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Don’t Wait For the Public Sector

If you haven’t seen this speech by Phil Baran, given at his induction into the American Academy of Arts and Sciences, it’s worth a look. His main theme is what organic chemists can learn from the business model of SpaceX, and he starts out by talking about how grant money for synthetic organic chemistry has been drying up over the years.

This, he says, is similar to the situation that Elon Musk noted when he wanted to establish human colonies on Mars: NASA had no particularly realistic plans for doing any such thing. So Musk decided to get into spaceflight himself. By building cheaper, more capable launch vehicles, he could win contracts to launch satellites commercially and to resupply the space station, which was something that NASA was spending money on, and these same launch vehicles would also be the necessary foundation for Mars missions. (As Musk himself has put it in interviews, “I would like to die on Mars, although preferably not on impact”).

So here’s where this applies to organic synthesis – Baran has partnered with drug companies for funding, which allows him to make interesting and useful compounds (and develop new methods to do so) while the private sector puts up the money. He’d like to come up with practical synthetic routes to things as complex as Taxol, but NIH funding for that sort of idea is increasingly difficult to get, so this is how the chemistry gets done.

 

Like going to Mars, such a mission can be hard to fund when a long-term vision is needed, so we turned to the private sector. Teaming up with a large pharmaceutical company, we developed some of the underlying techniques and mission plan we would later need for Taxol by targeting other bioactive terpene natural products that were of interest to them. The graduate students involved in the project were energized to be working on fundamental science with immediate commercialization potential, and the company was thrilled to have a solution to its problem. We are not finished with Taxol; not even close. But by partnering with the private sector, we are light-years closer to our goal than had we relied solely on public funding.

I think that’s an excellent way to look at it, and I’d submit that it’s a rediscovery of something that we seemed to know more about fifty or sixty years ago. Remember Bell Labs, or the Central Research departments at places like DuPont and Bayer? These were an alliance of blue-sky research with commercial potential, and (to my view) are an inside-the-same-organization example of just the sort of alliance that Baran (and Musk) are talking about. This sort of thing has gone brutally out of fashion for companies to do themselves, but the basic idea is still sound: industry can fund basic research, which can in turn throw off ideas and technologies for industry. It’s not like one of them is contaminating the other, or distracting it from what they’re “supposed” to be doing.

And if we’re going to get a lot of basic research done – and there’s plenty needed – then academic researchers are probably going to have to get used to doing some of it this way. Public funding is not going to be there for you when you want it:

Ladies and gentleman, society’s message to scientists is clear: simple curiosity is insufficient justification for our research. Scientists are great at thumping our chests and getting on our soap boxes about the importance of fundamental research. And, we are right. The problem is that nobody is listening. The average taxpayer has no idea what we do and the long-term benefits of basic science. Arguably, the public is more interested in the air pressure of a football than the atmospheric pressure on Mars. Moving forward, in addition to making the most of precious public funding and occasional philanthropy, perhaps we should follow Mr. Musk’s lead and turn to the private sector to help fund our own missions to Mars.

I think it’s long been this way. For example, there’s a myth that the Apollo moon landing program was enthusiastically supported by a majority of the country at the time, but the figures don’t bear that out. And that at least had a clear, concrete goal: I doubt if there’s ever been an enthusiastic majority behind just spending money on basic research to see where things go. I’m sure that polls can generate support for cancer research and the like, but Baran’s right when he says that most people don’t really know what that entails. An average taxpayer might have a vague mental picture of someone in a lab coat staring at a bunch of cancer cells in a dish and trying to find ways to kill them (obligatory XKCD), but the reality of (for example) spending time and money trying to find out what the chaperone proteins for XYZ kinase are under low-oxygen conditions, etc., etc., wouldn’t get nearly as much sympathy or understanding.

 

39 comments on “Don’t Wait For the Public Sector”

  1. Curious Wavefunction says:

    I agree with Baran’s sentiments. But he’s one (very talented) man: how many such Barans is Pfizer or Merck or Novartis willing to fund? For actual progress scale’s going to matter. I actually find that philanthropists like Kavli, Ellison and Allen are doing as much or more than any private company can right now. Perhaps that would be another model to look at.

