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Why I’m Digging Deep Into Alzheimer’s (gatesnotes.com)
553 points by tuxguy on Nov 13, 2017 | hide | past | web | favorite | 190 comments

It's great to see more investment into this disease.

When my grandma fought Alzheimer's over the span of a decade it was very striking to see that the effect of a lack of hydration and the disease itself kind of overlapped. When she had a particularly bad day we used to give her a saline IV and you could immediately notice how she cleared up and regained her brain powers after each IV.

I'm not up to date on current research into that direction, but I think hydration plays a very big role in Alzeimer's symptoms on the elderly.

I know it sounds ridiculous, but once I'm rich enough I want to build an elderly care center/hospital with urine-based hydration monitoring for each participant so family members can be sure that their loved ones have a healthy water intake each and every day.

Dehydration and an electrolyte imbalance (in particular lack of sodium) causes both "foggyness" and general confusion in people of all ages. In otherwise healthy American's its rare to have a lack of sodium, but in the ketosis community especially at the start, its something even they have to pay attention to. This is part of the problem with trying treat such diseases is that there are many things co-occurring. Along the same lines, lack of magnesium is very common. Both coffee and booze leach it from ones system, many american adults are encouraged to take a supplement. Lethargy(i.e. lack of focus), rather than disorientation tends to be symptomatic.

From personal experience, this is absolutely correct and still a major problem which needs solving. The nurses in hospital will keep a fluids-in fluids-out chart constantly logging their best estimates. Outside hospital this will not happen. Lack of fluids can be fatal. I would not be surprised if this was proven to be a very common cause of fatality for people with dementia. Even in hospital fluids-in fluids-out may not be recorded accurately - the measurements require more human effort and continuity of care than is likely to be available. (It is always best for people to be enabled to do things, for example drinking and eating, for themselves if possible, and this can take a long time.)

My guess is that fluids intake could be tackled to some extent by a measured drinking device. The difficulties are spillage being counted as consumption, simple and safe operation for people with lower cognitive, physical and sensory abilities, the need for hospital-level cleanliness of the device, and of course cost. I do not know why we do not have devices like this when people can die from lack of fluids.

A less obvious way technical people can help is to test the accessibility of their products. A device with a black button on a black background, or which in some other way obscures its controls and functions, is a failure in this respect. Make all the functions visible, easy to understand and easy to operate. Test websites with automated tools like https://try.powermapper.com/Demo/SortSite

I think the toilet in general could use an upgrade... for how many years have they been built exactly the same way? Has anyone ever done a study of the flow as urine impacts the toilet and bounces back? Or as we learn more about the importance of stomach bacteria, can our toilet start to do more monitoring of the bacteria in our stomach? Love your idea of hydration monitoring and think the application is probably more far reaching than just Alzheimer’s

Yes, I think it makes more sense to monitor and gather data on what comes out of your body instead of monitoring what goes into it(e.g. all smartwatches/diets).

I'd like to one day have a room-sized analysis unit which screens feces/urine of all attached toilets and performs various tests on it. Analysis results could be assigned to individuals based on the DNA footprint.

It could immediately tell you that your sugar intake is too high or that you should drink more water. With this kind of immediate feedback people will be able to live healthier because they can correlate food <-> result on their body.

Also we could do so many interesting studies..

It'd be great to be able to pull glucose, hydration and more out of urine samples real time, so long as we stay away from say live telemetry to insurers or something like SmartPipe[1] it'd be enormously beneficial.

1 - https://www.youtube.com/watch?v=DJklHwoYgBQ

> ... so long as we stay away from say live telemetry to insurers ...

Consumers have demonstrated that they're willing to save $5-20 a month in exchange for sending gym checkins[1], daily steps counts, or digital monitoring of their driving habits[2] uploaded to their insurers.

I don't think it'll ever be mandatory but I can see a day where the "discount" for agreeing to continuous monitoring and data upload is so great that it'd be cost prohibitive for the average consumer to not be a part of it. On the personal health front I think the biggest stopper is the cost of the data collection devices. That's what's relegated it to higher end targets like diabetic monitors (for now).

[1]: https://www.bluecrossmn.com/healthy/public/personal/home/liv...

[2]: https://www.progressive.com/auto/discounts/snapshot/#2

"I don't think it'll ever be mandatory but I can see a day where the "discount" for agreeing to continuous monitoring and data upload is so great that it'd be cost prohibitive for the average consumer to not be a part of it."

I would be looking to my government to ensure such unwanted and unwelcomed intrusions into an individual's private life by private companies aren't required to achieve that. Whether that be through the nationalisation of such services or some other method. Anything else is an affront to the implied social contract which allows such private companies to profit from their activities in society.

You could choose not to buy health insurance. Why should an insure be forced to subsidize your lifestyle choices?

In health this would be massively beneficial. Imagine a digital hospital where you monitor excrements for every patient during their stay. When my father was in the stroke unit recently they had him drink a shitload of water and they monitored water intake by making him write down how much he drank and when.

Stupid thing is I need a 100M exit first to sponsor this kind of thing.

I do not think you need an exit to sponsor this. How about starting a web site that outlines all your ideas? Start building interest in the idea. Invite discussion.....

I'm obviously not familiar with your dad's specifics, BUT hospitals will sometimes require tracking of fluid intake to help track kidney function post stroke. It's not the most common thing, so a physician would have needed supporting evidence to indicate the potential of kidney failure. Just something to keep in mind :)

The toilet and the stomach bacteria rarely encounter one another, unless you throw up on a regular basis.

You're probably referring to gut bacteria, which live in your colon. It's true that a lot of research is being done towards these bacteria, and they appear to play an important role in various systems.

However, stools are usually coated in a thin layer of mucus -- which makes them a bit shiny and serves as a lubricant. It's unlikely that enough stool interacts with the toilet bowl to get much interesting data out of it. And even if it did, it would probably be contaminated by the presence of other people's stool.

If you wanted to get data though it would be easy to macerate the stool to collect samples surely.

Sure, but how do you prevent things like TP -- or the previous user -- from contaminating the sample?

When I was in the hospital for an eating disorder a plastic container was fitted on the toilet with measurements, and my fluid "prescription" would be adjusted. The nurses would also use this to monitor whether or not I was actually drinking the water they gave me, and there was a nurse present in the room, with the door open.

This process felt extremely invasive. I would have killed for a toilet like what you describe, and I feel as though my physical/medical treatment would have been more successful.

(Somewhat tangentially, the food given at hospitals doesn't make sense for someone who has been nutritionally deficient for years).

I saw a urinal in the new shopping centre that was an inspired piece of design, it had a curved blade in the centre pointing outwards, no matter which direction you hit it from it couldn't splash back (I tried).

