Wednesday, April 25, 2018

Improving access to healthcare can usually make malaria go away

Drug resistant malaria has emerged in Southeast Asia several times in history and subsequently spread globally. When there are no other antimalarials to use this has led to public health and humanitarian disasters, especially in high transmission settings (parts of sub-Saharan Africa).

Currently there is a single effective antimalarial left: Artemisinin. But malaria parasites in Southeast Asia are already developing resistance to this antimalarial, leading many in the malaria research community and in public health to worry that we will soon be left with untreatable malaria.

One proposed solution to this problem has been to attempt to eliminate the parasite from regions where drug resistance consistently emerges. The proposed strategy uses a combination of increasing access to health care (so that ill people can be quickly diagnosed and treated, therefore reducing transmission) and targeting asymptomatic reservoirs by asking everyone who lives in a community where there is a large reservoir to take antimalarials, regardless of whether or not they feel ill (mass drug administration).

In Southeast Asia malaria largely persists in areas that are difficult to access and remote. The parasite thrives in conflict zones and in the fringes of society. These are the areas that frequently don’t have strong healthcare or surveillance systems and some have even argued that control or elimination would be impossible in such areas because of these difficulties.

Today on World Malaria Day my colleagues and I published the results after 3 years of an elimination campaign in Karen State of Myanmar.  The job is not complete. But this work has shown that it is feasible to set up a health care system, even in remote and difficult-to-access areas, and that most villages can achieve elimination through beefing up of the health care system alone. In places where there are high proportions of people with asymptomatic malaria, access to health care alone doesn’t suffice and malaria persists for a longer period of time. With high participation in mass drug administration, which requires a large amount of community engagement, these communities are able to quickly eliminate the parasites as well. We are hopeful that similar programs will be expanded throughout Southeast Asia, regardless of the geographic and political characteristics of the regions, so that elimination can be achieved and sustained.

Malaria (P. falciparum) incidence in the target area over three years. The project expanded over the three years, and overall incidence has decreased.

Link to the main paper:
Effect of generalised access to early diagnosis and treatment and targeted mass drug administration on Plasmodium falciparum malaria in Eastern Myanmar: an observational study of a regional elimination programme

Link to a detailed description of the setup of the project:

Tuesday, April 24, 2018

Throw 'em down the stairs! (making grant review fair)

When I was active in the grant process, including my duty to serve as a panelist for NIH and NSF, I realized that the work overload, and the somewhat arbitrary sense that if any reviewer spoke up against a proposal it got conveniently rejected without much if any discussion, meant that reviews were usually scanty at best.  Applications are assigned to several reviewers to evaluate thoroughly, so the entire panel doesn't have to read every proposal in depth, yet each member must vote on each proposal.  Even with this underwhelming consideration, the panel members simply cannot carefully evaluate the boxes full of applications for which they are responsible.  In my experience, once we got down to business, for those applications not immediately NRF'ed (not recommended for funding), there would be some discussion of the surviving proposals; but even then, with still tens of applications to evaluate, most panelists hadn't read the proposal and it seemed that even some of the secondary or tertiary assignees had only scanned it.  The rest of the panel usually sat quietly and then voted as the purported assigned readers recommended.  Obviously (sssh!), much of the final rankings rested on superficial consideration.

When a panel has a heavy overload of proposals it is hard for things to be otherwise, and one at least hoped that the worst proposals got rejected, those with fixable issues were given some thoughtful suggestions about improvement and resubmission, and at least that the best ones were funded.

But there was always the nagging question as to how true that hopeful view was.  We used to joke that a better, fairer reviewing system was to put the proposals to the Stairway Test: throw them down the stairs and the ones that landed closest to the bottom would be funded!

Well, that was a joke about the apparent fickleness (or, shall we say randomness?) of the funding process, especially when busy people had to read and evaluate far, far too many proposals in our heavily overloaded begging system, in which not just science but careers depend on the one thing that counts: bringing in the bucks.
The Stairway Test (technical criteria)

Or was it a joke?  A recent analysis in PNAS showed that randomness is perhaps a best way to characterize the reviewing process.  One can hope that the really worst proposals are rejected, but about the rest.....the evidence suggests that the Stairway Test would be much fairer.

