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Posted in Catablogic Blathering on December 1, 2011
I recently downloaded Frank Turner’s (relatively) new album, England Keep My Bones and was delighted to find what is now my favorite hymn!
~ Doc B.
I will never fathom how marketing comes up with brand names for Rx drugs. Anyway, the FDA officially approved telaprevir (see post below) on Monday, May 23.
From Zennie62’s blog on SFGates (San Francisco Chronicle), here’s an interview with Steve Goodwin, a chief engineer who was diagnosed with hepatitis C, who was treated with telaprevir/Incivek. In the video, Goodwin tells “how he came to find out about Incivek via the use of the website Clinical Trials, at clinicaltrials.gov, and how it’s helped him to a more normal path of life.”
“My baby” is about to graduate! FDA panel recommends Vertex Pharma’s telaprevir for approval to treat hepatitis C
This week, panels of non-FDA experts reviewed the clinical data for Merck’s* boceprevir and Vertex’s telaprevir for potential market approval as first-in-class** treatments for patients infected with hepatitis C.
Are telaprevir and boceprevir perfect drugs? No. Each has side effects. I’ll note, however, that the “nasty rash,” the most common adverse effect (AE) of telaprevir, was generally mild to moderate and treatable with antihistamines or corticosteroid creams. Only 2% of subjects discontinued treatment because of the rash. So it’s an AE that is tolerable.
The drugs will also be quite expensive: $35-40K per course of treatment. Yikes almighty! Yet these are complex molecules that are not facile to synthesize. Also, consider that a liver transplant costs in the order of $250K to $310K (and higher).
That’s the structure of “my baby” above. Of course, it’s not strictly mine. Not by a long shot, but with all the work I did on that molecule, I feel like one of its many parents. We had a hell of a team at Vertex, and there’s a critical piece of the molecule that was added by Mark T., a wicked smart medicinal chemist, who was then at Lilly (former collaborators; Lilly and Vertex had, uh, differences in approach and thus had a fairly amicable divorce). My contribution was to study the detailed inhibition kinetics of VX-950, using isolated HCV protease for in vitro assays. I demonstrated that VX-950 was a slow binding inhibitor with a slow off-rate. It’s sticky in other words, and hangs onto the the protease for a good while before being hydrolyzed off the enzyme by water in the cell.
The close teamwork of biochemists/enzymologists and virologists at Vertex proved to be a very powerful combination. The virology team was able to demonstrate the efficacy of the protease inhibition in their viral RNA replication assay, and that the slow off-rate appears to play a role. These experiments were performed in 2003/2004, and became pivotal elements of the package, which included major contributions from medicinal chemistry, protein chemistry, process chemistry, toxicology, and pharmacokinetics, which brought VX-950 (telaprevir) forward as a clinical candidate. And now…well, I wonder what its brand name will be?
The odds of a compound at the bench becoming a drug are incredibly small, e.g., for every 10,000 compounds that enter the drug discovery pipeline, only 250 will progress to pre-clinical development (2.5-5%); 5 move forward into human testing, Phase I studies (0.1-0.5%); and only a single compound will survive through Phase II and Phase III studies to be an approved drug (0.01%).
So this is a rare thing, and telaprevir is not just any drug. It will meet a significant unmet medical need. Anyway, forgive me for so much gratuitous backslapping, but I’m proud to have been part of the team — a great group of scientists, many of whom (including myself) no longer work at Vertex — who discovered the compound and brought it to clinical candidate status.
*Boceprevir is actually from the former Schering-Plough, which Merck acquired.
** Strictly speaking, boceprevir is the first approved HCV protease inhibitor and thus truly “first-in-class,” but I use the phrase collectively here, as the approvals were almost back-to-back.
Posted in Catablogic Blathering on April 24, 2011
She celebrates it with grilled leg of lamb, the company of loved ones, a respectful nod to her friends and family counted amongst the Rational Faithful, and with these scary, scary Peep cupcakes. Yes. Yes, I made these carcinogenic little morsels.
