
The Girl Who Turned to Bone - Steko
http://www.theatlantic.com/magazine/archive/2013/06/the-mystery-of-the-second-skeleton/309305/
======
habosa
This is a must-read, a very interesting article about a very terrible disease.
Dr. Kaplan is a professor at UPenn where I'm a Bioengineering major. He gave a
lecture to one of my classes about FOP and it was so inspiring to see how much
progress he has made on a disease with only a handful of cases that was
supposed to be impossible to cure. Imagine trying to cure a muscular disease
where you can't even biopsy the muscle of your patients! Dr. Kaplan is an
amazing man I hope he kills FOP in his lifetime.

~~~
drharris
Agreed, and fascinating. To me, an article like this is better than any action
novel. Found myself on the edge of my seat trying to figure out how far he'd
managed to get! I think it's a perfect look at how building on other people's
science is how we really get things done. What if he'd overlooked that paper
that unlocked everything for him?

------
redschell
For anyone interested, a link to photos of Harry Eastlack's skeleton:

[http://raregeneticdisorder.blogspot.com/2012/09/fop-
skeleton...](http://raregeneticdisorder.blogspot.com/2012/09/fop-
skeleton.html)

Wonderful article, as expected from Carl Zimmer, who does such a great job of
exploring biological mysteries like this.

~~~
raverbashing
Wow

This snipped sums it better: "To be displayed in human form, skeletons have to
be re-articulated or pieced back together with fine wires and glue. As a
result of the bridges of bone that formed from FOP flare-ups, Harry Eastlack's
skeleton is almost completely fused into one piece, which proved little
challenge for the articulator's craft"

~~~
Jabbles
How does the articulator go from body -> skeleton when preparing them for
display? Is part of the job to (for example), scoop out the brain?

~~~
caycep
I think basically, the family agrees to an autopsy and there is a branch of
medicine, pathology, which specializes in obtaining and preparing tissue
samples, primarily for investigation into the causes, progression, and
severity of disease. They are the ones that "scoop out the brain" then mount
them on slides, stain, etc. With whole skeletons, I'm not sure - usually after
autopsy, the "parts" are either put back into the body or otherwise interred
in a container. I think maybe the family arranges something w/ the embalmer to
remove the muscle and connnective tissue from the skeleton.

~~~
raverbashing
I think yes, the process is more or less this, really

After tissue is removed and preserved (samples), then in this case I believe
the removal of soft tissue is done chemically, probably with a caustic
substance.

Yes, this is as far as I go imagining this. Or maybe there are biological
means as well

~~~
jakejake
I saw a show where people make skeleton models and they used a type of bug to
clean off the bones. Using certain chemicals would make the bones rubbery,
whereas the bugs would leave a perfectly clean bone.

~~~
maxerickson
Dirty Jobs?

[http://www.episodeguide.us/dirty-jobs/skull-
cleaner/episode/...](http://www.episodeguide.us/dirty-jobs/skull-
cleaner/episode/814614/summary.html)

------
JunkDNA
This is a fantastic article that is extremely well written and does an
excellent job of conveying the science. I think one of the more interesting
side-effects of cheap DNA sequencing tech is that we're starting to find out
that while any individual rare disease is rare, in aggregate, rare diseases
are actually quite common. This also means that many common diseases
(especially ones whose causes have eluded researchers) may actually be a
constellation of rare diseases that look the same from our 20,000 foot view.

Fortunately, cancer is one such disease and it has the advantage of a healthy
funding stream plus significant public mindshare. I suspect many of the
techniques we are just starting to use to discover the causes of cancer and
personalize therapy will start to be applied to rare diseases. These diseases
will effectively get to capitalize on all the "infrastructure" that we've been
working on without having to bear the cost burden of the inevitable 10's of
thousands of dead ends that come with this kind of work.

~~~
pattern
To expand on your comment "rare diseases are actually quite common", I was
struck by this in the article:

    
    
        More than 7,000 such diseases exist, afflicting a total of 25 million to 30 million Americans
    

That's almost 10% of Americans! I suppose this shouldn't have been surprising
given the Birthday Paradox [1], but the ~1/10 statistic puts things into
perspective for me.

