Take on a Big Problem? A ton of money or a tub of water?

Two Nobel laureates were interviewed recently on the BBC Radio 4 program, The Life Scientific, and they said some relevant and interesting things.  The program is new series, interviews with some of the most influential scientists alive.

Paul Nurse, who won his prize for work on the genetics of cell division, was interviewed in October.  His prize was earned essentially because cell division is in many ways a similar process in all forms of life.  In light of evolution this could be said not to be a surprise: the same process might be expected to involve the same mechanism.  On the other hand, there is a lot of parallel evolution and given the complexity of many controlling mechanisms, one gene might substitute for another for the process.  But, at least in terms of some of the controlling genes, evolution somehow maintained the same mechanism over more than a billion years.

The other scientist of particular interest, interviewed in November, was John Sulston.  He innovated methods for mapping (locating) the genes on the genomes (chromosomes) of an important experimental model, the tiny flatworm called C. elegans, and then led the race to sequence the entire human genome.  A main part of this work was done at the Sanger Centre, near Cambridge, England, where I was fortunate enough to spend a sabbatical in 2005.  In his modest self-description, Sulston said that his job was just to identify the entire genome, and let people more clever than he have that information to do the work to find out what different parts of the genome do.

C. elegans; Weiss and Buchanan, The Mermaid's Tale, 2009

This moved the field from 'genetics' that dealt with single genes and classical hypothesis-driven science (where you have a specific, restricted idea, and then design experiments to test it), to 'genomics' or what is called hypothesis-free science: sequence everything in every individual you study, and search for unsuspected pattern to emerge that can then be specifically tested.  The latter is more like Victorian plant and beetle specimen collection, that we so often love to criticize as useless, not even 'science', really.

There are two aspects of this that are relevant to the current drive to understand life, largely from the genome perspective. First, Nurse said one should start out a science career by picking a really Big Problem.  Even if you work on a narrow scale, do it to solve a major problem about life--he started out with yeast, before turning to human cells and generalizing how cell division work.

Sulston got a similar prize but by taking a diametrically opposite view: his job was to collect the beetles and let everyone have a crack at the data to see what they could find.  Genomics has been driven by the technology that makes it possible. But it is in some ways the opposite--or even the antithesis--of Nurse's idea.  It is doing a really big study on a really small problem.

GWAS (genome wide association studies) to understand, say, the genomic basis of diabetes may not seem like a small problem.  If the genomic approach works, and it leads to major reductions in diabetes morbidity or mortality, it would be a big success.  But the problem itself is very local and particular, and there is no intent that solving it would apply to a bigger problem.  One can criticize the blind following of this Big Science approach, and it richly deserves the criticism for the manifest, numerous reasons we often point out.

But is this also a big problem hiding under a big budget for a small question?  It is often argued so.  In defense of ever-larger studies of biobanks, GWAS, and the like (or, in regard to evolutionary genetics, of ever more whole genome sequencing from ever more species, applying ever more detailed and exotic statistical tests for evidence of natural selection), defenders often argue that yes, it's expensive, and yes it may be decades before it bears fruit, and yes, GWAS may not identify major causal genes, BUT these studies will reveal biological mechanisms or pathways that will have much broader applicability.

There is no answer to this.  We are clearly, however, training a generation of technocratic scientists who think big budget and big technology either first, or immediately after whatever question they are asking.  And the questions are nowadays mainly applied ones: what causes diabetes or stomach cancer, for example, or what cause skull shape variation.  However the studies are routinely justified for what they will reveal more generally.  We often, if not routinely, point to chance discoveries in the history of science, and say that's what we're aiming for.

Of course, the vast majority of science is routine, if not hum-drum and with little likelihood of any impact other than to feed the investigator and his or her lab group.  It is vainglory of a high magnitude to promise serendipitous Eureka! moments as justification for dipping so deeply into the public treasure for each of our studies.

On the other hand, it is certainly true that Eureka! discovery moments do arise.  So is this an acceptable justification for investment in, say, big-scale genomic approaches?  This is for you to decide.

