Masal ve Hikayeler

İç Ses - 23

Bir mesaj, program yükleniyor arkadaşlar bir kaç dakika kaldı. Onun üzerine instagrama yüklenen biz bir iş yapıyoruz izleyin diye de heyecanla bekliyoruz demeye çalıştığım içinde kadın kahkahamız olan bir kamera arkası videosu. Sadece birkaç dakika sonra Ankara'da patlama oldu yayını gizliye aldık denilen bir bilgi mesajı. Uyuşma etkisi ile geçen bir akşam. Uyuşuk bir sabah, anneannemin uyanışı, çay koyuşum, televizyondaki eğlence programlarını yayınlamamışlar iyi bari diye içimden geçirişim, kahvaltıda yemek üzere haşladığım yumurta, okul için yaptığım tost, yürüdüğüm yol, telefonuma düşen mesajlar çalışarak ve birbirimize sarılarak aşmak zorundayız diyor hocam, öfkem burnumda okul yolundayım. Anlık insanı kaygılara düşüyorum. Üşüyorum, çamura basıp hayıflanıyorum sonra utanıyorum. Ahlaksızlığımıza yanıyorum. Okula gittiğimde patlamak üzereyim öfkem acımdan ağır basıyor. Başka bir hocam geliyor sınıfa, acısı onun da gözünün ucunda konuşuyoruz uzun uzun. Birbirinize yaklaşın diyor en sonunda, devam etmek zorundayız. Bilim ve sanat diyor. Devam ediyoruz. İyi geldik birbirimize hiç temas etmeden elimizi tuttuk birbirimizin. Biz devam ederken mail kutuma bağlantı kurmaya çalıştığım bir yazarın iletişim numarası düşüyor. Mutlu oluyorum. Arıyorum karşımda kibar bir adam kafam biraz bulanık bugün diyor , anlıyorum onu, kapatırken birbirimize baş sağlığı diliyoruz. Birbirini hiç tanımadan aynı yasta birleşmiş koca cenaze evinin insanlarıyız çünkü artık. Eve dönmeliyim annem ilaç almaya gidecek anneannem yalnız kalamaz. Toplu taşımada patlar mıyım ben de? Biz kendimizi ve o çocukları her şeye rağmen üretmeye ikna edebilmek için çalışmıştık, onlar izlesin, hayal etsin ve hep beraber daha iyiye dair umut edebilelim diye. O gençler,insanlar bir gelecek hayal ediyorlardı. O insanlar , biz, ölüm, otobüs, bomba ... Ne olacak, nasıl olacak hayat devam edecek tamam da biz ruhumuz çürümeden nasıl nefes alacağız. Bütün kelimelerimiz bittiğinde mi kazanmış olacaklar ? Ne zaman yetmiş olacak tam olarak ? Biz ne zaman yaşayabileceğiz ? Korkmadan, utanmadan, insanca ... Ne zaman ?

Nasihat

Dost

Bir dost'un varsa çok şeyin vardır ,

Ekmeğin vardır, suyun vardır,

Akan çatına kabın vardır,

Ağlarken güldürenin vardır,

En sinirli anında sana , dur sakin ol diyenin vardır ,

Seni senden çok savunanın vardır ,

Dost acı söyleyen değil acıyı, acıtmadan söyleyendir

Bir dostun varsa kısacası

Kalbinin kararmış köşelerini itina ile kazıyıp sıvayıp , bembeyaz yapacak biri vardır...

Murmurations and you

I have a doctorate in Public Health which means that, unlike a 'real doctor', I was trained to think in terms of the health of populations, not of specific individuals. Public Health of course, when done appropriately, can have an enormous impact on the health of individuals, but in a very real way that's a side effect of gathering group information and instituting measures meant to affect a group. Clean water, fluoridated water, vaccinations, window screens, anti-smoking campaigns, and so much more are all public health measures targeting whole populations, without regard for the specific cavities or cases of cholera or lung cancer that the measure will actually prevent. This is because, of course, smoking doesn't make every smoker sick, just enough of them that aiming to convince whole populations not to smoke can have a large enough difference on population health that it's worth the cost and effort.

