Calvin’s education: the education begins at home

The education begins at home, so does Calvin’s; these comic strips can attest to it.  The last one is Calvin’s idea of “home education” when he got a sick day staying home.  Calvin didn’t read Mark Twain; otherwise “I never let my schooling get in the way of my education” will be his motto.

Doctor, am I going to have Alzheimer disease?

I cannot recall how often I was asked “Doctor, do I have Alzheimer disease?” or “Doctor, am I going to have Alzheimer disease?”  I sometimes responded, “If you’re still asking you do not have it;” at least not yet.  My answer is based on the fact that Alzheimer patients have no or reduced insight, and not knowing their own limits or deficits.  The comic strip shows Calvin has insight for his behavior when he says, “Golly, I’d hate to have a kid like me”, although this may be too simplistic to assess whether Alzheimer patients have insight or not.

It is safe to say that memory is the first thing to go for Alzheimer patients.  But, memory is just part of the cognitive impairment that we call dementia (“senile” dementia is an obsolete term).  Our memory will not be as sharp as it used to be as we age (graciously or not).  Some years ago when James Watson’s entire genome was being sequenced, he asked the researchers to tell him any defect genes if he had (as he can take it) with only one exception of Alzheimer gene (ApoE4).  He said were he told that he had it, then he might begin to wonder whether he is falling victim of AD whenever his memory lapsed, which is almost unavoidable as he aged.

In addition to memory impairment, AD patients are gradually losing many other functions, such as executive function (planning, organizing, decision-making and strategizing), complex attention (paying the bill, balancing the checkbook, keeping the doctor’s appointment), language and learning skills, social cognition (losing ability to interact with others may lead to inappropriate behavior), reasoning, abstraction concept, judgment, everything so precious and so dear to us and to our loved ones.  Losing insight though they may be, the AD patients are frustrated, struggling, leading to emotional instability and personality change.

In evaluating the patient one needs to keep in mind that it is not any specific skill one lacks, it is the specific skill that one used to master and now lose.

Alzheimer patients shouldn’t drive.  But AD doesn’t occur overnight and driving can pose problems at the very early stage.  With the long term memory intact, they do not lose the driving skill and may be relatively safe on the road initially.  Some years ago I had a patient (who was apparently in the stage of so called “mild cognitive impairment” or MCI) who was planning to go to a local supermarket, and ended up in Virginia (5-hour drive away). The family didn’t know until they got a call from Virginia policeman.  She apparently forgot where she was going (a short term memory), and didn’t get out of any exit and kept driving and driving.

normal → mild cognitive impairment → Alzheimer disease

Mild cognitive impairment (MCI) is reserved for those who have dementia symptoms similar to that of AD, albeit much milder.  They are still able to function and to live independently, the Alzheimer patient cannot.  MCI patients may go on to have full blown AD if they live long enough, but the data is incomplete as of now.  The three beta-amyloid PET/CT scans show the progression of accumulation of beta-amyloid plaques from normal to MCI and to AD.

If memory lapse is the only problem you have, treat it as a nuisance, an inconvenience in life (and accept the fact that the old age is upon you, like it or not); rest assured that you’re not one of the 5 or 6 millions of unfortunate Alzheimer patients that this country has.

What a disappointment: Alzheimer’s immunotherapies failed to live up to the expectation

As we know the beta-amyloid plaques (and the resultant neurofibrillary tangles that destroy the nerve cells with tau proteins) is the hallmark of Alzheimer disease (AD).  But the currently available Alzheimer’s drugs (cholinesterase inhibitors: Aricept, Exelon, Razadyne, and NMDA receptor antagonist: Namenda) do not target the beta-amyloid.

There are two reports on the January 23, 2014 NEJM issue, reporting the disappointing outcome of the immunotherapy of AD.  One is bapineuzumab (from Pfizer, inherited from Wyeth), the other solanezumab (from Eli Lilly), both are humanized monoclonal antibodies that bind to amyloid, promoting the clearance/removal of amyloid from brain, tackling the problem at its root.

