It's not just about psych studies; it's about core aspects of inference.

A paper just published in Science by the "Open Science Collaboration" reports the results of a multi-year multi-institution effort to replicate 100 psychology studies published in three top psychology journals in 2008.  This effort has often been discussed since it began in 2011, in large part because the importance of replicability in confirming scientific results is integral to the 'scientific method,' but replicability studies aren't a terribly creative use of a researcher's time, and they're difficult to publish so they aren't often on researchers' To-Do lists.  So, this was unusual.

Les Twins; Wikipedia
There are many reasons a study can't be replicated.  Sometimes the study was poorly conceived or carried out (assumptions and biases not taken into account), sometimes the results pertain only to the particular sample reported (a single family or population), sometimes the methods in an original study aren't described well enough to be replicated, sometimes random or even systematic error (instrument behaving badly) skews the results.

Because there's no such thing as a perfect study, replication studies can be victims of any of the same issues, so interpreting lack of replication isn't necessarily straightforward, and certainly doesn't always mean that the original study was flawed.

The Open Science Collaboration was scrupulous in its efforts to replicate original studies as carefully and faithfully as possible.  Still, the results weren't pretty.  The authors write:
Replication effects were half the magnitude of original effects, representing a substantial decline. Ninety-seven percent of original studies had statistically significant results. Thirty-six percent of replications had statistically significant results; 47% of original effect sizes were in the 95% confidence interval of the replication effect size; 39% of effects were subjectively rated to have replicated the original result; and if no bias in original results is assumed, combining original and replication results left 68% with statistically significant effects.
Interestingly enough, the authors aren't quite sure what any of this means.  First, as they point out, direct replication doesn't verify the theoretical interpretation of the result, which could have been flawed originally, and remain flawed.  And it's impossible to know when a study is not replicated why that is, whether the original was flawed or the replication effort was flawed, or even both were flawed.

This effort has been the subject of much discussion, naturally enough.  In a piece published last week in The Atlantic, Ed Yong quotes several psychologists, including the project's lead author, saying that this project has been a welcome learning experience for the field.  There are plans afoot to change how things are done, including pre-registration of hypotheses so that the reported results can't be cherry-picked, or increasing the size of studies to increase their power, as has been done in the field of genetics.

We'll see whether this is just a predictable wagon-circling welcome, or really means something.  One has every reason to be skeptical, and wonder if these fields really are sciences in the proper sense of the term.  Indeed, it's quite interesting to see genetics held up as an exemplar of good and reliable study design.  After billions of dollars being spent on studies large and small of the genetics of asthma, heart disease, type 2 diabetes, obesity, hypertension, stroke, and so on, we've got not only a lot of contradictory findings, but most of what has been found are genes with small effects.  And epidemiology, many of the 'omics fields, evolutionary biology, and others haven't done any better.

Why?  The vagueness of the social and behavioral sciences is only part of the problem (unlike, say, force, outcome variables such as stress, aggression, crime, or intelligence are hard to consistently define, and can vary according to the instrument with which they are measured).  Biomedical outcomes can be vague and hard to define as well (autism, schizophrenia, high blood pressure).  We don't understand enough about how genes interact with each other or with the environment to understand complex causality.

Statistics and science
The problem may be much deeper than any of this discussion of non-replicable results suggests.  First, from an evolutionary point of view, we expect organisms to be different, not replicates.  This is because mutational changes (and recombination) are always making each individual organism's genotype unique and, second, the need to adapt--Darwin's central claim or observation--means that organisms have to be different so that their 'struggle for life' can occur.

We have only a general theory for this, since life is an ad hoc adaptive/evolutionary phenomenon. Far more broadly than just the behavioral or social sciences, our investigative methods are based on 'internal' comparisons (e.g., cases vs controls, various levels of blood pressure and stroke, fitness relative to different trait values) to evaluate samples against each other, rather than as representations of an externally derived, a priori theory.  When we rely on statistics and p-value significance tests and probabilities and so on, we are implicitly confessing that we don't in fact really know what's going on, and all we can get are a kind of shadow of the underlying process that is cast by the differences we detect, and we detect them with generic (not to mention subjective) rather than specific criteria. We've written about these things several times in the past here.

The issue is not just weakly defined terms and study designs. As Freeman Dyson (in "A meeting with Enrico Fermi") wrote in 2004:
In desperation I asked Fermi whether he was not impressed by the agreement between our calculated numbers and his measured numbers. He replied, "How many arbitrary parameters did you use for your calculations?" I thought for a moment about our cut-off procedures and said, "Four." He said, "I remember my friend Johnny von Neumann used to say, with four parameters I can fit an elephant, and with five I can make him wiggle his trunk." With that, the conversation was over. . . .
Here, parameters refers to what are more properly called 'free parameters', that is, ones not fixed in advance, but that are estimated from data. By contrast, for example, in physics the speed of light and gravitational constant are known, fixed values a priori, not estimated from data (though data were used to establish those values). We just lack such understanding in many areas of science, not just behavioral sciences.

In a sense we are using Ptolemaic tinkering to fit a theory that doesn't really fit, in the absence of a better (e.g., Copernican or Newtonian) theoretical understanding.  Social and behavioral sciences are far behind the at least considerably more rigorous genetic and evolutionary sciences when the latter are done at their best (which isn't always).   Like the shadows of reality seen in Plato's cave, statistical inference reflects the shadows of the reality we want to understand, but for many cultural and practical reasons we don't recognize that, or don't want to acknowledge it.  The weaknesses and frangibility of our predictive 'powers' could, if properly understood by the general public, be a threat to our business and our culture doesn't reward candor when it comes to that business.  The pressures (including from the pubic media, with their own agenda and interests) necessarily lead to reducing complexity to simpler models and claims far beyond what has legitimately been understood.