You've probably seen those murmuration videos showing enormous flocks of birds flying as if they were one; undulating, turning, responding as though they have a collective mind. Here's one is of a flock of starlings being hunted by a peregrine falcon one evening in Rome. The starlings fly so unpredictably that, at least this time, the falcon is unable to catch a meal.

Source: BBC One

According to the Cornell Lab of Ornithology, murmurations almost always arise in response to the detection of a predator; a falcon or a hawk that has come for its dinner, as the starlings in Rome. So, a bird or birds detect the predator and sound the alarm, which triggers the whole flock to take off. But, how do they stay together? Who decides where they're going next, and how does the rest of the flock get the message?

Young et al. report, in a 2013 paper in PLOS Computational Biology, that once in flight each bird is noticing and responding to the behavior only of its seven nearest neighbors. The murmuration, the movement of the group, then, is due to local responses that create the waves of motion that can be seen in the evening sky. There is no single leader, just many, many local responses happening almost simultaneously.

The same kinds of dynamics explain the movements of schools of fish as well. They work to some extent, but fish are routinely attacked by sharks, which can scoop up multiple individuals at a time, and surely sometimes birds of prey manage to snap up a luckless bird among the thousands or millions in a flock. But, most of the fish or the birds do get away, so it's a winning strategy for the group. Public Health in action.

Well-known, very prolific British epidemiologist George Davey Smith was interviewed on the BBC Radio 4 program The Life Scientific not long ago. He's a medical doctor with a degree in Public Health as well, so he's been trained to think in terms of both the population and the individual. He is currently interested in what genes can tell us about environmental influences on health. One of his contributions to this question is the analytical tool called Mendelian Randomization, which aims to tease out environmental triggers of a trait given a particular genetic risk factor. That is, the idea is to divide a study sample into individuals with and without a particular genetic variant, to determine whether their history of exposure to an apparent risk factor might be responsible for the disease. In this instance, the gene isn't modifiable, but exposure might be.

In the interview, Davey Smith said that his primary interest is in population health, and that if a Public Health measure can reduce incidence of disease, he's happy. So, if everyone in a population is on statins, say, and that reduces heart disease and stroke without major side effects, he would consider that a successful Public Health measure. Even if it's impossible to know just who's stroke or heart attack was prevented. Success of Public Health can only be evaluated on the population, not the individual level.

So much for personalized, predictive medicine. That's fine, my training is in Public Health, too, so I'm ok with that. Except that Davey Smith is also a fan of large, longitudinal studies maintained in perpetuity because, as he said, they have yielded more results at lower cost than most any other kind of epidemiological study.

But there are problems with such studies, and if the idea is to identify modifiable environmental risk factors, a major problem is that these studies are always retrospective. And, as we've written here so often, future environments are not predictable in principle. Presumably the aim of these large studies is to use Big Data to determine which Public Health measures are required to reduce risk of which diseases, and if that is done -- so that large segments of the population are put on statins or change from saturated to unsaturated fats or start to exercise or quit smoking -- this changes environmental exposures, and thus the suite of diseases that people are then at risk of.

So, Public Health has to always be playing catch up. Controlling infectious diseases can be said to have been a cause of the increase in cancer and obesity and heart disease and stroke, by increasing the number of people who avoided infectious disease to live to be at risk of these later diseases. So, in that sense, putting whole populations on statins is going to cause the next wave of diseases that will kill most of us, even if we don't yet know what these diseases will be. Maybe even infectious diseases we currently know nothing about.

Even though, after putting their favored Public Health measure into effect, all the starlings outwitted the falcon that particular night in Rome, they're all eventually going to die of something.

