Why you should go to Princeton if they accepted you

In a few months it will be 70 years since I entered Princeton as a freshman.  All alumni are asked to interview admission candidates and describe Princeton to them. I have nothing useful to tell applicants about the current situation at Princeton.  The campus ended at Pyne Hall back then and class size was just over seven hundred — both have doubled in size since 1956.

Alumni interviewers might still find what follows useful, assuming Princeton’s focus on the undergraduate hasn’t changed.  It would be helpful to show it to very high caliber candidates likely to be deciding on Princeton vs. other Ivies.  Feel free to share this with them or anyone else.

Back then Freshmen premeds took physics (not honors physics, not physics for poets).  The prof was a mild mannered man who wore a jacket and tie and could have been a shoe salesman, or so I thought until he brought in his friend and colleague Neils Bohr to speak to us.  Bohr was old and weak and had only a few years to live, but he sat in a chair and mumbled to us in what appeared to be Danish.  This fall it will be 70 years, but I can still see him. The physics prof was John Wheeler, he of the black hole and wormholes, teacher of Feynman etc.etc..  And this was why Princeton was such a great place for undergraduates.  They didn’t hide their best and made sure they taught undergraduates.  Hopefully it is the same now.

Similarly, the exposure to my undergraduate chemistry advisor Paul Schleyer Princeton ’52 was intense and formative.  Here’s what it was like — He was a marvelous undergraduate advisor, only 7 years out from his own Princeton degree when we first came in contact with him and a formidable physical and intellectual presence even then. His favorite opera recording, which he somehow found a way to get into the lab, was don Giovanni’s scream as he realized he was to descend into Hell. I never had the courage to ask him if the scars on his face were from dueling.

We’d work late in the lab, then go out for pizza. In later years, I ran into a few Merck chemists who found him a marvelous consultant. However, back in the 50’s, we’d be working late, and he’d make some crack about industrial chemists being at home while we were working, the high point of their day being mowing their lawn.

I’d say the intense interaction with faculty was typical back then, hopefully it is the same now.

So I switched to chemistry and in the fall of 1960, I was off to chemistry graduate school at Harvard (which Schleyer called Mecca).  The department was terrific and I personally interacted with 7 guys doing the work which would later win them the Nobel in Chemistry — Woodward, Corey, Lipscomb, Gilbert, Hoffman, Bloch and Karplus.  To my knowledge the only one teaching undergraduates was Konrad Bloch.  So who was teaching Harvard undergraduates — none other than yours truly 2 years further along in organic chemistry than they were spending 6 – 8 hours a week with them as a teaching assistant in orgo lab.  Compared to what I’d  received, I felt they were being cheated.

Hopefully things are the same at Princeton now.  They certainly were 10 years later.  Tony Zee ’66 friend and Physics Prof at UC Santa Barbara heard about a future physics Nobel in the monthly undergraduate physics major evening get together by the faculty member who did the work.

Luysii Princeton ‘60

January 17, 2026 – 11:53 am Categories: Chemistry (relatively pure), Social issues ( be civil ! ) | Post a comment

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Bari Weiss takes staff of 60 minutes back to journalism school

One son majored in journalism at the university of Minnesota.  Although he never wrote for a newspaper or TV, he found what he learned (focus on the important, be brief, be clear, get the facts straight) useful in whatever he did — MicroSoft, VH1, MTV, MFA at USC in animation, teaching it in Hong Kong and Taiwan, etc. etc.

So it was particularly interesting to read Bari Weiss’s reasoning as to why she cut a 60 minutes program 2 days ago.  Basically she listed the reasons the program was journalistically incompetent and effectively sent its creators back to journalism school.  Here is an exact copy of what she wrote to them. My comments  are interspersed in bold

“Hi all,

I’m writing with specific guidance on what I’d like for us to do to advance the CECOT story  (About the horrific prison conditions in San Salvidor the US sent Venezuelans). I know you’d all like to see this run as soon as possible; I feel the same way. But if we run the piece as is, we’d be doing our viewers a disservice.

