Hunting Down My Son's Killer

http://matt.might.net/articles/my-sons-killer/

by synacksynack • 14 years ago

1139 318 14 years ago

matt.might.net

euroclydon• 14 years ago

Where is the line drawn between medical research and healthcare for your son? In other words, what on earth does this cost?

mattmight12• 14 years ago

Remarkably, the cost of the exomic sequencing is a small fraction of what we spent on individual genetic tests over three years.

Exomic sequencing is so efficient that it will likely replace testing for individual genetic disorders one-by-one in the near future.

In the pilot study at Duke, they diagnosed 6 of the 12 children, each of whom had an ordeal very much like my son.

In the rare disease community, this technique is unparalleled.

Stwerp• 14 years ago

Your article is amazing. I was moved to tears many times reading through this. (My wife is 6 months pregnant right now.) Just wow. Good luck with it all, and the fact that Victoria does not have the same diagnosis is just amazing! I'm glad Duke could help and your story is beautiful and inspiring. I don't know what to say, just, thank you so much for writing this. I will certainly be passing this on to some friends.

pimentel• 14 years ago

When there's scientific interest in the case, will a university charge for exams and tests? What about research clinics? When does an institution say "from now on, we'll take care of costs"?

GFischer• 14 years ago

Hopefully, sharing this information and your story will lead to more informed doctors recommending this technique.

Thank you for an inspiring story and your exemplary perseverance.

lmm2• 14 years ago

I wonder if another jurisdiction would be more willing to let you try the enzyme? The FDA is famously slow in granting approval.

mattmight12• 14 years ago

The FDA has a special protocol in place for rare cases like my son.

If we get everything done properly, approval could be granted within 30 days.

But, before we can apply to the FDA, we have to get Genzyme to agree to make a variant suitable for human use.

My wife found studies where it was beneficial to mice that had chlamydia and pneumonia, so we know there's a form out that that's been used on mammals.

tincholio• 14 years ago

Dude, as a recently minted father, I can't begin to grasp what you guys are going through. I just want to wish you the best of lucks with this.

On a completely unrelated - and irrelevant - note, I find your writings fascinating.

tonetheman• 14 years ago

Wow this was crazy interesting. My thoughts are with his parents. I learned a ton just reading the article.

jasonlotito9• 14 years ago

As a father with a son with severe autism (not to suggest it's equivalent to Bertrand's condition), there is an important lesson here that might not be apparent at first read.

Before you have children, understand that it's for the rest of your life. Really understand the impact. Your concerns are second, beyond anything you've ever understood. Marriage is about compromise. Children, however, afford no such privilege.

Make no mistake, it's worth it. Looking into those eyes, seeing that smile. Getting your first smile, laugh, hug, or kiss. Nothing compares.

edwinnathaniel2• 14 years ago

This important lesson can only be detected by parents. People with no children won't ever understand this no matter how hard they try/re-read the articles many times.

Once the infant is out of the womb, everything change instantly without any interference by anyone, anybody, or anything else. The child will change your brain, your mind, your heart, your lifestyle, and your future at that moment of birth. The child IS that BIG.

I cannot say how much I respect parents, even more for those who have children with special needs.

Life is really beautiful isn't it? (^_^).

Havoc2• 14 years ago

>People with no children won't ever understand this no matter how hard they try/re-read the articles many times.

Halfway through the article I started re-evaluating whether I still want kids. Not sure I could carry that burden. [] Though that is probably more on a logical level than feeling the raw emotion that a parent would - which is probably what you were getting at.

More accurately I know I could out of necessity carry that burden. Its everything else in life which would be more difficult. Kinda like a warrior without family at home has the luxury of adopting a devil-may-care attitude to combat - once others depend on him that isn't possible anymore.

lotharbot• 14 years ago

One way I like to explain this to non-parents:

when you get married, it changes the way you relate to your spouse, to their relatives, and to others who used to be "dating prospects" -- so, maybe 1/10 of the people you come in contact with. That's a pretty big deal.

when you have a child, it changes the way you relate to almost everybody, even people you've known your entire life. Your parents become "grandma" and "grandpa"; your siblings become "aunt" and "uncle". Even you become "daddy" or "mommy". Your friends are no longer just people you hang out with, they're people who influence your child. Every decision you make now gets framed in terms of "how does this affect my kid?" It's an order of magnitude bigger than marriage.

Nobody is ever really ready for it, but most of us figure it out. And I think it's totally worth all the struggle. (My mildly autistic 2 year old just drew a letter F with sidewalk chalk, on purpose, and it made my day!)

altrego99• 14 years ago

Sorry, not worth it at all. Years 1-10 - you will loose all your time - cleaning diapers, making the child eat, making it study, teaching it values - waking up at night - and doing a lot of things for it. Yes you'll see it learn, smile, grow up and you're genetically conditioned to like it. But you will not be able to play your games, go to your parties - read book or contemplate on life, or code without expecting interruptions.

Years 11-20 - manage the child's other needs - worry about getting into a good school/college, making sure there is no bad company, and making sure no bad mistakes are made which can be made very difficult due to teenage defiance to old values etc.

Years 21+ - child will leave and stay separately - you should more or less start becoming free once again. That is if you do not have a second child!

celticninja• 14 years ago

Wow your kids must suck.

mgoulart• 14 years ago

Is that what your parents told you ? :)

mcmatterson5• 14 years ago

Balls to this. As your sibling commenter says, you simply don't get to pass judgement on this if you haven't had a child of your own.

Sure, we're programmed to behave with an otherwise inexcusable amount of irrationality with our kids, but that's not by accident. If anything, it demonstrates the level of evolutionary importance in keeping our offspring healthy and ensuring their success: it's such an important directive in fact, that evolution has deemed it more important than the needs of the parents to 'play [their] games, go to [their] parties -- read book[s]...or code'.

I'm not going to tell you you're objectively wrong on this, but I will tell you that you have no idea what you're talking about. Life is a squishy, inconvenient, and occasionally beautiful endeavour. Realize that.

maratd5• 14 years ago

You either don't have kids or you're a psychopath. I'm leaning toward the former. Don't presume in your arrogance that you know quite a bit about something you have zero experience with.

All your accomplishments are pointless without your child next to you.

> Yes you'll see it learn, smile, grow up

It? Nice.

> But you will not be able to play your games, go to your parties - read book or contemplate on life, or code without expecting interruptions.

Sophistry. You don't even understand why you do all of those things. You simply enjoy them and that's an end in itself.

No, you're not some amazing savant that has popped up out of the mass of mediocrity that is humanity.

You enjoy all of those things to gain the capacity to enrich the life of your child. No child? All the stuff you enjoy loses its meaning.

alain94040• 14 years ago

Ha. Can't wait for your [future] kids to discover your post on HN, 15 years from now, and give you a hard time about it.

aidenn04• 14 years ago

I posted a longer post as a sibling to this before I read your comment. In a lot of ways this is true, and I encourage anyone who agrees with you to not become a parent, rather than being a poor parent.

ceejayoz• 14 years ago

> Yes you'll see it learn, smile, grow up and you're genetically conditioned to like it. But you will not be able to play your games, go to your parties - read book or contemplate on life, or code without expecting interruptions.

Enjoying parties, games, books, and coding has its roots in genetic conditioning, too.

jasonlotito9• 14 years ago

And that's fine that you feel that way. It's good that you've thought this through. I'd much rather someone act this way than pretend like having children is what they want.

run4yourlives10• 14 years ago

This thing that can only cry learns to: talk, walk, read, express themselves, formulate opinions, ride a bike, conquer fears, grow etc. They do this all the while looking at you as a hero with nothing but complete and selfless love for you. All your minor faults are irrelevant to them. You are their everything.

Yes, it's genetic conditioning, but I have been on this planet 37 years and have never experienced emotion on any scale anywhere approaching what fatherhood has given me. Here's another secret - it's completely different the second time around too!

I'm struggling here to find an argument that would help illustrate this to a non-parent and I am failing. I'll leave it at this:

I would give up everything I'll ever do from now until death - my entire existence - in exchange for my children's without more than a 30 second thought. That is what parenthood does to you.

It's fucking great.

jakejake2• 14 years ago

I think a lot of people start out this way including myself. As you hit your late 30's I think is when even some hard-core no-kids people start to re-evaluate their thinking.

I still don't have kids but I'm not anti-kids anymore so if one day it happens I'll be ok with it. What changes is that you go around year after year and you start to see things become a bit repetitive. Holidays with the family, celebrations. Your family starts getting smaller. You start to see how much fresh new energy kids bring to life in general. You start to chill out about the crying and hassles that babies bring and not see them as so much of a burden. All of the things that you've done a million times are suddenly new and exciting because you have somebody to share them with and pass off all of your knowledge, show them all the tricks you've learned in life. I didn't really feel any of that until I had nieces, but I really love hanging around with them.

gyardley• 14 years ago

Kids are a lot of work, but you don't have to make it unnecessarily hard on yourself by raising them American-style.