Yağmur

yağmurlu bir gün çık karşıma sımsıkı sarayım seni

usulca dokun omzuma, doya doya koklayayım seni.

yoldan sessizce geçen bir kedi ,şahit olsun aşkımıza.

rüzgar usulca ,seni ne kadar sevdiğimi fısıldasın kulağına,

doya doya göreyim seni

yağmur sel olup aksın yollardan , aktığı yerlerde izler bıraksın,

sevdan nasıl aktıysa yüreğime , nasıl izler bıraktıysa derinlerde

yağmurlu bir gün çık karşıma,saçların yapışsın alnına

kirpiklerinden süzülsün ,gül yüzüne,

ıslandıkça kokun sinsin üstüme,sen soğuktan titre,
ben aşkından...

sımsıkı sarıl bana hiç ayrılmayacak gibi

öyle bir bak ki gözlerime,
gözlerimi kapadığımda silüetin gelsin karşıma

yağmurun sesi karışsın kalp atışıma,

hangi daha hızlı hissetmeyeyim öyle gül ki gözlerime

alıp götürsün beni buralardan ıssız vadilere.

yağmurlu bir gün gir yüreğime en kuytu köşelerine

öyle bir söz söyle ki bana,

seni neden bu kadar çok sevdiğimi

haykırayım kendime ...

When evolutionary-minded medicine gets it (possibly) wrong about childbirth interventions

No one is saying that medicine isn't brilliant and hasn't saved lives. But it does intervene more than necessary when it comes to pregnancy and childbirth.

Part of that unnecessary intervention is driven by lack of experience. Part is an economically-driven disrespect for time. (Give childbirth some motherlovin' time.) Another part, related very much to experience, is how difficult it is to decide when intervention is and isn't necessary, especially when things are heating up. But another part of the trouble actually lies in the evolutionary perspective. Unfortunately it's not all rainbows and unicorns when M.D.s embrace evolution. Instead, evolutionary thinking is biasing some medical professionals into believing that, for example, birth by surgical caesarean is an "evolutionary imperative."

Here's one recent example in The American Journal of Obstetrics & Gynecology of how the evolutionary perspective is (mis)guiding arguments for increased medical intervention in childbirth.

link to paper

It's a fairly straight-forward study of over 22,000 birth records at a hospital in Jerusalem. The authors ask whether birth weight (BW) or head circumference (HC) is more of a driver of childbirth interventions (instrumental delivery and unplanned caesareans) than the other. Of course, the focus is on the biggest babies with the biggest heads causing all the trouble, so the authors narrow the data down to the 95th percentile for both. Presumably they're asking this question about BW and HC because both can be estimated with prenatal screening. So there's the hope of improving delivery outcomes here. And, of course, the reason they ask whether head size or body mass is more of a problem is because of evolution. They anticipate that they'll discover that heads are a bigger problem than bodies because of the well-known "obstetrical dilemma" (OD) hypothesis in anthropology.

OD thinking goes like this: Big heads and small birth canals are adaptive for our species' cognition and locomotion, respectively, but the two traits cause a problem at birth, which is not only difficult but results in our species' peculiar brand of useless babies. (But see and see.)

So, since we're on the OD train, it's no surprise when we read how the authors demonstrate and, thus, conclude that indeed HC (head circumference) is more strongly associated with childbirth interventions than BW (birth weight), at least when we're up in the 95th percentile of BW and HC. Okay.

They use this finding to advocate for prenatal estimation of head size to prepare for any difficulties a mother and her fetus may be facing soon. Okay.

Sounds good. Sounds really good if you support healthy moms and babies. But it also sounds really good if you already see these risks to childbirth through the lens of the "obstetrical dilemma" with that OD thinking helping you to support "the evolutionary imperative" of the c-section. Okay.

Too many "Okays" you're thinking? You're right. There's a catch.

When you dig into the paper you see that "large HC" heads are usually about an inch (~ 2.5 cm) greater in circumference than "normal HC" ones. (Nevermind that we chopped up a continuum of quantitative variation to put heads in arbitrary categories for statistical analysis.) And when you calculate the head diameter based on the head circumference, there is less than 1 cm difference between "large" and "normal" neonatal heads in diameter. That doesn't seem like a whole lot considering how women's bony pelvic dimensions can vary more than that. Still, these data suggest that the difference between a relatively low risk of having a c-section and a relatively high risk of having a c-section amounts to less than a centimeter in fetal head diameter. And maybe it does. Nobody's saying that big heads aren't a major problem sometimes! But maybe there's something else to consider that the paper absolutely didn't.

Neonatal heads get squeezed and molded into interesting shapes in the birth canal.

The data say that normal HC babies get born vaginally more often than large HC ones. But this is based on the head measures of babies who are already born! If we're pitting head circumference (HC) of babies plucked from the uterus against the HC of babies who've been through hello! then of course the vaginally delivered ones could have smaller HCs.