I'm serious!  Many faculty members' careers literally depend on the grant system.  Those whose grants don't get funded are judged to be doing less worthy work, and loss of jobs can literally be the direct consequence, since many jobs, especially in biomedical schools, depend on bringing in money (in my opinion, a deep sin, but in the context of our venal science support system, one not avoidable).

The Stairway Test would allow those who did not get funding to say, quite correctly, that their 'failure' was not one of quality but of luck.  Deans and Chairs would, properly, be less able to terminate jobs because of failure to secure funding, if they could not claim that the victim did inferior work.  The PNAS paper shows that the real review system is in fact not different from the Stairway Test.

So let's be fair to scientists, and the public, and acknowledge honestly the way the system works.  Either reform the system from the ground up, to make it work honorably and in the best interest of science, or adopt a formal recognition of its broken-nature: the Stairway Test.

Wednesday, March 14, 2018

Thinking about science upon entering the field. Part II: What are 'probabilities'?


Below is the second installment in a short series of posts by a current Penn State graduate student in Chemical Ecology, Tristan Cofer. The thoughts are based on conversations we have been having, and reading he has been doing on these topics. The idea of the posts is to provide reflections by someone entering the next generation of scientists, and looking at the various issues in understanding, epistemology, and ontology, as they are seen today, by philosophers and in practice:

******************
Probabilities are everywhere. They come up in our conversations when we talk about making plans. They are there in our games as “chances”, “odds”, and “risks”. We use them informally when we make decisions about our health and well–being. And, in a more formal sense, we use them in science when we make inferences about data. Indeed, probabilities are so common that they can at times seem almost familiar.

But just what exactly are we talking about when we talk about “probabilities”? When I say, for instance, that the probability that a tossed coin will land heads up is 50%, am I saying something about that coin’s disposition to produce a certain outcome, or am I only expressing the degree to which I believe that that outcome might occur? Do probabilities exist out there in the real world as things that we can measure, or are they just in our minds as opinions and beliefs?

The short answer seems to be, yes, probabilities are both. They have an objective and a subjective element to them. This duality has apparently been there from the start, at a time when formal probability concepts were first developed in the seventeenth century. According to the philosopher Ian Hacking, during the Renaissance, the term “probable” was taken to mean “approved by some authority” rather than by evidence. It was not until the Enlightenment, when early Empiricists first began looking to Nature for “signs” to support casual associations, that “probable” came to mean “having the power to elicit a change”. Hence, “approval by testimony” from people and institutions was superseded by evidential observations. Transforming signs into evidence helped to advance what we might call frequentists–based induction, which was formalized as a mathematical concept in the Port Royal Logic in 1662.

Of course subjective probabilities have hardly disappeared, and in fact, it may be argued that we have seen their resurgence in the popularity of Bayesian– or conditional–based statistical inquiry. That being said, however, I am not sure that understanding how the term “probability” developed gets us much closer to understanding what probabilities really are.

It seems that in order to make progress here, we must talk about cause and effect. Namely, we need to discuss whether probabilities are like physical laws that define an event, or whether they are contrivances that we use to describe things after the fact. If they are descriptions based on the past, then what rational do we have for extending our inferences into the future? Is there any legitimate guarantee that future events will proceed at the same frequency as their predecessors? And even if they do, then for how long?

On the other hand, we might ask, if probabilities are only descriptive then what makes them so regular? Why does a tossed coin land heads up one-half of the time, almost as though it had some property that we might call its “probability”. Moreover, how are probabilities such as this determined? Could it be that we really are living in a clock–work universe, and that even our uncertainty is defined by deterministic processes? These questions are perhaps beyond what sciences and mathematics is able to answer. But maybe that is okay. This seems to be fertile ground for philosophical inquiry, which might provide insights where they are needed most.

