Saving Lydia(medium.com)
medium.com
Saving Lydia
https://medium.com/lydian-accelerator/saving-lydia-62a1c0bdf0fb
120 comments
If you know the specific issue -- the pathway the problem follows -- you may be able to do something about it more gently than some big irreversible drug.
My firstborn son has a genetic disorder and a long list of issues. I figured I had until he was about five or so to do anything meaningful about it. This turned out to not be true. The window for intervention was much longer.
He's 32 and much more functional than I ever expected him to be, though he still lives with me for now.
He still has zero interest in a romantic relationship. He and I have the same genetic disorder. I do not share his general lack of interest in romantic relationships.
I will suggest you try to not automatically lump in all of your child's characteristics with this one detail that he has a mutation. You might read up a bit on "ace" or "aromantic" people. There are people who just aren't terribly interested in romance. It's really not some bizarre defect.
My firstborn son has a genetic disorder and a long list of issues. I figured I had until he was about five or so to do anything meaningful about it. This turned out to not be true. The window for intervention was much longer.
He's 32 and much more functional than I ever expected him to be, though he still lives with me for now.
He still has zero interest in a romantic relationship. He and I have the same genetic disorder. I do not share his general lack of interest in romantic relationships.
I will suggest you try to not automatically lump in all of your child's characteristics with this one detail that he has a mutation. You might read up a bit on "ace" or "aromantic" people. There are people who just aren't terribly interested in romance. It's really not some bizarre defect.
To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells. Not having an interest in romance is but one of the least symptoms he has. I only took it as an example. His social emotional development age is somewhere between 3 and 5 years. He can use a computer and loves watching children programs on YouTube. He has an above average autobiographical memory especially with respect to people who were with him. Most of the time, he knows who has been introduced to whom. He immediately notices when someone is missing who should be there. Very remarkable, because in general people are not good at this, especially not for groups over twenty people.
To clarify, the mutation of my son is not inherited, it is a new mutation, which most likely occured in my sperm cells.
I did see your other comment. I did understand that this was new and apparently unique.
https://news.ycombinator.com/item?id=20524334
I did see your other comment. I did understand that this was new and apparently unique.
https://news.ycombinator.com/item?id=20524334
I'm really sorry to hear about your son. I'm Lydia's father (the author of the medium post). What you shared is my biggest concern about going forward with Lydia's treatment. We are confident that the treatment will help her brain development, but to your point, there's a chance that will hurt her quality of life. We just don't know. How do you make a decision like that?
I think about this a lot and don't have good answers. All I can say is that I have 3 goals for my daughter - and she doesn't need to be a 100% normal child to achieve any of those goals. 1) I hope my child is not in pain 2) I hope my child feels loved 3) I hope my child can find beauty in the world.
I think about this a lot and don't have good answers. All I can say is that I have 3 goals for my daughter - and she doesn't need to be a 100% normal child to achieve any of those goals. 1) I hope my child is not in pain 2) I hope my child feels loved 3) I hope my child can find beauty in the world.
If I may make a suggestion (not sure if English is your second language or not). Consider using 'typical' instead of 'normal'. It took me awhile to get used to that but my daughter is better off this way.
Flowers for Algernon by Daniel Keyes is exactly about this topic.
As is Asimov's The Secret Sense: https://archive.org/details/TheSecretSense
Beat me to it. Fantastic book.
I interpreted it more as a story about aging. I guess both!
Romantic relationships make lots of totally normal people very unhappy, to the point where perfectly healthy young people kill themselves over romantic rejection or kill partners for whatever reason. Learning how to do romantic relations is painful, and when it's not painful for a person, they usually experience the pain later when they get old or fall in with a terrible partner.
So, your example of the happiness / awareness tradeoff really applies to everyone. It probably applies to ancient myths like Adam+Eve, Prometheus etc. too. From history it is clear that seeking awareness at the risk of existential discomfort is something that people do.