C-sected babies tend to have rounder heads than the ones squeezed by the birth canal. It's impossible to know but I'm fairly confident about this, at least for a subsample of a population: Birth the same baby from the same mother both ways, vaginally and surgically, and its head after c-section will have a larger HC than its squeezed conehead will after natural birth.

Measuring newborn head circumference (HC). source

When we're talking about roughly 2.5 cm difference in circumference or less than 1 cm difference in diameter, then I'd say it's possible that neonatal cranial plasticity is mucking up these data; we're sending c-sected babies over into the "large HC" part of the story just because they were c-sected in the first place. So without accounting for this phenomenon, the claim that large head circumference is more of a cause of birth intervention, of unplanned c-sections, than large body mass isn't as believable.

If these thoughts about neonatal cranial molding are worthwhile, then here we have a seemingly useful and very high-profile professional study, grounded in the popular but deeply flawed obstetrical dilemma hypothesis, that is arguing for medical intervention in childbirth based solely on the difference in head size measures induced by those very medical interventions.

The circle of life!

Özelsin , Güzelsin ,Güzeliz...

İyi akşamlar sevgili Kuğucanlarım ,sessizliğime sesim ,bulutlu günlerime güneşlerim , İnşallAh iyisinizdir. Sessiz dostlarımız ,hayvanlara bir kap su bir kap yemek kampanyam çok güzel gidiyor ve çok güzel tepkiler alıyorum ,destekleriniz için çok teşekkür ederim ben o hayvanlara bir damla suyu pay edemem ama birlik olursak hepimizin birer damlası baraj olur , desteğiniz için çok teşekkür ediyorum ve bu dahada büyüyecek dillendirdikçe bilinçleneceğiz bilmediklerimizi öğreneceğiz sizi güzel dostlarla tanıştırayım, işte buyurun;

Ben KurabiyeciMiss Zehra Ertuğru size bahsettigim mama kaplarının resimleri aşağıdadır. Dilerim yardımcı olabilmişimdir. Sevgilerimle.

Birlikten kuvvet doğar,bu arada fidanlar aşılanmış :))

..................................................................................................................................................................................................................................................................................................................

River;

Küçüklüğümden beri kuşları seven biri olmuşumdur, daha ufaklığımdan kalma bir alışkanlığım vardır, her sabah kalkar camın önüne biraz buğday alır koyar, güvercinlerin doluşmasını izlerdim. Dim dememde ki etken, yan komşumuzun şikayeti ve dahası kuşlar gelmesin diye camın önüne poşet asıp korkutmaya çalışmasından sonra bir müddet şikayet üzerine bırakmak zorunda kalmıştım. Ama bu defa da evden çıkarken pencere kenarı yerine apartman kapısının önüne bırakma alışkanlığım başlamıştı.

Sabah blogunda etkinliği okuyunca lise zamanlarım aklıma geldi, ne denli evin kapısına biraz buğday bırakma alışkanlığım devam etse de dayanamayıp pencere kenarına da ilave ettim ve biraz da nostaljik ruh haline büründüm açıkçası. ^^

Ne var ki bu kez eskisi gibi güvercinlerle doluşması penceremin önü, yine de gelen bir ziyaretçi beni memnun etmeye yetip arttı. :)

Tül perdenin arkasına dikkat!

..........................................................................................................................................................................

Kirpik Kız;

bloğum yok ama sokak hayvanları konusunda oldukca hassas biriyimdir,bahçeli bi evde oturduğumdan kedimiz köpeğimiz eksik olmaz :)

Neşeli kitap vagonu

ECE EVREN;

LÜTFEN ONLARIN DA ACIYAN BİR CANLARI OLDUĞUNU,ACIKIP SUSADIKLARINI VE BİZLERE EMANETEN BIRAKILDIKLARINI UNUTMAYALIM. BUNLARI YAPAMIYORSAK EN AZINDAN İNSAFLI BİR GÖZLE BAKALIM. HESAPLARIMIZI KABARTMAYALIM.LÜTFENNN...

Ponçiği

..........................................................................................................................................................................

