“The beginning of wisdom is to call things by their right names.” — Chinese proverb
Imagine a young couple, happy, and bubbling with anticipation over the birth of their first child. Only a few months are left before the big day. But then a sonogram reveals an anomaly – maybe in the shape of the skull, or the size of the kidneys. Something isn’t quite right.
Hearing such news is among the most devastating things a parent can experience. Thrown into panic mode, parents hunger for more information, and grasp for something tangible to help them understand what is happening with their child. Will my baby be OK? Will she be healthy? Will he be normal? What kind of life will she have? How will we all have to function?
It is a situation that cries out for a diagnosis. It demands to be named.
Sara Huston Katsanis of Duke University’s Science and Society works with families who find themselves in these extremely trying circumstances. She uses the newest technique of whole genome sequencing of the child and parents to examine their billions of pieces of genetic code.
Sorting though this tremendous amount of genetic information, the goal is to find clues — places here or there which might point to the source of the anomaly. Knowledge can give us some sense of control, especially when we feel totally overwhelmed,. It gives us power to assuage the tempest inside.Read Transcript
I’m Sara Huston Katsanis and I work at Duke Science and Society and my research is in genetics policy as applies to law enforcement, and also medical testing and whole-genome exome testing. So at Duke, we have a program called the Task Force for Neonatal Genetics, and part of this program is we sequence the genomes of newborn babies or very young children that are born with an undiagnosed disorder. And by doing the whole genome, we’re able to look at as much of the information as we can for the child. We diagnose, or we seek to diagnose, what is causing the rare disease that we’re seeing and in small children or newborn children. And these children are usually – have something wrong with them that seems to be genetic, and the way we decide whether it seems to be genetics is usually when it’s more than one system. So if it’s both in the brain and in the kidney, or a structural anomaly of the face and also in the brain.
When we see these rare traits happening in a child, and the parents seem perfectly normal, it’s clear to us that there is something genetic happening. Now sometimes that is affecting behavior as well, and sometimes it is simply a structural change that doesn’t change behavior at all and just causes problems in the physical formation of the baby. Maybe they have problems with their kidney, or problems with their liver, or problems just breathing properly.
So the reason we do this genome sequencing is to find the underlying cause of their disease, and that might help to treat the child, but in many cases it doesn’t necessarily help to treat the child – rather, it helps the parents to understand and put a name to what is happening to their child. So there’s a lot of personal utility, rather than clinical utility, in doing the genome sequencing and finding this underlying cause.
When a parent then has a name for the [disease], what is happening, it changes how they’re able to interact and manage, just personally, how they’re able to manage what is happening to their family. It’s one of the worst news somebody could have, is when they have a newborn child and the doctor says there’s something very wrong, it’s probably genetic and it isn’t curable. This is devastating for a family. And when they then say if you can say, “OK, it’s cystic fibrosis,” then parents can say “OK, I can read about that, I can think about it, I can group with other parents and I can start to manage this and process it.” But when the doctor says, “we don’t know what it is, we’ve never seen this before, yours is the only one in the world like this,” then that’s a whole nother set of emotions that the parents have.
I’m passionate about my work with the families with these rare diseases, because they feel like islands to themselves, the parents. And it’s tough on parents, it’s really tough on marriages, it’s tough on families, they have to rely on external support from grandparents, aunts, uncles, the “village.” And it’s hard it’s really, really hard for them, and when you tell them that it is rare, they’re the only ones, they feel really alone.
So my role is to bring these families together. We host a Family Forum every year for all of our research subjects, so all the children and parents that are involved in the study are invited to come together and to have that – it’s not a support group so much as just a community of “we’re all struggling with the same thing.” Each family doesn’t know what is happening. Some of them will have answers, some of them won’t. Some of them will have a name to the disease, and some of them don’t. Some of them have kidney defects, others have heart defects, so they’re even different spectrums of phenotypes and traits.
