
Saving Lydia - dsr12
https://medium.com/lydian-accelerator/saving-lydia-62a1c0bdf0fb
======
fjfaase
My son too has a unique and disabling mutation. As far as I know, he is the
only person with this mutation, but there are more people with a mutation in
the same region of the gene, that are affected in the same way.

The problem with some mutations like this, is that they have an effect on the
development of the brain from the start of the development and that fixing the
gene (or better its RNA transscription) will not undo that development. The
results of IQ tests seems to indicate that with my sons mutation, there is a
problem with the myelination in his brain. Myeliniation is a process that
starts before birth and continues into adolescent. At the moment he is quite
happy and functioning well within his limits. His 'academic' IQ is rather low,
but in some areas, he surpases the average person by far. He has a great sense
of humor and people like him. In his case, I am really afraid what would
happen if we would administer him a drug that would compensate for the genetic
defect. Would he go through another fase of brain development and having to
cope with all kinds of changes. Could he end up being less happy, because it
would remove his ignorance about certain things. For example, at the moment he
has no desire for a romantic relationship, but getting such a desire and than
still not being able to satisfy it, could make him very unhappy.

~~~
sslapec
Flowers for Algernon by Daniel Keyes is exactly about this topic.

~~~
mhb
As is Asimov's _The Secret Sense_ :
[https://archive.org/details/TheSecretSense](https://archive.org/details/TheSecretSense)

------
DoreenMichele
_For Lydia’s, there are only two others in the entire world — one in Greece
and one in England._

That we know of. There may be many more who were, say, born in a developing
country and simply died without ever being identified as having this issue.

I generally agree with the impetus here to find some way to generalize
treatment for "orphan" diseases so that more people have some hope of
effective treatment. I have no idea if this particular approach will yield any
real benefits.

 _Orphan disease: A disease that has not been adopted by the pharmaceutical
industry because it provides little financial incentive for the private sector
to make and market new medications to treat or prevent it. An orphan disease
may be a rare disease (according to US criteria, a disease that affects fewer
than 200,000 people) or a common disease that has been ignored (such as
tuberculosis, cholera, typhoid, and malaria) because it is far more prevalent
in developing countries than in the developed world._

Source (I don't recommend actually clicking on it. It had at least two pop-
ups.):

[https://www.medicinenet.com/script/main/art.asp?articlekey=1...](https://www.medicinenet.com/script/main/art.asp?articlekey=11418)

------
amelius
> This is a classic long tail problem — no mutation is common enough, but
> collectively there are tons. The existing Pharma approach to treat these is
> broken — they look for common typos and fix them with long drawn out trials.
> This barely makes a dent. Worse, they have put each in its own bucket and
> labeled them as rare, so the majority of the world feels they‘re not
> important to fix.

Shouldn't this be viewed more at the pathway level than at the base-pair
level? Pathways have redundancies, and medicine can address a pathway.
Focusing on base-pairs seems like a race you can't win, unless we have the
technology that can reliably fix single nucleotide mutations.

~~~
DrAwdeOccarim
That's the super exciting and interesting part of literally today. There are
two new technologies that are about to combine that will probably get us to
"reliably fix single nucleotide mutations." in a platform sense within the
next 5 years.

The first technology is the production and delivery of messenger RNA made
synthetically, and the second is the fusion of the recognition portion of
CRISPR with a class of enzymes known as base editors.

Of course we'll have to start with the liver and with diseases that move the
needle (i.e., not N of 1), but once the technology is approved in this case
things get a lot more interesting for other genetic diseases that don't move
the needle. Tim Yu developing the ASO for Mila is the perfect example of how
once the technology is working for a money-making indication, less profitable
treatments can follow.

If you want to read more about this, check out Beam Therapeutics, Moderna
Therapeutics, Intellia Therapeutics, CRISPR Therapeutics, Editas, STRAND
Therapeutics, Translate.bio, BioNTech, Josh Rosenthal at Woods Hole, Feng
Zheng at MIT/Broad, and David Liu at Harvard.

------
deskamess
Parental hurt is an altogether different kind of hurt. I have felt it in a few
cases but 'life struggle' issues are likely on another level. I can empathize
only to the limits of what I know and can only wonder how, and hope, they
continue to stay strong.

