What have HIV and hepatitis C treatments, Tamiflu and breast cancer treatment got to do with particle physics?

The main theme of this post is to say “science for the science’s sake” makes more sense than “art for the art’s sake,” a French slogan in 19^th century.  We cannot be always sure where the pursuit of science may lead us to.  Science is to seek ‘truth’, to understand the nature; thus pursuit of it can never go wrong.

The difficulty to convince you that pursuit of gravitational waves will benefit mankind     

Why do we have to concern ourselves with the gravitational waves (so-called “ripples in spacetime”) that were caused by the merger/collision of the two colossal black holes, leaving behind a single black hole some 50 times heavier than our sun.  This event happened about 3 billion light-year away and some 3 billion years ago.  For better perspective of how far away it is, it takes sun lights 8 minutes 20 seconds to reach us, traveling at speed of light.

This is almost like a science fiction.  Accordingly it would be difficult for me to argue that gravitational waves matter.  But, it does matter, otherwise its observation/detection won’t yield three Nobel Prizes in physics this year.

Why particle physics matters?  It gave us synchrotron.

I have lost track of how many particle physicists who have been decorated with Nobel Prizes in physics. What is the use to study subatomic particles? Atom has long been not indivisible; but to know atom is composed of leptons (electron, muon and tau, not interacting with strong nuclear force, thus staying outside the nucleus) and quarks (interacting with strong nuclear force, thus found inside the nucleus, such as proton and neutron). Let’s not forget the force-carrying particles, bosons, that produced the 2013 Nobel Prize in physics.

All the subatomic particles are discovered by using particle accelerators or so-called Super Collider.  Synchrotron is a device/technology that is evolved from super collider; it gives off light of such brilliance that it illuminates molecular structures or ‘sees’ the details of it.

Using x ray crystallography to learn the molecular structures is the road to Nobel glory

Using X-ray crystallography (think about it like a CT scan for molecules) to unravel the molecular structure has helped 40 some laureates (and 29 prizes) to get the Nobel Prizes.  Some of the works have been done with the help of synchrotron, complementing to x-ray crystallography.

Synchrotron is a better tool when the molecule of interest cannot be crystallized or has to be studied in the presence of liquid.  Simply put, the synchrotron is to accelerate electrons in a circular path (see photo below), not to crush them to find subatomic particles, but to let them emit the most brilliant light possible, and use the light to 'see' the details of the molecules, almost down to the atomic level.

Dr. Ramakrishnan showed four synchrotron centers in his Nobel Lecture

Ribosome structure: Synchrotron propels the advance of basic science research

V. Ramakrishnan, in his 2009 Nobel Lecture for unraveling the structure of ribosome, (upon which genetic codes of DNA was translated into amino acid sequence to make proteins) said “It was made possible by many technical developments, not least the development of synchrotron radiation sources. . .”

RNA polymerase II and transcription: Synchrotron made it possible for Roger Kornberg’s Nobel glory

Arthur and Roger Kornberg are one of the few father and son (William Henry Bragg and William Lawrence Bragg; Niels Bohr and Aage Bohr) or mother and daughter (Marie Curie and Irene Joliot-Curie) who’re Nobel laureates:  All in the family.

The elder Arthur Kornberg was so honored by his discovery/isolation of DNA polymerase, leading to our understanding of DNA synthesis (I read his memoir, For the Love of Enzymes, twice, about 20 years apart).  The younger Roger Kornberg followed the father’s footstep and figured out RNA polymerase II structure almost down to atomic resolution, using the synchrotron technology.  His research was mostly done at Stanford Synchrotron Radiation Laboratory, located at the Stanford Linear Accelerator Center and also at the synchrotron light source, located at the Lawrence Berkeley National Laboratory.  (This info is proudly presented at the Department of Energy (DOE) online page as both synchrotron facilities are funded by DOE.)

Roger Kornberg (then 12-year old) was in Stockholm in 1959 when his dad was awarded the Nobel Prize.  He is the boy sitting on the left in the family photo [see above] taken then and there.  I am so glad that Arthur Kornberg lived to see his son also to get the Nobel Prize in 2006; he passed away one year later.

father & son: Arthur and Roger Kornberg at the 2006 Nobel Prize press conference

Structure based drug design

Applied science, of which clinical medicine is one, reaps what the basic science research has sown.  The structure based drug design is made possible by using synchrotron technology; the examples abound, the resultant drugs have been in clinical use for nearly 20 years.

