Chris X Edwards

I wonder what the future holds for the most disgusting and unsanitary practice Americans will not easily give up - accepting paper dollars.
2020-03-30 08:44
Alcohol leads to 88k US deaths/yr & those deaths forgo 30 yrs avg. (src CDC) Will the new focus on saving lives repeal the 21st Amendment?
2020-03-30 07:25
Profoundly thankful that I no longer must share a washing machine with disgusting strangers and their pets. Not missing Cali life in an apt!
2020-03-27 13:10
Read report predicting 5e5-4e6 US virus deaths. For context: at .0088 natural death rate, 2.9e6 will die for the same reasons we pay taxes.
2020-03-19 06:08
"For added security enter your pin," the phone tells me - while I'm on a call! Come on, that's not just me, right? That's bonkers UI, right?
2020-03-16 18:20
Blah Blah
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What Soap Really Does

2020-03-30 18:09

One of the more useful ways San Diego contributes to society is with world-leading biotech. Even though I’m really a computer specialist, I spent about 15 years working in molecular biology labs there. One does not hang around computational molecular biophysicists that long without learning some basics.

One of the fun benchmarks I used to do is assemble icosohedral hepatitis capsids into the full virus where every atom is properly placed. It’s interesting to see a machine where you know the location of every atom. I was thinking of assembling a COVID19 virus' helical capsid but I don’t think there are any solved structures of the proteins this virus is comprised of.

Searching PDB the only thing that seems to exist at this time is a cryo-electromicroscopy structure of the spike glycoprotein trimer. This is the structure, i.e. the placement of each atom, of the spiky protrusions sticking out of COVID19.

prefusion6VSB.jpg

You don’t have to be an expert to see that this is hasty work. This is a trimer, three identical protiens in a trigonal symmetry. But one of them clearly isn’t like the others, is it? They provide excuses in the paper.

While looking at that one thing caught my eye, a video titled Fighting Coronavirus With Soap. One thing that has always intrigued me is soap. How does it work? I mean how does it really work? The video is only a couple of minutes and graphically quite well done.

Watching the video, I was a little uneasy about the message. Let’s learn more about soap’s molecular physics and think this through.

This is how the video is representing a soap molecule.

soapmolecule.jpg

Here is a more technical representation of stearic acid which is found in many common soaps.

stearic-acid.png

The white spheres are hydrogen, the black spheres are carbon, and the red are oxygen. The carbon chain is a hydrophobic fat. This is why soap has some similarities to oily stuff; for example soap can be used to lubricate things.

So let’s say that you have dispersed a bunch of these molecules into water and the important property of the lipid tail is that it hates getting wet. Of course at molecular levels the idea of "wet" isn’t exactly a thing, but that’s fine. The tails of soap molecules are what’s called "hydrophobic" — if there’s a way for them to avoid water and bond to something else, they will. The heads are "hydrophilic", they love water!

Now let’s say you have some surface that is covered in oily lipids. The video illustrates such a situation like this.

lipidscum.jpg

The brown strands are just like the soap’s tails. The idea — and indeed molecular fact — is that when the soap tails get near these oil residue tails it is more "comfortable" (electrochemically) backing its soap tail into the lipids to get away from the water.

hydrophobic.jpg

If enough of this activity happens, the soap and lipid cluster can form a little ball called a micelle.

micelle.jpg

This ball is the most comfortable configuration (minimal energy state) for the soap and any lipids it gets near to avoid the water. Once the lipids are bound up in a little ball whose outside surface is happy to swim around in water, it turns out that it is easy to rinse the whole assembly away. This is why if you put soapy water in greasy cookwear, the stubborn residue can finally be rinsed clean. The oils of your food are generally the same stuff for the purposes of this topic.

We’ve seen soap form into little balls called micelles. There are other configurations such molecules can take. This Wikipedia image is called "phospholipids_aqueous_solution_structures".

bilayer_types.png

There’s the micelle as described. Then there are the bilayer types. These form as shown when two sheets are arranged tail to tail, again neatly avoiding the tail getting "wet". Next to think about are liposomes. Liposomes are small little spheres of this molecular configuration. Researchers are trying to figure out how to pack them with therapeutic agents in order to sneak drug metabolites into a patient in a way that otherwise would dissolve in water. They hope it can be a clever way to sneak something into some place it doesn’t usually go.

This is exactly how a virus works! A virus envelope (the round sphere you see in all the images of the covid 19) is the same topological bi-layer organization of lipids as a liposome — it is just somewhat bigger.

It is also interesting to note that soap bubbles are formed by the same mechanics, just sort of in reverse. This diagram illustrates it well.

lipidbubble.png

The video shows the virus' envelope bilayer sheet like this.

envelopebilayer.jpg

What exactly is that phospholipid layer of virus envelope made of? Wikipedia says "The envelopes are typically derived from portions of the host cell membranes (phospholipids and proteins)…" Did you catch that? Imagine two kids playing with a limited collection of Legos — one takes a break and returns to find their construction half-destroyed and the other’s now greatly expanded. Viruses steal your cell membranes to make their own membranes! At an atomic level virus skin is the exact same stuff as your skin! Well, the "skin" of your skin — and any other handy tissue — meaning the cell membranes. Viruses are perfectly effective even when they destroy their hosts' cellular machinery. And when cells fail and disintegrate, what is conveniently lying around in abundance for an ambitious virus to use? Your cells' membrane lipids!

