How does our body manage to make a vast array of diverse anitibodies?

Antibodies are proteins, which are encoded by genes; one gene one protein.  The human genome contains fewer than 50,000 genes, and yet we seem to have capability to make unlimited diverse antibodies as the need arises.  This puzzle was solved by Susumu Tonegawa who was awarded a Nobel Prize in Medicine in 1987.

Our immune system has evolved a unique genetic mechanism that enables it to generate virtually unlimited number of different antibodies by joining separate gene segments together before the codes (nucleotides sequence) are transcribed into messenger RNA, which are then translated into a different language—sequence of amino acids of a protein, or antibody in this case.

We all know it was Salvador Luria who sent James Watson to to meet with Crick.  It is less well known that both Luria and Renato Dulbecco had a strong impact on Tonegawa’s career.  In his autobiography (A Slot Machine, A Broken Test Tube), Luria wrote about his stay at Indiana University,

And my very first graduate student in Bloomington, in 1947, was a thin young man named Jim Watson, of twice double-helix fame—for his discovery of DNA structure (for which he shared a Nobel Prize with Francis Crick) and for the excellent book he wrote about that discovery.  With me Jim worked on the reactivation [of killed bacteriophage] phenomenon.  My role in arranging Watson’s fateful move from Copenhagen to Cambridge has been recounted many times in books on the DNA story.  That I arranged the move is true; that it was arranged when I met the British spectroscopist John Kendrew, and that John and I were congenial because we both were socialists is also true.

When the U.S. Immigration wouldn’t extend his stay in the States, it was Dulbecco sent him to to work with Niels Jerne.  On his Nobel Lecture in 1987, Tonegawa began with

One day in the fall of 1970, I received an airmail letter from Renato Dulbecco who was travelling in Europe. At that time I was a postdoctoral fellow in his laboratory at the Salk Institute. The letter, written on stationery of the Hotel Hassler in Rome said:

“Dear Susumu,

I don’t know what arrangements you have made for after your departure from La Jolla [where Salk Institute is] at the end of the year but I would like to mention to you another possibility. The Institute of  Immunology in Basel, Switzerland will start operating in a month. They already have an excellent collection of immunologists, but have not yet built an adequate background in molecular biology. I talked about you to Niels Jerne, the Director, and they are interested in having you there …

Thanks partly to this remarkably prophetic letter and partly to the immigration law that prevented me from remaining in the U.S.A., in February 1971 I found myself in this cozy Swiss town almost completely surrounded by immunologists.

Luria later recruited Tonegawa to MIT where he was at the time of his Nobel Prize award.  Tonegawa also bridged the molecular biology to immunology.

Antibody doesn’t always confer immunity or protection: even a Nobel laureate had a misconception about it

The invention of polymerase chain reaction or PCR by Karis Mullis (see photo) propelled the genetic science to a higher level—a quantum leap.  Mullis has been ‘carried away’ after he was awarded a Nobel Prize in Chemistry in 1993.  He has since made outrageous anti-science statements, saying things without merit and without taste.  I honored him sarcastically with a ‘Flamboyant Flame’ Intellectual Cologne (see the article of ‘Intellectual Cologne’)

Ted Koppel on ABC’s ‘Nightline,’ once said, rightly so.

Take all MVPs from professional baseball, basketball, and football.  Throw in a dozen favorite movie stars and a half dozen rock stars for good measure, add all the television anchor people now on the air, and collectively, we have not affected the current good or the future welfare of mankind as much as Kary Mullis.

In his Dancing Naked in the Mind Field (published 1998), questioning HIV causes AIDS, Mullis wrote,

I read the Papers in Science for which they had become well known as the AIDS doctors, but all they had said there was that they had found evidence of a past infection by something which was probably HIV in some AIDS patients.  They found antibodies.  Antibodies to viruses had always been considered evidence of past disease, not present disease.  Antibodies signaled that the virus had been defeated.  The patient had saved himself.  There was no indication in these papers that this virus caused a disease.  They didn't show that everybody with the antibodies had the disease.  In fact, they found some healthy people with antibodies.

His writing (as late as 1998) revealed he had misconception of antibody.  He only knew “Antibodies to viruses had always been considered evidence of past disease, not present disease.”  Little did he know that some viruses are smarter than he is (or all of us) and can master their genetic know-how to evade our immune system.

He wrote, “they found some healthy people with antibodies.”  It has been a common knowledge that HIV patients with antibody may remain ‘healthy’ until they fell ill with AIDS (after CD4 count drops to certain level).  And yet Mullis used this phenomenon refuting HIV as the cause of AIDS.  Ironically PCR (Mullis’ great invention) greatly helps the advancement of HIV research.

He did admit that “It was a little out of my field of biochemistry, and these men were specialists in retroviruses [HIV]”  This turned out to be his only correct statement.

Wearing a Nobel laurel, Mullis’s words carry weight and general readers would believe in every word he utters.  Thus he is recklessly irresponsible.  Reading may be hazardous to your mind or health.