  • Last month many outlets, most notably The New York Times, exposed the horrific conditions at CECOT. Our story presents more of these powerful testimonies—and putting those accounts into the public record is valuable in and of itself. But if we’re going to run another story about a topic that has by now been much-covered we need to advance it (you’re beating a dead horse and adding nothing new). Among the ways to do so: does anyone in the administration or anyone prominent who defended the use of the Alien Enemies Act now regret it in light of what these Venezuelans endured at CECOT? That’s a question I’d like to see asked and answered (here’s one thing you should have done but didn’t do).
  •  At present, we do not present the administration’s argument for why it sent 252 Venezuelans to CECOT (did you ask, or did you decide it was beneath contempt). What we have is Karoline Leavitt’s soundbite claiming they are evildoers in America (rapists, murderers, etc.). But isn’t there much more to ask in light of the torture that we are revealing? Tom Homan and Stephen Miller don’t tend to be shy. I realize we’ve emailed the DHS spox, but we need to push much harder to get these principals on the record.
  • The data we present paints an incongruent picture. Of the 252 Venezuelans sent to CECOT, we say nearly half have no criminal histories (an example of antiAdministration framing which is why few believe 60 minutes and the legacy press in general). In other words, more than half do have criminal histories. We should spend a beat explaining this (why didn’t you?) . We then say that only 8 of the 252 have been sentenced in America for violent offenses. But what about charged? My point is that we should include as much as we can possibly know and understand about these individuals.
  • Secretary Noem’s trip to CECOT. We report that she took pictures and video there with MS-13 gang members, not TdA members, with no comment from her or her staff about what her goal on that trip was, or what she saw there, or if she had or has concerns about the treatment of detainees like the ones in our piece. (You didn’t even ask hard questions to Noem or the administration) I also think that the ensuing analysis from the Berkeley students is strange. The pictures are alarming; we should include them. But what does the analysis add?
  • We need to do a better job of explaining the legal rationale by which the administration detained and deported these 252 Venezuelans to CECOT. It’s not as simple as Trump invoking the Alien Enemies Act and being able to deport them immediately. And that isn’t the administration’s argument. The admin has argued in court that detainees are due “judicial review”—and we should explain this, with a voice arguing that Trump is exceeding his authority under the relevant statute, and another arguing that he’s operating within the bounds of his authority (again something you should have reported on but didn’t). There’s a genuine debate here. If we cut down Kristi Noem analysis we’d have the time.

My general view here is that we do our viewers the best service by presenting them with the full context they need to assess the story. In other words, I believe we need to do more reporting here.

I am eager and available to help. I tracked down cell numbers for Homan and Miller and sent those along. Please let me know how I can support you (even though you belong back in journalism school).

Yours,

Ba”

I’ve never liked 60 minutes, and purely for medical reasons.  Back when I was a practicing clinical neurologist ’72 – ’00, they were a fount of medical misinformation.  I spent a fair of time cleaning up after the elephants.  Particularly loathsome was the time they argued that mercury in fillings caused multiple sclerosis.  They said it once.  It took me multiple one on ones with my frightened MS patients to try to clear things up.

December 23, 2025 – 3:38 pm Categories: Social issues ( be civil ! ) | Post a comment

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The New York Times is still sitting shiva for DEI

On page 1 of the New York Times for 13 December ’25 appears the following “University of Texas Is Brought To Heel by Conservative Critics”.  To which I say Mazel Tov.

Here is how UT treated Steven Weinberg, one of the giants of 20th century  physics.

“Steve also once told me that, when he (like other UT faculty) was required to write a statement about what he would do to advance Diversity, Equity, and Inclusion, he submitted just a single sentence: “I will seek the best candidates, without regard to race or sex.” I remarked that he might be one of the only academics who could get away with that.”

This from a blog of Scott Aaronson who taught at UT with Weinberg https://scottaaronson.blog/?p=5566.

That the intellectual Lilliputians of DEI would have the chuzpah to think they had the right to require him to write a statement like that shows how entrenched DEI was back then.

