7 ms·

This is an impressive article and an impressive couple. From the site's about page: My name is Eric Vallabh Minikel and I’m on a lifelong quest to develop a tr

by dcx 7y ago

This is an impressive article and an impressive couple. From the site's about page: My name is Eric Vallabh Minikel and I’m on a lifelong quest to develop a treatment or cure for human prion diseases. I originally trained as a city planner at M.I.T. and was working as a software engineer and data analyst in the transportation sector when, in December 2011, I got some bad news. My wife and the love of my life, Sonia Vallabh, tested positive for a mutation (PRNP D178N cis-129M) that causes genetic prion disease, and that had claimed her mother’s life one year earlier. Sonia was 27 at the time. The mean age of disease onset for her mutation is around 50, and the mutation is highly penetrant, meaning she is exceptionally likely to develop the disease unless a treatment or cure is found. Sonia and I set out on a quest to re-train ourselves as scientists. We both started taking night classes, reading papers, calling up scientists, going to conferences. We left our old careers and found jobs in research labs, and eventually enrolled at Harvard Medical School, where we are now PhD students in biological and biomedical sciences. One thing I've learned from smart family and friends about medical care is that you can sometimes improve outcomes quite a lot if you apply brains and effort. I have relatives who managed to convert their dad's brain cancer outcomes from a couple of months in palliative care (which the doctors were recommending) to five more mostly-good years, by finding better surgeons, signing him up for clinical trials, and getting to the cutting edge of the research and applying it. For example they switched him to a ketogenic diet back when this was just starting to show results for cancer. These guys are taking this approach to the extreme! I hope they get the result they're looking for.