And now we get to the problem. If soap can polarize bilayer lipid proteins of virus envelopes, well, I’ve got some bad news for you about what it will be doing to the membranes of your skin cells. Yes, viruses exposed to soap in high enough concentrations for long enough periods of time may start to become unstable for effectively the same reasons that sandpaper, battery acid, and open flames all can destabilize viral envelopes (i.e. the wrong energy in the wrong place) but I do not think this is what the essence of soap hygiene is all about.

I can accept that the action of soap can be a little rough. You certainly don’t like to eat it and it can irritate other sensitive areas like your eyes. An interesting property of skin cells (which are called keratinocytes) is that they usually are completely dead on the very outside of your body. You are covered in dead skin which protects you by absorbing damage that chemical assaults like soap entail.

Now we have some important facts that can help us understand the best way to use soap.

  1. Soap does nothing more than polarize lipids (making oily things easy to rinse away with water).

  2. Although your skin and virus envelopes are somewhat resilient to soap, both can be damaged by soap’s destabilizing effects on your tissues' lipid bilayer in the right circumstances.

  3. Your skin generally has a shell of dead skin cells that can absorb some environmental damage, including that of soap.

So what could this mean for washing and dangerous pathogen mitigation? Here are some things to consider.

  • If you have oil on your skin — and your sebaceous glands tell me that you do — it may be easy to trap viruses in that oil.

  • There are no sebaceous glands on the palms, but if you touch something icky (or someone), or your own body, you could pick up oil that could be carrying viruses.

  • Touching things other people touched could also transfer such oil.

  • Washing this oil off seems reasonable and soap will make it happen.

  • Poop is produced by the system where waste lipids are separated from waste water. If you have any reason to suspect there is poop on you, soap is a great idea.

  • Touching things will transfer oils. Think about what you’re touching and what kind of oils/lipids might be there.

  • Putting your hands in/near your mouth or eating food that you’re holding is especially problematic and needs your hands to be free of dangerous pathogens.

  • If you’re going to perform surgery or something like that, maybe scrubbing down until you damage your own skin is reasonable.

  • If you are a surgeon, and wherever anyone is in a serious situation, wear gloves.

  • Not only are the gloves important, but being mindful of what you touch while wearing them.

That’s all pretty normal sounding, right? You won’t be surprised to learn I have some more controversial notions. Of course I do!

  • Destroying your skin with harsh surfactants is harsh and perhaps not ideal.

  • Obsessive hand washing is obsessive. Think it through!

  • Destroying your skin’s natural oils completely can not be ideal. There is a balance!

  • For the same reason that putting skin oil in your mouth can be a bad idea when trying to avoid infection, that oil may also be helpfully trapping and immobilizing pathogens.

  • And here’s the hard one to sell - your body’s immune system builds upon measured exposure to bad things. It’s all about concentrations. If you are too aggressive about flensing your skin’s microbiome, you could damage your body’s ability to form a proper defense.

  • Some chemicals in soap may not be good for you or your skin’s microbiome. Maybe at certain concentrations. Maybe it’s fine when the skin is protected by oils but problematic once they are stripped. Remember, the FDA just banned triclosan from hand soaps in 2016. Before that it was ubiquitous.

The FDA is particularly interested in gathering additional data on the long-term safety of daily, repeated exposure to these ingredients by consumers, and on the use of these products by certain populations, including pregnant women and children, for which topical absorption of the active ingredients may be important. Emerging science also suggests that for some antiseptic active ingredients, systemic exposure (full body exposure as shown by detection of antiseptic ingredients in the blood or urine) is higher than previously thought, and that more information is needed about the effects of repeated daily human exposure to some antiseptic active ingredients.

Wash your hands — and other parts — the way that is best for your well-being. With a little biochemistry understanding, you hopefully can make some better guesses about what exactly that way is. Soap is a tool — use it correctly, in the right circumstances, and it will be good to you.

Thanks to the brilliant and kind biophysics professor, Ruben Abagayan for reviewing this topic with me. All errors are mine!

The Young Shall Inherit The Earth

2020-03-25 10:51

Last year I sent this to a friend who works in the cloud storage business as an idea for a good way to show off that product.

On Wed, Apr 17, 2019 at 11:13:26AM -0400, Chris X Edwards wrote:

My hasty calculations show that a Minecraft world (32meter X 32meter chunk at ~5MB each) would require about 2.5PB for a 1:1 server of the entire earth. A 1:1000 server has just started but I’m thinking ahead. :-)

That was just a very rough idea of what would be required but other people were apparently thinking of this more seriously. Check out this video describing a project that has successfully built a 1 to 1 scale model of the entire earth in Minecraft!

The special thing about MC is that it is actually quite coarse. That is why such a massive project is feasible. A map of this scale in some other kind of engine would have to be very sparse and even then it would be uncomfortably rough (like MC, but not in a pleasant structured way) and empty.

In ancient times (the early 1990s) AutoCAD shipped with a neat demo file containing a full scale 1:1 model of the entire solar system. They had a 1km object on the moon (ours) and all the other objects of our solar system were roughed in to scale. That demo was quite interesting to get a sense of what the capabilities and scale of computer floating point numbers were (2 to the 32 power is around 4.3 billion and that is about how many km Pluto is from the sun at perihelion).

In games like Space Engineers which have some minimal terraforming capabilities, you’re deforming a sparse shell. In MC, it’s real volume. This means that this Minecraft model of the earth is ready to incorporate bathymetric surveys of the ocean depths and subterranean geotechnical data (from petroleum exploration, for example).

Here is a wonderful project from the British Geological Survey that has modeled the real geology of Britain in Minecraft.

