers Squibb’s catalog for order by laboratories, so that other researchers may use it in their own work, including targeting compounds common in drug discovery, such as tetrahydroquinoline, benzooxazines, anilines, benzylamines, 2-phenylpyrrolidines and 2-phenylpiperidines. “All these are commonly used in medicinal chemistry either as final drug compounds or intermediate compounds from which the final compounds are made,” Yu notes.
 
And in the future, he expects to further refine the technique so that the nitrile groups can be used catalytically, rather than needing to be installed and later removed.
 
The other approach, developed by Matthew Disney at the Scripps Florida campus, also inverts a standard method of searching for binding opportunities, this time in microRNA folds. Where previously researchers had to take RNA structures and do high-throughput screenings to find binding opportunities, Disney has built a database of potential types of bonds between RNAs and small-molecule function groups.
 
Then, by comparing given RNA sequences—not structures—to the database, Disney’s method can pinpoint possible opportunities. Only then does attention turn to the structures themselves, he tells DDNews: “Once we identify these interacting partners, could we find them … and drug it?”
 
Every disease has a relation to RNA, he said, because proteins play key roles in the process.
 
“If there’s some toxic protein … we can potentially target the RNA that makes that protein,” Disney says. (Alternately, if a disease causes too little of a protein to be produced, his technique can boost production.)
 
As a test case, and proof of concept, Disney and his team identified a druggable target—and its corresponding drug—in MiR-96 microRNA, which is believed to delay cell death by obstructing apoptosis, a natural cell-death process that begins when cells begin to grow in ways that are otherwise uncontrollable.
 
“People think that RNA can’t be drugged with a small molecule,” Disney says, but his approach proves that belief wrong. And it offers the prospect of very tightly targeting cells, in a way much narrower than the broad targeting approach taken today, where non-disease-related cells are also affected by therapies.
 
Next, Disney will go after diseases without current cures, such as Ebola, as well as orphan diseases that may need therapeutic-research attention.
 
While resistance to microRNA-targeting drugs is possible, Disney said his approach would help respond: “If resistance were to happen, and the RNA structure were to change,” then they could go back to the database and find binding matches for the new structure, he says.

Pharmacyclics: First drug gets rolling

Published in Drug Discovery News

SUNNYVALE, Calif.—Building quickly on the November 2013 approval of its first drug to market, Pharmacyclics has already achieved accelerated approval for that drug, Imbruvica (ibrutinib), in a second disease, with future plans for additional diseases.
 
The first approval came, under Breakthrough Therapy Designation, in mantle-cell lymphoma (MCL) for patients with one prior treatment; that was followed in February by approval for patients with one prior treatment in chronic lymphocytic leukemia (CLL), which the company’s chief medical officer, Jesse McGreivy, described as “a slow-growing blood cancer of the white blood cells” that is “the most common form of leukemia in the Western world.”
 
Company- and third-party-sponsored clinical trials continue in several other leukemias. In February, Imbruvica, which targets Bruton’s tyrosine kinase (BTK), a part of the B-cell receptor signal system, was added to the National Comprehensive Cancer Network’s Clinical Practice Guidelines in Oncology for relapsed/refractory MCL and relapsed/refractory CLL, as well as Waldenstrom’s macroglobulinemia (which currently has no drug treatment).
 
Reuters reported in February that RBC Capital Markets analyst Michael Yee predicted Imbruvica’s eventual annual global sales could reach $5 billion. McGreivy said there are 16,000 patients diagnosed with CLL every year in the U.S., and that more than 40,000 of the current 115,000 CLL patients have had a first therapy.
 
 
The potential market strength for the drug is further suggested by the fact that in December 2011 Janssen Pharmaceuticals, owned by Johnson & Johnson, agreed to pay 60 percent of drug-development costs and milestone payments, for a total of up to $975 million, in exchange for half of the drug’s profits.
 
