Rare Disease Day and the promises of personalized medicine

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

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

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

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

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

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

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

By Ellen Weiss

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Thinking about science upon entering the field: Part I

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

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

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

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

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

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

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

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

Duchy Nursery

Today I decided to go to Lostwithiel to have a mooch around the antique shops, and then for lunch I took the short drive up to the Duchy of Cornwall nursery. The indoor cafe was full, but there were a few tables set up in part of the greenhouse, and I actually prefer to sit in there amongst all the interesting pots and plants. 
 This little robin was singing his heart out and hopping around the tables looking for titbits.
 They really do display the plants beautifully at this nursery, with imaginative use of antique props and a plethora of nice quality pots and planters.

 My particular interest is in cacti and succulents, so this display really caught my eye.
 Aren't the little ceramic pots lovely?

 And yes, one of these did come home with me......

 Afterwards I took a walk from nearby Respryn Bridge up to Lanhydrock House. The sun on the beech tree avenue was magical.
 I collected some twigs from a dead oak tree; these will come in useful for wreath-making.
 Then down to the banks of the fast-flowing River Fowey and a leisurely stroll back to the van, and home.

Dressing up

 The weather may be frightful, but in my bedroom this morning I got out some of my favourite vintage pieces and dreamt of hot summer days when I can once again float around in silk and lace - well, one can hope!
 The hollyhocks that 'grow' up from the base and the sleeves of this black dress are just stunning in their intensity of colour and design. I bought this last year but have not yet had an occasion to wear it. There is no label inside so I have no idea of its origins, or date for that matter, only that it is of a very fine quality silk chiffon.

 This bolero style jacket was originally the top layer of an Edwardian blouse, but the silk blouse had completely deteriorated so I painstakingly unpicked the black lace part to salvage it. Although it has a few holes the piece is still wearable with a little care. Over bare skin it looks very seductive.

The skirt above was a 1950's prom dress but the top half didn't fit, so I cut it off at the waist, keeping the lovely pink satin bow. I absolutely love wearing it now. The Edwardian blouse below was originally white, but I dyed it to give it a more contemporary look. I can wear it casually with jeans as well as a pretty skirt.
 I find modern clothes shops very bland and boring, do you? The delight of finding something completely unique at an antiques fair or from specialist vintage clothing dealers is so much more rewarding. For a start you know that you will be wearing a piece that no-one else has, and you can develop your own unique style. Of course there is that frustration of falling in love with something that simply doesn't fit, (aggghhhh!) but with a few rudimentary sewing skills you can usually adapt pieces to suit your size and shape.
 Silk under-slips from the 40's or 50's with a Chinese style silk jacket.
 The necklace is my own creation, made from bits of ribbon and embellished with mother-of-pearl buttons and a buckle.
 I loved dressing up as a little girl and I guess I have never grown out of that sense of fun and adventure.
 A 1920's fine see-through linen summer dress with a jacket fashioned from one of those simple French linen shifts dyed salmon pink and split down the front. Very much looking forward to wearing this for the first time when weather permits!

 I love my bedroom. It's the largest room in my house, and because I don't have a separate sitting room (my studio has to share space with the sofa and is usually too cluttered to sit down upon!), I spend a lot of time in it. My books and Selvedge magazines are all kept on shelves by the bed within handy reaching distance, and I do all my computer/blogging work sitting on a comfy deckchair in the corner next to the radiator. Going to bed is such a pleasure and I never tire of studying all the different patches of fabric on this quilt.

Hanging from the curtain pole is this little red dress with some of my favourite textile brooches pinned to it. Clockwise from top left they have been made by: Janine Pope (Mud Rabbit), Viv Sliwka (Hen's Teeth), Cat Rowe and Christine (Gentlework).

 On the mantelpiece are some handmade ceramic jugs and vases,
 and two textile figurines made by Janine Pope of Mud Rabbit. The painting in the background is by Cornish based artist Dana Finch. I have gotten really excited about her work; I particularly love her use of colour and the abstract plant forms which frequent her paintings.
Hope you enjoyed the little tour! xxx

"White Trash": the ugly reality and its import

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Green Card Süreci

  Buraya yerleşmekle  ilgili o kadar çok soru geliyor ki, şuraya bildiklerimi yazayım da kurtulayım, demeyeceğim aaa ne kadar ayıp. Umumu aydınlatma hizmeti veriyoruz yük değil reca ederim.