The problem is not just with weakly measured variables or poorly defined terms of, for example, outcomes.  Nor is the problem if, when, or that people use methods wrongly.  The problem is that statistical inference is based on a sample and is often retrospective, or mainly empirical and based on only rather generic theory.  No matter how well chosen and rigorously defined, in these various areas (unlike much of physics and chemistry) the estimates of parameters and the like fitted to data that is necessarily about the subjects past, such as their culture or upbringing or lifestyles, but in the absence of adequate formal theory, these findings cannot be used to predict the future with knowable accuracy.  That is because the same conditions can't be repeated, say, decades from now, and we don't know what future conditions will be, and so on.

Rather alarmingly, we were recently discussing this with a colleague who works in very physics- and chemistry-rigorous material science.  She immediately told us that they, too, face problems in data evaluation with the number of variables they have to deal with, even under what the rest of us would enviously say were very well-controlled conditions where the assumptions of statistics--basically amounting to replicability of some underlying mathematical process--should really apply well.

So the social and related sciences may be far weaker than other fields, and should acknowledge that. But the rest of us, in various purportedly 'harder' biological, biomedical, and epidemiological sciences, are often not so much better off. Statistical methods and theory work wonderfully well when their assumptions are closely met.  But there is too much out-of-the-box analytic toolware, that lures us into thinking that quick and definitive answers are possible.  Those methods never promise that because what statistics does is account for repeated phenomena following the same rules, and the rule of many sciences is that, in their essence they are not following such rules.

But the lure of easy-answer statistics, and the understandable lack of deeply better ideas, perpetuates the expensive and misleading games that we are playing in many areas of science.

Regatta Day



Today was our annual Regatta Day in Portscatho.......A sandcastle competition was followed by races on the beach for the kids; then a raft race and swimming races and kayak races. Unfortunately there wasn't enough wind for the working boats to compete, but they were towed round to the bay anyway so that we could enjoy their spectacle and the crews could come ashore for a pasty and a pint!

Sitting on the slip enjoying the events, and having fun on the sand....



The bunting was up in the streets,

and I took full advantage of the fine weather to spill out onto the pavement....

Such a lovely day meeting all sorts of lovely people; friends old and new, locals and visitors. Just a great way to round off the summer!
Have a happy Bank Holiday weekend xxx

İç Ses - 17

 Beklemek... 
 Yeryüzü laneti...
 Öyle bir lanetki sinsice ; bekleyenin tüm dünyasına yayılan, onu hayatın dışına atan, andan uzaklaştıran ... 
  Beklemek umut etmenin aksine insanı takatsiz ve yalnız  bırakan bir kabus. 
  Hayatın herşeye rağmen devam etmeye kurulu düzeninin içinde bekleme hali bekleyenini bir kenara itip şimdi sen bir dur diyor; hayat akacak, insanlar bir yerlere gidecek, yeni şeyler başlayacak, herkes için hayat devam edecek ama sen BEKLE. 
    Orta yerde , ne sağa bir adım ne sola...
     Ne başlayabil,  ne de vazgeç...
     Sadece bekle.  
      Bekle
        Bekle
           B.... 
            
                      ******
     Bu lanetin içine düşmüş, yavaşlayıp, yalnızlaşan ruhun elinde kalan tek şey gökyüzü oluyor bu durumda. 
Yeryüzünün insan eliyle oluşmuş zaman algısına yenilmek madem beklemek, sen de göğe bak yeniden. 
    Çünkü hayat bulutu umut geçiyor gökyüzünde. 
    Sen en iyisi göğe bak yeniden. 



Who should take statins? Is heart disease predictable?

Who should take statins.....besides everyone?  I thought a lot about this when I was working on a lecture about predicting disease. The purpose of statins, of course, is to prevent atherosclerotic cardiovascular disease in people at risk (how well they do this is another issue). The challenge is to identify the people 'at risk'.  I wrote about this in July, but I've been playing some more with the ideas and wanted to follow up.

Statins are a class of drug that, in theory, work by lowering LDL (low-denstity lipoprotein) levels. They do this by inhibiting HMG-CoA reductase, an enzyme that has a central role in the production of cholesterol in the liver.  LDL, the so-called 'bad' cholesterol, isn't actually just cholesterol, but has been linked to risk of heart disease because, as a lipoprotein, its job is to transport cholesterol to and from cells.  It is bound to cholesterol.  What's measured when we have our blood drawn for a cholesterol test is LDL-C, the amount of cholesterol bound to LDL particles (LDL-C), as well as HDL-C, the 'good' cholesterol package, which transports LDL-C from cells, leading to lower blood cholesterol levels.  Cholesterol makes plaque and plaque lines and hardens arteries, which occludes them and leads to stroke and heart attack.  Lower the amount of LDL, and you lower the risk of arterial plaque deposits.

The connection between cholesterol and heart disease was first identified in the Framingham Study in the 1950's and 60's, and this lead directly to the search for drugs to lower cholesterol.  Statins were developed in the 1970's and 80's, and after some fits and starts, began to be used in earnest in the late 1980's.  Statins work by inhibiting the liver cells' synthesizing of new cholesterol, that is, cholesterol that isn't due taken in in the diet.