[1]: <http://en.wikipedia.org/wiki/Birthday_problem>

~~~
mtdewcmu
That means most of them must be mild. Because, clearly, 10% of Americans don't
have something as serious as FOP. There's probably a long tail of increasingly
rare and increasingly mild diseases, so that the cutoff is arbitrary.

~~~
waster
Mild, or self-limiting or otherwise transitory. I know (closely) three people
in two different countries who have a 15/100,000 disease that is self-
limiting.

~~~
mtdewcmu
It wouldn't be very surprising to learn that every single person has some kind
of genetic defect -- perhaps dozens -- but usually the compensatory mechanisms
are strong enough to mask them, at least while you're young and strong
overall. It makes a lot of sense that health should be a spectrum or a kind of
dynamic equilibrium, rather than a binary on-off condition.

------
Sanddancer
I know someone with FOP, and this pretty much fits his experience. His is a
mild case, but he carries crutches because his knee sometimes locks from one
of his attacks -- muscle sprain in childhood -- and he needs its support. He's
also talked about the pain going to the doctors becomes at times, because
pretty much everything is handled by specialists, or with their consultation,
and he just wants to get on with life.

One of the things that this article doesn't touch on, though, is the
difficulty in getting treatment and effective care for comorbid diseases.
Because these diseases, especially things like FOP, can manifest in odd ways,
they tend to lump all of the other abnormalities together, even if the other
symptoms run completely counter to what the disease does to others. So,
standard diagnostic batteries for the other diseases aren't run, even if such
a diagnostic would be useful in managing body issues that can and do come up.
Thankfully, though, he's managed to get a decent amount of day-to-day coping
skills with his other disease (Ehlers-Danlos Syndrome) from the internet. It
still would be nice for him to get a firm diagnostic, so that interactions and
symptoms could better be monitored.

~~~
npsimons
The fact that the subject of the OP was diagnosed fairly quickly struck me;
more often than not, as you mention, rare diseases are misdiagnosed or
completely missed. I've often wondered if someone hasn't done a long term
statistical analysis of the probability of seeing rare diseases. It's one
thing to think you have a rare disease (and is statistically very unlikely),
but if you are a doctor seeing already self-selected ill subjects, wouldn't
that change the probabilities significantly? I know modern medicine is quite
mentally taxing, and most doctors are trained to be conservative, but maybe
just emphasizing the fact that the statistics are different for the population
of people seeing doctors might go a long ways to convince doctors not to
automatically lump illnesses into the most common categories.

That, and making the tests cheaper (like all of them, virtually zero cost; who
wouldn't just throw every test they can think of at a problem if the tests
were dirt cheap).

------
bobwaycott
A fascinating, excellently written article; a prime example of high-quality,
long-form writing I enjoy reading.

A very human story that includes one of the most intriguing forms of "hacking"
I know of--working to understand and manipulate our complex biology to improve
human life.

It is fascinating the ways in which studying rare diseases leads to
discovering more information about how our bodies work under normal conditions
--discovery that may not have been realized otherwise.

------
chiph
What amazed me is that Jeanne Peeper was able to essentially do a pre-internet
Kickstarter and raise funds for Kaplan to perform his research, hold a
conference, and hire a geneticist.

With the power of the internet and how easy it is to set up a phpBB forum,
sufferers of rare diseases don't have to live in isolation any more.

~~~
dangoldin
Yea - I had the same thoughts. Do you know if there are Kickstarter like
nonprofits dedicated to raising money this way for rare diseases?

~~~
caycep
I think there is a scientific "kickstarter"-like startup that made the rounds
here on HN a while back, though - maybe that could fit the bill? the name
escapes me at the moment though.

~~~
jtheory
Probably Microryza: <http://microryza.com>

~~~
dangoldin
Thanks for sharing. I know YC invested in Watsi (<https://watsi.org/>) but
this is more of what I was looking for.

------
DanBC
See also "The Human Mannequin" about a young woman with FOP who decides to
work in the fashion industry.

(<http://www.channel4.com/programmes/the-human-mannequin/4od>)

([http://www.atvtoday.co.uk/9987-fibrodysplasia-ossificans-
pro...](http://www.atvtoday.co.uk/9987-fibrodysplasia-ossificans-progressiva-
and-fashion/))

([http://www.huffingtonpost.com/2012/11/01/louise-
wedderburn-t...](http://www.huffingtonpost.com/2012/11/01/louise-wedderburn-
the-human-mannequin-raises-awareness-extremely-rare-condition_n_2058612.html))

------
dmd
> A rare disease is defined as any condition affecting fewer than 200,000
> patients in the United States. More than 7,000 such diseases exist,
> afflicting a total of 25 million to 30 million Americans.