Wednesday, February 28, 2018

Rare Disease Day and the promises of personalized medicine

Our daughter Ellen wrote the post that I republish below 3 years ago, and we've reposted it in commemoration of Rare Disease Day, February 29th, each year since. I wish I could include an update reporting that the cause of her rare disease has been identified. She would very much like to know, not only because it would explain this thing that has defined so much of her life, but also because, in this genetics age, being able to tell a new doctor the cause of her condition would mean they'd have no doubts. Sometimes a diagnosis isn't enough, and when you have a rare disease doubt can remain a frequent aspect of encounters with the medical system.

It's not there there has been no action. After a lengthy, ultimately failed attempt by a previous lab, which was unsuccessful for reasons unclear to us but probably technology-related, Ellen is currently included in another large sequencing project, and we're hopeful that we'll get some kind of an answer. They've done whole genome sequencing of her DNA as well as Ken's and mine, and are about to begin to look for her causal variant. To date, we know that she hasn't been found to have one of the known variants associated with her disease. There are occasional reports of new variants in other families with the same disease, and that could help identify hers, but what if she doesn't have one of these, either?

Finding a causal gene variant is easiest when a disease is rare and there are multiple cases in one family but Ellen is the only person in our family, for as far back as we can trace on both sides, with HKPP. When the disease is rare and only one family member has it, there's not really a peg to hang your hat on -- where do you start to look for the causal variant?

Ellen has classic hypokalemic periodic paralysis (HKPP), a disease for which causal DNA variants in a small number of ion channel genes have been identified in a number of families, where they essentially act as classical Mendelian variants. There are several possibilities here -- she could have a de novo mutation, a mutation new to her that she inherited from neither parent. If it's one that is shared by other people with HKPP, that would be easy to identify, but if not, even if it's on one of the three genes, to date, that have been found to be associated with the disease, how could it be shown that it is causal, rather than simply a mutation with no effect? And searches of 'her' genome are based on blood samples, and what if she carries a somatic mutation that arose after the embryonic separation of blood-related tissues from other tissues?

Some families with HKPP have members with the supposed causal variant who are symptom-free. This isn't unusual in genetics -- it's been called "incomplete penetrance" for a century, which basically means that one can have a causal mutation without the condition it apparently does cause in others. There can be various explanations for this. For example, when a disease responds to environmental triggers, as does HKPP, it's possible that gene by environment interaction at some critical age is required to set up the cascade of events that lead to paralytic episodes. Curiously, HKPP generally begins at puberty, for some unidentified reason -- perhaps some triggering event doesn't happen in disease-free family members with a causal variant, or perhaps the disease is polygenic rather than monogenic and those who are disease-free don't have the required critical mass of variants. This means that it's possible that Ken or I could have "the" causal variant but, because of incomplete penetrance -- whatever effect that would mean -- we don't have the disease. Or, we gave Ellen a mix of variants that together cause her disease but neither of us had the same mix that came together in her. But, at the very least, neither of us carries a known or plausibly relevant variant in the known HKPP-related genes that have been tested.

Ellen isn't the only person with HKPP whose cause is not known. Perhaps there are other ion channel genes associated with the disease, that are not yet identified. Or, perhaps in some people it's too genetically complex for causation to be parsed. Because of all these possible difficulties, identifying the cause of Ellen's disease is not likely to be straightforward. We are hopeful that the geneticists currently working on this will have something to tell her in the end, but whether it's something simple that she'll be able to tell her doctors we don't yet know.

This is one personal story for Rare Disease Day, but I think it's very relevant to all the promises of "personalized medicine" being made these days. Having your DNA sequenced isn't a magic answer. Sometimes the technology is limiting, sometimes the problem is actually impossible to solve.





By Ellen Weiss

Despite being the product of two of the authors of this blog – two people skeptical about just how many of the fruits of genetic testing that we've been promised will ever actually materialize  – I have been involved in several genetic studies over the years, hoping to identify the cause of my rare disease.

February 29 is Rare Disease Day; the day on which those who have, or who advocate for those who have, a rare disease publicly discuss what it is like to live with an unusual illness, raise awareness about our particular set of challenges, and talk about solutions for them.

