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Medicine

Open Source Drug Discovery Prompts a Fundamental Heart Failure Breakthrough 160

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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Open Source Drug Discovery Prompts a Fundamental Heart Failure Breakthrough

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  • by Anonymous Coward

    What does it mean for a molecule to have source? How is the "source" of the molecule distinct from whatever passes for a "compiled binary"?

    • 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 [wikipedia.org], 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.

      • by __aaltlg1547 ( 2541114 ) on Sunday August 04, 2013 @10:34AM (#44470111)
        When it comes to science, there is no need to license a discovery to make it available to all. Simply publish and don't attempt to patent it. Scientific knowledge is public once published.
        • by bunratty ( 545641 ) on Sunday August 04, 2013 @11:03AM (#44470237)
          Absolutely. And guess what would happen to any drug company that did not patent their drugs? How would they be able to compete with companies that did not have to pay the hundreds of millions in research to get the drug approved? The only reasonable alternative to patent systems that I can see are (a) trade secrets, which means that the discovery is not made available to all, or (b) go back to a patron system where a generous benefactor foots the bill for research, in which case the research that the scientists do is only what the benefactor wants, which may be the ultimate cure for baldness or a little dick. I think patents are better than the alternatives. That is, unless you can come up with a better idea. Just be sure to think it through...
          • trade secrets, which means that the discovery is not made available to all

            Which is extraordinarily difficult for drugs, because everyone will simply buy a bunch of their competitors' pills, and figure out exactly what they're made of down to atomic detail. A typical university chemistry lab could do this in a few days. There are some aspects that are more tricky - the exact packaging is sometimes key to getting the drug absorbed by the body at the desired rate, and the chemical synthesis can be messy - bu

            • by icebike ( 68054 )

              Can you get away with not telling the FDA what is in a drug?

              Seems counter-intuitive.

              • The traditional way is append the word "herbal" onto anything to avoid having to disclose the contents.
              • by pepty ( 1976012 )
                Nope. API (active pharmaceutical ingredient) and excipients (stuff in the formulation that has some function: stabilizer, solubility, crystallization aid) have to be disclosed.
          • by 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.

            • Perhaps government patents would be a solution. Let the government license its patents freely to education and research but take a percentage of profits for corporate use.
              • by pepty ( 1976012 )
                Government (university) patents and "taking a percentage for corporate use" has been happening for over 30 years. the "freely to education and research" part is a bit more tricky.
            • by pepty ( 1976012 )
              Bullshit. The vast majority of spending necessary to turn this discovery into a drug hasn't even been started yet. Even in cases where the drug is invented and patented in academia (~15-20% of drugs, and we won't know if that has happened here with JQ1 for at least another 5-10 years), universities license the molecule to a biotech or pharma to move it through clinical trials. The NIH is starting to spend more on translational research (the preclinical/clinical stuff Pharmas typically do), but it will be at
          • by gl4ss ( 559668 )

            they would compete in the way they used to compete.. by being the best in making the compound.

          • Drug companies don't have any "their" drugs. Scientists who works for drug companies do. The drug companies are the "generous benefactor" in the current scenario. Ditch the patents, change the FDA oversight to something closer to what you have for food... check production is as it should be, confirm what they are selling is what they claim and not something known to be dangerous. Then take away all legal immunity that is granted by going through the current process. Toss out grants and funding to encourage
          • I think government funded medical research is a completely viable alternative.
          • This generous benefactor could be the government, you know.

      • by pepty ( 1976012 )
        In this case it probably means a similar (but patented) molecule will probably be the first to market. It could also mean that their JQ1 inhibitor, while successful in model trials as a lead or tool compound, has already failed a preclinical test. Either way: 50:1 odds against a new drug candidate succeeding in preclinical trials, 10:1 odds against a new drug compound succeeding in clinical trials. 500:1 odds against success, on average. The big discovery here isn't the inhibitor they waived the rights to;
  • Awe Man! (Score:5, Funny)

    by Anonymous Coward on Sunday August 04, 2013 @09:40AM (#44469921)

    What's this?! Everyone jumping on the Socialist-Commie-Pinko Open movement?!?