December 13, 2025 – 9:44 pm Categories: Social issues ( be civil ! ) | Comments (1)

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The New York Times unintentionally resurrects an old Jewish Joke

First the joke, then its resurrection by the Times.

Back in the day when people read magazines, a gifted writer, Morris Paranoidowitz drove his editor crazy.   “Morris, Morris, give it a rest.  All you do is write about Jews and their troubles.  Surely you can write about something else.  Why don’t you write about Elephants?

Morris thought a bit, and a few weeks later over the transom came his manuscript “The Elephant and the Jewish Problem.”

Now for the resurrection

Two days ago in the Times opinion section appeared “The Thrill of the Heist”

It starts off reasonably enough “Every once in a while a story comes along formed by a perfect synergy of comprehensible crime and real-time intrigue” ….

Paragraph #2 starts off —  “There’s been a panoply of reactions to this incident.” . . .

Paragraph #3  is unexceptionable “Americans have a longstanding emotional connection with France” . . . and contains the word frisson showing the author took French 101

Paragraphs 4 and 5 are similarly on topic.

The sound of elephants charging across the veldt is heard in paragraph #6 (quoted in full)

“In some ways it’s a relief to read about quantifiable damage.  Devastating as the situation may be, it’s a release valve from the America we’re living in.  We’re daily being robbed in unwieldy ways as our cultural values are demonstrably diminished.  It’s hard to comprehend the full extent of the plundering the Trump administration is doing in plain sight: the endless conflicts of interest; the gleeful dismantling of the federal government.”

Morris lives ! !

Masochists can look up the article for 11 more paragraphs in the same vein.

Addendum: 26 October:  The NYT continues to show how depressed its staff is (and presumably its readership).  Here are some of the choices for the Sunday book review

l. Paper Girl:  A memoir of home and family in a fractured America.  The decline and fall of an Ohio town due to industrial closure.  Trump is mentioned but only for his attacks on transgender people.  The reviewer didn’t note that Trump won Ohio in part for trying to reverse industrial decline

2. 1929 Inside the greatest Crash in Wall Street history:  You’ve got to find something financially bad to put in the book review on a week when the stock market hit an all time high

3. McNamara at war:  reaching back 50+ years to wallow in a US military defeat

4. Goliath’s Curse: The History and Future of Societal Collapse  — I thought only religious cranks talked about end times.

These are half the nonFiction books the Times chose to review today.

You can call this mood syntonic/mood congruent if you want to impress, or just say the more informative “misery loves company”

 

October 25, 2025 – 5:20 pm Categories: Social issues ( be civil ! ) | Post a comment

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The dementia that wasn’t there

You don’t need a license to think.  That’s what’s so much fun about reading the scientific literature (Nature, Science, PNAS etc. etc.) and, even in this case, the New York Times.   You’re seeing fresh data that nobody except the authors has had their hands on.

An article in the Times 6 October ’25 even asks for your help.   It concerns Douglas Whitney, a 76 year old man who should be demented but isn’t.  He has one of three mutations (presenilin 2) known to cause Alzheimer’s disease.  His mother and 9 of her 13 siblings died young of Alzheimer’s.

Mr. Whitney made it to his 60s with no dementia and assumed he was free of the mutation, but a family member writing a book about Alzheimer’s asked him to  get checked.

He had the mutation. The docs tested for the mutation twice more because they didn’t believe it.

He is now 76 and doing well.   He has been studied out the gazoo, and a few things have turned up.  His brain is full of amyloid, the major component of the senile plaque of Alzheimer’s, more than those of his family members dying of it, probably because he has lived so long.  This is further evidence against the amyloid hypothesis of Alzheimer’s on which Billions of research and big Pharma dollars have been spent, with little of clinical use to the Alzheimer’s patient.

Clearly, finding out why Mr. Whitney isn’t demented will tell us tons about Alzheimer’s and, even better, probably suggest ways to treat it.

One of the researchers studying Whitney is quoted as saying “Hey, here’s a really important person, a really important case, and you need to help figure this out.”

