Open Source Drug Discovery Prompts a Fundamental Heart Failure Breakthrough

An anonymous reader writes "Case-Western researchers, led by Saptarsi Haldar MD., have made a fundamental discovery that could prevent heart failure after reviewing the "chemical recipe" for a cancer-treating molecule made open source by Jay Bradner MD. (whose TED Talk articulates the open source approach to drug discovery) This cross-discipline discovery, which was published in the August 2013 issue of CELL, is a fundamental breakthrough in heart failure research, and highlights the value of an open source approach outside of software development."

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TED talk explains how the OSS philosophy applies

[tepples]

Anonymous Coward wrote:

What does it mean for a molecule to have source?

It can refer to what Eric S. Raymond referred to as the "bazaar" model, or it can refer to a license that grants rights to the public analogous to those listed in the DFSG or FSF definition of free software. I see hints of bazaar in the transcript of the TED talk:

dissatisfied with the performance and quality of these medicines, I went back to school in chemistry with the idea that perhaps by learning the trade of discovery chemistry and approaching it in the context of this brave new world of the open-source, the crowd-source, the collaborative network that we have access to within academia, that we might more quickly bring powerful and targeted therapies to our patients.

And here I see the spirit of publishing a discovery instead of locking it up behind secrecy and exclusive rights:

We published a paper that described this finding at the earliest prototype stage. We gave the world the chemical identity of this molecule, typically a secret in our discipline. We told people exactly how to make it.

This leads up to the benefits of bazaar and publication:

the science that's coming back from all of these laboratories about the use of this molecule has provided us insights that we might not have had on our own. Leukemia cells treated with this compound turn into normal white blood cells.

And finally, a direct answer to your question as to what is the source code of a molecule:

This string of letters and numbers and symbols and parentheses that can be texted, I suppose, or [microblogged] worldwide, is the chemical identity of our pro compound.

Re:More pointless 'research'

[bill_mcgonigle]

Most heart disease is caused by eating animal products (which humans aren't supposed to eat), lack of exercise, and smoking.

That was considered very wise in 1982. Today we know that the main nutritional problem is excess fructose, which the liver turns straight into triglycerides, which stick to the arterial walls, and form nasty, sticky plaques. But go ahead and guzzle agave nectar - it's pure fructose, vegan, and trendy. :P

Exercise, sleep, low stress, and of course not smoking are also key components to a healthy lifestyle (diet is just one part).

Re:Well Duh: Open Source is better

[the gnat]

Don't even bother arguing that profit motivates progress. The overwhelming majority of researchers and engineers are motivated by the joy of success, not crushing the opposition and getting filthy rich.

The problem with drug development is that the huge majority of efforts end in failure, and depending on how far along the pipeline the drugs are, these failures can be painfully expensive. Truth is, it's not really all that difficult or costly to come up with a nanomolar inhibitor for some key regulatory protein involved in heart disease or cancer. But that doesn't mean you've cured the disease. You might synthesize a molecule that completely shuts down your target protein, and start doing in-vivo studies. Here's where the bad shit starts: maybe your compound can't get past the cell membrane. Or maybe it gets shunted to the liver and immediately degraded - unless it fucks up the liver, of course (which one of the major reasons for negative drug interactions, and why many medications have labels saying "do not consume alcohol"). Or let's say it gets to exactly where it needs to be, but it also binds with high affinity to seven other proteins, three of which we know nothing about, and all of these are essential for other processes. So you come in the next morning, and half of your test mice are belly-up, another quarter are bleeding rectally, and the remainder will promptly croak if you feed them Tylenol.

If you're really unlucky, your drug passes the animal models easily, and makes it into clinical trials with actual sick humans. If you're really, really unlucky, you make it all the way to Phase III trials, with thousands of patients, and only then do you discover that either a) your drug doesn't really work as well as it needs to, or b) a large fraction of patients manifest severe side effects over time, or c) both. At this point the cumulative expense of developing this candidate may be hundreds of millions of dollars. And companies fail at this stage all the time; it's always big news when this happens, and their market capitalization takes it in the ass.

Now, I don't feel terribly sympathetic for drug companies as a whole; they do some pretty sleazy shit, and have paid some well-deserved fines for their malfeasance. But I would find it incredibly depressing to sink years of my life (and millions of dollars of investor money) into a promising clinical candidate, only to have it fail just shy of the endpoint. I'm an academic scientist, and this is one of the reasons why I've stayed in academia so long, for all of its faults. I get paid less, but I don't have to devote myself to narrowly-scoped projects which have a depressingly high risk of failure. If I had to start doing drug discovery as part of some newly nationalized research plan, I would leave without hesitation. Sorry, but if you want me to spend my life doing something that mind-numbing and soul-crushing, you'd fucking better pay decently me for it. The overwhelming majority of people who know anything about drug discovery will tell you the same thing.

PS #1: Please, explain how the extraordinary improvement in computer hardware since WWII was encouraged by lack of patents. Another counter-example: genome sequencing technology has become orders of magnitude faster in the last dozen or so years. (No, I'm not arguing that we should patent everything; I'm still against patents on software and gene sequences.)

PS #2: Don't assume that scientists aren't motivated by crushing the opposition. That's part of the joy of success, and while we may not be doing it for the money, our egos are at least as big as everyone else's.

Re:Animal Studies & then years of human trials

[ColdWetDog]

Is it going to help or hurt?

Yes, it's created a lot of interest but that's pretty standard for a molecule that hits a relatively unique molecular pathway. What has happened in the past is that as soon as the basic science gets firmed up, the drug companies wander it and start trailing slightly different molecules (which are patentable). That's where the big money goes.

By explicitly opening up access to the molecule early, you might find more applications faster and perhaps get more people working on the same receptor system, but the end result is that the drug that treats multiple myeloma will look slightly different from the one that treats heart failure or is used as a male contraceptive. The drug makers will work hard to make them as task specific as possible so they can charge more and control things better. The only possible 'good' outcome (for the open source concept here) would be that the 'generic' bromodomain receptor blocker (JQ1) works equally well for all, doesn't do anything bad in humans (an unlikely scenario - most promising drug candidates die here along with countless dogs, monkeys and other critters) and can be reasonably easily synthesized by the Indian and Chinese generic drug manufacturers and they make a shitload of it.

Which will get blocked at the border so save us from commie chemicals.

Grump again.

Re: TED talk explains how the OSS philosophy appli

[Anonymous Coward]

The "patron system" is already in place - the gov't foots the bill for nearly all the research, and private corporations add the last 1% of the bill before patenting and reaping 100% of the profits.