    WTF!

    Before you know it, IP with be severely weakened and all of us will have increased standard of living - except for the poor poor billionaires!

    Won't someone think of the billionaires?!

    Without the billionaires lording over us, what will inspire us?

    We need IP to keep up the carriers to entry! We need to impede progress in order to preserve the billionaires! Our way of life will be destroyed!

    • Re:Awe Man! (Score:5, Insightful)

      by bill_mcgonigle ( 4333 ) * on Sunday August 04, 2013 @10:23AM (#44470077) Homepage Journal

      Before you know it, IP with be severely weakened and all of us will have increased standard of living - except for the poor poor billionaires!

      Look, if we don't run our society according to everything that seemed like a good idea in 1781, nothing will ever get invented.

      • Re:Awe Man! (Score:4, Insightful)

        by mspohr ( 589790 ) on Sunday August 04, 2013 @11:29AM (#44470371)

        I'm not sure that it was a good idea even in 1781.
        Basically, the mercantile class wrote the constitution and early laws. The American Revolution was a mercantile uprising against the "tyranny" of England and it's taxes and regulations.
        Today, of course, the mercantile "class" are the corporations who have completely captured the government.
        Numerous studies have demonstrated that patents slow the process of invention and only provide benefits for the entrenched last generation of science and technology.

      • The first patent act was in 1790. The Constitution only permitted Congress to have patents. Congress had to decide to do it.

    • Most science has always been that way.
      • Comment removed based on user account deletion
        • It's a bit trendy to hang the open source label on it, but that's TED for ya ... still there are differences between what was possible in the old days and what is possible now.

          Publishing reproducible research wasn't really possible in the past ... other researchers could beg for all the lab notes, good description of the lab set up etc etc etc to be send by snail mail, but it couldn't really be published. Only the tiny and most of the time insufficient bit of information from the paper was actually publishe

    • We need IP to protect the companies who are doing the research. But it can be difficult to know exactly where to draw the line between what can and cannot be patented. That's the real problem with our patent system -- too many obvious ideas being patented. As Jefferson himself said, "Considering the exclusive right to invention as given not of natural right, but for the benefit of society, I know well the difficulty of drawing a line between the things which are worth to the public the embarrassment of an e
    • The companies that those billionaires own are what drive the economy and do things like grow and distribute our food. I don't know about you, but I would prefer to protect those companies so I can keep eating. And of course I like my gadgets, books, music, and so forth. Sure, I can read an open-source book or listen to open-source music, but typically I prefer the commercial products. Just because an idea works with software doesn't mean it will work with everything. In other words, if you give a man a hamm
      • Re:Awe Man! (Score:5, Insightful)

        by ultranova ( 717540 ) on Sunday August 04, 2013 @12:17PM (#44470635)

        The companies that those billionaires own are what drive the economy and do things like grow and distribute our food.

        No, the people working the fields grow the food and the people driving the trucks and manning the cash register distribute it. And even the organizational work is mostly done by middle managers. All the billionaires do is get a cut of other people's work and occasionally destroy their livelihoods.

        Sure, I can read an open-source book or listen to open-source music, but typically I prefer the commercial products.

        And you think it takes a billionaire to write a book or a song?

        In other words, if you give a man a hammer, all he will see are nails.

        And if you give him a billion dollars, all he will see are the serfs he's entitled to.

    • Except we've run the experiment already where ideas can be stolen and used without paying the author for these virtual property rights. Measured results are far suboptimal compared to the current way.

      The OP is just an anecdote, and anybody with an ounce of scientific sense will realize it.

      It would be nice if these things could be presented as scientific advancements without trumpeting it through the lens of someone's political philosophy.

  • From the article

    Researchers from Case Western Reserve University School of Medicine and the Dana-Farber Cancer Institute have made a fundamental discovery relevant to the understanding and treatment of heart failure

    It does not say "prevent" heart-failure, anywhere in the article. It is implied in the article that treatment could be greatly improved by this therapy, however, I'm not sure where the line in the summary about prevention comes from.