But what we're doing clearly is proposing the kinds of studies to answer the kinds of questions that require big data and expensive, extensive, and often very complex instrumentation and statistical methods to address.  Inevitably and systematically, perhaps, some issues are being closed to us while others are being opened.   One can argue that the narrower your training or focus the less likely you'll have one of the major moments, but in any field in any era it has always been only the very rare, lucky person who has had one.  Also, without the investment, they certainly can't happen.

Or are these correct arguments in support of the way we do things today?  In the past, it was individuals slogging doggedly after a problem (Galileo, Newton, Darwin, Einstein, others) rather than big factory operations (which, to be fair, didn't really exist until fairly recently), that delivered Eureka! discoveries.  Will the lone, persistent, investigator have the next transformative insight?

Nurse had substantial though we think not enormous funding.  Sulston and the Human Genome project garnered enormous funding for their work.  Both got Nobel prizes for their work.  On the other hand, Darwin just worked in his backyard after a low-cost sailing trip round the world, Mendel in his modest garden out back of a monastery, Galileo with a cheap telescope and under house arrest.

And the real Eureka! moment?  That just required Archimedes to take a bath.

Follow....your instincts?....the leader?....the money?

All of us in science are only human.  We have at least our fair share of failings.  Still, we do try to make useful increments to our collective understand of Nature.

But  because we have to earn a living, want recognition, and need job security, and because science is not generally something you can do without funding, we are under pressures other than just the desire to follow our instincts and do the best science, for its own sake, that we can think of.

It's also true that science, like the rest of society (we're only human, after all!) goes in for fads and fashions.  So a question has been asked, whether the problems in science are due to its fad-following, or to its chasing after money.  That means playing politics.

The answer is that these things--intuition, imitation, and politics--are thoroughly intertwined.  Original thinking and deep insight are both rare commodities, despite each of our desires to manifest these notable traits.  And funding is a group decision: peer review, peer views on what's important for whatever reason, and funders' mandates about what they will support.  We have leaders in science and leaders in funding agencies who, however they got or earned their positions, determine within some bounds what will be funded.  Thus we have to keep an eye on that and do what we need to do to be part of the funded world.

Faddishness is part shallowness and part fish-schooling wherein we chase the smell of the green stuff.  None of these can be avoided, probably.  While each of us may dream that we're the conceptual leader or innovator, few of us really are.  Science does progress, even if more slowly or indirectly towards objectives than we might wish.  But in science, like society at large, utopian thinking--that what we want could, if people just did the right thing, be achieved--is probably more dream than reality.

We use our forum here on MT to note things we believe are misguided or mistaken, as well as hopefully pointing out what seems sound, or what might be a more sound way to view the evidence.  But others have alternative views and platforms for proclaiming them.  It's a hurly-burly world!

One view is that people should see the reality in which we live and go with the flow: do what people at a given time think is cool (follow the fad) and do what in a given time seems viable (follow the funds).  Another view, and basically one that we hold and try our best to practice, is to object and resist where we see that to be appropriate, and try at least to be a corrective voice even if few in power pay any attention or would act differently even if they agree with the points we try to make.  A minority view rarely 'wins', but science is supposed to be about Nature's truth, not just temporary fashions.

In the end of course as we know from history, only history shakes away the chaff so that the grain becomes clearly visible.

Another miracle cure -- the 3-minute-a-week exercise plan

Alas, another story that starts with "The Truth About...".  Why do these stories all seem to promote miracle cures?  Last week sugar was toxic, and now, exercise makes you fat, but there's a cure!  Maybe if you quit going to the gym, you can go back to eating sugar.  Though, the obvious next finding is that what's killing you is not just sugar, or exercise, but the sugar you eat because your exercise makes you hungry.

What's the story?  It turns out that three minutes of high intensity exercise (HIT -- High-Intensity interval Training) will make you fit.

