Thursday, December 29, 2011

Robert's genome sequencing: backstory

Some number of weeks ago, I walked from my office the few blocks through the parks that buffer the Senate office buildings from Union Station. The bank, the Senate Credit Union, was my destination. To reach it, I walk past guard booths and gates that mark what are now, post-9/11, blocked-off streets--major streets, like 1st & C Streets NE, as well as parts of Constitution and Maryland Aves. When I was younger and worked in the Dirksen Senate office building, which is joined with the Hart Senate office building, which is where the bank branch is located, all of these streets were bustling with traffic: buses and cabs and private and security vehicles. I still find the relative desertion of these streets jarring, especially as the traffic lights have still not, a decade later, been taken down, still blinking one signal or another.

One public entrance to the Hart building is at the rear, on C Street, reached by a series of broad sweeping steps in a soft-colored marble. Senator Debbie Stabenow's office with the Michigan State seal is still to the left of the entrance, although I suppose the security guards would stop you should you try to veer left before leaving your bags on the screening belt and stepping through the body scan.

The security check point wasn't there in the spring of 1987 when I ran into this guy I kept thinking would ask me out, the two of us walking in different directions on the pinkish marble tiles in the ultra-modern building. When we stopped to chat (and, again, he didn't ask me out), just beyond the hallway was the nine-storey atrium, which, had we simply walked past one another, would have revealed with each subsequent step closer more and more of the enormous steel sculpture that seems almost jammed into the atrium the way one would force an unwieldy object into a closet.

The sculpture has been in the Hart atrium as long as I can remember: I have no memories of the space without it, yet it forms merely a backdrop to whatever it is I've experienced there, whether the event of those first awkward run-ins with the man I would eventually marry, whether the sighting of Senator Barack Obama (post-presidential campaign announcement and pre-Secret Service protection) walking round and round in circles in front of this massive steel triangular-ish 3D multi-sided black riveted head-craning objet d'art, ignoring it as well as he talked on his cell phone, but catching my surprised face with its mouth open wide in surprise was not too busy to flash me one of his enormous beautiful grins. I have also seen Senator Shelby of Alabama walking near this sculpture, also ignoring it, but Senator Shelby doesn't smile much and, when he does, it's unconvincing.

Usually I blow through the corridor, the full scope of the atrium to my left, the black heavy legs and base of the sculpture at the edge of my field of vision, and push open the glass door of the Senate Credit Union just at the opposite edge of the atrium.

This time, exiting the credit union, I decided I would walk round it--maybe I did that, once, long ago, but the thing about the Senate, the thing about Congress, is that everyone (or most people) feel the need to affect that perpetual busyness, that inner compass of absolute direction, that does not permit letting aimlessness surface, an aimlessness sort of ambulation necessary to absorb the impact of art. Which is to say, everyone walks with purpose by and around this sculpture and no one ever looks up.

Vaguely worried the Capitol police might ask me what the hell I was doing wandering the full perimeter of the sculpture, I did just that. Calder, I thought, walking up to it, it must be Calder. Of course it was: Alexander Calder, Mountains and Clouds. Designed in 1975, Calder delivered the maquette to the Architect of the Capitol in 1976, returned to New York and died the next day. The sculpture was finally completed in 1986.

Looking at the image of this sculpture on the web, you might be tempted to believe you can "see" it. You can't. As I said, it fills the atrium, and my first thought was that the whole thing is misplaced and needs a far bigger display space. Even backing up toward the wall and the elevators next to it, the viewer cannot take the whole thing in. The neck is bent upwards, the eyes shift back and forth, but, from the ground, one only sees the work in pieces. From the ground, the 4,300 pound aluminum clouds are visible by tilting the head back so precariously as to invite vertigo.

Perhaps that's the point. Not the vertigo, but the closeness and the fragmentary nature of viewing the piece. The mountains are always there, some sort of geological joke about eternity, and, clouds, ubiquitous, so often above our heads. But how often do we look? And what do we really see? Especially of things that are so much a part of a backdrop, an experience, a life, as to be, therefore, in their omnipresence, invisible?