Bir yolcu;

O her zaman herkese dost kocaman bir kalbi var insanlar ve hayvanları çok seviyor....

Sıcacık son dakika bir Mail geldi bakın bakalım kimden:)

Cafe tigris;

benim annem de tam bir kuş delisi yıllardır pencerenin önünde beslediği güvercinlerin, kumruların torunlarının torunları olmuştur .

Benim de küçük balkonumda yumurtadan çıkıp uçan dört güvercin bebeğim oldu . Haaa bir de bizim aspiratör borusunu mesken eden serçelerimiz var onların resmini çekemedim ;))

Sizde bana resim , öykülerinizi , hikayelerinizi yada sadece bir şeyler yazmak , yollamak isterseniz;

one.black.svvan@gmail.com

Şimdiden Hayırlı Cuma'lar

Sevgilerimle...

Humans are master meaning generators

A hashtag in the sky above a school at dusk in southern Rhode Island.

Was it put there intentionally? What does it mean?

For as long as we’ve been writing about exquisite Paleolithic cave paintings and carefully crafted Stone Age tools we’ve been debating their meanings. And the debate carries on because meaning is difficult to interpret and that’s largely because “what does it mean?” is a loaded question.

“Meaning” is a hallmark of humanity and, as the thinking often goes, it is a unique aspect of Homo sapiens. No other species is discussing meaning with us. We’re alone here. So we’re supposed to be at least mildly shocked when we learn that Neanderthals decorated their bodies with eagle talons. And it’s supposed to be even harder to fathom that Neanderthals marked symbolic thinking on cave walls. But such is the implication of lines marked by Neanderthals in the shape of a hashtag at Gibraltar.

source: "The Gibraltar Museum says scratched patterns found in the Gorham’s Cave, in Gibraltar, are believed to be more than 39,000 years old, dating back to the times of the Neanderthals. Credit: EPA/Stewart Finlayson"

This sort of meaningful behavior, combined with the fact that many of us are harboring parts of the Neanderthal genome, encourages us to stop seeing Neanderthals as separate from us. But another interpretation of the hashtag is one of mere doodling; its maker was not permanently and intentionally scarring the rock with meaning. These opposing perspectives on meaning, whether it’s there or not, clash when it comes to chimpanzee behavior as well.

We’ve grown comfortable with the ever-lengthening list of chimpanzee tool use and tool-making skills that researchers are reporting back to us. But a newly published chimpanzee behavior has humans scratching their heads. Chimpanzees in West Africa fling stones at trees and hollow tree trunks. The stones pile up in and around the trees, looking like a human-made cairn (intentional landmark) in some cases. Males are most often the throwers, pant-hooting as they go, which is a well-knownscore to various interludes of chimpanzee social behavior.

source: "Mysterious stone piles under trees are the work of chimpanzees.© MPI-EVA PanAf/Chimbo Foundation"

Until now, chimp behaviors that employ nature’s raw materials—stones, logs, branches, twigs, leaves—have been easy to peg as being “for” a reason. They’re for cracking open nutritious nuts, for stabbing tasty bushbabies (small nocturnal primates), or for termite fishing. But throwing stones at trees has nothing to do with food. If these chimps do it for a reason then it’s a little more esoteric.

Maybe they do it for pleasure, to let off steam, or to display, or maybe they do it because someone else did it. It may be all of those things at once, and maybe so much more. Maybe you’d call that ritual. Maybe you wouldn’t. Maybe you’d say that they do it because that’s what chimps do in those groups: they walk on their knuckles; they eat certain foods; they make certain sounds; they sleep in certain terms in certain trees; and they do certain things with rocks, like fling them in certain places. Maybe we could just say that this behavior is the way of certain chimpanzees, hardly more mystifying than other behaviors that we’ve come to expect of them.

For comparison, I have certain ways. There are piles of books near my desk. They pile up on tables and shelves. I could fling books on the floor but I don’t. I’m not against flinging them on the floor; it’s just not how things are usually done. I share this behavior with many other, but not all, humans in the presence of books, tables, and shelves. Until I wrote this paragraph, I never gave it much thought, it’s not something that factors even remotely into how I see the world or my place in it, and yet the piling of books on tables and shelves is quite a conspicuous and, therefore, large part of my daily life.