HIV and hepatitis C protease inhibitors

The success of using protease inhibitors in treating HIV was applied to hepatitis C treatments, resulting in an even more stunning success.  HIV and hepatitis C viruses replicate by growing a long protein chain that must be cut into smaller pieces to work.  Protease, like a scissor, does the cutting; so by blocking this cutting will prevent the replication of viruses.

The first HIV protease inhibitor (Invirase) hit the market in 1996.  Thankfully viral protease is different from human protease, blocking the viral protease will not block the human one.

Synchrotron technology is used to figure out the viral protease structure down to the atomic resolution, including the active site of this enzyme, so a blocker/inhibitor can be designed.

The story of Herceptin (trastuzumab), a breast cancer drug, making of which was helped by synchrotron

EGFR is a receptor that sits on cell surface, transmitting signals into the cell to make it grow and divide.  HER2 (or HER2/ErbB2 or HER2/neu) is a member of EGFR family.  Overexpression of HER2 (which means the number of receptors increases from normally 20,000 to up to 2 million on each cell surface) is found in 20–30% (some say 25-30%) of breast cancers, and correlates with more aggressive behavior and a poorer prognosis.  Dr. Dennis Slamon (the son of a WV coal miner, a W&J graduate) from UCLA made this important discovery.

This is why HER2 is targeted in making drugs to treat breast cancer.  Art Levinson and Axel Ullrich (from Genentech) successfully cloned HER2 gene, which makes HER2 receptor.  The process involved synchrotron technology.  One needs to know the structure before elucidation of its function.

Axel Ullrich made the first mouse antibody to HER2 receptor that didn’t work as it was rejected as a foreign invader, until it was “humanized” (fusion of a mouse antibody with a human antibody, chimeric) in 1992.  The clinical trial went on from 1992 to1998 when FDA approved it for breast cancer patients who are HER2-positive (overexpression).

Tamiflu: Synchrotron is used to design a drug against influenza virus

Influenza virus has an enzyme, neuraminidase, that cuts the sialic acid which is found in a glycoprotein of the surface of human cell, thus releases new virions.  Tamiflu blocks the cutting action of this enzyme, preventing new viral particles (virions) from being released.

Elucidation of neuraminidase structure was done with the help of synchrotrons.

Radiation therapy also uses accelerator-based technology

Certain radiation therapies for cancers are made possible by using accelerator-based technology.  I do not know enough to elaborate.

The project that led to the detection of gravitational waves was funded by the National Science Foundation that spent $1 billion over the fore decades.  It was managed by Dr. Barry Barish (one of the three Nobel laureates in physics this year) who was also the director of the Super Collider that would have been the world’s largest particle accelerator (proposed by President Reagan) until it was canceled by the Congress that got cold feet.  The best U.S. particles physicists flocked to CERN in Switzerland.

Like Churchill, the scientists would say, “Give us the tools, and we’ll finish the job.”

Leon Lederman on photon and scientists who write well

I constantly look for scientists who write well and discovered Leon Lederman (the particle physicist) a few years ago. The following paragraph is what he wrote about photon in his “Beyond the God Particle”.  He has a gift of writing science for the general readers.  Photons are massless force-carrying particles (bosons).  Photon can have many faces.  Reading this paragraph will elevate the level of understanding of photons.

So, photons can behave like particles, despite their funny quantum waviness and their  imperative to always travel at the speed of light.  They do have something in common with marbles or billiard balls—each photon carries energy as it moves through the room at the speed of light.  Photons can have a lot of energy, and then we call them “X-rays”; still more energy, and we call them “gamma rays,” as when they are the product of such things as radioactive disintegration or supernova explosions.  Gamma rays readily will go “tick . . . tick . . . tick . . . tick” as they are counted in a Geiger counter.  It’s dangerous for living organisms to be exposed to too many X-rays or gamma rays because they tend to destroy biological tissue, such as DNA.  Bur photons can have less energy, becoming the light we see, and with still less energy, will fade off into the far red scale of visibility, becoming warm, gentle infrared light emanating from a soothing fire in the fireplace on a cold winter night, finally becoming at the lowest energy scales microwaves and radio waves.

My impression is that Dr. Harold Varmus is a Renaissance Man, whose 1989 Nobel Prize was for his discovery of oncogenes.  He went to Amherst College as a pre-med student (his father was a medical doctor), but his interest turned to philosophy and English Literature and entered Harvard post-graduate program studying English Literature. Fate had it that he somehow went back to medicine. 