To jump an order of magnitude linearly from 1m resolution to 10cm is harder than a 10x increase in resources — it’s 1000x because of this volumetric quality. But a decimeter model of the earth in real scale would be pretty amazing and useful. And probably in our future!

At least the kids now have something as useful as school to work on!

UPDATE 2020-04-01

Check out the wave of projects that students are working on to recreate their closed schools in Minecraft.

Frankly this is the best use of practical shared virtual reality I have seen.

Virus!

2020-03-23 15:06

I was in Iran just months before the hostage crisis. I had purchased plane tickets just before 2001-09-11. I was watching the economy closely in 2007 because I wanted to buy a house — I did not because of the subprime mortgage fiasco that ravished the world’s economy.

I’ve seen some shit! But I have never seen anything like this. Wow.

escalated_quickly.png

This novel coronavirus pandemic has been shocking. Well, not really. I’ve actually seen absolutely no evidence of any direct effects of the illness personally.

What has blown my mind is the response. That is affecting me personally quite a bit. But you knew that because the astonishing thing about this historical event is that it is affecting literally everybody.

The response has been so unbelievable that I don’t feel alone in being shocked and somewhat overwhelmed by it. I’m just reading the news and it’s a bit like 9/11 in that a lot of people are dying, and that’s obviously bad, but you can’t help realize that the real situation is much, much bigger and will have serious ramifications well into the future.

As the flood of profoundly unexpected news comes in, I can barely keep up. Here is a collection of thoughts I’ve jotted down. Better to post them now rather than wait for the thousand page book when this thing is all over. If it ever ends.

Telecommuting

Let’s start with some personal hobby horses.

For 15 years or so, Google tried to recruit me and I was very enthusiastic. However, I was stuck in a technology backwater (San Diego) with no Google offices and would need to work remotely. I was assured this was impossible. So Google, which is it: 1. You are evil? 2. Or your work-from-home products are incompetent and/or ill-conceived? It must be one of those. I don’t mean to just pick on Google - all the stupid Silicon Valley companies who should be better at using networked computers yet who stupidly pack computer nerds into tech bro mosh pits in a region with a terrible quality of life also deserve opprobrium.

Of course I’m talking about whoever is making these high level management decisions at tech companies. The people keeping the internet turned on deserve thanks and recognition which I know from first hand experience they are unlikely to get.

itheroes.jpg

I understand that people who are more socially excitable than I am might need to go chat at a physical water cooler or fetch sticks together or smell each other’s butts during meetings or whatever. But I’ve been horrified by the terribleness of that system since I first really didn’t want to live where the other computer nerds had to live — for at least 20 years now.

notremote.png

If this virus can get even the moronic Google (come on now, let me stress the point again: they make work from home tools) to get a clue and allow remote work ( "Google tells staff to work at home due to coronavirus"), well, that is somewhat of a silver lining to me.

Of course if you’re a white collar worker enjoying this transition to remote work, make sure you’re literally one of the best in the world at what you do because the next transition will feature you competing with those people directly.

On-line education

Just as the virus was entering the news and many schools knew they were going on-line (UB has moved all classes online) an extremely surreal event happened to my wife. She got a call from an HR person at a famous university in New York looking to hire on-line education experts, which has been my wife’s profession for many years. We are not interested or able to move to the city where this university is located and astonishingly they would not consider hiring someone to work remotely! That is as bad as the Google example! And at this point in history, I suppose even worse. Once again, these are supposed to be ostensibly intelligent people.

Ask yourself how many hours of live stage plays you have sat through in the last year and divide that by the number of hours of recorded dramatic entertainment you’ve watched. Or the number of hours of live concerts you’ve listened to versus the number of hours of recorded music. Why are we still using the live performance stage play model for education? It is apparent that no one but the performers care for this style of delivery on the whole, and maybe not even them. It’s just that kids don’t get to make sensible decisions about education. Can society finally move out of the 19th century with respect to education? I’m guessing the answer is… maybe. It’s looking more promising than ever which is another silver lining.

I feel that this virus will highlight what schools are really doing for families — baby sitting. That’s fine and a real need society has, but let’s call it what it is. Or I’m wrong and the future is doomed because of what rote attendance in schools formerly provided. Either way, all of San Diego schools seem closed indefinitely now.

Remote Service

Apparently even people smarter than me have finally figured out what I’ve know since I first saw a Skype video call: a huge number of trips to the doctor are now no longer essential or even beneficial - they are recklessly toxic. Why did it take this event to get people to notice that nosocomial infections are bad? Remember what I said about people with white collars needing to compete with international players if they did things efficiently?

I’ve always respected people who make remote services effective. One example I like very much was a fantastic guitar player who posted instructional videos on Youtube. Even though he lived in the serious middle of nowhere, he had no trouble filling his schedule with good paying students from all over the world - over Skype.

I wish I my attorney lived in the same town as me because she lives in Anchorage, Alaska (and I would love to return to there). Remote services can work!

One example I’m faced with right now is a need to visit to the DMV. Who are now closed with no recourse. (I have thought about making a license plate-sized sign saying "PULL ME OVER IF YOU CAN TELL ME HOW TO GET PLATES".) Yes, they need me to prove I’m really me, I understand that. But take it from me — faking an entire on-line video conversation is actually harder than having an imposter actor show up live. So why on earth are we waiting in line at the DMV for such tasks? Honestly, driving tests can even be done remotely too by now. I’m hoping that this calamity will spawn all kinds of creative thinking to improve situations where I didn’t really want to be standing in line for hours with masses of other people anyway.