Posted in Hootworthy on March 17, 2011
Have some Irish ale with a biochemical/physiological twist:
Tip o’ the leprechaun hat to Tarion Anarore!
Posted in Hootworthy on January 25, 2011
About a gazillion of my fellow scientist-pop culture aficionados have picked up on this fabulofuckingbrilliant parody of Lady Gaga’s “Bad Romance” by now, but what the hey. I’m posting it for posterity. Many who were/are
professors’ slaves graduate students in chemistry, biology, etc. laboratories can relate… ’cause it’s painfully true. The details of the costumes are great — the orange biohazard bags especially.
Blot, blot, Western baby!
Posted in We're Doomed on November 28, 2010
Something of a send-up of a homely fireside chat complete with the warmth of the hearth, the obligatory cat, and the old Oxford don all comfy with his Mac on his lap in lieu of a stack of parchment. It would have been far more effective had the derisive laughter and puerile giggling in the background been edited out. That’s just embarrassing.
Posted in We're Doomed on November 27, 2010
This video has been around for a while, but with a nod to Thanksgiving, this surely makes me thankful that all I have to do is negotiate traffic on the Boston-Providence Highway to stalk the wily strip steak at Whole Paycheck.
About 8 and a half minutes long.
Posted in We're Doomed on November 24, 2010
There are many little quizzes and bits out there in the ether that are about as accurate as a Magic Eight Ball or astrology, but nonetheless fun. Here’s the result of one I indulged in this morning. Surely with tastes that favor Islamic art, I will be put on someone’s list of Enemies o’ the State.
Edited to add: Jim, as he so cavalierly manipulated the quiz to obtain different results, pointed out that such quizzes rarely yield negative results, e.g., from Jim
But the real question is, how come these descriptors are always positive? I’ll bet that I if used a random number generator to create the responses, it would never come back with: Irritating, Back-biting, Dullard.
So, have any Chimp Refuge readers (all 10 of you) stumbled across a quiz that will parse one’s assholishness?
Your result for What Your Taste in Art Says About You Test…
Traditional, Vibrant, and Tasteful
21 Islamic, 19 Impressionist, 8 Ukiyo-e, -27 Cubist, -29 Abstract and 9 Renaissance!
Islamic art is developed from many sources: Roman, Early Christian, and Byzantine styles were taken over in early Islamic architecture; the architecture and decorative art of pre-Islamic Persia was of paramount significance; Central Asian styles were brought in with various nomadic incursions; and Chinese influences . Islamic art uses many geometical floral or vegetable designs in a repetitive pattern known as arabesque. It is used to symbolize the transcendent, indivisible and infinite nature of Allah.
People that like Islamic art tend to be more traditional people that appreciate keeping patterns that they learned and experienced from their past. It is not to say that they are not innovative personalities, they just do not like to let go of their roots. They like to put new ideas into details and make certain that they will work before sharing them with others. Failure is not something they like to think about because they are more interested in being successful and appreciated for their intelligence. These people can also be or like elaborate things in their life as long as they are tasteful. They tend to prefer geometric patterns and vibrant colors.
Posted in We're Doomed on November 15, 2010
From New Orleans-based funk and jazz band Galactic with Boots Riley, Chali 2na, and Laidlaw.
Yeah, yeah, I know. This is a drive-by post, but the new gig and unpacking have me pretty well knackered.
Posted in Better Living through Chemistry on July 3, 2010
Or rather it will be soon (again).
Hello there. Doc Bushwell, effectively erstwhile bonobo-matriarch here with a bit of good news. Last Wednesday evening, I signed the written offer for a new job: that of regulatory medical writer at a major biotechnology company in Cambridge, MA with a tentative starting date of July 26. On Thursday, I quietly scuttled off at lunchtime to go pee in a cup for the pre-employment drug screen. On Friday, I gave 2 weeks notice to my current employer.