So, why isn’t someone setting up a camera trap in my office and writing up “human accumulative book piling” in Nature? Because this type of behavior, whatever it means, is quintessentially human. No one could claim to discover it in a prestigious publication unless they discovered it in a nonhuman. And they did.

Normally what we do when we learn something new about chimpanzee behavior is we end up crossing one more thing off our list of uniquely human traits. “Man the tool-maker” was nixed decades ago. What should we cross off the list now with this new chimp discovery? Would it be “ritual” and by extension “meaning,” or would it be “piling up stuff”? About that Neanderthal hashtag, do we cross off “art” or “symbolism” and by extension “meaning,” or would we just cross off “doodling,” which holds a quite different meaning? Rather than crossing anything off our list, do we welcome Neanderthals into our kind so we can keep our monopoly on hashtags? Whatever we decide, case by case, trait by trait, we usually interpret our shrinking list of uniquely human traits to be clear demonstration that other animals are becoming more human-like the more we learn about the world.

That’s certainly one way to see it. But there’s another, more existential, and therefore, arguably, more human way to look at that shrinking list of uniquely human traits: Humans are becoming less human-like the more we learn about the world.

#WhatDoesThatEvenMean #PantHoot #Hashtag #ThisIsMyCaveWall

Bahar

Gül yeter, bahar olurum

Baktığın yerde yeşil , beyaz olurum

Sevildiğini bil, ben şiir olurum

Sev yeter ben her yerde nefes olurum...

Çekiliş Sonucu

Çok uğraştım siteden yapamadım Kusuruma bakmayın , bende klasik yönteme başvurdum katılımcı arkadaşlarıma çok teşekkür ederim , bir dahaki çekilişimde daha donanımlı olacağım inşAllah.

Çok güzel mailler aldım ileriki günlerde paylaşacağım etkinliğim devam ediyor yeni hediyelerle yeni çekilişlerle devam edeceğim .

Selime aydın

güle güle kullansın hediyesi hafta sonuna kadar elinde olur İnşAllah. Bir hafta içinde geri dönüş olmazsa tekrar çekerim , Son yazılarımda yorumları cevaplayamadım en kısa sürede cevaplayacağım özürler , sizi çooooooooooooook seviyorum sevgilerimle.

Not : çok güzel resimler geldi , detaylı olarak resimleri ve yollayan blogları , mail atanların hikayelerini tek tek tanıtacağım ...

Bakarmısınn ?2

Merhabalar ,
Bu gece dört güzel blog tanıtıyorum yaslanın arkanıza ve bu üç güzel insanı tanıyın hmm dört blog üç insan nasıl oluyor diyenlere birazdan geliyor cevap:))

Sevgili Şengülüm ameliyat olmuştu ve uzun süredir yoktu geçmiş olsun ziyaretinin şimdi tam zamanı diyorum sıcacık dost ziyaretleri ve yeni arkadaşlar ona iyi gelecektir... tık tık

İkinci ve üçünçü blogumuzu tanıdığınızda özellikle bloğu için bir şeyler yapmak isteyenlerin vaz geçilmez adresi olacak gibime geliyor ,ben çok yararlanıyorum seo , veb yazılımları ve blogla ilgili her şey var ücretsiz logo ve header yapıyor , ben bir çok tasarımcının bizim bloglarımızı baz istasyonlu apartmanlar gibi doldurmalarına kızıyorum bir yardım yapıyor karşılığında bana ait özel mekana bayrağını asıyor hemde benim bütün pencerelerimi kapatarak.

Kibarca adını yazarsın yada sana ulaşmaları için küçük bir linkini bir köşeye koyarsın ama kocaman bir logonu koy evimin ortasına tır çekmiş mübarek...

Ben şahsen sevmiyorum zaten dost kapım üye olduklarımı gösteren kutucuklar var birde onları koyarsam ne anladım ben özgürlükten burada özgür olmak değilmi amaç bloglarımızda.

