SeekerBlog

At The Atlantic Megan McArdle examines drug development. Demonstrating once again how capable she is, Megan quotes my favorite insider source Derek Lowe:

As NIH director, Elias Zerhouni was a great champion of “translational research” that would get academics into the business of trying to make drugs rather than doing basic research like identifying drug targets. Now that he’s the head of R&D at Sanofi Aventis, he seems to be realizing that discovering drugs is harder than it sounds:

When he arrived at Sanofi, “I thought the solution would be simple,” Zerhouni said at a recent R&D press event attended by the Health Blog. He thought the answer to the company’s R&D woes was to make it more creative and more nimble, like a small biotech.

But he realized that small biotechs are no more successful than large drug makers at coming up with new drugs. “At the end of the day, there’s a gap in translation,” he said. . .

At Sanofi, the goal now is to strive for “open innovation,” which involves looking for new research and ideas both internally and externally — for example, at universities and hospitals. In addition, the company is focusing on first understanding a disease and then figuring out what tools might be effective in treating it, rather than identifying a potential tool first and then looking for a disease area in which it could be helpful.

Derek Lowe adds:

With a lot of these things, if you’re going to first really understand them, you could have a couple of decades’ wait on your hands, and that’s if things go well. More likely, you’ll end up doing what we’ve been doing: taking your best shot with what’s known at the moment and hoping that you got something right. Which leads us to the success rates we have now.

On the other hand, maybe Zerhouni should just call up Marcia Angell or Donald Light, so that they can set him straight on the real costs of drug R&D. Why should we listen to a former head of the NIH who’s now running a major industrial research department, when we can go to the folks who really know what they’re talking about, right? And I’d also like to know what he thinks of Francis Collins’ plan for a new NIH translational research institute, too, but we may not get to hear about that. . .

Read the whole thing »

This is interesting. I wonder how practical it is to do a broader screening program for combos are effective against such as MRSA?

New research, published yesterday (April 25) ahead-of-print in Nature Chemical Biology, provides evidence that combining antibiotics with marketed drug compounds could be one answer, uncovering previously unknown antibacterial functions of drugs that boost the effectiveness of antibiotics.

(…) So Wright and his colleagues decided to broaden the search. They focused on minocycline, an antibiotic that inhibits protein synthesis, frequently used in the 1950s and 1960s until bacteria developed resistance. “It seemed like a good place to start as something that already had some intrinsic anti-microbial activity but had been largely abandoned by the clinical community because of the resistance problem,” said Wright.

They screened minocycline in combination with more than 1,000 previously approved bioactive drug compounds — most of which had no known antibiotic function — against three common and often resistant bacteria: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus.

The screen revealed a total of 69 compounds never before used to treat bacterial infections that, when combined with minocycline, decreased bacterial growth by at least 45 percent — significantly more than when treated with only the antibiotic . “It was very gratifying for us that our hypothesis was right,” said Wright. “We found all these unexpected interactions.”

Cite: L. Ejim et al., “Combinations of antibiotics and nonantibiotic drugs enhance antimicrobial efficacy,” Nature Chemical Biology, doi:10.1038/nchembio.559, 2011.

This is not good news. Organic chemist Derek Lowe discusses a new study that employed the latest DNA sequencing techniques. Personalized therapy is looking more and more distant.

You may have detected, here and there, a certain amount of skepticism on this blog about the direct application of genomic information to complex human diseases. And several times I’ve beaten the drum for the position that there is no such disease as “cancer” – just a lot of conditions that all result in the phenotype of uncontrolled cellular growth.

Well, here’s some pretty dramatic evidence in favor of both of those positions. A new study, one of those things that could only be done with modern sequencing techniques, has given us the hardest data yet on the genomic basis of cancerous cells. This massive effort completely sequenced the tumors from 50 different breast cancer patients, along with nearby healthy cells as controls for each case.

Over 1700 mutations were found – but only three of them showed up in as many as 10% of the patients. The great majority were unique to each patient, and they were all over the place: deletions, frame shifts, translocations, what have you. The lead author of the study told Nature News that the results were “complex and somewhat alarming”, and I second that, only pausing to drop the “somewhat”. I add that qualification because these patients were already more homogeneous than the normal run of breast cancer cases – they were all estrogen-receptor positive, picked for trials of an aromatase inhibitor.

Read the whole thing »

The European Academies Science Advisory Council (EASAC) has sponsored a report on the topic. There is a summary available for download [PDF].

On January 14, 2011, Caltech hosted TEDxCaltech, an exciting one-day event to honor Richard Feynman, Nobel Laureate, Caltech physics professor, iconoclast, visionary, and all-around “curious character.”

Don’t you wish Richard Feynman could be one of the presenters.

One of the talks that has already been uploaded is Venter’s Future Biology. These Caltech talks are not in the TED iTunes subscription list – so you won’t automatically see them unless you visit the Caltech site.

So says Randal J. Kirk. I’ve not heard of Intrexon before. The Forbes writers asked Craig Venter, who said the same thing. There is so much hype in synthetic biology, is this hype or the real deal?

(…) Kirk says everything he has done in the past pales next to the potential of his latest project: Intrexon, a secretive research-stage company that is working on the hot new field of synthetic biology—basically genetic engineering on steroids. Kirk and his investment fund, Third Security, have poured $200 million into the closely held 180-person company based in Blacksburg, Va., which has no drugs on the market.

“I’ve been a biotech investor for 27 years, and Intrexon is by far the best thing I’ve ever seen,” says Kirk, 56, who raises falcons and composes electronic music on a 7,200-acre cattle farm in rural Pulaski County, Va. He likens Intrexon to “the Google of the life sciences” and predicts that in a decade it could become “the largest, most significant company” in its burgeoning field.

(…) Lots of big scientific names are working in synthetic biology, which so far has produced lots of hype and headlines but few practical breakthroughs. Gene jockey J. Craig Venter, known for sequencing the first human genome in 2000, leads a company called Synthetic Genomics that has a $300 million deal with ExxonMobil to make designer biofuels.

Intrexon has released few details about which products it is pursuing. Its lead drug is only at the earliest stage of human trials. It is so obscure that three prominent synthetic biology researchers contacted by FORBES—including Venter—said they had never heard of it. Kirk shrugs. Among other colossal ambitions, he wants to revitalize the troubled field of gene therapy, make dozens of inexpensive protein drugs and produce better genetically engineered crops that will benefit consumers, not just farmers. The company is also working on biofuels, designer enzymes, bioplastics and unspecified consumer products. Keeping the work secret is part of the plan, Kirk says. “If we were in the business of publishing, we could get the cover of Science magazine any issue we wanted,” he boasts.

The scientist behind Kirk’s mystery company is the 45-year-old molecular geneticist Thomas Reed. He founded Intrexon in 1998 while still completing his Ph.D. and postdoctoral work in cardiovascular genetics at the University of Cincinnati. “I think of him as the Henry Ford of DNA,” says Kirk. “We are all living in his dream.”

(…)

Read the whole thing » See also Is Randal J. Kirk Biotech’s Best Investor? And this on the Intrexon/Ziopharm deal.

To sustain innovation, pharmaceutical companies will have to change the way they do research, says Derek Lowe. But does anyone know what changes to make?

That’s the lead for Derek Lowe’s Nature column. See what you think?