Dr. Varmus became the director of NIH in 1993 and the director of National Cancer Institute in 2010. His memoir (The Art and Politics of Science) has been on my must-read reading list, but never got a chance.  I wrote a post about him on Jan. 17, 2007.  A book review of his memoir in American Scientist does comment about his writing. 

“One of the striking characteristics of many NIH directors is how well they write (James Wyngaarden, Don Fredrickson and Bernadine Healy come to mind). They also recognize how important it is to address nonscientists—members of Congress and the general public—in language that’s easy to comprehend.”

http://doctorjytsai.blogspot.com/2007/01/boring-scientists.html

It is no coincidence that both Leon Lederman and Harold Varmus are Jewish.

Higgs boson—the God particle: An introduction

Peter Higgs

On July 4, 2012 CERN announced the discovery of Higgs Boson, existence of which was predicted by Peter Higgs, Francois Englert and Robert Brout nearly fifty years ago. Higgs presented his finding at Institute for Advanced Study in Princeton in 1964.

Brout didn’t live long enough to share the Nobel glory with Peter Higgs and Francois Englert next year in 2013; he died in 2011; he didn’t even live long enough to know the discovery of the elusive particle that is dubbed as God particle by Leon Lederman, he himself a particle physicist, a Nobel laureate and above all a good writer.

Englert & Brout

It was Leon Lederman (and reading his three books) got me interested in reading (reading and understanding are different things, but one got to have some basic understanding, real or perceived, in order to write) particle physics a few years ago, but that should be a different post.

Why is Higgs boson such a big deal?  

Why is Higgs boson such a big deal?  Without it the whole universe will be non-existent.  To say all particles have a mass is just assumed.  The universe came into being after the Big Bang nearly 14 billion years ago, evidence of which has produced several Nobel Prizes in physics.

The origin of mass of a particle puzzled the best and the brightest of physicists throughout the ages. Higgs boson is one that gives fundamental/elementary particles mass.  Standard Model (the ultimate theories of particle physics, a collective wisdom) postulates that the Higgs field is the source of mass for fundamental particles.  Massive particles feel a sort of drag as they pass through Higgs field.

Why the Higgs boson matters?

Isidor Isaac Rabi was awarded a Nobel Prize in physics (nuclear magnetic resonance) in 1944.  Shortly before his death in 1988 he had MRI (magnetic resonance image). He said, “I saw myself in that machine, I never thought my work would come to this,” nobody saw that coming.  It is hard to predict where the irresistible and inexorable progress of science will lead us.

Rabi returned to the U.S. in 1929 when Columbia University offered him a lectureship, a job recommended by Werner Heinsburg, who was then on his lecture tour there.  Leon Lederman (the one got me interested in reading particle physics) had high praise on Rabi in his Nobel Lecture, stating without Rabi he couldn’t have done what he did at Columbia University.

When Michael Faraday was working on electricity; he discovered the laws of electromagnetic induction.  Gladstone (then Chancellor of the Exchequer, the future Prime Minister, a great Lincoln admirer, whose first order of business when he retired from politics was to see Lincoln’s birthplace in Kentucky) asked him, “But after all, what use is it?” Faraday’s response was, “Why, Sir, there is every probability that you will soon be able to tax it.” A great man with a great vision; he saw things beyond the ordinary mortals did.

The examples abound; let’s stop here for the interest of the length of this post.

Even if the particle physics in general or Higgs boson in particular won’t lead to any practical fruition in our life time. Let’s make it “science for science’s sake”, as opposing to Oscar Wilde’s “art for art’s sake” aesthetics.

If I still cannot convince you of the importance of Higgs boson, I hope Carl Sagan could when he said, “everyone you love, everyone you know, everyone you ever heard of, every human being who ever was, live out their lives on the blue pale spot we know as Earth—and none of it would have ever existed without the Higgs boson.”

Why the Higgs boson matters to physicists?

Physicists always tried to unify all the four forces (more later) that govern the Standard Model of particle physics (more later).  Steven Weinberg and others worked on reconciling the electromagnetic and nuclear weak forces into a unified theory in 1960s.

We know the mass-less photon is the one carrying the electromagnetic force, so they have to come up with a comparable particle to carry the nuclear weak force, and they are W and Z bosons.  But these physicists “hit a snag”, as W and Z bosons have masses, which is incomparable to the photons that have no mass.  This is against the basic rule/law of not being “symmetric”, thus not a unified theory.