Janssen is pursuing regulatory approval in more than 50 countries, Pharmacyclics CEO Robert Duggan said in a conference call announcing the CLL approval. Janssen is also helping significantly with sales, Paula Boultbee, Pharmacyclics’s executive vice president of sales and marketing, said in that call. She said the MCL approval kicked off a “strong launch” that was bolstered by several programs to ensure affordability of the drug—including a 30-day free supply for patients whose insurance companies take longer than five days to decide about coverage, and help limiting monthly out-of-pocket expenses for Imbruvica to $25 for qualifying patients. The average age of CLL patients is 72, according to company documents.
 
Imbruvica posted net product revenue of $13.6 million in the six weeks between its November 2013 approval and the close of the fourth quarter, according to Pharmacyclics’s most recent financial briefing.
 
The company’s net revenue for 2013 was $260.2 million, up 58 percent from $164.7 million in 2012. The remainder of the 2013 revenue was from the Janssen funding agreement, under which the recent CLL approval triggers a $60 million milestone payment.
 
A Leerink Partners analysis suggested that for the first quarter of 2014, Imbruvica sales could reach $50 million.
 
The rapid approvals for Imbruvica were supported by BioClinica, a Pennsylvania-based vendor of information-technology tools supporting clinical trials, including patient randomization, data collection and validation, and online analysis.
 
BioClinica works with the world’s biggest pharmaceutical manufacturers and tiny ones too, and touts its experience. “We as a vendor have worked on more clinical trials than most pharmaceutical companies,” Peter Benton, executive vice president and president of the eClinical Solutions division at BioClinica, tells DDNews.
 
Its systems allow efficient management of the enormous quantities of information generated by trials (“I’ve been in the industry long enough to remember tractor-trailers …  lined up waiting to deliver boxes and boxes of information on paper,” Benton said), and help vet and clean the data so it is ready for rapid processing by the FDA.
 
The company continues to expand by merger and acquisition to fill “white space between our current products,” Benton said. And in mid-March, BioClinica did it again, merging withCCBR-SYNARC. Both companies are owned primarily by the equity firms Water Street Healthcare Partners, and JLL Partners, and their combined services will support the entire drug-development spectrum, a merger-announcement statement said. The merged companies’ chairman will be Jeffrey McMullen, a longtime industry executive who in 2012 serves as chairman of the Association of Clinical Research Organizations.