I have hypokalemic periodic paralysis, which is a neuromuscular disease; a channelopathy that manifests itself as episodes of low blood potassium in response to known triggers (such as sodium, carbohydrates, heat, and illness) that force potassium from the blood into muscle cells, where it remains trapped due to faulty ion channels.  These hypokalemic episodes cause muscle weakness (ranging from mild to total muscular paralysis), heart arrhythmias, difficulty breathing or swallowing and nausea.  The symptoms may last only briefly or muscle weakness may last for weeks, or months, or, in some cases, become permanent.

I first became ill, as is typical of HKPP, at puberty.  It was around Christmas of my seventh grade year, and I remember thinking to myself that it would be the last Christmas that I would ever see.  That thought, and the physical feelings that induced it, were unbelievably terrifying for a child.  I had no idea what was happening; only that it was hard to breathe, hard to eat, hard to walk far, and that my heart skipped and flopped all throughout the day.  All I knew was that it felt like something terrible was wrong.

Throughout my high school years I continued to suffer. I had numerous episodes of heart arrhythmia that lasted for many hours, that I now know should've been treated in the emergency department, and that made me feel as if I was going to die soon; it is unsettling for the usually steady, reliable metronome of the heart to suddenly beat chaotically. But bound within the privacy teenagers are known for, my parents struggled to make sense of my new phobic avoidance of exercise and other activities as I was reluctant to talk about what was happening in my body.

HKPP is a genetic disease and causal variants have been found in three different ion channel genes.  Although my DNA has been tested, the cause of my particular variant of the disease has not yet been found.  I want my mutation to be identified.  Knowing it would likely not improve my treatment or daily life in any applicable way.  I'm not sure it would even quell any real curiosity on my part, since, despite having the parents I have, it probably wouldn't mean all that much to this non-scientist.  

But I want to know, because genetics has become the gold standard of diagnostics.  Whether it should be or not, a genetic diagnosis is considered to be the hard-wired, undeniable truth.  I want that proof in my hand to give to physicians for the rest of my life.  And of course, I would also like to contribute to the body of knowledge about HKPP in the hopes that future generations of us will not have to struggle with the unknown for so many years.

For many people, having a rare disease means having lived through years of confusion, terrible illness, misdiagnoses, and the pressure to try to convince skeptical or detached physicians to engage in investigating their suffering.

I was sick for all of my adolescent and young adult years; so sick that I neared the edge of what was bearable.  The years of undiagnosed, untreated chaos in my body created irrevocable changes in how I viewed myself and my life.  It changed my psychology, induced serious anxiety and phobias, and was the backdrop to every single detail of every day of my life.  And yet, it wasn't until I was 24 years old that I got my first clinical clues of what was wrong.  An emergency room for arrhythmia visit revealed very low blood potassium.  Still, for 4 more years I remained undiagnosed, and there was horrible suffering during which my loved ones had to take care of me like a near-infant, accompanying me to the hospital, watching me vomit, struggle to eat or walk to the bathroom, and waking up at 3am to take care of me.  For 4 more years I begged my primary physician and countless ER doctors during desperate visits to investigate what was going wrong, asked them to believe that anxiety was a symptom not a cause, and scoured medical information myself, until I was diagnosed.  It wasn't until I was 28 that I found a doctor who listened to me when I told him what I thought I had, made sense of my symptoms, recognized the beast within me, and began to treat me.

My existence, while still stained to a degree every day by my illness, has improved so immeasurably since being treated properly that the idea of returning to the uncontrolled, nearly unbearable sickness I once lived with frightens me very much.  I fear having to convince physicians of what I know of my body again.

What I went through isn't all that uncommon among the millions of us with a rare disease.  Lengthy periods of misdiagnoses, lack of diagnoses, begging well-meaning but stumped, disbelieving, or truly apathetic physicians to listen to us are common themes.  These lost years lay waste to plans, make decisions for us about parenthood, careers, and even whether we can brush our own teeth.  They induce mistrust, anxiety, exhaustion.

Each rare disease is, of course, by definition rare.  But having a rare disease isn't. Something like 10% of us has one.  It shouldn't be a frightening, frustrating, lengthy ordeal to find a physician willing to consider that what a patient is suffering from may be outside of the ordinary since it isn't all that unlikely at all.  Mathematically, it only makes sense for doctors to keep their eye out for the unusual.