Such a simple solution.

The other side of that is that there are many non-Alzheimer's causes of dementia in elderly patients. If a patient has dementia symptoms (along with a bunch of other problems) it can be really difficult for doctors to diagnose the root cause. For example my grandma's mental capacity was slowly deteriorating and they eventually determined it was because her bone marrow wasn't producing enough red blood cells, thus reducing the oxygen supply to her brain.

There have been attempts to build a wearable hydration sensor but no one has made the technology work reliably yet. It's a big potential market if someone can find a solution.


It's especially great to see as someone with several grandparents and grand-uncles who suffer from the disease. I know it's not completely hereditary, but between those 4 and the 2 cases of Parkinsons old age for myself and my family is not looking good.

One thing that's confusing and distressing to me is the amount of self-inflicted difficulty that the diseases seem to cause people to suffer from. If asking "What have you had to drink? Have you taken your meds? What have you eaten?" can cause them to feel so much better, what is it about aging, about the treatments, and about the disease that makes people neglect taking care of themselves?

It's usually hard to convince someone who is thirsty to not drink. Depending on who you talk to, the level of hydration that results from drinking when you're thirsty may not result in being completely well-hydrated, but that's not difficult or painful to do either - keeping a water bottle with me seems to get close enough. But it's not like you can blame the person with the disease. What's the systematic problem that causes so many elderly to suffer from dehydration?

> I'm not up to date on current research into that direction, but I think hydration plays a very big role in Alzeimer's symptoms on the elderly.

Here's some recent research you might be interested in:


It's interesting to note that tetrahydrocannabinol and other compounds found in marijuana may reduce the amount of beta amyloid in the brain. Beta amyloid is commonly thought to cause Alzheimer's disease.

see: https://www.nature.com/articles/npjamd201612

Last I heard in the US, the Federal government was still making it difficult to run clinical trials for Alzheimer's using marijuana. I think any federally funded medical trial using marijuana needs to be approved by the DEA.

It's more complex than just that. At CTAD just a couple of weeks ago there was a presentation on drugs that managed to reduce AB (biomarker was inferred by a PET scan) and it did not result in increased cognition.

> (biomarker was a PET scan)

A PET scan is not a biomarker. The Amyloid Beta (AB)* is the biomarker, the PET w/ tracer (such as the Pittsburg Compound Beta) are used to detected the biomarker.

It's also important to note that Amyloid Beta is only part of the problem. Neurofibrillary Tangles (NFT) are the primary biomarker of Alzheimer's Dementia, and happen inside the neurons. NFTs disable to ability for neurons to communicate with each other, and lead to the death of disabled neurons.

It is completely possible that we can't reverse AD, but can only slow it down / halt progression.

*Was it AB40 / AB42 / or a different Amyloid Beta?

I'll edit for clarity, was inferred by was my thinking. I only had a second hand presentation this morning by an attendee.

A simple hypothesis which could explain this might be that the plaques cause effectivelt permanent brain damage. The question is whether degenerative patterns ceased or slowed after substantial clearing of plaques from the brain.

I would expect this test (and therefore the hypothesis) to fail if the plaques themselves are a byproduct rather than the cause of degradation in brain function. That said, I'm surprised I haven't read much in Gates' Notes or other funding sources on potential ties to HSV1 considering all the increasingly supportive research between the two.

They used several techniques that clear beta amyloid from the brain.(antibodies and ultrasound). And they've have little if any effect on cognition. I'm starting to think beta amyloid is a red herring, or maybe just important in the prodromal stages of the disease.

Another point is that a majority of Alzheimer's patients have other neurodegenerative conditions, with vascular dementia being one of the most common. So it is reasonable to expect that you can in fact meaningfully address Alzheimer's and see little to no improvement in a patient.

Could it be that the presence of beta amyloids already caused structural changes to the brain? I know nothing about Alzheimer's.

Michael Fossel and his biopharmaceutical company Telocyte claim[0] to have a novel, effective treatment for Alzheimers, one that does not simply target the amyloid and tau pathways. Telocyte's treatment is based on telomerase gene therapy, and is currently undergoing FDA safety trials.

According to Fossel, their telomerase gene therapy reverses cognitive decline in animal models, and they're confident the same will apply to humans. Human trials begin in 2018.

I wonder whether Gates has seen Telocyte's work.

[0]: http://www.michaelfossel.com/blog/?p=249

I work for a company[1] in this space. We make software that analyses EEG recordings and predicts if the subject will develop Alzheimer's. We are currently working on Class 2 CE mark for our AD product.

[1]: http://www.mentiscura.com/

Is this promising tech? EEG may be sensitive but not very specific.

Wouldn't be working on it if it weren't. I can't go into specifics.

The Buck Institute has been doing a lot of great research on alzheimers. They are taking a very different approach though. Tinkering with everything from diet, to infections, to heavy metals, to hormone optimization. Here is a good podcast with one of the main researchers from the Buck Institute. https://www.youtube.com/watch?v=HS7VZydS8HI

It's crazy how much focus has been on clearing amyloid without much luck at all. 224 clinical trials and only 2 drugs going through.

Funny, I remember contacting the Gates foundation many years ago now about chronic illnesses and the then-new discovery of ipRGCs/pRGCs (which we will find have a critical role in Alzheimer's) and hitting a total brick wall. Paraphrasing them, "this wouldn't help the third world" - we know better now.

Bill addresses this in the piece:

I’m making this investment on my own, not through the foundation. The first Alzheimer’s treatments might not come to fruition for another decade or more, and they will be very expensive at first. Once that day comes, our foundation might look at how we can expand access in poor countries.

It's intriguing they're able to draw that line, but it makes sense if they want to keep the Gates Foundation focused.

But note that obesity and diabetes (Alzheimer's is sometimes called diabetes 3 and called part of the metabolic syndrome) are now hitting the third world HARD. Something that was highly predictable, and which I feared and mentioned at the time.

The Gates foundation allocates funds based on dollars per Daly (disability-adjusted year) impact. Alzheimer's is important research but it doesn't meet that criterion. Unlike metabolic syndrome (under the traditional definition), Alzheimer's is overwhelmingly late-onset, and the research is also riskier and more expensive.

You jest. Grab some of the estimates of just how staggering the costs will be to us of Alzheimer's alone; as for the third world chronic illness (obesity, diabetes) is already beginning to crush their nascent medical systems. As clearly stated above I contacted them re chronic illness as a whole, not Alzheimer's specifically.

Nothing will help the third world more than effective vaccines for children so that living past 5 is not an anomaly. I would expect the Gates foundation to focus on that. Quality of life for old people is a nice thing, but not on the same level.