wallflower 7y ago
Amazing story! https://www.newyorker.com/books/page-turner/a-prion-love-story https://www.newyorker.com/books/page-turner/a-prion-love-sto... https://news.ycombinator.com/item?id=18653241 https://news.ycombinator.com/item?id=18653241
loceng 7y ago
It's instances like these that I believe why the medical-pharma industrial complex isn't necessary, and likely more inefficient and soaking up more money - directing them towards profits, or other less efficiently than individuals who are passionate for a solution; yes, we need the institutions like Harvard Medical School to support these people - however the capitalism that then takes advantage of innovation through rent-seeking behaviour for cures is questionable.
- loceng 7y ago
  Glad down voting has supported healthy community discussion on HN once again. I'm glad to find out that at least the 5 people to down vote me (so far) all agree it's great that people pay so much for medications.
  - loceng 7y ago
    News just from today: "Whistleblowers: Company at heart of 97,000% drug price hike bribed doctors to boost sales" - https://www.cnn.com/2019/04/30/health/mallinckrodt-whistleblower-lawsuit-acthar/index.html https://www.cnn.com/2019/04/30/health/mallinckrodt-whistlebl...
  - bigDICK 7y ago
    HN is community property. The community decides what is relevant and what is not.
dralley 7y ago
>For example they switched him to a ketogenic diet back when this was just starting to show results for cancer I'm curious as to how this would have an impact. Is there any research demonstrating that keto slows the development of cancer? Or hypotheses on why that would be the case?
- emit_time 7y ago
  Partially related to insulin and blood sugar levels largely. IGF. Depends on the cancer though, etc.
- dcx 7y ago
  If you google for studies, at this point you'll see an abundance of research on this with positive results, which apparently was just getting started when they dug into it and perhaps not well known to the average doctor. My memory plus a quick look into one [1] suggests it's because brain tumor cells largely feed on glucose, whereas normal brain cells can also metabolise ketone bodies for energy. So you're starving the cancer of resources. [1] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-4-5 https://nutritionandmetabolism.biomedcentral.com/articles/10...
  - comment1 7y ago
    [1] was a mouse study. Do you have any examples of human studies? I have this picture in my mind of someone showing up to a doctors office with a thumb drive of 30 PDFs of nonclinical studies they found through a Google search and demanding treatment x, diet y, and so on.
    - perfmode 7y ago
      Why throwaway?
      - manmal 7y ago
        Provably an affected person.
FabHK 7y ago
> One thing I've learned from smart family and friends about medical care is that you can sometimes improve outcomes quite a lot if you apply brains and effort. I'd be very careful with this sentiment though, because it is easy to turn it into the toxic notion that if a loved one dies from some disease (which is pretty inevitable), you didn't put enough brains or effort in it.
- DoreenMichele 7y ago
  Unfortunately, every medical "support group" I have ever belonged to bent over so far backwards to not "blame the victim" that you absolutely couldn't talk about what worked because, inevitably, the sickest people with the worst war stories were the same ones who smoked, actively dismissed the idea that replacing carpeting with wood and tile floors might make a difference, etc. No, it absolutely wasn't socially acceptable to suggest that there was some correlation between the folks being proactive and having positive outcomes and the people shit-talking such approaches and their horrendous prognoses. It creates an atmosphere where we can't realistically even try to investigate or develop a mental model for what actually works. So we just pretend that success or failure is some random number generator outcome. That always has me wanting to pointedly ask "So, why go to a doctor at all if it is basically totally random?" But I know how well that will go over, so I usually bite my tongue.
  - lysium 7y ago
    Off topic: why would replacing carpeting with wood and tile floors make a difference?
    - DoreenMichele 7y ago
      It's cleaner. I'm referencing discussions about lung issues in specific, if that helps you make sense of things.
burtonator 7y ago
> I have relatives who managed to convert their dad's brain cancer outcomes from a couple of months in palliative care (which the doctors were recommending) to five more mostly-good years That's literally NOT how this works and this line of thought is VERY dangerous. You have an N=1 sample size here. Doctors use probability distributions when making prognosis and recommendations for treatment. It's far more plausible that he was just an outlier. By all means take care of your family members but you have NO idea that this behavior changed his outcome. Correlation != causation.
- dickless-a-hole 7y ago
  Hey shit for brains, did you know that many experimental treatments for cancer are randomized double blinds that result in a total lack of treatment. Doctors frequently sign their patients up to roll the dice and get nothing. By all means shout down anyone you want but you have NO idea which cancer patients are actually being saved by their medication. Treatment != care.
- dcx 7y ago
  This was far more than just random chance. It's clear as day that quality of medical care makes a difference in outcomes, right? I have sent this discussion to the relatives in question so forgive me if I get the exact details wrong. But the median survival time for glioblastoma is fourteen months, and they were quite a while into that. Their original doctors were recommending palliative care (giving up on further medical treatment) with a couple of months expected survival. My relatives live in a small city not known for its quality of medical care. They found the very best neurosurgeon in the country for glioblastoma and transferred him over with some difficulty. They learned that the initial surgeries were not done to a high quality or possibly even slightly botched - and the new surgeon was able to perform additional surgeries that were able to remove a significant amount of the tumour (and did follow-up surgeries later on). Of course this would extend a patient's lifespan! The ketogenic diet now seems to be becoming a standard recommendation for glioblastoma treatment. There are TON of studies now. Here are a few more more. [1] [2] [3] Note the dates on these studies (2017-2018). Back when they looked at this, this was absolutely bleeding-edge stuff. Of course going to the cutting edge of the research, speaking to professors and using your brain to figure out what might help in your case will improve outcomes! Regarding clinical trials, one can read up on / sign up for trials of treatments at different stages of the drug research pipeline. As the modelling spreadsheet in the link above shows, between 1-in-10 and 1-in-2 of these trials will result in FDA-approved treatments that will hit the market between 2 and 10 years from now. If your current expected survival time is in months, it is statistically worth implementing as many of these as possible, because at least one of them will probably work, and you don't have the time to wait for the FDA! You don't really care which one as, like you say, your sample size is N=1. I shared this in the hope that some of the smart people on this forum would read this and know that this is something you may be able to do. We are engineers and scientists. We can read studies and think critically. We can spend a ton of time absorbing specialised information about the N=1 case that matters to us. Death comes for everyone and the above may not make a difference in many cases. But it turns out that sometimes it does! Don't treat medical care like a black box. [1] https://www.practiceupdate.com/content/sno-2018-clinical-trials-of-ketogenic-diet-for-glioblastoma-are-feasible/75971 https://www.practiceupdate.com/content/sno-2018-clinical-tri... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834833/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834833/ [3] https://www.sciencedirect.com/science/article/pii/S1040842816302323 https://www.sciencedirect.com/science/article/pii/S104084281...
rscho 7y ago
Maybe... but more likely no, this is random luck. What's sure is that you do not understand the medical system at all. I hope this poor man's family did not force him through too much suffering. FYI clinical trials, despite what some would like you to think, are absolutely not designed to help those participating in it. FYI 2: "average doctors" have to follow guidelines like everyone else. The "exceptional doctors" proposing "advanced new cures" are either dishonest or failed to communicate properly with their patient. It's always astonishing to me when I realize people think that practionners have such freedom in deciding their treatment plan. This is not how it works.