When I moved to New Jersey in 2004, I told myself that my long-term plans included moving back to the Boston area. So this is happening just a bit sooner. The family is gung-ho about returning even if the move will be a freakin’ nightmare. Well, most moves are like that.
I’ll miss certain things about Jersey: martinis at Mediterra in Princeton with my friends, ripe tomatoes, sweet corn and peaches (oh, those Jersey peaches!), the ability to visit NYC easily, and walks through the woods that border my home. My current employer, a small CRO that focuses on oncology clinical trials, provided excellent training for me, and I have considered these past two years with the company to be much like a post-doc. Nonetheless, whenever I left Boston after visits over these past six years, I always felt melancholy as if I were leaving my hometown to return to a place where I really did not quite belong. But now? Well, it feels like I am going home again: I’m shipping up to Boston!
While in the throes of working on my first investigational new drug (IND) application with its sketchy preclinical studies (and under a tight deadline), I happily distracted myself this evening with Jesse Bering’s Why do human testicles hang like that?
An e-mail this morning from one of my former Univ. of Wisconsin-Madison classmates informed me that JoAnne Stubbe, Novartis Professor of Chemistry, Professor of Biology at the Massachusetts Institute of Technology, and who was the first woman to achieve tenure in the biochemistry department at the UW-Madison, received the National Medal of Science from Barack Obama yesterday.
JoAnne is a fiercely brilliant woman who intimidated the bejeebus out of me when I was a fledgling grad student and later as a callow post-doc. She was one of five professors (including my advisor) who raked us over the coals during student research seminars. I also faced her wrath when I overtightened the valve to her lab’s French press. But later, when out and about in the real world, my encounters with Professor Stubbe were nothing but good. She’s funny, intense, and passionate about science. She’s a superb intellectual role model, and even though she was not my advisor, she nonetheless influenced me along with many of us in the biochem. department at the UW-Madison. Her award is a such fantastic and well-deserved achievement!
She was at the vanguard of women entering academia and industry in disciplines like chemistry and physics which were long dominated (and still dominated) by men, but these awards as well as the Nobels with 3 women winners in the sciences this year, including Elizabeth Blackburn and Carol Greider for telomeres/telomerase, indicate that “an old girls” network is forming at last.
Here’s a link to the article in the Boston Globe about JoAnne.
Her picture receiving the medal is here in the White House blog (scroll down) and below the cut is the press release (see bolded type a ways down for JoAnne’s award).
Posted in We're Doomed on September 13, 2009
For me, Creation, a much anticipated movie about Charles and Emma Darwin (based on Annie’s Box: Charles Darwin, his Daughter, and Human Evolution by Randal Keynes, Darwin’s great-great grandson) is — or rather was — a must-see flick. It premiered this weekend at the Toronto International Film Festival.
Paul Bettany is cast as Darwin. Bettany is a versatile actor whose performances have always impressed me, e.g., his roles as Dr. Stephen Maturin in Master and Commander: The Far Side of the World and John Nash’s imaginary friend in A Beautiful Mind (John Nash cinematic fan fiction at its most “interpretative”) among many. Jennifer Connelly (Bettany’s wife) — a lovely actress (Pollock, House of Sand and Fog, and A Beautiful Mind) is cast as Emma.
Darwin the man (as well as Darwin the naturalist) has long intrigued me. A few years ago, the American Museum of Natural History in NYC (where my great-great uncle — a paleontologist — had been a curator for a time) had a special exhibit of Darwin’s collections and notes, including a replica of his study. I took my kids to see it on February 12 — Darwin’s birthday a.k.a. “Darwin Day.” To see the notes that he had written with his own hand was marvelous and truly sent shivers down my spine.