The Higgs bosons come to the rescue.  When the Higgs field interacts with W and Z bosons, the Higgs field breaks the symmetry that would have kept W and Z bosons massless.  In other words, W and Z bosons would have been massless had it not been exposed to Higgs field, so the fact of W and Z bosons being massless was masked by Higgs field/Higgs boson.

Without the mass, electrons wouldn’t “hook up” with the nuclei to form the atom, the building block of life, of everything the All Mighty created, although I think, it took more than seven days.  “That would mean no valence bonding, so much of chemistry, essentially all, would vanish.  Therefore no solid structure, no template for life.” (by a physicist at Fermi National Accelerator Lab).

And again it is the Higgs bosons that given electron mass.

Approach the elementary particles in a systemic and coherent way

There are many ways to look at the subatomic particles.  One way is through the property of “strongly interacting”—strongly interacting with strong nuclear force.

God created only four forces that we came to know: (1) gravity, (2) electromagnetism, (3) strong nuclear force (the force of interest to this post), (4) weak nuclear force, which is responsible for radioactive decay.

All the elementary particles can be classified into three groups:

(1)   Non-strongly interacting particles

(2)   Strongly interacting particles

(3)   Bosons or strictly force-carrying particles

Leptons: non-strongly interacting particles

These particles do not interact with the strong nuclear force, thus not confined inside the nucleus.  There are lighter-in-mass, comparing to proton and neutron, which are “strongly interacting particles”; they are dubbed with the “light ones”; thus lepton in Greek.

There are three kinds of charged leptons (electron, muon, tau) and three kinds of neutral leptons (electron neutrino, muon neutrino, tau neutrino).

Quarks: strongly interacting particles

The Higgs boson was discovered in the Large Hadron Collider (LHC) at CERN.  Hadron is a composite, not elementary, particle, such as proton and neutron.  The constituents of hadron are quarks.

Gluon (a force-carrying boson) holds quarks together inside the hadron.

Bosons: force-carrying particles

Bosons have no mass; they create electromagnetic and gravitational field.  Examples are photon (particle of light), gluon (holds the quarks together inside hydron), graviton (particle of gravitation, a hypothetic one), W boson and Z boson that carry the weak nuclear force.

All bosons are force-carrying particles, except Higgs boson, which should be placed here.  As I mention above, Higgs boson is the one that gives fermions (include leptons and quarks) mass.  But, who gives the Higgs boson mass? That is a good question, which also means there is no good answer.  Not yet.

Another approach to classify elementary particles

Another way to classify elemental particles is to separate them into matter and force. Matter has mass occupies space whereas the force-carrying particle has no mass and occupies no space.

Fermions: the subatomic particles that have mass

The subatomic particles that have mass are called fermions (after my Italian American hero, Enrico Fermi), which include quarks (strongly interacting with strong nuclear force) that are constituents of hadrons and leptons (not interacting with strong nuclear force) which include charged leptons (electron, muon and tau) and neutral leptons (electron neutrino, muon neutrino, and tau neutrino).

Bosons: the force-carrying particles that have no mass

(see above)

Quarks are constituents of hadrons, the likes of proton and neutron

Murray Gell-Mann

There are so many hadrons (strongly interacting particles) that led the particle physicists to think they couldn’t be elemental/fundamental particles.  Murray Gell-Mann first proposed quark model in 1964 that subsequently proved quarks are indeed constituents of hadrons.  George Zweig independently came to the same conclusion, but calls it [quark] “aces”. Zweig somehow didn’t share the Nobel glory with Gell-Mann in 1969.

Murray Gell-Mann’s 1969 Nobel Lecture is somehow not available in the nobel.com site, but one can listen to an interview that took place in 2001, in which he did say the “quark” came from James Joyce’s “Finnegan’s Wake”, the book I checked out twice and couldn’t finish the first chapter; I will not pick it up again.

Let this post serve as an introduction of particle physics in general and Higgs boson (the God particle, if you will) in particular.

Higgs boson: What’s in a name? Goddamn Particle or God Particle?

I will write a series of posts about Higgs boson or better known (to the laymen) as God Particle, thanks to Leon Lederman, who got me interested in this Goddamn Particle.

