Tag Archives: Donald Trump

Is the era of precision medicine for chronic fatigue syndrome at hand?

If an idea of mine is correct, it is possible that some patients with chronic fatigue syndrome (CFS) can be treated with specific medications based on the results of a few blood tests. This is precision medicine at its finest.  The data to test this idea has already been acquired, and nothing further needs to be done except to analyze it.

Athough the initial impetus for the idea happened only 3 months ago, there have been enough twists and turns that the best way explanation is by a timeline.

First some background:

As a neurologist I saw a lot of people who were chronically tired and fatigued, because neurologists deal with muscle weakness and diseases like myasthenia gravis which are associated with fatigue.  Once I ruled out neuromuscular disease as a cause, I had nothing to offer then (nor did medicine).  Some of these patients were undoubtedly neurotic, but there was little question in my mind that many others had something wrong that medicine just hadn’t figured out yet — not that it hasn’t been trying.

Infections of almost any sort are associated with fatigue, most probably caused by components of the inflammatory response.  Anyone who’s gone through mononucleosis knows this.    The long search for an infectious cause of chronic fatigue syndrome (CFS) has had its ups and downs — particularly downs — see https://luysii.wordpress.com/2011/03/25/evil-scientists-create-virus-causing-chronic-fatigue-syndrome-in-lab/

At worst many people with these symptoms are written off as crazy; at best, diagnosed as depressed  and given antidepressants.  The fact that many of those given antidepressants feel better is far from conclusive, since most patients with chronic illnesses are somewhat depressed.

The 1 June 2017 Cell had a long and interesting review of cellular senescence by Norman Sharpless [ vol. 169 pp. 1000 – 1011 ].  Here is some background about the entity.  If you are familiar with senescent cell biology skip to the paragraph marked **** below

Cells die in a variety of ways.  Some are killed (by infections, heat, toxins).  This is called necrosis. Others voluntarily commit suicide (this is called apoptosis).   Sometimes a cell under stress undergoes cellular senescence, a state in which it doesn’t die, but doesn’t reproduce either.  Such cells have a variety of biochemical characteristics — they are resistant to apoptosis, they express molecules which prevent them from proliferating and — most importantly — they secrete a variety of proinflammatory molecules collectively called the Senescence Associated Secretory Phenotype — SASP).

At first the very existence of the senescent state was questioned, but exist it does.  What is it good for?  Theories abound, one being that mutation is one cause of stress, and stopping mutated cells from proliferating prevents cancer. However, senescent cells are found during fetal life; and they are almost certainly important in wound healing.  They are known to accumulate the older you get and some think they cause aging.

Many stresses induce cellular senescence of which mutation is but one.  The one of interest to us is chemotherapy for cancer, something obviously good as a cancer cell turned senescent has stopped proliferating.   If you know anyone who has undergone chemotherapy, you know that fatigue is almost invariable.

****

One biochemical characteristic of the senescent cell is increased levels of a protein called p16^INK4a, which helps stop cellular proliferation.  While p16^INK4a can easily be measured in tissue biopsies, tissue biopsies are inherently invasive. Fortunately, p16^INK4a can also be measured in circulating blood cells.

What caught my eye in the Cell paper was a reference to a paper about cancer [ Cancer Discov. vol. 7 pp. 165 – 176 ’17 ] by M. Demaria, in which the levels of p16^INK4a correlated with the degree of fatigue after chemotherapy.  The more p16^INK4a in the blood cells the greater the fatigue.

I may have been the only reader of both papers with clinical experience wth chronic fatigue syndrome.  It is extremely difficult to objectively measure a subjective complaint such as fatigue.

As an example of the difficulty in correlating subjective complaints with objective findings, consider the nearly uniform complaint of difficulty thinking in depression, with how such patients actually perform on cognitive tests — e. g. there is  little if any correlation between complaints and actual performance — here’s a current reference — Scientific Reports 7, Article number: 3901(2017) —  doi:10.1038/s41598-017-04353.

If the results of the Cancer paper could be replicated, p16^INK4 would be the first objective measure of a patient’s individual sense of fatigue.

So I wrote both authors, suggesting that the p16^INK4a test be run on a collection of chronic fatigue syndrome (CFS) patients. Both authors replied quickly, but thought the problem would be acquiring patients.  Demaria said that Sharpless had a lab all set up to do the test.

Then fate (in the form of Donald Trump) supervened.  A mere 9 days after the Cell issue appeared, Sharpless was nominated to be the head of the National Cancer Institute by President Trump.  This meant Dr. Sharpless had far bigger fish to fry, and he would have to sever all connection with his lab because of conflict of interest considerations.

I also contacted a patient organization for chronic fatigue syndrome without much success.  Their science advisor never responded.

There matters stood until 22 August when a paper and an editorial about it came out [ Proc. Natl. Acad. Sci. vol. 114 pp. 8914 – 8916, E7150 – E7158 ’17 ].  The paper represented a tremendous amount of data (and work).  The blood levels of 51 cytokines (measures of inflammation) and adipokines (hormones released by fat) were measured in both 192 patients with CFS (which can only be defined by symptoms) and 293 healthy controls matched for age and gender.