Akira Endo, one of the first scientists to look for cholesterol-lowering compounds, reviewed the history of statins in 2010.  He described the many studies of the effects of these drugs, saying "The results in all these studies have been consistent: treatment with statins lowers plasma LDL levels by 25–35% and reduces the frequency of heart attacks by 25–30%" (Akira Endo, Proc Japan Acad, Series B, 2010).

A systematic review of the literature on the effectiveness of statins was published by the Cochrane Organization in 2012. The review reports, "Of 1000 people treated with a statin for five years, 18 would avoid a major CVD event which compares well with other treatments used for preventing cardiovascular disease."  This suggests, of course, that 982 people took statins with no benefit, and perhaps some risk, as statins are associated with muscle pain, slightly increased risk of type 2 diabetes, liver damage, neurological effects, digestive problems, rash and flushing, and other effects.  But more on this below.

So, who should take statins? 
Until 2013, the recommendation was that anyone with a modest risk, as assessed by the Framingham Risk Calculator (I've read that that means from 6.5% to 10% 10-year risk) would likely be prescribed statins.  The interesting thing, to me, about this risk calculator is that it's impossible to push the risk estimate past "greater than 30%", even at maximum allowable cholesterol, LDL, and systolic blood pressure, and being a smoker on blood pressure medication.  Which means that there's a lot that this calculator can't tell us about our risk of CVD, based on the best risk factors known.

Framingham Risk Calculator

In 2013, the American Heart Association/American College of Cardiology revised their criteria for statins.  Now, they are recommended for people who have had one CVD event in order to prevent another; for people with primary elevations of LDL-C greater than 190mg/dL; people 45-70 years old who have diabetes and LDL-C between 70 and 189mg/dL, and people 45-70 years old with LDL-C between 70 and 189mg/dL and estimated 10-year cardiovascular disease risk of 7.5% or higher.

The first three criteria are straightforward.  If statins lower LDL, and lower LDL lowers risk of ASCVD (artherosclerotic cardiovascular disease), then taking them should be beneficial.  But then we're back to a risk calculator again to estimate 10-year risk.


ACC/AHA


It has been revised.  Now included are ethnicity (well, White, African American or other), and diabetic status (yes/no), and estimated lifetime risk.  And, now it's possible to push 10-year risk up past 70%, which I discovered by playing around with the calculator a bit.  Whether or not it's a more accurate predictor of a cardiovascular event is another question.

Here's the lowest risk I could come up with, 0.1% 10-year risk.  The recommendations offered are not to prescribe statins.

Lowest 10-year risk
Here's the highest risk I could force the calculator to estimate.  Ten-year risk for a female with these risk factors is higher than for a male, but lifetime risk is lower.  That seems strange, but ok, it must reflect association of risk factors including sex with disease at the population level.  


Compared with the Framingham calculator, risk estimation seems to be getting more precise. Or at least bolder, with estimates up in the 70's.  But is the new calculator actually better at predicting risk than the old one? A paper was recently published in JAMA addressing just this question ("Guideline-
Based Statin Eligibility, Coronary Artery Calcification, and Cardiovascular Events," Pursnani et al.) They identified 2435 people from the Framingham study who had never taken statins. Their medical history allowed the authors to determine that, based on the old guidelines, 14% would have been 'statin eligible' compared with 39%, based on the new 2013 guidelines.

Among those eligible by the old guidelines, 6.9% (24/348) developed CVD compared with 2.4% (50/2087) among noneligible participants (HR, 3.1; 95% CI, 1.9-5.0; P less than .001). Under the new guidelines, among those eligible for statins, 6.3% (59/941) developed incident CVD compared with only 1.0% (15/1494) among those not eligible (HR, 6.8; 95% CI, 3.8-11.9; P less than .001).

So, put a whole lot more people on statins, and you prevent an additional very small number of CVD events; 1.0% vs 2.4%.  And, 93% of those ‘eligible’ for statins did not develop disease. Nor, of course, do statins prevent all disease.  Actually, if everyone in the population were covered, statins would be preventing as many events as they could possibly prevent, but in a small minority of the population.  That is, 90+% of people considered to be at 'high-risk' of disease don't go on to develop disease.  Is it worth the side effects and cost to put so many more people on statins to prevent the 1.4% more CVD that these new guidelines are preventing?  Well, heart disease is still the number one killer in rich countries, and 40+% of the population is currently taking statins, so a lot of people have decided that the benefits do outweigh the risks.

Another question, though, is more fundamental, and it concerns prediction.  The calculator seems to now be predicting risk with some confidence.  But, let's take a hypothetical person with a somewhat elevated risk.  Her cholesterol is higher than the person above who's at lowest risk, but that's due to her HDL.  Her systolic blood pressure is high at 180, which is apparently what bumps up her risk, but her 10-year risk is still not over 7.5% so the recommendation is not statins, but lifestyle and nutrition counseling.  (Though, the definition of 'heart-healthy diet' keeps changing, so what to counsel this person with low risk seems a bit problematic, but ok.)


Low enough risk that statins aren't advised.

Now here's the same hypothetical person, but she's now a smoker, on medication to lower her blood pressure (and her b.p. is still high) and she has diabetes.  Her 10-year risk of ASCVD jumps to 36.8%.  This makes sense, given what we know about risk factors, right?  The recommendation for her is high-intensity statins and lifestyle changes -- lose weight, do regular aerobic exercise, eat a heart-healthy diet, stop smoking (easy enough to say, so hard to do, which is another issue, of course, and the difficulty of changing all these behaviors is one reason that statins are so commonly prescribed).





