Understanding E-coli

Hardly a month or a week went by without E. coli popped up in the news nowadays.  It happened again today (1/22/08): an AP news dispatch with a headline of “Ongoing health issues haunt some food-poisoning victims,” and E. coli is the major food-borne disease.

 

E. coli is short of Escherichia coli in honor of the German scientist Theodore Escherich, who discovered it in 1885.  If you can be famous you might as well have an easier name to remember, otherwise, you’ll be reduced to an E. (Not an E!, for those over indulged in entertainment!)

There are hundreds of strains of E. coli, and I am wise enough not to bore you with its classification.  The E. coli of interest is the notorious E. coli O157:H7, which was first isolated in an outbreak of bloody diarrhea in 1982.

Strain of E. coli is determined by its antigen (a molecule that can elicit an immune response).  O antigen is in the outer membrane and H antigen in the flagellum.  The emergence of new strain tells us the evolutionary biology is alive and well.  This mutation (a freak of nature event in Nature) renders it to produce Shiga (originally from Shigella) toxins that wreak havoc in its victims.

The most dreaded complication is hemolytic-uremic syndrome, which often occurs in children younger than 5 to 10 years of age.  The initiated event is that the Shiga toxin damages the lining of tiny blood vessels, causing a cascade of events that lead to clogging the vessels and hemolysis (breakdown of red blood cells) and kidney failure.

The major reservoir for E. coli O157:H7 is the gastrointestinal tract of cattle; the organisms are excreted by up to 10% of healthy cattle.  Beef can be contaminated during slaughter or processing if the intestinal contents of an infected (not sick) cattle contact the meat.  And if the hamburger is undercooked; it is likely that a small number of E. coli O157:H7 can survive in the center of an undercooked hamburger.

Like shigella, only 10 to 100 E. coli O157:H7 bacteria needed to sicken people, this is amazingly small numbers, considering the fact that 10⁵ to 10⁸ Salmonella or Cholera bacteria needed to make one sick.
A number of outbreaks of E. coli O157:H7 infections have been associated with the exposures and contacts with animals in petting zoos and county fairs.

Food borne illnesses (caused by Salmonella, Campylobacter, Listeria, and E. coli O157:H7, etc) result in 325,000 hospitalizations and 5,000 deaths a year. The great majority recover without lasting sequelae.  

Published in Kidney International, 2006 August; 70:807, an article reported none of  the 951 victims (those developed hemolytic-uremic syndrome were excluded from the study) of a drinking water outbreak of E. coli O157:H7 had no evidence of kidney disease 4 years later.

Today’s AP dispatch may cause unnecessary anxiety to those who recovered from a food borne illness.  Rest assured the data so far indicate that serious health problems may occur years later only in those unfortunate who had a very serious disease in the outset. 

A special strain of E. coli (E. coli K1) can cause meningitis in infants, rarely in adults.  It is of interest to learn this K1 antigen is very similar to that of another meningitis-causing Neisseria meningitides.  Pregnant women are susceptible to colonization of E. coli K1, even though they do not get sick.  This is what I like to say that bacteria are smarter than you thought; they know the best way to get hold the infant is through the pregnant mother.

Enough bad things said about E. coli, which has a ‘complicated’ personality; they are part of the normal flora in our intestines doing all sorts of good deeds.  They participated in many scientific researches greatly expanding our understanding about life.

When I began my practice in mid 1970s, diabetic patients taking either ‘beef’ (cow) or ‘pork’(pig) insulin (like serving in a restaurant, I might ask “beef or pork?”); the pharmaceutical companies collected pancreases in the slaughtered houses.  Thanks to recombinant DNA technology developed by Paul Berg and (Stanley Cohen and Herb Boyer discovered the restriction enzyme made it possible to 'cut' the DNA) this practice has since become a thing of the past. Using ubiquitous E. coli as the manufacture factory by inserting insulin-producing genes into E. coli genome, and that makes E.coli produce human insulins faithfully and dutifully.  The race to make human insulin between Genentech and Biogen is a fascinating story.

The fact that we share the same nucleotide bases (adenine, thymine, guanine, cytosine—the ‘language of God’) with bacteria should be the best argument for those advocate Intelligent Design as it must have been designed by the same Creator.  Gee! I thought I am writing science, I better stop. : )

In search of memory

My main criticism of A.J. Jacobs’ The Know-It-All is his lack of understanding of science and that makes him only half qualified to cover Encyclopaedia Britannica.  I feel I was not alone after reading Joe Queenan’s “The Know-It-All: A Little Learning is a Dangerous Thing” in the New York Times book review (10/3/04)  Jacobs’ rebuttal (also published in the same book review) proves he is indeed a good writer, but is one who cannot take criticism; if I were him, I would write a different rebuttal, borrowing or even ‘plagiarizing’ Samuel Johnson’s sharp tongue and wit of insults.