And what does this have to do with Robert?

When I walked to the bank that day, I was, by late afternoon, to become extremely frustrated with our latest queries into Robert's diagnosis and treatments. But I didn't know that quite yet, the way one cannot see something very looming and large and beyond the scope of whatever the eyes will frame in increments.

At about 4 pm that day, I received an email from the genetic counselor for Dr. Gropman, Robert's neurologist at Children's Hospital. In October, we'd decided to repeat a neurotransmitter test we'd first done in 2003. This test, performed at a single lab at Baylor University in Texas, analyzes the byproducts of the metabolism of neurotransmitters found in cerebral spinal fluid. The analysis can tell you which neurotransmitters appear to be deficient, but it can't explain why: whether these neurotransmitters (which assist with chemical signals within between and among cells and organs, involved primarily with movement, but also aspects of cognition) are deficient between metabolism is faulty or failing, or whether the body cannot produce enough of them to begin with. Seeing the parts and pieces and bits, but not the whole structure.

In 2003, when we discovered that Robert was deficient in the byproducts of the metabolism of dopamine and serotonin and a couple of other lesser-known biochemicals, we were ecstatic. In 6 years of searching for any sort of data that would provide clues to Robert's profound illness and related disabilities, this test finally gave us something, something we could point to and use to frame, nay, lay a foundation for understanding Robert's problems. My son can't move well because dopamine helps to conduct the signals that enable fine and gross motor movements. My son responds to Sinemet because the drug gives the body the precursors to the manufacture of dopamine. My son can't repeat motor tasks indefinitely because insufficient dopamine re-uptake causes a faltering inability to make the same motion more than a few times (imagine the teacher who claims your child doesn't know an answer because he can't endlessly raise one hand for yes and one for no for the full hour it takes to administer a test). My son cries at sad music uncontrollably because serotonin regulates the brain's emotive centers.

In 2011, Dr. Hyland of Baylor University told us that all of these tests were normal. And, in fact, that these tests of the byproducts of the metabolism of certain neurotransmitters seemed to indicate that Robert did not even have a metabolic disorder--which every single esteemed neurologist he has seen over the course of 13 years has recognized as a distinct possibility based on the clinical presentation and the limited medical data. Not the least of which was his most recent MRIs, which showed the classic brain damage of a person with Leigh's syndrome, a mitochondrial disorder (a category of metabolic disease). No matter that we can't find the gene defect for this; at least we had a concept.

It was like this: for 8 years, a city grid was laid out for us and our doctors and teachers and friends. Vehicles traveled through this grid--we didn't know where each and everyone of them was going and most were occupied by strangers, but they traveled on city streets we could name and intersections that appeared to be governed by functioning stoplights with the occasional red light runner and the tourist who pauses at the green light wondering whether right or left is the proper direction. Then. Then someone barricades off those streets so that traffic can no longer travel on them. Suddenly everything is empty, yet the traffic lights of our understanding and expectations continue to flash in a coordinated manner, the way the mind moves for a while after a shock as though life might still be quite normal.

Fortunately, life moves on multiple parallel tracks. This summer, we'd been connected to Jimmy Lin, who has started a nonprofit to enable families with undiagnosed children to access genome sequencing. Rare Genomics Institute, the nonprofit, had established its website in the fall, interviewed 3 or 4 families to pilot its work, and begun to connect those families with the specialists who could help them. The funding mechanism is crowd sourcing, a form of fundraising through social networks.

Robert's fundraising page had been set up. In fact, I'd agreed to be interviewed by the Baltimore Sun as part of an article about Rare Genomics, an article that appeared about 10 days before the Baylor tests came back negative, unexpectedly. Wire services had picked up the article, and it ran in papers in Indiana, Arizona, South Caroline, Illinois, California, and Oregon. By early December, we'd raised $1,400, almost all of it from total strangers who had read those articles. I cannot describe my reaction without using the simple cliche: I was blown away by American generosity.