As long as your child is healthy, it's perfectly possible to wean them early, send them to child care, get them to sleep through the night by not rushing to their side every three seconds, train them to play quietly by themselves, teach them not interrupt their parents when they're busy, get babysitters whenever you have a social occasion, and put your relationship with your spouse first and foremost. Your kids will be just fine.

acuozzo• 14 years ago

> Sorry, not worth it at all.

Does your comment assume that the hypothetical subject (i.e., ``you'') has a stay-at-home spouse?

goggles99• 14 years ago

"Sorry, not worth it at all."

Beware - selfishness feels great but is short lived. Traveling, working, partying, loafing around in your free time. These things get old and eventually you feel empty and Unfulfilled...

How can you predict what brings fulfillment to others anyway? Others may say to you that you will likely spend your latter years and die a miserable lonely recluse in a filthy nursing home. While they are cared for and having a happy existence with their children and grandchildren.

tomjen33• 14 years ago

It is only 'worth it' because your genes needs you to protect the next generation.

Rationally there is no point in having children at all.

And speaking statistically, research shows that parents are no more happy than are those who are not parents.

simonh3• 14 years ago

So what you're saying is you were a complete waste of time and your parents would have been better off without you?

Seriously - I'm not trolling or trying to be abusive. It seems to me that's literally what you're saying.

Life isn't rational. Pleasure isn't rational. In the grand scheme of things, no achievements are significant or meaningful. But that's no way to live a life, IMHO. I know I'm far happier with my children than at any other time in my life, and I only had them when I was in my mid 30s, so I have plenty of perspective on life with them and without.

Yes it was hard work, but so are most things worth doing in this world. I may not really believe that which does not kill you makes you stronger, but I some of the hardest things I've done in life (armed service, relationships, children) have enriched me the most as a person.

I can't say the same is true for everyone. We all have different hopes and needs, desires and goals. I'm happy with mine, and sincerely hope yours work out as well for you.

cturner• 14 years ago

Rationally there's no point in living at all.

I've found it's a good idea to avoid thinking too hard at the level you're taking.

ericb• 14 years ago

I think what you're missing is the emotion, the meaning, and the beauty of having children. And sure, if you leave all that out by willfully ignoring it, then your point makes sense. One could argue that, by the same token, living is just to protect and create the next generation and rationally has no point.

waffle_ss3• 14 years ago

Rationally, there is no point in a lot of things (up to and including just sitting idle as a respiring organism). Do you get your sustenance from an IV bag of the basic chemicals your body needs to survive, or do you eat food that you enjoy the taste of? Do you cover yourself with a burlap sap, or do you wear clothing of a design you prefer? Do you get to work on your own locomotive power (walk, ride bicycle) or use a vehicle?

Variety is the spice of life. We do things that we find intellectually and emotionally stimulating.

donohoe• 14 years ago

  Rationally there is no point in having children at all.

Rationally there is no point doing a startup.

Arjuna• 14 years ago

"And speaking statistically, research shows that parents are no more happy than are those who are not parents."

"Contrary to recent scholarship and popular belief, parents experience greater levels of happiness and meaning in life than people without children, according to researchers from the University of California, Riverside, the University of British Columbia and Stanford University. Parents also are happier during the day when they are caring for their children than during their other daily activities, the researchers found in a series of studies conducted in the United States and Canada. [...] The findings are among a new wave of research that suggests that parenthood comes with relatively more positives, despite the added responsibilities. [...] The consistency of their findings across all three studies 'provides strong evidence challenging the widely held perception that children are associated with reduced well-being.'" [1]

These findings are from this paper, entitled In Defense of Parenthood: Children Are Associated With More Joy Than Misery [2], to be published in Psychological Science. [3]

From the abstract, "The results indicate that, contrary to previous reports, parents (and especially fathers) report relatively higher levels of happiness, positive emotion, and meaning in life."

[1] http://www.psychologicalscience.org/index.php/news/releases/...

[2] (Note: PDF) http://www.faculty.ucr.edu/~sonja/papers/NKEDLinpress.pdf

[3] https://en.wikipedia.org/wiki/Psychological_Science_%28journ...

tzs2• 14 years ago

> Rationally there is no point in having children at all

Nonsense. When used as service animals, children have several advantages over the alternatives. They can be trained to do much more than dogs, for example, have a longer service life, and when they get too big to keep safely they yield more meat after first training their successors for you.

runjake• 14 years ago

And speaking statistically, research shows that parents are no more happy than are those who are not parents.

[citation needed]

Also, since we're being rational and all, define happiness. Contrast it with "fulfillment".

galactus• 14 years ago

"Rationally there is no point in having children at all"

What does that even mean?

Is it "rational" to stay alive? (isn't it only "worth it" because your genes order you not to kill yourself?)

maratd5• 14 years ago

> Marriage is about compromise.

...

> Children, however, afford no such privilege.

Well, at least you're 50% there. Don't compromise with your wife, either.

Lead your wife and children to a better place. Lead them to a place where all of you are happy and yes, it is possible. It's very easy to "compromise" ... just divide by two, right? Much harder to use your noggin and figure out a position where everybody is genuinely happy. You can compromise with your business partners or whoever else is largely irrelevant. With your family, spend the few extra calories, burn the oil, and figure out a path toward making everyone optimally happy.

Lead them there.

aiscott• 14 years ago

I believe the intended meaning of compromise with regards to marriage is about not always getting "your way."

aidenn04• 14 years ago

As a father of 3, I think the question of "is it worth it" is not as cut-and-dry as you suggest.

As I am an extreme introvert, in the near-term, having kids definitely makes me less happy in many measurable ways.

That being said, taking care of children is something I have always been drawn to, and is the way I have chosen to leave my mark on the world, as it were.

We fostered our first two kids for 18 months before we were offered the opportunity to adopt them, so I was in the situation of being able to choose to go back to having no kids in a socially acceptable manner, which is not an opportunity most people get.

I'm going to make the obvious comparison here to starting a company (which I haven't done but am inferring from the numerous articles I've read on it). It's not for everyone, it's a lot of work, and at times you will think you were crazy for ever attempting it. However, for a certain type of person, it's extremely rewarding.

Just like not everyone would be happier if they quit their job and started a company, not everyone would be happier if they became a parent, but if it's something you are drawn to, then by all means, do it!

jasonlotito9• 14 years ago

> As a father of 3, I think the question of "is it worth it" is not as cut-and-dry as you suggest.

I never meant to imply anything was so cut and dry. Apologies for making it seem so. I just wanted to point out something people should learn from this post. No one should have children because they feel as if they are expected to. They really need to understand what kind of commitment it entails.

yason4• 14 years ago

Marriage is about compromise. Children, however, afford no such privilege.

No, marriage is having one heck of a good time living your life with your spouse.

Being a single parent is better than a bad marriage. And marriage can only be good if the parents know and acknowledge that they together go first, kids come second. Period.

Your spouse is the person you spend rest of your life (or at least decades, if you're lucky) and if you give up too much of that for the kids, you won't necessarily have a relationship once the kids move out in twenty years or so.

It's not my intention to lure you into thinking that parents should do whatever they need to do and mostly ignore the kids. (A whole lot of good people have been raised that way over the centuries, though.) However, nobody promised the kids a rose garden and neither did anyone promise the same to you.

It's just those times in life when there's too much everything and good times are sparse. That is when you need to take care of yourself first, because that's a prerequisite for a relationship. Then you need to take care of your relationship because that's a prerequisite for a working family of two parents and one or more kids. When the relationship is all right, then you can truly take care of the kids too, not just mechanically play a role for a decade while getting more and more bitter every year.

Most of the time you do all three—yourself, your relationship, your kids—but you must know which comes first in the tight spot. It's like oxygen masks on the plane.

After all, your kids will first try to learn how to live and be happy by mimicking how you live your own life.

You don't ever own your kids' lives and you won't even have much control over theirs for more than the 10-15 early years.

So be sure you take care of yourself and your marriage because that's what makes you happy for a long time, in your own life.

throw-a-way-3• 14 years ago

> And marriage can only be good if the parents know and acknowledge that they together go first, kids come second. Period.

Eye-opener for me. This is very true, and a harsh truth at that.

You made me finally understand what broke my parents' relationship. One of them focused on children, with "at all costs" mindset. And the cost was great indeed.

> and you won't even have much control over theirs for more than the 10-15 early years.

