I’ll take a double dose of the “or”

Over the thanksgiving holiday I found myself picking up and reading lots of ‘wellness’ articles in various newspapers and magazines.   Tis the season.   The recipe for not feeling our best during November and December: a dollop of overindulgence at holiday gatherings, a bowlful of reasons to miss exercise and sleep, and a heaping serving of list-generated stress.    Blend it all with short days and colder temps and voila — lots of column inches filled!    The remedies?   Oh – need we say pharmaceuticals ( for example antidepressants) and devices (think light therapy)?   The answer for whatever ails us has to be external to us.

I can not resist reading these articles.   The game for me is quessing how far buried in the text will be what I am looking for — the or.

After the discussion of some aptly-named syndrome and the various interventions offered (usually making someone $) there usually is the gratuitous “or.”    You can spend a fortune on prescription medications, treatments, special equipment… or – you can eat sensibly and get some outdoor exercise.    When are we going to get it?

The more natural we live — eating the freshest, least mucked-with food we can find and using our bodies for purposeful movement in whatever way is possible for us – the better we feel.

The mystery to me is why all the health charities and foundations have thrown in their lot with the medical-ag-industrial complex (MAIC).   In my view -the real purpose for much of what goes on in the MAIC is to generate ever-more syndromes that need to be diagnosed and treated.     Why are we not supporting research that really looks at what it is that makes us well — and for the most part keeps us well?

Our physiologies are complex systems and sure, things can go wrong — but in general, they work most of the time.   Particularly if kept in balance.   Clean water, good food, fresh air, purposeful activity.   Medical care appropriately provided is part and parcel of the overall package – but think about it — how many times do we find our interactions with the medical establishment unsatisfactory?   Too often – when they have little to offer for what ails us they deflect to something they can provide.    The recent epidemic of Vitamin D deficiency being a perfect example – they can test for it and they can give you something to take.   And the likelihood of doing harm is small while the chances that you may eventually feel better on your own are high.

Foundations with a professed interest in health should be more willing to challenge researchers to question the basic ideas we currently use to think about what it means to be well.

People or projects?

The big news in scientific philanthropy right now is the Wellcome Trust announcement that it is shifting some of its funding from projects to people.

http://www.nature.com/news/2009/091111/full/462145a.html

In this way, they are following in the footsteps of HHMI and in the older traditions of the Rockefeller Foundation (“make the peaks higher”) and Carnegie (” find the exceptional man”).   The reaction is predictable.    Some scientists are enthusiastically supportive of awarding funding to a person while others argue that the typical 3 year investigator-initiated project grant is the right and proper way to fund science.   underlying both views is the certainty of each camp that there is a best way to fund scientific research.

In reality – the “people” people have always reviewed proposals valueing the person over the project.    We have all sat on review panels where the first thing said about a proposal is that Dr. X is a great guy (and in such discussions Dr. X is typically a guy).   We then hear about how well the person knows Dr. X, the wonderful person Dr. X trained with, and how if given the money Dr. X will do great things.   ‘Nuff said.    My own advisor (a great guy) often said grants were about “the man, the plan, the fan.”

But what if you are Dr. Y?   When your proposal is introduced with “I don’t know Dr. Y…”, you can almost feel the oxygen being sucked out of the room.   Dr. Y may or may not get funded when all is said and done, but the chances are slimmer than Dr. X’s.   And in today’s tight funding climate slim may actually be closer to slim to none.

And so the rich – right schools, right pedigree, right pals, right meetings, and the right way of thinking about a question – get richer.     And for foundations – who should be taking chances, supporting alternative models, and questioning the status quo, especially when it turns out the status quo might be teetering on a less secure foundation than common wisdom suggests – making the rich richer may be a less than ideal strategy.

There is another way to think about the people vs. project funding dilemma.

Think about programs.   Not the aim 1, aim 2, aim 3 projects and not just the reputation of the proposer.   Rather, focus on what it is that this line of research will tell us?   What will we know if it is pursued?   Will we care?    Besides personal knowledge of the PI, what is it in his or her record that supports the belief that this person is likely to do something interesting?  Make the proposal focus on the program — because sometimes it becomes obvious that while someone (even a great guy) might have a lot of good projects it is not quite clear that it adds up to a serious  program.  