Web tasarımı yapıp bir çok siteye renk katan iki arkadaşımızı tanıtmak istiyorum birincisi iki bloğu aslında bir çok bloğu var ben ikisini tanıtmayı uygun gördüm isteyen diğerlerinede bakar zaten..

tık tık ve diğer bloğu tık tık

ve çok tatlı bir arkadaşımız ne arasanız mevcut :) web tasarımcılığıyla harika işler çıkarıyor tasarımının altına çok şık kibar minik imzalar atıyor ona ulaşabilmemiz için ben en trend web tasarımcısı diyorum:)) tık tık

Küçük bir not; bu gün sözlenen , nişanlanan , evlenen yada biriyle tanışıp çıkmaya başlayan var mı?

Sevgilerimle ...

Rare Disease Day 2016

My daughter Ellen wrote this post last year for Rare Disease Day. We repost it today. It's frustrating that, in the age of genetics, when finding single genes for rare diseases is what the field does best, she is still seeking answers.

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.

Elizabeth Barrett Browning had a rare disease

In the spring of 2011, Ken and I took a bit of a pilgrimage to England. We were moved by following Darwin's footsteps in Malvern, as we described here, and even to see the gravesite of his beloved daughter Annie, but the real goal of that trip was to find several of the places that were important to the Victorian poet Elizabeth Barrett Browning when she was young. Barrett Browning was ill for most of her life, with a disease that her doctors were unable to diagnose during her lifetime, and which medical historians have been unable to definitively diagnose since. However, while reading her letters to Robert Browning, and much more of her writing, because our family has been touched by the same rare disease, it dawned on us that we knew what she had. We have blogged about this a few times but it seems fitting to re-publish that post today because it's Rare Disease Day 2016, a day established by a number of rare disease alliances and organizations around the world to raise awareness of the impact of rare diseases on patients' lives.

Elizabeth Barrett Browning

Born in 1806, Barrett Browning lived at Hope End in Malvern from age 3 to 25. Her father made his money by managing sugar plantations in Jamaica, and he had plenty of it. He built a very large house on a 200 or so acre estate near the Malvern Hills, and brought his growing family to live there in 1809. Eccentric this house was by all accounts, with Turkish minarets and other such out-of-place characteristics, but EBB loved it. As a child she rode her pony through the woods, and down the lanes that stretched to Ledbury and Great Malvern, and beyond. She and her beloved brother Edward spent many many happy hours running up and down the hills behind the house, until at age 12 or so her aunt scolded her for playing too rough.

But, when Elizabeth reached puberty she experienced the first extended episode of an illness from which she suffered all her life, but that her doctors never were able to diagnose, to their and EBB's great frustration -- and her readers and EBB scholars have tried to puzzle it out ever since.

Apocryphally, it was said that she fell from her horse at age 15 and injured her spine, but she always insisted that that had nothing to do with her illness. Recent scholars have suggested that she had anorexia, or TB, neurasthenia, pertussis, an encephalomyelitis, non-paralytic poliomyelitis, paralytic scoliosis, or opium addiction or a mental illness including anxiety and agoraphobia. At least one biographer has suggested that ‘escape into illness’ was her way of dealing with the frustration of being an intelligent woman in Victorian England or a reaction to the exceptional sternness of her widowed, religiously strict father. She was also described simply as a malingerer. She was sent to a spa in Gloucester for a year during her teens, to recover, and she was better at some times than others, but she was never truly well for any length of time again.

While we will never know for certain, I think that she may have been suffering from a rare and elusive muscle disease called hypokalemic periodic paralysis (HKPP). It's an ion channel disorder, marked by a deficit of potassium, and involving episodes of weakness or frank paralysis with numerous triggers including heat, cold, exercise, rest after exercise, carbohydrates, salt, temperature change, and change of seasons. Causative mutations have been identified in three ion channel genes, but they explain only a minority of cases. And the disorder can run in families or it can be sporadic. And, age of onset at puberty is classic.

I've published an article suggesting this diagnosis, and because I've been thinking about this woman and her illness for so long we decided to go see the place of her childhood home, where she was so happy, as well as a place where she was exceedingly unhappy. (The home Barrett Browning's father built was torn down by the next owner of the estate, and replaced by a home that burned at the beginning of the 20th century. The picture here is the house that now stands on the site.)

