Category Archives: Biotech/Pharma

Getting patients back to normal

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All opinions my own and do not necessarily reflect those of Novo Nordisk.

Inspired in part by this column from David Shaywitz

Here is a story I had the privilege to hear from Fred Modell, one of the founders of the Jeffrey Modell Foundation (check them out; they’re a great group):  Fred was at their annual picnic, where they host kids with immune system defects.  Fred walked by two early teenage girls, and as he passed by he heard one of them asking the other, “You really kissed a boy?”  Which seems like a common enough thing for two teenage girls to be talking about.

Only in this case it wasn’t.  If your immune system doesn’t function like most everyone else’s, then kissing a boy is not just part of growing up.  It can be dangerous to your health. It’s something  about which you have to think hard, and try your best to understand the implications, and you need to be careful, cautious and measured.  Everything your first kiss really shouldn’t be.

For these girls, though, because of groups like the Modell Foundation and the treatments they’ve helped pioneer and support, these girls could experience the spontaneity of an event that so many kids take for granted.  And they could feel normal, like their friends in school. Continue reading →

3D printers, DIY Bio, French bistros and one possible future path for drug development

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All opinions are my own and do not necessarily reflect those of Novo Nordisk

The Long Tail is Everywhere There’s Information

Several years ago I happened upon Chris Anderson’s great book The Long Tail.  He wrote about the amazing changes that were taking place in commerce because of the digitization and electronic dissemination of information.  Mix incredibly cheap (essentially free) data storage with the Internet and reasonable bandwidth, throw in the power of search and individual customization algorithms, and suddenly business models no longer had to rely on bulk consumption and the generation of popular hits.

The first industries to feel the change were in entertainment:  music, movies, books, where having a physical copy was once necessary to enjoy Madonna, Star Wars, or Carl Hiaasen’s latest thriller.  Digitization turned that upside down.  It became clear that what we’re really paying for is information, and it’s a lot harder for the entertainment industry (or any industry) to keep control over the dissemination of information than when they sold that information packaged in shiny plastic discs.

Anderson also described how in this digital world, and aided by the powers of personalized search, niche markets could not only survive but thrive.  Once, something like Tuvan Throat Singing was a niche musical form that you might have heard of on a trip to Siberia, but you’d have had no luck finding a CD at your local Tower Records (remember them?).  Now, you can not only find several tracks from iTunes or Amazon, you’ll also get suggestions for what else you might like based on your fondness for overtone singing.  Since it costs Amazon basically nothing to store the music and associated information, they can afford to have it available for the 20 people who might want to buy it.  Tally that up across all the niches in the world and it’s a hefty sum.

This is pretty neat.  But it’s still uncertain how the business of entertainment will shake out financially and logistically among the producers, distributors and promoters.  I’m not real fond of chaos like that in my professional life, and for a long time felt secure that my job–drug development scientist–was not in danger of becoming part of a long tail phenomenon.  Only now I’m not so sure. Continue reading →

Gastric bypass surgery and the ever expanding world of GxE interactions

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All opinions are my own and do not necessarily reflect those of Novo Nordisk.

An early publication article from the Proceedings of the National Academy of Sciences reports the fascinating finding that children born to mothers before and after gastric bypass surgery show differences in the expression of  genes involved in, among other things, glucose metabolism and immune function.  The study is small, with only 50 children evenly split between cohorts born to moms before and after gastric bypass, but if it replicates, it’s another piece of evidence  showing how the environment influences the way our genes function.

Epigenetics has been a hot topic in genetics research for a while now.  It’s clear that DNA methylation changes over time and within an individual and can affect gene expression.  Studies in a number of institutions such as Washington State University in the lab of Michael Skinner have shown that changes can even persist through multiple generations (in rats, at least).  The PNAS report adds another twist in that the gene by environment interaction arose due to a change in maternal health induced by surgery.

There are a lot of implications to this, including the rather theoretical one of whether this knowledge would induce more potential mothers to undergo gastric bypass surgery, and also practical ones of whether weight loss alone without surgery or via, for example, a lap band, would have the same effect.  But the one I wonder about is what this might imply for drug development.

While many genetic variations are known to affect disease risk and progression, and drug metabolism, there has been considerable debate on how to use such data.  In many cases, such as with the majority of Genome Wide Association Study hits, the relative risk of discovered variants have been statistically significant but small.  However, as we have seen with Amgen’s purchase of DeCode, drug development companies are keen to use genetic information to help inform their drug development efforts, to find an edge.

In this PNAS report, however, I see a flag of caution.  I applaud the efforts of Amgen and other companies taking these risks, but this report of possible epigenetic effects following maternal surgery also points out how much we’re still discovering about basic human biology, how much we still don’t know about the diseases we study.  Understanding Gene by Environment interactions is, I think, one of the key factors we deal with in developing drugs, and not one to ignore.  And yet, it feels currently like one of those “unknown knowns,” the things we willfully decide not to think about, even though we know it’s there.