    1. Frank Claire says:

      Yeah this is like LeBron saying “why don’t more basketball players just drive to the basket and dunk?” or Warren Buffet saying “why don’t more people make large capital investments under favorable terms to build wealth?”

  2. Ch says:

    So, while private pharma is cutting applicable research left and right we should be hoping for it to find an interest in less obviously applicable research? I think this might be a case of sampling bias on Baran’s part. Just because he is able to stir up more support each year from the private sector does not mean that the private sector is interested or able to do that generally.

    Moreover, doesn’t most of SpaceX’s revenue come from DoD and NASA contracts? Sure, SpaceX is a private enterprise, but its success hasn’t come about because it has changed the public’s perception of the utility of space exploration (as presumably Baran is implying is necessary to encourage private funding of basic chemistry). It’s successful because it operates at lower costs than other launchers (United Launch Alliance, Lockheed/Boeing).

    The extension of that to chemical research would be the advent of startup biotech companies that, if they operate with lower costs and similar returns, get supported (read: bought) by larger biotech companies. Sound familiar?

    1. anon says:

      You nailed it. Start up biotechs are the modern form of Bell/Dupont/Bayer’s research centers. Only one who is losing out in this new arrangement are the start-up employees who have less security and benefits. Although, every sector has been trending that way for decades so I don’t think it could have gone differently.

    2. Derek Lowe says:

      I don’t think that Baran is talking about changing public perception at all – in fact, since he’s not trying, he feels that he’s better off going for private funding. Your point in your first paragraph is well taken, though. . .

      1. Ch says:

        I don’t see the comparison to Musk then. If Baran is about to abandon the next grant season and found ChemX, then I could see the similarities in approach.

        How about Craig Venter as a comparison? How much of his stuff is funded with public grants? Would be interesting to know, since he strikes me as the closest person to being a chemist’s Elon Musk.

    3. Daniel Barkalow says:

      It’s plausible that the private pharma in question deals better with the management and accounting aspects if it’s done externally on a per-project basis rather than externally. It’s certainly easier to let Baran work for a different private pharma company for a while and get him back the next time you need some synthesis work if he and his lab aren’t on your payroll. Even if the industry isn’t cost-sharing labs with different specializations, it’s easier to justify paying the going rate for synthesis only when you need it and just not worrying about the fact that he’s charging you the amortized cost of the Taxol work as well.

    4. Born on Third Base says:

      Baran only made it as far as he has at the pleasure of NIGMS. What company would be crazy enough to give these sweetheart collaborations to some hotshot assistant prof with no independent track record??? Public money effectively de-risked his group’s initial rise to prominence…I find this speech to be pretty disingenuous

  3. bad wolf says:

    Derek’s previous analyses of “progress” seemed to indicate that overall you don’t want a handful of geniuses in well-funded superlabs; rather it was a random walk process in which many small labs with decent funding would provide real novel discoveries.

    Unfortunately that would probably be a harder “sell” for industry to support. But yes, public-private partnerships seem like the way to go, since no-one has really solved the problem of how to assure constant funding from a relatively uninterested government/population. Benign indifference is one of the better policy options, all things considered.

  4. Anon says:

    I will play devil’s advocate here: The danger in academia-industry collaborations is that industry outsources research that it should do on its own and pay their own researchers for in a decent way. Of course it is appealing for industry to give some peanuts to universities, where PhD students or Post Docs get paid only a fraction of what they should get and reap the profits. Will industry hire the students afterwards or not?

    Another problem is that research is open ended. Often, one cannot see the full consequences of an initial discovery. Many small, “boring” steps have to be taken to fully develop the potential of a finding, and mostly it will be a dead end. Basic science needs to be funded by society because exploration has value in itself, and it has to be understood that it’s effectiveness and impact cannot be measured by citation counts or other factors. The focus on reachable short term goals and grants is an evolutionary process, which only the fittest survive. For long term scientific progress, this is highly detrimental.