The two bapineuzumab studies lasted for 78 weeks.  One trial includes patients who carried ApoE4 genes, the beta-amyloid PET scan (with Pittsburgh compound B) showed no increase in beta-amyloid plaques, compared with increase seen in the controlled group.  And yet no improvement in the clinical outcome was observed.

The four studies of these two agents have been many years in the making, consuming enormous resources, time and effort.  I am sure there will be no attempt to make an application for FDA approval.  One wonders why medicines are so expensive. 

Beta-amyloid accumulates starts many years before onset of dementia symptoms, and to try to remove it from brain after dementia develops may be too late to make a difference, as the involved nerve cells have been destroyed.  The worst fear, unlikely though it may be, would be that the beta-amyloid is not the culprit or it is not the only culprit, there may be some un-identified accomplices. 

This is another example that pharmaceutical companies reap what basic bio-research sows, but only if the basic science is sound and complete.

Beta-amyloid PET/CT scan: a new tool to diagnose Alzheimer disease

beta-amyloid plaque

I gave a talk (at Taiwanese Bible Study) last night about Alzheimer disease, focusing on the recently available tool (beta-amyloid PET/CT scan) to detect the beta-amyloid, which is the hallmark of Alzheimer disease.  If autopsy done on those who died with a clinical diagnosis of Alzheimer disease, some of them failed to show the presence of beta-amyloid plaques.  The exact incidence is unknown, but the conservative estimate is greater than 20 percent. 

Alzheimer disease is just one of the many conditions that can cause dementia, the others include frontotemporal dementia, dementia with Lewy bodies, Parkinson disease with dementia and vascular dementia.  Many Alzheimer’s disease research centers (ADRC), such as the one associated with University of Pittsburgh is conducting such study, examining the brain postmortem.  Years from now they may be able to shed further light as to how often these conditions were mistaken as Alzheimer disease during their life time.

The beta-amyloid PET/CT scan enables us to detect the beta-amyloid without doing a biopsy or autopsy.  It is done by injecting a radiotracer (Florbetapir or 18F-Pittsburgh compound B) with affinity to beta-amyloid, thus attaching to it, the emitting positron will be picked up by PET scan and the images constructed by CT scan.

A negative beta-amyloid PET/CT scan practically rules out Alzheimer disease.  The interpretation of a positive scan is more problematic; it simply indicates the presence of beta-amyloid, but not diagnostic of Alzheimer disease, as many with positive scan have no cognitive impairment at all.  It is assumed that if one with positive scan and lives long enough one will become the victim of AD.

Florbetapir F 18 (AMYViD) was approved by FDA (4/2012).  It is developed by Avid Radiopharmaceuticals of Eli Lilly.  18F-labeled Pittsburgh compound B (PIB or PiB) was approved by FDA (10/2013).  Pittsburgh compound was developed by University of Pittsburgh, the test was first conducted in 2002, published in 2004.  The one approved by FDA was the second generation, compound B, thus Pittsburgh compound B (PiB).

red = amyloid

What do we do with this expensive ($3,000) tool? The use of which will evolve as time goes by.  For the time being in the clinical practice, it should be limited to those rare occasions that finding out the presence of absence of beta-amyloid in a well-documented demented patient may alter the treatment plan or those participated in a clinical research trial.

The beta-amyloid PET/CT scan shouldn’t be done in the following conditions:

1. Classical Alzheimer dementia with typical age of onset
2. To determine the severity of dementia
3. Solely based on positive family history or presence of ApoE4 gene (3% of population have two copies of ApoE4 gene and 25% have one copy)
4. Asymptomatic individuals (a positive scan will offer one no benefit other than a worry for uncertain future)
5. Non-medical usage (legal, insurance coverage or employment screening)

This tool may affect how the clinical therapeutic trial should be conducted.  A positive scan may be a prerequisite before entering the trial in the future.  Of course, that may increase the cost of a clinical trial.  As we know the response to the currently available Alzheimer disease (AD) drugs are variable, as many of them in the trial might not have AD at all.