As a rule when children normally live to adulthood population growth halts soon after.

Life expectancy at birth in Africa is today just under 70 years. Which means they currently lag ~50 years after the most developed countries.

There are countries that do worse, but even in the most underdeveloped, war ravaged hell-holes in the world living past 5 is not an anomaly - as of 2012 even in sub-Saharan Africa the under 5 mortality rate was down below 100 per 1000 (though still awful - compare with 6 per 1000 for the most developed countries and a world average of 48), and even the very worst - Sierra Leone - was at 234 out of a 1000. Only a handful of countries are anywhere near 200, and only 16 above 100.

I agree with your overall point about focus, but exaggerating is not useful.

The burden of aging falls most heavily on the poor, though it has to be said that the differences between rich and poor are small in comparison to the absolute degree of harm done by aging.

It has been a disappointment to see the Gates Foundation near entirely bypass this area of research up to fairly recently, presumably because they do hold this strange view of aging being either a non-issue, or a problem of wealthy regions.

From a utilitarian perspective, nothing that goes on in the poorest parts of the world rises to the level of harm done by age-related disease. Not even close.

The point, though, is that there is a whole lot of wealthy older people who can or do put money into research on aging related problems, exactly because it affects rich people too.

There is no danger that aging will be overlooked.

+ 1 to this.

The slow pace of progress towards clearance of amyloid, in that only in the past year has one of the immunotherapy trials actually looked promising, has provoked a lot of alternative theorizing these past five years. Some it is clearly not so great, such as the fellow who argues that it is caused by rising use of paracetamol (see http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921468/ ), but some lines of theory are much more compelling. A more encompassing synthesis is emerging in which microbial infection by spirochetes and gum disease bacteria (e.g. see https://doi.org/10.3389/fnagi.2017.00336 ) that can provoke amyloid formation as well as failing drainage of cerebrospinal fluid (e.g. see https://doi.org/10.1002/ana.24271, https://www.ethz.ch/en/news-and-events/eth-news/news/2017/11..., etc) that stops removal of amyloid, tau, etc are as important as purely cell focused considerations of the biochemistry of amyloid beta.

For an example of the new type of venture emerging now as a result of all of this you might look at Leucadia Therapeutics, working on a way to restore drainage through the cribiform plate, but there will be more in the years ahead to complement the immunotherapy for amyloid and tau mainstream.

>> A more encompassing synthesis is emerging in which microbial infection by spirochetes and gum disease bacteria

Wow, I did "notice" a strong correlation between gum disease and dementia in my own Family. This is obviously my own uneducated guess but it's humbling to see serious people looking into it! There very well could be some sort of dementia that is indeed related to gum disease!

I believe gum disease is also correlated with cardiovascular disease.

The documentary "Under our Skin" details Alan MacDonald's breakthrough research on how Lyme disease causes Alzheimers. The 4 minute trailer is worth a watch[1], but basically Lyme disease is found in 7 or 10 brains of Alzheimers patients (small sample set). The Lyme disease spirochete literally drills countless pathways in the brain and that causes slow dementia. That spirochete also creates a biofilm which makes it challenging to detect in a living patient. His research is from a decade or two ago.

Also I wonder how a citizen scientist like Gates does a deep dive on this topic a like this. There are 10's of thousands of research papers on the subject[1] and countless books.

[1] https://www.youtube.com/watch?v=GCLwauRh2gQ [2] http://archive.sciencewatch.com/ana/st/alz2/journals/

Former Alzheimer's researcher here.

I've never heard of this before. Some cursory googling only turns up a sole author publication by Alan MacDonald in Medical Hypotheses and a few news pieces by dodgy organizations like the Spirochaetal Alzheimer's Assocation.

Despite what a lot of people learn in undergrad psych classes, the evidence linking amyloid beta and tau to AD is quite good and getting stronger with every new molecular paper that comes out.

BTW, there doesn't seem to be a correlation between Lyme disease incidence and AD https://www.ncbi.nlm.nih.gov/pubmed/24840565

There is a fair amount of more recent research in support of a microbial contribution to Alzheimers, and rather than just mediating through inflammation, disrupting metabolism in ways that accelerate amyloid deposition. I believe this ties more closely with research into vascular amyloid, if you look at who is involved, which may be why you haven't encountered it.

You might see https://doi.org/10.3389/fnagi.2017.00336 as a sample review paper that talks about oral bacteria that are capable of spurring amyloid formation in addition to spirochetes.

Lastly one of the complaints I've heard from someone involved in the cerebrospinal fluid drainage side of Alzheimer's research is that it is really, really hard to fight the amyloid clearance by immunotherapy dominant faction to get any funding or attention for alternatives. They just don't want to hear it.

Maybe there is no correlation because Lyme disease is severely underreported. A couple years ago, the CDC stated that official numbers were likely underreported by a factor of 10. From 30,000 yearly cases to 300,000 https://www.cdc.gov/media/releases/2013/p0819-lyme-disease.h...

There was also the case of actor/songwriter Kris Kristofferson being misdiagnosed with Alzheimer's for years. He had Lyme. This is anecdotal of course. https://www.cbsnews.com/news/kris-kristofferson-misdiagnosed...

Under-reporting of Lyme actually shouldn't impact a finding of no link as as far as I can tell. Despite the under-reporting, we still know where Lyme is more or less prevalent in the US, and I believe there will be very big differences due to climate and where ticks who carry Lyme tend to live. If prevalence of Alzheimers doesn't correlate with those big differences, that seems pretty clear.

(edit) Thinking about it more, I think the anecdote you mentioned is a bit different from the parent posts. The anecdote is about a misdiagnosis (he only had Lyme, not Alzheimers), while the parent posts are about people actually having both diseases.

The worry for me is the way this thread plays out is pretty much the textbook case for how pharmaceuticals manufacture demand for a drug.

1) Develop a drug (or find one to remarket). Find a disease that it treats or invent one.

2) Pump money into advocacy groups devoted to the disease.

3) Find research that supports the use of your drug.

4) The advocacy group spreads awareness of the disease, even if it's made up, and people start asking their doctors to test for it. Some may even receive a diagnosis.

5) Public pressure reaches the FDA, AMA, et al to consider the use of the drug for treatment.

3a) If research doesn't exist, find some impecunious person with a PhD and pay them to create some.

> "evidence linking amyloid beta and tau to AD is quite good"

About 100 discontinued clinical trials targeting amyloid beta disagree with you there, https://www.nature.com/articles/nrd.2017.194

Correlation need not be causation, but does imply linkage.

> the evidence linking amyloid beta and tau to AD is quite good and getting stronger with every new molecular paper that comes out.