That much just as well.

run4yourlives10• 14 years ago

I don't mean to be rude, but I think your comment illustrates the attitude prevalent in countries with 50% marriage failure rates. Your ideal is simply unsustainable and impossible.

First: Are you married now (or have you been) and do you have kids? I'll assume you are married/committed but I'm not sure you are a parent, given your views. This is a tremendously important point to help frame this discussion. I fear you probably won't understand my points at all with out first hand experience.

What you are saying isn't technically wrong, but it requires precise compromise in order to be successful. That's exactly what jasonlotito is saying: You can't get what you want all the time, especially with your partner, most certainly with your children.

You and your partner need to understand, respect, and tolerate each other, first and foremost. Some people are simply incapable of doing this, period. Some people conflate this with making their life completely about the other person. Both of these people will be miserable regardless. For the rest of us though, simply understanding that statement means the marriage is a compromise - sometimes you get your way and your partner tolerates, sometimes you tolerate and your partner gets to do their thing, most often you are both getting your ways, as they are the same, but sometimes both of you are tolerating, for the good of the family/marriage.

Of course, with children, that last point becomes a vast majority of your life. Kids are the centre of their worlds and don't really understand how to be anything else. It takes literally years to impact the knowledge that life is better when they look outwards towards others into their little heads. Until then, you and your partner will do a lot of tolerating in your lives. How well you can do this (and when not to) will pretty much define how successful a parent you will be. It's an approach governed by the exact opposite thoughts that you are presenting however: Child first, couple second, self last.

Be clear than I'm not suggesting your entire life should be one of self-sacrifice, That doesn't work either. But it must be the last of your concerns 90% of the time if you are to make raising kids and marriage - especially marriage - work. Ensure the kids are alright (not necessarily that they get their way all the time), ensure your spouse is alright (happy wife, happy life after all) and ensure you are alright in that order, and you have a winning formula.

Looking out for yourself first is a guaranteed path to conflict. It's very rare that you can do this and remain in sync with other people, even best friends and spouses aren't going to want to do the same things all the time. Your children will never want to do the same things as you in any consistent fashion, which is way most happy family spend time in parks during the day as opposed to bars late at night.

jasonlotito9• 14 years ago

You're really reading a lot more into that than was intended. Indeed, you completely miss the point, which is clear with this:

> you won't necessarily have a relationship once the kids move out in twenty years or so.

Right here is the problem. You assume a healthy child, one that is capable of living on their own. But you have a responsibility to that child if they can't.

This doesn't mean you give up your dreams. This doesn't mean an end to your life. But it means taking care of your children. It's your responsibility.

I can't just ignore my child's care and go on a long vacation with the wife. Oh, I mean, I could, but that would be tantamount to child abuse. I need to make sure he's cared for, appropriately, or adjust my vacation to accomodate his needs.

> You don't ever own your kids' lives and you won't even have much control over theirs for more than the 10-15 early years.

This is why you can't just quote a part of the comment, and take it out of context. I'm faced with the very real possibility that I'll be responsible for my son's life for much longer than that. You can't just make assumptions like you are.

So no, you are wrong. Wrong, because you make some obviously wrong assumptions that simply don't hold up to any amount of scrutiny. I think your intent is honest, but frankly, you're trying to argue a point that is, frankly, pointless.

Edit: I do want to point out though, that neglecting your marriage isn't good either. So, please dont' think I'm suggesting that by putting children first, you aren't leaving room for your spouse.

jakejake2• 14 years ago

I do agree with you that people flame out because their lives evolve around kids and they lose touch with each other. It can't really be underestimated the amount of energy required to stop that from happening. You always see on TV that marriage takes work but I doubt many people understand what that actually means until they're in it. Little things can creep up on you. Your spouse may feel neglected and you won't even know it until it's gotten to be a serious problem. You might think you're being the perfect parents because you dote on your kids and meanwhile your spouse is lonely and unhappy. You might not even be aware that you're being selfish. Children tend to consume every ounce of energy that the parents have, especially in the early years. That doesn't leave a lot of time or energy left for each other. It really takes a constant effort and work to keep the marriage healthy.

mibbitier5• 14 years ago

> "And marriage can only be good if the parents know and acknowledge that they together go first, kids come second. Period."

That's a terribly sad outlook. Your children are extensions of yourself. They should come first forever. They're not pets that you just take in and look after. They're your babies...

I don't know if you have kids or not, maybe you don't have very strong parental feelings :/

tzs2• 14 years ago

> Before you have children, understand that it's for the rest of your life. Really understand the impact. Your concerns are second, beyond anything you've ever understood. Marriage is about compromise. Children, however, afford no such privilege.

Related to that, understand that marriage is (generally) with someone who had a choice in the matter. If your spouse is not happy with some aspect of you that was reasonably discoverable before they married you, they can request that you change but have no right to expect you to.

For instance, if they know going into the marriage that you a workaholic who places the success of your business above doing "people" things, and they are going to have a problem being married to someone who only will have time for "couple" things maybe one night a month, then they should have declined to enter into the marriage.

Kids, on the other hand, have no choice. You made them, they are your responsibility, and if that means you have to limit your work to around 40 hours a week and do that on a regular schedule so you can be there to tend to them, play with them, entertain them, teach them, go to their school plays, and so on, that's what you have to do. As jasonlotito notes, your concerns now come second.

perlgeek3• 14 years ago

> Before you have children, understand that it's for the rest of your life. Really understand the impact.

As a father with a son with severe autism, and remembering the time before you were a father, do you think that anybody can imagine what it's like?

I have a healthy daughter (16 months old), and that alone changed my live beyond anything I could have imagined before.

I don't want to belittle anybody's imagination, but in my experience imagination only works well for envisioning things happening to you in short time scales.

jasonlotito9• 14 years ago

> do you think that anybody can imagine what it's like?

Oh, no. Of course not. But they should consider the possibility. You cannot assume that it's going to be 18-20 years and they are on their own. That it's diapers for only a couple years and then you don't have to change them.

No, there is no way they can fully grasp what it means. But they can't just assume everything will be fine. My wife and I did this, and we waited, and prepared, and we had kids once we were ready. Really ready, and I'd like to think it shows in our children, in our marriage, and in our lives. No, we weren't ready for autism, but we did understand that things could go wrong.

So yes, you are right. But it still can't hurt to think about it. Really think about it. More than what some people do.

nicholassmith• 14 years ago

Wow, just wow. A parent will go to any limit for their child but that was one of the most truly detailed descriptions I've ever heard of diagnosing a new genetic condition. Thank you for being willing to share it.

I genuinely hope you find a solution, will you keep updating on the progress?

mattmight12• 14 years ago

Thanks for the kind words!

My wife updates his progress regularly here:

http://overcomingmovementdisorder.blogspot.com/

The blog is oddly titled now, since we named it back when he was 8 months old.

djb_hackernews• 14 years ago

This is extremely interesting.

Whats the best case scenario for your son? Suppose everything works out perfectly with the treatment/therapy, is it expected he'll start to develop normally?

mattmight12• 14 years ago

Sadly, since he's four and a half, "normal" is probably too much to expect.

But, if we can stop the seizures, he might be able to start learning.

He advanced very rapidly during the two month break from seizures that he got from ACTH.

If we stop them soon, there's a good chance he might be able to walk and talk some day.

Regardless of how far he develops, he'll be much happier than he is now.

aarondf• 14 years ago

I've just finished the article and I must say, my feelings are mixed. I'm reading along and it reads like an epic tale where the hero will surely win in the end, it's both mysterious and exciting. I got caught very caught up, wondering what you were going to try next. (Note: It's never Lupus.) But then I would come out of my Dr. House fantasies and realize, this is real. This is your son. And my heart would break for him and your family.

Thank you for sharing, in great detail, the story of your struggle and I hope that in the end it is a story with a wonderful outcome.

Either way, it certainly a story of heroism.

Keep us updated.

apaprocki• 14 years ago

Just as a useful data point, exome sequencing is now in the sub-$1000 range.[1] There will definitely be a shortage of skilled people able to interpret the data and find mutations like the one mentioned in this article as the sequencing price point continues to drop.

[1] https://www.23andme.com/exome/

ykaranfil• 14 years ago

Just ordered a kit from 23andme

hirenj4• 14 years ago

First thoughts reading up on this pretty cool bit of detective work: Since this is a deficiency in production of Pngase F, I'm not sure a simple injection of Pngase F is going to work. I'd guess you'd need to target Pngase F into the ER to kick start the proper clean-up process, and the human form (http://www.uniprot.org/uniprot/Q96IV0) is different to the recombinant form that you can get synthesised (http://www.uniprot.org/uniprot/P21163). I'm not really sure how native Pngase-F is regulated!