by dcx 7y ago

wallflower 7y ago

Amazing story! https://www.newyorker.com/books/page-turner/a-prion-love-story https://www.newyorker.com/books/page-turner/a-prion-love-sto... https://news.ycombinator.com/item?id=18653241 https://news.ycombinator.com/item?id=18653241

loceng 7y ago

It's instances like these that I believe why the medical-pharma industrial complex isn't necessary, and likely more inefficient and soaking up more money - directing them towards profits, or other less efficiently than individuals who are passionate for a solution; yes, we need the institutions like Harvard Medical School to support these people - however the capitalism that then takes advantage of innovation through rent-seeking behaviour for cures is questionable.

loceng 7y ago
Glad down voting has supported healthy community discussion on HN once again. I'm glad to find out that at least the 5 people to down vote me (so far) all agree it's great that people pay so much for medications.
- loceng 7y ago
  News just from today: "Whistleblowers: Company at heart of 97,000% drug price hike bribed doctors to boost sales" - https://www.cnn.com/2019/04/30/health/mallinckrodt-whistleblower-lawsuit-acthar/index.html https://www.cnn.com/2019/04/30/health/mallinckrodt-whistlebl...
- bigDICK 7y ago
  HN is community property. The community decides what is relevant and what is not.

dralley 7y ago

>For example they switched him to a ketogenic diet back when this was just starting to show results for cancer I'm curious as to how this would have an impact. Is there any research demonstrating that keto slows the development of cancer? Or hypotheses on why that would be the case?

emit_time 7y ago
Partially related to insulin and blood sugar levels largely. IGF. Depends on the cancer though, etc.
dcx 7y ago
If you google for studies, at this point you'll see an abundance of research on this with positive results, which apparently was just getting started when they dug into it and perhaps not well known to the average doctor. My memory plus a quick look into one [1] suggests it's because brain tumor cells largely feed on glucose, whereas normal brain cells can also metabolise ketone bodies for energy. So you're starving the cancer of resources. [1] https://nutritionandmetabolism.biomedcentral.com/articles/10.1186/1743-7075-4-5 https://nutritionandmetabolism.biomedcentral.com/articles/10...
- comment1 7y ago
  [1] was a mouse study. Do you have any examples of human studies? I have this picture in my mind of someone showing up to a doctors office with a thumb drive of 30 PDFs of nonclinical studies they found through a Google search and demanding treatment x, diet y, and so on.
  - perfmode 7y ago
    Why throwaway?
    - manmal 7y ago
      Provably an affected person.

FabHK 7y ago

> One thing I've learned from smart family and friends about medical care is that you can sometimes improve outcomes quite a lot if you apply brains and effort. I'd be very careful with this sentiment though, because it is easy to turn it into the toxic notion that if a loved one dies from some disease (which is pretty inevitable), you didn't put enough brains or effort in it.