So, your example of the happiness / awareness tradeoff really applies to everyone. It probably applies to ancient myths like Adam+Eve, Prometheus etc. too. From history it is clear that seeking awareness at the risk of existential discomfort is something that people do.
That's a very powerful point.
Every treatment (nay everything) is a one-way door: You do something, and there's no going back. With general medicine you can at least infer some knowledge based on other people's reaction to the same drug. But in "N-of-1" drugs, you're left completely in the dark. It's (going to be) a very hard call to make.
Flowers for Algernon explores this issue and had a profound effect on me as a teenager. Probably the best book included in the school curriculum.
Happiness is only understood in contrast. On the one hand you obviously want to protect your child and ensure their happiness, but on the other, by doing so, you might be robbing them of the essential human experience.
Happiness shouldn't be an end goal to a life, but a byproduct of one. Negative experiences shouldn't be looked down upon and avoided, after all that is how we learn and improve ourselves - by overcoming adversity.
Having said all that, this is an incredibly tough decision to make and is solely up to your family.
Having said all that, this is an incredibly tough decision to make and is solely up to your family.
I have one as well that is herideraty but no relatives have it (tested after finding out I had it). I think it's usually something like 1 in 400k people having a mutation of a specific gene.
De novo mutations (DNM), that is new mutations, is rather high and increases stronly with the age of the father, because sperm cells are produced by continued cell divisions, where the egg cells of women are produced before birth. With the mother there is also a slight increase over time, but the number of even old mothers is lower than that of young fathers. Luckily, only a small part of the DNM occur in genes and some mutations are not even harmfull, due to how triplets of base pairs are decoded into amino-acids. And then there are also many mutations that do have an effect on the protein being produced, but that the difference does not have a great effect. For most genes there are many variants, which all leads to working proteins, some of which might work slightly better than others in some area and maybe (slightly) better in another area. (Just recently there was a news item about how humans lack a certain gene compared to other mamals, which increases our risk with respect to cardiovascular disease, but apparently also increases our ability to walk/run long distances.)
> the egg cells of women are produced before birth
just fyi this is actually an active research topic, c.f. https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research
just fyi this is actually an active research topic, c.f. https://en.wikipedia.org/wiki/Oogonial_stem_cells#Research
Is his motor function affected?
Yes, his motor function is also affected, but has improved a lot, such that now as an adult, it is primarily his fine motor skills that are poor. But he has no problems using a mouse. The wear pattern of his shoes is still a little abnormal.
The poor motor function is probably related to poor myelination of the nerves in his body, as his proprioception and pain perception are affected.
The poor motor function is probably related to poor myelination of the nerves in his body, as his proprioception and pain perception are affected.
Yeah, myelination usually has more pronounced effects on peripheral nerves as they had long wrapped axons. I’m glad your son did not have severe demyelination problem. I don’t want to sound brutal but the mild effect mutation caused could also be the reason he survived the mutation
He probably would not have survived when born a hunderd years ago or in a less developed country, because he relied on tube feeding for several years. To me, you did not sound brutal. A side effect of having better medical intervention techniques, is that the general fitness of human genetic material is getting lower. If you combine this with the higher age at which children are conceived, it might make genetic genering inevitable in the future for the human species to survive.
Yeah, I totally agree your point. The better medical condition inevitably making those mutations deadly years ago now survivable. These conditions are also called rare diseases by NIH. They won’t worth the effort for pharma to develop traditional treatment. But genetic manipulation like crispr might help to cure, it might be late for your son, but might still helps.
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...
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...
> 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.
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.
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.
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.
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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.
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.
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.
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)
Or does the medicine supplement the role of whatever that cell is supposed to do? (Assuming this affects some specific roles cells)
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.
I am trying to donate from Germany but can't because of an error. Not a valid phone number. Any body faced the problem?
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.
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
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.
If you catch the problem at conception, the easiest way seems to be to abort and try again.
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...
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.
Most people don’t even know when they conceive. A significant number of pregnancies end in miscarriage without the woman ever knowing. Lack of a catalog of issues is only the first obstacle to any kind of “correction at conception”.