~~~
kohanz
This. My heart aches on a whole new level when I hear/read/experience children
and parents going through such hard things. We've had very close friends lose
children at a very young age and it's heartbreaking.

I have nothing but sympathy for everyone involved and admiration for the
strength of the parents. Few people are more motivated and capable than
parents being told that a problem that affects their children cannot be
solved.

------
fareesh
What does it mean to "silence" a mutation? If that particular gene is
different compared to humans who don't have the same developmental condition,
then is the medicine able to instruct the cells to replicate in a way that
ignores the mutation and not carry the defect created by the mutation?

Or does the medicine supplement the role of whatever that cell is supposed to
do? (Assuming this affects some specific roles cells)

~~~
sjg007
There are two alleles for this gene. You get one from your mom and one from
your dad. In this case one allele has a mutation that is causative. So you
inject some anti-sense RNA matched to that mutation, it will bind to the mRNA
of the transcribed mutated gene DNA. Since it is now bound up, the mRNA cannot
be translated by the ribosome and turned into protein. This means that only
the other allele (without the mutation) is translated into protein.

------
rohittidke
I am trying to donate from Germany but can't because of an error. Not a valid
phone number. Any body faced the problem?

------
dusted
The article makes the excellent point that, although various genetic mutations
have wildly different consequences, the root problem is the same: Genetic
mutation. Sounds like there should be a generic fix somewhere.

~~~
shultays
I am not a doctor but i would imagine most genetic problems would be too late
to fix once you are born. And the one that are fixable would require you to
fix syptoms rather than dna itself. So "a generic fix" is probably impoasible

~~~
mikepurvis
It might be too late for today's babies, but if you could build a big enough
catalog of mutations and suspected/confirmed ill effects, then you'd
potentially be able to catch thousands of these mutations essentially at
conception and supply a custom therapy right then and there to correct it
before any brain development has begun at all.

~~~
adrianN
If you catch the problem at conception, the easiest way seems to be to abort
and try again.

~~~
mikepurvis
That is fair, and indeed, there are a bunch of genetic disorders that can (and
are) screened for prenatally, see:

[https://women.texaschildrens.org/program/high-risk-
pregnancy...](https://women.texaschildrens.org/program/high-risk-pregnancy-
care/conditions/genetic-disorders)

~~~
rohanseth
Lydia's father here. If I wasn't fighting this fight, my fight would be to
push for prenatal exome sequencing. I acknowledge it's not as black and white
-- there are some ethical concerns about how to process the data, but give the
parents the choice.

------
acomjean
There is a whole network of undiagnosed diseases. They’re getting better at
replicating these mutations in model organisms which can help figure things
out faster and less expensively.

[https://undiagnosed.hms.harvard.edu/](https://undiagnosed.hms.harvard.edu/)

------
Causality1
Excellent article. It's my belief the medical industry suffers from a "take no
action" bias. They believe letting ten thousand people die from inaction is
better than a treatment that will kill half of them and save the other half.
When it comes to people who are going to die or suffer for the rest of their
lives, I don't see anything wrong with "move fast and break things".

------
JPLeRouzic
Would not it be possible to create an open source project for a generic
platform for antisense oligonucleotide therapies.

I mean publishing the hardware for a high-performance liquid chromatography,
possibly 3D printed and the controlling software?

And the platform would produce the desired antisense oligonucleotides from an
easy UI, like just describing the desired mutation, and the software would
deal with the details?

------
vasilia
Hope that will help Lydia to have a good long life and other people.

------
mangatmodi
So there is a cure, but it is not profitable and no body is doing it? Society
has evolved so wrong, when we can't provide basic needs to everyone despite
(probably) having enough for everyone.

