Author Archives: luysii

see first post

At a wedding . . .

I was a wedding last weekend which was the first Jewish wedding in the bride’s family in 100 years, the parents having emigrated from Russia 28 years ago where such things were banned. It shows what progressive secular religion can do if given a chance and the power to do it.

Like all religions, it seeks to dominate others.

The parallels between progressive secular religion and others are so uncanny and complete, they’re not even parallels.

Example1  — sinecures — a device used by the clerisy to support incompetent progeny — Hunter Biden and Burisma and the Chinese fund.

Example 2 — indulgences — buying forgiveness for sin by donating to the church — Jeffrey Epstein’s contributions to Planned Parenthood and NOW.  Martin Luther would have no problem recognizing this as such.

Example 3 — good works buying absolution for sin.  Clinton’s rape and abuse of women forgiven by legislation on reproductive rights.

Those are just the low hanging fruit.  Moving on to actual theology, social guilt and white privilege is simply original sin in modern garb.  You need do nothing to acquire it, and you can’t get rid of it.

Moving on to the old testament — there are sins which can not be forgiven, for which the punishment is personal destruction — wearing blackface as an adolescent, writing against homosexual marriage decades ago etc. etc.  Here comes the twitter mob.

Then there is heresy.   One such is admiring conventional religion.  This calls forth the twitter mob experiencing the rush that comes from expressing their moral superiority.

The worst (recent) example is the opprobrium heaped on Botham Jean for hugging his brother’s murderer.  The harpies were in full cry, but it is impossible for me to watch that video without being moved.  Viewed through the narrow lens of race it is disturbing, but viewed in the much wider and more appropriate lens of human emotion it is incredibly powerful.

Progressive secular theology (for that is what it is) gives no quarter.



Eat meat without worry (but you can feel guilty if you want)

From an article in the New York Times 1 October 2019  “In a statement, scientists at Harvard warned that the conclusions “harm the credibility of nutrition science and erode public trust in scientific research” “.

Strong stuff indeed.  Are they talking about Trump and the post-truth era?

Not at all. They are talking about a study in the Annals of Internal Medicine saying that the evidence that meat is bad for you is lousy, and not to be relied on.

To which I say, Amen.

— Here’s a link to the actual article —  — which the journal claims is freely available.

The authors looked at large numbers articles on the health effects of meat consumption to see if the conclusions that meat was harmful were warranted by a statistical analysis of the study.  In most cases they weren’t, or if they were, the evidence was weak.

Naturally there has been a counterattack, saying that one of the authors accepted money from the meat industry.  So what.  The studies are out there in print.  Statistical analysis is statistical analysis, and critics are welcome to perform their own statistical analyses of the papers.

This is far from the only example of dietary advice based more on hope and ideology than anything else.  A copy of two old posts (11/18 and 3/15) on the subject appears after the **

“erode public trust in scientific research”

This is exactly what I used to worry about when hysteria about common things causing cancer was at its height.  Joe sixpack’s logical conclusion to such things was — what the Hell, if everything causes cancer I might as well smoke.

Here are four things which medicine knows which are very likely to be true 50 years from now

l. Don’t smoke
2. Don’t drink too much (over 2 drinks a day), or too little (no drinks). Study after study has shown that mortality is lowest with 1 – 2 drinks/day
3. Don’t get fat — by this I mean fat (Body Mass Index over 30) not overweight (Body Mass Index over 25). The mortality curve for BMI in this range is pretty flat. So eat whatever you want, it’s the quantities you must control.
4. Get some exercise — walking a few miles a week is incredibly much better than no exercise at all — it’s probably half as good as intense workouts — compared to doing nothing.

Not very sexy but likely to still be true in 50 years.

There is tremendous resistance of researchers to having their conclusions disputed.  Another brouhaha concerns how much you should weigh.  Over 50 the lowest mortality rates occur with body mass indices (BMIs) between 25 and 30 (which currently is called overweight). A post on the subject appears after the ****BMI


Published 11/18

Eat what you want, no one really knows what a healthy diet is.