As yet the test is not paid by Medicare or other insurance; Medicare recently announced that it may pay for those participating in a clinical trial.  The final decision will be made later this year.

If the day will ever come (Obama has declared war on Alzheimer disease in 2012 that we’ll be able to prevent and treat AD by 2025; let’s hope he is not overly optimistic. But we have to take it what it is worth for a politician’s promise.) that the build-up of the beta-amyloid plaque can be slowed down or the progression of dementia thwarted, then this scan will be in high demand.

Grain of truth: Celiac disease, gluten sensitivity and wheat allergy

Suddenly the gluten-free diet is fashionable; it was reported up to one third of population is doing or thinking about doing gluten-free diet, or at least cutting back the gluten intake. No wonder all the food manufacturing companies are pouring out gluten-free products, treating gluten like pest.  I never chased the fashion, but I better talk about this, lest people might suspect I do not keep up with the medicine.

bread made by Janice

Gluten is a protein made of glutenin and gliadin, forming a reticular matrix, trapping the carbon dioxide that comes from the yeast fermentation; thus the dough rises.  When Janice made the delectable and chewy ciabatta breads (see photos) and Miao-Chi and Xiao always let me take some specialty breads home when I visited the Bean Town; I gave thanks to Janice, Miao-Chi and Xiao and gluten, which gave us the texture we love.  Glutens are found in wheat, barley and rye.

Celiac disease is an autoimmune disease in that our immune system treats the gluten (especially its component gliadin) as a hostile invader and attacks it, thus one of the serology test is the IgG-deamidated gliadin peptide antibody.  It only happens in susceptible individuals that bear certain gene such as HLA-DQ2 haplotype that is expressed in 90% of patients with celiac disease, whereas it is expressed in one third of the general population.  Imagine autoimmune response is like using the small intestines as the battle ground and the end result is the damage to the intestine mucosa (villi).

bread made by Janice

One with celiac disease usually presents with chronic diarrhea, abdominal pain, bloating, nutritional deficiency, osteoporosis/osteopenia, or may have abnormal liver function, and rarely a skin rash called dermatitis herpetiformisis.  It is estimated that up to 1% of population may have celiac disease; it is obviously under diagnosed; a doctor needs to keep vigilant; when in doubt, check it out.  If suspicion is raised, you doctor will first order some blood tests including liver function test.

The serology test of first choice is IgA anti-tissue transglutaminase antibody; in case of IgA deficiency, the alternative tests would be IgG anti-tissue transglutaminase antibody and IgG-deamidated gliadin peptide antibody. IgA antiendomysial antibody is another choice.

If these antibody tests turn out to be positive, then do an endoscopy with small bowel (duodenum) biopsy to obtain the most definite diagnosis.  The treatment is to remove the culprit—gluten—from the diet.

Celiac disease was first described around Jesus time by a Greek doctor; in fact “celiac” comes from Greek, koiliaki, which means “abdominal”.  Wheat was first implicated in 1944; during a Dutch famine, a doctor observed celiac disease almost disappeared when wheat was no longer available.

Then what is the “gluten sensitivity” or “gluten intolerance”? It spreads like a wild fire.  Those with gluten sensitivity present with similar, albeit milder, symptoms of celiac disease.  It is not an autoimmune disease, thus the serology tests are negative, as is HLA-DQ2 haplotype. The small intestine biopsy would be normal, if done.

Many people claim their symptoms improve following a gluten-free diet, at present the medical professional is hesitated to say it is a placebo effect.  However, the prevalence, pathophysiology and natural history remain elusive.  Gluten sensitivity is not a celiac disease; that much we’re sure, but if there were any relationship, nobody knows.  Following strict gluten-free diet unnecessarily may not be in the best interest of one’s health, it may deprive you of the fiber and many nutrients, not to mention the indulgence.

If celiac disease is under diagnosed, the gluten sensitivity is definitely over diagnosed and many of them self-diagnosed.  The fact many celebrities proclaimed they are on gluten-free diet helped adding the fuel to the fire.  This is not to say that gluten sensitivity is not considered a disease entity, though.