Well, here’s my two cents based on the NYT story (I haven’t read the paper about him, and have no idea where to find it).

They mention that Mr. Whitney was in the Navy for two decades working for 10 years in the engine room of a steam propelled ship, where he was exposed to 110 Farhrenheit heat for 4 hours.   One of the zillion things they tested him for were heat shock proteins, something that goes all the way back to bacteria, to prevent the increased molecular motion (that heat actually is) from disturbing the delicate 3 dimensional structure of proteins.

It’s time to look at other Navy men with similar heat exposure and find out what the incidence of Alzheimer’s is in that population.  It’s also time to mine the United Kingdom biobank for people who take saunas (assuming they asked such a question), and see if they, in some way, have less Alzheimer’s disease.  Is the incidence of Alzheimer’s lower in northern populations where saunas are popular?   When I practiced in Montana I heard about ‘sweat houses’ that the Indians used, which sounds quite similar to saunas.

Here are a few of my notes on the the UK biobank.   It grows more impressive with each passing year.

      [ Nature vol. 562 pp.  163 -164, 194 – 195, 203 – 209, 210 – 216 ’18 ]  The UK biobank is based on 500,000 volunteers enrolled at ages 40 – 69.  All will be followed for over 30 years.  Blood and urine samples were obtained as well as a questionnaire about life style.  Initial enrollment took place from 2006 – 2010.  94% had European ancestry.

        [ Science vol. 382 pp. 980 ’23 ] The UK biobank just release the WHOLE genome sequences of 500,000 people.  Funding was from UK government, Wellcome, Amgen, AstraZeneca GSK and Johnson & Johnson. 

        BY 2010 the UK biobank had a prospective cohort of 500,000 people age 40 – 69 at recruitment (all of whom donated urine, saliva and blood in addition to filling out questionnaires, and consented access to their electronic health records).  Thanks to this the NHS will grow the 100,000 genomes project to sequence the genomes of 1,000,000 people through the NHS and the UK Biobank. 

      The only thing wrong is that these people are volunteers, hence atypical. <  [ Proc. Natl. Acad. Sci. vol. 119 e2203327119 ’22 ] — the inclination to participate in the UK BIobank is associated with educational attainment, BMI and participation in a dietary study. >  The All of Us Cohort study in the USA is trying targeted recruitment.

It’s time to look at the data we already have from the sauna angle.

As Mark Twain said ” There is something fascinating about science. One gets such wholesale returns of conjecture out of such a trifling investment of fact.”

 

 

 

October 15, 2025 – 9:24 pm Categories: Molecular Biology, Neurology & Psychiatry, Philosophical issues raised | Comments (1)

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How you know the New York Times is in trouble

When things aren’t going well for them, the New York Times trots out that reliable old villain, Richard Nixon.  And who better to do it than  legal analyst and reformed masturbator Jeffrey Toobin.  See “We’re in a Worst Place Then We Were Under Nixon” in Sunday’s NYT Opinion section 12 October 2025.  He’s a moral beacon for us all.

https://www.huffpost.com/entry/jeffrey-toobin-masturbation-disaster_n_64534da4e4b04616030ff32f

Addendum 12 October: From a good friend I choose to keep anonymous:

“We do seem to be in a worse place than Nixon since the vast majority of people disapproved of what he did. I don’t care much about Toobin one way or another, although his book on the Supreme Court is worth reading.”

If Toobin (or Hitler) says 2 + 2 = 4, I’ll buy it, but I won’t buy moral judgements from either. Nonetheless your distinction between Watergate times in the early 70s and the present is quite valid (having lived through both)

October 12, 2025 – 3:44 pm Categories: Social issues ( be civil ! ) | Comments (1)

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The war between Cajal and Golgi heats up after 120 years

Well, so much for ‘Settled Science’ Stare at the picture just below long and hard. It’s where the brain probably does its calculation — no, not the neuron in the center. No, not the astrocyte just above. Enlarge the picture many times. It’s all those tiny little circles and ellipses you see around the apical dendrite. They all represent nerve and glial processes. A few ellipses have very dark borders — this is myelin (which insulates them allowing them to conduct nerve impulses faster, and which also insulates them from being affected by the goings on of nerve processes next to them). Note that most of the nerve processes do NOT have myelin around them.