VR

I’ve been interested in virtual reality for a long time. (Mark Zuckerberg and) I have always felt that it could provide a really compelling way for people to collaborate remotely. I’m not going to make any predictions because the best prediction one can make about VR is: won’t live up to hype. However, it really seems plausible that it could do some good if everyone was as keen as Mark and I. And I’m not sure you have a choice these days.

Vegetarianism

My personal reasons for minimizing meat consumption are: catastrophic environmental problems, dubious health effects (antibiotics and other residual veterinary drug metabolites), hard to clean messes in my kitchen, and generally poor value - other people have other reasons. This virus highlights another very sensible reason: livestock practices seem related to big pandemics. The penultimate paragraph of this NIH article talks about how SARS and other diseases made the jump to humans because of "animal husbandry and marketing practices". Not saying it’s true but an idea to think more about than you did a few weeks ago.

Unsustainability

I do not find the direct victims of this illness especially interesting. Flu. Like always. Maybe twice as bad this year. Old people should be twice as worried as they were before. Other than that there doesn’t seem much to say. I’m sorry if that sounds insensitive and awful but consider that in December I did have pneumonia and was lucky to survive — for all anyone knows, I could have had the famous virus! Any worse off, I’d have been dead and being dead is bad. I get that and so I totally understand what the victims are going through. But my little brush with such an illness and the other putative (stats are very bad at this point) victims of the illness are not what’s really impressing me.

What is really blowing my mind is the response. My response to the response is: There is no fucking way we can sustain everyone simultaneously taking dozens of consecutive vacations. That is the end times. This Atlantic article describes the non-health aspect of current events as "a consumer-economy apocalypse". And, "…not a recession…an ice age." A Bloomberg article says "…the economy is headed toward its worst quarter in records since 1947." Etc.

I’m not usually one to care much about the markets or GDP etc., but you can’t have all humans just stop contributing to civilization. I’m sorry — that is worse than a bunch of old people dying because it also includes a bunch of old people dying.

Of course it’s not all humans that must put aside any productivity. Remote workers are still working. And so are "essential" workers. This made me wonder, who likes being called "non-essential"? Ouch. Isn’t capitalism supposed to tell us who is essential? I think what they mean to say is "essential during an actual emergency". But emergencies, pretty much by definition can’t last a long time. Just as you can stop breathing if you encounter an underwater emergency, we can stop all kinds of things in the economy for a short while. But if people think that’s going to work for months… I am very skeptical.

essential.jpg

I saw this anonymous comment somewhere and thought it was kind of funny: "The irony of COVID is that medical bills is the #1 cause of bankruptcy in the US so its fitting that the whole country will soon be bankrupt because of a medical emergency. Nothing could be more American." Unfortunately the problem is not just related to the bad health care idiosyncrasies of the USA.

Politics

This kind of a stress test on civilization is a great time to re-evaluate priorities in our elected representatives. Will Americans get their shit together and elect people who respect science, facts, and the complexity of the world? Will public health care become a priority in the USA, the backwater of public health care? Will public transportation (and air travel) become even less fun than it already is?

I mentioned the DMV and (non-hypothetically) that without the government functioning, I can not secure property rights; will "libertarians" get a clue? Well, of course not. But they should!

Contrarian Thoughts - Virus As A Blessing?

shootingless.jpg

Unlike the characters in this absurdly prescient satire, I don’t want to see Baby Boomers dying but I can’t help feel that the most powerful generation in history made their own bed on this one to some extent.

boomer.jpg contraboomer.jpg

Remember, 2.9 million Americans will die this year just because people die at the end of their lives. Boomer deaths by normal mechanisms (such as respiratory infections) will seem statistically out of place because the entire Boomer cohort was statistically out of place. Will we call it a pandemic? We’ll all be very annoyed if this turns out to be a statistics mistake. We’ll only know once actual data is collected — still waiting on that!

testing.jpg

Another interesting thing to think about is population immunity based on interactions. Not just to novel corona viruses. It could be that once we reintegrate, we, as a population, are much weaker because we have all been isolated. I have speculated that handshaking, for all its obvious cootie potential, may also serve as a mild form of inter-human inoculation. Will handshakes become permanently uncool in the future?

It occurred to me that this virus is a big social Darwinism experiment. Introverts will presumably be reproducing at the same rate they always have (improbably, some how), but one can imagine a slowdown in the phenotype of humans who can only reproduce as a result of large drunken gatherings. And as far as I can tell, that’s most of them in countries that speak European languages.

introvertftw.jpg

I’ve seen lots of reports in the pseudo-press about this virus saving lives overall because of reduced air pollution. I can affirm that with much less traffic out there, the air quality on my bike ride this morning was better than it ever has been. Think also about the number of people taking a healthy walk outside who now have vastly fewer other entertainment options. How many lives will that save?

And on the topic of "saving lives" by sticking a huge stake into the heart of the economy? I’m not sure that WEIRD people want to go there. Let’s… Talk… About…

Cars!!!! No this has been long enough and that deserves its own post!

Prognosis

I believe there is no way a complete shutdown of society globally can last more than a few months. I also believe that society can not shutdown completely enough to confidently suppress a very virulent virus. I am guessing that this disease will mysteriously disappear in a few months. This has happened in many of the pandemics of the last century. Of course no one knows what’s ahead and it’s quite likely any and all of those predictions are wrong. Whatever happens, we’re in uncharted territory and it’s going to be interesting. And hopefully not in the worst way it could go.

Stay well!

