Tag Archives: beta actin

Book Review: Hawking Hawking

To this neurologist, Stephen Hawking’s greatest contribution wasn’t in physics. I ran a muscular dystrophy clinic for 15 years in the 70s and 80s. Few of my ALS patients had heard of Hawking back then. I made sure they did. Hawking did something for them, that I could never do as a physician — he gave them hope.

Which brings me to an excellent biography of Hawking by Charles Seife “Hawking Hawking” which tries to strip away the aura and myths that Hawking assiduously constructed and show the man underneath.

Even better, Seife is an excellent writer and has the mathematical and scientific  chops (Princeton math major, Yale masters in math) to explain the problems Hawking was wrestling with.

Hawking was smart.  One story tells it all (p. 328).  Apparently there were only 3 other physics majors at Oxford that year.  They were all given a set of 13 problems on electromagnetism and a week to do them.    One of the others (Derek Powney) tells the tale. “I discovered very rapidly that I couldn’t do any of them”.  So he teamed up with one of the others, and by the end of the week they’d done 1.5 problems.  The thrd student (working alone) solved one. 

At the end of the week “Stephen as always hadn’t even started”. He went to his room and came out 3 hours later. “Well, I’ve only had the time to do the first ten.”  “I think at that point we realized that it’s not just that we weren’t on the same street, we weren’t on the same planet.”

Have you ever had an experience like that?  I’ve had two.  The first occurred in grade school. I was a pretty good piano player, better than the rest of Dr, Rudnytsky’s students.  Then, someone told me that at age 3 his son would tell him what notes passing trains were whistling on, and that later on he’d sit behind a door listening to his father give lessons, and then come in afterwards and play by ear what the students had been playing.  The second occurred a within day or so of starting my freshman year in college. My roommate told me about a guy who thought he ought to know everybody in our class of 700+.  So he got out the freshman herald which had our pictures and names and a day later knew everyone in the class by name. 

The reason people of a scientific bent should read the book, is not the sociology, or the complicated sexuality of Hawking and his two wives, and god knows what else.  It is the excellent explanations of the problems in math and physics that Hawking faced and solved.  Even better, Seife puts them in context of the work done before Hawking was born.  

Two  examples

1. pp. 14 – 18 — a superb explanation of what Einstein did to create special relativity. 

2. pp. 240 – 245 an excellent description of the horizon problem, the flatness problem and how inflation solved it. 

Any really good book will teach you something.  People in physics, math and biology are consumed with the idea of information.  The book (pp. 131 – 134) explains why Hawking was so focused on the black hole information paradox.  It always seemed pretty arcane and superficial to me (on the order of how many angels could dance on the head of a pin).  

Wrong ! Wrong !

The black hole information paradox is at the coalface of ignorance in modern physics.  Why?  Because the two great theories we have in  (quantum mechanics and general relativity) disagree with what happens to the information contained in an object (such as an astronaut) swallowed by a black hole.  Relativity says it’s destroyed, while quantum mechanics says that’s impossible. 

So reconciling the two descriptions would lead to a deeper theory, and showing that one was wrong, would discredit a powerful theory. 

So even if you’re not interested in the sociology of the circles Hawking moved in or his sex life, there is a lot of well-explained physics and math to be learned for the general reader.  

The black hole information paradox resembles a similarly unresolved pair of phenomena in the world we live in, the Cartesian dualism between flesh and spirit.  It is writ large in biology.

Chemistry is great and can provide mechanistic explanations what we see, such as the example from the following old post, produced after the ***

It’s quite technical, but is an elegant explanation of how different cells make different amounts of two different forms of a muscle protein (beta actin and gamma actin ).  I never thought we’d have an explanation this good, but we do.  Well that’s the flesh and the physicality of the explanation.  Asking why different cells would want this, or what the function of all is puts you immediately in the world of spirit (ideas, which are inherently noncorporeal).  Physical chemistry and biochemistry are silent, and all the abstract explanations science gives us (the function, the why, the reason) is essentially teleological. 

*****

The last post “The death of the synonymous codon – II” puts you exactly at the nidus of the failure of chemical reductionism to bag the biggest prey of all, an understanding of the living cell and with it of life itself.  We know the chemistry of nucleotides, Watson-Crick base pairing, and enzyme kinetics quite well.  We understand why less transfer RNA for a particular codon would mean slower protein synthesis.  Chemists understand what a protein conformation is, although we can’t predict it 100% of the time from the amino acid sequence.  

Addendum 30 April ’21:  Called to task on the above  by a reader.  This statement is no longer true.  The material below the *** was bodily lifted from something I wrote 10 years ago.  Time and AI have marched on since then.

So we do understand exactly why the same amino acid sequence using different codons would result in slower synthesis of gamma actin than beta actin, and why the slower synthesis would allow a more leisurely exploration of conformational space allowing gamma actin to find a conformation which would be modified by linking it to another protein (ubiquitin) leading to its destruction.  Not bad.  Not bad at all.

Now ask yourself, why the cell would want to have less gamma actin around than beta actin.  There is no conceivable explanation for this in terms of chemistry.  A better understanding of protein structure won’t give it to you.  Certainly, beta and gamma actin differ slightly in amino acid sequence (4/375) so their structure won’t be exactly the same.  Studying this till the cows come home won’t answer the question, as it’s on an entirely different level than chemistry.

 

Phillip Anderson, 1923 – 202 R. I. P.