Now look at the bar at the lower right in the picture which tells you the magnification. 5 um is 5 microns or 50,000 Angstroms or roughly 10 times the wavelength of visible light (4,000 – 8,000 Angstroms). Look at the picture again and notice just how closely the little circles and ellipses are applied to each other (certainly closer than 1/10 of the bar). This is exactly why there was significant debate between two of the founders of neuroHistology — Camillo Golgi and Ramon Santiago y Cajal.

Unlike every other tissue in the body the brain is so tightly packed that it is impossible to see the cells that make it up with the usual stains used by light microscopists. People saw nuclei all right but they thought the brain was a mass of tissue with nuclei embedded in it (like a slime mold). It wasn’t until the late 1800′s that Camillo Golgi developed a stain which would now and then outline a neuron with all its processes. Another anatomist (Ramon Santiago y Cajal) used Golgi’s technique and argued with Golgi that yes the brain was made of cells. Fascinating that Golgi, the man responsible for showing nerve cells, didn’t buy it. This was a very hot issue at the time, and the two received a joint Nobel prize in 1906 (only 5 years after the prizes began).

Finally with the advent of electron microscopy with magnifications far higher than visible light, could we see how closely the elements of  brain cells were plastered against each other, much closer than anything visible light could see.

That’s where things stood until this week (e.g. the brain was made of distinct separated cells).  Well technology has marched on and we now know that what we thought were separated neurons are actually connected to each other by small tubes (called nanoTubes) whose diameter is about hundreds of nanoMeters (2,000 – 4,000 Angstroms or .2 to .4 microns) too small to show up even on the electron micrograph shown above.  So the brain is a syncytium just as Golgi thought — so much for settled science.

    The paper [ Science vol. 390 pp. 25 – 26, 43, eadr7403 pp. 1 –> 17  ’25 ] used superResolution radial fluctuation imaging, volumetric deconvolution, and optimized tissue preparation to see them. This allows the visualization of dendritic filopodia at nanoMeter scaled voxels.  This allowed preservation of the main component of nanotubes (actin a mucle protein).  A fibrous actin fluorogenic probe was used allowing visualization in cultured mouse cortical neurons and in ex vivo mouse cortex.

The authors were able to show the main component of the nanotubules is the muscle protein actin.  Stuff moves through the nanotubes between neurons, and one of them is the aBeta peptide of the senile plaque.  At this point we don’t know whether this is helpful (lowering the concentration of aBeta so plaques don’t form) or harmful (spreading the poison from one cell to another.  

In culture the nanotubes aren’t permanent but are always forming and breaking down in minutes to hours (but this is in cultures of neurons).

So add Nanotubes as another mechanism of communication between neurons along with synapses, gap junctions and extracellular vesicles.  The wiring diagram of the brain has just become even more complicated, and certainly more chanable with time.  It’s time to look at this old post again — https://luysii.wordpress.com/2011/04/10/would-a-wiring-diagram-of-the-brain-help-you-understand-it/

It’s good to be posting again.  My wife is doing better

October 7, 2025 – 11:28 pm Categories: Neurology & Psychiatry | Post a comment

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Matt Taibbi writes the Sunday NYT lead 4 days before they do

Addendum 18 September:  After dishing out cancel culture for a decade, the left finds a week of it after Kirk’s assassination intolerable and discovers freedom of speech.

Here is Matt Taibbi 10 September (written and published before the Kirk murder of that day) writing about the way the mainstream press covered the murder of a young woman in Charlotte, North Carolina.

He exactly predicts the lead of Sunday’s 14 September front page NYT article “Trump Escalates Attacks on Political Opponents after Charlie Kirk’s Killing”.  The Times often labels what are really editorials as analysis.