The HIT approach, combined with gentler exercise such as walking and even fidgeting (yes, there’s an acronym for it and it’s NEAT – Non Exercise Activity Thermogenesis), will do the trick.

Walter Mosley at work -- briefly

Yep, much better than 3 hours a week, because those three hours make you hungry, and worse, give you visceral fat, which is the kind that kills you.  A BBC presenter, Michael Mosley, was put through the paces -- or rther, lack of paces -- at Nottingham University, where investigation into the effects of HIT vs traditional exercise are underway.

Scientists at Nottingham University who measured Mosley’s reaction to the High-Intensity Interval training (HIT) sessions recorded a 30 per cent improvement in the effectiveness of his insulin action: that’s the body’s ability to move glucose out of the bloodstream — where it can become a toxin and lead to the build-up of dangerous visceral fat — and into muscle tissue, where it is of benefit.

Just for the record, this sounds suspiciously like what cutting sugar out of your diet is supposed to do for you, as well. And you don't have to have a gym membership for that!

Who knows?  Maybe these guys are onto something.  But, this 'everything in moderation' taken to the extreme seems .... a little extreme.  The paper on this work hasn't yet been published (but will be soon), but it does seem as though whether this method works for you depends on what you exercise for, and thus how you measure it.  And, if you're exercising to lose weight, clearly it shouldn't be the only thing you do, so the idea that exercise alone will help is iffy; if you're exercising because it's how you meditate, or you really love doing it, 3 minutes a week isn't going to do it.

Ken was in the Air Force a while back (a long while back), and they had adopted an exercise/fitness program developed by the Canadian Air Force.   It was called 5BX, and was only a few minutes a day, but at a graded intensity level.  If you progressed through that you really were fit, at least for some short-term exercises.  But that was before the aerobics era, in which you had to do exercise for enough time to shift your energy use from short-term to stored (anaerobic to aerobic), and the point was to get your heart in shape.

Since then the jogging fad or habit spread widely, again led by various gurus and their claimed magical ideas.  Lot's of us run, bike, swim, or whatever, and while some of the gurus have died of coronaries while running or whatever it is they do, overall it seems to be quite salubrious.  But, what it's good for depends on what you're doing it for.

Ism-itis!

People adhering to a particular faith, say X, are often called Xists or those who believe in Xism.  Sometimes this is just a descriptor, but often it's used as a criticism, or worse.  That's what happens when pole-headed right-wingers call President Obama a 'socialist' (something the pole-heads apparently know nothing about).

Sistine Chapel; Wikimedia Commons

This kind of ism/ist description applies in cultural combat but also in science.  Thus people can be reductionist, frequentist, or falsificationist and so on, in the words of their detractors -- so these aren't compliments.  People actually would not use the word about themselves if they feel that others use the term in a derogatory way.

Creationists (and they really are ists in the sense of holding tightly to a specific ideology or creed!) often denigrate people who understand the real world as 'evolutionists',as it is not clear exactly what these terms mean, which can be important.  It is a castigating characterization when used by creationists, and it may imply that one is an ideolog about, rather than an explorer of, the subject of evolution.

We often refer critically on MT, to evolutionary or Darwinian or genetic 'determinists' or 'determinism.'   However, our meaning is important to understand.  At a seminar in our department a couple of years ago, when we questioned the nature of genetic determinism being invoked in some darwinian adaptive Just-So story-telling, someone stated that he was a determinist--"and isn't everyone?" Well, in science the answer is clearly yes, and no.

Here's where language gets in the way.  If determinism means that Nature is causal and that every effect must have some cause, then most scientists would plead guilty to the charge.  To invoke effects without cause is to be mystic, and certainly that has nothing to do with science.  That doesn't mean that we have identified or understand the causation of effects under discussion, and there is where the legitimate issues lie.

