Cheetahs hunting and the quantified self

Who doesn’t love cheetahs?  A young person of my acquaintance went so far as to spend a large portion of her time, at a certain age, cavorting on all fours and yipping and chirping like a cheetah.  And of course we all know that cheetahs are the fastest land animals, and that’s how they catch their prey, by outrunning them.

Only that’s wrong.

Yes cheetahs are wicked fast, reaching about 60 miles per hour, but a recent report in Nature has shown, via novel monitoring techniques, that maneuverability and deceleration skills are the keys to successful hunting.  The researchers designed a new type of monitoring collar that included GPS and accelerometers.  No word on whether the collars also allowed cheetahs to play Words with Friends.

This report highlights the things we can learn as we get better and better at measuring.  Conventional wisdom may remain or be turned on its head, and either outcome is fine.  The key is that we have a better  basis upon which to understand that wisdom, that we don’t take things for granted, that we question our assumptions.

The cheetah collars also point to how we can gather so much more data on individuals, whether furry or bipedal (or both), than we ever could before.  I’ve recently been made aware of the quantified self movement (HT @bkolko), and what they hope to do is in line with what was done with these cheetahs.  Take individual monitoring and data gathering to new heights.  No, it won’t involve tracking collars (unless, you know, that’s your thing).  But it will involve using technology to measure what previously we could only guess at, and enable decision making and research in new and powerful ways.

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Why Derek Jeter being a lousy defensive shortstop gives me hope for innovation in industry

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Hat tip to Jeff Sullivan of Fangraphs.com for the article that sparked this idea.

It used to be we knew what a good defender was in baseball.  And Derek Jeter was a good defender.  He had balletic grace, he scooped up balls and threw them with flair and panache, with an all-but-patented jump-throw that made announcers gush and coaches shake their heads in awe.  He was the complete package, a player who could hit, field, throw and lead, a first ballot hall of famer.

Except that, when you look closely, it turns out his defense is lousy.

Defense used to be measured (still is, by many) via the eye test.  How does a player look when catching balls in play?  And this was backed up by the statistic of fielding percentage.  How many balls did a player field cleanly?  It makes intuitive sense.  The more balls a player fields correctly, why, the better defender he must be, right?

Except that’s only part of defense.  It’s nice if a player can catch a ball well.  But what about balls that get by him?  In the last decade or so, baseball analysts began studying the concept of range.  All things being equal, the realization came, range is actually more important than errors or how a player looks.  It’s one thing to catch everything that gets to within a few steps to the shortstop’s right and left.  It’s another thing entirely to catch 98% of everything spanning the third baseman’s left pocket to the grass on the far side of second base.  When you consider the huge number of balls that are hit in the vicinity of the shortstop every season, and the relative value of a hit versus an out, those extra feet of range translate into saved runs.  And saved runs contribute to wins.

Just as an aside, current defensive metrics suggest Derek Jeter has cost the Yankees over a hundred runs relative to an average shortstop over his career.  Still a hall of famer.  Not a great defender.

However, those saved runs and that increased range come with a cost.  By definition, the best shortstops will have more chances to make a fielding play, and if you make more chances, you are likely to make more errors.  Indeed, the very fact that a great fielding shortstop is able to get to more hard hit balls on the edge of his range may well lead to a lower overall fielding percentage as well as a higher number of errors.

Fortunately for those shortstops, baseball teams are getting smarter and are realizing the tradeoff is worth it.  Scouting reports regularly cite range in addition to how a player looks, and fielding percentage is low on the list of statistics an organization cares about in evaluating a player.

And that gives me hope for innovation in two ways.  The first is the point above about the eye test.  We trust what we see and feel.  However, that’s not always the complete story.  Often in trying to implement innovation, there’s a gut feeling by those doing the evaluation–this is innovation, that isn’t, I can tell.  Only anecdotal evidence suggests that no, in fact, often people can’t tell.  Just ask Kodak.  However, if baseball can come to realize that the eye test, while important, is just one part of the evaluation package, industries can also learn that lesson and look for other, possibly less subjective ways to measure innovation.