I wonder how many people are living a miserable lives, without knowing they
can b e treated. Do I have to Ph.D in every medical science to make sure my
kids get a treatment what they deserve?

~~~
carlmr
>Society has evolved so wrong, when we can't provide basic needs to everyone
despite (probably) having enough for everyone.

I mean there are 3 people (as far as they know) with this specific mutation.
Time, money, and capable scientists are limited. Allocating these resources
efficiently means that the more rare disease don't get as much attention, but
this also means that you're saving more people. Just not those with the rare
conditions.

From the article

> The rare label is wrong and limits progress. These are not rare. These are
> genetic and have the same root cause. We need a systematic, platform-driven
> approach to fix these typos. We need a spell check.

Yes, there are millions with some mutation. But changing around mutations
needs to go through some form of medical process to see if it's safe. The
current processes are there because historically there has been a lot of abuse
for profit. We can't just platform allow any genetic editing. Some of these
edits might be dangerous.

~~~
luma
While I agree with your first point, I think you're off base on the second.
If, as the OP suggests, it would be possible to develop a toolkit such that
the concerns about time/resources you raise in your first point are moot, then
I think it's worth chasing that down. The result isn't saving 3 people but
rather making it possible (profitable?) to do the same for anyone with these
sorts genetic transcription errors.

While you're correct that an individual treatment using this approach can
never be tested against thousands of patients to determine safety (as it might
only be needed by 3 people), it's either try it or watch thousands of people
die.

~~~
carlmr
>f, as the OP suggests, it would be possible to develop a toolkit such that
the concerns about time/resources you raise in your first point are moot, then
I think it's worth chasing that down.

I do agree that this is something worth following. If it's really provable
that this platform solution is universally safe, that's amazing. But that
doesn't mean the system is broken. Just that until now, this was probably not
the proverbial low-hanging fruit of medicine, even with a million people there
are diseases affecting billions. It may still be worth more investing in those
disease that affect billions.

>it's either try it or watch thousands of people die.

How many of these genetic diseases are deadly? A lot of these mutations may be
bad but not deadly. If now the treatment is universally approved and kills
some people, think about who's going to take the responsibility for it?

~~~
luma
> If now the treatment is universally approved and kills some people, think
> about who's going to take the responsibility for it?

Same as any other medical intervention. A substantial number of people die as
the result of routine surgery for problems that themselves weren't life-
threatening. Medicine, like engineering, involves tradeoffs and risk
assessment, and there is not likely to be a perfect outcome. All we can do is
work on the "best" outcome for the most people.

------
hkai
With whole exome sequencing now at 500 USD, personally I will start by testing
myself and my partner for hereditary diseases before having kids.

------
dusted
It is an excellent point, genetic mutations may have wildly different
consequences, but they are all the same fundamental issue: genetic mutation.

------
ycombonator
This is heartbreaking. Thank you for bringing the awareness. Hold that child
tight.

------
inmate4587
Well.. it is an excellent idea.

------
b_tterc_p
The headline has changed for me to include a typo? “... sourcing my haby”?

~~~
ModernMech
Only reason I clicked was to find out what a haby was.

~~~
monkeydust
Likewise. Guess it worked then!

------
lettergram
I’ve seen the title of this article change at least three times. I actually
think the “saving Lydia: open sourcing by baby” may be the most descriptive.

------
ailideex
> I’m Open Sourcing My Baby to Save Her and Others

Nope, that is not what you are doing.

~~~
amdavidson
In a way, that is what he is actually doing:

    
    
      Over the next few months, we will start by asking our 
      collaborators to open source everything from Lydia’s 
      N-of-1— the process, costs, contracts, protocols, 
      assays, cell lines and data.

~~~
ailideex
I'm not sure how you get from open sourcing "process, costs, contracts,
protocols, assays, cell lines and data" to open sourcing a baby as "process,
costs, contracts, protocols, assays, cell lines and data" is not a "baby" nor
is it the source code of a baby.

If they licensed their Baby's DNA under some open source license then maybe we
could say that they were open sourcing their baby, but:

\- Don't think that is what they were doing.