Can that really be true? 1 in 10 Americans has a rare disease?

~~~
PebblesRox
I haven't been able to find a good source, but here's what the NCBI says: "In
part because data on many conditions are limited to case reports or special
population studies, no well-supported estimate exists for the number of people
collectively affected by rare diseases. A 1989 government report stated that
10 million to 20 million Americans had a rare condition (NCOD, 1989); the
corresponding estimates in 2009 range from 25 million to 30 million (see,
e.g., ORDR, 2009). The estimates were not accompanied by analyses or
substantive citation of sources."
<http://www.ncbi.nlm.nih.gov/books/NBK56184/>

The links in the footnotes lead to 404s, but this might be what they're
referring to:
[http://rarediseases.info.nih.gov/asp/resources/ord_brochure....](http://rarediseases.info.nih.gov/asp/resources/ord_brochure.html)
It doesn't cite sources though and it calls it an estimate. It also says
disease or condition, so I'm guessing it includes minor stuff that most people
wouldn't really consider a disease. For example, my friend and her mom both
have weird ridges on their thumbnails; definitely rare but it doesn't affect
their health. Things like that are probably included in the estimate.

------
kschua
I actually find this case far more intriguing. Probably 1 of 3 in the world

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

------
advisedwang
I know this is a stupid question, but the article states there are more than
7000 (but presumably less than 8000) diseases effecting 1 in 200000 or fewer,
with 25-30 million suffers in the USA.

With a population of 300 000 000, * 7000 / 200 000, shouldn't that be about 10
million?

~~~
jacalata
You misread it - it says a rare disease is a condition affecting _fewer than
200,000 patients in the United States._ , not _1 in 200,000 or fewer_.

~~~
advisedwang
I was providing the largest estimate, fewer than 200 000 means less than 10
million, which is even further from the articles 25-30 million.

~~~
Someone
You misread it - it says a rare disease is a condition affecting fewer than
200,000 patients in the United States., not 1 in 200,000 or fewer (in other
words: those rare diseases aren't that rare; according to this definition, 1
in 1,500 people can suffer from a rare disease)

So, the math should be 7,000 rare diseases times at most 200,000 sufferers per
rare disease = at most 1,400,000,000 sufferers for all rare diseases combined.
The actual number will be way lower because many of those 7,000 will be much
rarer, because some people may have more than one rare disease and because
there simply aren't that many people in the USA.

------
tokenadult
From farther down in the article: "'I’ve seen 700 patients with FOP around the
world, and it’s clear that there’s a lot of different ways to divide
patients,' Kaplan said. One identical twin might be only mildly affected,
while the other would be trapped in a wheelchair. Some patients developed a
frenzy of bones as children, and then inexplicably stopped. 'I’ve seen it go
quiet for years and years.'"

Wow. That's an important clinical clue, that discordance between identical
twins. That suggests that the disease is not best described by a single-gene
mutation, strong expressivity

[http://www.nature.com/scitable/topicpage/same-genetic-
mutati...](http://www.nature.com/scitable/topicpage/same-genetic-mutation-
different-genetic-disease-phenotype-938)

simple Mendelian model. And that means that there is something else going on
in the clinical expression of the disease besides the gene mutation, which
might provide some traction for effective treatment.

The last part of the article sums up some interesting ways that insights from
rare disease research can help physicians better understand human physiology
and perhaps come up with ways to treat more common diseases. A very
interesting read.

~~~
fallous
It could also be difference in circumstance. Note that the bone growth occurs
as a response to muscle damage, so a more active child who suffers a higher
incidence of standard bumps and bruises would be more likely to have more
ossification.

------
woodchuck64
Some closeups of the condition:
[http://www.tumblr.com/tagged/fibrodysplasia%20ossificans%20p...](http://www.tumblr.com/tagged/fibrodysplasia%20ossificans%20progressiva)

------
speeder
How I disable the annoying popup that prevents me from reading the article at
all on a Android?

~~~
ISL
Perhaps the only permanent fix for such things might be to email the
magazine's editor?