The second relates to two contradictory things that are often said about innovation, sometimes one right after the other.  We need to innovate.  And we need to de-risk it to make sure that it will work.  Unfortunately, there can be no real innovation without the very real risk of failure.  In an interview with Wired magazine, the inventor James Dyson is described as having worked his way through 5127 prototypes of his bagless vacuum cleaner before hitting success.  But if baseball can come to realize that a decreased probability of fielding success is actually a good thing when it means a shortstop is reaching defensive heights few others can, maybe industries can finally realize that failure, in the right cause, is something to be celebrated and embraced.

Gastric bypass surgery and the ever expanding world of GxE interactions

All opinions are my own and do not necessarily reflect those of Novo Nordisk.

An early publication article from the Proceedings of the National Academy of Sciences reports the fascinating finding that children born to mothers before and after gastric bypass surgery show differences in the expression of  genes involved in, among other things, glucose metabolism and immune function.  The study is small, with only 50 children evenly split between cohorts born to moms before and after gastric bypass, but if it replicates, it’s another piece of evidence  showing how the environment influences the way our genes function.

Epigenetics has been a hot topic in genetics research for a while now.  It’s clear that DNA methylation changes over time and within an individual and can affect gene expression.  Studies in a number of institutions such as Washington State University in the lab of Michael Skinner have shown that changes can even persist through multiple generations (in rats, at least).  The PNAS report adds another twist in that the gene by environment interaction arose due to a change in maternal health induced by surgery.

There are a lot of implications to this, including the rather theoretical one of whether this knowledge would induce more potential mothers to undergo gastric bypass surgery, and also practical ones of whether weight loss alone without surgery or via, for example, a lap band, would have the same effect.  But the one I wonder about is what this might imply for drug development.

While many genetic variations are known to affect disease risk and progression, and drug metabolism, there has been considerable debate on how to use such data.  In many cases, such as with the majority of Genome Wide Association Study hits, the relative risk of discovered variants have been statistically significant but small.  However, as we have seen with Amgen’s purchase of DeCode, drug development companies are keen to use genetic information to help inform their drug development efforts, to find an edge.

In this PNAS report, however, I see a flag of caution.  I applaud the efforts of Amgen and other companies taking these risks, but this report of possible epigenetic effects following maternal surgery also points out how much we’re still discovering about basic human biology, how much we still don’t know about the diseases we study.  Understanding Gene by Environment interactions is, I think, one of the key factors we deal with in developing drugs, and not one to ignore.  And yet, it feels currently like one of those “unknown knowns,” the things we willfully decide not to think about, even though we know it’s there.

Metrics and the Heisenberg quality of gathering data about behavior

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Thinking more about the Global Health Metrics Conference, one element that resonated was that measurement does not occur in a vacuum.  When metrics are gathered, and especially when they are gathered out in the open by global health surveys, for example, there’s the real issue of the act of measuring changing the validity of what’s being measured.  I’ve been thinking about this in the context of hiring and workplace management.  For example, if the media were to report that viewership of Khan Academy videos on YouTube was found to correlate highly with creativity in the workplace, I expect two things would happen.  One, viewership of Khan Academy would spike, and second, the metric would rapidly begin to lose what correlative and predictive power it had.  People would try to game the system.

In Global Health, where countries are incentivized to meet certain milestones, it requires real thought to either make sure the milestones are strongly causally related to the health goals, or else that the metrics undergo continual fine-tuning to ensure the desired effect.  If the metric were something like number of healthcare facilities, a country could ensure that number increases but there wouldn’t necessarily be a concomitant increase in actual health services delivery.  I’m sure these are topics the Global Health community wrestles with every day.

It’s kind of like with relationships.  While on the one hand, we can tell our partners what we want, and often see them do it, on the other hand don’t we really secretly want them to already know and behave accordingly, because somehow that’s more genuine?  It’s certainly why social science researchers often mislead their study subjects on the actual purpose of behavioral experiments.  Or, to quote from the movie Buckaroo Bonzai, “Character is what you are in the dark.”

Ultimately, it seems best to try to measure behavior as closely as possible to the desired outcome.  That’s why baseball is nice.  We want good hitters, and to find good hitters it’s simple:  we measure how well a player can hit.

