
A Battle Plan for a War on Rare Diseases: Conversation with Matt Might - onuralp
https://www.nytimes.com/2018/09/10/health/matthew-might-rare-diseases.html
======
dang
This has a touching backstory on HN:

[https://news.ycombinator.com/item?id=8050106](https://news.ycombinator.com/item?id=8050106)

[https://news.ycombinator.com/item?id=4038113](https://news.ycombinator.com/item?id=4038113)

I didn't realize that he had switched fields and moved. That info is here:

[https://www.uab.edu/medicine/news/latest/item/1411-white-
hou...](https://www.uab.edu/medicine/news/latest/item/1411-white-house-
strategist-to-lead-uab-s-personalized-medicine-institute)

and [http://www.pl-enthusiast.net/2016/03/24/interview-matt-
might...](http://www.pl-enthusiast.net/2016/03/24/interview-matt-might/), via
[https://news.ycombinator.com/item?id=11366150](https://news.ycombinator.com/item?id=11366150)

------
the_grue
Matt Might (the subject of this article) gave a jaw-dropping talk a year ago,
named "Winning the War on Error - Solving the Halting Problem and Curing
Cancer" [1]. At least you can't blame him for the lack of ambition! But the
best part is he's really getting it done. His security research led to
developing very successful static analysis tools that exposed security bugs in
real code. And he did manage to find a treatment for his own son's rare
genetic disorder.

[1]
[https://www.youtube.com/watch?v=MdmQUlD7P40](https://www.youtube.com/watch?v=MdmQUlD7P40)

~~~
cellularmitosis
Off topic, but he also gave a great talk on parsing with derivatives
[https://www.youtube.com/watch?v=ZzsK8Am6dKU](https://www.youtube.com/watch?v=ZzsK8Am6dKU)
which was used by the clojure team [https://paperswelove.org/2016/video/david-
nolen-parsing-with...](https://paperswelove.org/2016/video/david-nolen-
parsing-with-derivatives/)

------
shubb
Rare family diseases tend to be genetic diseases with a relatively simple
genetic cause that can be found by comparing family members.

This article is about treating rare diseases, but there is a simpler way -
having identified the genes for the disease, we could screen for them, and
then advise people carrying them to reproduce only via selective IVF. That
way, the next generation of that family can be free of carriers, eliminating
the disease in the long term even if a treatment isn't found. (This is not an
either or with finding a treatment)

The above approach is much cheaper, effective, but raises important moral
questions we need to think hard about. At what point does a disease become bad
enough that it needs to be excluded like this? Slippery slope, etc.

~~~
dbbolton
Perspective from a US physician:

Pre-implantation genetic diagnosis (or PGD, what you described as 'selective
IVF') is not cheap. It costs upwards of US$100,000 and no commercial or
government insurance will cover it.

Genetic screening is also not cheap. An exome (essentially looks at all
~22,000 _known_ exons, or the genes that directly contribute to protein
formation) costs US$6,000 - $8,000 and most insurances will fight tooth and
nail not to have to cover it even when it is ordered by a geneticist. You
might think "but there are much cheaper genetic tests besides an exome" which
is true, but remember we are talking about rare diseases. Exome testing is
still imperfect but it is essentially the only realistic option if your goal
is to rule out as many known genetic diseases as possible, or if you know
there is a high pretest probability of a genetic disease but less exhaustive
testing was negative or inconclusive.

Actually, current PGD doesn't use exome testing but much more selective
testing often based on the parents. One technique is FISH which can
essentially only tell you if there are any "large" genetic abnormalities, like
(micro-) duplications or deletions, which are large relative to, say, a point
mutation. As an example, FISH testing would not reveal cystic fibrosis. The
other is PCR, which is currently the technological limit for PGD testing
because of the small number of cells and minimal amount of genetic material
available for testing. There are several PCR assays available for _specific
conditions_ in the setting of PGD, which is where the parents fit in. We will
probably see more and more assays becoming available, but it is unlikely that
anything resembling an exome will be feasible for PGD in the foreseeable
future.

Disclaimer: I am not a geneticist or reproductive specialist. If you can find
sources by physicians in these fields, I would defer to them.

------
baldfat
> he’s begun to create a road map for other families facing rare diseases — as
> much as 10 percent of the population, or 30 million Americans.

10% of our families are effected by "rare" diseases.

September is Pediatric Cancer Awareness Month: 100% of Pediatric Cancer is
classified as "rare." It is used to give so little in research and most money
is used to help the families financially. 4% of the US Cancer Grant is
allocated to Pediatric Cancer research.

    
    
      Lost a sister at 15 to brain cancer and a son at 12 to bone cancer. The worst thing to do is to call it rare. How many thousands didn't start school this year? How many thousands of families have lost

~~~
ams6110
Well it is rare, though. More kids are killed by automobiles than die of
pediatric cancer.

That doesn't make it any easier for those families dealing with pediatric
cancer. But it is rare, and if your goal is saving the most lives with a
limited amount of money, there is lower-hanging fruit.

