
Hunting Down My Son's Killer - synacksynack
http://matt.might.net/articles/my-sons-killer/
======
postfuturist
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.

~~~
its_so_on
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.

~~~
CWuestefeld
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.

~~~
btilly
Just curious. Have you tried Helmetic therapy?

I have a friend with Crohn's disease. After 10 years on medication he injected
himself with hookworm. He has now been medicine free for over a year with
fewer symptoms than he had before.

~~~
kernelPanicked
There was a This American Life/Radiolab story about a guy who rolled his own
Helminthic Therapy. If it weren't for the fact that the therapy was illegal
(which is a whole other issue) and therefore very difficult for him to get, it
would hardly have been a "story." Just an amazing cure for
allergies/autoimmune problems. But the story was really in how he had to
wander all over Africa shuffling through latrines to get a few hookworms.
[http://www.thisamericanlife.org/radio-
archives/episode/404/e...](http://www.thisamericanlife.org/radio-
archives/episode/404/enemy-camp-2010) . It's act 3.

------
hirenj
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.

~~~
mattmight
Wow! This is fascinating.

Thank you so much for the pointers!

Are you a grad student/postdoc/faculty?

~~~
hirenj
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.

------
nicholassmith
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?

~~~
mattmight
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.

------
aarondf
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
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
Just ordered a kit from 23andme

------
waffle_ss
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.

~~~
mattmight
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
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.

------
ramanujan
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.

------
Dn_Ab
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>

------
fghh45sdfhr3
_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.

~~~
ars
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
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.

------
mohawk
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.

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

~~~
mattmight
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
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.

------
orbenn
"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.

~~~
meepmorp
> 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.

~~~
ef4
I don't think this is an approved drug. It's sold as a reagent to
laboratories, but not used for anything medical.

~~~
meepmorp
I think you're right. I just checked a manufacturer product page, and it looks
like its just used in labs currently.

------
mattiask
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...](http://www.informationweek.com/news/healthcare/clinical-systems/229900102)

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

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

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

------
joshu
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.

------
hexagonal

      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.

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

~~~
mattmight
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
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.

~~~
mattmight
Thanks for sharing!

Becoming a parent is an awesome experience--one I wouldn't trade for anything.

I can still remember time freezing the moment each of my kids was born.

I wish you, your wife and your little one the best.

------
ne0codex
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.

------
chubbard
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.

------
rickyconnolly
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?

~~~
mattmight
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.

~~~
mcguire
There's always the excellent PR opportunity.

------
djb_hackernews
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?

~~~
mattmight
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.

------
josscrowcroft
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!

------
engtech
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.

------
sgt
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.

~~~
valencourt
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_...](https://secure.wikimedia.org/wikipedia/en/wiki/Introduction_to_genetics)

------
Mz
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!

~~~
danparsonson
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.

~~~
Mz
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.

~~~
mattmight
N-Glycanase is responsible for removing N-linked glycans from misfolded
glycoproteins.

~~~
Mz
Thanks for answering. Is that absolutely the only thing it does? Because I am
getting the vague impression the miscoded protein has some other functions as
well.

~~~
sandipc
it's certainly possible that it has other functions.

There are many, many, many proteins for which we are discovering new functions
each day or for which we know of no known function in cells.

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

------
alexrson
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>

------
bad_user
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.

------
vectorpush
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.

------
kamaal
>> _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.

------
zaroth
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.

------
matmann2001
This reminds me so much of the story of Lorenzo's Oil.

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

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

------
nightcomer
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.

------
hobbyist
Thanks Matt. You are amazing. period.

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

~~~
perlgeek
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?

~~~
luminaobscura
"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.

------
djt
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.

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

------
antman
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...](http://blog.scienceexchange.com/2012/04/the-need-for-
reproducibility-in-academic-research/) 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...](http://blog.scienceexchange.com/2012/04/the-need-for-
reproducibility-in-academic-research/) 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.

------
AliCollins
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!

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

------
pmiller2
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.

------
sneak
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?

~~~
mcmatterson
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.

~~~
sneak
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".

~~~
valencourt
Do you have children? Do you have a good relationship with your parents?

I don't think it's unreasonable to assume that my kids will turn out to have
traits that I liked in me and my parents. Just because of that, I would rather
conceive.

~~~
slurgfest
Nobody has any idea how your kids will turn out - we have even less control
over this than over how our marriages will turn out. But best of luck to you.

------
jasonlotito
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.

~~~
altrego99
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!

~~~
maratd
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.

~~~
slurgfest
It is not necessary or helpful to be uncivil about this.

altrego99 is expressing a considered personal view with which you disagree,
not insulting you or the mass of humanity. You are entitled to your personal
view as well. But you could recognize consideration of the issue as a good
thing and the disagreement as normal and healthy. Instead, you are calling
people terrible names and picking on grammar, without provocation. Please
don't continue in that vein.

I think for most people, you are right that having a kid is a fulfilling
thing. I am personally glad that someone is having kids (particularly if they
are doing a good and thoughtful job of caring for them). But the implication
that no one with kids could ever disagree with you is not correct - though it
is unlikely that they will bother to do so in public. I have talked to several
people who do regret having kids (particularly in a certain time or situation)
but they are not so likely to say it - both because of the kind of aggressive
reply you have given but maybe also because they are likely to be wrongly
taken as saying that they do not love their children, or that they wish the
child did not exist. A person can believe that having kids is not necessarily
altruistic, or that there is no moral or practical imperative to have kids,
without being an awful arrogant psychopath.

Before you have a child, there is no child to wish the nonexistence of. And
since it is an irreversible long-term decision, you should definitely think
about the pros and cons in a rational way. Many people do come to parenthood
by a reasonable, conscious choice and that is a blessing. Other people decide
not to. If that is in their best interests then good for them. Perhaps there
will be a future time where it does make sense to have kids. Leave them be.
It's a personal decision, not a moral necessity.

Not everyone has to get married, either; not getting married doesn't make you
a psychopath or a pathetic unfulfilled person, even if it's a nice thing and a
great life work for many people.

~~~
maratd
> But the implication that no one with kids could ever disagree with you is
> not correct

It is impossible to speak about any subject intelligently unless you have
experience with it.

That's just how reality works.

If that offends your sensibilities, may I suggest you're a tad too sensitive?

~~~
megablast
So you can't have experience of having kids unless you have kids. This is
almost along the lines of saying you don't know that getting hit by a car is
bad, until you have been. I have plenty of experience with kids, my brothers
and sisters have plenty. Not as much experience as a parent, clearly, but
enough to know what I want.

~~~
jmathai
Not the same. Getting hit by a car is physical and having a child is very much
psychological and emotional.

Someone who's never loved can't say that love is overrated.

Edit: fixed typo

------
shpoonj
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
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.

~~~
shpoonj
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.

------
sevenstar
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.

------
sevenstar
Colloidal silver will probably help as well.

~~~
Mz
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.

~~~
sevenstar
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?

~~~
Mz
People also got "spectacular" results from antibiotics. Initially, optimists
announced that we were ushering in an age free from disease. Fast forward a
few decades and we now have frightening antibiotic resistant infections to
contend with.

I am not claiming there are zero short term benefits to be had. I am only
claiming there is a long term cost and I deem it to be too high since there is
no known means to reverse silver poisoning. My genetic disorder is deemed to
be degenerative and fatal. I have reversed a lot of the symptoms, gotten off
eight prescription drugs and gotten my life back. I recommend against
colloidal silver any time anyone asks me. I am clear the build up of poisons
in the body is why my condition is degenerative.