Will supporting her or his program take us someplace?

The “person”-centered review always makes me a little nervous.   There are lots of bright, creative researchers who didn’t go to the right lab for training, don’t look just like the review panel, don’t mingle effectively at meetings, and don’t ever question authority.

I do think that long term, flexible funding is one of the best ways to support science.   And focusing on programs rather than people or projects tends to help spread the wealth.   Most likely Dr. X will still get funded.   But maybe so will Dr. Y.

A call for bold action

The buzz right now is “public-private partnerships”.    What does this mean in the sphere of biomedical research?   What is often meant is that private donors should join their dollars with those provided by federal funders to cost-share large projects.   One selling point for such projects is the efficient use of resources.  What becomes lost when private dollars are yoked to centralized goals is the diversity of decision making that allows for new, and sometimes unpopular, ideas to flourish.   private dollars should take more risks, fund ideas early in their inception, provoke new thinking, and question the perceived wisdom of authority.   It is this idea of distributed decision making increasing the likelihood that a less than mainstream idea will get funded somewhere that, to me, makes private funding of research and scholarship appealing.

So, it is surprising to me that the study on the utility of screening for breast cancer was funded, not by private dollars, but by a government agency.   Of course, it was funded by the government agency that is supposed to look at questions of health care effectiveness.   But still, it is a bold study bringing into question common wisdom assumptions.

We assumed that annual mammography for all women over 40 was effective.   In reality the data — and not just from this most recent study but from a number of studies over the years has indicated that the truth was more complicated.   So why didn’t one of the breast cancer advocacy groups fund a study to answer the question?     Why wasn’t ongoing assessment part of the huge public education effort that has made an annual mammogram part of many women’s lives.

False positives have real effects.   They require follow-up.  They create anxiety.   They undermine confidence in our body’s integrity.   They turn us from well people into diseased people.

I am completely bemused by the headlines shouting how confused women are about the new recommendations.   I am not confused.   They make perfect sense to me.  All tests carry the risk of error.   There is the risk of diagnosing cancer where there is no cancer.    There is also the risk of being given a clean bill of health in January and finding out that you have agressive, metastatic disease months later.   Diagnostic tests should be used carefully.

Private funders with an interest in breast cancer should have been the ones questioning the common wisdom of authority.    There is still much that we do not know about breast cancer.   Too many women die from it every year.    Diagnosing more and more women with small changes that are unlikely to alter the course of their lives is not progress.    Private funders could refocus the question.   They could keep researchers’ eyes on the truly ill and keep us all from being distracted by the worried well.

Advocates should embrace the new recommendations and call for bold action.  Ask new questions.   Fund new ideas.    Diversify thinking.    We might actually make some real progress.

Whither Philanthropy?

The Monday Nov 10 WSJ contained a special section offering solutions to the problems with charitable giving.   I immediately noticed that one of the “problems” not given special attention is that many pundits of philanthropy seem to know very little about the history and philosophy of organized philanthropic giving and charitable giving in the US.   The one basic thing they always seem to overlook is why we have such a rich tradition of giving.   One reason is, our history of distrusting central authorities.   Private giving allows a distributed system of decision making that allows ideas to be tried and tested.    And maybe inefficiency is necessary.    Philanthropy is not business.  It need not make a profit.   It does not have to follow common wisdom or yield to political whims.   These are core characterisitcs that should not be casually trifled with.

There is an unfortunate tendency in most of the articles I have read, and the collection in the WSJ this week falls into the trap, of the lumping together what are very different forms of giving with very different purposes and outcomes.