But now I've lowered her total cholesterol by 70mg/dL, which is what statins ideally would do for her.  Even so, the American College of Cardiology/American Heart Association recommendation is for 'high-intensity statin therapy' and lifestyle counseling.  The calculator doesn't know this, but statins have already done everything they are likely to do for her.




So, let's add lifestyle changes.  But, even when she quits smoking, her 10-year risk is 20%.  So let's say we cure her diabetes -- even then, she's still at high enough risk (9%) that 'moderate to high-intensity statins' are recommended.  I'm confused.  I think even the calculator is confused.  It seems there's a fuzzy area where statins are being recommended when what's left to do is, say, lower blood pressure, which statins won't do.  This hypothetical woman probably needs to lower her weight to do that, and statins aren't going to help with that, either, but still they're recommended.  Indeed, one of the criticisms of this risk calculator when it was released in 2013 was that it overestimates risk.  Perhaps so, but it also seems to overestimate the benefit of statins.  


Further, it seems there are a lot of type 1 errors here.  That is, a lot of people are considered 'at-risk' who wouldn't actually develop cardiovascular disease.  Risk of 7.5% means 7.5 of 100 people with a given, equal set of risk factors are expected to develop disease.  That means that 92.5 would not.  And that means that we have a pretty rough understanding of heart disease risk.  The strongest risk factors we know -- smoking, high LDL-C, diabetes and hypertension -- can be expected to predict only a small fraction of events.

And that means that either something else is 'causing' cardiovascular disease in addition to these major known risk factors, or something is protecting people with these risk factors who don't go on to develop disease.  Family history is a good or even the very best single predictor (why isn't it taken into account in these calculators?) which suggests that it's possible that genetic risk (or protection) is involved, but genome wide association studies haven't found genes with large effects.  Of course, family history is highly conflated with environmental factors, too, so we shouldn't simply assume we need to look for genes when family history indicates risk.  Anyway, it's unlikely that there are single genes responsible for ASCVD except in rare families, because that's the nature of complex diseases.  Instead, many genes would be involved, but again as with most complex diseases, they would surely be interacting with environmental risk factors, and we don't yet know understand how to identify or really understand gene by environment interaction.

And then there's the truly wild card!  All of these risks are based on the combinations of past exposures to measured lifestyle factors, but the mix of those and the rise of other new lifestyle factors, or the demise of past ones, means that the most fundamental of all predictors can itself not be predicted, not even in principle!

So, statins are a very broad brush, and a lot more people are being painted with them than in fact need to be.  The problem is determining which people these are, but rather than zoom in with more precision, the updated calculator instead paints a whole lot more people with the brush.  This isn't the calculator's fault.  It's because understanding risk is difficult, ASCVD is a large and heterogeneous category, and prediction is very imprecise -- even for many 'simple' Mendelian disorders.  If ASCVD were caused by a single gene, we'd say it had very low penetrance.  And we'd want to understand the factors that affect its penetrance.  That's the equivalent to where we are with cardiovascular disease.

I was interested to see that the 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk says something that I have said so many times that I decided not to say it again in this post.  But, I'm happy to see it elsewhere now.  The guideline committee itself acknowledges the issue, so I'll let them explain the problem of assessing risk as their calculator does.
By its nature, such an approach requires a platform for reliable quantitative estimation of absolute risk based on data from representative population samples. It is important to note that risk estimation is based on group averages, which are then applied to individual patients in practice. This process is admittedly imperfect; no one has 10% or 20% of a heart attack during a 10-year period. Individuals with the same estimated risk will either have or not have the event of interest, and only those patients who are destined to have an event can have their event prevented by therapy.
It's the problem of using group data, which is all we've got, to make clinical decisions about individuals.  It's the meta-analysis problem -- meta-analyses compile data from many individual studies to produce a single result that certainly reflects all the studies, because they were all included in the statistics, but it doesn't represent any of them with precision.  Ultimately, it's the problem that these sorts of inferences must be based on statistical analysis of samples -- collections -- of individuals.  We do not have an easy way around this, including the N of 1 studies currently being proposed.

Finally, here's a meta-thought about all this.  Ken and I were in Finland this month co-teaching a course, Logical Reasoning in Human Genetics, with colleagues, including Joe Terwilliger.  Joe said multiple times, "We suck at finding candidate genes because we don't know anything about biology.  We're infants learning to crawl."  The same can be said about epidemiological risk factors for many complex diseases -- we suck at understanding the causes of these diseases, and thus we suck at prediction, because we don't really understand the biology.

İç Ses - 16

Huyu bu her akşam batacak, 
       olanın olmayanın üstünü örtsün gece ; karanlıkta  huzur bulsun bekleyen diye ille de batacak. 
       Turuncuyla bitip turuncuyla başlayacak.
Huyu bu her akşam batacak ki .... 


The Rosse Leviathan and the acceptance of evolution

It is well-known that the 19th century realization by Darwin and others that life evolved through historical processes rather than divine creation and intervention dealt a staggering blow to many religious believers at the time.  It still does.  Divine creation was a complex idea, before evolutionary theory allowed the text to be seen as a metaphorical idea, at least for biblical literalists rather than deists, who could accept that God started everything and then let it roll on by itself.

Pre-evolutionary thought
The idea of evolution can be seen in early writings in ancient classical times and in the Islamic glory years.  But these were rather speculative and not what we now would call 'scientific'.  Instead, it was far more obvious and natural to think of creation as static.  That is, one of the important concepts of pre-evolutionary thought was permanence.