All dietary recommendations are based on sand so eat what you want and enjoy your Thanksgiving meal.  How can I say this? Just in time for Thanksgiving, the  august pages of Science contain the following article entitled “Dietary Fat:  From Foe to Friend ?” [ Science vol. 362 pp.  764 – 770 ’18 ].  Think I’m kidding?  Here is a verbatim  list of NINE current controversies (translation — not settled science) from the article.

1. Do diets with various carbohydrate-to-fat proportions affect body composition (ratio of fat to lean tissue) independently of energy intake? Do they affect energy expenditure independently of body weight?

2. Do ketogenic diets provide metabolic benefits beyond those of moderate carbohydrate restriction? Can they help with prevention or treatment of cardiometabolic disease?

3. What are the optimal amounts of specific fatty acids (saturated, monounsaturated, polyunsaturated) in the context of a very-low-carbohydrate diet?

4. What is the relative importance for cardiovascular disease of the amounts of LDL cholesterol, HDL cholesterol, and triglycerides in the blood, or of lipoprotein particle size, for persons on diets with distinct fat-to-carbohydrate ratios? Are other biomarkers of equivalent or greater importance?

5. What are the effects of dietary fat amount and quality across the lifespan on risk of neurodegenerative, pulmonary, and other diseases that have not been well studied?

6. What are the long-term efficacies of diets with different carbohydrate-to-fat proportions in chronic disease prevention and treatment under optimal intervention conditions (designed to maximize dietary compliance)?

7. What behavioral and environmental interventions can maximize long-term dietary compliance?

8. What individual genetic and phenotypic factors predict long-term beneficial outcomes on diets with various fat-to-carbohydrate compositions? Can this knowledge inform personalized nutrition, with translation to prevention and treatment?

9. How does variation in the carbohydrate-to-fat ratio and in sources of dietary fat affect the affordability andenvironmental sustainability of diets?

Then totally ignoring the above controversies — they say they agree on such bromides as

l. With a focus on nutrient quality, good health and low chronic disease risk can be achieved for many people on diets with a broad range of carbohydrate-to-fat ratios.

2. Replacement of saturated fat with naturally occurring unsaturated fats provides health benefits for the general population. Industrially produced trans fats are harmful and should be eliminated. The metabolism of saturated fat may differ on carbohydrate-restricted diets, an issue that requires study.

Basically I think you can eat what you want. Perhaps some day the research needed to base dietary recommendations on solid data will have been done, but that day is not here.

Here is an older post (March 2015) written when the dietary guidelines were changed yet again.

The dietary guidelines have been changed — what are the faithful to believe now ?

While we were in China dietary guidelines shifted. Cholesterol is no longer bad. Shades of Woody Allen and “Sleeper”. It’s life imitating art.

Sleeper is one of the great Woody Allen movies from the 70s. Woody plays Miles Monroe, the owner of (what else?) a health food store who through some medical mishap is frozen in nitrogen and is awakened 200 years later. He finds that scientific research has shown that cigarettes and fats are good for you. A McDonald’s restaurant is shown with a sign “Over 795 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 000 Served”

Seriously then, should you believe any dietary guidelines? In my opinion you shouldn’t. In particular I’d forget the guidelines for salt intake (unless you actually have high blood pressure in which case you should definitely limit your salt). People have been fighting over salt guidelines for decades, studies have been done and the results have been claimed to support both sides.

So what’s a body to do? Well here are 4 things which are pretty solid (which few docs would disagree with, myself included)

l. Don’t smoke
2. Don’t drink too much (over 2 drinks a day), or too little (no drinks). Study after study has shown that mortality is lowest with 1 – 2 drinks/day
3. Don’t get fat — by this I mean fat (Body Mass Index over 30) not overweight (Body Mass Index over 25 and under 30). The mortality curve for BMI in this range is pretty flat. So eat whatever you want, it’s the quantities you must control.
4. Get some exercise — walking a few miles a week is incredibly much better than no exercise at all — it’s probably half as good as intense workouts — compared to doing nothing.

Not very sexy, but you’re very unlikely to find anyone telling you the opposite 50years from now.

Typical of the crap foisted on the public (vitamin D and fish oil prevents cancer, heart disease and all sorts of horrible things) is it’s refutation once a decent study has been done

A large-scale trial has found no evidence that two popular supplements reduce the risk of cancer or the combined risk for a trio of cardiovascular problems.