Darwin, Museum of Natural
History, London;
Wikimedia Commons

Things are less transparent when it comes to 'selectionism'.  If one makes the Darwinian assumption that whatever is here had to have got here by adaptive natural selection, then it is perfectly legitimate not to be a selectionist.  Much in evolutionary reconstruction is of this type, and it often includes behavioral evolution or even morphology, where traits themselves can be hard even to define. If the trait must (by assumption) be the result of specific adaptive natural selection, then our task is to identify that selection.  But we can always find some such reason, since the function today can be equated to having been the advantageous function in the past.  This is entirely circular, and it's not science!

This doesn't mean that eyes or birds' wings or hominid locomotory apparatus got here 'by chance', as creationists still falsely often suggest, but it can mean that some functional elements ended up in our genomes by chance, if their initial harmfulness or helpfulness was slight compared to the populations they were in (in genetic terms, they got into the genome by 'drift').  Duplicate genes that have no harmful effect but provide redundancy that can subsequently be used for new function constitute one of many examples.

Selection must build on what's there, however it got there.  Such chance-installed elements don't suddenly produce wings out of reptilian forelimbs, because complex traits involve too many changes.  But the elements themselves need not have got here by selection, since most will have slight effect.  Likewise, truly harmful things are eliminated by not being viable, and that is a form of selection, but not Darwinian or adaptive selection, since the defunct forms weren't really competing with anybody or anything.  They just didn't work.

The bottom line here is that determinism depends on the degree to which (1) truly probabilistic cause exists, and/or (2) one believes that a specific cause under consideration perfectly predicts a specific outcome, and/or (3) the cause acts alone but only has predictive power if very accurately measured, and we can't get such quality measures.  If a causal effect is truly probabilistic, it does not in the usual sense 'determine' the outcome.  And if the cause is but one of many contributors, and hence has weak predictive power, or does so if inaccurately measurable, then arguing for 'determinism' stretches the truth and merits criticism.  It doesn't mean there is no cause, but in these instances we cannot reliably or accurately predict the outcome from observing the cause. 

Likewise for adaptive selectionism or 'Darwinism'.  If selection is weak, sporadic, erratic, or distributed over many different contributing factors, or if there is no selection but only drift, or if there is selection but we have no serious way to argue what its mechanism was, then the adaptationist argument stretches the truth and merits criticism.  Knowing the genes involved in a trait doesn't predict their change from on generation to the next and, indeed, different genotypes can generate the same phenotype, so that we cannot infer the cause from the result.  Again, this doesn't mean there is no cause, but it does mean that selectionism is over-stated.

What we argue when criticizing what we think are excessive claims of genetic determinism or selectionism is that the assertion being made does not bear scrutiny in these above senses.  We're not arguing for mystical causation or effects that are not 'determined' by physical causes.  We may be arguing that we have little idea or way of knowing what the cause(s) was or were, or that the assumption of a kind of causation can be made self-fulfilling rather than really scientifically testable.  It often seems to be true that based on methods and criteria we use today, some of these causal situations simply cannot in principle be worked out beyond some very imperfect level of precision.  Things too probabilistic, or too weak to be understood from the kinds of samples we can actually collect, are simply not accurately predictable from observing putative causes, and that also means we have inadequate ways of even identifying the causes.

We do seem to live in an orderly causal world.  There are 'laws' of Nature, even if the word is a human one that doesn't imply a law-giver.  Whether causation can be truly probabilistic, and whether there may be causal aspects whose very existence humans have not learned to detect or characterize, we have no idea.  Nor does anybody else.  There are wild theories of multiple universes to get around pure probabilistic causes, and things like dark matter and energy to get around some of what we observe in ordinary matter.  Who knows what else someone may some day discover.  Given this, we believe that more circumspection is in order about causal claims in the life sciences.  In part this is because science has practical implications for society, can be used towards evil or harmful ends (even if unintentionally), and costs resources that could be used for other things, if we had a less lobbying-based or ideological social environment in terms of making such decisions.