Wheat allergy is also an immune system disease, but it involves IgE, an innate immunity, whereas celiac disease involves IgA and IgG, an adaptive immunity. Gluten-free diet also benefits one with wheat allergy, but they can consume barley and rye with no problem.

The “molecular war” cost Harvard a Nobel Prize

I subscribed the Scientific American with an All Access option (12-issue of print and digital access and the access of all archive since 1845—the treasury I am going after).

I’m reading Howard Temin’s “RNA-directed DNA synthesis” in the issue of January 1972.  Students of genetics would know this is a big deal then; it is against the law of so-called “central dogma” (DNA → RNA → protein; this concept was conceived by Francis Crick, but he never published it; it was mentioned in a letter to the RNA Tie Club). Temin shared the Nobel Prize in 1975 with David Baltimore, who discovered the reverse transcriptase and Renato Dulbecco, under whom Temin was a post-graduate student. I was disappointed that the Wall Street Journal didn’t even have a Remembrance (obituary) for Dulbecco when he died in 2012.

Scientific American asked Temin to write this article three years before he was honored by the Nobel Prize.  Joy, I believe you had a textbook authored by Temin; either in undergraduate or medical school, I forgot.

Many years ago I wrote an article about the “Molecular War” fought between E.O. Wilson and James Watson at Harvard, detail of which is not the topic of this writing, but I can show you what Matthew Meselson said in 2002,

 “Yes, at Harvard there was a war between classical biologists and molecular biologists, but it wasn’t a war over science. There was never any discussions of science between—there was a war over space and money! Like any other war! And personalities, maybe, entered in somewhat. But it was mainly a war fought at faculty meetings.”

This molecular war cost Harvard a Nobel Prize in 1975. Prior to that Harvard was trying to recruit Temin from University Of Wisconsin, Temin accepted with a condition of giving his wife (a population geneticist) a faculty position.  Considering hiring a population geneticist was “out of mind”, James Watson vehemently objected; All Watson wanted was molecular biologist, nothing else.  And the result is University of Wisconsin got a Nobel Prize in 1975, not Harvard.

Joy, have you remembered that Matthew Meselson was the keynote speaker on your undergraduate graduation? He and Franklin Stahl demonstrated the DNA replication back in 1958 basically proving the DNA structure Watson & Crick hypothesized was correct. Meselson witnessed the molecular war first hand.

My beloved uncle and aunt

I came to the States in 1971 and when I went back to Taiwan to “claim my bride” in December 1973.  I chatted with my 3^rd uncle (my mom’s younger brother, who was a physician) on many occasions during my 2-week stay.  He asked me about every aspect of medical care in the States with the topics large and small, ranging from the infrastructure of the healthcare delivery system to the detailed technique of the central venous catheter placement via subclavian vein.

Here is the photo of my 3^rd uncle and my aunt, posted by his son, my cousin.  It comes with a very beautiful and moving Chinese writing; I translated it with reluctance as the beauty of the language would be lost.

“My parents were most happy when I took the job as the chair of ophthalmology department of the hospital in my hometown in 1986.  After graduating from elementary school, I spent the next 20 years studying or working away from home; I hardly had any time seeing or staying with mom and dad for any interval of significance.  The first lunar New Year after coming back to my home town, I took a picture of my parents in their backyard.  Dad and mom put on their best dress, smiling on their face, surrounded by the crimson red poinsettia and the green flower pots and bonsai.  The picture captured the most beautiful memory of their deep and unquenchable love. People and things are now gone with the wind; never more! Dad and mom had been home in heaven; the old home had since changed hand.  Looking back, seeing the old photo and thinking about the loved ones, my heart is heavy with mixed emotions; life is ephemeral; here today and gone tomorrow.  Live for today and seize the moment; lives one’s fleeting life to the fullest with no regret.”