That said - I'm about to start work on very similar work now (also in the area of glycobiology). With dirt cheap exome sequencing, we're going to get a whole bunch of really interesting leads from the data. This means that the follow-up research into the mechanism behind the action of the gene can be more likely to yield results.

Right now, I see the bottle neck in this whole process being the actual experimental analysis of these mutations. Once we solve how to scale up this hard work successfully, we can start looking at curing these incredibly rare diseases.

Dn_Ab3• 14 years ago

In what way is experimental analysis of such mutations a bottleneck?

hirenj4• 14 years ago

Well, once you pinpoint a potential mutation on a gene - that gives you a starting point into the pathway that could be possibly producing this particular disease. From there, it's sort of like clicking outwards from a wikipedia page, except instead of wiki pages, its related genes. Every one you go to, you read and find out what people know about it. You then start to form a picture in your head as to what the mechanisms of action are for this particular gene - what it does and how it is regulated.

From there, you build your model for how the gene works, and do some knock-outs / knock-ins, test it in various cell lines, verify the kinetics, try to find out the 3D structure. Really, anything you can do to get a handle on how this actually works in the system. It's quite normal for people to spend their entire PhD studying the mechanism of action for a single gene!

mattmight12• 14 years ago

Wow! This is fascinating.

Thank you so much for the pointers!

Are you a grad student/postdoc/faculty?

hirenj4• 14 years ago

I'm afraid it isn't the most in-depth of a write-up!

I'm a postdoc computational biologist at the Copenhagen Center for Glycomics, so you could say this is somewhat up my alley ;)

Feel free to fire off an email (in the profile) if you've got any questions, and I can try to help out.

sneak2• 14 years ago

Why on Earth would you conceive another child with the risks involved here?

There are thousands of unwanted children that would benefit from having such a thoughtful and dedicated set of parents.

Is it pure egocentrism that keeps high-risk parents from adopting?

drivebyacct2• 14 years ago

>Is it pure egocentrism that keeps high-risk parents from adopting?

If it's not, I'd love to know what it is. Aww, downvotes from selfish people. Love doesn't require blood.

lostlogin2• 14 years ago

Cost, complexity, difficulty, perceives trouble bonding, how?, risks, issues with the child's family. There are some.

mattmight12• 14 years ago

When we decided to have a second child, we'd ruled out every existing disorder that could possibly explain him.

After consultation with our medical team, they concurred that a de novo mutation for Bertrand was a strong possibility.

And, in truth, the conditional probability of de novo mutation for Bertrand was much higher than what actually happened--two independent mutations in the same gene colliding with one another.

If we had known the probability for Victoria was 1/4, we never would have gotten pregnant.

Ignorance was bliss.

mcmatterson5• 14 years ago

As a parent of a child who was born with a near-fatal congenital disorder (malignant sacrococcygeal teratoma), I can attest that the decision to try for #2 is a difficult one that we're still wrestling with.

On the one hand ours was a one-off event and subsequent kids should be fine. We've always wanted two, and it's been such a wonderful experience that we want more of. So there's that.

On the other hand, the months of treatment after diagnosis were the most emotionally draining experience we've ever gone through, and we don't know if we have it in us to go for number two. We're still in the early days (diagnosis + 9 months, all signs pointing to cured) so this may change, but active parenting causes healing and recovery to happen much slower.

My wife (and her brother) are also both adopted, so we're well aware of the dynamics involved there. We've said since before we started trying for kids that we weren't going to beat ourselves up if we'd had problems conceiving (we gave ourselves nine months of trying before we'd look at adoption. As it turns out it only took us one). One could probably argue that the truly optimal thing to do would have been to forego trying biologically at all and to jump right into adoption, but that didn't feel right either.

All of which is to say that I don't think it's egocentricity per se, but a natural desire to at least try and see your genes successfully expressed in the world. While that's not ideal from a rational perspective, I don't think you can go too far down that line of thinking without verging into eugenics.

sneak2• 14 years ago

To be clear: I think it's unconscionable to conceive a child while there are un-adopted ones, even if it's your first and guaranteed to be healthy.

There are perfectly good babies out there that need love and care, and by making your own you are basically saying "fuck them, the one that shares my DNA is better".

jseliger2• 14 years ago

Is it pure egocentrism that keeps high-risk parents from adopting?

Interestingly enough, adopted children tend to resemble their birth parents much more than adopted parents in the "Big Five" personality traits, and twins raised apart from each other resemble one another to a shocking degree. Bryan Caplan's book Selfish Reasons to Have More Kids discusses many of the studies that have examined these issues.

If you want a kid who is "like you," your optimal choice is probably to have biological children. The joys (and problems?) of being a parent, however, appear to be universal. Note that the first paragraph and Caplan's book are not an argument against adoption, but they are a reminder that genetics appear to have a much more powerful influence on people's personality than most Americans / Westerners wanted to believe for a very long time.

vectorpush• 14 years ago

This was a fascinating and inspiring read. It's astounding to consider the granularity with which we can debug the software of human biology, even if it requires incredible resources. That protein visualization is dumbfounding, but it feels comforting to know that human source code isn't completely intractable.

fghh45sdfhr3• 14 years ago

Even though his disease is life-threatening, his seizures are worsening and he continues to lose white matter, we'll need to prove that it's safe.

A good argument could be made, that bureaucratic regulators who get nothing if your son is cured, but could get in trouble if something they allow hurts him even more, are partly responsible for slowly killing him.

For individuals in a dire enough state, a more intelligent set of regulations could be something like if enough well known and respected doctors agree this is worth trying, go for it. But bureaucracies are rarely intelligent.

It's just that most of the time bureaucratic involvement creates frustration, costs money, takes time, kills economic growth, etc.

But when it comes to life threatening disease and potential cures, bureaucratic involvement might actually cost lives. Because it is not optimizing saving lives, it is optimizing "safety" over lives, because it is actually optimizing bureaucratic ass covering.

waffle_ss3• 14 years ago

I find this to be a very interesting idea, although I'm still a little dubious about it. I first heard it from an interview with famous Libertarian [Milton Friedman][1] (whom I adore) in his twilight years. The self-regulating mechanism of a system like this would be tort law, allowing consumers to sue companies if they haven't done adequate research and testing on their drugs before selling them. I have mixed feelings about this because I have a hard time picturing a class action suit being able to adequately take on a large pharmaceutical company with its own dedicated legal department.

[1] http://www.youtube.com/watch?v=KUDV0YII6lk&t=4m10s

ef42• 14 years ago

People win class action suits against big corporations quite frequently.

And the pharma industry's own actions show that they know they're vulnerable to torts. That's why they lobbied for laws like the Vaccine Act of 1986, which limits their liability for damage caused by vaccines.

ars• 14 years ago

The FDA has a concept of http://en.wikipedia.org/wiki/Compassionate_use which would allow them to use the drug even without any proof.

Symmetry• 14 years ago

Much as I might complain about the FDA sometimes, things have changed for the better since the days when thousands of people were dying for lack of treatments that had been approved in most European states a decade ago.

asdf25• 14 years ago

Thanks for answering the whole issue I came here to complain about, always a nice change to see laws functioning semi-rationally.

waffle_ss3• 14 years ago

Thanks so much for the fascinating and emotionally stirring article. I will definitely be passing this on to others I know.

The thing I kept thinking during the article is, "Is there something that I, as a programmer, can do to help people like Bertrand?"

Is there some way that we programmers could use our talent to augment or advance existing technology in this area? I realize that the science involved here is non-trivial, but it seems like a really fascinating subject area to get involved in. Perhaps I just need to bear down and brush up on my biology.

mattmight12• 14 years ago

Computational biology is a field with much room to grow.

Finding a mutation is just the start of the journey for someone like Bertrand.

Once you find the mutation, you have to figure out what the mutant gene does versus the normal gene.

Duke had to work with a lab, culturing cells from my son and poking at them to figure this part out.

If we were better at predicting the structure of proteins from the DNA that encodes them, we've taken a big first step toward automating/simulating the "functional work."

Protein folding is a nasty research problem at the intersection of chemistry, biology and computer science.

bhickey• 14 years ago

I've spent a bit of time waffling about writing this. I hope I'm not crass.

There's a major problem with incentives in attracting people to research. Why should supply and demand behave differently at universities? I believe that research is an example of the tragedy of the anti-commons.

If I were to jump back to computational biology my lifetime wages would conservatively decrease by $5 million, non-inflation adjusted. Many people are unable to accept lower wages for more interesting work. The wheels of scientific progress will turn slowly as long as it is the sole realm of those able and willing to accept substantial economic sacrifices.