And my favorite passage from The Origin of Species:
Thus, from the war of nature, from famine and death, the most exalted object which we are capable of conceiving, namely. the production of the higher animals, directly follows. There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one; and that, whilst this planet has gone cycling on according to the fixed law of gravity, from so simple a beginning endless forms most beautiful and most wonderful have been, and are being, evolved.”
That is poetry.
Olivia Judson wrote a wonderful essay on Creation in her blogThe Wild Side, hosted by the New York Times. Judson’s eloquent essay further reinforced my desire to see the flick.
So yesterday afternoon, when my spawn and I were on our way to see Ponyo (a feast for the eyes: gorgeous color and images, all dream-like with those delightful characters and weird touches I have come to expect from Hiyao Miyazaki), we talked about the upcoming Creation film with no little excitement. However, my 18 year old daughter wondered aloud if the film would be released in all markets in the United States.
Prophetic pondering that. Today, Co-Chimp Kevin sent the link to this article from the Daily Telegraph:
Excerpts from the article by Anita Singh:
However, US distributors have resolutely passed on a film which will prove hugely divisive in a country where, according to a Gallup poll conducted in February, only 39 per cent of Americans believe in the theory of evolution.
Jeremy Thomas, the Oscar-winning producer of Creation, said he was astonished that such attitudes exist 150 years after On The Origin of Species was published.
“That’s what we’re up against. In 2009. It’s amazing,” he said.
“The film has no distributor in America. It has got a deal everywhere else in the world but in the US, and it’s because of what the film is about. People have been saying this is the best film they’ve seen all year, yet nobody in the US has picked it up.
“It is unbelievable to us that this is still a really hot potato in America. There’s still a great belief that He made the world in six days. It’s quite difficult for we in the UK to imagine religion in America. We live in a country which is no longer so religious. But in the US, outside of New York and LA, religion rules.
“Charles Darwin is, I suppose, the hero of the film. But we tried to make the film in a very even-handed way. Darwin wasn’t saying ‘kill all religion’, he never said such a thing, but he is a totem for people.”
When I was growing up, I was a member of the United Methodist Church. My favorite minister was “Reverend Mac,” a gifted speaker and a scholarly man (almost rabbinical!) who was also the substitute science teacher at my public high school. He embraced the theory of evolution and the entire concept of a universe that is billions of years old. As one of the Faithful, he did not see such concepts as incompatible with an Abrahamic God. In his mind, these added to the mystery and glory of God rather than negating the idea. He even brought beautiful scientific imagery into his sermons — for example that laws of physics that govern an atom’s motion and that of a galaxy.
So that is what I grew up with as well as a household where evolution was considered fact. That is what I thought was theologically “normal.” Many of my Roman Catholic pals were taught much the same way. In essence, we (as kids) were already experiencing what the late Stephen Jay Gould called “separate magisteria,” that is Faith and Science in parallel — not overlapping but co-existing.
Now, as an atheist, I respect the beliefs of the Rational Faithful — like Rev. Mac and many others I know for whom science poses no difficulty in their faith in God and who honor the concept of non-overlapping magisteria — even if I have no need for belief in the supernatural. Again, I (naively) tend to think that is what most believers are like.
Apparently that is not the case in the United States.
The lack of balls on the part of US distributors is appalling. I had anticipated the possibility of limited distribution, that is, the film would not make it to markets in certain areas of the country, but I fully expected it would show in venues like the Angelika in NYC or the Garden Theater here in Princeton or the Kendall in Cambridge among many of the independent US theaters in the Northeast, the West Coast and certain areas of the Midwest. Maybe in Houston, too. But not distributed AT ALL!? Does the Christian Right have that much power in this country such that US film distributors cave into their lunacy? That smacks of an especially horrific censorship.
Yet Mel Gibson’s bloody Passion of the Christ was A-OK.
Here’s a trailer for Creation. Enjoy it. It may be the only bits we idiot Americans will get to see.