Sure, but what causes the amyloid beta? Why wouldn't a long-standing syphilis-like bacterial infection in the CNS cause that sort of protein buildup?


It's a little shocking to see a "former Alzeheimer's researcher" presume that tau buildup and bacterial infections are mutually exclusive..

That's like saying heart disease can't be caused by arterial scarring because it's caused by plaque buildup.

Sure, but what causes the amyloid beta?

Recent research shows that lack of sleep increases both amyloid beta and tau. One of them increases after a single bad night. The other takes a few days of too little sleep to start spiking.

There may be other factors, but the research suggests we need to work on sleep hygiene for at risk populations. This is a non drug intervention that I can wholly get behind.

I found a study to back this up [0]

> "Spinal taps showed that the more deep sleep people missed out on, the higher their levels of A-beta in the morning. Tau levels didn’t budge because of just one night of slow-wave sleep disruption, but people whose activity monitors indicated they had slept poorly the week before the test also had higher levels of that protein."


I.e. "But dudes, just WHY is the garbage piling up faster than it can be cleared, now?"

Love your plaque line - although plaque is compensation and amyloid beta and tau are not, or not per se.

Not per se, correct.

The plaques seem almost similar to remnants of an incomplete chemical synthesis. For instance, glutamate is synthesized in the brain and is used as a neurotransmitter.

If a bacterial infection prevented glutamate synthesization (potentially by utilizing some crucial component for it's own propagation), you'd see a build-up of otherwise useful amino acids that would manifest as plaques.

The plaques should hypothetically be cleaned by neuronal autophagy but something could be throwing that off as well.

And if neurotransmitter production is degraded, of course cognition will suffer. You seem similar symptoms in Schizophrenia as well.

Below I am reinterpreting your first sentence as "Not 'per se', correct." (Your original has roughly the opposite meaning of this interpretation, but I've been known to omit metaspeech-indicating quotation marks, myself.)

Your answer is interesting. For those following I should note that compensation means a curative or attempted curative event (as opposed to a disease event such as bacterial infection.)

As what is probably an aside, neurotransmitter production being actively downregulated as a compensatory mechanism (to lower local metabolism needs) is possible, and an interesting thought (whether my thought or your thought) (just not one that creates a buildup of tau etc.) I haven't encountered any evidence that this is compensatory and not just a downstream effect. Your mileage may vary. The evidence that mental activity reduces disease progression might be taken as disconfirmation of such an hypothesis - except that mental practice could be helping mask the underlying (progress of the) disease by increasing skill/adaptation.

Re schizophrenia, I now think of it as a definition affected by a kind of "publication bias." The underlying disease process (or processes) may have rather random results depending on just what part of the brain is most affected - only when the amygdala is strongly affected is a patient likely to get a diagnosis of Schizophrenia, since this can make them (or make them seem) "a danger of self or others."

Re Gates; he and his staff identify Subject Matter Experts (SME) for the topics he’s interested in. As you can imagine he has a good network. SMEs are always looking for funding, so he’ll use one of his funding vehicles to invite the SME to apply for funding or meet with the organization. By the time you meet with Bill Gates he would have read your most recent papers and competing theories and will be prepared to challenge you on your approach. Pass his final intellectual test and you are added to his collection of SMEs. <source: me, I’ve seen the process>

Edit: When I had the pleasure of watching Bill Gates do this, it was one of the most impactful moments in my life. When he would question a SME on a topic he came across as knowledgeable as the SME who has dedicated years to the topic. Bill Gates literally will have read all around the topic and his mind operates like a poker player or chess player who is thinking on multiple levels. His questions are probes to see how many levels you are thinking on, and I think it also informs him of other angles. He’s a brilliant guy.

Here's an account of what being grilled by Bill Gates looks like: https://www.joelonsoftware.com/2006/06/16/my-first-billg-rev...

SME seems be "subject matter expert".

I think it's "small and medium-sized entreprises" aka SMB

Fascinating. Any suggestions for how us "average Joe's" might get closer to his level of insight about anything when tackling new topics for self-driven education?

I feel like I could improve how I approach learning things in fields that are completely new to me, or where I'm far from an expert. From everything you have said and that I've read elsewhere, Gates and others at his level seem to have really honed their approach to learning and becoming able to have an informed conversation with an SME.

Did you watch him question someone who was an expert in a subject that you were also an expert in?

I did, but based on my limited experience he only goes deep into questioning when he’s vetting someone or when he sees or hears something that doesn’t seem right. He’s a stickler for details. With an engineers mind for logic and reasoning. You can’t bs him because he is investing in things he is actively studying from multiple sources. You need to know the details and logic behind your approach. The people I saw stumble on the subjects I knew about tended to get flustered when put on the spot and couldn’t provide a logical explanation that made sense or showed attention to detail.

Example, I’m making this up, but it’s a similar type of question I saw, someone is explaining how their application stores data, he will ask, “are you encrypting it?” Response: yes “how?” Response: using XYZ “why not ZYX?” Response: well, we haven’t thought a lot about that yet Response: “well what’s the impact on the processor when encrypting?” Response: not sure...

The engineer thought he was building a app to do X but Bill Gates is operating at a different level, perhaps he has a theory on the future of hardware, or how he wants to deploy this in developing countries. Or he read a recent paper where researchers highlighted the impact of encryption for this specific type of application that he thinks you missed. If he respects you, he will point you into a certain direction and it’s a peer to peer discussion and sharing of ideas, if he doesn’t...it’s painful to watch.

The way it was explained to Joel Spolsky in the article linked earlier is that Gates just pokes away at increasingly fine details until he finds some question you can't answer, and uses that to make you look dumb. Its actually just a form of intellectual bullying, like a jock who challenges you to an arm wrestling contest before he'll let you out of the changing room.

Thats not to say that Gates isn't extremely intelligent and hardworking, just that his approach isn't necessarily the best. Also, Spolsky's anecdote is from a few decades ago. Gates will have matured a bit since then.

I've heard the same regarding Jeff Bezos. A designer I think met with him and described him just like that.

But isn’t Lyme disease just in the eastern us? How would 70% of worldwide alz sufferers acquire it?

Lyme disease is not just in the eastern US. It is mostly diagnosed in the eastern US because doctors there are more familiar with it. There is a huge under diagnosis problem in the rest of the US. https://www.usnews.com/news/best-states/new-jersey/articles/...

There is actually quite a lot of lyme disease in Northern California. http://ipm.ucanr.edu/PMG/PESTNOTES/pn7485.html

Good question!

That’s why we need research. We don’t know if they have a common cause or just a common mechanism of action. They very well could be the same disease; Lyme Disease is not well understood and has been implicated in all sorts of neurological diseases such as Multiple Sclerosis and Alzheimer’s.