I want to help, I'm just not able.

chaud2• 14 years ago

Sure, go in to bioinformatics research. You might even end up doing something that benefits humanity more than trying to make the next Facebook! Data is piling up faster than we know what to do with it.

There are a lot of problems to be solved that might benefit from computer science. De novo Protein structure and function prediction, better alignment from noisy data, drug target discovery, homology modeling in the twilight zone, better ways to share the data that we do have, better databases to store the data from high-throughput experiments, better ways to compare pathways and biochemical networks, and all of the other things that I could go on to list.

There is no shortage of problems to be solved, only shortages of good people and funding.

lmm2• 14 years ago

>You might even end up doing something that benefits humanity more than trying to make the next Facebook! Data is piling up faster than we know what to do with it.

It's worth mentioning that some of the best tools for letting us do something with it come from the current facebook. I'm constantly tempted to move into academic research rather than helping people get their porn faster, but it seems like a very superficial judgement to say that would be better for humanity in the long run.

ramanujan2• 14 years ago

waffle_ss: Counsyl is a group of computer scientists working on literally this exact problem. We've already put a big dent in the issue with our v1 assay. We are now working on our v2, which is optimized for detecting mutations of the kind that Prof. Might and his wife carried. Take a look at the job description here for more info:

http://goo.gl/kMrxk

Tell me what you think.

sunsu• 14 years ago

It seems like one of the biggest ways we can help is in trying to find more people with the same mutation.

Dn_Ab3• 14 years ago

As not a parent I will not even pretend to relate with what you are going through. But this is one of the most moving and amazing things I have ever read. A book could not contain the details of just how incredible your story is.

Science does work. The confluence of technologies - search, websites,email, computers, bioinformatics, pharmacology, medical technology (and if hirenj's* advice proves useful then forums, it should be at the top), such that someone can identify, diagnose, commision/customize medication and possibly treat a completely new disease in the span of a few years..The future really is here. An ode to the open source technologies and not so open research that made this possible. Of course it is worth pointing out that the skill required to research, evaluate possible leads, try then untry possible treatments, contact and manage communication with the researchers is also not to be underestimated.

*http://news.ycombinator.com/item?id=4038495

postfuturist3• 14 years ago

It pays to become an expert in your own (or your family members') medical conditions, because you'll quickly become more of an expert than 99% of the doctors you will rely on for care. It helps when they all ask the same dumb questions, which they will do. If your condition is mildly rare, you'll notice when you see a new doctor, that their knowledge will be limited to what you found out in the first hour of internet research on the condition, unless they are a specialist on that particular condition.

I have a slightly rare genetic condition, and I've only met 2 doctors who know more than I do, and that's because they do active research on the exact condition and have authored or co-authored multiple research articles on it.

mattmight12• 14 years ago

This comment rings too true.

Most doctors quickly realize that they're outgunned when my wife and I start talking about our son.

We have a lot more luck with PhDs than MDs.

jseliger2• 14 years ago

Part of the problem is that diagnoses and treatments are expanding faster than the ability of humans to memorize and learn about all of them. IIRC there are close to 14,000 diagnoses—just diagnoses!—that we know about. Combine that with the numerous drugs, treatments, and other changes, and it quickly becomes apparent why people with unusual conditions are better off making themselves experts than in relying solely on the expertise of doctors who aren't specialists in whatever they have.

EDIT: Here's the article I was referencing: http://www.newyorker.com/online/blogs/newsdesk/2010/06/gawan... :

Half a century ago, medicine was neither costly nor effective. Since then, however, science has combatted our ignorance. It has enumerated and identified, according to the international disease-classification system, more than 13,600 diagnoses—13,600 different ways our bodies can fail. And for each one we’ve discovered beneficial remedies—remedies that can reduce suffering, extend lives, and sometimes stop a disease altogether. But those remedies now include more than six thousand drugs and four thousand medical and surgical procedures. Our job in medicine is to make sure that all of this capability is deployed, town by town, in the right way at the right time, without harm or waste of resources, for every person alive. And we’re struggling. There is no industry in the world with 13,600 different service lines to deliver.

Note that this was published in 2010. By now those numbers have probably grown.

I've also had personal experience with the doctor-doesn't-know problem: I had an unusual disease seven years ago, and the first specialist I saw said that she Googled it a few hours prior. Her partner gave me completely wrong information; he didn't even know how to treat what I had. Fortunately my family found a research center where some of the major researchers in the field worked, and the treatment I ultimately got had been published a few months before I started (it had become standard two or so years prior). If you're curious about specifics, send me an e-mail—it's in my profile.

crosh• 14 years ago

Sir, your story is absolutely amazing. You, your wife, and your son deserve to be recognized for your struggles that will undoubtedly help others in the future.

crag2• 14 years ago

From 1995 though 1998 I had full blown AIDS. I knew more about care, medication and treatments for AIDS then (almost) any doctor I met.

It was one of the reason so many AIDS patient groups formed (I sat on the board of PWAC and was a member of ACTUP). Because at that time, either doctors did not or could not educate themselves on the subject.

Now, of course, it's a different matter. With HIV being a "manageable" condition (in the West anyway)every ID doctor worth his weight can talk on the subject.

From experience I can tell you, you have to manage your care. You can not expect (nor should you either) a doctor to do it for you.

wpietri• 14 years ago

So true.

My brother nearly came to blows with an emergency room doctor who didn't know the difference between a cancer grade [1] and a cancer stage [2]. Confusing the two, he started to give us the "time to let go" speech, when the appropriate medical action was immediate treatment to suppress brain swelling. Had we not known the difference, she could have died right there.

And there were a number of other less dramatic occasions when being on top of the details solved all sorts of problems when dealing with non-specialist doctors. Which is not to knock them; there are a lot of ways that bodies go wrong, and trying to extract any sense out of the phone book of printouts and scribbled notes in my mom's medical charts is not something anybody could do quickly.

[1] http://en.wikipedia.org/wiki/Grading_%28tumors%29 [2] http://en.wikipedia.org/wiki/Cancer_staging

krschultz2• 14 years ago

To be fair to (most) doctors, especially your primary physician, have to diagonose a huge range of conditions. The edge cases are rare and so they are not as well versed on them.

System specialists are an order of magnitude better. I.e. going to an Ear, Nose & Throat doctor if you have Asthma.

Disease specialists are the pinacle. Sometimes these are researchers rather than normal doctors.

zug• 14 years ago

I have a genetic disease that shows up in 4/100k people, so rare, but not that rare. Any sizable town has at least a few dozen people with my disease.

In my experience, "an order of magnitude better" in specialists means they've at least heard of it, but know nothing about it. Every time I move, I have to spend some time educating my new specialist on the disease. I know damn well that every time one of them excuses themselves in the middle of the exam, they're going to look it up on the internet. It's pretty disheartening.

quantumhobbit• 14 years ago

It is actually counter-productive for doctors to learn too much about rare diseases.

When a patient presents with a set of symptoms, the doctor has to decide whether the patient has a boring common disease or the cool disease which is 100 times rarer. Human beings can't make good judgements about probabilities like that. If every doctor were trained to recognize a rare auto-immune disease that looks just like the flu, plenty of flu sufferers would be misdiagnosed. Far better to teach doctors the treat for flu and refer the cases that don't respond to a specialist.

It is a common problem with doctors fresh out of med school. Common enough that most doctors are taught to "not look for zebras when horses are more likely." If you spend enough time in a hospital you will hear veteran doctors dismiss interns and residents saying, "she's just looking for zebras."

its_so_on2• 14 years ago

I don't like your tone. I have no horse in the race and am not a doctor, but doctors aren't Gods. They learn certain foundational things (names of bones and muscles; organic chemistry) then they learn thing related to the practice that doesn't necessarily rely on any of that stuff. (Diseases; drugs)

For diseases, you should try reading through the Merck manual (available online). Everything from gynecology, oncology, psychiatric conditions, is all there. If your doctor does a correct diagnosis by asking the correct "dumb questions" that is already amazing. Why should a general doctor be more of an expert in every condition than a person who has it? Look up any individual thing in the Merck manual and it has 2-7 pages. Why shouldn't a person who has that particular disease know more about it?

Let's make an analogy. Say your computer has obscure memory errors because you work in a place that bombards them with alpha particles (or whatever). ECC memory is very important to you. And, therefore, I would expect you to know more about ECC memory than "anyone except two engineers doing active research in this exact condition."

It's just one tiny thing in a myriad list of things to know. There is no reason individuals shouldn't take control over their individual conditions and become educated on this subject.