Wednesday, April 2, 2014

Physicists are building an NSA-proof internet

Published on GlobalPost
BOSTON — It’s long been the Holy Grail of communications: technology that not only maximizes privacy, but also reveals when a message had been intercepted or copied.
The quest began in antiquity, with encryption and with the humble envelope — which not only kept out prying eyes but also showed if a message had been opened by someone other than its intended recipient.
More recently, Edward Snowden's revelations of spying by the National Security Agency have heightened concerns over electronic privacy, espionage and meddling.
Despite centuries of innovation, today’s methods for secure communication are basically the same — and in some ways are even more vulnerable, given how easy it is to copy, store, and search electronic data.
Scientists say a solution for truly private, tamper-free digital communication is underway, and should be commercially viable within a decade.
For theoretical physicists, the solution has already existed for several decades, but the technology needs refining before it’s available on a mass scale across the internet. Still, the pieces of this ultra-secure, high-speed communications web are beginning to take shape in labs around the world.
The system is based on quantum physics, and more specifically on the concept of “entanglement.”
Entanglement is a topic that even hardened scientists discuss with a degree of wonder. “It’s quite mysterious, in fact,” said Félix Bussières, a senior researcher in the Group of Applied Physics at the University of Geneva in Switzerland.
Physicists have long struggled to come up with metaphors and analogies to describe entanglement, which is so hard to actually wrap the mind around that even Albert Einstein gave up and settled for calling it “spooky.” It involves creating two photons (particles of light) that, while independent of each other and free to travel long distances apart, are still tightly interrelated, almost as if they are not two separate photons but one indivisible photon pair. As photons travel, they spin; each part of the entangled photon pair spins in the exact opposite direction from the other. If something happens that causes either of the pair to change its spin, the other instantaneously changes its spin to compensate.
Entangled photons act like a tripwire for any outside tampering — which is what makes a quantum internet so secure. In other terms, “quantum mechanics tell us that if you look at a quantum state you perturb it,” wrote Thomas Jennewein, an associate professor at theInstitute for Quantum Computing and in the physics and astronomy department of Ontario'sUniversity of Waterloo, in the institute’s 2013 annual report. (If you want to read more on the science, start by looking up the Heisenberg Uncertainty Principle and the Schrödinger’s catthought experiment.)
The good and bad of the quantum internet
So in the ideal case, wiretapping a quantum message system is impossible, Bussières said, because the wiretap will disturb the system, and the disturbance can be detected by the sender and recipient.
“The principle is perfectly secure,” Bussières said. “One can use in principle the quantum properties of light ... to ultimately cipher communication ... in a way that is ... provably unbreakable.”
This now works in the lab. It has even gone commercial: There is a small industry doing what is called quantum-key distribution — using quantum methods to generate encryption keys that are substantially more secure than more conventional ones. But the keys can only be shared across relatively small distances, no more than about 125 miles of optical fiber.
The challenge is that the technology depends on photons (instead of electrons), and photons attenuate, or lose, their momentum over distance.
It also means that quantum connections are quite slow (about one megabit per second, Bussières said) compared to standard internet communications speeds. That’s why the technology is being used for keys instead of entire messages. And as such, while messages with quantum keys are more secure than others, they can still be monitored and copied for storage and later cracking by hackers or spies.
Quantum-key distribution could be poised for widespread commercialization right away, Bussières said, if technological advances threatened the security of conventional electronic encryption.
“If we want to go beyond these distances” with actual quantum connections, “other technologies are being intensely researched around the world,” he said. It would take several years to develop quantum-enabled devices that are small enough, cheap enough, and efficient enough to be mass-produced and widely used, “but considering the amount of research put in that direction, there is a great chance that it will become a reality,” Bussières said.
For nerds: solving the quantum quandary
To transform quantum communications from a lab project to a commercial application, three major approaches are in development: wavelength optimization, quantum repeaters, and satellite connections.
Scientists say the progress is encouraging, in part because much of the research involves adapting existing, conventional optical-communications gear to quantum uses, rather than inventing all-new equipment.
First, it’s not enough to simply connect photon-entanglement sources and detectors to opposite ends of optical-fiber cables. Because eventually photons attenuate — getting absorbed or scattering away from their detectors — even non-quantum-carrying fibers need help to keep the signal alive across long distances.
Steven Olmschenk, an associate professor of physics at Denison University in Ohio, is working to lengthen the distance entangled photons can travel in optical fiber. While previously he had also been working on quantum repeaters at the Joint Quantum Institute, he and others realized they were researching themselves into a bit of a corner.
Most of the photons used in quantum research so far, he said, are in ultraviolet wavelengths, which attenuate too quickly to be truly useful in fiber-optic transmissions. Internet and telecom companies already use infrared signals in fibers, because they attenuate more slowly.
Olmschenk’s research focuses on taking existing capabilities for UV quantum communications, and adapting them to infrared transmission and reception. It has only been a couple of years, though, and he told GlobalPost that while he is optimistic, he does not yet have any results to report.
If he is successful, he and others will also have to translate into UV the accomplishments of other researchers figuring out how to extend signals in other ways.
Bussières is working to improve quantum repeaters, which combine a photon detector, a quantum memory, and a photon source so that when a quantum signal needs to be transmitted, say 600 miles, that trip can be split by repeaters into shorter segments with less attenuation.
But for distances (or geographic features) too large to handle usefully with optical fiber, there is another option: sending quantum signals by satellite.
Jennewein, of the Institute for Quantum Computing, is on that task. He and his team have set their sights on sending entangled photons to satellites in low Earth orbit, likely somewhere around 300 to 360 miles above the ground. At present, open-air quantum transmissions have been achieved at around 100 miles, using transmitters and receivers that are very precisely aligned. (This gets harder when involving a satellite moving 15,000 miles per hour.)
Jennewein’s current work covers several aspects of the puzzle, including aiming photons accurately at distant receivers that are moving, determining how much attenuation will happen in the atmosphere as it thins at higher altitudes, and improving detection of the weak signals that will arrive.
One crucial challenge has not yet been undertaken: Because quantum sources need to be smaller and more energy-efficient before they are ready to fly in space, nobody has yet sent a quantum signal from a satellite back to Earth.
Other efforts, which would expand bandwidth over those extended distances, are also in the works. "Quantum dots," nanocrystals that conduct electricity, can simplify and even automate the process of emitting photons with particular entanglements on demand, which could help increase transmission rates, as would using light from LEDs instead of lasers. And repeaters capable of handling multiple quantum signals simultaneously would speed things up as well.
But the crucial part is building the connections that can span the world so that people can, it is hoped, finally communicate with complete privacy.