Jacobs wrote if he doesn’t have ‘waxy pallor’ he doesn’t have aplastic anemia. Not only did he not tell the essence of aplastic anemia, he laid bare his ignorance in understanding medicine.

Knowledge is yours only when understood (and remembered, since the topic is 'memory'.)

My 1987 EB defines memory as “the retention and retrieval in the human mind of past experiences.”  This is not quite correct, as animals obviously have memory, too; and the model organism that Eric Kandel used in studying memory is a marine organism Aplysia.  Kandel was awarded a Nobel Prize in Medicine in 2000 for elucidation of the molecular mechanism of memory.  Here is the story:

In his 2002 Nobel Lecture (“Nature’s Gift to Science”), Sidney Brenner talked about the importance of choosing a model organsim for a given project.  He used the ‘elegant’ C. elegans (a nematode with about 1000 cells in all, among them 302 cells in nervous system, its genome is only 20 times that of E. coli).  Alan Hodgkin (1963 Nobel Prize in Medicine for ionic channels in nerve cells) used squid for its “giant nerve fibers, which may be as much as a millimeter in diameter.”  and Kandel used Aplysia, which has only 2 x 10⁴ neurons (nerve cells) in its brain, comparing to 10¹² that human brain has, and its capability of simple learning.  Aplysia also has very large nerve cells in brain so the microelectrodes can be inserted.

The most striking finding is that short term memory doesn’t require the protein synthesis whereas the longterm memory does, although both use the same synapses. Thus whenever we remember something for the long-term, our chromatin (complex of DNA and protein) structure in brain changes and synaptic strength enhances, and the neural networks of the brain are not fixed but dynamic.

Kandel said ‘repetition’ and ‘practice makes perfect’ is the only sure way to convert short-term to long-term memory.  This was well documented in his 48-page Nobel lecture or one-hour video.  This may be the best ‘take home’ message of this writing.

A synapse is how the nerve cells communicate each other:  it usually works by neurotransmitters which are secreted by a presynaptic cell, sending the message to the postsynaptic cells.  We have hundreds of billions of nerve cells, one can imagine how many synapses that we have.

Signal transduction of synapse involving memory storage, complex though it can be, is where the beauty of science lies; there is CREB-1 which is a stimulatory protein, and inhibitory CREB-2.  That is, for a memory to be stored, CREB-1 has to be activated and inhibitory constraint has to be removed. (i.e. CREB-2 to be inhibited)

This may explain why some people can remember well without effort and others have trouble remembering.  Kandel said (in the lecture video, I cannot find this in the text format.  I have noticed that, the text formats of many Nobel lectures are somewhat different from the videos) “I have a friend, Sigbund ?, seems to remember every thing, I always thought he was a bright kid at Columbia [Kandel is at Columbia University], now I am afraid he is a mutant with a specific defect in CREB-2 protein.” (laughter erupted)

A few days ago, either CNN of Fox news interviewed a man who can remember everything happened any given day in his life. (He didn’t get 100% correct.)  He most likely has a defect CREB-2 protein (due to a mutant CREB-2 gene) and if one is without an inhibitory constraint, one remembers every thing.

Kandel became philosophical when he explained why there is a need of inhibitory CREB-2 gene when it comes to memory storage, “It is clearly evolutionary advantage for an animal to learn and store in long-term memory only facts important for survival, rather than retaining everything.”

By now one should get an idea why memory capability is not considered a component of intelligence (analytic, creative, or whatever) by the experts in this field.  And this is why we have those absent-minded professor anecdotes.

Shortly after Einstein arrived at Princeton’s Institute of Advanced Study in 1939, he was a hot pursuit of paparazzi [did we have paparazzi in his days?] so school officials were asked not to give away Einstein’s where about.  One day the university president received a call asking where Einstein lived, the president responded by saying he was not supposed to tell, an embarrassing whisper came from the other end of the line, “but, this is Einstein” who forgot where he lived and happened to carry with him the president’s phone number [I doubt he could remember the phone number.]
 