Permanence didn't mean that nothing ever changes.  After all, planets move.  But motion isn't the same as coming into existence anew.  The problem was that God has purportedly created 'the' universe, as such, reflecting His glory in our lives.  Likewise, animals and plants move and are produced, but not out of thin air, only as offspring of existing members of their kind.  What was seen as not changing were the types of animals and plants--species, and the specific objects in the cosmos. These were permanent, it was widely believed, because God made it so.

Evolution suggested that basic things came into existence on their own, as it were.  If that were so, then God's work would be harder to understand, or so it would seem given the biblical literalist view of things before the age of science, even into the 19th century.

The point is that 'evolution' was a threatening idea not just to the world of biology in relation to Darwin's and Wallace's work, but more generally.  Or, more generally, Darwin's and Wallace's ideas flopped down amidst what was already a controversial area.  This can be seen in an interesting way in an area of science that otherwise might not seem to be threatening in this way......except that "In the beginning, God created the heavens and the earth".

19th century astronomy
Astronomy is more than just star-gazing in awe of Nature's wonders.  It is about the cosmos, existence itself.  It was long comforting, and pretty well consistent with known facts, to think of the cosmos as centered around the Earth, with the revolving Sun to warm us, and the Music of the Spheres, the stars painted onto crystal spheres, rotating more distantly around the skies.

Galileo's use of the telescope, and work of others tracking planets (mainly, Copernicus), had started to cast doubt on some of these ideas.  The moon and planets weren't perfect spheres, and orbits weren't perfect circles and the Sun was the center of the solar system.  Uncomfortable facts like these did shake religious orthodoxy (in the West, at least), but they really were mainly mathematical re-ordering of the same objects.  More to the point, perhaps, and vital for Isaac Newton, was that the cosmos was orderly--specified by mathematic laws laid down by God (Galileo had had similar ideas). There was absolute location and time, in space, with things moving like clockwork, following the Laws.

One exciting way to study God's work was through telescopes, which had been getting better and better, by far, than what Galileo had to work with.  A famous example is what became the largest telescope in the world in 1854 for nearly a century, in Ireland, affectionately called the Rosse Leviathan. (Rosse was one of the supporters and developers)  A good discussion of this subject is the BBC Radio4 program, Science Stories, July 8, 2015 edition.

Here is an image of the Leviathan:


The Rosse Leviathan, finished 1845
This was a 6-foot reflecting telescope.  Among the amazing things that had been seen in the prior days of astronomy, with weaker instruments, were vague, smeary 'things'.  They were called, appropriately, nebulae.  What were they?

Here are two images from modern telescopy, not the mid-1800s.  Let's look at the top one first.




It was indeed a big smear in earlier telescopes, as if it were a cloud of gas.  If that were the case, perhaps it was condensing into a star with the aid of gravity.  And if that were the case, then the stars in the heavens were not fixed at all, but could come (and perhaps go)!  And in turn, that would mean that the heavens themselves were not permanent: they evolved!  And then what of Genesis and its like?

But what if it's just too far away, and only looks like a smeared cloud of gas?  The new telescopes began to resolve some of these objects, and to show that, in fact, they were points of light--stars--so that, whew!, the Universe was static after all!  Still other nebulae were too far to resolve in that way and the debate was about whether they were, in fact, even more distant stars, or were star-forming clouds.

Spiral formations, now known as galaxies, like the bottom image, were also thought perhaps to be swirls of gas that might be condensing, until they, too were resolved as stars.  But this still left others too far to resolve, or truly gaseous condensations.  Only in the 20th century did light spectrographs show that some of these were, indeed, gas clouds.

We now have a consistent understanding of these various phenomena, and no longer debate whether the universe is constant in the ways religious doctrine had taught.  Nobody was exactly wrong. Swirling spirals can be galaxies, but dust can swirl in as gravity pulls it together in the formation of stars.  The original appearances were ambiguous and the questions about what the clouds were were legitimate.  The interesting aspect is the way in which the interpretation filtered through, and affected, the broader world-views about the nature of existence.  And the relevance of this to biology is (and was) clear.

When all is ready
Exobiologists muse about life elsewhere in space and to date it's no more than musing, really.  But real biologists, who study actual known life on earth, were discovering many facts about life in the mid-19th century that dovetailed with issues about cosmic constancy.

Even as far back as Aristotle's time, fossils of plants and animals were known.  The knowledge was fragmentary and largely ignored rather than studied scientifically, but by Darwin's time two major aspects of change had become very clear.  First was geological change, on land and regarding island chains.  Erosion and mountain building were becoming clear as true phenomena.  This may not really have changed religious feelings if the time periods were consistent with biblical events, like the great flood.  But time was becoming more and more obviously far longer than what Genesis implied.

Fossils had more ominous import.  Species that used to exist, had disappeared, and new species including modern ones appeared here and there.  Georges Cuvier, a believer, suggested, reasonably, that these were events of catastrophic loss but new creation, as part of the Divine plan.

However ideas about biological change and evolution were beginning to swirl.  It was one thing to know that agricultural species had changed (cows gave more milk, sheep had woolier wool, grain yields rose) because of active selection by breeders.  It was not clear up unil then that new species had arisen (agricultural breeding never really produced new species).  But the complex of worldwide data on plants and animals and their distribution, along with fossils and the idea (from agriculture and hobby breeding) that change could be brought about by selection, were forcing a realization that the living world, like the cosmos, might not be as static as dogma held it to be.