In general, individual charitable giving (think supporting your local soup kitchen or putting money in the buckets or boots thrust at you at intersections or the entry to a supermarket) tends to be palliative.   The hungry are fed, the sick are cared for, the local child gets the needed operation paid for by strangers.    More organized public charity -(think civic organizations or voluntary health organizations focused on curing a particular disease)- often raise funds broadly from the public, usually on an annual basis, and tend to spend funds via a number of directed programs.   Organized strategic philantropy by foundations that spend incomes from private endowments and do not raise funds from public campaigns tend to support strategic initiatives intending to be alleviative.   Private foundations using a social venture capital model (private funds investing in the public good) often aim their efforts at root causes.    How can we not just care for the sick, but understand the causes of illness and how they can be better treated?    How can we not just feed the hungry but understand why in a world of plenty people are hungry?   Private foundations also invest in the public good through their support of educational and cultural institutions so that we all have access to art, music, history, and other opportunities for informal learning.

In my experience, most attempts to discuss “problems” with charitable giving bog down in worrying about “processes.”    How to write proposals?  How much funding for how long?   What should be the reporting requirements?   In reality – the mechanics of giving and granting are easy.    The problem with philanthropy is not the 5% payout.    The hard part of philanthropy is thinking carefully about what you are doing.    Believe it or not – this is hard.    It is expecially hard in a profession filled with outer humility masking inner hubris.  it is hard to maintain skepticism.  It is hard to ask the right questions.    It is hard to risk failure.  There is no magic way to solve social problems.   There is no right way to make grants.    Non-profits needing to raise funds to support themselves are not all equally deserving.    Sure, most non-profits can do a better job.   But they do not need confused “experts” selling them trendy advice.

Nothing Ventured Nothing Gained

Over the last decade or so a new group of biomedical/disease research funders have burst on the scene getting quite a bit of attention – the self-named and self-promoting “venture philanthropists.”   Styling themselves after high risk venture capitalists VPs are supposed to be doing something very different from what I imagine must be the plain, old,  non-adjectified philanthropists.  In practice, from what I can see, the VPs do what most of us in biomedical philanthropy do – look for good ideas and fund them in the hope of moving the knowledge ball further down the field.    They are not uncovering the “genius in the garage” or finding some hidden gem no one else has been able to find.   They often fund researchers at the top biomedical institutions – don’t have to venture too far afield to find them!    VPs hold meetings, sponsor workshops, make grants.   In many ways their playbook looks much like the one used by the plain old Ps.   The risk for VPs (and of course VP is all about high risk, novelty, outside the box, on the edge, pushing the envelope – you get the picture) is the lure of what is presented as a bold move and sometimes, (to continue along with the sports metaphors I imagine are fairly popular in VP strategy sessions) they simply fall for the long lob or the field goal too far.   Intentions are one thing, reality is another.   But hey – in the game of public relations, you DO get points for trying!

I for one am tired of theVPs.   More importantly, I think they do not do science, philanthropy, or patients any good.

For us plain old Ps it is always a bit worrisome to think that we do not yet have treatments or cures for some of the most devastating and complex diseases affecting humans because we haven’t been stamping our feet forcefully enough.    Is advancing (or accelerating, VPs love the word accelerating) much needed clinical interventions just a matter of demanding them of the “blue ribbon” panel munching Danish at a fancy resort!   How terrible if all this time the plain Ps just didn’t know that wishing (or asserting) could makes things so.    Don’t get me wrong – I am not saying that there may not be ways that private investment could spur clinical advances.   I just don’t believe there is A way.   What we are all doing – VPs and plain old Ps – are experiments.   We should try different approaches; this after all is the beauty of philanthropy.  Private funders should represent a diversity of thinking on trying to figure out how to take knowledge into practice.   Because if anyone asserts they know how to do this – they are wrong.

Part of the problem is that there are yawning knowledge gaps between research and care.  The goals of the research enterprise are not even matched to clinical needs. The most promising preclinical work can fall apart when put up against real diseases in real people.   We may need some radical new ideas – or we may need just some basic knowledge.   We may even need a better understanding of exactly what it is we are trying to do.   Curing cancer is not a real goal. Monolithic “cancer” doesn’t exist.   Real risk is thinking a slogan is a research goal.     What we really need is honesty – what do we know, what don’t we know?  What assumptions are we making about disease that are just wrong?   Are we studying human disease – or are we focused on the experimental models we’ve created?   When funders demand progress – researchers will respond with what looks like progress.   We’ll have mice, and chips.   We’ll get scans and cascades.   We’ll be told that we have to break silos, invest in career development, fund collaborations, host a meeting (and the more exotic the location the more senior the participants).