    1. CMCguy says:

      Anon I think you have hit on a key point about the necessity of finding value in basic exploration. I also would suggest the comparison of SpaceX mission and Pharma’s objectives are analogous to apples and oranges. SpaceX’ s activity being more toward engineering applications is actually likely to spawn off shoot utility more quickly and generally to inspire public support (just like Apollo missions did) while fundamental biology and even chemistry discovery are almost always much further from any direct implementations, even if often clouded by over-hyped claims of capability to cure some disease in 5 years. In the end although because funding ultimately is not limitless there it does require majority directed to short term reachable goals however can not lose recognition that there must be sustained support for learning about new things where future un-imagined innovations will grown from even if means have to endure significant non-success rate to identify. Its a hard sell on inattentive public but proclaiming the truth against the tide is what leadership should be about.

  5. Hap says:

    Lots of NIH’s money is supposed to help train grad students; if you’re using that (or related funding) as yeast and private companies to help fund the research, then unless there’s a place for the trained to work (some of which the public/private research is replacing, some of which is elsewhere, some of which is nowhere, and some which still exists), you’re basically training people for unemployment or to be cheap labor. I imagine everyone but the (relatively small) labor pool of science students would find that OK, but I wonder how long you can sustain that model. Minor leagues aren’t going to attract so many people in the absence of a major league to make the idea of low pay playing baseball attractive (for some, that’s enough, but lots of people you might want have other opportunities, and you have to convince them to choose yours and not others).

  6. MoMo says:

    This model is sustainable as long as the PI can talk grad students into doing work for the Pharma elite, or until a smart Grad student sues the institution for royalties for an invention that made it to commercialization.

    1. Kaleberg says:

      Sounds like the NCAA and the NFL.

  7. Peter S. Shenkin says:

    Sputnik put me through college and grad school. The huge increase in government funding for science that took place to compete with the Russians resulted in an American “golden age of science” which, I believe, we are now seeing the end of, and I’m not sure that a continuation of government funding at high levels would prolong that age. I’m old enough to remember when the Petroleum Research Institute was a highly significant source of funding for basic scientific research in the ’50s and into the ’60s. But this kind of consortium funding, without IP rights accruing to the funding oil companies, doesn’t seem to be what Baran is proposing. Everyone, including university professors, wants to be an entrepreneur these days. That was unheard of back then, but the description certainly fits Musk. There are certainly VC-funded startups built around developments in organic chemistry; think peptoids, stapled peptides, combinatorial chemistry. And around biological concepts as well, of course. It seems to me that these are analogous to what Musk is trying to do with SpaceX. In addition, some consortium efforts have continued. For most of the ’90s I was responsible for the care and feeding of Clark Still’s Macromodel program, which was funded in full by a consortium of major pharmaceutical companies. That effort moved to Schrodinger, Inc. in 1999. And a number of open-source software projects get strong funding from large hardware and software companies. So I don’t think I see just what Baran is proposing that we don’t already have examples of in the VC and commercial marketplace.

  8. Ann O'Nymous says:

    This may be a contrarian viewpoint, but the problem doesn’t seem to be so much coming up with those early adopter ideas as crossing the gulf to full-scale, mass market commercialization. I’m very much reminded of the book Crossing the Chasm which covers the analogous process in the technology industry.

  9. tcmJOE says:

    I always generally felt that the heyday of an industrial research center (Bell Labs, Xerox PARC, IBM New York, Microsoft Q, etc etc etc) is tied to the parent company being in a highly dominant position, perhaps even at a full-or-near monopoly. I’m guessing that a similar statement could be made for a company’s willingness to fund university labs to work with(/for) it.

    The virtue of that situation is up to the reader.

    1. Kaleberg says:

      Good insight. It was also about avoiding government anti-trust sanctions. Back then, a company could dominate a market, but if it could demonstrate some level of restraint and that it was serving some public service, it could retain that position. Xerox, Kodak, IBM, and others were forced to license their technologies. Funding blue sky research was part of their probation so to speak.

      This attitude towards large corporations is unthinkable nowadays.