It may be, there may be several classes of "generic fixes".
Could it be that we identify a way to improve the genetic machinery itself, so that replication errors are less likely. or maybe a way to maintain DNA already in place in an individual (be it that the individual is born with it or gets it later, like cancer)
Could it be that we identify a way to improve the genetic machinery itself, so that replication errors are less likely. or maybe a way to maintain DNA already in place in an individual (be it that the individual is born with it or gets it later, like cancer)
I mean, you'd have to have a reference genome basically, right? How do you even define such a thing...
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/
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".
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?
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?
Hope that will help Lydia to have a good long life and other people.
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?
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?
>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.
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.
@carlmr, I understood the position better now. Maybe states should completely fund or control medical researches. This is one thing which should never be done for profit.
>For Lydia’s, there are only two others in the entire world — one in Greece and one in England
Both countries with socialized medicine and yet they still didn't come up with a cure. It happened in one of the most, if not the most, capitalistic tech-hubs in the world. Maybe there's just something about the private sector that gets things done.
Both countries with socialized medicine and yet they still didn't come up with a cure. It happened in one of the most, if not the most, capitalistic tech-hubs in the world. Maybe there's just something about the private sector that gets things done.
> Both countries with socialized medicine and yet they still didn't come up with a cure.
This is misleading. The original post was about medical research, which neither in Greece nor in England is any more "socialized" than elsewhere. They might have national health services, but those buy their medicines from the same private actors as any hospital in the United States.
Also note that the original article is specifically not about profit-driven R&D but about a donation-funded, non-profit venture. The (hopeful!) success of such a venture does not really translate well into an argument for private, for-profit medicine R&D.
You could argue that it's the raw capitalistic drive of SV that is uniquely able to generate the wealth necessary for such non-profit ventures, ok, fine (there are also counter arguments to this), but this was not really the point of the original comment.
This is misleading. The original post was about medical research, which neither in Greece nor in England is any more "socialized" than elsewhere. They might have national health services, but those buy their medicines from the same private actors as any hospital in the United States.
Also note that the original article is specifically not about profit-driven R&D but about a donation-funded, non-profit venture. The (hopeful!) success of such a venture does not really translate well into an argument for private, for-profit medicine R&D.
You could argue that it's the raw capitalistic drive of SV that is uniquely able to generate the wealth necessary for such non-profit ventures, ok, fine (there are also counter arguments to this), but this was not really the point of the original comment.
As the article argues, there's no profit to be made because of lack of patentability. If this is the case, maybe an adjustment in incentives on the side of the law would fix this and make the private sector interested.
A lot of the big medical innovations still come from the private sector. The question is only whether we can get the interests aligned here.
A lot of the big medical innovations still come from the private sector. The question is only whether we can get the interests aligned here.
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.
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.
> 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.
The amount of work that goes into making sure that any single treatment isn't going to have unknown side effects is non-trivial. Just because there is a common toolkit doesn't make this safety testing go away. It automates the design of the safety tests somewhat, but doesn't make them any less important. This means that for every... single... anti-sense oligo that's designed, there needs to be significant testing done to make sure that it does what is expected and doesn't have any adverse side effects.
In many cases, it's the first part -- the design of the treatment -- that is rate limiting. The benefit of something like these N-of-1 ASO trials is that you're streamlining the first step in the process. But that doesn't mean you can just skip the other steps. And yes, these steps are expensive.
The amount of work that goes into making sure that any single treatment isn't going to have unknown side effects is non-trivial. Just because there is a common toolkit doesn't make this safety testing go away. It automates the design of the safety tests somewhat, but doesn't make them any less important. This means that for every... single... anti-sense oligo that's designed, there needs to be significant testing done to make sure that it does what is expected and doesn't have any adverse side effects.
In many cases, it's the first part -- the design of the treatment -- that is rate limiting. The benefit of something like these N-of-1 ASO trials is that you're streamlining the first step in the process. But that doesn't mean you can just skip the other steps. And yes, these steps are expensive.