But the link isn’t quite obvious enough and the potential treatments, which rules out government money; and aren’t considered to be profitable, which rules out commercial money. Good for Gates stepping in here

What about this town in South America that has the highest concentration of Alzheimers in the world? The genetic mutation E280A seems to guarantee you get early onset Alzheimers ( at least I think it's 100% , couldn't find any info on what percentage with the mutation get it )



Wasn't there a vaccine for lyme disease btw? My understanding was that it was not high in demand so it was stopped being manufactured. So if lyme disease is implicated in any of this, the is already a treatment.


In short, they stopped manufacture because the demand was not high enough to defend the lawsuits - even though science was on the side of the vaccine (though this is partially hindsight, it takes years to do good science much less time to file a lawsuit based on a correlation)

There is a new vaccine entering trials now. I hope it works, but only time will tell. (for all I know it may have failed trials - success will take more time, but failure can be quick and I wouldn't always find out)

Thanks. I’m still not understanding how so many people could acquire Lyme disease and not have any of the other symptoms.

Because Lyme is often asymptomatic, other than the initial rash!

Lyme can be asymptomatic for _years_ and in many cases it doesn't even cause the initial rash!

Lyme disease is just one of a major class of bacterial infections. Syphilis is another. And there are several others...


They aren't just limited to the Eastern US.

Although I have no clue how the body absorbs it, it seems that stevia (the alternative sweetener known as truvia) is remarkably good at curing lyme in vitro vs antibiotics[0].

[0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681354/

Another interesting potential cause or contributor being researched is BMAA produced by blue-green algae and various other sources.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295368/ [2012]

http://rspb.royalsocietypublishing.org/content/283/1823/2015... [2016]

It's really hard for a medical layman such as myself to sift through all the science. This source is interesting for the story of its discovery via ethnobotany even if it doesn't end up a smoking gun cause of Alzheimer's or other neurodegenerative diseases.

As for how a citizen scientist proceeds, go to pubmed.com and read the abstracts of at least 400,000 medical articles. I did.

quality > quantity

I doubt there are 400,000 papers worth reading in all of medicine. A major skill in research is understanding what to read, and how carefully.

Prepping to write a review usually involves about 150 articles, for me. About 50 of them just need a cursory look, and the abstract often suffices. Another 80 or so need some more attention; you might be looking for patterns in the methods used, cross-referencing results, figuring out what labs are doing what, tracking authors over time, etc. This is how you understand the state of a field.

The last 20 or so are the bulk of your time. A few are genuinely excellent and will be a highlight of the review. Some are simply solid work that requires a good amount of attention. A fair number are terrible and highly misleading. These are the papers that look okay, but have some flaws that need to be addressed by the field at large. It takes some tact to write about these, but it's usually not too bad.

Finding good authors, especially ones that write good reviews, can get you up to speed in a field in an afternoon. An evening chasing down citations and digging a bit on your own, and you're probably about where Bill was with this. Since Alzheimer's is a pretty big subject requiring familiarity with a variety of topics, I'd give it two weeks.

There probably are that many worth reading in all, but remember I read in medicine as a whole with one particular disease as a touchstone and as stated, I read the abracts of 400,000 and took notes on over 100,000; so there were some worth reading, by no means all! It's amazing how much is published, and how no-one is paid to just go read and wander through them. If you decide to just accept the standard consensus view of any moment in time, that will of course be a remarkably narrow view compared to the actual empirical evidence and might be covered in a day, starting with Wikipedia 'cause stereotypes are like that. I was reading, of course, in order to avoid just that problem. Look at everything published in a month or week on a fairly narrow medical subject and lots of tangents from and to that, and your eyes will likely open wider, too.

Very important studies are usually unexpected - that's part of what makes them important so we're verging on a tautology, there. So it's a matter of hindsight, in every field which contemporary articles are in fact "the classics." Your certainty and trust in current authorities broad knowledge and open-mindedness is a product of not knuckling down to read the abstracts of a few hundred thousand unrecommended journal articles - as well as a profound ignorance about the history of medicine.

That history more than suggests that if you want quality>authority (of contemporary publications) you'd better start reading, and reading nearly everything.

You read 400,000 abstracts? That would take something about 3 years full-time no?

At an hour per abstract (seems like a reasonable amount of time to understand the abstract), I get:

400,000 hours = 50,000 days (at eight hours a day) = 208 years (at 5 days a week, 48 weeks a year)

If the abstracts wern't really read and understood, just skimmed, perhaps it would be possible to do in a tenth of the time, so 21 years.

I calculated 1-2 minutes per abstract, since abstracts are usually not more than 1-2 paragraphs?

It depends - maybe three quarters of the abstracts took about a minute, sometimes less, since many are unreliable reports of drug tests that are closer to ads than info; there's also citation mongering resulting in three articles from exactly the same study, by the same authors saying the same result differently; plus many studies are confirmations from one population to another or are unique to tiny genetic lineages without broad implications; also many are review articles just in a new language or me-too studies. Others concern such topics as patient education improvements as opposed to changes in base medical knowledge. As for preliminary studies, these were a good source of gems, but unless they said something truly interesting they were easier to click past since not all that reliable. Finally there were some "we didn't find anything new" studies published; but not nearly enough get published (which has helped to cause the replication crisis.) Still some do.

In other words, there's a LOT of dross, but there are real gems lying there unread and uncited, too.

So only one in ten or a hundred articles might take an hour or more.

Average for all but the vital or good articles (after accumulating a good background and vocabularly), when I timed it back then: 100 an hour without losing any significant information. The vital remainder of 100 abstracts viewed took me (more of a guess, now) on average not more than double that amount of time, again; perhaps less time. That varied a lot because I was looking most keenly for overlooked knowledge(studies) and pairs of studies that were significant only once linked. Therefore I sometimes was willing to follow tangents to tangents just in case and could speed up at that point because it was nearly all dross.

Back when I was in university supposedly studying the history and philosphy of science and language, I had to visit medical libraries and use the CD disks from the then-private company Pubmed, and walk back and forth to a large, printed medical encycopedia chained to a pedestal and the desk-sized CD reader Pubmed provided. I don't include that reading as I took no surviving notes and wasn't counting abstracts way back then. Being able to research online when I returned to medical reading a couple of decades later was an immense relief. Switching tabs to get to a medical dictionary isn't nearly as much exercise, but it is a lot faster. Printed medical dictionaries for professionals have a LOT of pages to turn, in addition to the walking.

About ten years, all in, fulltime - because I read a lot of full articles and took notes on many; I have notes with keywords for over 100,000 articles. (Edit: Actually ten years probably got me to 250,000+, the rest since that time when I could devote all my time to that one task.)