I hope that one day the messages we spread on Rare Disease Day will have swept through our public consciousness enough that they will penetrate the medical establishment.  Until then, I will continue to crave the irrefutable proof of my disorder.  I will continue to worry about someday lying in a hospital bed, weak and verging on intolerably sick, trying to convince a doctor that I know what my body needs, a fear I am certain many of my fellow medically-extraordinary peers share.

And that is why I, this child of skeptics, seek answers, hope and proof through genetics.

Saturday, February 24, 2018

Thinking about science upon entering the field: Part I

Below is installment number one in a short series of posts by a current Penn State graduate student in Chemical Ecology, Tristan Cofer.  The thoughts are based on conversations we have been having, and reading he has been doing on these topics.  The idea of the posts is to provide reflections by someone entering the next generation of scientists, and looking at the various issues in understanding, epistemology, and ontology, as they are seen today, by philosophers and in practice:


For the past few weeks now, Ken Weiss and I have been sitting down over coffee to talk about our shared interest in the ‘philosophy of science’. Our conversation started last fall when I met Ken after he lectured in the genomics class that I was taking here at Penn State. I had just finished reading E. O. Wilson’s Sociobiology at that time, and I was curious about its legacy in contemporary science. Ken was nice enough to share his thoughts with me on the subject and, after exchanging a few emails, we decided that a reading course on the history and philosophy of this thing called ‘science’ might be useful.

Since then, I have read through several good introductory books, alongside works from Paul Feyerabend, Ludwick Fleck, and others that I suspect many MT readers, and those of you who followed Ken’s Crochets and Quiddities column in Evolutionary Anthropology, may already know well. Of all the readings that Ken has recommended to me so far, perhaps none was more insightful, not to mention downright entertaining, than Paul Feyerabend’s book, Against Method (AM).

Feyerabend was a radical, and he knew it. But like any radical worth his salt, he was also too good to dismiss. In AM, Feyerabend challenges what he sees as our unhealthy fascination with defining an universal, atemporal scientific method. After taking a long, hard look at how science had historically been done, Feyerabend concludes that there is in fact no such thing as one, true, holy, and apostolic way to ‘do science’. Instead, what he finds is that folks tended to use whichever method worked best for them to accomplish whatever it was they were attempting to do. To quote, “…there is only one principle that can be defended under all circumstances and in all stages of human development. It is the principle: anything goes’.

Many have criticized Feyerabend for being too extreme in his proclamation. And while maybe not ‘anything goes’, it seems reasonable to point out here that the standards that we use to decide what counts as science have indeed changed over the years. So then, where does this leave us? One possibility may be that science is not so much a methodology as it is an ideology.

An approximation of this idea was first proposed by Ludwick Fleck in the 1930s in his book, The Genesis and Development of Scientific Fact. Fleck’s thesis was that ideas could only develop in a society if they were styled in such a way that they conformed to the prevailing norms. New ideas that were accepted by what Fleck called the ‘thought collective’, were granted the status of ‘facts’. Ideas that were not, were ignored, dismissed, or outright attacked, often times alongside their creators. Facts became facts not because they were true, but because they were popular. There was no logical structure to the history of scientific knowledge; there was only an idealized average that came about through the interactions of different thought collectives falling in and out of vogue across time.

Fleck’s ideas were largely reiterated some thirty years later by Thomas Kuhn in his now famous book, The Structure of Scientific Revolutions. Here, Kuhn uses the term ‘paradigms’ rather than ‘thought collectives’ to describe the conceptual framework on which scientific discoveries are made. In contrast to Fleck, Kuhn focuses less on the vague accumulation of scientific knowledge over time, proposing instead that paradigms ‘shift’ at distinct points in their history, thus giving way to previously unconceivable new ways of thinking.