>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?
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?
> 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.
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.
it seems like business people need to wrap their mind around creating a process that allows these one off solutions to be made more easily. There are probably over a million people with a one off genetic problem that would be worth at least 100,000 to solve. Making a one off solution once is obviously not the solution, but instead engineering the process to allow the one off solutions to be generated more quickly and easily.
1,000,000 * 100,000 = 100,000,000,000
A possible 100 Trillion dollar industry seems like a very stupid thing to ignore.
The other thing to remember is that making a genetic toolkit to fix genetic errors is a potentially low liability solution, if well tested, documented and proven. The liability would still rest primarily with the practitioner.
1,000,000 * 100,000 = 100,000,000,000
A possible 100 Trillion dollar industry seems like a very stupid thing to ignore.
The other thing to remember is that making a genetic toolkit to fix genetic errors is a potentially low liability solution, if well tested, documented and proven. The liability would still rest primarily with the practitioner.
"A possible 100 [b]illion dollar industry seems like a very stupid thing to ignore."
Even taking your optimistic numbers at face value, that's revenue, not profit. A 100 billion dollar industry with what I would conservatively estimate as having several trillion in costs is not something we can pursue.
I've got my own boutique genetic problems in my house (not quite a one-off in effect, but probably technically novel), so I've got skin in the game, but this is just wishful thinking. Even just funding all the known rare diseases is not something we can really afford, let alone dedicating millions to every one-off mutation. We aren't that rich.
I'm sympathetic to claims we ought to have enough for food and water and basic housing for everybody, but that does not translate into having enough to create custom bespoke medical research programs for everybody, or even a significant fraction of "everybody". If nothing else, food, water, and basic housing are widespread skills; fixing genetic errors would always bottleneck on the number of available people who can do it, which is never going to be as large as the number of people who can build some sort of house.
Even taking your optimistic numbers at face value, that's revenue, not profit. A 100 billion dollar industry with what I would conservatively estimate as having several trillion in costs is not something we can pursue.
I've got my own boutique genetic problems in my house (not quite a one-off in effect, but probably technically novel), so I've got skin in the game, but this is just wishful thinking. Even just funding all the known rare diseases is not something we can really afford, let alone dedicating millions to every one-off mutation. We aren't that rich.
I'm sympathetic to claims we ought to have enough for food and water and basic housing for everybody, but that does not translate into having enough to create custom bespoke medical research programs for everybody, or even a significant fraction of "everybody". If nothing else, food, water, and basic housing are widespread skills; fixing genetic errors would always bottleneck on the number of available people who can do it, which is never going to be as large as the number of people who can build some sort of house.
$100B, but I think your point still stands.
> 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.
Let me rephrase this less charitably: You are willing to rob millions of suffering people the chance of a cure, by mandating a system that effectively prevents a cure from being developed. This is in order to save some of the very same people from the effects of unsafe treatment. It is patently absurd, but that's exactly the system that we have right now. Nobody wants to take on the legal liability of killing a terminal cancer patient with an experimental treatment unless they have military-grade legal assistance at their disposal.
It's also clearly not working when countless desperate people opt for "alternative medicine" and various quackeries that aren't held to those standards, simply because they're not advertised as "medicine" in the legal sense.
If you've ever asked yourself why health care is so expensive in the US, don't overlook the safety standards and the legal liabilities that medical practitioners incur. Look at the value of settlements in US courts. Practitioners require expensive legal insurance, and they'll charge you for it.
Let me rephrase this less charitably: You are willing to rob millions of suffering people the chance of a cure, by mandating a system that effectively prevents a cure from being developed. This is in order to save some of the very same people from the effects of unsafe treatment. It is patently absurd, but that's exactly the system that we have right now. Nobody wants to take on the legal liability of killing a terminal cancer patient with an experimental treatment unless they have military-grade legal assistance at their disposal.
It's also clearly not working when countless desperate people opt for "alternative medicine" and various quackeries that aren't held to those standards, simply because they're not advertised as "medicine" in the legal sense.