Phil Anderson probably never heard of Ludwig Mies Van Der Rohe, he of the Bauhaus and his famous dictum ‘less is more’, so he probably wasn’t riffing on it when he wrote “More Is Different” in August of 1970 [ Science vol. 177 pp. 393 – 396 ’72 ] — https://science.sciencemag.org/content/sci/177/4047/393.full.pdf.

I was just finishing residency and found it a very unusual paper for Science Magazine.  His Nobel was 5 years away, but Anderson was of sufficient stature that Science published it.  The article was a nonphilosophical attack on reductionism with lots of hard examples from solid state physics. It is definitely worth reading, if the link will let you.  The philosophic repercussions are still with us.

He notes that most scientists are reductionists.  He puts it this way ” The workings of our minds and bodies and of all the matter animate and inanimate of which we have any detailed knowledge, are assumed to be controlled by the same set of fundamental laws, which except under extreme conditions we feel we know pretty well.”

So many body physics/solid state physics obeys the laws of particle physics, chemistry obeys the laws of many body physics, molecular biology obeys the laws of chemistry, and onward and upward to psychology and the social sciences.

What he attacks is what appears to be a logical correlate of this, namely that understanding the fundamental laws allows you to derive from them the structure of the universe in which we live (including ourselves).   Chemistry really doesn’t predict molecular biology, and cellular molecular biology doesn’t really predict the existence of multicellular organisms.  This is because new phenomena arise at each level of increasing complexity, for which laws (e.g. regularities) appear which don’t have an explanation by reducing them the next fundamental level below.

Even though the last 48 years of molecular biology, biophysics have shown us a lot of new phenomena, they really weren’t predictable.  So they are a triumph of reductionism, and yet —

As soon as you get into biology you become impaled on the horns of the Cartesian dualism of flesh vs. spirit.  As soon as you ask what something is ‘for’ you realize that reductionism can’t help.  As an example I’ll repost an old one in which reductionism tells you exactly how something happens, but is absolutely silent on what that something is ‘for’

The limits of chemical reductionism

“Everything in chemistry turns blue or explodes”, so sayeth a philosophy major roommate years ago.  Chemists are used to being crapped on, because it starts so early and never lets up.  However, knowing a lot of organic chemistry and molecular biology allows you to see very clearly one answer to a serious philosophical question — when and where does scientific reductionism fail?

Early on, physicists said that quantum mechanics explains all of chemistry.  Well it does explain why atoms have orbitals, and it does give a few hints as to the nature of the chemical bond between simple atoms, but no one can solve the equations exactly for systems of chemical interest.  Approximate the solution, yes, but this is hardly a pure reduction of chemistry to physics.  So we’ve failed to reduce chemistry to physics because the equations of quantum mechanics are so hard to solve, but this is hardly a failure of reductionism.

The last post “The death of the synonymous codon – II” — https://luysii.wordpress.com/2011/05/09/the-death-of-the-synonymous-codon-ii/ –puts you exactly at the nidus of the failure of chemical reductionism to bag the biggest prey of all, an understanding of the living cell and with it of life itself.  We know the chemistry of nucleotides, Watson-Crick base pairing, and enzyme kinetics quite well.  We understand why less transfer RNA for a particular codon would mean slower protein synthesis.  Chemists understand what a protein conformation is, although we can’t predict it 100% of the time from the amino acid sequence.  So we do understand exactly why the same amino acid sequence using different codons would result in slower synthesis of gamma actin than beta actin, and why the slower synthesis would allow a more leisurely exploration of conformational space allowing gamma actin to find a conformation which would be modified by linking it to another protein (ubiquitin) leading to its destruction.  Not bad.  Not bad at all.

Now ask yourself, why the cell would want to have less gamma actin around than beta actin.  There is no conceivable explanation for this in terms of chemistry.  A better understanding of protein structure won’t give it to you.  Certainly, beta and gamma actin differ slightly in amino acid sequence (4/375) so their structure won’t be exactly the same.  Studying this till the cows come home won’t answer the question, as it’s on an entirely different level than chemistry.

Cellular and organismal molecular biology is full of questions like that, but gamma and beta actin are the closest chemists have come to explaining the disparity in the abundance of two closely related proteins on a purely chemical basis.

So there you have it.  Physicality has gone as far as it can go in explaining the mechanism of the effect, but has nothing to say whatsoever about why the effect is present.  It’s the Cartesian dualism between physicality and the realm of ideas, and you’ve just seen the junction between the two live and in color, happening right now in just about every cell inside you.  So the effect is not some trivial toy model someone made up.

Whether philosophers have the intellectual cojones to master all this chemistry and molecular biology is unclear.  Probably no one has tried (please correct me if I’m wrong).  They are certainly capable of mounting intellectual effort — they write book after book about Godel’s proof and the mathematical logic behind it. My guess is that they are attracted to such things because logic and math are so definitive, general and nonparticular.

Chemistry and molecular biology aren’t general this way.  We study a very arbitrary collection of molecules, which must simply be learned and dealt with. Amino acids are of one chirality. The alpha helix turns one way and not the other.  Our bodies use 20 particular amino acids not any of the zillions of possible amino acids chemists can make.  This sort of thing may turn off the philosophical mind which has a taste for the abstract and general (at least my roommates majoring in it were this way).

If you’re interested in how far reductionism can take us  have a look at http://wavefunction.fieldofscience.com/2011/04/dirac-bernstein-weinberg-and.html

Were my two philosopher roommates still alive, they might come up with something like “That’s how it works in practice, but how does it work in theory?