      (There were also the outrageously high marginal tax rates (personal and corporate) that discouraged dividend payments and buy backs. It made business sense to spend earnings on something, even anything, that might benefit the long term growth of corporation. Again, unthinkable.)

      1. Curious Wavefunction says:

        Good point. I don’t think investors explicitly supported the kind of basic Nobel Prize winning research that Bell Labs did. It was only made possible by the humongous profits which AT&T generated as a virtual monopoly. Those profits were what kept investors happy, not information theory or the discovery of the cosmic microwave background. I think it’s largely the same with the public.

  10. Phil of Chem says:

    I reached out to Baran recently to discuss a similar topic and got a great answer. He truly seems to be one of the most thoughtful people in the field nowadays…

    “Just as art has needed to adapt, the field of synthesis needs to come to grips with the fact that the artistic elements of synthesis are, alone, not enough to justify societal investment in the field. Whereas painters can sell to a large audience, the art of synthesis can only appeal to a small (non-paying) audience. Thus, in order to stay relevant, the field needs to focus on how it can increase efficiency (by inventing new reactions or strategies), deliver targets people actually care about (beyond structural intrigue), and provide a fast-track to medicinally-oriented goals. That said, I see no reason why the artistic, elegant approach can’t be employed at the same time. After all, the soul of synthesis is the art. What’s not publishable these days are the routes that could have been dreamt up by a computer and carried out by a robot.”

  11. Chrispy says:

    A lof of drug discovery is completely inappropriate for graduate-level study. Much of it is simply boring and repetitive, and oftentimes the chemistry is pretty simplistic by design. If you are Baran and you can get funding to pursue taxol-like molecules then great, but doing variations of the same amide coupling over and over is more likely to be the kind of chemistry that is required. The students do need to publish, too, something that can be difficult if you are in bed with a corporate partner. Having been on both sides of this issue, I can say, too, that academia has a well-earned reputation for promising a lot and then under-delivering. This may be an effective strategy for grants but it is disconcerting for corporations. Add to this that all the work is being done by trainees (students, postdocs) and not experts, throw in the patents that everyone will want a piece of, and facilitate the interaction with a slow and bureaucratic tech transfer office, and you have yourself a pretty rocky foundation for a productive collaboration.

  12. milkshake says:

    I am not a big fan of academia-industry funding partnership in general – the short term considerations tend to prevail and the golden rule is that whoever has the gold can dictate the rules. Very few research groups have the prestige of Baran’s lab and can negotiate conditions that are beneficial for both parties. Then there is also a greedy university administration that likes to gobble 50-70% of funding on the overhead – which means the harder you and your students work, the more they end up subsidizing crappy unproductive groups and departments.

  13. Barry says:

    Ashish Arora (Duke) has been studying this, and documents that while total R&D expenditure in U.S. industry is roughly constant over the last decades, increasings, its ‘D’ and not ‘R’ that gets done. The days of Bell Labs doing and publishing basic science in the private sphere are in the past. American industry now overwhelmingly publishes patents, not papers, development, not research.

  14. Blunderbuss says:

    The American people are smart enough to realize that they should not be in the business of subsidizing science that will be conducted primarily in the third world. Most of the methodology and synthetic advances from academia will not be implemented here (or probably anywhere). I appreciate what Phil’s work and he is certainly a better chemist than I am, but this research model of funding the synthesis of Neatomycin for the 25th time to test your pet theories about your favorite catalyst or reactive intermediate is mostly just mental masturbation. God bless those who can woo a billionaire.

    We should always fund both basic and applied research but we should go even further and give basic research scientists more freedom with little strings. Would anyone suggest that the NEA respond to some sort of democratic agenda? If so we would all be looking at a lot of Thomas Kincaide and quilts. Fundamentally we need to make sure that any PhD. scientist is actually able to do his or her own science in acadmia on some scale. A lot of very basic research can be done without fancy equipment or 10 postdocs. We should imagine ways to involve more institutions and people in very basic research. It does not need to be 600MHz NMR and 800L of solvent. He likes astronomy, well look at all that has happened with backyard astronomy. Maybe not sexy like Neatomycin but we could tap the potential of the large mass of disaffected organic chemists who are just teaching premeds a subject they hate. A lot of this research could be at the interface of chemistry with biology and materials. He should get used get used to the back seat because this century belongs to biology.