The Sunday front page has no ‘analysis’ of why the recent political violence has all been from the left.  Nor do they have an ‘analysis’ of the absence of rioting and looting by the right after Kirk’s murder.

Here is Taibbi’s post of 10 September

“A brief note on headlines inspired by the Charlotte murder of 23-year-old Iryna Zarutska: “A Gruesome Murder in North Carolina Ignites a Firestorm on the Right” by the New York Times, and “How the lives of a Ukrainian refugee and a Charlotte man with a criminal history converged in a fatal stabbing,” by CNN:

When you cover everything in the world through the lens of Donald Trump, and Trump must not only always be wrong but the avatar of ultimate evil, outlets like the Times and CNN are forced forever to find opposing angles to anything he criticizes. A horrific murder can’t just be that, but an “accelerant for conservative arguments about the perceived failings of Democratic policies.” CNN’s account was like the screenplay to Crash, about how “the paths of two people fatally converged,” culminating in an act “decried by the Trump administration and conservative politicians as an example of the violent crime they say plagues many Democrat-led cities.”

Forget about attacker Decarlos Brown’s mental health, these stories (and others, like the Axios report “Stabbing Fuels MAGA’s crime message” and Brian Stelter’s bizarre outburst about the reaction being “baldly racist”) show the press is in the grip of severe monomania and madness. Nothing exists outside of Trump, the subject of every line of every story. Incredible, and unsettling, to watch.”

Addendum 18 September:  After dishing out cancel culture for a decade, the left finds a week of it intolerable and discovers freedom of speech.

September 15, 2025 – 11:08 am Categories: Social issues ( be civil ! ), Uncategorized | Comments (5)

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Bad three months

It’s been a bad 3 months for us personally, and the country generally (which I’ll talk about in the next post).  We were celebrating our 61st wedding anniversary in June when my wife fell and broke her hip.   Recovery has been considered quite good by the assembled orthopedic surgeon, visiting nurses, physical therapists and occupational therapists, but it’s still quite slow and she only now is in the process of transitioning from walker to cane.

Fortunately, having spent decades taking care of the sick, I knew what to expect, but most people are unaware of just how debilitating physical trauma can be.  Just a 55 mile ride for followup by the orthpod made her sleep from 5 to 8 PM when she got back.  The near total lack of independence is extremely hard psychologically for people previously leading a fairly normal life (so be prepared for reactions to it).

 

Nutrition is important, but most aren’t hungry and ALL are in negative nitrogen balance (breaking down more protein than making new ones which the trauma patient needs to do).  Back in my med school in the 60’s the chief of Surgery (Rhoads) and his chief resident (Dudrick) worked on high intensity nutrition (hyperalimentation) to put people into positive balance, but it must not have worked as my internist never heard of it.

Being married to a lifelong dieter was suddenly changed to pushing food.  Let’s hear it for Ensure.  Most of this was due to the trauma, but some was definitely due to the pain meds (particularly the opiates in the first week or so).

I’m sure that many cheerleaders getting out of high school, college etc.  go in to PT, visiting nursing and OT.  They are some of the most positive people I’ve met.

Do not disparage OT, as one of the most useful things done for us, was showing that the front wheels of the walker, could be placed on the inside, allowing her to get into her studio.

Finally, some history.   In the 60s the mortality of a broken hip in an octagenarian was around 25%.  Now it is under 5%.  It wasn’t a miracle drug or better surgery.  It was because we were keeping them in bed to let them rest and the fracture to heal, which to an 80 year old meant thrombophlebitis of the legs, hypostatic pneumonia and death.  Now people are getting up the day of or the next day after surgery.

Next up — some social commentary on the events of the last 3 months, and after that how changing one nucleotide out of  2.7 billion in the horse genome (we have 3.2 billion) changed history.   For want of a nail . . ., is now For presence of a different nucleotide . . .