If you've ever asked yourself why health care is so expensive in the US, don't overlook the safety standards and the legal liabilities that medical practitioners incur. Look at the value of settlements in US courts. Practitioners require expensive legal insurance, and they'll charge you for it.
>You are willing to rob millions of suffering people the chance of a cure, by mandating a system that effectively prevents a cure from being developed.
The cure may be worse than the disease, I bet not every one of these one-off mutations is deadly, and how debilitating it is may vary. I'm not trying to rob anyone from the chance of a cure, I'm just saying that to save the most people, resource allocation makes sense.
Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.
The cure may be worse than the disease, I bet not every one of these one-off mutations is deadly, and how debilitating it is may vary. I'm not trying to rob anyone from the chance of a cure, I'm just saying that to save the most people, resource allocation makes sense.
Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.
> I'm not trying to rob anyone from the chance of a cure, I'm just saying that to save the most people, resource allocation makes sense.
I wasn't arguing with resource allocation, I was arguing with your "safety concerns". My takeaway from the article is that with the current framework, any treatment needs to go through countless trials individually, hence it is literally impossible to do any trials to prove the safety or efficacy any treatment that is bespoke to a handful of people.
In our system, it's the responsibility of private companies to productize findings from research and development. As a result, resources aren't allocated to save the most people, they're allocated to make the most money. If you make it expensive to develop treatments for diseases, or you limit the profit that can be made from these treatments, those treatments will never be developed. No pharma company loses money just because people die. They lose money from dead people they could have treated at a profit.
> Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.
The incentives are aligned towards not taking risks. You will not read a headline "Millions of people died as a result of overly strict safety standards". Even though that may very well be the case, it would just be a conjecture. On the other hand, if a handful of people die from some FDA-approved drug, it's all over the news, people will demand consequences, million-dollar lawsuits will be filed, and so on.
I wasn't arguing with resource allocation, I was arguing with your "safety concerns". My takeaway from the article is that with the current framework, any treatment needs to go through countless trials individually, hence it is literally impossible to do any trials to prove the safety or efficacy any treatment that is bespoke to a handful of people.
In our system, it's the responsibility of private companies to productize findings from research and development. As a result, resources aren't allocated to save the most people, they're allocated to make the most money. If you make it expensive to develop treatments for diseases, or you limit the profit that can be made from these treatments, those treatments will never be developed. No pharma company loses money just because people die. They lose money from dead people they could have treated at a profit.
> Now if the incentives are misaligned by virtue of the laws we write, we might need to change those.
The incentives are aligned towards not taking risks. You will not read a headline "Millions of people died as a result of overly strict safety standards". Even though that may very well be the case, it would just be a conjecture. On the other hand, if a handful of people die from some FDA-approved drug, it's all over the news, people will demand consequences, million-dollar lawsuits will be filed, and so on.
> If you've ever asked yourself why health care is so expensive in the US, don't overlook the safety standards and the legal liabilities that medical practitioners incur. Look at the value of settlements in US courts. Practitioners require expensive legal insurance, and they'll charge you for it.
Texas did some malpractice law changes back in 2003. It would be interesting to see if in impact their health care costs.
Texas did some malpractice law changes back in 2003. It would be interesting to see if in impact their health care costs.
I had 2 experiences recently where an acquaintance would’ve died, if not for called in favors to doctors who were personal friends.
The doctors they went to wrote things off and sent them on their way multiple times, but they reached out to close friends for recommendations on second opinions because they still didn’t feel right. Doctor A tells Doctor B to do him a favor and take a closer look, and lo and behold, emergency surgery saved their life.
We’re obviously talking upper middle class people with great insurance. The system is very broken.
The doctors they went to wrote things off and sent them on their way multiple times, but they reached out to close friends for recommendations on second opinions because they still didn’t feel right. Doctor A tells Doctor B to do him a favor and take a closer look, and lo and behold, emergency surgery saved their life.