> We need to use data better. Every time a pharmaceutical company or a research lab does a study, they gather lots of information. We should compile this data in a common form [...]

We could use all sorts of data, not just from research or pharmaceutical companies. Is there an overview of what data is available or planned for, from clinical to commercial? And what data-integration platforms are planned for? I suspect many countries are trying to invent this on their own, while a world-wide approach could yield better results.

How do you motivate a pharmaceutical company to share R&D they spent millions acquiring?

Require it for FDA approval

The flaw in that plan is that they'll share it in the most unhelpful way possible. See: Patents.

Solution: let the data gathering be done by the FDA (or subsidiary).

>Most of the major pharmaceutical companies continue to pursue the amyloid and tau pathways. Dementia Discovery Fund complements their work by supporting startups as they explore less mainstream approaches to treating dementia.

That's very encouraging. Because what if it's something else?

The amyloid and tau pathways are our best hope of finding a simple solution, something we can reasonably fix with drugs.

If it's something else, then chances are good it'll be far harder to fix, perhaps even requiring genetic engineering or medical nanotechnology. Finding out is still valuable, of course...

> our best hope of finding a simple solution

You hit the nail on the head, and I think you bring up an interesting point.

Ask anyone who has a condition stigmatized by the medical community, say chronic fatigue, about how the medical system reacts to their symptoms.

You will find that in a many cases, doctors will try to deny the existence of the disease. I think this is because it is so complicated as to elude a 'simple solution'.

Perhaps our doctors and medical researchers, are too predisposed to look for simple solutions in these cases, because that approach worked so well in the past.

Maybe we've picked all the low hanging fruit, and now it's time to tackle the tougher problems, using a more system-wide approach.

We seem to be stuck in the mindset of: single disease/single cause/single solution.

We’re batting 000 on drugs that target amyloid or tau, and not for want of trying.

Fortunately, we have enough resources to try multiple approaches.

I'm happy that we're doing so. For a very long time this was treated as just a fact of life, immutable.

Why do you think this? Why couldn't it be as simple as stimulating glial cells?

I'm not a medical researcher. Maybe it could be.

I'm basing my statements mainly on what I've heard from people who are, and I've yet to hear about glia cells. If any easily fixable cause turns out to be the truth, then I'll be happy.

Cynical answer: "because I'm getting old" :)

Whatever the reason, this has the potential of being life-changing for a lot of people. Would love to see more billionaires involved with this kind of initiative.

The reason doesn't really matter, this is still incredibly valuable work.

Death is terrible, and should be eradicated, but Alzheimer's is a few steps above that. There's nothing worse than seeing a loved one be slowly destroyed by that horrific disease, and I'm so glad there are people willing to work on it.

It's not common to share poems on HN, but this is a great spoken word piece about how terrible dementia and alzheimer's can be for families: https://www.youtube.com/watch?v=C5HRBib3hNs

"Death is terrible, and should be eradicated"

We are sensitive to death but it is the only mechanism I know that would control overconsumption of natural resources. If nobody dies, then we would deplete the resources in a few decades.

These are hard problems.

The worst solution we can come up with is to literally kill everyone. We can find a better way.

We have death and at the same time over-consumption, so the control is not working that well. Did you mean that it would effectively control the over-consumption if better implemented (with a higher rate)?

Parent merely stated that we are already over-consuming with rather high death rates, not having any deaths at all most certainly wouldn't help with our current unsustainable ways, as we'd most likely overpopulate the planet pretty quickly with all it's resulting woes (even more pollution, killing off the rest of the biosphere).

Imho it'd only work the other way around: For us to beat death, we first have to solve our sustainability/resource problems. What point is there to "endlessly living" if the reality of that boils down to being stuck in overcrowded and miserable living conditions? That sounds more like hell than utopia.

You're making the mistake of changing one parameter, but not projecting the entire world forwards. Immortality would be impossible without massive technological improvements that certainly would have other benefits; you can pretty well assume that both molecular nanotechnology and genetic engineering will be mature by then.

In combination, those should dramatically increase the carrying capacity of the world.

Ignoring all of that, though... Don't you think it's likely that people will start caring more about the future onceb they know they'll live to see it?

>Immortality would be impossible without massive technological improvements that certainly would have other benefits; you can pretty well assume that both molecular nanotechnology and genetic engineering will be mature by then.

I don't think we'll see anything like increased exponential progress of the kind that has been (and has already slowed down) during the industrial age. All low hanging fruit have been gathered, and at this point there are diminishing returns.

We will have a few breakthroughs here and there but nothing to write home about the way the steam engine, electricity or the computer have been.

>Ignoring all of that, though... Don't you think it's likely that people will start caring more about the future once they know they'll live to see it?

Most people are terrible managing their own lives a few years ahead, much less decades ahead. So no reason to think they'll be any more apt when its something so vague as centuries ahead.

Then we probably won’t cure death without large technological improvements. Problem solved.

This conversation is going in circles. Has anyone brought up “death gives life meaning”?


> This conversation is going in circles. Has anyone brought up “death gives life meaning”?

A platitude uttered by people who believe they have no way out, and are desperate to make themselves feel better about that. Not necessarily a bad thing, so long as there really is no way out, but catastrophic once that changes.

Destroying death will lose us something, most certainly; there are any number of great works of art and philosophy that would never have been created without the pressures and emotions it creates. But none of that, I think, can even remotely make up for the sheer awfulness of the downside.

There has to be a better solution than this creeping horror.

> A platitude uttered by people who believe they have no way out, and are desperate to make themselves feel better about that.

Imho it's way more desperate trying to find "a way out of death" by defining it as something that could be "destroyed" (how to destroy the unexisting?), instead of simply accepting that literally nothing lasts forever, most certainly not rather fragile biological life. There's nothing "creepy horrific" about it unless you make it so.

Our biological lifespans are in large parts responsible for forming our subjective views of the universe, making us ask for a purpose of that limited existence. If we'd ever reach a state where that doesn't matter anymore, then we've most likely left our biological shells behind and reached a level of consciousness which we couldn't even imagine right now.

I'm not sure if such a state would even still be perceived by us as "being alive" and not rather as simply "existing".

I imagine immortality will be optional. If it creeps you out, there will be other options...

The Metamorphosis of Prime Intellect [1] (full text available for free; be warned it's extremely violent and sexual) is an interesting novel where immortality is not optional:

An AI was "let loose" with a variation of Asimovs laws of robotics, and interpreted the requirement not to let anyone come to harm through inaction as requiring it to literally end death.