A Genomics Researcher’s Take on the Global Health Metrics Conference 2013

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Over the past three days I had the opportunity to attend the Global Health Metrics Conference here in Seattle.  This is not my field; I’m a genomics researcher working in biomedical research and drug development, but I’ve also been curious about what’s going on in the area of public and global health.  This seemed like a good place to get a crash course.  The Lancet has kindly published all the abstracts and I wanted to give my impressions of what I heard.

First takeaway:  I was surprised and intrigued by how many parallels I saw between the work I do (primarily transcriptomics and genomics) and the work I saw reported.  Sure, global health researchers use surveys rather than high throughput sequencing, and gather data on nations rather than patients, and deal with the complexities of culture and government instead of human biology, and work in the public sphere as opposed to the private, and use a completely different vocabulary than I do, but other than that it was really similar.  So similar I put together this table:

Biomedical Genomics Research Global Health  Metrics
Increasing amount and types of data Yup
Biomarkers Indicators
Growing emphasis on efficacy measurements ditto
Lots of Acronyms, NIH, AMA, EULAR, ADME GBD, DALYs, CDVS, USAID
Struggle to understand what tissue, cell, analyte to measure Struggle to characterize the right metric to demonstrate effects/efficacy
Gene X Environment interactions poorly understood Local environment effects beginning to be captured
Personalized medicine Nation specific solutions
Noisy data, lots of unknowns Maybe even noisier data and, yeah, unknowns
More focus on longitudinal studies Already there

And so on.  I’ll elaborate on a few more below.  Another immediate takeaway:  I wasn’t even aware of the Institute for Health Metrics and Evaluation (sorry guys).  Now that I am, it’s a place I’d like to visit.

One thing that really impressed me was the work that IHME has put into making the Global Burden of Disease survey lucid, simple and accessible.  The data presentation by Kyle Foreman and Peter Speyer (@Peterspeyer) was terrific.  Not so much for any specific piece of data (although the trends and findings are all pretty fascinating), but rather for their demonstration of the power of dynamic presentation and facile web-based tools.  Static powerpoint charts are clearly so last decade.  Anyone wanting to check out their presentation can go here, or even better just go directly to the site.  As a scientist who also works with large, multifactorial datasets, I know the struggle to condense that data into a usable, comprehensible form.  I think Peter and Kyle have done a great job, and I also like the potential crowdsourcing aspect of it.  As I’ve commented on before, crowdsourcing methods, whether via games or other techniques, have a real potential to fully utilize large datasets and also to solve big problems.

Of the many talks I heard, a few I’ll highlight, just for the specific points I took away.  On the first day, Tanya Marchant showed interesting and cautionary data about making sure that what you’re measuring really measures what you think you’re measuring.  In this case, measuring the presence of skilled birthing assistants as a proxy for maternal care during childbirth turns out to be incomplete because of other factors such as availability of basic medical supplies.  Reminds me of debates over things like how best to measure drug efficacy in clinical trials–for example, response versus progression free survival in oncology.

Joseph Dieleman presented his work on looking on the effects of external aid to developing nations for health.  In a perfect world, external aid would just be added to pre-existing health expenditures, and after aid expired, local governments would maintain spending at pre-aid levels, or even higher.  Well, turns out this isn’t always the way this happens.  Aid comes in, local health budget gets shifted “temporarily,” but temporarily turns to permanently when the external aid leaves.  One of the thoughts that went through my head during this conference was to remember the law of unintended consequences.

I enjoyed Michael Wolfson‘s talk on functional health status.  Coming from an industry that really likes it’s tried and true measures like HDL/LDL levels, the concept of looking holistically at factors relating to actually feeling good was a nice contrast, and food for thought.

Bruce Hollingsworth had a great quote in his part, “People need incentives to provide accurate data.”  Yeah.  Tell me about it.  In transcriptomics it’s been a mantra for years that “Garbage in, garbage out,” in terms of incoming biological sample integrity and resulting data quality.  From what I saw, the data you can get trying to measure Global Health is maybe even noisier than the kinds of data that I normally deal with.  My main conjecture for why all hope is not lost due to data quality in Global Health is that GH researchers are able to bias the indicators they sample towards things with (hopefully) real meaning, else they would be adrift in a sea of not very useful data.  Maybe they feel that way anyway?  Bruce also made the point that there are external factors, again, which influence health.  Even people who know where to go for the best treatment may not because the facility is too far away.  Location, location, location.