So whether you’re a new VP or just a plain old P – be humble.   Be skeptical of claims.   Be even more skeptical of your own claims.

Not at Neuroscience

This week, the Society for Neuroscience is holding its annual meeting in Chicago.   Everyone who is anyone in the field neuroscience, along with 30,000 of their friends, postdocs, and students will converge to hear hundreds of presentations, view thousands of scientific posters, and race importantly from committee business meeting to committee business meeting squeezing in some hits at social event to social event.   So why am I, a neuroscientist working for a private funder of neuroscience research and living 250 miles from Chicago not at Neuroscience?  Why, if given the choice between going to Neuroscience and having root canal without anesthesia would I choose the dentist office?

In part, my answer says a lot what I think is problematic in the current climate of academic research.

1)     Most attendees are charging every expense against research grants while bemoaning the lack of research funding.  (Note: even gobs of stimulus funding has not diminished the academic indoor sport of whining for dollars – the behavior is so ingrained in academic scientists that nothing shuts it off.)

2)     The atmosphere tends towards self-conscious self importance.   The important and powerful neuroscientists are readily distinguished by their plumage of colored ribbons hanging from their meeting badge.    A lack of ribbons marks one’s relative anonymity (and lack of clout) in the Society.

3)     A depressingly large number of presentations – both platform and poster – will after the first few hours, sound and look alike.

4)     The highlighted big name talks are primarily geared to attract press coverage – with little concern about the accuracy of the results.   The primary goal being to engender public enthusiasm (and ideally funding) for neuroscience – and not necessarily understanding.

To be fair, Neuroscience does serve some positive purposes.   Old friends catch up.   Graduate students rub shoulders with some of their heroes.  Jobs are offered and accepted.   Business is accomplished. The local economy gets a little bump.  One friend, defending why he was going – told me he found it “humbling” to see the size and breadth of the field.   I guess.   I just find it crowded and boring.   And if anything really exciting gets presented – I’ll read it in the paper with my morning joe in the comfort of my own home.

The Nobel Prizes and the best way to advance science

Each year, the announcement of the Nobel Prizes in Chemistry, Physics, and Physiology and Medicine creates an opportunity for scientists to capitalize on the (temporary) public interest and lobby for increased science funding.  If scientists at US institutions essentially sweep the prizes (and this year is one of those), scientists in other countries wail, gnash their teeth, and exhort their governments to increase funding.    If the US does not dominate the prizes, American academia howls about lost prestige and the inevitable loss of economic competitiveness that will come back to bite administrations if research funding does not increase.   When, in years like this one, the science prizes are awarded for work tending towards the more basic end of the research spectrum, we hear calls to invest in undirected, unfettered, blue skies research – because we just never know when something is going to turn out to be interesting.

Really, is this true?   Or do such statements reflect part of the mythology science likes to feed funders and the public?

 

I propose that the prizes this year were awarded to work done:

1)      A long time ago (Physics) at an institution known to allow unfettered research – but was the scope of the work performed at Bell Labs completely undirected?  A review of much of the most celebrated work at Bell Labs indicates a shared theme – how can information be packaged and transmitted.   It also took a lot of post-discovery research to make digital images commercially viable.

2)      Over time (Physiology and Medicine and Chemistry) – during which much interest has been generated and many labs have contributed beyond the initial discoveries.    Rather than a surprise, it has been anticipated that the topics of telomerase and ribosomes would eventually garner Nobels.    It has and will take much work and investment to translate these basic findings into applications.

 

To point out that Nobel prizes often recognize original contributions that then take the work of many other individuals to expand on and develop does not in any way detract from the excitement in and importance of the work lauded.    But it does raise the question of whether these prizes provide justification for investing in basic science research preferentially?  Rather, should it not be the entire enterprise of research and entrepreneurship that should be celebrated and supported? How many basic research findings DO NOT win prizes, jumpstart new fields of research, or yield new products?    How much undirected, unfettered basic science research is simply gray, rather than blue, skies – uninteresting, derivative, and unimportant?

 

Ah, we just never know.