JoAnn Manson at Brigham and Women’s Hospital in Boston, Massachusetts, and her colleagues recruited more than 25,000 healthy men and women in their fifties or older for a trial examining the effects of fish oil and vitamin D supplements. Some participants took both, others took only one type and the remaining participants took two placebos.

After an average of 5.3 years in the trial, participants who had taken fish oil had essentially the same likelihood of cancer as people who hadn’t. Compared with the placebo group, the fish-oil group had a lower rate of heart attack but the same rate of total cardiovascular events, a category that included heart attacks, strokes and death from cardiovascular disease.

Vitamin D supplements conferred no clear health benefits against cardiovascular disease or cancer, compared with a placebo.

The incredible chemical intelligence of an inanimate enzyme

God, I love organic chemistry.  Here’s why.  A recent Nature paper [ vol. 573 pp. 609 – 613 ’19 ] shows that an enzyme uses a Newton’s cradle to shuttle an allosteric effect some 25 Angstroms between two catalytic centers.  I’d never heard of Newton’s cradle, but you’ll recognize it from the picture when you follow this link —  It is a device used to show that most classic example of classical (e.g. nonQuantum) physics — the conservation of momentum.

This despite Feynman’s statement in the Feynman Lectures on Physics Vol I. p 12 – 6 “Molecular forces have never been satisfactorily explained on a basis of classical physics” it takes quantum mechanics to understand them fully.”  True but chemists think of reactions in terms of classic physics all the time (harmonic oscillators as bond models, billiard ball collections hitting each other as in SN2).

To understand what is going on, you must understand the low barrier hydrogen bond. [ Proc. Natl. Acad. Sci. vol. 95 pp. 12799 – 12802 ’98 ] which is a type of hydrogen bond postulated to occur in enzymes, in which the potential barrier to shifting the hydrogen from one nucleophile (oxygen or nitrogen) in the bond to another is quite low (2 Kcal/mole). The nucleophiles are closer together than they usually are ( e. g. the interatomic distance between the two heteroatoms is smaller than the sum of their van-der-Waals radii (≤ 2.55 Å for O–O pairs; ≤ 2.65 Å for O–N pairs), and the hydrogen is essentially covalently bonded to both. This makes the hydrogen bonds quite strong (10 – 20 Kcal/mole). They think that such bonds stabilize intermediates in enzymatic reactions (such as that formed by the catalytic triad of a serine protease).

Regard the low barrier hydrogen bond as what glues the balls together in the Wiki picture.

The enzyme described in the paper (transketolase) uses a chain of low barrier hydrogen bonds as a communication channel between the two remote (25 Angstroms away) active sites in the obligate functional dimers.

The still pictures have to be seen to be believed.  I can’t wait for the movie.

Neurons synapsing with tumor cells, unbelievable but true

As a neurologist, I’ve seen more than enough breast cancer metastatic to the brain.  I never, in a million years, would have though that brain neurons would be forming synapses with them, helping them grow in the process.  But that’s exactly what two papers in the current Nature prove [ Nature vol. 573 pp. 499 – 501, 526 – 531 ’19 ]

The evidence is pretty good.  There are electron micrographs of brain metastases showing breast cancer cells acting like glia, surrounding a synapse between two neurons.  There are synaptic vesicles right next to the presynaptic membrane of the neuron which is apposed to the postsynaptic neuron (that’s what a synapse is after all). They are also present in the same neuron, whose membrane is tightly apposed  to a tumor cell, which stains positive for a type of glutamic acid receptor (the NMDAR).

Breast cancer types have been subdivided by the proteins they contain and don’t contain.  A particularly nasty one, is called triple negative — lacking the estrogen receptor the progesterone receptor and the herceptin receptor. Triple negative breast cancers account for 15 – 20% of all breast cancers, and some 40% of this group will die of brain metastases.  This paper may explain why.

The paper did some work using immunodeficient mice, transplanting human triple negative breast cancer cells into the brain.  Synapses formed between the mouse neurons and the breast cancer cells.

It is known that NMDAR signaling promotes growth tumor growth in other cancer types, and that increased NMDAR expression in breast cancer cells is associated with poor prognosis.

It is incredible to think that the brain is forming synapses with metastatic tumor cells to help them grow, but that’s what must be faced.