Friday, March 21, 2014

Three little maids from Maine: Opera stars come home for ‘Three Divas’ concert

Published in Out In Maine

When you’re a diva, you don’t have to meet the people you’ll be singing with before the day of the show. And you only need one group rehearsal — even if it’s for a big event like the 20th year of an opera company. Or so it might seem.

“It used to be a good thing” to be called a diva, laughs Suzanne Nance, who is one of three female opera singers slated to perform a show called “Maine’s Divas Come Home” at the University of Southern Maine’s Hannaford Hall on April 1 as part of PORTopera’s 20th anniversary celebration.

Nance, a soprano who is also a former Maine Public Broadcasting Network radio host now working at Chicago’s WFMT, will sing with another soprano, Ashley Emerson, and a mezzo-soprano, Kate Aldrich, a member of PORTopera’s advisory board and the first Maine native to fill a principal role in one of the company’s major productions — the title role in Carmen.

None of the three have ever sung together before, and Nance will be meeting Aldrich in person for the first time; she has met Emerson in the past. “We’re going to rehearse the day of” the show, with pianist Martin Perry, who himself is a well known musician in Maine and around the world. “We’ll basically run the whole show, while saving our voices,” Nance says. “We’ll just meet, put it together, and make a show of it.”

That show will be varied in terms of song choice and format.

“The open and close we’re going to go a la the Three Tenors,” Nance says, plus “three or four of the most beautiful duets in all of opera,” and several arias, from pivotal moments in significant shows that nevertheless “can come out and stand on their own.”

The songs are diverse, including works by classical masters Mozart and Verdi alongside modern standouts like Englebert Humperdinck.

Noting that the evening’s program will begin with an ensemble performance of “The Three Little Maids From School,” from Gilbert and Sullivan’s The Mikado, Ann Elderkind, PORTopera’s board president, says it’s appropriate the singers themselves “started as three little maids from Maine.”

Aldrich, originally from Damariscotta, “is so big in Europe,” Nance says. Based in Rome and New York City, Aldrich first sang the role of Carmen at PORTopera and has gone on to sing it across Europe, Elderkind adds.

Emerson, who grew up in Bangor, is a recent graduate of USM’s music program, focusing on voice performance. She was involved in PORTopera’s Emerging Artists program, and made her mainstage debut in the company’s 2003 production of Lucia di Lammermoor. Right out of college, she was accepted to a residency at the Metropolitan Opera in New York, where her career is “just taking off,” Nance says.

The singers are so busy, in fact, that it took about a year to coordinate everyone’s schedule, says Elderkind. And they had to pick the program in a Skype session, Nance says. When planning it, “we were all sort of giddy” about coming back to Maine, singing together, and seeing friends and family during the trip. “It’s great for us to come back and celebrate a place we love,” Nance says.

The event will also be celebrating the strength of the opera company, which has weathered a worldwide economic slump that forced bigger cities’ operas to close (including the New York Opera and the Baltimore Opera). Elderkind credits “the community of Maine coming forward” to support the company, especially in difficult times.

“Maine’s Divas Come Home” | Tuesday, April 1 @ 7:30 pm | Hannaford Hall, USM Abromson Center, Bedford St, Portland | $65 | porttix.com | portopera.org

The new normal: Conservatives try a different approach in fight against equality

Published in Out In Maine

In the last six months, as marriage equality and other LGBTQ rights have continued their inexorable expansion across the United States, it has become clear that instead of shaking the country to its core, or undermining America as we know it (as opponents have long alleged), protecting the rights of everyone in our society has benefited tens of thousands, perhaps even hundreds of thousands, of Americans in countless ways throughout their everyday lives.

