This week brought the incredibly sad but not really unexpected news that the bapineuzumab trial, one of a series of drugs being tested in the search for long-hoped for breakthroughs in the treatment of AD, was being halted for lack of efficacy. http://www.msnbc.msn.com/id/48547963/ns/health-alzheimers_disease/
Why did I write “not really unexpected?” Because the results are not surprising in light of the failure of similar agents from similar trials. No one likes writing this — there is not a single individual I know in the neurosciences and in neurological disease research that would have wept at the news of a successful outcome. But, it is also time for the neurodegenerative disease community to burst our hypotheses about AD wide open and be willing to pursue heterodox ideas and alternative approaches. I have written this before and I know how difficult it is to write it.
But there has, from the very beginning, always been conflicts and contradictions within the Amyloid hypothesis. There has always been questions about the over-use of rodent models (particularly rodent models developed with circular reasoning) for what is quintessentially a human disease. It is painful to criticize the brilliant men and women who have spent decades dedicated to research. It is hard to fault the Pharmaceutical companies who have spent millions and millions of dollars on trials. It is heartbreaking to consider the patients and their families (and in truth, who among us has not been touched by this horrible disease?) when they read the disappointing news. In the end, however, I do believe science can win. But we can’t turn any ideas away. The philanthropic organizations dedicated to advancing AD research and treatements have an obligation to seek alternative approaches and create an environment receptive to boldness.
Regardless of whether you cheered or booed the recent Supreme Court decision on the Affordable Care Act – reading the opinions provides a valuable lesson in federalism and distributed decision making that Foundations would do well to review. I’ve written about this before -but sometimes it seems to me that non-profits have lost sense of why it is that they are tax exempt. In reality private foundations could simply turn all their assets over to the Federal Govt and let the Govt dole out grants for the arts, or for science, or for service organizations. So why do we have a tax code that encourages tax exemptions for gifts to charitable organizations? It derives in part from a tradition dating back to the founding of this country – that is that NOT all decision making should rest in the hands of a central government. Having a host of decision makers involved in charitable activities encourages diverse decision making and ensures a variety of approaches. Non-profits would do well to heed the characterization of non-profits “…as not business and not government.” We who work in this sector should ever be on guard to defend its independence through our actions.29
It took all my strength to keep the top of my head from blowing off while having lunch with a senior academic scientist who also advises a few private funders supporting research in the neurosciences and neurological disease. What lit the fuse? Besides his treating me like I emerged from some dark cocoon only yesterday? It was that nothing said did not come straight from a decades old play book of the clichés, tired old lines, or semi-truths scientists have traditionally used when talking to donors. Language I assiduously worked to eliminate in a quest for more honest and authentic communication among researchers and reps from philanthropies. Sadly, funders still buy this stuff. My problem with this kind of dialogue, of course, is that I am a scientist. And I am a scientist that brings a scientific way of thinking into philanthropy. What does that mean? I question common wisdom assertions, I ask for data, I challenge the status quo, and I know what really goes on in the lab. Scientists talking to donors, particularly donors interested in diseases such as the topic at lunch, neurological disorders, tend to use a few well-trod pitches: 1) the need for collaboration, 2) the need for multi-disciplinary approaches, and the real point 3)the need for more money so that more of the same can be done. And it is always more of the same no matter how much “novel” lipstick is applied. To get something different you have to do something different. The reason we are not making progress against neurological diseases is not because there is not “enough.” It is not a question of quantity. It is not a simple problem of scale. The other problem is that “pitches” are always about the enterprise. Growing the field, the institution, the department, the lab. Pitches are always resource grabs – what is really desired is the opportunity for defenders of the status quo to control resources and direct it in ways that benefit a particular club. To be fair – they often truly believe that their club is pursuing the right line of research because it is comprised of the brightest, the elite, the prestigious, and the deserving. They are right. The difficulty is – the problem gets lost – the unique opportunity provided by small targeted investment gets lost – the ability to look at a problem in a harsh, critical, unsympathetic way gets lost. Philanthropic leaders interested in advancing science are NOT doing the scientific community any favors if they keep going back to the standard bearers in a field expecting new ideas. It is not possible to lead by following. It is not possible to lead without rolling up your sleeves and working hard. Leading means reading, questioning, thinking, exploring, and challenging. It means not getting to hang out with nobel laureates and the smartest guy in the room. It means risking that you will not be admired and liked for not rocking the boat. It means being scientific about science.