    • Since it's not linked to an actual scientific article, just a press blurb, who knows? It might not do anything.
      • it's not linked to an actual scientific article

        The transcript of the TED talk mentions articles in Cell.

        • So does the summary, but the paper is behind Cell's paywall, so it really isn't all that open-source, is it?
  • It sounds promising, but there is a lot of work ahead before it hits the market, if ever. Dosing, administration mode, side effects, when it can be used, what other drugs it will interact with and which it won't are all a part of what needs to be determined. The "drug" may have been discovered, but is really just a tiny part of what needs to be known before you can safely prescribe the use in people under all the varying conditions of use where it might be needed.

    Thus, just because the molecule is "open s

    • by sjames ( 1099 )

      Even there, the open source nature is helpful. The same drug has stirred interest for multiple myeloma, heart failure, contraception [cell.com], and HIV treatment [oxfordjournals.org] (it is thought that it can activate latent HIV in the presence of anti-viral therapy to wipe out the reservoir). All 4 could share the phase I safety trial (and it's costs).

      • by ColdWetDog ( 752185 ) on Sunday August 04, 2013 @11:22AM (#44470317) Homepage

        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.

        • by sjames ( 1099 )

          A back handed benefit is if the rest of the world considers those conditions a thing of the past while Americans are still dying of them. That would certainly bring demands for change that couldn't be fended off for long.

          I do find it interesting that the free trade cheerleaders in DC stop cheering when retired people want to freely buy inexpensive prescription drugs from Canada.

        • by b4upoo ( 166390 )

          It seems to take a lot more than having a great new product to get it into public use to any great degree. For example the US Navy released Nitinol about 30 years back so that anyone can use it without patents. Despite being an amazing and wonderful product it sees very little use in the market place. We have some expensive eyeglass frames made of it and also some bras use memory metal to restore their shape every time they hit how water. But really we don't see it used much at all. How about car fe

  • The only thing drug patents do is make drug companies rich. If we as a nation (USAians here) truly wanted to maximize progress in medical treatment, we'd nationalize all drug research. 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.
    As we've seen over and over again in nearly every technology area, the greatest progress occurs either in "open source" areas or when patents expire and everyone can innovate.
    (Yes, I'm a socialist. No, I don't think that in any way invalidates the fundamental claims I'm making here.)

    • the drug in the article has been proven to do exactly nothing.

      no trials yet.

      put it back in your pants.

      • You didn't read a word of what I wrote, did you.

        No comfy chair or chocolate for you.

        Molpy down.

        • I did read it. please provide a single instance where "open source" has created a medicine to cure disease

    • by the gnat ( 153162 ) on Sunday August 04, 2013 @11:08AM (#44470259)

      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.

      • 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 #1: go back and read about the (then legal) reverse-engineering of the IBM BIOS, without which most of our current software and hardware wouldn't exist.

        Re #2: Neither you nor I represent the median ego of "scientist" -- class humanoids. Sure, getting there first is more fun, but that sort of competition is rather different from locking down your knowledge so nobody can review your results, reproduce your results, or improve upon them.

      • by Rich0 ( 548339 )

        Yup - this is just discovery work. This kind of research often happens in university and other open settings.

        The problem is that 95% of the cost comes in during the boring and expensive process of testing the drug.

        That's a good FOSS analogy as well. Notice how few FOSS projects REALLY test their products? Now consider that testing a piece of software just consists of people or scripts spending a few hours rigorously exercising the software on commodity hardware. In the drug research world you have to ge

        • Right now the NIH does the early research, but doesn't spend the boatload of money needed to actually test the stuff they come up with. They usually abandon research when it gets to the point where this article is at.

          Not really - what actually happens is typically that the universities patent the discovery and license it to a company which performs the development work. Which does have an element of "socialize the risk, privatize the profits", except that the expense of the product development is typically

          • by Rich0 ( 548339 )

            Right now the NIH does the early research, but doesn't spend the boatload of money needed to actually test the stuff they come up with. They usually abandon research when it gets to the point where this article is at.