鶼鰈情深

1986年我奉調回老家擔任署立醫院眼科主任一職，最高興的就是爸爸媽媽了。自國小畢業後，二十年間，幾乎都在外鄉求學就業，難得回家與爸媽相處。回鄉後第一次過年，就在自家後院為爸媽留影紀念。爸媽盛裝上場，面露微笑，四週聖誕花紅、綠色盆景圍繞，為他倆鶼鰈情深留下最美麗的回憶。如今人事已非，爸媽魂歸天國，老家也已易主。回首往事，睹照思人，百感交集，倍覺滄桑。只有把握當下，於此一無常人生，瀟灑走一回

How not to complain about this bitter winter? Read the stories in the Eastern Front

While digging ourselves out of the drive ways under the bitter cold, I was not complaining at all; I was thinking about the German and Russian soldiers fighting in the Eastern Front.  I recently finished reading two books: In Deadly Combat: A German Soldier's Memoir of the Eastern Front by Gottlob Herbert and Hitler’s War by David Irving.  I am hoping the hell is not just a human invention; it is an absolute necessity; without hell where could Hitler go?

When Hitler forbade the German army to retreat; the German soldiers had to dig the fox holes or trench in the white tundra; they had to use explosives to make holes.  Initially when they went to sleep under the bitter cold (-22º F), they’re afraid they might not wake up.  After surviving in the living hell for so long; when they went to sleep, they’re afraid they might wake up again.  (Mark Twain said something to this effect).

It was said that Russian soldiers could take the cold better; whoever said that was apparently not there to see how Russian soldiers suffered; they might have better fortitude and took it as it came, the suffering was just the same.  I’ll list a few statistics to make the point.

^ 27 million Russian died, of whom 16 million were civilians.

^ June 1944: estimated 90% of all Russian young men between the ages of 18 and 21 are already killed in action.

^ The Russian lost 20 casualties for every German, 6 tanks for every panzer; in 10/1941 their losses were even worse than those of summer, with 64 divisions written off.

^ Hitler launched Barbarossa on 6/22/1941 and by 2/20/1942 German army had counted 112,627 of frost victims, of which no fewer than 14,357 were amputees. "Barbarossa" had now cost the German forces close to 1,000,000 casualties, including 200,000 dead.

Americans in Paris and French in Monticello

It is perfect fitting for the visiting French President Francois Hollande to visit Thomas Jefferson’s estate, Monticello, before going to the White House.  A noted Francophile, Jefferson was thinking about returning to France when he, after spending 5 years as the second Minister to France, returned to the States In September 1789.  It is difficult to characterize his relationship with the French lady, Maria Cosway, who wrote a letter to Jefferson on 6/11/1790, “I fear my Dear friend have forgot me: Not one line ever since your Departure from this part of the world!”  Jefferson was also a good friend of Lafayette’s aunt in his Paris years.

The French president must be proud of the French’s influence on our third president and the author of the Declaration of Independence.

John Adam’s house was Jefferson’s second home when he first arrived at Paris on 8/6/1784; his wife, Martha, died of child birth in 1782. When the Adams left for London in 1785, the lonely Jefferson missed them terribly, we read his letter, “The departure of your family has left me in the dumps, my afternoons hang heavily on me.” (John Quincy Adams, the 6^th president, left Paris for Boston, so he could enroll into Harvard).

Jefferson’s autobiography was only up to his 5-year stay in Paris.  Sally Hemings accompanied Jefferson’s daughter Mary (Polly) to Paris in 1787.  It was said that Sally wished to stay in Paris when Jefferson returned to the States in 1789 for she would be a free woman in Paris and a slave in Charlottesville, Virginia.  Jefferson had to persuade her to return with him, promising her that her children would be free once they reached adulthood.

The First Lady, Michelle, didn’t accompany president to Monticello for obvious reason, as the French president came alone, after the recent split with his longtime partner (the official French First Lady), Valerie Trierweiler.  The president was caught slipping out of the Palace in the deep (and heat) of the night to meet with the glamorous French actress Julie Gayet.  Our First Lady must be disappointed for not being able to visit her beloved Monticello.  She might take comfort in knowing that this is not the garden season and at least she didn’t miss Jefferson’s garden.