I find it almost mystifying that so many students are protesting business when the real target of their angst should be Academia – particuarly academic scientific research. Where else is there such blatant exploitation of the young by the old? Universities constantly raise tuition so that campuses can look more and more like 4 star resorts (see prior blogpost. Universities are all about creating your ‘experience’ (read future alumni donor) while the primary mission of providing a challenging education creating nuanced minds and deep thinkers becomes a sideline (or maybe a sideshow?). But even I have to admire the real cleverness with which they hoodwink students into believeing the real villain is the institution that loans you the funds to pay for the extravagant costs. The real outrage should be why listening to re-cycled lectures should cost $50 K per year – lectures delivered by professors very used to living in posh houses, dining at nice restuarants, and collecting wine. WHere is the outrage?? For the rest of us non-students — we should be equally outraged that our tax dollars are pouring into more and more buildings housing more and more research in a self-driven expansion of knowledge only a fraction of which is applicable to the very real and important problems facing humankind. Time to stop believing universities are “cool” – they are now pure business and no kinder and gentler than any other.
Any program a university wants to implement, from the mundane to the obvious, gains legs and cachet if it secures external funding. Even very wealthy private colleges with endowments dwarfing many private foundations will claim that unless a sponsor is found for the coffee and bagels that seminar series on (pick one of substitute your own topic) improving undergraduate education, or transfering educational skills to workplace skills, or how to better communicate your ideas to journalists is simply not going to happen. Similarly, despite the big bucks paid to build new research infrastructure with that all important “mingling space so needed to cross-fertilize new ideas across disciplinary silos” (or some other cliche about innovation) – don’t try to actually act on an interesting idea that emerges from that fortuitous bumping of heads unless you can identify an external source ready to fund it. The reality is – there is just not that much external funding available. In my neck of the woods – private foundation funding – grants are precisou and hard to come by. The funding rate at many private funders for scientific projects is probably around 5%. This makes the government funders like NIH and NSF look easy! What’s the solution – I am not sure. But it does seem to me that universities should be thinking about how they deploy their institutional resources to allow good ideas to seed. They may also need to re-evaluate their value system. AN idea should not be considered good because someone ELSE is willing to fund it. A strong internal compass and small amounts of discretionary funding might go along way. Now this may mean cutting back on the 5 star dorms, on campus sushi bars, and work out facilities that make a luxury resort envious. Never mind the university delegations to tour the gardens of Japan. Might be time to bring intellectual shabby chic back in style.
A recent issue of Nature included this piece:
Philanthropy: The price of charity
Nature 481,260(19 January 2012)doi:10.1038/481260aPublished online 18 January 2012
Philanthropists should pay their fair share of research costs, says Patrick Aebischer.
I have no idea what this means. If it is about indirects I have already addressed this issue — oddly enough in the pages of Nature.
The idea that philanthropy is free riding on research Universities is should be utterly laughable except in that this misunderstanding shows up the pitiful state of understanding of institutions that we have reached. Philanthropists, unlike governments, are not asking Universities to do anything. Philanthropy is not outsourcing its own research agenda to academics. Universities ask philanthropists to help them fulfill their twin missions of teaching and scholarship. Universities are SUPPOSED to carry out research and scholarship. So a grant to a university is budget relieving; it frees up resources the University would have to spend on salaries or equipment or other resources. There are no costs not being covered – this is a ruse of the worst kind and is a deliberate attempt to divert philanthropic resources. It is time for individuals to learn some history.