September 14, 2025 – 9:30 pm Categories: Social issues ( be civil ! ) | Post a comment

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Molecular Biology of Human Evolution from the Chimpanzee for the complete novice

We’re in the process of discovering just how we humans evolved from the chimpanzee in molecular detail.  This knowledge is almost blasphemous (the work of creation)  and should be widely understood.  You don’t need to know the chemistry of molecular biology at all to understand it, if I’ve written the post correctly.  It is simply too important (and beautiful in a sense) to keep locked up in the minds of people who’ve spent most of their adult life studying the chemistry and biochemistry of life.

Papers on human evolution use terms like selective pressure, force of evolution giving it quasi-conscious properties (now called agency in better circles).  You might as well substitute God for these terms.  Your choice. We are now beginning to understand how these terms are brought about on a molecular level, but they can be understood on a more abstract level with almost no chemistry at all which is what this post is about.

First, what is natural selection.  Darwin’s great book  of 1859, “The Origin of Species”,  is full of letters back and forth with animal breeders (cattle, horses and even pigeons) and their attempts to improve them for human utility (more meat, more speed, prettier pigeons).  He called this selection. He thought that species arose and changed by similar activity in nature — which he called Natural selection.

Parenthetically, it is worth reading Darwin’s book in the original.  You know a lot more than he did, and it is humbling to watch Darwin’s powerful mind dealing with the fragmentary and limited information available to him back then.  If you have the time, I suggest that you read the Darwin’s 1859 book chapter by chapter along with a very interesting book — Darwin’s Ghost by Steve Jones (published in 1999) which updates Darwin’s book to contemporary thinking and knowledge chapter by chapter.  Despite the advances in knowledge in 166 years, Darwin’s thinking beats Jones hands down chapter by chapter.

Proteins are what you see when you look in the mirror. DNA and RNA lurk behind the scene. A protein is just a chain of lagos strung together.  The lagos come in twenty different varieties, each with different shapes and (chemical) properties.  Individual lagos are known as amino acids, and all twenty have names.  Examples are glycine, tryptophan, phenylalanine and 17 more.  Most proteins are a single chain of 100 or more lagos strung together all in a row.   The exact type of which lago goes in each position is crucial.  Sickle cell anemia is due to a change in just one lago in the 7th position of hemoglobin (which has 147 lagos in its chain).   Normally the glutamic acid lago is there, but sickle hemoglobin has lago valine in position 7, the other 146 lagos being identical in both.

DNA and RNA are simpler than proteins. Their elements (called nucleotides) come in 4 varieties  whose names are abbreviated to A, C, G, T in English for DNA.  RNA also has 4 elements, so close  chemically that you can regard their 4 elements as A, C, G, T written in Cyrillic (and I’ll use the same 4 letters for both, capitalizing them when they occur in RNA).  Again, they form linear strings, just as words, sentences, paragraphs etc. etc. are linear strings of alphabetic characters.

Our genetic material (genome) is found in chromosomes which are enormous linear strings of  letters (nucleotides).  Our largest chromosome (#1) has 249,000,000 nucleotides all in a row. Our smallest (the Y chromosome has 62,000,000).  The total number of nucleotides in our  46 chromosomes is over 3 billion.  It’s hard to get your mind around a number like that.  The 7 Harry Potter books contain about 1 million words.  Figuring 5 letters (nucleotides) per word that’s 5 million which is just under 1,000 copies of the 7 books for the 3 billion letters sitting in each of our cell’s DNA

The order of the letters is crucial in chromosomes, just as it is in words (consider united and untied).

There are 16 possible combinations of 2 of the 4 letters AA, AC, AG, AT,   CA, CC, CG, CT,   GA, GC, GG, GT,  TA, TC, TG, TT.  This isn’t enough to code for 20 lagos (amino acids), so the genetic code uses groups 3 nucleotides (called triplets) to code for the 20 amino acids.  So there are 64 possible nucleotide triplets for our 20 lagos  leading to redundancy.

Now its a long story from getting from a nucleotide sequence of triplets in our DNA to actually stringing together the lagos to form a protein involving all sorts of beautiful and intricate molecular machines which I’ll have to skip.