  5 yıl önce, öylesine, gerçekten öylesine, green carda başvurmuştuk. Bir danışmanlık şirketi vasıtasıyla. İlk yıl çıkmamış. İkinci yıl onlar yine başvurmuş. Çıkmış. 
Başvuru kaydı dışında külliyen bizden habersiz gelişmiş bunlar. 
  Eğer çekilişe kendiniz başvurduysanız çıkıp çıkmadığını listeden bakıyorsunuz. Şirketle başvurduysanız ve çıktıysanız onlar size haber veriyor. 
   Bundan sonrası biraz karışık. 
Ananızın kızlık soyadının sondan üçüncü harfi nedir sorusuna benzer bir yığın sorulu, boşluklu İngilizce evrak var ki illallah türünden. İlkokulu nerde okudun, kaçta girdin, kaçta çıktın, daha bir sürü şey. 
   Bu noktada şirket size diyor ki, biraz daha para ver, ananın kızlık soyadını ben bulurum. İngilizce bilmiyorsanız veya her Türk gibi derdinizi anlatacak kadar bildiğinizi düşünüyorsanız, hiç girmeyin bu işe. Verin şirket halletsin.
 Evraklar hazırlandı, gönderildi. Size vize görüşmesi için gün ve saat veriyorlar. 
 Ankara'daki Amerika onaylı bir sağlık merkezinde check up yaptırıp, cd ve raporu alıp size verilen saatte yine Ankara'daki Amerika konsolosluğuna gidiyorsunuz. 
 Sıranızı beklerken reddedilenleri görüyorsunuz. Yani çocuğum gelmişsin bohem kıyafetle, turistik vize alacağım diyorsun, yer mi bunu o kadın. Gidersen geri gelmeyeceğini ben bile anladım. 
  Sıra size geldiğinde evraklarla görüşeceğiniz kişiye gidiyorsunuz. Sarışın tatlış bir Amerikalı. Gülümsemekten bir şey soramadı kız bize. Bastı möhrü. 
  Şimdi bundan sonra Amerika size diyor ki yerleş veya en azından altı aydan fazla Amerika dışında kalma. 
   Biz biraz ortam görme, araştırma niyetiyle 3 yıl, senede bir kez geldik. Hal böyle olunca girişte uyarıyorlar sizi. Kardeşim millet green card diye divane olir, size çıkmış gelmirsiz. 
  Eğer girişlerinizi senede bir yaparsanız, sisteme takılıyorsunuz ve sizi sonraki girişlerde almayıp kartınızı kırabiliyorlar. 
  Kesin giriş yaptınız, yerleştiniz. İlk iş security number, yani sosyal güvenlik numarası almak. 
 Artık oturum sahibisiniz ve oy kullanmak dışında her şeyi yapabilirsiniz. 
  Kartı aldığınız tarihten itibaren giriş çıkışlarınız hesaplanıyor, bunun bir süresi var, o dolunca vatandaşlık sınavına giriyorsunuz. 
  Bu sınav Amerika'yı tanıdığınızı gösteren sorulardan oluşuyor. İşte başkanları kim, kaç eyalet var vs. 
 Bu sınavdan sonra Amerika vatandaşlığı alıyorsunuz ve oy da kullanabiliyorsunuz.

Kısaca bazı noktalara değineyim

  Green card Amerika'ya gelmenin en avantajlı ve ucuz yoludur. Diğer vize alanlar gibi sürem bittiydi, nasıl barınacağımdı, yatırım yapayım da şurda durayımlı işler sizi bağlamaz.
Elbette Green card dışında çok yol var ama ben pek bilmiyorum.


 Burda devlet okulları eğitim kalitesi olarak 10 üzerinden puanlı. Ev tutacağınız zaman buna göre tutuyorsunuz. Mesela bazı siyahilerden veya başka sebeplerden ötürü güvenliğin az olduğu yerlerde, fakir eyaletlerde okul puanları da, ev fiyatları da düşük. 
  Puanı iyi ve çok iyi olan devlet okulları bizim kolejler ayarında. Arkadaş kızlarının okulunda ev eşyalarını kullanmayı öğrendikleri bir sınıf olduğunu söyledi. Küçük fırın, çamaşır makinesi vs. her şey var. Orda çalıştırıp öğreniyorlar dedi. 
Kavramları somutlaştırarak veriyorlar. Bizdeki gibi ezberden değil. 