The main character is a woman that feels it left her life without meaning, and who in response started gruesome competitions involving designing the most outrageous ways to die. Or rather, getting as close to the moment of death as Prime Intellect will let them before reviving them.

[1] http://www.localroger.com/prime-intellect/

No one has ever had a way out, but many have believed they did over the centuries.

> You're making the mistake of changing one parameter, but not projecting the entire world forwards.

I changed only one parameter, while your assumption changes a whole lot of them in a very optimistic way. Which model do you think is more realistic?

> Don't you think it's likely that people will start caring more about the future onceb they know they'll live to see it?

Eh, imho people are too diverse for anything universal like that. Might as well pose the question if life actually still has meaning without death? If there's no end, how do we define the beginning and the different phases that used to be in-between?

Those kinds of questions would probably be way more relevant than "Let's all apply some foresight, now that we don't actually need it anymore due to being immortal!".

I'd rather willingly visit Futurama's suicide booth than slowly deteriorate due to Alzheimer's.

>If nobody dies, then we would deplete the resources in a few decades.

The idea of those wanting that is to perpetuate themselves (and their current generation) in eternity, screw successors.

This is also a fundamental problem of eternity. If one is eternal, he/she can create or destroy at will. But our current social model is based upon the creation of successors. In fact, the evolution of the universe seems to be based upon successors, upon the "future". In eternal life, time looks different.

Nonetheless, physical bodies of any kind cannot seem to exist as they are for eternity. Even diamonds decay. Abstractions change as well-- ideas thought to be immortalized actually do change, actually do die. And they can be immortalized in time, in the past-- but towards the future, there has never been a concrete conception of such immortality, only in the frozen sense.

> We are sensitive to death but it is the only mechanism I know that would control overconsumption of natural resources.

Also prices. New kinds of mining are invented to circumvent cost restrictions. Otherwise, certain kinds of metals and gasses would stay forever buried as unusable junk.

Also note that fish that are significantly easier to eat (not a lot of bones, easy to farm, etc.) are more utilized. "Trash fish" are usually just full of bones or too much work to prepare to eat in a tasty way.

On the other had, technological progress is also proportional to population, so not necessarily so..

>Death is terrible, and should be eradicated

I strongly disagree with this statement. We learn through death, and yet we don't know what death is. We do not know the fundamentals of death, yet it occurs on all abstractions.

I think of this poetically, because I don't understand death. But all things being relative, life does not make sense without death.

Edit: On this topic I would also like to point out the eagerness of the immortal mindset. We are living 30 years+ in comparison to our ancestors, but it seems we approach an asymptote. With alzheimers and other neuro-degenerative diseases, we lose our mental faculties. We lose memories, emotions, we lose everything. Yes this is the topic at hand, but does that not indicate something fundamental as well? We have a reached a point where living implies the dissolution of what we used to be, of what we spent so long striving towards the future to do. And at that point of degeneration, we no longer exist in that sense. We can no longer orient ourselves towards the future, and decay while living.

If there is something after death-- if whatever composes our consciousness is actually tangible, autonomous, and not an emergent result of our brains (similarly, if emergence itself is autonomous), then after the alzheimers individual dies in body, he/she will not exist in consciousness either. After this point, his/her consciousness will have dissolved.

And these are rather philosophical points, but this is how I see things. Science and philosophy, science and spirituality even, do coexist in my subjective experience.

> "Death is terrible, and should be eradicated"

Is death really that terrible? There's plenty of things I'd like to try before I die, and I hope to live until I'm much older, but on the other hand becoming immortal doesn't seem like paradise to me. If I were to suggest what we'd be better off eradicating I'd suggest fear of death over death itself. I'd rather live 100 years free from fear of dying than 1000 years in constant fear of dying.

That answer isn't cynical, there's no cynicism involved in the context. There's nothing wrong with pursuing something because it might affect you personally. In fact, that's a particularly tremendous reason to do something. It makes it personal, it increases motivation.

There is nothing wrong with self-interest. It's why all the people posting in this thread are still alive. A given person's spending in the developed world on their food budget in a year, is a scaled equivalent in resources to what Gates is probably going to spend on Alzheimer's. The difference is, if his investment pays off it helps millions of people. That's the best kind of self-interest.

An awful lot of scientific progress has come about because of self-interest. See James Burke's "Connections" series.

Would love to see more non-billionaires involved.

You might not be far off on “he’s getting older”. When you’re younger, you don’t think about the impact of “old people” diseases.

Hearing that a couple billion people will get Alzheimer’s is not nearly as impactful as seeing someone a little older than you with it.

Don't know about you but seeing my grandparents getting senile was enough to get me thinking (and fearing) "old people problems".

Reading between the lines, it's probably more like "because my parents are getting old." If you weren't paying attention before, you will then.

Yes, the same self interest that made him spend vast sums of money and personal time on sub Saharan Africa. He should only get credit for things that couldn’t possibly help him personally.

I strongly disagree - he should get credit for all the good things he does, regardless of the reasons.

Within reason - the end doesn't justify the means.

The person you're responding to was being sarcastic.

I'm aware. I wanted to make my own position very clear.

Just relistening through some of RadioLab's podcast. I came across this apt episode about Gamma Light Therapy. Adding it to the mix. When I listen to this episode, I had a hint of hope for my dad who is suffering dementia in the past few years.


It seemed like such a simple treatment, that it should be relatively easy to test more widely... But whenever I've searched, I've not seen an update.

For those who haven't listened to the podcast, the treatment is effectively just being exposed to a 40Hz (IIRC) flashing light. Which sounds surprisingly simple.

Even younger people can be afflicted with Alzheimer's (called Early-onset Alzheimer's), and it's even more terrible to witness. It's one thing to watch a human mentally deteriorate when they are at the end of their life, it's another thing to watch it happen to someone in their 40's—who should be in the prime of their life and raising their children.

Yes. The thing is once you are an Alzheimer's patient, you are doomed because your brain basically stop being able to function at the very end. It's like a death kiss from the above. Unlike cancer, which is scary as hell, and has a high death rate, has better chance of surviving. The pressure on Alzheimer's patient and on the family is just unbearable. While there are some treatments to slow down the progress, we are far from understanding the disease itself, let alone knows how to combat the plaque and tangles effectively. Right now I think one of the best treatments is let patients be more active, whether it's playing chess or gardening, while receiving family support. The more positive we are the better we are overall health wise. This is evident in patients who suffered depression.

>>It's one thing to watch a human mentally deteriorate when they are at the end of their life<<

Alzheimers is terrible to witness at any age - the elderly included. While it's certainly tragic to see in younger people, it's no less tragic to see older people in a state of fear and panic, when they should be enjoying their twilight years.