DoreenMichele 7y ago
Unfortunately, every medical "support group" I have ever belonged to bent over so far backwards to not "blame the victim" that you absolutely couldn't talk about what worked because, inevitably, the sickest people with the worst war stories were the same ones who smoked, actively dismissed the idea that replacing carpeting with wood and tile floors might make a difference, etc. No, it absolutely wasn't socially acceptable to suggest that there was some correlation between the folks being proactive and having positive outcomes and the people shit-talking such approaches and their horrendous prognoses. It creates an atmosphere where we can't realistically even try to investigate or develop a mental model for what actually works. So we just pretend that success or failure is some random number generator outcome. That always has me wanting to pointedly ask "So, why go to a doctor at all if it is basically totally random?" But I know how well that will go over, so I usually bite my tongue.
- lysium 7y ago
  Off topic: why would replacing carpeting with wood and tile floors make a difference?
  - DoreenMichele 7y ago
    It's cleaner. I'm referencing discussions about lung issues in specific, if that helps you make sense of things.

burtonator 7y ago

> I have relatives who managed to convert their dad's brain cancer outcomes from a couple of months in palliative care (which the doctors were recommending) to five more mostly-good years That's literally NOT how this works and this line of thought is VERY dangerous. You have an N=1 sample size here. Doctors use probability distributions when making prognosis and recommendations for treatment. It's far more plausible that he was just an outlier. By all means take care of your family members but you have NO idea that this behavior changed his outcome. Correlation != causation.

dickless-a-hole 7y ago
Hey shit for brains, did you know that many experimental treatments for cancer are randomized double blinds that result in a total lack of treatment. Doctors frequently sign their patients up to roll the dice and get nothing. By all means shout down anyone you want but you have NO idea which cancer patients are actually being saved by their medication. Treatment != care.
dcx 7y ago
This was far more than just random chance. It's clear as day that quality of medical care makes a difference in outcomes, right? I have sent this discussion to the relatives in question so forgive me if I get the exact details wrong. But the median survival time for glioblastoma is fourteen months, and they were quite a while into that. Their original doctors were recommending palliative care (giving up on further medical treatment) with a couple of months expected survival. My relatives live in a small city not known for its quality of medical care. They found the very best neurosurgeon in the country for glioblastoma and transferred him over with some difficulty. They learned that the initial surgeries were not done to a high quality or possibly even slightly botched - and the new surgeon was able to perform additional surgeries that were able to remove a significant amount of the tumour (and did follow-up surgeries later on). Of course this would extend a patient's lifespan! The ketogenic diet now seems to be becoming a standard recommendation for glioblastoma treatment. There are TON of studies now. Here are a few more more. [1] [2] [3] Note the dates on these studies (2017-2018). Back when they looked at this, this was absolutely bleeding-edge stuff. Of course going to the cutting edge of the research, speaking to professors and using your brain to figure out what might help in your case will improve outcomes! Regarding clinical trials, one can read up on / sign up for trials of treatments at different stages of the drug research pipeline. As the modelling spreadsheet in the link above shows, between 1-in-10 and 1-in-2 of these trials will result in FDA-approved treatments that will hit the market between 2 and 10 years from now. If your current expected survival time is in months, it is statistically worth implementing as many of these as possible, because at least one of them will probably work, and you don't have the time to wait for the FDA! You don't really care which one as, like you say, your sample size is N=1. I shared this in the hope that some of the smart people on this forum would read this and know that this is something you may be able to do. We are engineers and scientists. We can read studies and think critically. We can spend a ton of time absorbing specialised information about the N=1 case that matters to us. Death comes for everyone and the above may not make a difference in many cases. But it turns out that sometimes it does! Don't treat medical care like a black box. [1] https://www.practiceupdate.com/content/sno-2018-clinical-trials-of-ketogenic-diet-for-glioblastoma-are-feasible/75971 https://www.practiceupdate.com/content/sno-2018-clinical-tri... [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834833/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834833/ [3] https://www.sciencedirect.com/science/article/pii/S1040842816302323 https://www.sciencedirect.com/science/article/pii/S104084281...

rscho 7y ago

Maybe... but more likely no, this is random luck. What's sure is that you do not understand the medical system at all. I hope this poor man's family did not force him through too much suffering. FYI clinical trials, despite what some would like you to think, are absolutely not designed to help those participating in it. FYI 2: "average doctors" have to follow guidelines like everyone else. The "exceptional doctors" proposing "advanced new cures" are either dishonest or failed to communicate properly with their patient. It's always astonishing to me when I realize people think that practionners have such freedom in deciding their treatment plan. This is not how it works.