Going back to hemoglobin and its 147 lagos.  It is coded by 147 x 3 = 441 letters all in a row.  The change from glutamic acid at position 7 in the gene for normal hemoglobin (coded for by GAG) to valine (coded for by GTC) is even smaller.  This is what a mutation actually is, a change in the sequence of nucleotides in our genome.

We now know the complete sequence of letters in our DNA (genome).  We also know how to look for portions of our DNA coding for our proteins (of which we have about 20,000)  It came as a huge surprise that the letters coding for the 20,000 accounted for only 2% of the 3 billion letters in our genome.

In an earlier more hubristic era, the 98% of genome not coding for protein was called junk.  Now we know better.  As I said earlier, the proteins making us up can be considered the ‘bricks’ making us up and we are a collection of them.

We also have the complete sequence of letters (nucleotides) making up the chimpanzee genome (and the gorilla and two types of orangutan).  This was recent.  Long before we could sequence DNA we knew that human and chimpanzee proteins were 98% identical (in the lago sequence coding for them).  This is the origin of the idea that we are 98% chimpanzee.

The facts are correct, the interpretation wrong. We are far more than the protein bricks that make us up.

This is like saying Monticello and Independence Hall are just the same because they’re both made out of bricks. One could chemically identify Monticello bricks as coming from the Virginia piedmont, and Independence Hall bricks coming from the red clay of New Jersey, but the real difference between the buildings is their plans.

It’s not the proteins, but where and when and how much of them are made. The control for this (plan if you will) lies outside the genes coding for the proteins themselves, in other 98% of the genome.

It’s been a long conceptual slog getting to this point, so get up and stretch, HARs, the main point is coming up.

The obvious way to find the plan is to lay the human and the chimp genome sequences out side by side and look for areas that have changed (mutated) the most between us and the chimp and not between the chimp and other animals (such as the chicken which has also been sequenced).  These areas are called Human Accelerated Regions (HARs).  An early example (2006) was in a sequence of 118 nucleotides which had 18 changes (mutations) between us and chimp but only two between chimp and chicken.

We have some 2,772 HARs in our genome averaging 269 nucleotides long.  When you think about it, that isn’t very much change.  2,772 x 269 nucleotides is just 745,668 positions in our 3,200,000,000 genome or averaging less than one change every 3,000 positions. But the point of HARs is that the changes aren’t averaged within them, but lumped together.

All 2,772 HARS have occurred in the 5 to 12 million years since the last common ancestor of the human and the chimp.  We are literally looking at what makes us human, which is why it might be considered blasphemous — reducing human creation to 745,668 mutations.

Well, we all knew that our proteins and the chimps are pretty much the same, so it should come as no surprise that most (96%) HARs occur in regions of the genome not coding for protein.

We are just starting to look at what the HARs do.  Many of them involve increasing the number of brain cells (neurons) formed during development.   This is what makes it a privilege to be alive now.  Research on what the HARs do and how they do it will be coming thick and fast. One mechanism is known: binding of a HAR segment of the genome to a protein gene segment of the gene can turn it on (e.g. cause protein to be made by cellular machinery that I haven’t discussed) or turn it off.

Discussing exactly how HAR binding turns off/on proteins would require discussing induced pluripotent stem cells, promoters, transcription factors, enhancers, long coding RNA etc. etc.  This is fascinating stuff and the subject of decades of work and thousands researchers’ careers, but discussing it would detract from thinking about the inner logic of the chemistry and biochemistry producing the plan, an abstract nonphysical object.  Also it would take way too long. So I’m going to avoid describing how the spirit (the ‘plan’) is made flesh (the proteins that carry out the plan).

HARs target many genes for proteins important in nerve cell (neuron) function.  Controlling how much of a protein is made is certainly part of the plan and it is exciting to think HARs are controlling what makes us so different from the chimp — the proteins in our brains.

“Sneaking a look at God’s Cards” is a book about quantum mechanics.  That’s what the human enterprise is doing with HARs.

 

June 9, 2025 – 4:03 pm Categories: Molecular Biology, Philosophical issues raised, Theological implications of simple chmistry | Post a comment

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