In praise of physicist: Linus Pauling (the greatest chemist of last century—the first one to name a moleculat disease)

(Linus Pauling is the greatest chemist the last century, not a physicist; but it is still fitting to place this article in the series of “In praise of physicist”).

Janice introduced me Alan Lightman’s The Discovery (see photo); it must be in early 2006, as I wrote about it in a “winter discontent” on 2/26/2006.  I wrote “summer reading” or “winter discontent” as the series of “letters to my daughters”, which predated this blog, which was evolved from it.

Many years ago I wrote an article of “Molecular biology is quantum mechanics of biology, why?” and never liked it myself.  I’ll use Linus Pauling (see photo) as an example to state my case.  Lightman’s writing about Pauling’s work on chemical bond is enlightening.  Pauling’s concept of hybrid (orbital hybridization) and resonance nature of chemical bondings is not the focus of this writing, but that is a genuine beauty and wonder through the application of quantum mechanics.

The above diagram shows hybrid orbital formation: one “s” and three “p” orbitals hybridized to form four new sp3 hybrid orbital.  These hybrid orbitals are equivalent and directed to the corners of a tetrahedron, making angles of 109.47º with each other.  In his 1927 paper, he wrote, “It has been further found that as a result of the resonance phenomenon a tetrahedral arrangement of the four bonds of the quadrivalent carbon atoms is the stable one. . . .A surprising result of the calculation, of great chemical significance . . . is that the second best [most pointed] bond orbital is equivalent to the first . . .  and that its bond direction makes the tetrahedral angle of 109.47º with that of the first.” (Pauling's italic)

Pauling went to two of the three “birth places” of quantum mechanics right after he received his Ph.D. at Caltech in 1926-1927.  He studied under Arnold Sommerfeld in Munich and Niels Bohr in Copenhagen and Erwin Schrödinger in Zürich.  Werner Heisenberg and Wolfgang Pauli were also around.  If this doesn’t impress you, nothing will.  He was literally there when the quantum mechanics was being born.  There is absolutely no doubt in my mind that he couldn’t come up with the hybrid concept of the carbon bonds without these exposures.  In his Nobel Lecture in 1954, he said, “After the discovery of quantum mechanics in 1925 it became evident that the quantum mechanical equations constitute a reliable basis for the theory of molecular structure.”

Pauling had an advantage of being the only chemist among the giants in physics.  Now I have explained how Pauling formulated his concept of chemical bonding using the quantum mechanics calculations.  But one may ask: What’s this got to do with molecular biology?

Pauling was the first one to identify sickle cell anemia as a molecular disease in his paper published in Nature in 1949, using the technique of electrophoresis that was just became available.  His contribution to molecular medicine is enormous.  He almost beat Watson and Crick in figuring out the DNA structure.  I recall reading Watson’s Double Helix, Watson wrote he read Pauling’s “The Nature of the Chemical Bond” (the Bible of chemical bond; I once checked it out from Carnegie Library; the price of $74.18 at Amazon.com deterred me from owning one.  I do have his book of General Chemistry—see photo) as Watson felt he needed to know everything Pauling knew about chemical bonding; little did Watson know that was impossible.

Science is artificially divided as physics, chemistry, and biology.  One who can integrate and master all fields often emerges triumphantly; the examples abound.  This is my observation and the main point I am trying to convey.

In praise of physicist: Walter Gilbert; from theoretic physicist to molecular biologist

 (This is one of the series of physicists contributing to the advancement of life science)

Wally Gilbert, one of the Jewish Nobel laureates in science, is Harvard and Cambridge University-trained theoretic physicist.  He majored in chemistry and physics and his doctorate degrees in mathematics.  He taught theoretic physics at Harvard for many years.

He first met James Watson at Cambridge University in early 1950s.  James Watson got him interested in molecular biology after the former joined Harvard faculty.  Messenger RNA was first identified in their Lab.  He shared the Nobel Prize (in chemistry) with Frederick Sanger for their independent developments of rapid DNA sequencing in 1980.  I believe Sanger’s method stood the test of time better.

(photo credit to Watson's book: Avoid Boring People, Gilbert is on the left, at Cold Spring Harbor in 1968)

I was amused on reading the following note on Janice’s molecular biology course book at college; this professor once received a $1,000,000 teaching (not research) grant,

“Wally Gilbert was originally a physicist doing biology.  And so he didn’t know much chemistry.  So he turned to his friend our Dean Jeremy Knowles who was and is one of the foremost bioorganic chemists in the world.  Wally would take Jeremy to lunch in the [Harvard] Square where he would pick his brain about how to obtain base-specific cleavage reactions.”  (I delete the paragraphs preceding this as they are too “technical” for the general readers.)

Gilbert also identified one Lac repressor in the field of gene expression that made Francois Jacob and Jacques Monod Nobel laureates.  He also made contribution in recombinant DNA technique.  He helped found the biotech company, Biogen, and was the CEO between 1982 and 1984, when he returned to Harvard.

I read a sad story in James Watson’s Avoid Boring People: Lessons from a life in science, that around the time when Wally Gilbert identified the first Lac repressor in 1967 when their three-year-old daughter was diagnosed with an incurable metastatic sarcoma.  He and his wife, Celia, made constant visits to Children Hospital, at times when he got back home late evening in the lab.  Such was the life of the first-notch scientist.

In his Nobel biography he wrote, “We [he and his sister] loved reading and raided the adult section of the public library,” his mother was a psychologist who often took them to the library.

(photo credit to Watson's book: Avoid Boring People, Wally & Celia Gilbert are on the right, at the 1968 Cold Spring Harbor symposium)

In praise of the physicists who contribute to the advancement of life science

Wally Gilbert

While writing about the “man of sequence”, Frederick Sanger, in the series of Hitler’s gift, I mentioned Walter (Wally) Gilbert (see photo), who shared the Nobel Prize (chemistry) with Sanger in 1980 for devising a method of sequencing the bases in DNA.  Although he is not a so-called gift from Hitler, he is a physicist who contributes to the advancement of life science—also my favorite topic.

Lawrence Bragg

Numerous astonishing discoveries in life science depend on the diffraction of x ray of crystal structure and this technology comes from the father and son (William Henry & William Lawrence Bragg) who discovered the diffraction principle, for which they shared the Noble Prize (physics) in 1915.  Lawrence Bragg (see photo) is still the youngest Nobel laureate at age of 25 to this date.

Lawrence Bragg (see photo) was the director of the Cavendish Lab (at Cambridge University) when James Watson and Francis Crick (also a physicist by training, see photo) were trying to figure out the DNA structure, Max Perutz was deciphering the hemoglobin structure, and John Kendrew myoglobin.  These two pairs were awarded Nobel Prizes (medicine & chemistry) in 1962.  All of them depend on x ray crystallography.  (Watson and Crick went to Perutz’s Lab.)

Francis Crick

Without x-ray crystallography, which is based on Bragg’s diffraction theory, Rosalind Franklin and Maurice Wilkin couldn’t make the beautiful x-ray crystallography of DNA, and Watson and Crick (see photo) couldn’t come up with the DNA structure that “changed the course of the life science history”.

Dorothy Hodgkin

Dorothy Hodgkin (see photo) was also awarded a Nobel Prize (chemistry) in 1964 for her x-ray analysis of complicated molecule, vitamin B12 (cyanocobalamin) specifically.  British Prime Minister, Margaret Thatcher, studied x-ray crystallography under Dorothy Hodgkin at Oxford University before she went into politics.

Let this serve as the introduction of the series of “In praise of physicists who contribute to the advancement of life science.