Let me put it this way. If you have a pet guinea pig with asthma, then within a day of learning that you should (or at least could) know more about asthma in guinea pigs than your vet does, because guinea pigs are just 1 species he or she deals with, and asthma is just one condition. Why shouldn't you know more?

Of course, there are systemic things that are very hard for you to understand about what you're reading, and on this you might have a much poorer understanding than your vet...you don't know how the parts work together. it might be obvious to your doctor that asthma puts the guinea pig at risk of - whatever, lung cancer if you smoke near it or whatever, I'm just making it up - just due to the organs involved, whereas you don't know this unless you read it. The point is that you can read all about one CONDITION but not about the whole system, which is what takes so much time to learn. If you MEMORIZE 3 pages of facts about your condition and read them out loud, then there are parts that you would read aloud that say nothing to you, but are deeply meaningful to a doctor.

When it's prescriptions and proscriptions, it's obvious. ('don't feed it raw meats'). When it's general descriptions then it is harder.

Basically, the proper relationship between a person with a rare illness and a GENERAL doctor is, person: "I read that this condition also puts me at risk of a stroke. Could you tell me what that means?" Because you don't UNDERSTAND what a stroke even means, the way a doctor does.

Then your dr. can proceed to fill you in on the parts you don't understand...even though they might not have even recalled that your condition increases the risk of stroke. (or heart attack or whatever). They're not walking encyclopedias, you know: they're experts, just like any other expert in any other field.

CWuestefeld2• 14 years ago

I think I know what you're trying to say: that it's not hard for us to learn some facts, but they're less useful without a broader knowledge of human physiology that an MD would be presumed to have, and we don't. And there's certainly truth to that.

On the other hand, there really are things the lay person can learn and understand well, even in the complex human body.

I have an unusual, if not rare, condition (Crohn's Disease, which GPs now usually seem to have a decent handle on, but that wasn't the case 20-30 years ago). I've had the condition for over 30 years. Barring advancements in science (which I follow anyway) and other possible complications (which I would be discussing with my GP and GI docs anyway, much of what the system forces me to use them for is not only a waste of their time, but problematic for the patients like me because it forces me to wait for an appointment to get the necessary care.

When I have a flare-up, I know exactly what needs to be done. If I walk into a GP's office, or even a GI doc, all they're going to do is rubber-stamp the prescription I know I need, and ask me to come back later to follow up. I already know what I need, the system is just wasting everyone's time, and withholding necessary care.

The thing is that the human body doesn't really follow a strict blueprint: my own deviation from the norm is the reason I'm there in the first place! So by definition, the doctor can't just give me a textbook answer. It all depends on the way the disease affects me personally.

Now, it's true that I may not have sufficiently broad understanding to see when a complication is arising, to handle it specially. But that's no reason to forestall proper care. I'm perfectly capable of starting the treatment on my own, and visiting for further consultation in the timeframe that first available appointment allows. (If such a consultation is so critical, surely getting the treatment rolling is just as much).

But the way care is delivered now, the doctors comprise a priesthood to which we must show obeisance. In my experience, the system could work both more efficiently as well as more effectively if treatment were more of a partnership, with the doctor contributing the deep understanding that he's worked hard for, but a patient also contributing based on the very focused opportunity to learn about his own condition, especially given the unique and personal ways that illness can affect each of us.

WalterBright3• 14 years ago

I think an analogy would be with the 9-11 "truthers" who trot out various facts and conclude that the towers were brought down by demolition charges rather than the plane strike.

Their facts are not wrong, they are just misapplied and someone with a more general understanding of physics knows that.

One of the facts quoted is that jet fuel doesn't burn hot enough to melt steel. By itself, that is true. But the temperature at which jet fuel burns varies depending on all sorts of conditions, and the standard lab setup is not at all what the towers were. For example, fuel in a jet engine certainly burns hot enough to melt steel, it's the limiting factor in jet engine design.

e40• 14 years ago

I don't like your tone.

Wow, I love it when people make an accusation and it's better leveled at them. It's your tone that I don't like.

The original posted was expressing a well-formed opinion, one that is backed up by a lifetime of experience, his and mine.

I can't claim to have an exotic or serious disease, but I do have a lot of chronic medical issues. I cannot tell you how many years I've wasted dealing with Dr's that 1) thought they knew what they were doing (YES, behaving God like!), and 2) had no clue.

The problem with Dr's is they are taught to project confidence, at the expense of their patients.

earnon• 14 years ago

There's a doctor named Paley in Florida who specializes in lengthening limbs. I've talked to many of his patients and their parents.

Most doctors, when presented with a child who has one short leg, recommend amputation (the difference in length causes hip and back problems down the line). I'm sure the doctors could easily find out about Paley if they looked into it.

The parents I've talked to are the few who have refused to accept that they have no choice and have done their own research. My heart aches for the kids whose well-intentioned parents didn't question their doctor.

wslh• 14 years ago

Not only with doctors, but every professional have problems when there are more than one cause, they try to find one cause to the current effect. This is something where developers and it administrators used to solve better because they "breath" problems with multiple causes.

rogerbinns• 14 years ago

Here is wonderful explanation of "DNA seen through the eyes of a coder". It makes Intercal seem sane.

http://ds9a.nl/amazing-dna/

jcmoscon• 14 years ago

It's crazy when people think we evolved from something. The DNA is our source code and God is the programmer!

kanghaz• 14 years ago

Reminds me of the Odone story as dramatize in the film "Lorenzo's Oil"

hexagonal• 14 years ago

  When a mutation occurs, there are four possibilities for 
  the mutant...

I'd nitpick this slightly, since there's a slight anthropocentric bias here.

You could say there's three types of mutations: genes that do not affect evolutionary fitness, genes that increase fitness (faster running, better eyesight, etc) and genes that decrease fitness. (chromosomal trisomy, which either instantly kills the host, or greatly reduce its fitness)

And, of course, fitness is relative. Heterozygous HbgS makes you resistant to malaria, homozygous HbgS gives you sickle cell anemia. Being tall adds fitness in a calorie-rich environment, but reduces it when food is comparatively expensive. Etc etc etc.

But you probably won't want to double the length of the article, by going into even greater depth on genetics.

engtech3• 14 years ago

Thank you for posting this, Matt.

It's amazing that you were able to learn so much about his condition. It gives me hope for the future of medicine, because I sometimes feel like we are still in the dark ages.

I hope you have success with the treatments.

ne0codex• 14 years ago

Kudos to the mother and father for not giving up and to figure out the medical mystery, it read like a House episode with the various diagnoses then you realize that it's real life, not a TV plot. I truly believe that future technological advancements have an obligation to serve humankind for the better and that real progress is made though breakthrough medical and scientific breakthroughs.

orbenn• 14 years ago

"Unfortunately, we can't just order a batch and inject Bertrand.

We need to get FDA approval, and we'll need Genzyme's cooperation.

Even though his disease is life-threatening, his seizures are worsening and he continues to lose white matter, we'll need to prove that it's safe."

It's shit like this that makes me hate the FDA.

meepmorp3• 14 years ago

> It's shit like this that makes me hate the FDA.

So, what? You'd prefer no enforcement of basic drug safety testing?

There are reasons why we have the controls we do in medical trials, other than just to provide busy work to career bureaucrats and generally make trouble for sick people. There is a process for getting patients access to investigational drugs, but you still typically need to do some paperwork in order to provide the drug to the patient.

Given this is a new use of an existing, approved drug, this should go fairly quickly.

CamperBob22• 14 years ago

You'd prefer no enforcement of basic drug safety testing?

If only there was a middle ground of some kind.

ef42• 14 years ago

I don't think this is an approved drug. It's sold as a reagent to laboratories, but not used for anything medical.

sgt• 14 years ago

I honestly appreciated this read. To me this is "Genes for Dummies". Exactly what I need. I tried reading about genetics on wikipedia once but I got lost in all the details and thus failed to see the bigger picture.

valencourt3• 14 years ago

Wikipedia also has an article called Introduction to Genetics. There are more and more of these lately, introduction articles which try to break down topics that are naturally technical: https://secure.wikimedia.org/wikipedia/en/wiki/Introduction_...

hobbyist• 14 years ago

Thanks Matt. You are amazing. period.

sevenstar4• 14 years ago

That guy knows how to get attention... Science shows that human DNA is degenerating. We are not getting "better and better" as some priests would say.

sevenstar4• 14 years ago

Colloidal silver will probably help as well.