In a sense, 'evolution' was 'ready' to be discovered, here, there, and as a more general theme. Ideas about the evolution of society (e.g., Marxism, social Darwinism) were right there with the times, too. This intellectual foment in the new sciences undoubtedly contributed to the discoveries, eventually of the vastness of space and truly gaseous precursors of stars, and of biological evolution.  The discussions 'in the air' set the stage.  But at the same time, the ready resistance was also primed.  That is why, I think, Darwinism hit such a brick wall of resistance from so many intellectuals at the time, and why so many found these ideas so deeply disturbing.

The context of history is important to the development of new ideas, but also to the reaction to them.  Often, ideas in one area of life have impact, or perceived impact, on many others, including deep beliefs about the nature of things.

I think we've now mainly settled into complete comfort with the idea of biological evolution, with no longer any rational arguments against, even if peering into the microscopic nature of genomics still yields a picture as blurry in many ways as the Rosse scope's images.  This is because many aspects of genetic causation remain subtle and elusive, because life seems not as rigidly law-like as physics.  As to cosmology, visual telescopes were only the beginning of a technological odyssey that has shed light onto the origins and development of the universe and has led to general acceptance of the fact of change.  But this hardly diminishes the truly mind-blowing matters, light and dark, that we are learning about, or now know that we still don't know about, regarding the size and scope of the universe(s).

CÂNIM KADINLAR

 

    Küçükken çocukluğumun yazları olduğunu bilmediğim, tüm hayatımın yazları sandığım yazlar (Çanakkale) Biga'da geçerdi. Anneannem başta olmak üzere ,bütün tanışlar, akrabalarımız okulların kapandığı o cumadan sonraki birkaç gün içinde orada olmamızı beklerdi. Ve yaz tatilinin ilk birkaç günü başta mahallenin bakkalı olmak üzere çevredekilere ne zaman geldiğimizi anlatmakla geçerdi.  Bir hafta içinde gelişimizin haber değeri ortadan kalkmış olur , bir yaz önce bıraktığımız kasaba gündemine karışırdık. Annem anneannemin evini dip bucak temizlemiş olur, gidilecek düğünler sıraya konurdu. Birkaç hafta içinde annemin bir sürü teyze kızı, hala kızı, amca kızı akşam oturması olup düşerdi bİzim kapının önüne. Çok kadınlıydı yani benim yazlar. Bu bir sürü kadın farklı kombinasyonlarda farklı evlerde toplanır yemekler yerdi. Etrafta bir sürü çocuk , bol kahkaha ve aslında incir çekirdeğini doldurmayan sebeplerden meydana gelen dargınlıkların barışmaların muhabbeti olurdu. 
  Bir de incir zamanı gidilen köylerde çocukların eline sürülüp verilen salçalı ekmekler. O köy bahçelerinde bir elde salatalık bir elde ekmek dolanan "kızancıklar" . Demlik demlik çay içen anneler, ablalar , teyzeler , ananeler ... 

       

   Bugün o yazların üzerinden neredeyse on sene geçmişken, anneannemin zihnindeki hatıralar gibi zaman da o yıllardan hızla uzaklaşmaya başlamışken yolum yine bir sürü kadının annenin, ablanın , teyzenin , anneannenin olduğu bir bahçeye düştü. Çocukluğumun kulağımdaki tınısına benzer bir tınıda konuşan kadınlar, el birliğiyle kurulan sofralar, öyle gereksiz şatafatla değil hayata rağmen hatta hayata inat mutlu olmaya el çırpan bir sürü kadın... Hayatın ağırlığı karşısında ezilmişliği karşısında bitimsiz bir hüzne ve ağır başlılığa hapsolmuş orta anadolulu kadınlara inat, kemoterapi gününü unutacak kadar hayata karışmaya niyet etmiş Trakyalı kadın bütün yeşiliyle eşlik etti kardeşinin çaldığı darbukanın ritmine. İki demlik çaya karıştı kadınların kahkahaları... Annem ve ben dahil olmak üzere hepimizin kafasında bir sürü soru(n) varken hepimiz el çırptık unutmaya. Ve tüm bunlar olurken  benim zihnimde varlığından bile habersiz olduğum o odada çocukluğumun en güzel anları canlandı. Karşımda yüzünü ilk defa gördüğüm ama ruhlarını çok iyi bildiğim kadınlar, tenimde tanıdığım rüzgar ...

     Yazmalıyım dedim başta kendim sonra bütün kadınlar için yazmalıyım. Buralarda, aynı gök altında canının, cananının kemoterapi gününü unutarak şarkılar türküler söyleyen , torunlarını uyutan ve erişte yapmaya hazırlanan kadınlar var. Ortak kadınlık kederine diklenen kadınlar var. 

Cânım kadınlar .... 







The solution to all professors' wardrobe dilemmas

I swear. The regularly scheduled Mermaid's Tale programming that you've come to expect (and to love?) is gearing up to return in full force.

But because so many of us are also gearing up to return to campus...

And while doing so, we're coming across articles like "Female academics: don't power dress, forget heels – and no flowing hair allowed" ...

I need to share something about what I'll be wearing my first semester as a tenured professor.

But to get us there, I'll need to pose a string of rhetorical questions:

  • Tired of students rating your course according to what you wear?
  • Can't find a way to make the professional looks that you prefer pair with flats or sneakers or anything other than torturous high heels or other dressy shoes?
  • Tired of spending precious time and money on work clothes that you change out of the second you get home?
  • Tired of choosing between this garment made in a sweat shop and that garment made by children?
  • Hate suits?
  • Work clothes feel like a costume? Especially out-of-style ones that are too expensive to replace as trends change?
  • Tired of spending money on dry-cleaning and all those chemicals?
  • Hate the unfair fact that some faculty (like those with white hair, white privilege, or beards) can get away with comfortable and often inexpensive t-shirts, jeans, and flip-flops but others cannot or cannot take the risk to find out if they can?