Alzheimer’s disease is a clinical disease characterized by gradual decline of cognitive function from a previously higher level and the impairment of recent memory.  There are no laboratory tests can confirm it, although an MRI finding of hippocampal atrophy is suggestive, but not specific or sensitive.  It is of interest that synapses involving memory and learning are highly concentrated in hippocampus.

In his memoir, In Search of Memory, Kandel spent many pages praising the pioneer in neuroscience, Santiago Ramỏn Cajal who shared the 1906 Nobel Prize in Medicine with Camillo Golgi to whom Kandel had many negative comments, though.

Cajal proposed in 1894 “a theory of memory storage: memory is stored in the growth of new connections [synapse in modern term]” A great mind tends to have prescient idea, it never fails. 

What is a Classic?

What is a Classic? This was the topic of the Presidential Address to the Virgil Society delivered by T.S. Eliot in 1944.  Eliot said classic is used “as an indication of the greatness, or of the permanence and importance of a writer in his own field.” and “for it is only by hindsight, and in historical perspective, that a classic can be known as such.” And a classic requires “a lifetime of labour” of a writer with a matured mind.
    

EB says the classical literature is used for “the literature of any language in a period of any notable for the excellence and enduring quality of its writers’ works.”

T.S. Eliot was awarded the Nobel Prize in Literature in 1948 “for his outstanding, pioneer contribution to present-day poetry.” His verse departed from the ‘classic’ of the age that he had so arduously studied and produced a classic--The Waste Land.  James Joyce’s novels were shockingly revolutionary in technique comparing to the classical novels that we come to know, and yet one needs not apologize if one declares Ulysses or Finnegans Wake a classic.

This is my way to convey the concept of classic, which is also defined as “A book which people praise and don’t read.” by Mark Twain.

Pop culture

After writing a critical review of A.J. Jacob’s The Know-It-All, I decide to write a series of articles, loosely based on Encyclopaedia Britannica (EB).  I’ll aim to convey a concept or add to understanding in science or otherwise.  

I can do a better job when it comes to science, although I may also use Jacob's ‘pop culture’ style to comment on ‘current event’, which deviates from the style of EB which is not a newspaper.  “Imitation is the most sincere form of flattery.”  This should please Jacobs.  I may spice it up in good taste when appropriate or dumb it down when it comes to more esoteric stuff.

What is pop culture? My 1987 Encyclopaedia Britannica has a listing of popular art, but no pop culture; pop culture derives from popular culture.  If you lived in Shakespeare time, you don’t want to be popular, which is associated with base and vulgar.

Pistol                                                                            Modern translation

     Discuss unto me, art thou officer,                               Declare yourself, are you an officer.

     Or art thou base, common, and popular?                   Or are you low, vulgar, and of common people?

King Henry                                                                   King Henry

     I am a gentleman of a company.                                I am a gentleman of a company.

                        Henry V  Act 4  Scene 1

It is not until after 18^th Century that ‘popular’ took the present meaning and began to be used as ‘widespread’  Now you know why the writings in my blog are not popular; I have good reason for it.  My EB defines popular art as arts “intended to be received and appreciated by the largest possible audience, ” like Katy’s flower picture postings.  And that is never the intention of writing my blog.

It is said that James Watson is very ignorant about pop culture, although he may recognize Paris Hilton, who, by the way, is going to Harvard to pick up her “The Woman of the Year” award from Hasty Pudding Club Feb. 9, 2008.  Watson may even call her one of his own now.  I am hoping Paris Hilton’s handlers can come up with a good speech that fits the institution and the occasion, making her worthy of the award.   

I doubt Watson knows Christina Aguilera, though.  If he watches TV often enough, he may have heard Lindsay Lohan, but I doubt he knows what she’s been doing, nor does she.  Lohan may have heard James Watson, but likely has no clue who he is.  And both are notorious; each in his or her own way. 
  
In The Know-It-All, Jacobs wrote “My wife is upset there’s no mention of Tom Cruise.” (He used 2002 edition of EB)  Pop culture has limited coverage in EB.  Jacobs also wrote, EB guys “want to beef up the pop culture coverage [there goes my EB!], to make the Britannica more accessible without sacrificing the gravitas or dumbing it down.  Man, if I get the Cruise in I would be golden with Julie [his wife].  I could forget a half dozen anniversaries, but, I’d always have that.”

The Know-It-All is to know-it-too-little, failing pathetically in covering science: a book review

Even though I enjoy reading A.J. Jacobs’ The Know-It-All, my critique will be in more negative than positive tone.  The first and foremost is the topic selection; he chose the topics for his own convenience, not trying to cover something of substance or enlightening.  He only commented the topics to which he had something funny to say and he succeeded if this book is placed in the ‘humor’ section in the bookstore.