Several questions came to mind after reading the various works mentioned above: How do we decide who gets to participate in science? Can we anticipate a Kuhnian paradigm shift, or is it really only observable after the fact? What credentials are required for membership into a thought collective and how are they awarded? Is there an initiation? Maybe a password or a secret handshake? I guess I’ll just have to wait and see.

Thursday, February 8, 2018

"White Trash": the ugly reality and its import

I've been reading the recent book White Trash:  The 400-Year Untold History of Class in America, by Nancy Isenberg, Penguin Books edition, 2017.  This book documents the history of class divisions in our country, noting that it is not just racial minorities--native Americans and African Americans--who have been an integral part of our nation's history.  The white lower class, who have eked out their livings slaving away (one might say) for the wealthy elite, have been a part of the country since it's founding by European settlers.


The history of our 'democracy', including even our civil war, is one of gross oppression of the many by the few.  In post-WWII times, with industrial-scale materialism, we have distributed material goods and a better standard of living to a wide swath of the population, but the large underclass, that is unable to share in this, is still very much with us.  Somehow, it seems impossible to dispossess those who can afford yachts and private planes and multiple mansions, even enough just to even out the quality of lives of the many who still suffer deprivation here today.

This blog isn't social commentary as a rule, but one can ask about the degree to which genomic promises can be delivered nationwide, when living circumstances are so varied.  Among other things,  Big Data is in vogue, but how can there be large enough sample sizes to relate genetic variants to trait risk when, given so much disparity in access to resources, environmental variation is so great and so essentially unmeasurable?  If there are so many G and E combinations, then the assessment of their statistical correlation with various outcomes will be very shaky, at best.

Of course, in the nature of our history, white trash--the poor white population--was denigrated not just as being disgusting but also as genetically degenerate.  This idea fed the fervid eugenics movement, as Isenberg relates in some detail, which managed to rationalize the poor's situation as due to bad genes, casting the fear that they, being ethically unrestrained, will out-reproduce the rest of us--that is, the good guys.  This was of course just one of the convenient rationalizes that the elites always manufacture to justify the inherent worthiness of their privilege.  It has been thus since Plato, at least.  And we see much the same today, though usually implicit rather than crassly explicit.

The evil of social inequity, visited upon the many by the few, seems inevitably with us in history, and has led to a string of protest movements and even revolutions.  Whether equity is ever actually possible is something social scientists can ponder, but from a genetic point of view, there are some relevant issues, given what we've got.

Returning to bite: Sample size alone militates against biomedical/genomic equity
The promise of genomic miracles for "All of Us", the current slogan from NIH that promises to lead to precision medicine for everyone, sounds so laudable that its risibility may seem surprising. But such a promise is vacuous at best, and cynically self-serving of NIH. But the promise reflects some loss of memory by the Director of NIH.

Once upon a time the NIH, wanting some Big Money for some Big Data for genomics, proposed the HapMap project.  A smallish sample of a few tens of thousand individuals mainly from the majority populations (whites in the US, by some odd chance) would be genotyped for tens of thousands of markers across the genome, and these could be used for statistical association studies for, well, just about any trait you would want to name.

But wait a sec!  What about the needs of the many minority groups in the US and around the world?  How would or how could they benefit from this largely majority population sample?  The HapMap rational was that common diseases--the ones we really are targeting with association studies--were caused by common variants, and would hence apply to all populations; this was known as the CDCV 'hypothesis', though it was never justified on scientific grounds and was mainly a ploy to pry big long-term money out of NIH for the gene worshippers, and as some said quietly at the time, finally to pry funds from the grasping hands of environmental epidemiologists.

The problem, we now know, is that common diseases or even normal traits are due to countless individually minor, usually uncommon (low allele frequency) variants.  What we know now is that even for the 'major' populations (the whites and Asians with money for Big Pharma to collect), causation is not simple, not due to a couple of 'druggable' target genes, even if one should think of these common traits (diabetes, obesity, schizophrenia, IQ, etc) as typically genetic in the first place.

But let us here not be cynical about the implicitly racist or elitist aspects of NIH's Big Data schemes.  Let us think of how the failure of CDCV shows the hollowness of this year's NIH slogan, "All of Us", as any sort of real promise.