The excellent study confined itself to breast cancer metastatic to brain, but the study of other tumors (particularly lung) is sure to follow.

Book idea proposal

While up in Nova Scotia (where the people are as friendly as midwesterners) on vacation reading Feynman I got an idea for a book.  Unfortunately, I don’t think anyone has the breadth of knowledge of physics that Feynman did, so no single person can write it.

Remember that the Feynman lectures were delivered in 1963 – 4.  The authors of the Millennium edition noted that > 1,000 errors were corrected in the various editions (which is a good reason to buy it, if you’re studying it on your own).  But almost none of them were conceptual.

So the lectures are  true as of 1964 and brilliant to boot.  As Kip Thorne notes in “Modern Classical Physics”  — “The three-volume Feynman Lectures on Physics had a big influence on several generations of physicists and even more so on their teachers.Both of us (Blandford and Thorne) are immensely indebted to Richard Feynman for shaping our own approaches to physics”.

The idea for the book came as early as p. 2-7 in Volume I, where Feynman says “no phenomenon directly involving a frequency has yet been detected above approximately 10^12 cycles per second”.  Well we’re up to 10^18 presently and shooting higher.

p 3-5 “all enzymes are proteins.”  Not so and a Nobel was won for the first RNA enzyme to be discovered.

p. 7 – 7  What is holding galaxies together — a mention of dark matter would be interesting.

p. 9 – 9 “A very good computing machine may take 1 microsecond to do an addition”  — we’re up to 10^18 exaFlops (of floating point calculations) not addition.

Well you get the idea.  I have no idea what the size of the market would be, but I’d love to see something like this.

Something similar was actually done with the Origin of Species.  Darwin’s Ghost by Steve Jones (published in 1999) updates Darwin’s book, the Origin of Species (published 1999)  to contemporary thinking (and knowledge) chapter by chapter.   It is fascinating to go through both together.

The book would be one of the few things better done by a committee

Off to Nova Scotia

No posts for a week or two.  If you’re ever up that way, the Hopewell Rocks in New Brunswick are not to be missed.  Our friends say Cape Breton is magnificent.  We hope to see it.   Taking Feynman vol. I along.  I can’t say enough good about it, but I doubt that it’s the way to learn physics the first time, but if you’ve had undergraduate physics, it will explain what is really going on.

Hell of a way for a cell to defend itself

Imagine it’s Dodge City in the 1880’s and rustlers and gunslingers are shooting up the town.  What do Wyatt Earp and Bat Masterson do?  They don’t call in the cavalry.  They open the jail.   With the town in flames the army moves in, destroying much of the town in the process.

Crazy?  Yes.  But this is a pretty good analogy to how retroviruses are used to help fight off infection if Proc. Natl. Acad. Sci. vol. 116 pp. 17399 – 17408 ’19 is correct

Endogenous retroviruses constitute around 10% of our genome — that’s 320,000,000 nucleotides. Normally they are kept locked up in a tightly condensed mess of DNA and proteins called heterochromatin, so their genome can’t be transcribed and cause trouble.  It takes a lot to lock them up — TRIM28 acting in concert with zinc finger proteins, SUMO, a histone methyltransferase (SETDB1) and last but not least NuRD (not NeRD) — Nucleosome Remodeling and Deacetylation complex.

But when a variety of cells are infected with a variety of influenza viruses, they are let loose because the heterochromatin breaks up, the endogenous retroviruses are freed producing lots of double stranded RNA.  This is sensed as nonSelf, by Pattern Recognition Receptors (PRRs) strongly activating antiviral immunity.

The key thing in the repressive complex is SUMO, a protein resembling ubiquitin which gloms onto lysines like ubiquitin.  To be efficient in repressing the retroviruses, TRIM28 must be SUMOylated.  In some way influenza virus infection results in nonSUMOylated TRIM28.  The authors note that the mechanism of the switch in SUMOylation status ‘has yet to be precisely defined’.  I’m sure the authors are working on it, but who in the world would have thought that cells would use retroviruses as a defense mechanism.  Not me, certainly.