Our own press forward with fundraising had been held back a bit--we wanted to get past that round of testing we'd been waiting on, we wanted to think carefully through how best to approach friends and relatives, we wanted to be careful and do it right. And we were side-tracked with the enormous number of holiday and end-of-year tasks that constitute the medical and social services bureaucracy of Robert's care and treatment.

[And, my dear regular readers, if you're still out there after my spotty posting this fall, on November 4, I was notified that I'd been awarded a MacDowell fellowship in non-fiction, which gives me a month of support at their artist colony in New Hampshire to work on the book I'm writing about Robert. And I thank each and every one of you for reading as I've worked on this material, because the project started with this blog. So--the award was also its own kind of special distraction.]

But, on December 11, after 3 weeks of living with the shock and awe of those test results, I couldn't stand it anymore. Years ago, as tests came back negative and normal, as what-was-wrong loomed obvious and frightening and damaging, the lack of diagnosis relieved me. No one could prove to me that Robert would die or be profoundly limited or impaired. I was free to treat him normally, to believe in him because no one could definitively tell me otherwise.

But now, after all of this, after my city in ruins, so to speak, I want to know. And genome sequencing offers the best chance at knowing. No, it cannot promise miracles, it cannot absolutely promise it will find the defect in the winding haystack of the same four proteins that in different patterns constitute our height, our hair, our skeletal structure, our propensity for disease--but it's my best chance. Like Mountains and Clouds, the answer is there somewhere, and, even if at ground level we can only see it in bits and pieces, maybe there's another platform from which we can see much more.

So I posted the Baltimore Sun article on Facebook on December 11, just threw it out there, as well as the link to Robert's page. And I asked people to re-post. And they did. And the money just started coming. In 48 hours, we were about 75% there, and by last week, when Robert was hospitalized with pneumonia, we went over the top of the $7,500 we needed to raise.

And this experience was like having walked by Mountains and Clouds every day, never looking up. Every day, I see only a portion of my friends, my acquaintances, and the faces of strangers I've made eye contact with while taking Robert out and about. Sometimes, the vast sculpture of the people whom we know--who are, in themselves, a work of art, people from all the parts of my life, connected and constellated and omnipresent the way we all are in a socially networked universe--becomes visible, all at once.

And I thank you all for that--those of you whom I know, those of you whom I didn't. Those of you who passed the message on, even if you couldn't give, those of you who gave even if it was a sacrifice to donate only a few dollars, those of you who gave more than I had any right to expect--all of you who cared to in one way or another contribute your support, monetary, emotional, both, all.

I praise you. And my New Year's resolution is to pick up the slack reins of this blog and let you know how it all proceeds for us as we move through the next rounds of medical intake eval, treatments, and tests. In early January we start meeting with doctors about sequencing. This story may not have a definitive end, but I will post as many of the chapters as I can. And I'll continue to write, as I have in the past, about the other challenges Robert faces.

And the guy who seemed as though he would never ask me out thanks you, too. Because eventually, a question is asked and the answer is yes, and then yes, and then yes, again.


A said...

Congratulations on the fellowship! As for the apparently conflicting test results, been there, and to say it is disconcerting is of course gross understatement. No diagnosis, diagnosis, no diagnosis. I hope the full genome testing will uncover some clues.

The Professor said...

So happy to hear that Robert's testing will go forward and praying that an answer can be found for you all. Keeping you in our prayers here at Winthrop!

Elizabeth said...

I so understand the ups and downs and rowing in and then back out of the testing thing despite the differences in our situations. I hope that this time you WILL discover something or the not-discovering will be conclusive enough for peace. As for your writing, I just knew it was a matter of time before the rest of the world was let in on its wonder and genius. I'm so looking forward to reading your book and claiming prescience --