We’re obviously talking upper middle class people with great insurance. The system is very broken.
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That's actually just a thing called "fallibility".
We live in an age where so much stuff is so readily fixable we don't remember how common this used to be.
We keep eliminating sources of error, but there will always be a long tail of small-scale mistakes with large-scale consequences
We live in an age where so much stuff is so readily fixable we don't remember how common this used to be.
We keep eliminating sources of error, but there will always be a long tail of small-scale mistakes with large-scale consequences
Let's just agree it is broken and do nothing about it. We have connections after all and only the other people will suffer so who really cares.
> Do I have to Ph.D in every medical science to make sure my kids get a treatment what they deserve?
When you live in a society you have duties and rights. We count on each other. Some people gets an education with help and resources of society and then there is an expectation for them to take responsibility and do their part. That is expected from everybody whatever your role, studies or background.
You are right that this social contract seems broken. That we are told that everyone is on their own and if you don't profit as much as possible from the system you are a sucker. That cheaters are right. This doesn't work on the long run. Too much cheaters in a society and it is doomed to fail.
We should take care of ourselves and others. We have rights and we should be willing to fulfill our duties. And have expectations on others to do the same.
When you live in a society you have duties and rights. We count on each other. Some people gets an education with help and resources of society and then there is an expectation for them to take responsibility and do their part. That is expected from everybody whatever your role, studies or background.
You are right that this social contract seems broken. That we are told that everyone is on their own and if you don't profit as much as possible from the system you are a sucker. That cheaters are right. This doesn't work on the long run. Too much cheaters in a society and it is doomed to fail.
We should take care of ourselves and others. We have rights and we should be willing to fulfill our duties. And have expectations on others to do the same.
It might be worth reading through https://80000hours.org/key-ideas/. There is a lot of much lower hanging fruit if you want to spend money without the profit motive, to help people.
I think might be misunderstanding this. Its more akin to developing an entire new medicine than applying a diff patch.
When you have finite resources you have to ask whether its worth spending those resources on something that can help 1 person or a million.
When you have finite resources you have to ask whether its worth spending those resources on something that can help 1 person or a million.
>Do I have to Ph.D in every medical science to make sure my kids get a treatment what they deserve?
Not necessarily. What are you doing to contribute?
Not necessarily. What are you doing to contribute?
The best I could do, a responsible citizen. Taking care of others as much as I can.
I'll admit that I engage in recreation when I could be advancing humanity. Even my job does little to advance humanity compared to other jobs I could take if I was willing to make some personal sacrifices. But I don't, I'm selfish, and the best reason I can give why is that I too have things I desire which others are not willing to sacrifice to provide for me, thus I have to prioritize myself.
I find most people work this way. A few are true saints, a few are pure evil, the rest are selfish with varying degrees of outcome.
One could even say that the resources spent on saving this baby could be better spent on saving far more others, and that prioritizing a single person over a group is a selfish action.
So are you really doing the best you can do?
I find most people work this way. A few are true saints, a few are pure evil, the rest are selfish with varying degrees of outcome.
One could even say that the resources spent on saving this baby could be better spent on saving far more others, and that prioritizing a single person over a group is a selfish action.
So are you really doing the best you can do?
With whole exome sequencing now at 500 USD, personally I will start by testing myself and my partner for hereditary diseases before having kids.
It is an excellent point, genetic mutations may have wildly different consequences, but they are all the same fundamental issue: genetic mutation.
This is heartbreaking. Thank you for bringing the awareness. Hold that child tight.
Well.. it is an excellent idea.
The headline has changed for me to include a typo? “... sourcing my haby”?
Only reason I clicked was to find out what a haby was.
Likewise. Guess it worked then!
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.
> I’m Open Sourcing My Baby to Save Her and Others
Nope, that is not what you are doing.
Nope, that is not what you are doing.
Exactly, I just read the title and it was very confusing for me to understand what the article was about.
Sometimes when I see titles like this, it is better to just get to the point rather than confuse readers with these silly titles. Apart from that, it was a very good read.