Perhaps the oddest thing about the change in year is the reality of how much one day is like another. You go to bed Saturday 2011 and you wake up Sunday 2012. That is not to say that I do not see the reason for the all the hoopla. It is wonderful that we have these celebrations that get us through the dark days of winter. In St. Louis the days are already noticeably longer and despite the cold air it is hard for thoughts not to drift to gardens and to spring. So is it with philanthropy — the fiscal years will be ending. The glossy annual reports will stuff mailboxes. AFter a brief respite the charitable organizations will launch their drumbeats for funds. And there will be the claims of great strides and revolutionary progress. But not really. Each day will be much like the others. Some of us will keep on with the daily work of learning as much as you can about the opportunity for funding and worrying about philosophy and principles. I hope you will continue to visit this blog and send me your thoughts. Happy 2012!
Holiday music, the enforced cheerfulness, the sugary food everywhere – not a problem. The one aspect of the holiday season I truly dread it is the hokey appeals from disease-specific organizations. The promise of cures around the corner. The hyped “breakthroughs” that on closer inspection are slight, incremental gains in our knowledge (and usually of animal models not people) at best. And the gratuitous claim that just as the cure is within reach the feds are yanking the funding and slowing progress (and you know who to blame for that!). It is all nonsense. And yet – I appreciate that for individuals with diseases and for their families hope is what keeps you going through the dark days. Raising money and pushing the science forward is how you gain control over this terrible occurrence over which we have no real control. SO what’s my beef?
My beef is that all this rhetoric actually has the opposite effect from what is intended. Our unquestioning acceptance of the assumptions explicit and implicit in these appeal missives does not drive progress. It enables the status quo. There is no need to really reach, to really try new kinds of studies, to re-evaluate our knowledge, or to challenge the reigning dogma if we consider it our duty to clamber aboard for the sake of holiday-feel-good. One of these years, MY holiday wishes will come true and some disease charity somewhere will write something authentic. And no one but me will respond. Because serious thought is so much harder than hype and hope. Pass the eggnog!
In an opinion piece in today’s wsj Professor Kaku asserts that in science – authorities are not what counts. Experiments count.
I used to believe this. I wish I still could. In several conversations recently, friends and I (sadly shaking our heads at what is a sure sign of official geezerdom) have wondered at the apparent disdain for objective truth among the scientists we know. What seems to matter is what one asserts – particularly if it fits with a certain view of the world. Meaning: public enthusiasm is good for science funding. Alternative meaning: we should run the world because we are smarter than those currently running it and we know what is best for you. Of course, historians could correct this latter assertion – but they are too busy protecting their own patch of turf. Perhaps Kaku can still believe that experiments are what matters because he is a physicist. Perhaps we have become cynical because we live in the world of neuroscience and psychology. If so – then I hope the “physics envy” dogging the biological and social sciences wins the day.
Recently, a colleague generously agreed to go over a presentation he had made at a leading summer course for graduate students and post docs in his field. It was a textbook example of what such lectures should do — presented an alternative idea concerning an important topic in the field, surveyed the experimental findings that called the “orthodox” theory into question, discussed new data, reviewed why the old and new data supported the “alternative” hypothesis, and then closed by pointing out why the alternative hypothesis could also be wrong. Beautiful. With the number of retracted publications due to fraud or misapplications of science on the rise it is important to remind young researchers that finding what is true is more important (and, of course, scientifically more interesting) than proving your idea right. Don’t fall in love with your idea – it makes it hard to admit that it’s wrong. Instead, fall in love with the search, with inquiry, with the process of finding out what is really going on. Funders, too, should take caution to heart. It is too easy to fall in love with your ideas, with your programs, with your goals — such that the truth gets altered to fit your preconceived reality. Better to be willing to always remember to ask yourself — what would it take to convince me that this program, this grant, this idea could be wrong? A dose of healthy skepticism keeps us all honest.