If you answered yes to even one of those questions (or to related questions that didn't dawn on me to ask) then may I suggest you try wearing an academic gown to teach?

If your profession comes with its very own costume, why not take advantage of it? It's what I'm going to do starting this semester. I bought a cheap academic gown on-line and I've even started decorating it:

Kind of makes my chair look professorial, doesn't it?
I know this is tradition at a few American schools, but do any of you do this where it isn't? Anyone want to start?

"Mar not my face......"



Near the entrance to a cave on Crantock Beach near Newquay, a woman's head and a horse are carved into the sloping rock face, along with four lines of verse. Sometime in the 1920's a young woman on horseback became trapped in this cave by the swift incoming tide, and tragically both she and her horse were drowned. So distraught was the young woman's lover that he carved this permanent memorial to her, though no trace of her name seems to remain.

"Mar not my face but let me be
  Secure in this lone cavern by the sea.
  Let the wild waves around me roar
  Kissing my lips for evermore."

I have been going to Crantock Beach all my life, but I did not know of this carving's existence until this summer.

A little splash of colour to brighten up these dismal days.......is the weather as bad where you are?

Dram...

Yeni işin ilk günleri...

Yenilikler dönemi. Bir Kasım günü. Davanın üzerinden geçmiş koca 1 sene ve fazlası...

Ne bir adım ileri gidebilmişim, ne de bir adım geri. Kendi davamdan geçmişim; babamın kaybettiklerinin peşine düşmüşüm. Gençliğim gidiyor oysa. Birini yeniden sevmeye dair umutlarım var bir de endişe ile sarılmış cesaretim. Çünkü her an, o en çok korktuğum ile yüzleşebilirim. 

Hep gizli saklı duygular, liseli kızlarınki gibi. Flört yasak, aşık olmak suç. Kimseye de kabul ettiremiyorum zaten. Diyemiyorum; kırık kolum-kanadım. Unuttum kadın olmayı, genç kızlığı yeni geçmişken karaları bağlamamı bekledi eş-dost-akrabam. Diyemedim ki; benim ben, Neslihan. Bırakın sevsin biri beni, kırık yanlarımı, egolarımı, duyguları iyileştirmese de yamalasın en azından. 

Dört tarafı suyla çevrili bir Adadaydım ben, Sonbaharda. Suları derin Adanın, yüzme bilmiyorum. Karaya ulaşmak için de yok hiçbir vasıtam. Esaretim kendime, esaretim içimde gizlediklerime. 

Daha ben kendimi ikna edememişken bir rüzgarla oradan gidebileceğime; oradan buradan bir iki kare ile dedi ki bana; yakalandın sonunda. Kaçmıyordum ki.... Neden kaçacaktım zaten? Ne kaçmaya, ne saklanmaya, ne de kendimi savunmaya halim yoktu ki sonra.

Yıkıldım, küçük evde bir koltuğun üzerine. Açık değil televizyon, tam karşımda. Ama ben izliyorum,bir kadın oynuyor başrolde. Senaryo, bitmeyen bir dram. İçerde uyuyan bir Masal.  Ağlıyorum. Ya onu benden alırlarsa?

Birazı pişmanlık hissettiklerimin, neden? Üzerime atılan çamur çıkar mı saatlerce suyun altından çıkmasam? Kalkamıyorum ki çakılıp kaldığım yerden. Sesi kulağımda hala kızımın: Almasınlar beni senden.... 2,5 yaşında daha, nereden bilecek ne demek ayrılmak? Ağlıyor işte içten içten. Ona bugüne kadar verdiğim en büyük zarar! Saatler geçti bence ömre bedel. Belirsizliği kovalıyor akreple yelkovan, durmadan.

Kapım açıldı. Bir kadın girdi içeri, biraz bana benzeyen. Daha önce anlattıklarımdan. Kalk dedi buradan. Bir daha doğmayacaksın, bir daha olmayacaksın bu yaşlarda, hayat sadece bu an! Sevdiklerin öldü kollarında daha sen vedalara hazırlanmadan. Ara dedi onu, sor ne istiyor daha senden? Kolay mı bir bebeği almak Annesinin koynundan. İkna eden o olmadı beni. 

Telefonda duyduğumdu ne gereksiz bir savaşta olduğumu beynime kazıyan. Seçenekti bana sunulan; benim şu an yazmaya utandığım. Saraylar versen, geçtiğim yollara dünyanın en pahalı çiçekleri sersen, dört bir yanımı mücevherlerle çevrelesen, kızım yoksa eğer; gülemem ki ben. Düşünmedim bile. Kendime yakıştıramadım, pazarlığı. Hadi dedim affettim seni, herkes yoluna... Çok sürmedi imzaladım birşeyler. Bitti Gitti. 

Saklayacak, utanacak, gizlenecek birşeyim yok. Açıldı bir kere bu Masal, anlatacaklarım var. Evet, ben sevmiştim de birini. Pek çok şeyi sever gibi hem de. Sonrasını öğrenecek devamını okuyan.

Sevmek değil ayıp, değil günah.

Seven kalplere yakıştırdığınız ayıplar sizi günahkar yapan. 

Ve ben...

Ben hiç günahkar olmadım....






Başladım...

Bana dedi ki: "Kanserim! Bir süre evden gitmem gerek, tedavi olmalıyım""

Onun kendine yakıştırdığını ben daha kimselere yakıştıramadım, yıkıldım!