To argue that someone is a 'determinist' is not to label them with a slur as if they should instead by a mystic or crystal ball reader.  It is to argue that assertions should be tempered, and we should take more seriously the things that are clearly inadequately known but could be quite fundamental.  To be a 'Darwinian' or 'adaptationist' can mean not just that one recognizes the clear truth of evolution as a fact, and that survival requires success by definition, but can refer to someone who goes beyond that, to and assumes what is to be shown, and that certainly is not good science.  One wants to have an interpretive framework, without which science would be difficult if not impossible, but the framework needs to be tested rather than assumed.

Assuming a framework--being an 'ist'--may be good for hustling attention or grants, but not for a more serious--if avowedly less complete--understanding of things that we now have or than the ists of this world would lead you to believe.

Progress -- complex diseases are still complex

Ciliopathies are a class of disorders recognized only relatively recently.  They are genetic disorders that affect the function of the primary, or non-motile, cilium, of which most mammalian cells have one. The normal function of these organelles still isn't well-understood, and they were long thought to be vestiges of the eukaryotic cell's evolutionary past, but now they are thought to be 'cellular antennae', involved in sensing a wide variety of signals -- chemical sensing, temperature sensing, and the sensing of movement, at least, and in vertebrate development.  Here's a useful description of primary cilia.


Eukaryotic cilium.

A number of rare diseases have been associated with cilial dysfunction, including spina bifida, some forms of retinitis pigmentosa, some obesity, some diabetes and liver disease, some breathing disorders, and so forth.  A paper in last week's Science by Lee et al. describes one ciliopathy, Joubert's syndrome, a rare genetic disorder that affects the cerebellum, and thus balance and coordination.  This is of general interest because, as a commentary in the same issue points out, it elucidates just one aspect of why complex diseases can be so difficult to understand.

Lee et al. identified a gene, a TMEM (transmembrane) gene, that seemed to be responsible for Joubert's syndrome in 5 of the 10 families in their study.  The disorder in the other families, who did not carry the same gene variant, seemed to be phenotypically identical, so they resequenced the area around the gene in question to look for possible causative variants nearby.  Sequencing of the 'exome' has become de riguer in recent years (that is, all the exons, or coding regions, in a genome; as this is only ~1% of the genome, it's a lot cheaper and faster than sequencing the entire genome).  But, as this paper and commentary point out, restricting the search only to exons can miss important variants.

Indeed, Lee et al. found mutations in the neighboring related TMEM gene.  Both genes, TMEM138 and TMEM216, encode transmembrane proteins, that is, proteins that rest across cell membranes with part sticking out into the space surrounding the cell where it can monitor aspects of the environment, and the  other part remaining inside the cell.  But the authors found no homologous regions in the genes or the resulting proteins, and thus nothing that explained why the disease could be the same in all families.  This prompted them to look for shared sequence in the regulation of the expression of the two genes.  

To test for coordinated expression, we examined tissue-expression patterns of human TMEM138 and TMEM216 using the microarray database and in situ hybridization of human embryos. We found tight coexpression values of human TMEM138 and TMEM216 across the major tissues, including the brain and kidneys, and similar expression patterns in various tissues, including the kidneys, cerebellar buds, and telencephalon, at 4 to 8 gestational weeks (gw) of human embryos. To test whether this coordinated expression was due to the adjacent localization, we compared mRNA levels in zebrafish versus mice, representing species before and after the gene rearrangement event. Using quantitative polymerase chain reaction (qPCR), we detected tightly coordinated expression levels in mice compared with those in zebrafish (correlation coefficient r = 0.984 versus 0.386), which suggests that TMEM138 and TMEM216 might share regulatory elements (REs) within the ~23-kb intergenic region. We further examined several experimental features and found that regulatory factor X 4, a transcription factor regulating ciliary genes, binds a RE conserved in the noncoding intergenic region to mediate coordinated expressions of TMEM138 and TMEM216

Further analysis leads them to suggest that both genes are necessary for normal development of the cilium, and that this is because they are regulated by a shared intergenic region, a 'cis-regulatory module', or CRM, a binding site for transcription factors that regulate nearby genes but that is not itself part of those genes.  How these modules arise or how the coordinated expression of genes evolves is not well-understood, but this CRM seems to explain the pattern Lee et al. found in the Joubert syndrome families they studied.