 My great-great uncle was told to resign from the faculty of Butler University because he embraced Darwin’s theory. He went on to work at the AMNH in NYC and the Carnegie Institute in Washington DC. He published a number of monographs on the vertebrate paleofaunas of North America, and a big tome (800+ pages) on fossil vertebrates of North America and the Pleistocene of North America.
A few of those Chimp Refuge readers who inexplicably followed the troop to this new already beshatted domain are not doubt familiar with J.R.R. Tolkien’s The Hobbit, or There and Back Again, soon to be released as cinematic fan fiction under the guidance of Guillermo del Toro (Pan’s Labyrinth, Hellboy 1 and 2 — although I think Quentin Tarantino would have been the better choice for director) as The Hobbit Movie. Anyway, I live in Mirkwood or something that approximates it. Let’s compare:
Posted in We're Doomed on May 28, 2009
It does a menopausal old broad’s estrogen-deprived heart good to be inked on a skanky athlete’s six-pack:
Generated by Loonapix.
Posted in Catablogic Blathering on May 28, 2009
This popped up on New Scientist’s online news this morning: Christians battle each other over evolution by Amanda Gefter.
So the Discovery Institute insists that to be a Christian means that theory of evolution must be rejected as espoused in their new Faith and Evolution web site. The web site, Geftner speculates, may be a response to Francis Collin’s launch of the BioLogos Foundation. Collins and crew — with funding from the Templeton Foundation — are proponents of theistic evolution which purports that the supreme being of Christianity chose to create life via evolution.
That actually sounds much like the belief of the minister of my childhood church (United Methodist). Rev. M. loved science, was fascinated by modern cosmology, embraced the theory of evolution, and in fact was a substitute science teacher at my high school. I daresay he’d look askance at being told he could not be a Christian for his scientific inclinations.
Strictly speaking, he was a creationist (divine hand behind the Big Bang, etc.). I recall a sermon in which he compared the imagery of an atom to a galaxy (a loose connection to physical laws) as a tribute to the Christian supreme being. To his credit, he never conflated God with science in the public high school classroom. So even if the magisteria of faith and science might have become entangled when he stood at the pulpit, they certainly did not when he spoke in the secular public arena.
So this is what concerns me about Francis Collins. He’s speaking from the pulpit on BioLogos — analogous to Rev. M’s paean to God via atoms to galaxies. However, Collins is rumored to be a potential pick for head of the NIH. Will he be able to keep the magisteria non-overlapping in a secular venue?
To echo Gefter, allowing the magisteria of faith and science to become entangled serves neither well. The DI’ers and BioLogos just conflate them in different ways.
From a random pro-life blog discussing the recent goings-on in Brazil:
There are many details that people do not seem to know or care about.
These wackos really do have a fondness for a conspiratorial blogging style. They’re always prepared to offer information that they’re just certain others haven’t heard about.
The Church recognizes, through the theory of Double Effect, that when the pregnant woman’s life is in danger, the pregnancy can be terminated PROVIDING there is no alternative, and that no direct killing or any other evil is performed on the fetus.
There is no reason why those unborn children could not have been delivered intact, without feticide.
Hmmm…medical opinions on one side, voracious pro-Jesus ravings on the other…I think I’ll go with the idea that the girl could not have carried her twins to term.
In other words, it is acceptable to let nature its course– that is, allow the fetuses to die once delivered– but it is never okay to provoke death.
This sort of moral confusion would seemingly make someone’s head explode, but the blogger was really just warming up:
The abortion proponents wanted the unborn twins dead.
Let me re-state it: they didn’t just want the girl to be free of a pregnancy that might have killed her. They wanted those fetuses dead.
That’s right, because abortion proponents are not merely people who personally enjoy their abortions, but have a frankly murderous bent.
The Church wants as many as possible to live. It’s not always possible– pregnancies are sometimes lethal to the mother, and to save the mother, a termination is necessary. But the pregnancy termination does not have to result in a dead baby.