Ne bir çorap, ne bir kazak, herşey asılı kaldı bıraktığı yerde aylarca. Büyüdü ama kızım, sütüm azaldı. Büyüdü acım, inancım azaldı.

Kapının önüne bırakılan alışveriş poşetleri de gördüm ben, paspasın altına gecenin bir yarısı, sadaka niyetine bırakılan paralar da! 

Öldürmedi kanser, olmayınca öldürmüyormuş meğer! Lüks arabalara sebep oldu yan etki olarak, evin faturaları dahi ödenmezken! 

İmitasyon olan giydiği tişört değildi, kalbiydi! Kirlenmişti bir kere... İyileşsin diye dua eden bir kadınla bebeğini, binbir gece yalanlarıyla zindana atan bir vicdanın karasıydı, oturan gözlerine... 

Bitmişti bile... Hem de çoktan... Geçince aylar, cevapsız kalınca sorular, uyunamayınca uykular; aydınlandı zihnim de... En yakınım sandıklarımdan gizlediklerim, geldi dile. Şahit oldular, yemediğim her lokmaya, her lokmada tükenişime, konuşmadılar. Konuşacakları başkaymış, öğrendik mahkemede!


Bir çanta dolusu para, bir lüks araba, az biraz fiyaka, üç beş de avcı hatun bulunca, adam olunur mu bu devirde?

Beklerken ben, git dediler bana evden, süren doldu! Çocuğunu mağdur etmeyeceğine yemin eden Adam, kanserli hali ile tam da bize ev tutacakken kalp krizi geçirdi aniden! Yersen... Ben hastanede ararken onu, çıkıverdi bir gece klubünden... Tam bir Yeşilcam entrikasıydı sergilenen! 

Toplandık mecbur, sattık eşyaları, dağıttık ona buna, minicik bir kız çocuğu kucağımda. Babamın evine yollamaya çabalarken o, beni, kurdum kendime bir yuva! Ben evi değil, hayallerimi yıkıp geçerken haberi bile olmadı! Kızım gece ateşlendi, haberi olmadı. Bahçenin ortasına geçip onun yolunu gözledi, haberi olmadı. Düştü, ağlamadı,  haberi olmadı. İstediği alınamadı, haberi olmadı. Korktu, omzunu aradı, haberi olmadı. Kırıldı, incindi, haberi olmadı. Anne işe gitme diye boynuma sarıldı, haberi olmadı. Bisiklete hiç binmedi, haberi olmadı.. Büyüdü 5 yaşına geldi, haberi olmadı!

Bu kısmını hiç anlatmadım ben bu Masal"ın... Hep bundan sonrası yazıldı benim için. O evde 9 ay neler yaşadım, bırakın yazmayı daha kimseye anlatmadım! Neden?? Bilmem...

Belki de affettiğimden.

Ama birileri affetmesin bence, benim yerime... Bilsin herkes. Utanmadan mahkemeye çıkıp yalancı şahitlik yapanı da, işbirlikçi olanı da, kalbini satılığa çıkaranı da... En çok da ; utanmadan, Yıktığı evin üzerine ev kuranı, Babalığı  parayla satın almaya kalkanı, kendi gölgesinden dahi korkanı, yine yeniden bir başkasını kandıranı!

Bir ömür geçirmek için yemin ettiğimden, kardeş dediğimden- sığındığımdan yediğim kazıktan bu denli tokum ben, inanmalara...

Diyeceğim şu ki; yaşadıklarım bunlar! Eksiği çok, fazlası hiç yok. Değişmez bazı şeyler; saf-yalın-sadece Anne"yim ben ve herkes kendi kalbinin ekmeğini yer! 

Cennetle Cehennem değil uzakta, hepsi bu dünyada... 

Ben izleyeceğim hepsini çooook uzakta!

Selametle:)

İç Ses - 15

Gitmek ve kaçmak…
Aslında birbirine çok benzer süreçlermiş gibi  görünen birbirinden çok farklı iki hamle.
Gitmek düşünülmüş üzerine uykulara yatılmış, hayal edilmiş, zamanı beklenmiş, bütün doğruların bir araya gelmesinin kollandığı bir insanlık hali.
Kaçmaksa çat diye gelen , hiç akılda yokken , ruha dahil değilken  birden yoluna düşen bir alev topu. Kırıcı, hayatı birden tak diye tam orasından bölen bir yalnızlık hatta belki yanlışlık hali.
Birbirine ne kadar karışıyor ne kadar ayır edilebiliyor orası belirsiz
  Gitmeleri kaçmak sanmalardan mı kaynaklı acaba bu tuhaf kendini garantiye alma hissi.
Adamlar ve kadınlar sevdikleri kaçacak sandığı için mi gitmelere dayanamıyorlar, analar babalar evlatları kaçıyor mu sanıyorlar o kapı her dışarıdan örtüldüğünde ?
   Gitmek olağandır aslında ve bazı ruhlar için elzemdir hatta korkulacak bir şey değil ki.
   Mevzu kaçmak zorunda kalmamak, kaçmak zorunda bırakmamak.
 Gitmelerinin tarihçelerinden şiir , kaçmaların yarım kalmışlıklarından  keder doğuyor.
Aynı şey değil yani …
Arada derin bir gam farkı var.
Korkma.
Bil.
Bil ama istersen de kullanma demişler ata kadınlar sen de bil.
Bil ama istersen kullanma .  

Rare Disease Day and the promises of personalized medicine

O ur daughter Ellen wrote the post that I republish below 3 years ago, and we've reposted it in commemoration of Rare Disease Day, Febru...