Little, if any, can be found about science; if found, he said something irrelevant and superficial, and nothing of sorts in enhancing understanding.  He had good insight about this shortcoming; at the end of M section, he wrote,  “I’m worried, in particular, about my science knowledge.”  (may click the photo to enlarge it)    

The above example illustrates my point; how can one become ‘smarter’ if this is one will learn about reproduction (and that was not even funny).  He threw in Avogadro’s number (that is not a bad writing), but failed to say a thing or two about it for the uninformed.  He even misspelled Avogadro as Avogrado, let’s hope the typo is not his fault.

He tended to use ‘scientific’ words to show off his readings EB, it all but revealed his ignorance.  In talking his Millionaire fiasco, he sent Eric [brother-in-law] an e-mail.

Thanks for being my lifeline.  We didn’t win, but we went down fighting.

Your brother (by marriage, not by erythrocyte)

“Erythrocyte” [red blood cell] is used inappropriately here.  Knowing a few medical terms doesn’t equate any medical knowledge or understanding.  Medical terminology is never taught in medical schools; they just throw them at you, assuming you know them when you’re born!

He sacrificed serious knowledge to trivial stuff; he over stretched and talked too much barely relevant stories. He seemed to be obsessed by their infertility; and poor Julie [his wife], her sex life also graced the pages.  I think this is the complication of writing for Esquire [he is an editor-at-large].

He tried too hard to be funny, where and when it is not called for.  Writing for Entertainment Weekly, he aimed to entertain you, not to enlighten you, and that is certainly not what EB intends to be.

In the section of Bernard Shaw, after his posing nude himself as an editor of Esquire, he wrote, “And colleagues told me this was the end of my serious journalistic career, as if I ever had one.”  So keep in mind what kind of journalist he is while enjoying his book. 

Admittedly, I came across many amusing stories, such as Puccini’s scandal, Bonaparte Napoleon lore, the comparisons of various versions of Encyclopaedia Britannica (EB), just to mention a few.

Jacobs wrote two and half pages on vegetarianism, which is informative and fun to read, even though he talked about his aunt Marti; it seems like all of his family and relatives are smart aleck with an IQ of 200.  My 1987 EB says, “Voltaire praised, and Shelley and Thoreau practiced, the diet” Jacobs dropped “Thoreau” and I don’t know why; he should also mention other famous vegetarians, such as George Bernard Shaw and Leo Tolstoy, although he did mention the former in other section.

I like his quote (about animal) of Jeremy Bentham, “The question is not, can they reason? nor can they talk? but, can they suffer?” Let me add more of what Bentham said, “Why should the law refuse its protection to any sensitive being?  The time will come when humanity will extend its mantle over everything which breathes . . .” and he said this in 1789.

In the section of vegetarianism, he again misspelled Pythagoras as Pythagorus.  It is a trivial matter, but he has a penchant for it.

I have no clue as to why he talked about the potential Millionaire questions in the section of Vassar College.  My 1987 EB didn’t even list Vassar College; I think it is an unforgivable oversight to such a venerable liberal college.

What prompts my harsh tongue is the subtitle of “One man’s humble quest to become the smartest person in the world” which is misleading.; even if Jacobs wrote 10 books of “Know-It-All” covering different topics, it still will not be a fraction of knowledge that the educated should possess, although it may improve your chance when audition for Jeopardy.  

Both Janice and Jo mentioned his The Year of living Biblically, which I am afraid to read lest I believe that will be the Great Book [Bible].  Having a set of EB since 1987 and was an online EB subscriber for a while, I was disappointed by his choice of topics.  Having limited knowledge of the Bible I may be misled.

If you want to read something intellectual or sophisticated to enlighten you, forget it.  If you are looking for lighthearted readings between Bertrand Russell’s A History of Western Philosophy and Albert Camus’ The Plague, pick it up.

Seeing Janice reading it on our recent visit to Boston, I picked it up lest my ‘kids’ will know more than I do.  It turns out that was an unfounded fear.  I have no reservation in recommending your reading it, but I wouldn’t buy one to put in the reference shelf where my David & Ben Crystal’s Shakespeare’s Words sits.
Inscribed in the inside cover of EB, “Let knowledge grow from more to more and thus be human life enriched”,  A.J. Jacobs will be rich, but his The Know-It-All will not enrich you.