12 ms·

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],

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

joewee 9y ago
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.
- skybrian 9y ago
  SME seems be "subject matter expert".
  - pouetpouet 9y ago
    I think it's "small and medium-sized entreprises" aka SMB
- woah 9y ago
  Did you watch him question someone who was an expert in a subject that you were also an expert in?
  - joewee 9y ago
    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.
    - paulajohnson 9y ago
      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.
- jlampa 9y ago
  Here's an account of what being grilled by Bill Gates looks like: https://www.joelonsoftware.com/2006/06/16/my-first-billg-review/ https://www.joelonsoftware.com/2006/06/16/my-first-billg-rev...
- gech 9y ago
  I've heard the same regarding Jeff Bezos. A designer I think met with him and described him just like that.
- shostack 9y ago
  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.
mrfusion 9y ago
But isn’t Lyme disease just in the eastern us? How would 70% of worldwide alz sufferers acquire it?
- exelius 9y ago
  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
  - mrfusion 9y ago
    Thanks. I’m still not understanding how so many people could acquire Lyme disease and not have any of the other symptoms.
    - belenos46 9y ago
      Because Lyme is often asymptomatic, other than the initial rash!
      - eric_h 9y ago
        Lyme can be asymptomatic for _years_ and in many cases it doesn't even cause the initial rash!
  - gecko39 9y ago
    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 ) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019728/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019728/ https://www.newscientist.com/article/dn28514-conquistador-brought-early-onset-alzheimers-to-colombian-town/ https://www.newscientist.com/article/dn28514-conquistador-br...
kuwze 9y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681354/
jdpigeon 9y ago
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 https://www.ncbi.nlm.nih.gov/pubmed/24840565
- Danihan 9y ago
  > 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? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ 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.
  - Nomentatus 9y ago
    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.
    - Danihan 9y ago
      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.
Nomentatus 9y ago
As for how a citizen scientist proceeds, go to pubmed.com and read the abstracts of at least 400,000 medical articles. I did.
- wellboy 9y ago
  You read 400,000 abstracts? That would take something about 3 years full-time no?
  - richk449 9y ago
    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.
    - wellboy 9y ago
      I calculated 1-2 minutes per abstract, since abstracts are usually not more than 1-2 paragraphs?
      - Nomentatus 9y ago
        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.
digikata 9y ago
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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295368/ [2012] http://rspb.royalsocietypublishing.org/content/283/1823/20152397 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.

joewee 9y ago

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.

skybrian 9y ago
SME seems be "subject matter expert".
- pouetpouet 9y ago
  I think it's "small and medium-sized entreprises" aka SMB
woah 9y ago
Did you watch him question someone who was an expert in a subject that you were also an expert in?
- joewee 9y ago
  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.
  - paulajohnson 9y ago
    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.
jlampa 9y ago
Here's an account of what being grilled by Bill Gates looks like: https://www.joelonsoftware.com/2006/06/16/my-first-billg-review/ https://www.joelonsoftware.com/2006/06/16/my-first-billg-rev...
gech 9y ago
I've heard the same regarding Jeff Bezos. A designer I think met with him and described him just like that.
shostack 9y ago
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.

mrfusion 9y ago

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

exelius 9y ago
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
- mrfusion 9y ago
  Thanks. I’m still not understanding how so many people could acquire Lyme disease and not have any of the other symptoms.
  - belenos46 9y ago
    Because Lyme is often asymptomatic, other than the initial rash!
    - eric_h 9y ago
      Lyme can be asymptomatic for _years_ and in many cases it doesn't even cause the initial rash!
- gecko39 9y ago
  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 ) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019728/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019728/ https://www.newscientist.com/article/dn28514-conquistador-brought-early-onset-alzheimers-to-colombian-town/ https://www.newscientist.com/article/dn28514-conquistador-br...

kuwze 9y ago

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

jdpigeon 9y ago

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 https://www.ncbi.nlm.nih.gov/pubmed/24840565

Danihan 9y ago
> 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? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399390/ 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.
- Nomentatus 9y ago
  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.
  - Danihan 9y ago
    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.

Nomentatus 9y ago

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

wellboy 9y ago
You read 400,000 abstracts? That would take something about 3 years full-time no?
- richk449 9y ago
  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.
  - wellboy 9y ago
    I calculated 1-2 minutes per abstract, since abstracts are usually not more than 1-2 paragraphs?
    - Nomentatus 9y ago
      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.

digikata 9y ago

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/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3295368/ [2012] http://rspb.royalsocietypublishing.org/content/283/1823/20152397 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.