If (sample) size matters, than size matters!
Well, does size matter?  If not, if what we need are genetic variants common enough to be useful, then we can scrap the Big Data romance and go back to focused sample sizes in genetic studies.  This was the CDCV rationale.  But if that were true, why then today's push for massive samples, each person genome-sequenced?  Is this just a grab for money, or a way to hide behind a lack of actual ideas about how genomes work?

The nominal rationale is that to identify all the relevant causal genomic sites for a trait, we need very large sample sizes, since individual effects are by now known to be generally weak and rare in the population.  To find them, if statistical testing is our criterion, we need big samples.  That's convenient because it also means Big Data and regally funded projects too big and costly to terminate once started.

The CDCV rationale meant that modest sample sizes and sequence markers rather than whole sequence, would suffice to identify the genetic bases of the common later-onset diseases that we want to deal with (and, as a sort of freebie, other traits normal and otherwise, early and late onset).  And, conveniently, since these were common they would be shared among populations.  But that was wishful thinking.  If we are to include 'All' of us equitably, what would that mean?

First, how do you even devise a sample of "All' of us?  Given admixture and what that means for sampling, the inexact correlation between self-defined 'race' and gene history, differential accessibility of different populations, and so on, how do you get comparable representation of every subgroup in the US?  Whites are easy.  But should the same fraction of Cheyenne and Navaho and Mohawk and Cree be sampled, or just a fraction of "Native Americans"?  And this does not yet consider environments, socioeconomic status, and the like.  And, smaller populations mean fewer very rare variants, but at what point does the unavailability of sufficient samples mean less ability to detect relevant variables?

By the time CDCV failed to materialize, the justification for GWAS that it would be equitable became clearly false, but it was too late to stop the gravy trains of Big Data and 'omics-everything.

White Trash shows the persistent socioeconomic problem of inequity in our country.  It is about the sociology, and the sometimes biological rationales used to ignore or suppress the large fraction of the nation who are not among the yacht-owning privileged.  It discusses the eugenic and other pseudo-biological excuses that have been dreamed up by the privileged classes in the country, to justify or explain as inevitable and inherent in the poor.

GWAS proclamations, like "All of Us", are another reflection--perhaps unintentional, but nonetheless--of privilege and unfairness.  If traits really were genetic in the way being so widely promised (they aren't!), and even if we could accurately measure relevant environmental contributors (we can't), inequity is built into the statistical-significance nature of the game now being played because of sample-size issues that mean we cannot achieve comparable resolution among our different sub-populations.

Of course, clear secular trends in disease and other traits, like IQ and just plain height, show that genomes are not the major determining factor in the first place.  But who would want to give the money back to the greedy environmental epidemiologists?  And who would want to invest in real societal economic equity, to remove or reduce the disease-associated lifestyle factors that we know predominate?

Until we have a better way, we are in a sense in an ethical trap because genomics in its current form cannot deliver equity.  Environmental fairness would be more attainable, in principle, but human history has few if any real or lasting examples of that sort of societal equity.  The book White Trash makes the problem starkly clear, but provides no answers and perhaps rests on the idea that awareness of the problem might awaken some drive towards remediation.  Don't hold your breath.

Sunday, February 4, 2018

Pogophilia--60 years ago but as fresh as ever!

For those readers of this blog who are old enough, or aware enough, to know about Pogo, the greatest of all the comic strips ever, I was reading my reprint of strips from 1956*.  Antics galore, of course, with sophisticated word play and subtlety that only Walt Kelly, in the entire history of comic pages, could master.  But in Pogo there was often a political point to be made, and I came across this  strip and thought it so appropriate it was worth putting in a post:





Here we see the always gentle and innocent Pogo (a possum) with the always scowling and grumpy, but ever true-hearted Porky Pine.  I think it speaks for itself, for its time 62 years ago, and for our times today.


*This is from a 2017 reprint of the 1955-56 years: Under the Bamboozle Bush: The complete syndicated comic strips, vol. 4, copyright Okefenokee Glee and Perloo, Inc.  If you like or might like Pogo, this series' 4 volumes to date would be just the thing for you!