Speaking of garbage (but not in a bad way), David Phillip‘s talk later that day referred to the problem of trying to extract useful data out of vital health records full of things like garbage codes.  That is, causes of death that are supremely unhelpful from a public health perspective, such as (I’m exaggerating here) death by lack of life.  His work on extracting useful proportions from this data based on the overall data distribution reminded me of imputation techniques that are used in genomics.

There were many more engaging talks, and I also had great conversations at lunch with different people. I suppose I shouldn’t be surprised by the similarities.  I think many research fields these days are converging on a similar emphasis on big data, analytics, efficacy, and finding the right metrics.  I also appreciated the long view shown by so many of these programs.  One of the drawbacks of private industry is the prevalence, often, of the short term view.  I could wish we had the decades-long commitment shown by various Global Health initiatives.

The aspect I find daunting in Global Health is how much uncertainty that community is dealing with, which greatly affects efficacy and efficiency.  An intervention might be exactly the right one when viewed in isolation, but can be so easily derailed by external factors.  Like biology, like baseball, it seems the key thing is to find the metrics that at least tell you that you made the change you hoped for, with the understanding that what happens at the end is so often, unfortunately, out of our control.

To TED or not to TED…that is the question (for researchers)

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Sharon Begley on Twitter (@sxbegle) pointed out an interesting article today about the effect of giving a TED talk for academic researchers.  The authors use a variety of library science techniques to characterize the TED-giving population.  Among other things, they found that presentations by academic researchers were generally more cited and liked on YouTube, but also that the number of citations of an academic researcher’s work did not increase after giving a TED talk.  This might suggest TED talks help researchers raise their public profile, but not necessarily their academic reputation.  There are caveats here, one of the main ones being that the scientists giving TED talks generally were measured as relatively “impactful” in terms of their publication history.  So, maybe these guys (and they’re mostly guys) were already cited as much as they would ever be.

On the other hand, getting a Nobel Prize does increase the number of times scientists are cited, so it is possible to increase your citations in some ways.  Just, you know, win a Nobel Prize.

This topic could go in a lot of directions–the role of scientists in popularizing science, the general TED phenomenon, public hunger for science versus science literacy, and maybe at a later point I can come back to that.  But in reading this study the first question I found myself asking was:  Does giving a TED talk get you more grants?  If we think about the academic research ecology, grants are the sun that feed the fields of academic research.  No grants, no research.  Also, no grants, no position.  And so I turned to the senior author on the study, Cassidy Sugimoto of Indiana University Bloomington.  I asked whether she thought grant funding might increase with a TED talk.  Her response via email:

“My hypothesis, motivated from our data, is that you would not see a significant difference. The scholars invited to present at TED were already in the scientific elite, cited significantly more than average for their fields. I would hazard a guess that they are also more likely to receive grant funding, but not because of TED. They are chosen for TED precisely because they are already elite. It’s a perfect example of the Matthew Effect at work–to those who have, more shall be given.”

And that led me to think of another question:  could giving a TED talk decrease your odds of getting a grant?  While we would like to think of the grant-awarding, peer review system of the NIH, for example, as fair and impartial, I have yet to meet a scientist who believes this.  This may not be a terrible thing–to paraphrase Winston Churchill, “It has been said that ‘NIH peer review’ is the worst form of  ‘grant awarding’ except all the others that have been tried.”  However, it does allow bias to creep in.  Studies have looked at the presence of biases in grant awarding under such theories as accumulative advantage.  Reviewers are human.  Humans have feelings and opinions.  If the human reviewing the grant of a TED speaker has strong negative opinions on the value of public engagement, or perceives TED presentations as grandstanding, would that lead unconsciously to a lower score?

On a practical level, the N is far too small and the timeframe too short to see the effect, if there is one.  Check back in 20 years and we’ll see.  But let me take this one step further and now ask, even if giving a TED talk doesn’t help in citations or grants, can it be a net positive for a researcher’s funding because it increases the probability of being able to use crowdsourcing approaches?