Mz9• 14 years ago

Yes, if you want irreversible metal poisoning. If you want to try poisoning yourself with an old fashioned treatment, then mercury -- at one time a treatment for syphillis -- is probably a better bet if only because there are well established chelation protocols for getting it out of your system. In contrast, I can find no well established, proven means to remove silver. And I have tried, repeatedly, since colloidal silver is a popular alternative treatment in the CF community and I wish I had something better to offer them than the bad news they are likely making their situation worse in the long run.

sevenstar4• 14 years ago

Ha.. Mercury? Really? You are right, mercury is poison. But... there are too many people who have had spectacular results with colloidal silver, including myself, who would disagree with your post. Hospitals still use it in the eyes of newborns today to combat infections. Did you know that arsenic is not poison in the body if it is in organic form?

GigabyteCoin2• 14 years ago

No, it won't. http://en.wikipedia.org/wiki/Medical_uses_of_silver#Adverse_...

sevenstar4• 14 years ago

Thanks, it looks like the medical industry is trying to bury my post.

philwelch• 14 years ago

Thank you, Stan Jones: http://en.wikipedia.org/wiki/Stan_Jones_(politician)

joshu• 14 years ago

Inspiring and amazing.

A few impressions:

Although the author removes much of the emotion of the story, I still sense the undercurrent.

The future is going to be strange. Way more complicated than science fiction, our guidestar for so long, led us to believe.

I hope that when the time comes, I will be able to measure up to the author as a person, as a parent, etc.

chubbard• 14 years ago

That was an awesome article. I couldn't finish it as it was too long, but the technical detail in it was really awesome. Just the biology and relating it to computer nomenclature was really interesting. I think what's really amazing about blogging about the topic is you've created a brain dump of your most of your knowledge on the subject. Everyone who reads that is now much more versed than most medical staff anyone might run into, but because it exists they can educate themselves on your child's history as well. You've created a piece of fairly rare scientific information that exists in the public free for comment. That's not something we'd have done even 10 years ago.

Mz9• 14 years ago

This is incredibly long and seems like it will probably never tell me the info that interests me. As I understand it, in most genetic disorders, all of the problems are rooted in a miscoded protein. I am wondering if it has been determined which protein is miscoded and what it does?

Edit: I have managed to read the whole thing and, no, it doesn't answer my question. The closest I get is that some enzyme is not being produced. For me, that is insufficient info. Moving on to the blog but would still be happy to get an answer here. Thanks!

Scaevolus• 14 years ago

"Cristina and I each carried a different mutant NGLY1 gene."

NGLY1 is also the name of the enzyme.

Mz9• 14 years ago

Um, it's possible I am just stupid and I am still trying to look up info on this. But that doesn't help me adequately understand it.

This piece is interesting to me because I have a form of cystic fibrosis, which is a genetic disorder. Long QT waves -- the heart problem the child had from an antibiotic -- can be caused by a magnesium deficiency. Magnesium supplementation helps a lot of people with CF. Also, they mention a possible treatment for this condition that is currently used for some people with CF. So I am wondering how it relates to my condition, basically. But I have gotten well by framing the question different from the medical community and others with my condition.

In cystic fibrosis, the miscoded protein is the CFTR, which handles traffic into and out of the cell for certain specific molecules. Understanding which molecules are impacted was enormously useful info. People with CF are routinely put on digestive enzymes, which I no longer require. So I am trying to understand what is going on with this child in terms which make sense from my mental framework regarding my genetic disorder and "enzyme deficiency" doesn't sound to me like it is really the root problem (but maybe I am an idiot -- it would hardly be a first). That may not be possible to achieve but I will work on it anyway.

Thank you for replying.

danparsonson2• 14 years ago

Different proteins for different disorders - from what you wrote it seems like you read it as one particular protein that's commonly implicated in many different disorders?

Imagine one part of your car was randomly the wrong shape. You'd have Twisted Wheel-Nut Syndrome or Split Spark-Plug Disease or whatever, all of which could be caused by badly copied blueprints for the car.

Mz9• 14 years ago

Sorry I wasn't clear. I am currently looking at info on NGLY1 and trying to parse out its exact function in order to try to understand the commonalities this seems to have with my condition. "Lacks x enzyme" doesn't give me a picture of what functions are missing. I am not a medical professional. I need laymen's explanations of specific functionality, which are quite hard to come by.

Thanks for replying.

luminaobscura2• 14 years ago

why not just perform euthanasia and focus your energy into raising the healthy child?

perlgeek3• 14 years ago

Because parents love their children, even if they aren't healthy.

diaphoros• 14 years ago

^ this. How is keeping this profoundly sick & disabled child alive not abuse?

snowwrestler4• 14 years ago

Ethical objections aside, clearly he doesn't want to do that.

sgtgrumbles• 14 years ago

I believe luminaobscura is referring to the following position: http://www.slate.com/articles/health_and_science/human_natur...

perlgeek3• 14 years ago

It took me a while to realize what exactly it was that disturbed me about your question. I don't have any problems with talking about euthanasia, but the casualness with which you mention it shocks me.

Would you "just" kill your son if he wasn't healthy enough?

luminaobscura2• 14 years ago

"just" refers to easiness of the alternative route, nothing more. i didn't mean it should be an easy decision.(I am not a native English speaker.) I realize that this is a very painful situation for the family.

regarding your question, there are two different scenarios:

1- my son reaches the necessary neural development stage so that he is conscious, self-aware, interacts with other humans etc. then we can't kill him unless he requests it.

2- he has never reached that stage so he has not any personality, memory etc. then we can kill him. because there is not really a "son" here, not yet.

in fact, we humans continously kill pigs, dolphins and other animals that are more intelligent and conscious than a newborn.

shpoonj4• 14 years ago

So there was a paternity test, right? I'm assuming there was and it just wasn't mentioned in the write up.

The author states with authority that he is the father, but doesn't mention the tests confirming it whereas every other finding is linked to the tests involved.

Please don't tell me, in an article praising science, that this was left to faith or trust or whatever.

dangoldin• 14 years ago

Other than the fact that this is offensive and shouldn't have been posted - did you read the article? The conclusion was that they both had a recessive trait that manifested itself in their son.

shpoonj4• 14 years ago

Who are you to decide what is offensive and what should and should not be posted?

And yes I read the article and no I am not so foolish as to believe that there is only one possible cause for every result.

Havoc2• 14 years ago

I thought about this too - but concluded that even without a test, its reasonable.

A caring parent wouldn't keep such a thing secret when its causing (continued) suffering for their child. I'm sure there are psychopaths out there where this is not true, but given that they are married, a judgement call is acceptable in my view - even if not ideal.

shpoonj4• 14 years ago

I would argue that the same callous personality evidenced in a person capable of infidelity would also come into play when considering whether or not to reveal said infidelity.

Wouldn't you agree?

shpoonj4• 14 years ago

Downvoted for asking for evidence of claims... Claims that the author admits many of the professionals he trusted enough to ask for guidance also raised.

You've gone soft, HN.

mcguire3• 14 years ago

"Downvoted for asking for evidence of claims"

How about downvoted for not reading the article?

mattmight12• 14 years ago

I can't believe this needs stating, but the result of the exome sequencing implies that Bertrand is my son (with a certainty higher than any conceivable paternity test).

And, to be clear, I never doubted for one second that he was mine.

surrealize• 14 years ago

His son has the exact same (rare) mutation as he does. It's not clear how common it is, but it's clearly rare enough that it's safe to say he's the father.

rickyconnolly• 14 years ago

I have a question for Matt, if you are still here. How did you get in touch with Genzyme? What do they have to gain by helping you? Developing a recombinant therapeutic drug is an exceedingly expensive and technically-difficult undertaking. Why are they developing a treatment for a condition for which the potential market size is one single patient?

mattmight12• 14 years ago

We're contacting Genzyme via friends of friends.

Your question is valid. I wouldn't expect Genzyme to do much unless there's profit (or at least little cost) involved.

Fortunately, Genzyme might not need to do much, since the enzyme is already in production, but for laboratory rather than human use.

I'll admit I don't know much more will be required to take what they injected into mice to the point where we can inject it into Bertrand.

We're learning on the fly.

Since Genzyme holds the patent, I think we'll at least need their permission to use it in a clinical setting.

We're also actively searching for other NGLY1 patients. There may yet be a market.

We're also investigating other possible clinical applications of N-Glycanase 1. My own early research indicates that it may help in cases of severe jaundice--a much larger market.

I'm optimistic that we can get Genzyme's attention.

mcguire3• 14 years ago

There's always the excellent PR opportunity.

matmann2001• 14 years ago

This reminds me so much of the story of Lorenzo's Oil.

http://en.wikipedia.org/wiki/Lorenzos_Oil

arvin• 14 years ago

My thoughts exactly, especially about the hardships and perseverance experienced by the parents.

zaroth• 14 years ago

I have two healthy children (0 and 3) and can't even begin to relate with what you've gone through and are going through. It sounds like the worst kind of hell mixed with small moments of the very best life has to offer.

josscrowcroft• 14 years ago

Fantastic read and story. Thanks for writing it and best wishes to you all.