{it should be ‘in the deep and hot of the night’ grammar wise, but I still like ‘heat’ to go along with the ‘deep’}

What’s Moby Dick got to do with Charing Cross in London?

One doesn’t just read Moby Dick, one studies it or even has to do research and this keeps many away from it.

In chapter 32 Cetology (study of whale; a branch of zoology), we read,

“This is Charing Cross; hear ye! Good people all, the Greenland whale is deposed, the great sperm whale now reigneth!”

While strolling in the Charing Cross, one may wonder: is this the Charing Cross Herman Melville was referring to? I think it is.

In the chapter of cetology Melville was talking about how Greenland whale had long been enthroned as monarch of the deep undeservedly as it “usurper upon the throne of the seas”.  And the time has come to right the wrong to proclaim that the great sperm whale should reign.  The followings are how he wrote,

The Greenland Whale, or Balaena mysticetus, has so frenetly been described in a popular manner, that the public voice has long enthroned him as monarch of the deep.” The Greenland whale “usurper upon the throne of the seas . . . not even by any means the largest of the whales.”  And “the time has at least come for a new proclamation.  This is Charing Cross; hear ye! Good people all, —Greenland whale is deposed, —the great sperm whale now reigneth!”

Melville visited London in 1849 and stayed in the house on Craven Street (Benjamin Franklin house is also nearby on the same street), next to Charing Cross (the house has since been demolished and is now marked by a blue plaque).  It is here that he conceived Moby Dick. It was also said he saw a one-legged beggar, the survivor of a whale attack; and that gave us the one-legged captain Ahab.

equestrian Charles I

While staying in Charing Cross Melville must have seen the statue of the equestrian Charles I; he must be familiar with the British Civil War story (American Civil War was still 11-12 years away in the making).  Melville might liken Oliver Cromwell (Parliamentarian) to Greenland whale, usurping the British throne, although Cromwell himself never claimed the throne.  Proclaiming the sperm whale as the king of the sea is like the restoration of the throne by Charles II—son of Charles I.

That is the best explanation I can come up with;  Moby Dick was first published in Britain and was never recognized in America up to his death in 1891.  British authors, the likes of Virginia Woolf and W.H. Auden acclaimed Moby Dick as “a modernist work before modernism was invented.”

Even the British are not sure why it is called Charing Cross.  Some say the old English word “cierring”, as there is a nearby bend of River Thames.  There was an Eleanor Cross back in 13^th century, commemorating wife of King Edward I, Charing came from chere reine—“dear queen” in French.  But some doubt it as the name predated Eleanor’s death by one hundred years.

The muse while walking in the Trafalgar Square, Charing Cross and the Tower of London

Charles I

While on the walking tour in London, one for sure will walk around Trafalgar Square, Charing Cross and the Tower of London.  I’ll be thinking about Charles I, Churchill or even Herman Melville’s Moby Dick.  I’ll tell you why.  I have talked about Charles I previously.  The majestic statue of Charles I mounted on a horse has been in the Charing Cross since 1675 and the statue was made 30-40 years earlier.

There is quite a story of this statue, which almost “died” when Charles I was executed in 1649.  It was also removed for safety during the London Blitz.

http://doctorjytsai.blogspot.com/2013/11/mourning-of-charles-i-in-front-of.html

Trafalgar Square

In the beginning of WWII Hitler really didn’t want to fight the British if he had his way (he was also careful not to provoke America).  He thought if he could conquer Russia, England will come to term with him and that’s why he launched the Barbarossa in June 1941.  German had propaganda trying to make peace with the British.  I read the followings in George Orwell’s diary.

“The frightful outburst of fury by the German radio (if rightly reported, actually calling on the English people to hang Churchill in Trafalgar Square) shows how right it was to make this move.”