------
jmadsen
For me, one of the most important things to take away from this story is the
possible link to osteoporosis (& a cure for it, although not directly stated).
Looking into a disease that affects almost no one might help find a cure for a
different one that affects one in ten people.

This is why we must also fund the study of "pure science" - of studying things
purely for the sake of learning, with no idea ahead of time if we will learn
anything "of value" or not.

Because there is so much that we don't understand yet, that it is impossible
to study the "why" of anything that exists in the world without stumbling
across something of more practical value.

------
datdo
Oh yeah. A classmate at my high school had FOP. I never thought the disease
would garner this much attention from the masses.

------
conanite
Wow. See also "Tupac Shakur and the End of the World", a short story about a
similar condition, caused by a latent virus and triggered by minor injuries.
Everyone dies.

I hadn't realised when I read it that there was a real-world equivalent ...

[http://futurismic.com/2010/03/01/new-fiction-tupac-shakur-
an...](http://futurismic.com/2010/03/01/new-fiction-tupac-shakur-and-the-end-
of-the-world-by/)

by Sandra McDonald

------
abecedarius
_The Mayo doctors didn’t tell Peeper’s parents that. All they did say was that
Peeper would not live long._

It's unclear from the article how much was known yet, but if they knew the
growths could be triggered by bruises and other insults, I sure as hell
would've wanted to be told.

------
zenith2037
One of the most interesting articles I've ever read. Nice research too.

------
Crake
I love Carl Zimmer. Great article, it was super interesting.

------
dfkf
No, no, no. Don't like. Don't want. Why does mother nature keeps coming with
shit like this? :(

~~~
masklinn
It's actually impressive, that's a single mutation which causes bruises to
heal as bone instead of muscle.

~~~
anoncow
Histidine to arginine. CAT becomes CGT.

------
kaichanvong
Found it fascinating. At the same time so upsetting that I am unable to
completely read it all. Will come back to it later.

Time to Google if this is 'normal' Starts to Google. Does anyone else feel
this way about this and other things?

~~~
kaichanvong
Would be nice to know why I'm being down voted for having an opinion on an
article I'm not used to reading that I deem as being quite emotionally
upsetting.

Are other people devoid of emotion and enjoying reading it?

~~~
ksmiley
It's possible you're getting downvoted because of the way you phrased your
post.

>> At the same time so upsetting that I am unable to completely read it all.

At first I interpreted this as, "[it is] so upsetting [because] I am unable to
read it all". It makes it sound like you're complaining that the page didn't
load all the way, or something. I had to read it a few times to understand
what you meant. It could have been less ambiguous worded as, "At the same
time, I am unable to completely read it all because it's so upsetting". If a
reader misinterprets this sentence, the rest of the post becomes
incomprehensible.

>> Time to Google if this is 'normal'

"this" is a bit vague here. What do you want to know is normal? Being upset by
articles in general? Being upset by articles specifically about rare diseases?
Being upset by this specific article?

>> Starts to Google.

Narration is the kind of thing I'd expect to see in a chat room, but not HN.
It makes your tone much less formal, and some might see that as
inappropriately flippant for a serious topic.

>> Does anyone else feel this way about this and other things?

"about this" is vague, again. The "and other things" clause makes this
question so broad that it becomes tautological. "Does anyone else feel [upset]
about [things that are upsetting]?"

~~~
kaichanvong
Thank you for explaining how you read my comment.

I didn't mean anything around the page loading, just that simply was
interested if people found the story of the girl's experiences heavy to read
on an emotional level. Thus I was interested if I am emotionally weak dealing
with this compared to others, why that is and if it's normal to be so shocked
by something.

Perhaps I should just not have said anything :)

~~~
abraininavat
Someone is deleting random words from your posts.

------
Ygg2
I'm half sorry, but this article is great example why eugenics is wrong and
why empathy and weird mutations trump it every day.

~~~
jkn
It shows the value of rare genetic disorders for biological and medical
research, but I'm not sure it speaks for or against eugenics, it's a complex
question...

Look at it from the point of view of an eugenics proponent: this disease is a
good example of a genetic condition that you don't want spreading in future
generations. Once we have treatments for the 7000 rare diseases mentioned in
the article, we will have removed the evolutionary pressure that was keeping
these diseases rare. Some eugenics supporters are afraid we are heading
towards a society where everybody has to undergo a dozen lifelong treatments
due to medicine effectively undermining the process of natural selection.

I can also imagine parents suffering from this disease, not wanting to pass it
on to their children. So people affected might strongly disagree with you...