I constantly look for scientists who write well and discovered Leon Lederman a few years ago and had read two of his books (The God Particle: If the Universe is the answer, what is the question? and Quantum Physics for Poet) I bought his second book about Higgs boson (Beyond the God Particle) but never finished it.  The secret of finishing the reading of a book is to check it out from library, and not to buy it.

We read in The God Particle (published in 1993),

“This boson is so central to the state of physics today, so crucial to our final understanding of the structure of matter, yet so elusive, that I have given it a nickname: the God Particle.  Why God Particle? Two reasons. One, the publisher wouldn’t let us call it the Goddamn Particle, though that might be a more appropriate title, given its villainous nature and the expense it is causing.  And two, there is a connection, of sorts, to another book, a much older one . . .”

In The God Particle there is an imaginary conversation between Lederman and Democritus, who said “Nothing exists except atoms and empty space” nearly 2500 years ago:

Democritus: Higgs boson—not a very poetic name.

Lederman: I call it the God Particle.

Thus the Higgs boson is sometimes referred to as the “God particle,” to the chagrin of many scientists, especially Jon Butterworth, whose book (Most Wanted Particle) I checked out this past weekend.

Butterworth called the invention of “God particle” regrettable and “really silly” (see the scanned copy). He never mentioned Lederman’s books about this Goddamn particle.  It is sad that Lederman (now in his 90s) has since developed dementia and cannot “fight” back to make a witty comment to return the favor in kindness.

自古文人相輕; it is still so for the scientists in modern time.

Leon Lederman (a 1982 Nobel laureate): the scientists who writes well

I began to read “God particle” when I discovered Leon Lederman as a scientist who writes well.  In his The God Particle, Lederman had an imaginary conversation with Democritus who said everything is composed of atoms nearly 2,500 years ago.

No sooner was The God Particle published in 1993 than the Superconducting Super Collider (proposed by President Reagan) was canceled by the Congress after spending $1 billion to dig up the hole (and another $1 billion to fill up the hole.)  One can only imagine what a devastating disappointment for scientists like Leon Lederman.

After reading the library book of The God Particle, I bought the Beyond the God Particle, but never finished reading it. Lederman’s Quantum Physics for Poets is the best book for a non-physicist who wants to understand quantum physics.

During the following imaginary conversation Lederman said his ancestor built the Pyramids; it reveals that he is Jewish.

Lederman: The field is represented by a particle we call the Higgs boson.
Democritus: A particle! I like this idea already.  And you have found this particle in your accelerator?

Lederman: Well, No.

Democritus: So you found it where?

Lederman: We haven't found it yet.  It exists only in the collective physicist mind.  Kind of like Pure Reason.

Democritus: Why did you believe in it?

Lederman:

Because it has to exist.  The quarks, the leptons, the four forces—none of these makes complete sense unless there is a massive field distorting what we see, skewing our experimental results.  By deduction, the Higgs is out there.

Leon Lederman

Democritus:

Do you have any ideas about when & where I should go to see some greater progress in the search of my atom?

Lederman:

Two times, two difficult places.  First, I suggest you come back here to Batavia in 1995.  After that, try Waxahachie, Texas, around, say 2005.

Democritus: . . . And where is the Waxahachie?

Lederman:

In Texas, in the desert, where we're building the largest particle accelerator in history.  In fact, it will be the largest scientific tool of any kind built since the two great pyramids (I don't know who designed the Pyramids, but my ancestor did all the work! The Superconducting Super Collider, our new machine, should be in full swing by 2005—give or take a few years, depending on when Congress approves the funding.

Democritus: Higgs boson—not a very poetic name.

Lederman: I call it the God Particle.

CERN and the discovery of the God Particle

The large hadron collider (accelerator) at CERN is hard working again.  Good news about CERN always saddens me, leading me to lament the cancellation of an even larger (3 times larger) hadron collider in Waxahachie, Texas (outside Dallas) by the short-sighted politicians in 1993.

In 1964 Peter Higgs and two other scientists proposed a theory that there got to have a particle (Leon Lederman called it “God Particle”) to explain why other particles have a mass.  The elusive particle was finally discovered at CERN (it could have been at Waxahachie, Texas) in 2012.  Peter Higgs and Francois Englert were quickly awarded the Nobel Prize in Physics in 2013.  Robert Brout didn’t live long enough for the Nobel glory.

I recall there was a good article (“A Second Big Bang In Geneva?”) in the Wall Street Journal a few years ago.  All the best and the brightest U.S. particle physicists have all emigrated to Europe where CERN is.