“There are now rumors that Lloyd George is the potential Petain of England, . . . The Italian press makes the same claim and says L.G’s silence proves it true.” (7/25/1940)

Lloyd George was pessimistic about the prospect of winning the war against Nazi Germany, advocating a negotiated peace in May 1941; this led Churchill to compare him with Philippe Petain, who headed the Vichy government—a Nazi’s puppet.  Petain was the French general and hero during WWI and Lloyd George led the British government as the Prime Minister during WWI.  It is sad that the fighting spirit apparently faded as one aged.

 

Trafalgar Square is to London what Red Square is to Moscow or Tiananmen Square (The Gate of Heavenly Peace) is to Beijing.  The name commemorates the 1805 Battle of Trafalgar (off the coast of Cape Trafalgar, Spain) with British fleet victory over France, led by Admiral Nelson, who died when the battle was won, so it is fitting to have the Nelson’s column in the center of the Square.

Nelson Column

Herman Melville also saw the Nelson column when he lived at the Craven Street next to Charing Cross in 1849, when and where Moby Dick was conceived.  We read in Moby Dick Chapter 35 The Mast-Head,

“Admiral Nelson, also, on a capstan of gun-metal, stands his mast-head in Trafalgar Square; and ever when most obscured by that London smoke, token is yet given that a hidden hero is there; for where there is smoke, must be fire.”

Churchill has other thought about where he would be hanged if the Nazi Germany won.  In the early stage of the war Churchill said the War Cabinet (comprised five men: Churchill, Chamberlain, Attlee, Halifax and Grenward)—“the ones who had the right to have their heads cut off on Tower Hill if we did not win”

Charing Cross

Before the Battle of France was all over in June 1940 Churchill hurried to Paris 3 or 4 times trying to shore up France.  In mid June 1940, on his last flight from France, he asked Ismay, “Do you realize we probably have a maximum of three months, to live?”

Charing Cross is the south edge of Trafalgar Square.  In Chapter 32 (Cetology) of Moby Dick, we read “This is Charing Cross; hear ye! Good people all,--the Greenland whale is deposed,--the great sperm whale now reigneth!”  I will tell you on another post why Melville said “This is Charing Cross”, or so I thought.

My letter-to-the-editor about chronic fatigue syndrome

I have another letter-to-the-editor published at the Observer-Reporter today (Feb. 2).  I basically wanted to say that chronic fatigue syndrome is the worst “poster boy” to criticize the NIH biomedical research cut back and the failure of Big Pharma to come up with the therapy for it.  The essay author (Mr. King) is apparently a fervent chronic fatigue syndrome advocate.

I use the example of BCR-ABL1 fusion gene (Philadelphia chromosome), a very specific exact science, to emphasize the stark contrast to the chronic fatigue syndrome, which remains in a “murky” state as our understanding of the disease goes. 

(the following is the letter).

I disagree with what Llewellyn King said in his essay, “The shame of biomedical research across the U.S.,” which appeared on the Observer-Reporter's commentary page Jan. 26.  In the essay, King faults the pharmaceutical companies and National Institutes of Health for their failure in developing therapy for chronic fatigue syndrome.   This reflects his lack of understanding for the potential and limits of biomedical research of pharmaceutical companies.

Dr. Janet Rowley who died Dec. 17, discovered the specific cross over between chromosome 9 and 22, resulting in the BCR-ABL1 fusion gene, also called Philadelphia chromosome, which is responsible for chronic myeloid leukemia (CML).  The subsequent development of tyrosine kinase inhibitor, such as Gleevec (imatinib), has since rendered the once dreaded CML into a chronic disease, with over 90 percent of the patients enjoying the normal life span.  This is a perfect example of the pharmaceutical companies reap what the basic biomedical research sows.

Chronic fatigue syndrome is a totally different story.  Experts have difficulty defining it.  The Center for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Disease have both published and revised its definitions several times.  The theories of the causes and psychopathophysiology abound, but there is no consensus.  [There is nothing for the pharmaceutical companies to tackle the problem at its roots yet.]

King lamented the cut back of NIH funding for the basic biomedical research, which, I agree, is short-sighted.  This is not to say that NIH shouldn’t fund the research on chronic fatigue syndrome, but blaming the Big Pharma at this point is missing the point.