One of my best friends recently had a son with a rare bowel disorder, requiring a full bowel transplant, and he's been saying that every day they are educating the doctors on what to do, up at all hours calling all different countries. They've been by his side in hospital since his birth, but it's incredible to see the pics of that baby laughing like a champion!

mohawk• 14 years ago

First i wish to say good luck to your family, i hope you can find something.

Ok here's a guess:

Assuming missing deglycosylation and N-Glycanase's involvement in ERAD (endoplasmic-reticulum-associated protein degradation), perhaps there is amyloid fibril formation due to faulty protein degradation?

If yes, you may want to try out green tea or some kind of extract from it, in particular Epigallocatechin gallate sounds interesting. Besides antioxidant activity (which i guess could help with excessive glycosylation causing an oxidative environment), EGCG is thought to help in various diseases where protein aggregation plays a role. You can find lots of papers on this if you search for "epigallocatechin gallate amyloid" on Google scholar. I'm not a doctor, just a grad student (thanks for the guide!), so you should check with one first if that makes sense.

djt• 14 years ago

Hi matt, I used to work on MPS 3a and did some studies on non-viral gene therapy to treat it in the central nervous system.

Do you know if the enzyme crosses the blood brain barrier?

It was a few years ago, but feel free to ask questions.

aksx• 14 years ago

I used to follow Matt's blog. Reading the title of this post really upset me.

kamaal• 14 years ago

>>Laughter

The morning after Bertrand was weaned from ACTH and the ketogenic diet, we heard something we hadn't heard before: laughter.

Still bloated and near death, in his hospital bed, he was laughing.

Everytime the laugh track came on the hospital TV, he chipped in.

It was the most direct sign of Bertrand's humanity we had ever seen.

Cristina was in tears.

As some one who is not married, has no friends, doesn't understand women and kids, Spends whole day in front of a computer. I hope someday I will have a family to truly understand what you are going through.

I hope and pray your boy recovers. The conviction and faith in which you write has me convinced that being parent is a sublime emotion which every human being must experience.

ramanujan2• 14 years ago

I just saw this thread. If you are a computer scientist interested in making a difference on problems like this, consider joining Counsyl:

https://www.counsyl.com/about/jobs

http://goo.gl/45yBz

There are a lot of Hacker News people working here. And while it's sadly not in time for Matt and his son, we are launching a version 2.0 assay soon that should save couples in the future from ever going through something like this again.

pmiller22• 14 years ago

Matt,

I hope you are able to take at least some comfort from actually knowing the cause of your son's illness. Some people aren't so lucky.

I had my own medical struggle while in the middle of grad school. Mid October a few years ago, I contracted a rather nasty respiratory infection. Among other things, I was severely fatigued and needed to sleep for extended amounts of time (think 12+ hours a day). The excessive sleeping didn't worry me while I was busy hacking and coughing, but when the respiratory symptoms had gone away a couple weeks later, I was still left with the extreme fatigue and hypersomnia.

Normally, I'm not one to run to a doctor at the slightest sign of any illness, but I began to get worried a week or so after the acute infection passed and I was still sleeping a minimum of 12+ hours a day. (I should emphasize, too, this really was a minimum, not an average -- I'd typically wake up around 8 am, go to class and do other things until around 2 or 3, come home and fall asleep around 4 PM and wake up and do it again the next day. One weekend, I think I was awake for a total of about 8 hours over the two days.)

I went through the usual struggle anyone who has anything that's at least mildly rare goes through, and, after visiting a sleep neurologist, I got my diagnosis: post-infectious idiopathic hypersomnia. I then knew this was a problem that was going to take months or years to resolve, and, for a while, I thought my life was effectively over.

But, the real kick in the teeth was that word, "idiopathic." There's a great line on an episode of House where one of the fellows suggests a diagnosis of idiopathic something-or-other, and House responds "'idiopathic,' from the Latin meaning we're idiots because we can't figure it out." So, there I was, with a diagnosis that amounted to "you sleep a lot and we don't know why," and the only treatment available was basically stimulants to treat the symptoms (which didn't work well at all -- I slept less, but I was walking around like a zombie by early afternoon every day).

Looking back, I consider myself lucky that it happened while I was in school, since I could have easily found myself unemployed and broke if I were in less flexible circumstances at the time. I'm also quite lucky that it resolved itself within about 9 months. I effectively lost a semester of grad school that I had to make up later, but I recovered, and it should never recur.

I don't know if what I had is what would be considered a "rare" disease by the strict definition, but it's rare enough that your average primary care physician might not ever see a case in his or her life, and a sleep specialist might see a handful. It's rare enough that there don't seem to be any studies or research available on the condition, on top of the obvious difficulties of studying people who effectively have to sleep 1/2-3/4 of the day.

So, back to my original point: my best wishes to you and your son, of course, but please take comfort in the fact you know exactly what is wrong.

mattiask• 14 years ago

Every time I watch an episode of House or read a story like this I think "Why isn't there an expert system for diagnostics". The notion of a person being able to manage such vasts amount of knowledge seems ridiculous and cost-ineffective.

If you could enter a bunch of positive and negative statements together with various medical records, and have the computer being able to ask additional queries, it seems a good system would be able to narrow down a list substantially. It would also side-step a lot of cognitive problems we humans face.

Now, I'm sure there are systems like this but they probably just aren't sophisticated , widespread enough or don't have large enough database. Or have they simply not yet reached widespread use because they cost too much, what's holding them back?

* Found this article on the topic: http://www.informationweek.com/news/healthcare/clinical-syst...

AliCollins• 14 years ago

Seriously, one of the best stories I have read on the web. Thank you for sharing this with us all...and hoping for better news in the future!

alexrson• 14 years ago

I stongly urge you to look into Ataluren (also referred to as PTC124, in the literature). It has a number of advantages over gentamicin and may be a better long term solution. It is currently in clinical trials for a number of premature termination codon (PTC) diseases. Check out this paper: http://ajrccm.atsjournals.org/content/182/10/1262.long

antman• 14 years ago

If one's condition is a usual one then the doctor is the best approach. Similar symptoms can appear in meningitits or west nile virus (arbitrary example) but the doctor knows how many people he treated in the area recently and can quickly come up with an answer. Others can't have sense of analogy and size. It's the same thing as reading posts regarding NOSQL databases where the best way to learn the caveats is to wait a little for the "why it was a bad idea for us" posts. If you have some rare condition and you have reached to the conclusion that you can't find what it is, a solution is to try and improve on the symptoms by using simple statistics or machine learning. Here is a simple tutorial of machine learning with WEKA where the guy uses data from his heart condition: http://www.youtube.com/watch?v=m7kpIBGEdkI If you have a rare condition and you found what it is, then be prepared yourself. Unfortunately reproducibility in scientific experiments has problems http://blog.scienceexchange.com/2012/04/the-need-for-reprodu... so it is better to use books that come from established groups or organizations. What if research was absolutely trustworthy? For more daily things you can read forever (try putting "cognitive" and "daily" to pubmed http://www.ncbi.nlm.nih.gov/pubmed to see thousands of post relating to cognitive function). It's too much work, so stick to what's important for you. If you have some rare condition and you have reached to the conclusion that you can't find what it is, a solution is to try and improve on the symptoms by using simple statistics or machine learning. Here is a simple tutorial of machine learning with WEKA where the guy uses data from his heart condition: http://www.youtube.com/watch?v=m7kpIBGEdkI If you have a rare condition and you found what it is, then be prepared yourself. Unfortunately reproducibility in scientific experiments has problems http://blog.scienceexchange.com/2012/04/the-need-for-reprodu... so it is better to use books that come from established groups or organizations. What if research was absolutely trustworthy? For more daily things you can read forever (try putting "cognitive" and "daily" to pubmed http://www.ncbi.nlm.nih.gov/pubmed to see thousands of post relating to brain function). It's too much work, so stick to what's important for you.

bad_user2• 14 years ago

I have a son that was born prematurely at 7 months and the doctors weren't too optimistic about his chances of survival or about his long-term health. And we've had problems with him, like manifestations of Lyle's syndrome. He's fine and healthy now, but I'm afraid the battle ain't over.

I know what the author goes through and it's hearth breaking to see your own child suffer. It's the worst kind of pain imaginable.

nightcomer• 14 years ago

Your story brought tears in my eyes. Thanks for sharing with us all. Surely someone or the other will benefit from your findings. Also, salute to your patience, and the hope that kept you on. I have never been outside India, but if I ever came to US, I will surely meet you.

Hunting Down My Son's Killer

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