            Not really - what actually happens is typically that the universities patent the discovery and license it to a company which performs the development work.

            Really two ways of saying the same thing. I realize that university labs often patent the stuff they come up with (something I don't have a problem with - the part I don't like is that the license fees that result don't predominantly go to the US Government). The bottom line is that they don't spend the huge sums of money that happen after an initial lead is developed.

      • by jfengel ( 409917 )

        Thanks a lot for this. Slashdot is full of very smart people who say, "I'm very smart, and I don't understand why it takes you so much time, effort, and money to do the thing that you do. Here, let me teach you your job." It's nice to have the occasional interjection from somebody who actually understands what's going on to explain at least a few of the complications glossed over in the process.

  • For a long time, commercial activities have claimed that only through commercial enterprise could quality and value be achieved. This has been claimed of software for a long time as well as with other industries. Among these is the drug/pharmaceutical industry because only they can afford the R&D needed to make important things happen. (Conveniently we forget that many of the most important drugs predate the big pharma industry.)

    With 3D printing edging into device manufacturing space, just about ever

    • With 3D printing edging into device manufacturing space, just about everything is going to face free/public competition, not the least of which will be energy production. Big business with its dependency on having the public dependent on them has its days numbered. I look forward to those days... I wonder if I will live that long?

      No you won't.

      Because 3D printing isn't going to replace anything much beyond the utensil selection in Walmart for the foreseeable future. Hell, you'll be lucky if you can shoot yourself in head with a 3D printed object in your lifetime. You'd be most likely to blow up your hand and have to go the the hospital and get treated with stuff that's been woven, extruded, grown, spun or glued.

    • Among these is the drug/pharmaceutical industry because only they can afford the R&D needed to make important things happen.

      It's less the "R" than the "D". The government spends large amounts on basic research, including some expenses which drug companies, at least individually, can't afford. For instance, the US Department of Energy builds massive X-ray generators called synchrotrons, which are used by biologists to determine the structures of proteins, and drug companies make heavy use of these to i

    • by King_TJ ( 85913 )

      Well, first of all? Who are these commercial activities you speak of who supposedly claimed quality and value were ONLY achievable via commercial enterprise?

      I can't think of a single business making that claim today? Clearly, technological progress means that ideas starting out as massive, costly endeavors become mundane with time. I remember when recordable CDR technology was brand new, for example. The only people possessing CD writer drives were generally government contractors and educational institut

    • by Rich0 ( 548339 )

      Among these is the drug/pharmaceutical industry because only they can afford the R&D needed to make important things happen.

      They're not the only ones who can afford it, but right now they're about the only ones willing to spend it.

      The research in this article did NOT develop a new drug. It only discovered a compound that has biological activity. That is the very first step in drug research, and usually it takes about 5 years and $100M to prove conclusively that it won't work in the real world. Maybe 5% of the time it will take 5 years and $100M to prove that it actually does work.

      I'm all for expanding the publish research mod

  • Collaboration and sharing results is standard in science and has been for the last few hundred years. Practically speaking, patents on their own are meaningless for new scientific advancements and do nothing to prevent or encourage scientific advancement. They're a non-issue. What does matter is how much it costs to read the published results.

    The equivalent to open source in science is open access. CELL is not open access. As a result, I (as a scientist without access to CELL) don't have access to their

  • What's claimed is pretty impressive. They say they've gotten 60% improvement in heart function from a month long treatment course in mice and even quicker protective effect against declines in function. The caveat, as always, is that many things work well in mice, but don't translate into human therapies.

    This is still paywalled, but it has many of the figures from the article as well as the abstract.

    http://www.sciencedirect.com/science/article/pii/S0092867413008842 [sciencedirect.com]

    This is of direct interest to me as I have

  • Let's see. This is a molecule in pre-clinical testing. I would give this specific molecule about a 1 in 1,000 chance of actually being marketed. Those are damn good odds for a molecule at this stage. This is why you always have to take the word "potential" with a boulder of salt.

I don't have any use for bodyguards, but I do have a specific use for two highly trained certified public accountants. -- Elvis Presley

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