Aravinda Chakravarti and Ashish Kapoor say in their commentary on this paper, and Mendelian disease in general, that this work represents a maturing of the understanding of complex genetic disease.  The genetics community should no longer be focused on single gene mutations, or even exomes (the protein-coding sections of 'genes'), but instead should recognize that complex diseases will require complex explanations.

Mutation analyses of single-gene defects have identified two puzzles: One is that not all individuals with a specific disorder have identifiable coding mutations; the other is that not all individuals with identical mutations, even in the same family, are equally affected, and some may be symptom-free. The first mystery has many suspected causes: The disorder may be due to another gene—even the adjacent one, as Lee et al. demonstrate—or arise from mutations in a gene's regulatory sequences, or be a phenocopy (a trait that is not of genetic origin but is environmentally induced and mimics the phenotype produced by a gene). This is a persistent challenge in studying an outbred organism like humans; just because a disorder is monogenic does not imply that it is monocausal. The second problem is more mysterious and far less understood. Phenotypic discordance, or variation in disease penetrance, between identical mutation bearers could result from differential environmental exposures (such as normal intelligence versus mental retardation in diet-treated versus untreated phenylketonuria). 

The goal remains to determine causation as well as to predict disease.  The pendulum keeps swinging between the search for common and rare variants with which to do this -- as this commentary says, "Studies of Mendelian disease should also move from its preoccupation with rare variants to a focus on common polymorphisms, particularly at regulatory sequences affecting either rare disorders like Hirschsprung disease or common disorders like myocardial infarction."

One reason for the current focus -- should we call it a 'fad'? -- on rare variants is that the heavily touted promise that everything in the universe would be explained as being due to common genetic variants (and hence attractive to pharmaceutical companies and useful for widespread risk prediction) was that the theory has proven largely to be a bust.  So since nobody will give up on predictive genotyping, the move was to rare variants which, not incidentally, will require extensive DNA sequencing, data bases, analysis and the grants that go with them, to find and document.  It's difficult not to wax cynical in this way.

As we have written many times, here and elsewhere, when there are many pathways to the same phenotype, including gene by environmental interactions, and when everyone is genetically unique, the idea that most cases of rare or common diseases can be explained or predicted is likely to be an unattainable goal. As a rule, causation involves a spectrum of strong and weak, common and rare, interacting effects.

Still, it is a sign of progress when major players, not just those of us working on a smaller scale or even those on the sidelines, are cautioning about the ineffectiveness of looking for answers only at single genes or coding regions, or in enormous studies. 

The ethics of artificial meat

A lab at Maastricht University in the Netherlands has just announced the successful use of stem cells to grow muscle artificially.  They took some stem cells from a cow, and grew them in tissue culture, and now have strips of muscle 2cm long, 1 cm wide and a mm thick.  It's currently very pale in appearance, but they will eventually add fat and blood to better mimic actual meat.  Getting it to taste like meat is a another matter, but the researchers believe it's possible. 

Why make artificial meat?  As the world population grows, the demand for meat grows as well, but raising meat the natural way is very costly, and is likely to only get more so.  Agriculture is in many ways a destructive enterprise -- as currently practiced it requires many tons of fertilizers, herbicides, pesticides, and the diversion of much water, not to mention land, to produce what we eat.  And, no matter how you feel about killing animals to eat, the production of meat is particularly inefficient and wasteful -- 100g of vegetable protein yields only 15g of animal protein -- it's only 15% efficient.  Mark Post, the Dutch researcher whose lab is making the meat, believes that artificial meat can be 50% efficient.  It would also have less of an impact on natural resources.  And, the stem cells from just one cow (it's not clear from the reports whether the cow has to be killed for the stem cells to be harvested) can potentially feed millions.