~~~
kryogen1c
I really appreciate level-headed moralism like this. Many of our problems
today are because we get painted into corners by people making emotional
arguments and winning because the other side is unwilling to appear uncaring
in the implied false dichotomy.

~~~
baldfat
Forget that. How is that a win. I make a statement and then he can say only a
few thousands kids die so tough. Sure I'm emotional but I can give some good
reasons why Pediatric Cancer Research needs more funding.

Pediatric Cancer went over 20 years without a single chemo? How is that
reasonable? [https://www.theatlantic.com/health/archive/2013/01/our-
dispr...](https://www.theatlantic.com/health/archive/2013/01/our-
disproportionate-focus-on-adult-over-pediatric-cancer-research/266684/)

1) Pediatric Cancer Treatments are beneficial to adult cancers. They have less
side effects and are usually more effective due to the fact that children's
bodies and cells are all growing. Most adult treatments are too harsh and
attack all the cells.

2) Treat a 60 year old smoker for lung cancer and you gain maybe 10 years.
Treat a 10 year old and you have 60+ years saved. Most adults get cancer
because of poor life choices.

3) Save your own life as a full grown adult or save a child. MOST of us would
choice to save the kid. [https://phys.org/news/2014-08-driverless-car-child-
life.html](https://phys.org/news/2014-08-driverless-car-child-life.html)

------
Nasrudith
These rare diseases are interesting in their utility. Previously one would
think ignore them budgetwise - not out of callousness but because of
compassion for others affected by more common diseases. However their oddball
effects also boost understanding of otherwise obscure effects. Sonic hedgehog
was named for the protein shape - and then it turned out defects in the linked
gene can lead to horrifying birth defects and well SHH is a less frivolous
term for it.

~~~
agvaughan
"Sonic hedgehog was named for the protein shape"

FWIW, Shh was named for the phenotype in Drosophila. It makes their bristles
spiky.

I can't find a pic of Shh off the top of my head, but here's a gene with a
similar phenotype in flies:
[https://twitter.com/kirkmmaxey/status/577886323912015872](https://twitter.com/kirkmmaxey/status/577886323912015872)

------
mattip
I appreciate the intensity and urgency of this attempt, but surely there is a
way to frame the work without resorting to militaristic metaphors. Surely
there are other forms of expressing an effort than “the war on ...”?

~~~
ausbah
If there’s one thing worth waging war on, I think it’s all these diseases
since they have a “common enemy” position against mankind as a whole.

------
jbrambleDC
I worked with Matt at the US Digital Service. Amazing stand up guy!

------
teslabox
Dr. Matt Might is one of the few people that I remember from high school [0].
He's the only one from that school whom I've communicated with post-
graduation. [edit: one other, actually...]

[0]
[https://news.ycombinator.com/item?id=11366288](https://news.ycombinator.com/item?id=11366288)

I think it important to put medicine's lack of progress in adequately treating
many conditions in context, and only consider genetic factors as one
consideration in the web of causality. Too often doctors make a diagnosis and
treat the diagnosis. Much more work needs to be made in respecting the
complexity of even the simplest of diagnoses.

Consider the simple ear infection. Sometimes children have regular ear
infections, but these usually go away as the person grows up. I started having
chronic ear infections in college, well after the usual age that one
experiences chronic ear infections. The prescribed antibiotics took care of
the problem for a few weeks before the infection returned. After a year of
this I figured out how to take care of my ears myself with non-prescription
interventions, and after maybe 6 years I figured out how to treat the causes
behind my ears' poor drainage.

The GQ story "Sperm Count Zero" was recently discussed here:
[https://news.ycombinator.com/item?id=17942744](https://news.ycombinator.com/item?id=17942744)

GQ didn't really drill down into the causes behind the male population's
shrinking sperm counts, because the experts themselves aren't at all sure
about the causes behind the symptom. While the causes of an individual man's
low sperm count are unique in every case, it is a combination of factors that
causes our society's shrinking sperm counts. The causes that I suspect include
evolutionary-inappropriate modifications to our diet, mass exposure to
endocrine disruptors (xeno-estrogens), etc. The Mayo Clinic's page about this
condition [1] shows there's a few known simple causes for a man's low sperm
count, but there is no effort to put society's condition in context.

[1] [https://www.mayoclinic.org/diseases-conditions/low-sperm-
cou...](https://www.mayoclinic.org/diseases-conditions/low-sperm-
count/diagnosis-treatment/drc-20374591)

Women are having similar responses to the causes behind men's shrinking sperm
counts. Because women are supposed to release one egg a month rather than
millions, their condition gets a label (PCOS/Endometriosis/anovulation/etc)
and standardized treatments. Women are often subjected to palliative
treatments for their diagnosis -- frequently this is some form of birth
control. While some women find their condition to be helped with these
prescriptions, medicine has failed to 'cure' their problem. They've just shut
down the symptoms enough to make the patient's life a little more tolerable.

Sometimes women think they have "polycystic ovaries" [PCOS] because their
mother had symptoms of polycystic ovaries, and think their own condition
"must" be genetic. But habits get passed down too, and "stress" is a major
factor in many women's conditions. Poverty is not genetic, but it usually gets
passed down with all the other habits we learn from our parents.

Treating a woman's diagnosis of PCOS with birth control is using hormone
analogues to suppress the normal functioning of the reproductive system. The
use of these drugs for PCOS is a 'palliative' rather than 'curative'
treatment.

There are certainly 'rare diseases' with genetic causes, but an effort also
needs to be made to clear obsolete and harmful treatments from medicine's tool
chest. Sometimes "war" is appropriate, but war can also be prevented with good
diplomacy.

~~~
Nasrudith
By definition obsolete treatments get removed only when something better comes
along or it is proven lack of treatment leads to better outcomes. The least
aggressive forms of prostate cancer defy conventional wisdom and are left
untreated - putting aside quality of life treating it is more likely to kill
the patient who would probably die of something else before it becomes a
problem.

The place of doctors is to treat with today's proven means - experimenting is
usually left to researchers unless there is little to lose. Medicine is a
conservative field in the roll out. Given how many "advances" of newly
discovered aspects don't work quite as expected like megadosing antioxidants
it is pretty prudent.