  Kütüphaneler ayrı bir okul gibi. Anne baba çocuk birlikte gitsin, deney yapsın, şarkı söylesin, masal dinlesin. Sıradan bir mahalle kütüphanesinden söz ediyorum.  


  Burda herkesin yakındığı ortak konu. Bilhassa çocuklu arkadaşlardan dinlediğim vakalar, saatlerce beklemeleri, ücretlerin çok fazla olması, yetişkinlerin diş dolgusunu yaptırmak için bile yazın izne gitmeyi beklemeleri, tanı konulurken doktorların ağır davranmaları söz konusu. Obama zamanında Obama Care uygulaması varmış. O biraz rahatlatmış ama şimdi geçerli değil sanıyorum. Özel ve kapsamlı sigorta yaptırmanız şart.

Bizim meşhur angry bird kuşu cardinal, bahçede.

Dil öğrenme

Önceki yazılarımda mevcut idi. Oraya bakınız.


Bunu da yazmış idim. Bakarsınız zaar.

Peki Amerika bir göçmenin gelebileceği en güzel ülke olabilir mi?  


 Kara peçeli Hintlisinden, turuncu örtüsüne bürünmüş budistine kadar bütün dünya burda. Kimse sizin şalınıza şulunuza bakmaz. 
 Yeter ki nazik olun, trafikte içinizden hayvan çıkmasın, diliniz tatlı söz söylesin, selamı sabahı bilin, insana doğaya saygılı olun. E bunlar pek güzel, pek hasret kaldığımız şeylerdi zaten.

Başka soru yoksa çayımı içiyorum ben.
Ve tabi sevgiler ta Yeni Dünya'dan.

İç Ses- 33

İçimde hep bir karmaşa var.
İnsanların kendilerini oturttukları ve bir biçimde sakin bir halde o standart içinde aktıkları zamanda ben hep dalgalanıp durulma halindeyim.
Kafamın içinin meşgul eden her şey kalbimden çıkıp geliyor. 
Yetişkinler dünyasında dalga geçilen sevme hali ile açıklayamadığım şeylere tutunamıyorum. 
Kimse kimseyi sevmek zorunda değil elbette ama sevmediğin herhangi bir şey ile aynı düzlemde devam etmek de çok kolay değil.
İçimde çok derin bir his var. 
Biliyorum kötülüğü reddetmenin, ne olursa olsu tercihini sevgiye dair şeylerden yapmanın kıymeti baki olacak. 
Belki bugün dalga geçilip hafife alınan bir romantiklik gibi karşılık buluyor ama yarının üzerine kurulacağı temelin bu olduğuna hayatta hiçbir şeyden emin olmadığım kadar eminim. 
Günlük koşturmacaların, boşlukların, haksızlıkların, kalp kırıklıklarının ve kaygılarının daha kolay üstesinden gelmek için hep tekrarlamam, yüksek sesle tekrarlamam lazım belki de. 


''Ben" Kapalı uzun bir heceydim,
yeni bir kelimeye yüklememek için anlamları, 
Seni hep yumuşak bir g ile bitirdim.... 

"Sen" Açık ve kısaydı ismin, birleştirip kendimle,sana bir buçukluk bir söz ile seslendim: Aşk! .... 

"Sen ve ben" birbirinin peşinde ahenkli, birlikte ulama, yan yana bir musiki... Anlamları aynı, yazılışları farklı iki kişi,

"Biz": Yükte hafif, manada ağır,
Tam Kafiyeli,
Bazen serbest, bazen aruz, 
Ölçüsü kaçık biraz,
Birlikte bir beyit,
şiirin konusu bir nevi!

Ve yine "ben"
Şairin kalemindeki son mısra gibi,
Sevdim seni! 

 Sometimes an idea will brew in my head for years before it takes shape in reality.
Thinking about Matisse's paper cuts I cut out a series of stylised leaf shapes in brightly coloured papers, and began playing around with arrangements on old envelopes.

 Working on these has sparked off a further idea to produce 'paintings' using paper cutting and collaging, but maybe this idea will germinate in my head for another few years before it becomes a reality, who knows......
Have you been having a creative January so far?

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...