EBB's father lost much of his fortune when she was 25, and so he sold her beloved Hope End and moved the family to London. Elizabeth was particularly unwell during the move, suffering from weakness and palpitations of the heart, her usual symptoms, and as usual her doctors had no idea how to treat her. They had started her on opium in her teens, and she took it the rest of her life, and they now started her on Digitalis for her heart. Unfortunately this drug made her weak.

Her doctors recommended that she leave London not long after the move, which was not good for her health, so her father sent her to the seaside to recuperate. She spent three years in the Hotel Regina in Torquay, on the coast of Devon, where she suffered the most devastating heartbreak of her life when her brother, Edward, was drowned in a sailing accident.

Hotel Regina, Torquay, Devon

She was desperate to leave Torquay after the accident, but too unwell. Her doctors cautioned the trip would surely kill her. She eventually decided that she would bear the consequences and traveled back to London, where she spent more years in her room at 50 Wimpole St, not leaving the house, and often not even well enough to leave her couch.

But she continued to write and publish poetry, which came to the notice of the poet Robert Browning. He wrote to her, and eventually prevailed upon her to allow him to visit her. They quickly fell in love, as detailed in the beautiful and deeply emotional letters they sent to each other throughout 1845 and 6. But Elizabeth's father wouldn't allow any of his children to marry, and Elizabeth herself told Robert she didn't want to burden him with an invalid. But when EBB's father announced that he was moving the family to the country for a month, they realized they couldn't bear to be parted, so they married in secret and ran away to Italy where they lived until Elizabeth died, in 1861.

Elizabeth was much healthier and happier in Italy than she had been since she fell ill. She had spent years in her room, writing poetry, many many letters, and expecting to die. But she was never truly healthy, and she often wrote of her illness in her letters. It's in these letters, and the diary that she kept at age 25, that I found the clues to her disorder.

For example, Elizabeth wrote from Torquay to a friend:

…the last ten days have been dreary, uncomfortable ones to me, haunted throughout by weakness, an oppressive sense of weakness, and a lowness of spirits from which I am generally free. Such lowness of spirits, that I could have cried all day if there were no exertion in crying… This was the result of taking digitalis for three weeks instead of one… [She was aware that digitalis caused weakness, though it did calm her heart.]

And weeks later she wrote to the same friend:

I wanted to write to you very very soon in reply to your last welcome note. I wanted to say to you very soon some words which it suggested. But I have been exceedingly unwell—confined to my bed nearly a week by a sudden return of bad symptoms and so weak since as scarcely to bear without fainting even the passive fatigue of being carried from this bed to the sofa down stairs, by all the gentleness of my brother’s love for me. The prevalency of the east wind and sudden coldness of weather connected with it, are considered the causes of the attack.

And so on. But, many others have read these same documents and none has reached the same diagnosis as mine. The explanation for this is easy -- HKPP is rare, and the diagnosis is frequently missed even today, but we've got the disorder in our family, so I read EBB's words through a lens not shared by most readers, that of knowing the nature of the disease, and the profound and disabling weakness it can cause. I should add that two neurologists and two cell biologists agree with my diagnosis. It's pretty obvious when you know what you're looking for.

This has been a fascinating exercise, and not in small part because it is a stark reminder that we can only see what we are prepared to see. EBB scholars, who know much much more about the poet than I, haven't deciphered what has jumped out of the page at me because they don't know HKPP.

This is a sleuthing quest for me, but it's relevant to MT, because it is a combination of attempts to infer biological causation by combining circumstantial, informal evidence from the past with modern science. In the case of HKPP, several ion-channel genes are known, a couple of which appear to be causal for HKPP. But as with so many traits, most cases do not manifest changes in these genes, phenotypes are highly variable, so that even the name (HKPP) masks complexity.

In this case, retro-sleuthing is not about evolutionary fitness or long-term evolution, but even with direct first-person evidence, causal inference is a serious challenge. Any conclusions about specific past incidences, as in EBB's case, are conjectural -- and will remain so even if modern genetic methods identify the basis of most cases. But even then, inferring fitness effects, and hence the effects of evolution on the relevant genes, is problematic-squared: even the persistently ill EBB bore a child.

As with many attempts to delve into the biological past, however, the delving is what makes it interesting.