Abortion always does.
Someone will have to explain how an elective abortion differs materially from a prengancy termination, since that’s, you know, the definition.
I actually do grasp what this idiot is saying–that if you attempt to force a delivery (again, a virtual impossibility in the Brazilian girl) and let the newborns die peacefully on their own, this is morally acceptable, but a formal, outright abortion is not. Again, the mental gymnastics these people engage in can be boggling..
But that’s not what this is about. This is a PR campaign to ge Brazil to legalize abortion. The abortion lobby is intensely pressuring Latin American countries to legalize killing its unborn citizens.
There’s no such thing as an unborn citizen, but at this point who’s keeping track?
This is nice too:
As the publisher of a 13 year old periodical which targets Black gays and lesbians, I have had the opportunity to publicly address thousands, influencing closeted people to ‘come out’ and stand up for them selves, which is particularly difficult in the African-American community.
I’m concerned because people who abandon homosexual behaviour only to go back to it give the faithful bad PR. The liberal press often does not scrutinize their story. We don’t know how much these “ex-ex-gays” prayed; we don’t know their theology; we don’t know anything of their personal life. And so there’s no way to “cross-examine” them on their decision to leave the faith. For all we know, they have been extremely orthodox and observant, but inside their hearts, they still harboured many unseen sins and nurtured evil inclinations that may have had nothing to do with homosexual behaviour, but sparked a rejection of Christ that eventually led to the return to homosexual behaviour. Or they may have had unresolved psychological issues that they led them to reject the faith.
The last sentence is a real winner. Yes, people do reject faith on the grounds of a psychological condition. It’s called “sanity.”
Finally, in a different post:
“[T]he tone of public discourse on the internet is very abrasive and anti-intellectual.”
But….but you just…aw, never mind!
Posted in We're Doomed on March 9, 2009
Clusterfuck Nation is always good for a grim chuckle. From “Forget about ‘Recovery‘”:
Last week, New York State Attorney General Andrew Cuomo hauled Bank of America chief Ken Lewis into his office to explain who, exactly, received an aggregate several billion dollars in bonuses late in 2008 after the US Treasury forked over billions of dollars in TARP money to his bank. That was a good start. Mr. Lewis, being lawyered-up to the max, had the temerity to reply that answering the question would compromise his ability to keep talented people in his employ. For that impertinence alone, Mr. Lewis ought to be dragged over fifteen miles of broken chardonnay bottles behind a GMC Yukon — but that is not how we do things in American jurisprudence. To be more realistic, a simple indictment would be in order, and then Mr. Lewis can answer this question, and a few others, in the comfort of an air-conditioned courtroom. Ultimately, that might lead to Mr. Lewis becoming the wife of a bodybuilder in one of New York State’s houses of correction — a just outcome that would go far in rejiggering the nation’s expectations about how people in authority ought to behave. And such an outcome might lead to the conviction of many other brides-to-be from the Wall Street debutante pool.
Posted in Sheer Procrastination on March 9, 2009
From “plum greenville” on Pharyngula:
[R]idicule and anger have a time-honoured role in social change. You’re confusing what is effective (sometimes) in dealing with people one on one with what is effective in changing the social climate en masse.
In many cases people’s idiotic beliefs are too entrenched to be amenable to reason, evidence, or polite discussion. The only way to prod such a person into reconsidering their views is to convey to them that those views have made them a laughingstock and/or object of contempt.
Attitude change is not fundamentally a rational process.
You want to be a “good ambassador” – a nice guy in other words. That’s a valid and useful role and it obviously suits your personality better than snarkiness. But the snark brigade is not working at cross purposes to you. History strongly suggests that their role is essential in softening people up for your more polite form of persuasion. The good cop needs the bad cop for the routine to work.
Name one social change movement that succeeded through polite persuasion alone. What you’re comfortable with is not the measure of what works.