2016年首届美中药源翻译比赛隆重开始了!
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(四)奖项设置
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第一篇
Same but Different
How epigenetics can blur the line between nature and nurture.
Why are twins different? Well, because idiosyncratic events are recorded through idiosyncratic marks in their bodies. If you sequence the genomes of a pair of identical twins every decade for fifty years, you get the same sequence over and over. But if you sequence the epigenomes of a pair of twins you find substantial differences: the pattern of epigenetic marks on the genomes of their various cells, virtually identical at the start of the experiment, diverges over time.
Chance events—injuries, infections, infatuations; the haunting trill of that particular nocturne— impinge on one twin and not on the other. Genes are turned on and off in response to these events, as epigenetic marks are gradually layered above genes, etching the genome with its own scars, calluses, and freckles. Prospero, raging against the deformed Caliban in “The Tempest,” describes him as “a devil, a born devil, on whose nature/Nurture can never stick.” Caliban is destined to remain a genetic automaton, a windup ghoul—vastly more pathetic than anything human. He experiences the world, but he has no capacity to be changed by it; he has a genome that lacks an epigenome.
It is a testament to the unsettling beauty of the genome that it can make the real world stick. Hindu philosophers have long described the experience of “being” as a web—jaal. Genes form the threads of the web; the detritus that adheres to it transforms every web into a singular being.
An organism’s individuality, then, is suspended between genome and epigenome. We call the miracle of this suspension “fate.” We call our responses to it “choice.” We call one such unique variant of one such organism a “self.”
A strange thing happened on the way out of Reinberg’s ant room. One of the ants leaped out of the Tupperware box onto my shirt. There was a momentary commotion—“They bite,” Yan said, matter-of-factly—and then we found the ant on my shoulder, making a desperate break for my ear. Yan pulled out a pair of forceps and, after a few attempts, she was returned to the colony.
The retrieval had been masterfully delicate, but the ant was injured: a leg had been bruised, and she waddled lopsidedly for a while. The wound would heal, I knew, but a scar would remain. She had done it: she had made difference out of similarity. The clone was somehow no longer quite a clone. I watched her make her way back to the colony—the One That Almost Got Away, to be memorialized in song and verse—until she vanished into the metropolis of soldiers, workers, and queens.
第二篇
It’s a loser: BioMarin writes off its $680M Duchenne drug gamble
Back in late 2014, BioMarin put up $680 million in cash for a risky gamble. It bought up Prosensa and its failed Duchenne drug drisapersen, betting that it could leverage its experience on rare drugs and take it on to a near-term regulatory approval.
On Tuesday evening, the biotech conceded a near-complete failure. After seeing the door slammed in its face at the FDA, European regulators sent a clear message that the same fate awaited BioMarin’s application across the Atlantic. BioMarin is now withdrawing its application, ending its work on drisapersen and three follow-on therapies: BMN 044, BMN 045 and BMN 053, now in Phase II studies.
But BioMarin vows to make a comeback, eventually.
“Our plan now is to invest in research of next generation oligonucleotides with the goal of making a safe and effective treatment available for boys with this devastating disorder,” said
Jean-Jacques Bienaimé, BioMarin chairman and chief executive officer. BioMarin has also been fighting to protect its patents on using antisense oligonucleotides for exon 51 skipping, winning an initial ruling last fall against Sarepta.
Prosensa's drug failed to beat a placebo in significantly improving boys' ability to complete a 6-minute walk test--the classic measure of success in this field. Soon after, GlaxoSmithKline walked out of its collaboration and washed its hands of the drug. But left to its own devices, the small biotech completed fresh analysis of extension study data that backed a theory that providing the drug earlier while extending treatment could delay disease progression.
That argument, though, was slapped down by outside and insider experts at the FDA, who failed to see any evidence of efficacy. The same experience awaited PTC Therapeutics, which saw its rival application spurned by an agency that refused to even accept it for review. Only Sarepta, which was subjected to a blistering internal review at the FDA, is still awaiting a final decision in the U.S. on the Duchenne drug eteplirsen following two delays, though a panel voted to reject. And PTC is waiting to see if European regulators will keep its drug on the market after failing its pivotal study.
Bienaimé indicated to me back in April that the final fate of drisapersen rested entirely on the
Europeans’ attitude. An approval in Europe could have pointed the way forward, but a rejection raised questions of just how practical it was to carry on.
The biotech has experienced several setbacks recently, including a secondary endpoint miss for pegvaliase in March that raised a cloud of doubt about its prospects.