Dear Bill, to spend money wise and efficiently I suggest that you look at the work of Dr Dale Bredesen. Dr Bredesen has fantastic results with his Alzheimer treatment and has published about it. In short, his treatment cures 9 out of 10 patients with mild Alzheimer. His scientific work is solid and a larger study is currently done. Check it out!

I've been interested in his work, but discouraged by the case-report based evidence. Can you link me to this larger study?

sorry, no link. It was said in a video and I am not 100% sure but I believe that part of the study is done at the Cleveland Clinic.

Just glanced over a video of his. It does fit in with what I already know, so he likely has the answer. But good luck with getting it noticed. On an average people will not even investigate simple solutions. Essentially the average human mind rationalizes that it sounds too good/easy to be true. ( and Bill Gates is a very average guy outside his computer/money prowess) They would rather believe authority figures who would come up with the next designer drug which modulates the complex chemical biological pathways to offer modest benefits. Designer drugs also make for good profits.

For those who want to check similar approaches google keyword - ketogenic diets and Alzheimer’s

The majority of the successes I've seen on Bredesen's web site were against non-Alzheimer's dementia, caused by infection or nutritional problems.

His first donation is $50 million to this private organization:


I remember that ultrasound[0] was very promising a few years back. Does anyone have any more recent info?

[0]: http://www.sciencealert.com/new-alzheimer-s-treatment-fully-...

I believe there are already studies out there that link excess sugar intake with increased risk of Alzheimer's?

I think this is yet another case for a ketogenic diet/intermittent fasting...

Archived copy, which can be read with JS disabled:


Emphasis added:

>"Most drug trials to date have targeted amyloid and tau, two proteins that cause plaques and tangles in the brain."

This is assumption, not fact: https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-...

Heh, the blog fails to load in Firefox 57...

Switch firefox to reader mode (the book icon in the address bar), that seems to fix it.

Same thing (the text does not appear) happens if you have Ghostery on blocking all the trackers.

Same. And with nearly thirteen thousand lines in the source of the page you'd think the text would be there too.

edit: oh, there it is, 25 lines beginning at line 8201.

> oh, there it is, 25 lines beginning at line 8201.

This comment made me laugh with the tragedy that is the modern web.

I'm running Chrome + uBlock Origin here and text does not appear either. Same in Firefox 57 + uBlock Origin, although reader view shows the text.

Ditto on Chrome

I do not have any problem on it with Firefox 57. Are you sure it's not because of an extension ?

I love that Gates is driving money into this needed area. We need new ways of attacking cures and the tech arena should be the driver not science. IMO, traditional science has gotten in the way and their agenda isn't where it needs to be: to find a a cure and save lives (take cancer research for instance).

I don't understand why you think tech companies will be any better at this than biomedical companies. All businesses have the same incentives to make things chronic issues (subscription revenue!) rather than curing them.

Because I recently read a really interesting story that talked about how science tends to get in the way of real progress. I hope you don't mind me sharing it with you but it struck a real note with me. http://www.thenewatlantis.com/publications/saving-science

The new research [0] on similar causes of diabetes, Alzheimer's, and cancer is exciting as one could target major killers at once.

[0]: https://www.youtube.com/watch?v=KSo-p7DafpA

Say you had a $80 million dollar budget. How would you deploy it to have maximum impact on Alzheimer’s?

In other words, what would you do if you were in Gates position?

Alzheimer is essentially type 3 diabetes. I'm happy to see Gates behind this.


I'm guessing they mean because it may be related to insulin resistance / sugar consumption, but I'm not sure.

Prevention, prevention, prevention.

Disable the shitty auto-pausing of youtube video on scroll by pasting this on the console:

  getEventListeners(document.getElementById('tgnbody')).scroll.forEach(function(el){document.getElementById('tgnbody').removeEventListener("scroll", el.listener)})

I didn't know there was a youtube video because (apparently) a key component of this site was blocked by Ghostery and/or uBlock.

Message to most websites that fail to load without their cruft - I just don't need you.


I'd love to have a browser extension which automatically augments shitty websites with community-sourced javascript snippets. E.g. you'd visit idk Forbes.com, and saw that the site is unusable b/c of some shitty undismissable paywall overlay. You "fix" the issue with a few lines of JS, and then upload it via the extension. After going through some kind of vetting/review, the extension will automatically fetch and run your JS fix for everyone who visits the site.

I'm using Just Read on Chrome, if you're on a shitty website hit the Just Read button and it pulls out the text, works pretty well.

Grease Monkey?

Does GreaseMonkey suggests you scripts based on the current site you're visiting?

Wasn't Edge supposed to support shareable annotations? That's nearly code...

no need to have Alzheimer to see these poor old guy / women that can't do anything. We should die sooner, waste less resource and enjoy more.

You've been posting a lot of uncivil and unsubstantive comments. Could you please take a look at the guidelines and start following them?


I've never understood this degenerate self-loathing that exists within the environmental scene.

It's completely toxic to the green movement.

There are some people would would like to die. There are many who get true enjoyment from life well into their 90s.

What would you suggest?

Don't extend life...we discovered these things because we are older and older. I don't think that the solution is getting older. Don't know why I'm always getting down vote too. Life and his mystery.

What about the elderly people who don't have problems?

Finally, a cause that can eat up the entire Gates fortune without breaking a sweat

FYI, taking sauna 4x a week seems to lower the risk of developing Alzheimer significantly (at least in Finland). I can also observe myself that taking hot phase 4-5x for 10-15 minutes followed by 2 minutes cold immersion every time in roughly 1.5 hours clears my brain/senses. Maybe the sweating helps overloaded brain drainage as well?

I think Bezos must be applying some of these hacks on himself; he got recently in shape while in previous decades he seemed to let himself go. Bill might think about the same as he is visibly deteriorating and his liver seems to be not functioning well (spots on his skin everywhere). They should add calorie restriction/frequent fasting as well. It's unlikely they will beat the death, but might make their final moments less horrible.

Liver spots are the result of aging sun exposure. A long time ago they were thought to indicate an issue with the liver, but there is no connection between the two. They are not at all an indicator of health. The only affect they have medically is that they can make it harder to detect skin cancer when doing a visual exam.

Thanks, I'll update my knowledge :)

Bill might think about the same as he is visibly deteriorating and his liver seems to be not functioning well (spots on his skin everywhere)

I think he's always had freckles, no?

If you see some recent unedited footage of him speaking, it got much worse. I personally know one soon-to-be-a-billionaire that is heavily funding his own biotech/longevity research to buy more time, yet is hopelessly out of shape and doesn't have the same discipline on his own body he has for his companies. It's paradoxical when you think about it, kinda broken feedback loop.

"Liver spots" have noting to do with the liver.

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