  15. eugene says:

    I agree with Hap on this one. The money from industry here is sustaining the professor in their job, but the people that are doing the chemistry are trainees who have to be gone in five years at most. If the industry outsources the research that they themselves should be doing in-house, then there is no job waiting for the trainees at the end of the road. So it’s great that your program is thriving, but you’re burning through a lot of people who are going to end up unemployed in the field that they trained for.

    A lot of the ‘research’ done in pharma, as mentioned by milkshake and Chrispy, is inappropriate for a research project in graduate school (simplistic chemistry and/or short-term considerations with patent minded partners). If the pharma companies are funding Baran with the knowledge that the students are not doing something that is applicable to their bottom-line, and are willing to hire them later to do their actual industry research job, then I guess that’s fine.

  16. milkshake says:

    The thing is, Pharma companies love to have someone like Prof. Baran on their advisory board and have a prestigious collaboration. So in his case the terms of the collaboration are probably very good and it allows his group member to work on interesting problems. But I have seen different kind of collaboration, which I think is far more common, that served to keep the underfunded groups afloat, and this leads to sort of a prostitution of the grad student time.
    An extreme case: Fairly famous group in Canada supplemented its income by producing by fermentation pretty useful chiral intermediates and was selling them to Sigma Aldrich. They had a monopoly on it, and suddenly there was a substantial demand – many tens of grams of the stuff. My friend working there put his thesis research on hold in order to manufacture and purify all this material. The bulk of it was bought by Taiwanese group, that had exactly the same synthetic plan, and managed to finish his molecule with his material and publish it half year earlier.

  17. Anonymous says:

    A great example of a productive academia-industry collaboration between David Liu’s lab at Harvard and Monsanto is reported in the current issue of Nature
    http://www.nature.com/nature/journal/v533/n7601/full/nature17938.html

  18. Ph.D. Organic Chemistry 1972 says:

    Agree with eugene that Hap nailed it. Prompted by one or another of Derek’s topics du jour, we have had this discussion of the Great Ponzi Scheme of Academia many times. Each time, we come to the conclusion that the prospects for PhDs coming out of academia don’t match the pitch they had been given going in. We have read about the ghost cities in China–massive stretches of empty residential buildings, malls devoid of stores or shoppers, etc., all a product of a system where keeping the machine producing is more important than whether there’s any demand for the product. Baran’s scheme is great for him, his industrial sugar daddies, and the massive bureaucracy that’s taken hold in today’s universities but as Milkshake alluded to, it smacks of pimps sweet-talking young innocents.

  19. anon says:

    all of these comments invoke the “student” as a kind of child-laborer. what makes you think students are doing this industry-sponsored research? there are research staff and postdocs, which are a) more experienced b) might be training for a position in industry and c) removes much of the conflict of interest. Imagine a scenario where the money from one of these collaborations allows for a new postdoc position – they do some work on the industrial project and then get to work on something more interesting as an academic project to advance their careers, which would not exist otherwise. I don’t see the problem here

    1. Blunderbuss says:

      If industry wants researchers, be it postdocs or otherwise, they can hire them. If industry hires you via Baran are you “training” or just being taken advantage of under the auspices of “training”, likely on a student visa? Sounds like a good way for de facto H1B expansion under F1. If Baran is so interested in these industry projects he could just go ahead and employ existing industry personnel to work on his ideas or have his students hired on at full salary while he “trains” them. Clearly the only angle here is exploitation of hidden labor reserves (foreign students and postdocs) and resources (instruments etc) subsidized by the university and the US grant system. As to career advancement, if you think there is a pot of gold at the end of this project industrially probably you don’t work in this field.