What’s especially interesting is how quiet the ridiculous deep-seated opposition has actually become. The radical conservatives who for many years preached that recognizing the LGBTQ rights — same-sex marriage equality, employment non-discrimination, and more — would harm families, or kids, or communities, or the government, or the society, or something, have, it would appear, realized that marriage equality is not ending the world after all.

Writing in The Atlantic in early March, researcher Robert P. Jones reported that his studies showed nearly half of all Southerners now support same-sex marriage. Despite all the legal action and court decisions, he wrote, “these changes cannot be explained away as merely another example of federal judicial activism circumventing the will of the people in southern states. Rather, we are witnessing dramatic cultural transformations, which include changing minds even among culturally and religiously conservative Americans in the South.”

Even conservative pundits seem to be noticing this progress. Fox News commentator Howard Kurtz wrote in early March about a Washington Post/ABC poll with showing 59 percent of Americans support same-sex marriage, and only 34 percent opposing. That’s almost an exact reversal of the numbers from the same poll in 2004, which Kurtz calls “a headspinning shift.”

He observes that “even GOP politicians who are against [same-sex] marriages are muting their opposition,” attributing that decision to the fact that “three-quarters of Americans under 30 back same-sex marriage (as opposed to less than half of senior citizens).”

With same-sex marriage recognized at the federal level and legal in 17 states — and with marriage inequality under siege in most of the 33 states where it is not yet legal — conservatives are in retreat. (See sidebar, “Scorecard.”)

Surrender?
In fact, conservative New York Times columnist Russ Douthat’s March 2 column was entitled “The Terms of Our Surrender.” Spoiler: It’s not really a surrender. Rather, it highlights a change in the scale and scope of the fight to one much larger and broader than the terms of civil marriage.

No longer inveighing against what he and others called the “redefinition” of marriage to include all consenting adults, Douthat asked his readers to redefine the idea of “religious freedom” to mean protecting, effectively, anything they feel like doing at any time, for any reason.

A great many people around the country are now objecting to laws barring their businesses, places of public accommodation, and workplaces from discriminating against same-sex couples, on the grounds that, somehow, discrimination is part of their religious philosophy and therefore outside the realm of government control.

Douthat came to a spirited defense of that prodiscrimination perspective — even terming it a “subculture,” simultaneously admitting its small and dwindling numbers and suggesting it should be preserved. He lamented the prospect that wedding photographers and adoption agencies might “be treated like the proprietor of a segregated lunch counter,” and face penalties for continued discrimination.

Continuing his sad hypothetical, Douthat posits that “eventually, religious schools and colleges would receive the same treatment as racist holdouts like Bob Jones University, losing access to public funds and seeing their tax-exempt status revoked.”

Carving out religious-freedom protections is a common method of ensuring religious institutions are not compelled by the government to change their teachings; Maine’s law, like those in many other states, was strategically written to allow churches and ordained ministers to decide for themselves whether they consecrate or celebrate same-sex marriages.

But Douthat wants much more. For him, individuals should be able to decide for themselves whether they treat other humans with dignity and respect — or whether their religious beliefs allow them to discriminate.
In fact, in March, the US Supreme Court is expected to rule on whether corporations can hold religious beliefs and, if so, whether those beliefs can exempt corporations from a great many state and federal laws.

Douthat wraps up with a weird pronouncement that seems to blame the people he views as victims: “Christians had plenty of opportunities — thousands of years’ worth — to treat gay people with real charity, and far too often chose intolerance. (And still do, in many instances and places.) So being marginalized, being sued, losing tax-exempt status — this will be uncomfortable, but we should keep perspective and remember our sins, and nobody should call it persecution.”

And his final line could be called fatalistic if it weren’t such a call to arms: “all that’s left is the timing of the final victory — and for the defeated to find out what settlement the victors will impose.”

Scorecard: Where discrimination is under attack
What Russ Douthat and other conservatives are seeing, and recognizing the inevitability of, is the march to the courthouse of LGBTQ Americans across the country. Sadly, most of them are not yet heading there to get married — rather, they’re suing to force states to allow and recognize their marriages.

According to NBC News reporter Pete Williams, “cases are now pending in all but eight of the 33 states that forbid gay couples to marry.” Last June’s US Supreme Court decision striking down Section 3 of the Clinton-era Defense Of Marriage Act has opened the floodgates.