From a humanitarian point of view, with artificial meat no cow needs to suffer feed-lot crowding and the kind of manipulation and minimal life that big herding often involves.  No fear, no line-up to the abattoir.  We presume that while muscle cells 'want' to live and stay alive, they do not have consciousness or sentient fear or suffering of the kind that whole animals with brains have.  So, regardless of efficiency considerations, this seems like a good use of science.

But then, one can ask, why make artificial meat when we can just not eat any meat at all?  That would be an even more truly efficient solution.  The demand for meat is rising especially rapidly in countries with a rapidly expanding middle class, such as India and China.  To expect them not to eat meat, when those of us in countries that have long been rich have been eating our fill for a long time, would just like expecting them to take equal responsibility for global warming, or to not destroy the rainforest when what they really need is land to plant vegetables.  Arrogant on our part.

Is this as proper use of technology, or should one resist it because it simply avoids facing up to the real global needs for food efficiency?  McDonald's will have their answers to these questions, but you as world citizens must have yours -- and express it.

Claiming more? Show it! Faster than a speeding neutrino!

Marcello Truzzi, sociologist and founder or co-founder of a number of organizations investigating extraordinary claims, is said to have coined the phrase, "Extraordinary claims require extraordinary proof."  Carl Sagan popularized this phrase as "Extraordinary claims require extraordinary evidence."  And so it is with the recent claim that neutrinos can exceed the speed of light, the proverbial c in e=mc^2.

We posted about this remarkable claim when it first came out (here), and then when the same group claimed to have replicated their own results (here), and of course the story was all over the web.  As it should have been, because if true, it would have overturned one of the most robust theories in physics.  The finding was not only extraordinary, it was revolutionary.  (Ethan Siegel's blog, Starts With a Bang, has a bunch of very fine, accessible and detailed explanations of the whole story as it has unfolded.)

Flaws in the experiment are now being reported.  Here's the piece in Nature, but it's also everywhere -- like on the BBC.  Science Insider broke the news, and Siegel explains the possible alternative scenarios here.

The same group, OPERA, that made the original finding is now identifying their likely errors.  As the Nature piece explains it:

...according to a statement OPERA began circulating today, two possible problems have now been found with its set-up. As many physicists had speculated might be the case, both are related to the experiment’s pioneering use of Global Positioning System (GPS) signals to synchronize atomic clocks at each end of its neutrino beam. First, the passage of time on the clocks between the arrival of the synchronizing signal has to be interpolated and OPERA now says this may not have been done correctly. Second, there was a possible faulty connection between the GPS signal and the OPERA master clock.

The Science Insider story writes that if the group does the equivalent of rebooting their computer -- simpler, actually; just tightening the connection between the fiber optic cable that connects to their GPS receiver -- that one fix would add those missing 60 nanoseconds back to the neutrino travel time.

Oops.


Though, the BBC tells the story differently.  As they tell it, OPERA says there's another possible explanation, which has to do with "the oscillator used to produce the events time-stamps in between the GPS synchronizations.  These two issues can modify the neutrino time of flight in opposite directions."   The BBC says that tightening the connection would increase the apparent already ultra-fast speed, while fixing the oscillator would slow it down.  That is, either they are more right, or they know why they're wrong.

So, apparently, within the group there's still hope of a revolution.  They'll keep us posted.  And while they work on tightening up experimental conditions, a group at Fermilab in Illinois and a group in Japan are hoping to test this themselves.

While we leave this to the physicists to sort out, there are still some lessons to be learned for the rest of us. The speed of light is a given in physics -- it has been tested without serious challenge for a century, and any suggestion that it can be exceeded must be met with skepticism. There are simply too many direct experiments, and zillions more indirect ones, that seem consistent with the theory. Were he alive today, Marcello Truzzi would surely have written the neutrino results up in his journal, The Zetetic (The Skeptic).

We don't have the same kinds of laws in Biology, as a rule, but evolution and the nature of genes are aspects that seem to come about as close to fundamental theory as we currently can get. And there are important lessons to learn about life at large, compared with what we learn from the ultra-tiny neutrino.