Not losing versus playing to win in Baseball and drug development

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All opinions are my own and do not necessarily reflect those of Novo Nordisk

Another in a series about parallels between baseball and drug development

A recent post by Phil Birnbaum, who runs a baseball research site, did a nice job of highlighting how he feels stastisical analysis may best serve baseball organizations:  by ensuring that they don’t make losing moves.  While everyone is trying to win, in an industry where so much is uncertain, in many cases, it may be most effective to  “First, concentrate on eliminating bad decisions, not on making good decisions better.  And, second, figure out what  everyone else knows, but we don’t.”

This is a terrific observation, and one he backs up through the body of his post with examples from baseball and gambling strategy.  I think it applies quite well to drug development too.  I’ve made the earlier conjecture that drug development can be thought of as existing on the adaptive landscape, with improvements to drugs or drug classes getting harder and harder as you climb up that mountain of efficacy.  But when you’re on a slope, it’s really easy to go sideways or backwards.  So, the analogy here is that drug development, like baseball, needs to throw a lot of resources (not just statistical and analytical ones, either) into preventing a bad decision.

This thinking is also influenced by the ecology of pharma and biotech.  Let me be very clear about my initial assumption:  drug development is filled with really smart people, almost all of whom are dedicated, sharp, innovative, and really interested in winning.  So is baseball, (well, except maybe for the Kansas City Royals).  But it’s hard to put together a good drug development pipeline.  Resources help.  Resources often help.  But they aren’t enough.  And since the talent is there, the explanation for lackluster drug development progress may partly be found in companies still making poor decisions on assets.

Let me zero in on the second part of the quote in the first paragraph:  “And, second, figure out what everyone else knows, but we don’t.”  Here’s something else that companies could possibly do differently:  share data.  A really fascinating blurb in ScienceInsider just highlighted an effort by people at Johns Hopkins to try and get clinical trial information published, as long as it’s been publicly released in other formats such as through litigation or Freedom of Information Act requests.  While all the companies would prefer this not happen, if it happens uniformly, that can only be good for drug development as researchers learn more about why given trials were halted or failed.  If R&D costs as much as it does, part of the reason lies in duplicated effort.

To conclude, let me throw out another thought on decision making:  send in the crowds.  Crowdsourcing as a method for making decisions has been tried in a number of contexts and often has been found to lead to better overall decision making than more traditional methods.  If we want to make decisions on, for example, which drugs should move forward, setting up a system to poll everyone in the organization in a controlled, anonymous way might be enlightening.  I know this would not be a popular development for people in the C-suite, since, after all, that is their domain.  And I believe the assertion Malcolm Gladwell makes in Outliers that initial, small differences in environment can eventually lead to great differences in ability down the road as individuals get training and experiences not widely available.  Therefore those who are in the C-suite are different in their knowledge and outlook and know more about strategic decisions.  But they still don’t know everything, they still are human, they still have biases.  And a technician working in a lab in Boston may have noticed something in his cell cultures that  no one else is aware of.  If we want to make good decisions, shouldn’t we make sure that everyone possible has a voice?

Reining in Hyperbole About the Role of Drug Development

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All opinions expressed are my own and do not necessarily reflect those of Novo Nordisk

“The traditional pharmaceutical research and development operating model is no longer sustainable,” says Dennis Liotta, PhD, founder of the Emory Institute for Drug Development (EIDD) and co-inventor of multiple approved drugs. “The marked decrease in the development of new therapeutics is having a uniformly negative effect on global health and threatens life expectancy, quality of life, economic development and national security. Emory’s new public-private enterprise is a bold new approach that can help solve this problem.”  From a press release from Emory University

Yesterday Emory University announced the creation of a non-profit entity, Drug Innovation Ventures at Emory, LLC (DRIVE), that aims to take discoveries made by Emory scientists and bring them to the point of proof-of-concept clinical trials.  I think this is a great idea.  While this press release is what I would call a bit overstated (while at the same time understating the real problems involved in translating discovery science into actual drugs), drug development is in need of different ideas and different approaches, and I’m all in favor of various organizations trying different things to develop drugs.  I’m also in favor of any system that gives academic researchers exposure to the steps leading to a lead candidate drug.

What concerns me, though, is the quote above.  Again, this is a press release and some hyperbole is to be expected, but at the same time is it fair to say that the reduced number of new drugs being developed is having a “uniformly negative effect on global health?”  Digging into DRIVE’s webpage, it’s clear the organization plans to focus on viral diseases, which makes the connection to global health direct.  However, I can’t help thinking that there’s a lot more involved in helping the health of people in developing countries than new vaccines and antivirals, and that while new drugs could help, the lack of new drugs doesn’t condemn those populations into some kind of downward spiral.  I doubt Dr. Liotta meant this explicitly, but his comment supports a view of a specific kind of technological innovation–drug development–as providing a cure, when I’d rather see expectations managed with a little more circumspection.  I think the industry suffers when presenting cures as being accomplished with a simple pill or a shot.  Many times, maybe most times, health problems are best viewed as the result of multiple, intertwined factors, of which biology is just one.