\- Not sure they own the copyright of their baby's DNA.

\- Don't think that would be legal to do.

~~~
monkeynotes
I think you guys are unnecessarily being pedantic about the semantics here.
Obviously the parents are software tech people, and so there is some poetic
license with the headline. It's not really click bait as it is in good faith,
and it isn't really misleading to anyone who can understand the bias of tech
people to relate everything they do to their passion.

It isn't a journalistic article and so the writer should be forgiven for using
a touch of their creativity with the title. Had this been from a news
organization I would probably feel rather differently.

------
elcomet
"My haby"

~~~
alberto_ol
the typo in the headline should be fixed

------
dlphn___xyz
its crazy how people support medical experiments on a child but will call
child protective services if you feed your child a vegetarian diet

~~~
logiclogic
I know many parents who feed their children a vegetarian diet without any
health issues whatsoever. The cases I have read about in the newspapers were
parents feeding their kids a vegan diet without a sufficient amount of
calories and their kids literally starved from not getting enough energy to
live. You can not live off eating only tomatoes and salad every day but you
will be buff if you eat beans and lentils every day. Edit: A vegan diet
requires more knowledge to get all the sufficient vitamins and these parents
obviously fucked it badly.

------
fevangelou
If modern medicine was 10% open source, the world would be 110% a better
place.

------
ausbah
This sounds like an absolute lifesaver for a bunch of people! I'm surprised
more people in the comments aren't even a little more enthusiastic.

~~~
remeq
Playing around with words like "open sourcing" is not a good idea in
semantics-sensitive dev community. Not even what it comes to pretty little
babies

------
blueboo
Something weird is going on with this lady...wasn't the campaign originally 1
or 1.5m? Now it's 2.5m for a vastly more ambitious goal?

Kickstarter tawdriness is creeping into what was otherwise a gold-plated
medical GoFundMe.

~~~
rohanseth
This is our bad. When we had shared at Google, we thought the cost would be $2
million. We didn't include the money we had put in or received, so we shared
our goal as $1.5million.

Before sharing more publicly, we decided to update to the actual amount and
had also learned that some costs would be higher than expected (toxicology
package would be higher, clinical care wasn't going to be covered by insurance
etc.). We had put a little note describing this in the FAQ, but I understand
that no one reads those.

For what it's worth, our goal from the very start was to openly share the
process and logistics because we are truly convinced that this N-of-1 process
can be repeated quite easily. Perhaps, at the very least we can squeeze the
time for the next motivated parent to learn all this from 6 months to 1
months.

------
AtlasBarfed
Genetics-specific treatment is what medicine should be working toward.

Currently it is structured to make-pill-mint-money for drug companies. If a
disease/treatment isn't mass produced, THEY DON'T CARE.

Medical devices are a bit closer to what is needed, but fundamentally they are
run by the same business models.

Instead what will probably be required is a lot of specific testing (labor
intensive), computational analysis (some labor and analysis) that produces the
necessary treatment formula (or CRISPR design, etc), and then something that
produces it.

The margins won't be great, so no MBA-driven healthcare will care about that.

The biggest disease that needs this approach to approach a "cure": CANCER.
Cancer, even the "common" ones, are the result of dozens of
varieties/combinations of gene malfunctions.

First world nations should pool money to start a multinational infrastructure
that includes continuous improvement. Sections of this can probably be make
profitable, but those will probably be lots of small companies.

All of which would be GREAT for employment.

~~~
dmix
I don't see why you repeatedly accuse MBA people or the pharma scientists of
not "caring" then proceed to explain multiple reasons why it's infeasible as a
private business or even an academic or public organization.

There's plenty of serious health issues constantly competing for a small pool
of smart medical peoples attention and with a limited capital.

Genetic tailoring still currently involves a high amount of specialist
attention per individual and there is plenty of research and money going into
it. I've heard multiple doctors tell me it's the future of medicine.

Whether it could use more attention and capital is certainly a good question.