But by bringing them together, all of these – we call them ns of one, n=1 – bringing all of these families together makes them feel like they’re part of a community and makes them feel less alone. And that’s why I do that, that’s the most rewarding part of what I do, even if they don’t have an answer, even if we can’t find the answer, because we looked through the genome, we’ll look for that change. All of the genome, billions of bases, and we still can’t find it. So maybe it isn’t genetic. Maybe it somewhere we didn’t look; we don’t know. But we can still at least engage with the family and let them have some community as they’re struggling through this.
So if knowledge is power, then more knowledge would lead to more power. And that’s where “big data” comes in. Through big data, one can “see” how evolution creates, molds and destroys. Such processes can be seen in individuals, in groups of people and in all of humanity over time.
That’s why Dr. Greg Samsa, biostatistician in the Duke University School of Medicine, likes big data. He takes billions of pieces of genetic information from studies like Sara’s, reaches deep down inside, and tries to pull out its meaning.
In addition to finding the small clues that may diagnose rare conditions, Greg can look for patterns across many people and discern a view of life that most of us can’t possibly imagine. Big data forces us to think about numbers we don’t live with on a day to day basis. Whether it’s our genetic code or the age of the universe, big data creates billions and billions of pieces of information. Yet when we are able to make sense of the data, we can begin to see where we’ve come from, how we came to be and, perhaps, how we may be constrained in becoming who we want to be.
I’m Greg Samsa, I’m a biostatistician from Duke University. In my spare time I’m a character in a Kafka novel. We, basically statisticians, analyze data, genomic and otherwise – and I’m particularly interested in personalized medicine and how health systems learn.
So it’s been asked whether statisticians have a particular perspective on genomic data and genetic data, and I think we do. The first component of the perspective is, I think it gives statisticians a particular intuition about how evolution works, because evolution basically works with variation and the play of chance over time. And it’s utterly remarkable, once one does simulations, once one looks at the play of chance, how profound the changes are given in populations. So you really get a sense of of how evolution works. In fact, many of the early statisticians were evolutionary biologists. So statisticians kind of sprang from that field.
Kind of additionally, another insight that I’ve had, if not necessarily as a statistician, but as someone who’s had the privilege to do science over many years and to work with some very talented scientists over the years – as a matter of fact, that’s one of the wonderful things about being a statistician, is who you get to hang out with. One of the insights is, kind of, the word “billions.” If we were to compare, say, the year 1815 with the year 2015, and we think “how far could we see?” We had telescopes, we could see the rings of – we could see to the rings of Saturn, we could see mountains on the moon. Probably, if we put it in terms of light years, probably less than an hour. A light-hour, as many miles as light can travel in an hour. Which is a long way, it’s way farther than you can see with the naked eye. The telescope was a wonderful invention.
But now, 200 years later, we can see to within a split second of the Big Bang, and that’s 13 billion light years. So we can see more than a billion times farther than we could 200 years ago. Now we can make an analogy with the genome. We can see three billion letters of our genetic alphabet now, and we could see none then. We can see probably more than a billion times more deeply. I think, though, genomics won’t meet the dreams of its developers until we can see a billion times farther. We’re going to have to see that far to understand how this wonderful, complex, finely tuned system works.
The ability to see more allows us to find more patterns, make more meaning and assign more names so we confront and even change the human condition. But that leaves us with several questions.
First, are we nearing a place where technology can tell us all or most of what we need to know? And if we are, do we let big corporations and institutions lead the way, with the regulatory agencies following behind slowly? If knowledge is power, then how should we use this power?
Even more importantly, where do questions of purpose, right and wrong come in? What happens when we are able to change our genes?
We welcome your thoughts to this discussion!
(This post is part of the Sinai and Synapses Discussion Forum, a collection of perspectives on specific topics. It is part of our series “Are We More Than Our Genes?” For more on our series of videos exploring this question, please look at the post Our Genes, Our Selves).