A number of researchers have sought research funding via Kickstarter and other sites.  However, I believe potential funders have a limited amount of disposable, impulse-driven income (I think of this as the iTunes/Latte pool), so this isn’t an endless new resource.  Right now the opportunity for crowdfunding is still pretty open but soon we could see many more scientists trying this route, especially as government sources of funding dry up.  In that case it will be a competitive market, and fame, such as might come from a nice TED talk, could be one of the factors leading to people choosing one project to fund over another.  Which could lead to what Cassidy Sugimoto refers to above as the Matthew effect.  The rich get richer.

And there are other possible negatives to crowdfunding, such as when researchers become driven to self-promotion to get crowdfunding support. To quote again from Cassidy’s email:

“…I think there are more disturbing issues in terms of branding of scholars. It is no longer sufficient to just do high quality research and publish it in reputable venues. Scholars must engage in personal branding–through social media and other means–to raise their value. Citations are not enough–now scholars also need to demonstrate their value in terms of tweets, media mentions, and the like…However, the negative implication is incentivizing branding over scholarship.”

But that’s a topic to expand upon some other day.  In any case, the possible negatives for giving a TED talk seem far outweighed by the real and possible benefits, and I’m in favor of anything that makes scientists talk to the public.

Not losing versus playing to win in Baseball and drug development

All opinions are my own and do not necessarily reflect those of Novo Nordisk

Another in a series about parallels between baseball and drug development

A recent post by Phil Birnbaum, who runs a baseball research site, did a nice job of highlighting how he feels stastisical analysis may best serve baseball organizations:  by ensuring that they don’t make losing moves.  While everyone is trying to win, in an industry where so much is uncertain, in many cases, it may be most effective to  “First, concentrate on eliminating bad decisions, not on making good decisions better.  And, second, figure out what  everyone else knows, but we don’t.”

This is a terrific observation, and one he backs up through the body of his post with examples from baseball and gambling strategy.  I think it applies quite well to drug development too.  I’ve made the earlier conjecture that drug development can be thought of as existing on the adaptive landscape, with improvements to drugs or drug classes getting harder and harder as you climb up that mountain of efficacy.  But when you’re on a slope, it’s really easy to go sideways or backwards.  So, the analogy here is that drug development, like baseball, needs to throw a lot of resources (not just statistical and analytical ones, either) into preventing a bad decision.

This thinking is also influenced by the ecology of pharma and biotech.  Let me be very clear about my initial assumption:  drug development is filled with really smart people, almost all of whom are dedicated, sharp, innovative, and really interested in winning.  So is baseball, (well, except maybe for the Kansas City Royals).  But it’s hard to put together a good drug development pipeline.  Resources help.  Resources often help.  But they aren’t enough.  And since the talent is there, the explanation for lackluster drug development progress may partly be found in companies still making poor decisions on assets.

Let me zero in on the second part of the quote in the first paragraph:  “And, second, figure out what everyone else knows, but we don’t.”  Here’s something else that companies could possibly do differently:  share data.  A really fascinating blurb in ScienceInsider just highlighted an effort by people at Johns Hopkins to try and get clinical trial information published, as long as it’s been publicly released in other formats such as through litigation or Freedom of Information Act requests.  While all the companies would prefer this not happen, if it happens uniformly, that can only be good for drug development as researchers learn more about why given trials were halted or failed.  If R&D costs as much as it does, part of the reason lies in duplicated effort.

To conclude, let me throw out another thought on decision making:  send in the crowds.  Crowdsourcing as a method for making decisions has been tried in a number of contexts and often has been found to lead to better overall decision making than more traditional methods.  If we want to make decisions on, for example, which drugs should move forward, setting up a system to poll everyone in the organization in a controlled, anonymous way might be enlightening.  I know this would not be a popular development for people in the C-suite, since, after all, that is their domain.  And I believe the assertion Malcolm Gladwell makes in Outliers that initial, small differences in environment can eventually lead to great differences in ability down the road as individuals get training and experiences not widely available.  Therefore those who are in the C-suite are different in their knowledge and outlook and know more about strategic decisions.  But they still don’t know everything, they still are human, they still have biases.  And a technician working in a lab in Boston may have noticed something in his cell cultures that  no one else is aware of.  If we want to make good decisions, shouldn’t we make sure that everyone possible has a voice?