~~~
LekkoscPiwa
>Some eugenics supporters are afraid we are heading towards a society where
everybody has to undergo a dozen lifelong treatments due to medicine
effectively undermining the process of natural selection.

So if you get cancer and there is a cure for it, you won't forego treatment to
help natural selection work? What type of twisted logic is that?

~~~
jkn
The eugenic view I was referring to is not saying

 _People should not be treated because it would spoil the gene pool_

but rather

 _We certainly want to treat diseases, but this will spoil the gene pool
unless we prevent the spread of bad genes_

Solutions to prevent the spread of bad genes range from quite evil (forced
sterilization has been used extensively before WWII but I have never heard of
something as bad as denying treatment) to slightly controversial, e.g.
screening of embryos [1].

By the way, I have just stumbled on the Wikipedia page on dysgenics [2], which
is more specifically what this argument is about.

[1]
[http://en.wikipedia.org/wiki/Preimplantation_genetic_diagnos...](http://en.wikipedia.org/wiki/Preimplantation_genetic_diagnosis)

[2] <http://en.wikipedia.org/wiki/Dysgenics>

~~~
LekkoscPiwa
Thank you for your time and effort to explain this.

Well, honestly, this smells national socialism from a mile.

Which genes are bad? Is it really that genes are bad? What about their
mutations?

I have (not really suffer) ehlers-danlos type 2. Which is genetic disorder.
Some people with it - like me - are lucky and have it really benign. It
doesn't really affect my life in any way. It doesn't affect lifespan in my
case. Then there are some others - with exact same gene mutations - who suffer
constant pain to the point they would like to die (literally). Not to mention
constant medical emergencies.

Now, I have almost no problems because of eds. And one benefit - apparently I
have lower risk of colon cancer. (there is more bile in the system which is
laxative which helps preventing colon cancer, plus the colon is built
differently, in my case causing "stuff" to move quicker). So, how would you
know my gene mutation is good or bad?

And how do you know that if you change it, something else won't be totally
messed up instead? There is always the problem of unintended consequences.

Not to mention that once you would open this pandora box, you'd also need to
deal with prospect parents demanding "gene therapy" for their future kid
because of a gene _they_ think is bad. Like with cosmetic surgeries. People
with gene A have higher risk of being short, so please doctor, please, let's
"fix" that. Our boy can't be short! Can't have red hair! Can't have 40% higher
risk of being depressed or obese too.

And here we go, all blond, tall, beautiful.

Wouldn't you agree?

~~~
jkn
Totally! I think your example is a good illustration of the difficult
questions we will face as genetic screening becomes more and more practical
and affordable, thanks a lot for sharing. (I can't help but wonder what you
would say to a doctor that tells you, "So do you want me to press this little
button to make sure your children won't have the same condition?")

However, it might also be that in the long term, the quality of the gene pool
objectively deteriorates. Taking it to the extreme, imagine if nobody can grow
older than five years without medical assistance... I guess this is also
something we should consider.

~~~
LekkoscPiwa
>imagine if nobody can grow older than five years without medical assistance

I think that way before that happens we'll have something like "virtual",
"immortal" "bodies".

In other words I think that before we need all that medical care the original
William Gibson's idea that we'll all end up stored somewhere in a computer
memory connected to a network will happen. No body or genes really needed - we
just "sit" in RAM, interact with others via network and are - immortal. Ray
Kurzweil says it may even happen in our lifetimes. Heard Stephen Hawking
mentioning something similar. Reaching point that we can live forever and
don't really need our body for that. Or our body can be strengthened by armor,
hardware of various types, to be much better and advanced than our bodies are.

This reminds me a little bit the dilema local Government in Paris had in 1890s
-- what we'll do with all the horse dung if the number of horses grows at the
current rate? And then cars came along and it was all irrelevant.

Seems to me it's also the same with depopulation. Who cares if there will be
20 billion of us in 50 years if we finally start colonizing other planets and
the Moon?

------
ramigb
I seriously thought this article was about converting to backBONE.js