Williams’s tally says 17 states permit same-sex marriage, 29 ban it under an amendment to the state constitution, and the remaining four ban it in state statute.

With cases in almost every state, and appeals in process in several circuits, “it seems a near certainty that the issue will be back at the US Supreme Court soon, either by the next term that begins in October or the year after,” Williams wrote.

Here, compiled primarily from pro-marriage groups Marriage Equality USA and Freedom to Marry, is a rundown of where all 50 states stand:

ALABAMA | A case was filed in December 2013 to overturn ban, and to force recognition of marriages performed in other states.

ALASKA | The state Supreme Court is considering a denial of survivor benefits as a result of constitutional and legal bans.

ARIZONA | Two cases, one in state court and another in federal court, are pending against the 2004 constitutional band; in January, the state asked for dismissal of the federal case.

ARKANSAS | In January, a class-action suit was filed seeking to overturn the state’s bans, a 1996 law and a 2004 constitutional amendment. That builds on a 2010 case seeking to preserve health benefits for state workers. They are getting benefits now, under current rulings, but the case just received class-action status covering all Arizona state workers with same-sex partners.

CALIFORNIA | Legal

COLORADO | Four cases, all in state court, seek to overturn the 2004 constitutional amendment ban, which also created non-marriage civil unions.

CONNECTICUT | Legal

DELAWARE | Legal

FLORIDA | State and federal suits are pending, trying to overturn the 2008 constitutional amendment ban.

GEORGIA | no challenges

HAWAII| Legal

IDAHO | A federal case seeks to reverse the 2006 constitutional amendment ban, which is being defended by the state attorney general; in may, a judge will consider whether to skip the trial and just issue a ruling.

ILLINOIS | Legal

INDIANA | in early march, four couples sued in federal court seeking marriage rights and to overturn the state’s statutory ban.

IOWA | Legal

KANSAS | A December 2013 lawsuit asks permission for a same-sex couple married elsewhere (Kansas has a constitutional ban) to file joint income-tax returns.

KENTUCKY | On February 12, a federal judge ruled the state’s ban unconstitutional; if an appeals court does not issue a delay, same-sex couples will have full legal rights starting March 20. The state attorney general says he will not appeal the case, but the governor says he will. Also, marriages performed elsewhere are recognized.

LOUISIANA | Three cases seek to overturn statutory and constitutional bans; the state is defending those bans.

MAINE | Legal

MARYLAND | Legal

MASSACHUSETTS | Legal

MICHIGAN | Federal judge will rule in late March on challenge to 2004 voter-approved state ban.

MINNESOTA | Legal

MISSISSIPPI | A case seeks to force the state to recognize an out-of-state same-sex marriage for the purpose of granting a divorce; there is no active challenge yet to the state’s constitutional ban, but preparations are under way.

MISSOURI | There is not yet a case directly challenging the state’s constitutional ban, but two cases do seek to require recognition of out-of-state same-sex marriages.

MONTANA | A case in state court now seeks “all of the benefits of marriage, other than marriage itself,” according to Marriage Equality USA.

NEBRASKA | no challenges

NEVADA | In 2012 a federal judge rejected a challenge to its 2002 constitutional ban; an appeal will be heard by the 9th circuit soon, but the state’s attorney general and governor are not supporting the ban.

NEW HAMPSHIRE | Legal

NEW JERSEY | Legal

NEW MEXICO | Legal

NEW YORK | Legal

NORTH CAROLINA | Republican lawmakers are defending the statutory and constitutional bans; a county register of deeds has also said he will ask the state attorney general to decide whether marriage licenses can be issued to same-sex couples.

NORTH DAKOTA | no challenges

OHIO | In December 2013, a federal judge overturned the state’s 2004 constitutional ban; the attorney general has appealed the ruling to the 6th circuit.

OKLAHOMA | In January, a federal judge overturned the state’s constitutional ban; the state’s appeal will be heard in April in the 10th circuit.

OREGON | A federal suit challenges the state’s constitutional ban; arguments will be heard in april, but the state attorney general has said she will not defend it.