UPDATE 2020-03-27

I just remembered Google Flu Trends. That was actually a reasonable data set to analyze. Let’s put that creepy surveillance capitalism to use! Sure the data is terrible, but there is so damn much of it. Of course with the massive reaction, the data are going to be tricky to understand. Here is another interesting project along the same lines: https://healthweather.us/ Surely companies like this and this are collecting interesting data about exactly how feverish their customers are.

Ice Boom

2020-03-03 19:15

A loyal reader sent me this image of a house which is about 20 miles from mine. Full story.

icehouse.jpg

It is apparently right on the Lake Erie shore which is why my house looks nothing like that. What happened here?

This has been a very strange winter. Although it has been uncharacteristically warm, that is actually what caused this ice build up. A few days ago, we had some very high winds while the temperature dipped down to the low 20sF. This created big waves on the lake and the splash and spray on the shore was able to travel horizontally quite a bit more than usual. That’s how that house got coated in ice.

To see why it is extraordinary and why the generally warm temperatures caused this, take a look at this image from April 30, 2019.

iceApril30.jpg

This shows the ice boom which is deployed every winter at the end of Lake Erie. This prevents too much ice from damaging the Niagara River shoreline or overwhelming the power plant intakes at Niagara Falls. That image shows they are just releasing the ice.

Now compare it to this morning, nearly two months earlier in the season.

boom2.jpg

It was foggy, but you can see the boom is still strung together in its winter configuration and yet there is absolutely no ice this year at all! None. This is why that house on the shore was seeing more water spray. Usually there is shore ice that keeps that house separated from water spray. (You can see a bit of shore ice on the Canadian shore, but it’s very light.)

You can also see a boat in today’s photo; that boat is preparing to remove the boom.

NASA points out that on February 14, the Great Lakes should be 41% covered with ice and this year they were 17%. Definitely some interesting weather.

Review: The Body - A Guide For Occupants

2020-02-16 21:44

I just finished reading The Body - A Guide For Occupants by Bill Bryson. Bryson is a genius and a delightful writer who makes reading a real pleasure. If you’re interested in the human body — and you are an owner of one, so yes, you are — this book is worth reading. There you go, that’s all the review you need.

But this post has a deeper purpose. I spent about 15 years working in the top levels of biomedical research. I had an extraordinary ringside seat to watch the show of how medical progress is produced. If you’re young enough to not be dead from old age and if you’ve ever visited a doctor in the USA, the overwhelming odds are that you were told to eat some magic beans. I was able to see where those magic beans come from — not physically, but rather the idea forge of the conceptual chemistry behind it all, pharmacology.

I had a special place in pharmacology — I was not an expert but I provided technical engineering support to some of the world’s most competent and knowledgeable molecular biochemistry experts. I did not have to compete with them by writing papers or begging for their grant money. I believe this gave me a more realistic view of this work.

I worked with some incredible and brilliant super geniuses. I was always impressed with their ability to attack absurdly complex problems as if they were going to succeed. However, the entire time I was involved in the life sciences, everything I saw and experienced led to a coherent and strong impression which was this: humans know nothing about biology.

When I say that, think of filling your pockets with sand — you may think that with bulging pockets you’ve got a lot of sand. But if you’re standing on a beach, well, no, that’s probably a poor way to describe it. To say you have any sand when looking out over the vast sand-lined ocean would seem slightly pathetic. So it is for saying we humans know anything about anything related to molecular biophysics, biochemistry, genetics, molecular biology, cell biology, physiology, neurology, zoology, oceanography, and so on. It is probably more hubris than truth to not accept our profound ignorance.

Rather than me opine about it, I’ve excerpted quotes from this book which (incidentally!) make the case pretty clear.

…where the human body is concerned, the details are often surprisingly uncertain.

— p4

How this [genetics] works in detail is still largely a mystery to us.

— p7

…only 2 percent [of DNA] does anything demonstrably and unequivocally practical. Quite what the rest is doing isn’t known.

— p8

…techniques for analyzing ancient DNA means that we are learning more all the time and much of it is surprising — and some is confusing and some disputed.

— p18

The answer is that nobody knows. Your body is a universe of mystery. A very large part of what happens on and within it happens for reasons that we don’t know — very often, no doubt, because there are no reasons.

— p21

As early as 1945, in his Nobel acceptance speech, Fleming warned that microbes could easily evolve resistance to antibiotics if they were carelessly used. Seldom has a Nobel speech been more prescient.

— p43

Thinking is our most vital and miraculous talent, yet in a profound physiological sense we don’t really know what thinking is.

— p54

But what scientists learned from [a notable brain injury patient] was not so much how memory works as how difficult it is to understand how it works.

— p61

…there is a great deal that we still don’t know about smell, including exactly how it works.

— p88

As with every other part of your head, the mouth is a realm of complexity and mystery.

— p94

Take the tonsils. We are all familiar with them, but how many of us know quite what they do? In fact, nobody knows quite what they do.

— p94

Also mentioned: One notable study has shown that people who have their tonsils removed while young had a 44% greater chance of suffering a heart attack later in life. Who knew? The point is, apparently no one.

Discussing an opiorphin found in the mouth:

Because it is so dilute, no one is sure why it is there at all. It is so unassertive that its existence wasn’t even noticed until 2006.

— p99

For years, even textbooks spoke of a tongue map, with the elemental tastes each occupying a well-defined zone: sweet on the tip of the tongue, sour at the sides, bitter at the back. In fact, that is a myth…

— p101

Taste buds are actually present in the roof of the mouth, in the throat, in the stomach, heart, lungs, and even testicles. Why? No one knows.