Sometimes when I see titles like this, it is better to just get to the point rather than confuse readers with these silly titles. Apart from that, it was a very good read.
True, but this is one of the cases where I don't mind clickbait as much. Getting attention should be the goal.
I do mind it. If your cause is meaningful enough, you don't need to resort to click baity titles.
So, how would you suggest it be titled or framed?
It's a new approach. There's a serious language issue here in that truly new things don't really have proper words or phrases for them yet. They need to be invented.
That's usually done by initially borrowing on existing concepts that are as similar in some way as possible.
This problem space also seems particularly thorny. Even people who have genetic disorders -- or who have a child with a genetic disorder -- may not understand some basics about how genetics works.
It's a new approach. There's a serious language issue here in that truly new things don't really have proper words or phrases for them yet. They need to be invented.
That's usually done by initially borrowing on existing concepts that are as similar in some way as possible.
This problem space also seems particularly thorny. Even people who have genetic disorders -- or who have a child with a genetic disorder -- may not understand some basics about how genetics works.
You people discussing semantics and even "clickbait" in this context truly make me sad.
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.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.
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.
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.
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.
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On the face of it that's just publishing. Open source is more about the license you publish with.
The only bit that seems like open source is "anyone performing an N-of-1 should be able to tap into this repository as long as they contribute back into it", which implies a share-alike kind of license. Not sure how copyrightable this type of thing is though, so it might be just reliant on good will.
I think the title is total clickbait and not what's happening at all.
The only bit that seems like open source is "anyone performing an N-of-1 should be able to tap into this repository as long as they contribute back into it", which implies a share-alike kind of license. Not sure how copyrightable this type of thing is though, so it might be just reliant on good will.
I think the title is total clickbait and not what's happening at all.
Yes, that's really confusing, is it seriously only referring to posting photos on Instagram?
Even in that ridiculous analogy, that's sharing binaries with the source kept closed!
Even in that ridiculous analogy, that's sharing binaries with the source kept closed!
If a program was created in machine language, it's binary IS its code, you don't need the abstraction. If you chose to share this data freely, it's open source.
Even if you just play on the words; You open a source of information.
He may be talking about publishing genomic sequence data, and the data on the treatment he/they created. Maybe some tools to come up with such a treatment.
He should be more specific. Conflating a treatment for some illness with a human infant seems needlessly careless use of language.
Never heard of clickbait?
Would that even be legally possible?
I don't know of significant legal obstacles to publishing your own genomic data, or that of your children.
And except for intellectual property issues, I don't see a problem with publishing treatment details, either.
There are some issues about providing medical advice without license, but that can be circumvented with a few disclaimers.
And except for intellectual property issues, I don't see a problem with publishing treatment details, either.
There are some issues about providing medical advice without license, but that can be circumvented with a few disclaimers.
Many genomicists (such as Craig Venter and George Church) have already made their own genomes available to the public, so no issues there. And I doubt there would be any legal issues for making one's child's genome available either. Obviously there is the ethical issue because an infant can't give consent, but traditionally parents can give consent for medical issues.
This feels like possibly the worst article for you to be coldly pedantic about?
I know it's an HN tradition, but empathy is important, friend.
I know it's an HN tradition, but empathy is important, friend.
Yup, that's fair. We took some creative license here, but couldn't quite figure out how to succinctly explain that we want to go beyond just academic publication and share everything.
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pi-squared(2)
its crazy how people support medical experiments on a child but will call child protective services if you feed your child a vegetarian diet
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.
One can lead to normal life for the child if the condition is severe. Not doing anything can hinder child's future, while medical experiment can save the child.
Other has no positive benefits, while it can be dangerous to the child.
Other has no positive benefits, while it can be dangerous to the child.
Who does that?
If modern medicine was 10% open source, the world would be 110% a better place.
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.
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
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.
Kickstarter tawdriness is creeping into what was otherwise a gold-plated medical GoFundMe.
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.
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.
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.
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.
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.
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.
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.