PENNSYLVANIA | Several state and federal cases oppose the statutory ban; the attorney general has said she will not defend it.

RHODE ISLAND | Legal

SOUTH CAROLINA | A federal suit was filed in August 2013 seeking to overturn the state’s constitutional and statutory bans.

SOUTH DAKOTA | no challenges

TENNESSEE | A federal suit asks a judge to overturn the statutory and constitutional bans.

TEXAS | Numerous state and federal cases challenge the constitutional ban and other statutory restrictions on equality, including an appeal before the 5th circuit of a February ruling striking down the bans.

UTAH | In December 2013, a federal judge struck down the state’s constitutional amendment; its appeal will be heard in April in the 10th circuit. another federal case seeks to protect about 1300 same-sex couples who were legally married in Utah after the December decision and before the US Supreme Court’s January stay of the ruling.

VERMONT | Legal

VIRGINIA | In February, a federal judge overturned the 2006 constitutional ban; the decision is stayed pending an appeal decision by the 4th circuit. the state attorney general has not defended the ban, and instead intends to join the plaintiffs seeking to have it struck down.

WASHINGTON | Legal

WEST VIRGINIA | A federal suit, which is opposed by the state attorney general, seeks to overturn the statutory ban.

WISCONSIN | A case before the state supreme court challenges the 2006 constitutional ban and a 2009 domestic-partnership law; a decision is expected this summer. a federal suit also challenges those bans, as well as a Wisconsin-only law banning same-sex couples from marrying elsewhere under penalty of fine and imprisonment.

WYOMING | In March a state lawsuit was filed seeking to strike down the statutory ban.

WASHINGTON DC | Legal

Equality Overseas
Same-sex marriage rights are an equally hot topic in other countries. The most attention has been given to Russian president Vladimir Putin, who continues to enforce his country’s sweepingly vague ban on “gay propaganda,” while his people overwhelmingly object to same-sex marriages.

In Africa, serious legal barriers are still being erected. (Only South Africa has legalized same-sex marriage.)

Uganda, the most aggressively anti-gay country on that continent, recently enacted a law that could sentence homosexuals to life imprisonment. Faced with Western objection to that law, president Yoweri Museveni complained about “social imperialism,” saying foreigners were trying to “impose social values” on his people.

The Uganda-based Civil Society Coalition on Human Rights and Constitutional Law recently released 20 guidelines for national and international allies on “how to offer support now that the anti-homosexuality law has been assented to.” among their suggestions:

-“call on multinational companies that have businesses in Uganda [such as Heneiken, British Airways, and Barclays Bank] to go public about their concerns [about] the act and their future economic engagements in Uganda.”

-“expand investment in funding for service delivery and advocacy in defiance of the law, targeting LGBT populations, to attempt to mitigate the harmful impact this law will have on access to services, and on human rights.”

-“call for your government to issue travel advisories on Uganda...alerting their own LGBT citizens to the risk of traveling in Uganda.”

-“draw international public attention to issues such as corruption, human trafficking...land-grabbing, as well as the suppression of media freedom and civil society space... so that attention shifts to where it properly belongs: in the best interests of the country’s population as a whole.”

Asia is another place with little-to-no recognition: the best status for same-sex marriage is in Israel, where marriages themselves are not allowed, but where the government recognizes them if legally performed elsewhere.

Nepal, Taiwan, and Vietnam are among the countries that do have active discussions under way. and the Dalai Lama recently became the first Buddhist leader to endorse same-sex marriage.

In the Pacific, Australia bans same-sex marriage; New Zealand allows it. Most of the island nations don’t recognize same-sex marriages; several also ban all homosexual activity.

In the Americas, Canada allows same-sex marriage; Mexico and several other Central American countries only recognize same-sex marriages performed elsewhere. South America is fairly split, though powerhouses Brazil and Argentina (as well as smaller nation Uruguay) have same-sex marriage. Colombia and Ecuador have some legal rights for same-sex couples.

Most Western European countries (though not Italy) recognize same-sex marriages or offer some sort of government-registered partnership; Eastern European countries are uniform in not recognizing same-sex marriages, and several nations in that area have specific opposite-gender requirements for marriage.