Whether the speed of light is actually 100.000000000000% constant in every 'vacuum' and every part of the universe, apparently has to do with various theoretical issues or explanatory frameworks that are beyond what we know anything about. However, it is close enough and a robust enough finding that we can argue about whether a neutrino can violate this law at all. Any deviation, no matter how tiny, will grab major headlines and be good for the physics professor business!

We are not qualified to say whether a quadzillionth of a percent deviation from the proverbial c, will change much that is of even theoretical importance. Does every single last photon always stream along at exactly the same speed all the time? That kind of constancy would be basically unprecedented in the word of even science's everyday life. What if it simply showed that c is not an eternally totally fixed value but that photon-travelers, like neutrinos, sometimes hustle, sometimes dawdle a tiny tad?

Be that as it may, we have little if anything that is anywhere near so precise, exact, and universal about life or evolution. The proof of this is how easily--routinely, even--professors and their reporter-acolytes proclaim essentially revolutionary, major, dramatic, or transformative new findings.

A new fossil often is claimed to entirely overturn everything we said we knew about human evolution, or so the media and the discoverer will have you believe (as we have commented recently in MT). A fossil found sucking its thumb would be argued to completely revolutionize our understanding of the evolution of thumbs (and depending on its age at death, perhaps also about the length of childhood in our ancestors!).

In contemporary genetics, which is Gee!Wash in GWAS, first the idea that would revolutionize everything was that common variants cause common disease; then that to a great extent the same gene variants cause the same disease in all populations; then it was rare variants are the culprits to be discovered with wholegenome sequence; then epigenetics; then copy-number variation; then gene regulatory networks. The chain of 'omics' revolutions is, so far, endless. Medicine will be revolutionized by being genomically personalized.

We are truly learning a lot about life, but the major changes in views claimed for each new finding or paper shows clearly that we simply do not have our theoretical 'neutrinos'. Our knowledge is too easy to 'revolutionize' by the next technology that comes down the pike, to be considered theoretically very sound knowledge.

Now, physicists will be melodramatic about whatever is found in those little hyper-travelers, just as biologists are about how every new genetic variant they discover that will guarantee immortality. And, not least of the physicists' worries in all this is whether it will affect their funding. They have their sick side just as we do: that finding out truth will determine whether we can keep our jobs--even though our jobs are, supposedly, to find out truth!

The educated public, and scientists ourselves, need to realize and acknowledge how very far we are from physics-like understanding of life. And given that, and the topsy-turvy claim-laden recent history of genetics, medical genetics, and evolutionary biology, there should be some slowing down, taking stock, and tempering of our claims. When we are this far from absolute truths, and no really sound underlying theory, we have no business over-promising, much less being in such a frenzied (fund-seeking-based) race.

Perhaps it's time for some medicine for our ailment: some sanctions for claiming too much, and not acknowledging the depth of our own loose connections. Or some accountability for real progress in (say) curing disease, rather than the moving target of promises not met. This is because if we had some accountability or didn't rush for headlines and snow-jobs at every turn, we might temper our thoughts as well as our claims, and spend more time and effort understanding how multiple, variable, hard-to-measure causal elements worked together, and varied, in relation to biological traits normal and disease, and their evolution.

We face very challenging and legitimate issues in biology, both to understand evolution and to bring about major biomedical advances. We should be able to make much better progress if we knuckle down more intensely to understand the complexity of life's complexity, rather that slicing and dicing it up into this or that one-size, large-scale, comprehensively enumerative ('omic') style approach that essentially promises to turn complexity into simplicity. We know the professional pressures that push us in the latter direction, and we all feel them, and we inculcate new members of the guild into that environment. But nobody seems to be resisting these pressures.

Basically, like physicists, we should own up to our rather large array of loose connections. Until we do, there is something well-known that's Faster than a Speeding Neutrino. It is the speed with which biologists rush to call a press conference to announce their latest Discovery.