Prolegomena to reading Fall by Neal Stephenson

As a college freshman I spent hours trying to untangle Kant’s sentences in “Prolegomena to Any Future Metaphysics”  Here’s sentence #1.   “In order that metaphysics might, as science, be able to lay claim, not merely to deceitful persuasion, but to insight and conviction, a critique of reason itself must set forth the entire stock of a priori concepts, their division according to the different sources (sensibility, understanding, and reason), further, a complete table of those concepts, and the analysis of all of them along with everything that can be derived from that analysis; and then, especially, such a critique must set forth the possibility of synthetic cognition a priori through a deduction of these concepts, it must set forth the principles of their use, and finally also the boundaries of that use; and all of this in a complete system.”

This post is something to read before tackling “Fall” by Neal Stephenson, a prolegomena if you will.  Hopefully it will be more comprehensible than Kant.   I’m only up to p. 83 of a nearly 900 page book.  But so far the book’s premise seems to be that if you knew each and every connection (synapse) between every neuron, you could resurrect the consciousness of an individual (e.g. a wiring diagram).  Perhaps Stephenson will get more sophisticated as I proceed through the book.  Perhaps not.  But he’s clearly done a fair amount neuroscience homework.

So read the following old post about why a wiring diagram of the brain isn’t enough to explain how it works.   Perhaps he’ll bring in the following points later in the book.

Here’s the old post.  Some serious (and counterintuitive) scientific results to follow in tomorrow’s post.

Would a wiring diagram of the brain help you understand it?

Every budding chemist sits through a statistical mechanics course, in which the insanity and inutility of knowing the position and velocity of each and every of the 10^23 molecules of a mole or so of gas in a container is brought home.  Instead we need to know the average energy of the molecules and the volume they are confined in, to get the pressure and the temperature.

However, people are taking the first approach in an attempt to understand the brain.  They want a ‘wiring diagram’ of the brain. e. g. a list of every neuron and for each neuron a list of the other neurons connected to it, and a third list for each neuron of the neurons it is connected to.  For the non-neuroscientist — the connections are called synapses, and they essentially communicate in one direction only (true to a first approximation but no further as there is strong evidence that communication goes both ways, with one of the ‘other way’ transmitters being endogenous marihuana).  This is why you need the second and third lists.

Clearly a monumental undertaking and one which grows more monumental with the passage of time.  Starting out in the 60s, it was estimated that we had about a billion neurons (no one could possibly count each of them).  This is where the neurological urban myth of the loss of 10,000 neurons each day came from.  For details see

The latest estimate [ Science vol. 331 p. 708 ’11 ] is that we have 80 billion neurons connected to each other by 150 trillion synapses.  Well, that’s not a mole of synapses but it is a nanoMole of them. People are nonetheless trying to see which areas of the brain are connected to each other to at least get a schematic diagram.

Even if you had the complete wiring diagram, nobody’s brain is strong enough to comprehend it.  I strongly recommend looking at the pictures found in Nature vol. 471 pp. 177 – 182 ’11 to get a sense of the  complexity of the interconnection between neurons and just how many there are.  Figure 2 (p. 179) is particularly revealing showing a 3 dimensional reconstruction using the high resolutions obtainable by the electron microscope.  Stare at figure 2.f. a while and try to figure out what’s going on.  It’s both amazing and humbling.

But even assuming that someone or something could, you still wouldn’t have enough information to figure out how the brain is doing what it clearly is doing.  There are at least 3 reasons.

l. Synapses, to a first approximation, are excitatory (turn on the neuron to which they are attached, making it fire an impulse) or inhibitory (preventing the neuron to which they are attached from firing in response to impulses from other synapses).  A wiring diagram alone won’t tell you this.

2. When I was starting out, the following statement would have seemed impossible.  It is now possible to watch synapses in the living brain of awake animal for extended periods of time.  But we now know that synapses come and go in the brain.  The various papers don’t all agree on just what fraction of synapses last more than a few months, but it’s early times.  Here are a few references [ Neuron vol. 69 pp. 1039 – 1041 ’11, ibid vol. 49 pp. 780 – 783, 877 – 887 ’06 ].  So the wiring diagram would have to be updated constantly.