That was the problem with bleeding [as a therapeutic medical treatment]. If you could tell yourself that those who survived did so because of your efforts while those who died were beyond salvation by the time you reached them, bleeding would always seem a prudent option.

— p132

This classic lack of a falsifiable hypothesis is what makes most of health care unscientific. Generally, only epidemiological studies, as opposed to explicit individual patient interactions, can even plausibly qualify as topics of proper scientific investigations. I believe senseless pharmacology is today’s therapeutic bleeding. The new field of pharmacovigilance could change that, but the fact is that pharmacology clearly quacks like quackery precisely because that field finally exists and is so new.

Our understanding of [hormones] is far from complete, and much of what we do know is surprisingly recent.

— p141

The immune system…There is a lot of chemistry involved. If you want to understand the immune system, you need to understand antibodies, lymphocytes, cytokines, chemokines, histamine, neutrophils, B cells, T cells, NK cells, macrophages, phagocytes, granulocytes, basophils, interferons, prostaglandins, pluripotent hematopoietic stem cells, and a great deal more — and I mean a great deal more.

— p199

On top of all that, every person’s immune system is unique, making immune systems harder to generalize, harder to understand, and harder to treat when they go wrong.

— p200

Much of what happens in the immune system at the cellular level is still very imperfectly understood. Quite a lot is not understood at all.

— p204

Sinuses are strange. … [They are] riddled with a complex network of bones, which are thought to help with breathing efficiency, though no one can say quite how. … Thirty-five million Americans suffer sinusitis every year, and about 20 percent of all antibiotic prescriptions are for people with sinus conditions (even though sinus conditions are overwhelmingly viral and thus immune to antibiotics).

— p213

What is perhaps surprising is how little we sometimes understand the causes of [respiratory] problems, and of no condition is that more true than asthma.

— p216

[At the beginning of the 20th century] asthma was a rare disease and not well understood. Today it is common and still not understood. The second half of the twentieth century saw a rapid increase in asthma rates in most Western nations, and no one knows why. … Indeed, where asthma is concerned, no one knows much of anything.

— p217

"You probably think asthma is caused by dust mites or cats or chemicals or cigarette smoke or air pollution", says Neil Pearce, professor of epidemiology and biostatistics at the London School of Hygiene and Tropical Medicine. "I have spent thirty years studying asthma, and the main thing I have achieved is to show that almost none of the things people think cause asthma actually do. They can provoke attacks if you have asthma already, but they don’t cause it. We have very little idea what the primary causes are. We can do nothing to prevent it."

— p218

Vitamin D, one of the most vital of all vitamins, can both be made in the body (where it really is a hormone) or be ingested (which makes it a vitamin again). … In the case of many micronutrients, scientists don’t know quite how much you need or even what they do for you when you get them. … Chromium levels fall steadily as we age, but no one knows why they fall or what this indicates. … For nearly all vitamins and minerals, the risk of taking in too much is as great as the risk of getting too little.

— p232

For all their importance, proteins are surprisingly ill-defined. Although all proteins are made from amino acids, there is no accepted definition as to how many amino acids you need in a chain to qualify as a protein.

— p234

Eight of the twenty amino acids cannot be made in the body and must be consumed in the diet.

— p235

Does this make them vitamins? No. Is the concept of a vitamin stupid? Yes.

Trans fats are essentially a form of slow-acting poison. … [in the mid-1950s] a biochemist … reported clear evidence of a link between high intake of trans fats and clogged coronary arteries, but his findings were widely dismissed, particularly with the influence of lobbying by the food processing industry.

— p236

It’s possible for doctors to go through medical school without being taught nutrition. … Perhaps nothing is more emblematic of the unsettled state of knowledge on the modern diet than the long and unresolved controversy over salt.

— p244

A possible contributing factor to this salt controversy: A 2016 study in the International Journal of Epidemiology found that researchers on both sides of the argument overwhelmingly cite papers that support their own views and ignore or dismiss those that do not.

— p245

That’s why you are told to eat more fiber: because it keeps your gut microbes happy and at the same time, for reasons not well understood, reduces the risk of heart disease, diabetes, bowel cancer, and indeed death of all types.

— p249

He addresses an ontological problem I’ve always found confusing: why is some E.coli bad and yet…

…most strains do us no harm and some are positively beneficial…

— p250

But is the problem now resolved and I have some kind of sensible answer? No. There are good strains and bad strains — the difference between them seems to be, tautologically, that one is good and one is bad. Later (p258) he points out that, "Two strains of E.coli have more genetic variability than all the mammals on Earth put together." Not helping!

The incidence of acute appendicitis in the rich world is about half today what it was in the 1970s, and no one is quite sure why. It remains more common in wealthy countries… though the rates in developing countries have been rising rapidly… but again no one knows why.

— p255

On the topic of the composition of poop:

We are a long way from understanding it all.

— p257

Sleeping is the most mysterious thing we do. We know that it is vital; we just don’t know exactly why. We can’t say with any certainty what sleep is for, what is the right amount for maximum health and happiness, or why some people fall into it with ease while other struggle perpetually to attain it.

— p260

Why the eyes move during REM sleep is uncertain.

— p263

How exactly melatonin relates to sleep is still not understood.

— p267

A seventy-year-old produces only a quarter as much melatonin as a twenty-year-old. Why this should be, and what effect it has on us, remain to be determined.

— p268

We are really at the beginning of our understanding of the importance of circadian rhythms for all living things…

— p269

No one understands why we yawn.