    2. Hap says:

      The problems are that 1) there aren’t many staff scientists in academia (they cost more and expect to get benefits – like any other job) – professors use post-docs in general for that, 2) while some of the research industry wants to do is interesting and within the scope of academic research, some (most) is asking academia to do research that would have been done by their own chemists, if they still had them, 3) graduate students and postdocs are paid far less than employees of companies because they’re supposed to learning stuff and training for jobs elsewhere – if collaborations are replacing industrial research to any significant degree, then the jobs they are ostensibly training for won’t exist. They can (in some cases) create their own companies, but for a variety of reasons (lack of training, lack of desire, want to have families, fraction of rewards likely to accrue to the startup initiator is too low to justify the risk) not many are going to be able or willing to do this. In addition, the output of industrial collaborations may not be publishable (or publication may be more limited than usual), which limits the ability of the people on such projects to get the jobs that do exist.

      I don’t think grad students and postdocs are kids, but the process is long and so they can’t update their labor choices based on current employment data, and the labor prospects for graduates seem to be misrepresented to maximize the supply of students entering the field, so it is hard to accord them full responsibility for the results of their choices. I think industrial-academic collaborations could be cool and useful, but in this environment I fear that they will mostly be harmful to the students in whose benefit they are partly conducted. They may also not benefit the professors (if you’re not as powerful and desired as Baran, say).

  20. This is another debate where funding and scale are going to be key. The private sector, by nature, are going to be highly reluctant to putting in the kind of money that can make a difference without the possibility of seeing gains in return.

  21. Mydegreeisworthless says:

    Too bad private industry (pharma) has already pumped billions into research only to come up with empty pipelines. Investors have proof that funding chemistry research provides little ROE.
    The reason why so many of us are not making a living sitting in front of a fume hood any more?

    1. Hap says:

      If there’s a cheaper way to get them, lots of people would be interested, but I suspect that drugs do not grow on trees (or rather, you can’t harvest the drug and the trial data from the same trees). If the model of relying on small companies depends on cheaper labor (more hours, similar pay, lower benefits) to make acceptable returns, then it’s unlikely to last (people are going to want to get paid reliably, and equity doesn’t usually pan out); doing less work on candidates initially and then derisking through contractual arrangements will mean that the costs of buying research will increase (above what you would have paid yourself). So how is getting rid of R+D (without which you don’t have anything to sell) to increase yields going to work again (without “paradigm shifts” or other terms which seem to mean “magically it will”)?

      1. Negative Externality says:

        Vaneant had it right: the value that you create doesn’t even have to exist! Simply hire some creative accountants/consultants and re-balance your balance sheets until the stock goes up

  22. Oliver H says:

    “Ladies and gentleman, society’s message to scientists is clear: simple curiosity is insufficient justification for our research. ”

    Who’s “society”?

    No, the message of large parts of society IN THE US right now is clear: Education is overrated and science is all just a scam.

    Luckily, there are nations in which science enjoys constitutional protections that ensure its freedom and which thus separate decisions as to how much money out of public coffers is spent on research and on what research precisely it is being spent on. If “society” or politics wants more data on a specific issue than is generated in that way, they can order and pay for a custom study just like anyone else.

  23. loupgarous says:

    Science funding’s a zero-sum game. If we fund a Mars shot, cancer research (among other things) will suffer. I’ve participated in clinical trials of two new, drastic-improvement-in-the-state-of-the-art scans for a very rare and hard-to-detect cancer, and one powerful way of killing the same class of cancer at the metastasis stage. If I hadn’t shelled out a large slice of my monthly disability pension for supplemental health insurance which covered the research, I’d be at a later stage of my cancer than I am now, because the studies weren’t publicly funded, and Medicare alone wouldn’t cover that expense.

    Meanwhile, the proponents of manned Martian and lunar exploration haven’t really presented any rationale for doing that science with humans and not robots. Robotic exploration just keeps getting better and better, while life support for humans on the Moon and Mars doesn’t.

    We’ll always be able to build better and cheaper robots for space exploration. It’s on the outside possible Elon Musk could assemble a large part of the necessary funding privately for a Mars colony. Everyone else is simply proposing to add to the national deficit for more Manned Space Science with limited benefit potential to the nation and world.

    1. Nilesh Jain says:

      Nice Reply…Very Good Answer

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