3. Not all communication between neurons occurs at synapses.  Certain neurotransmitters are generally released into the higher brain elements (cerebral cortex) where they bathe neurons and affecting their activity without any synapses for them (it’s called volume neurotransmission)  Their importance in psychiatry and drug addiction is unparalleled.  Examples of such volume transmitters include serotonin, dopamine and norepinephrine.  Drugs of abuse affecting their action include cocaine, amphetamine.  Drugs treating psychiatric disease affecting them include the antipsychotics, the antidepressants and probably the antimanics.

Statistical mechanics works because one molecule is pretty much like another. This certainly isn’t true for neurons. Have a look at  This is of the cerebral cortex — neurons are fairly creepy looking things, and no two shown are carbon copies.

The mere existence of 80 billion neurons and their 150 trillion connections (if the numbers are in fact correct) poses a series of puzzles.  There is simply no way that the 3.2 billion nucleotides of out genome can code for each and every neuron, each and every synapse.  The construction of the brain from the fertilized egg must be in some sense statistical.  Remarkable that it happens at all.  Embryologists are intensively working on how this happens — thousands of papers on the subject appear each year.


Feynman and Darwin

What do Richard Feynman and Charles Darwin have in common?  Both have written books which show a brilliant mind at work.  I’ve started reading the New Millennium Edition of Feynman’s Lectures on Physics (which is the edition you should get as all 1165 errata found over the years have been corrected), and like Darwin his thought processes and their power are laid out for all to see.  Feynman’s books are far from F = ma.  They are basically polished versions of lectures, so it reads as if Feynman is directly talking to you.  Example: “We have already discussed the difference between knowing the rules of the game of chess and being able to play.”  Another: talking about Zeno  “The Greeks were somewhat confused by such problems, being helped, of course, by some very confusing Greeks.”

He’s always thinking about the larger implications of what we know.  Example: “Newton’s law has the peculiar property that if it is right on a certain small scale, then it will be right on a larger scale”

He then takes this idea and runs with it.  “Newton’s laws are the ‘tail end’ of the atomic laws extrapolated to a very large size”  The fact that they are extrapolatable and the fact that way down below are the atoms producing them means, that extrapolatable laws are the only type of physical law which could be discovered by us (until we could get down to the atomic level).  Marvelous.  Then he notes that the fundamental atomic laws (e.g. quantum mechanics) are NOTHING like what we see in the large scale environment in which we live.

If you like this sort of thing, you’ll love the books.  I don’t think they would be a good way to learn physics for the first time however.  No problems, etc. etc.  But once you’ve had exposure to some physics “it is good to sit at the feet of the master” — Bill Gates.

Most of the readership is probably fully engaged with work, family career and doesn’t have time to actually read “The Origin of Species”. In retirement, I did,and the power of Darwin’s mind is simply staggering. He did so much with what little information he had. There was no clear idea of how heredity worked and at several points he’s a Lamarckian — inheritance of acquired characteristics. If you do have the time I suggest that you read the 1859 book chapter by chapter along with a very interesting book — Darwin’s Ghost by Steve Jones (published in 1999) which update’s Darwin’s book to contemporary thinking chapter by chapter.  Despite the advances in knowledge in 140 years, Darwin’s thinking beats Jones hands down chapter by chapter.

Good luck, RBG

Once again the press seems to dancing around a serious health problem of major public figure without saying just what it is.  Just about everyone admires RBG, but saying “The tumor was treated definitively and there is no evidence of disease elsewhere in the body” as the Supreme Court announced yesterday sounds wonderful doesn’t it?  Except that it isn’t.  8 months ago she had two metastatic tumors removed from her lung.  Sometimes it is possible to tell the tissue of origin from slides made from the tumors, but, as far as I can tell, this information was never released.  Now they say there is no sign of tumor elsewhere in her body (just as they said 8 months ago).

One hopes for the best for her.  Agree or disagree with her political philosophy, she is an admirable, brilliant and likable individual who has overcome a lot over the years.

Unfortunately Justice Ginsburg has metastatic cancer.  Her prognosis is not good.  As President Trump said “I’m hoping she’s going to be fine. She’s pulled through a lot. She’s strong, very tough.”

She had better be.

Addendum 28 August ’19

We’ll see how the right responds when RBG passes.  Here’s leftist folk hero Bill Maher on the death of one of the Koch brothers.  There are other similar responses.