— p273

…until recently drug trials very often excluded women, largely because it was feared their menstrual cycles could skew results…. People had been assuming that women are just 20 percent smaller then men, but otherwise are much the same. We now know that there is much more to it than that… Such findings are seriously consequential because women and men can respond to drugs in very different ways — ways often overlooked by clinical trials.

— p283

Examples: phenylpropanolamine, Hismanal, Pondimin, and Ambien.

…Vaginal secretions were the only bodily fluid about which virtually nothing was known despite their importance to conception and a woman’s general sense of well-being.

— p284

This is quoting Mary Roach’s book Bonk and doesn’t say if anything more is known today.

Even now, there is a huge amount concerning female anatomy about which we are uncertain.

— p285

Discussing two large surveys that showed from 1950 to 1997 the length of an erect penis went from 6 inches to nearly 1 inch shorter:

Why is this? The bottom line is that we don’t know.

— p288

Why are sperm counts in Western countries lower than they formerly were? Among the suggested causes have been diet, lifestyle, environmental factors, frequency of ejaculation, and even (seriously) wearing tight underpants, but no one knows.

— p290

Also on sperm production:

…why such an extravagance of production, even at the lower end when only one sperm is required for conception, are questions that science has yet to answer.

— p291

For a decade or so [around 1900], [oophorectomy, removal of the ovaries] was the operation of choice for well-off women with menstrual cramps, back pain, vomiting, headaches, even chronic coughing. In 1906, an estimated 150,000 American women underwent oophorectomies. It more or less goes without saying that it was an entirely pointless procedure.

— p295

If you think that was fun times in the history of medical care, check out Walter Freeman jamming icepicks in the eyes of 2500 people to give them lobotomies.

Despite its lavish spending, the United States has one of the highest rates of both infant and maternal death among industrialized nations… The average cost of childbirth in the United States is about $30,000 for a conventional birth and $50,000 for a Cesarean, about three times the cost for either in the Netherlands. Yet American women are 70 percent more likely to die in childbirth than women in Europe…

— p298

I like to point out that the cost of childbirth as "health care" is absurd when you consider that a human being can not be more healthy than to have just given birth.

We are only beginning to understand the importance and nature of a woman’s vaginal microbiome. Various studies have found that people born by C-section have substantially increased risks for type 1 diabetes, asthma, celiac disease, and even obesity…

— p300

On top of all that [thwarting of microbiome functions], about four women in every ten are given antibiotics during delivery, which means that doctors are declaring war on babies' microbes just as they are acquiring them. We have no idea what the consequences this has for their long-term health, but it’s unlikely to be good.

— p301

Why can phantom pain in a lost limb last a lifetime? No one can yet explain why.

— p305

Exactly how pain works is, as you will gather, still largely a mystery.

— p305

We still don’t know exactly how the brain constructs the experience of pain…

— p307

Spinal cord injuries are dismayingly common. More than one million people in the United States are paralyzed from them.

— p311

Holy shit. Can that be true? More of the devastation of our horrific transportation mess.

Migraines are almost wholly a mystery.

— p313

Almost! I’ll return to that topic.

Medical science offered very little in the way of safe, lasting relief [from pain] back then [100 years ago]. We are not much further along now… …some 75 percent to 85 percent of people get no benefit at all from even the best pain drugs, and those who do get benefit don’t usually get much. … Pharmaceutical companies have poured billions and billions into drug development but have not come up with a drug that controls pain effectively and doesn’t cause addictions.

— p314

Opioid use has become such big business that we have now reached the surreal situation that pharmaceutical companies are producing drugs to alleviate the side effects of opioid overuse. Having helped to create millions of addicts, the industry is now profiting from medications designed to make their addiction a little more comfortable.

— p315

Nobody knows quite why placebos work, but they do… Placebos don’t shrink tumors or banish plaque from narrowed arteries. But then, come to that, neither do more aggressive painkillers, and placebos at least have never sent anyone to an early grave.

— p316

A report in The Journal of the American Medical Association concluded that the victims had been suffering from a "subtle but nevertheless primarily organic illness whose effects may include exacerbation of underlying psychogenic illness." Which is another way of saying, "We have no idea."

— p320

Though Paget’s findings [about breast cancer treatment] were correct and incontestable, no one paid any attention to them for about a hundred years, during which time tens of thousands of women were disfigured to a far greater degree than was necessary.

— p345

Quite early on, it was realized that radium accumulated in the bones of people exposed to it, but this was thought to be a good thing because it was believed that radiation was wholly beneficial. Radioactive products were liberally added to many medications, with sometimes devastating consequences.

— p345

E.g. Radithor.

During WW1 it was realized that mustard gas slows the creation of white blood cells. Thus was born chemotherapy. "What is quite remarkable," one cancer specialist told me, "is that we are basically still using mustard gases [as a foundation for chemotherapy]."

— p348

The unfortunate bottom line is that breast cancer screening doesn’t save a lot of lives. For every thousand women screened, four will die of breast cancer anyway (either because the cancer was missed or because it was too aggressive to be treated successfully). For every thousand women who are not screened, five will die of breast cancer. So screening saves one life in every thousand.

— p362

But at least it is a lot of fun for women and costs society nothing! Not!

We have reached the decidedly bizarre point in health care in which pharmaceutical companies are producing drugs that do exactly what they are designed to do but without necessarily doing any good. A case in point is the drug atenolol, a beta-blocker designed to lower blood pressure, which has been widely prescribed since 1976. A study in 2004, involving a total of 24,000 patients, found that atenolol did indeed reduce blood pressure but did not reduce heart attacks or fatalities compared with giving no treatment at all.

— p364

We rarely know, for instance, what happens when various medications are taken in combination.

— p366

See the relatively new field of polypharmacy for the full mess.

We don’t have any idea why we age, or actually we have lots of ideas; we just don’t know if any of them are correct. … It may be that [multiple] factors work together… Or it may be something else altogether. No one knows.

— p370

In sum, it’s clear that telomeres are important not just for understanding aging but also for understanding cancer, but unfortunately we are still a long way from fully understanding either.

— p371

Reviewing the animals that experience menopause: sheep, humans, narwhals, and humans:

Why any animals get it is a question yet to be answered.

— p373

Nobody is quite sure what amyloids do for us when they are working properly… How tau proteins relate to amyloids and how both relate to Alzheimer’s are also uncertain…

— p378

We can’t even definitively diagnose Alzheimer’s. The only certain way to identify the condition is postmortem…

— p379

[Alzheimer’s] is the third most common cause of death among older people… and we have no effective treatment for it at all.

— p380

That’s a lot of stumbling in the dark!

I would like to dig into one area of obnoxious ignorance a little more carefully because it is something I am forced to take personally: antioxidants. Have a look at this depressing situation.

Antioxidants are molecules that neutralize free radicals, so the thinking is that if you take a lot of them in the form of supplements, you can counter the effects of aging. Unfortunately, there is no scientific evidence to support that.

Most of us would almost certainly never have heard of either free radicals or antioxidants if a research chemist in California named Denham Harmon had not, in 1945, read an article about aging in his wife’s Ladies' Home Journal and developed a theory that free radicals and antioxidants are at the heart of human aging. Harman’s idea was never anything more than a hunch, and subsequent research proved it to be wrong, but nonetheless the idea has taken hold and will not go away. The sale of antioxidant supplements alone is now worth well over $2 billion a year.

"It is a massive racket," David Gems of University College London told Nature in 2015. "The reason the notion of oxidation and ageing hangs around is because it is perpetuated by people making money out of it."

"Some studies have even suggested that antioxidant supplements can be harmful", The New York Times has noted. The principal learned journal of the field, Antioxidants and Redox Signaling, noted in 2013 that "antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death."

— p372

Ok, fine, some suckers waste their money on useless supplements — what’s the big problem? The problem for me is that people believe antioxidants are categorically beneficial for health and I know for a fact that is not correct. I know this because antioxidant preservatives will reliably trigger devastating migraines in my head.

What is very insidious is that "vitamin" E is one such molecule. The so-called vitamin E is something almost no humans ever have a deficiency of. Ingesting huge quantities can not make any sense at all when promoting health. However, at a high enough concentration, this kind of molecule (tocopherols) has the property of killing microbes. This is why it is liberally added to many processed foods.

I always read the ingredients of everything I eat and if I ever see vitamin E or any kind of tocopherols I will not eat it. While the quote from the book says that migraines are almost wholly a mystery, I have at least figured out exactly what cause mine and it’s garbage not-food like tocopherols. One of the things you often see next to the tocopherol item in an ingredients list is in parentheses: "(for freshness)".

I strongly advise anyone to avoid eating anything which has on its ingredient list "for freshness". (Especially TBHQ, BHT, BHA, and vitamin E aka d-tocopherols). Sure, unlike me, you may be able to not have your next 20 hours destroyed by pain far worse than any other you’ve ever imagined. But consider when a packaged food company has to add that crap, the product is definitely not fresh. Or wholesome in any way. It really is quite suspect. By avoiding such garbage, you will find that you’re eating real food that is simply higher in quality and better for you in all ways.

Some people believe that you can ignore those weird mystery ingredients in processed food. I however believe that you can have only one of the following two beliefs about small molecule chemistry.

  • Small molecule chemistry doesn’t do much and is safe to apply arbitrarily in food products.

Or!

  • Small molecule chemistry does something and pharmacological products are not completely inert.

Common sense and I lean heavily toward the latter. The complication is that even when a small molecule ligand binds correctly with its targeted receptor perfectly, it is inevitable that it will also bind with other unintended receptors. Which ones? As with almost everything that could be known about biochemistry and biology in general: we just do not know.

UPDATE 2020-02-20

Although this website has a bit of the character of a crazy homeless person on the bus, this description of the essential function of what antioxidants (endogenous and otherwise) decompose make it clear that simplistically getting rid of all reactive oxygen species (free radicals) may not be such a brilliant plan.

Even though the presentation of this material on this website is bizarre it seems reasonably well grounded and as factual as it can be. If nothing else this website is interesting and shows clearly that things are more complex than a simple "unlimited antioxidants are always good" narrative.

UPDATE 2020-03-11

You don’t have to read the article or the paper it’s writing about. Just check out the title and subtitle.

Bacteria in our guts break down dozens of popular drugs - Study suggests drugmakers should consider bacterial metabolism when designing and testing new drugs

The point there is that no matter what drugs you ingest, the metabolites that slosh around your system after your microbiome finishes randomly modifying them are going to be individual-specific and very hard to usefully predict. Let’s not even think about the implications to the endeavor I spent a lot of my career working on, rational drug design.

And…

My blog post here may answer a question posed in the title of another article I found today: Why Doctors Still Offer Treatments That May Not Help.

Regarding medical treatments initiated by doctors, the article says…

According to the analysis, there is evidence of some benefit for just over 40 percent of them. Only 3 percent are ineffective or harmful; a further 6 percent are unlikely to be helpful. But a whopping 50 percent are of unknown effectiveness.

Note that this says "some" benefit, not a cure!

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