In this paper, levels of 17 of the 51 cytokines correlated with severity of CFS. This is a striking similarity with the way the p16^INK4 levels correlated with the degree of fatigue after chemotherapy).  So I looked up the individual elements of the SASP (which can be found in Annu Rev Pathol. 21010; 5: 99–118.)  There are 74 of them. I wondered how many of the 51 cytokines measured in the PNAS paper were in the SASP.  This is trickier than it sounds as many cytokines have far more than one name.  The bottom line is that 20 SASPs are in the 51 cytokines measured in the paper.

If the fatigue of CFS is due to senescent cells and the SASPs  they release, then they should be over-represented in the 17 of the 51 cytokines correlating with symptom severity.  Well they are; 9 out of the 17 are SASP.  However although suggestive, this increase is not statistically significant (according to my consultants on Math Stack Exchange).

After wrote I him about the new work, Dr. Sharpless noted that CFS is almost certainly a heterogeneous condition. As a clinician with decades of experience, I’ve certainly did see some of the more larcenous members of our society who used any subjective diagnosis to be compensated, as well as a variety of individuals who just wanted to withdraw from society, for whatever reason. They are undoubtedly contaminating the sample in the paper. Dr. Sharpless thought the idea, while interesting, would be very difficult to test.

But it wouldn’t at all.  Not with the immense amount of data in the PNAS paper.

Here’s how. Take each of the 9 SASPs and see how their levels correlate with the other 16 (in each of the 192 CSF patients). If they correlate better with SASPs than with nonSASPs, than this would be evidence for senescent cells being the cause some cases of CFS. In particular, patients with a high level of any of the 9 SASPs should be studied for such correlations.  Doing so should weed out some of the heterogeneity of the 192 patients in the sample.

This is why the idea is testable and, even better, falsifiable, making it a scientific hypothesis (a la Karl Popper).  The data to refute it is in the possession of the authors of the paper.

Suppose the idea turns out to be correct and that some patients with CFS are in fact that way because, for whatever reason, they have a lot of senescent cells releasing SASPs.

This would mean that it would be time to start trials of senolyic drugs which destroy senescent cells on the group with elevated SASPs. Fortunately, a few senolytics are currently inc linical use.  This would be precision medicine at its finest.

Being able to alleviate the symptoms of CFS would be worthwhile in itself, but SASP levels could also be run on all sorts of conditions associated with fatigue, most notably infection. This might lead to symptomatic treatment at least.  Having gone through mono in med school, I would have loved to have been able to take something to keep me from falling asleep all the time.

 

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A bit of history

I’ve been reading Nature since I’ve been able to afford a subscription, e.g. since about 1972. To put their undoubted coming hysteria about Trump’s withdrawal from the Paris agreement into perspective, consider the fact that they bought the arguments of the Club of Rome, hook line and sinker. The Wikipedia article is quite sanitized, but here’s a direct quote from the jacket flap of the club’s book “The Limits to Growth” which came out in 1972.

“Will this be the world that your grandchildren with thank you for? A world where industrial production has sunk to zero. Where population has suffered a catastrophic decline. Where the air, sea and land are polluted beyond redemption. Where civilization is a distant memory. This is the world that the computer forecasts. What is even more alarming, the collapse will not come gradually, but with awsome suddenness, with no way of stopping it”

Well, it’s 45 years later and their grandchildren have seen no such thing. Nature’s online available archives go back to 1975, but I’ve been unable to find a link to one of their articles. If anyone out there has found one, post a comment.

When we were down in New Haven, I picked up a book by a Yale Prof, Paul Sabin called “The Bet” concerning the intellectual conflict between Paul Ehrlich — he of the population bomb and Julian Simon. Ehrlich said we’d run out of just about everything shortly (presumably because of too many people), so economist Simon bet him that we wouldn’t. The intellectual war began in earnest in the 80’s and dragged on for a decade or so.

I recommend the book. In it you will find John Holdren, Obama’s ‘science’ advisor, also a devout malthusian, although with a degree in physics.

Perhaps Nature has it right this time, and that the models of warming which failed to predict the climate stasis of 17 years duration (the term pause gives away the game implying that temperature will continue to increase) are a reliable guide to the future.

Even if Nature is right, the Paris Agreement was terrible, no verification, no penalties for missing targets etc. etc. A massive expansion of governmental control and clamps on economic expansion, for minimal benefit.

So relax. Protest if you wish, it’s a cheap display of virtue which costs you nothing, even though you’re quite willing to fight global warming down to the last coal miner.

A book recommendation

If you’re Irish and your family looks like it’s been at a wake since 8 November or if you’re Jewish and your family has been sitting shiva since Trump won, I’ve got a book for them. They’ll hate it of course and reading it will be painful for them, but if they want to defeat him in the future they’d best buckle up and read it.

The book is called “How Trump Won” by Joel B. Pollak, and Larry Schweikart. Pollak is Breitbart Senior News Editor at Large, and Schweikart is an emeritus American history prof.

Why should the mourners read it? Simply this. If  you want to defeat Trump in the future you should know just how he beat you. The celebrators of his victory will need no urging.

It’s pretty well written, and the chapters alternate between the two with Pollak describing his experiences in the last days of the campaign starting 19 October and Schweikart covering American history starting with Martin van Buren to put things in context. It is disconcerting as Schweikart also covers the Trump campaign from its inception in 2015, so there are jumps in time from chapter to chapter.

Even though a political junkie I was as bamboozled by the press coverage of the election as anyone else, going to bed at 10PM election night because I knew it would be a rout of Trump — “Hispanics surging to the polls” etc. etc.

A few points to whet your interest. Giving the lie to Breitbart’s antisemitism, Pollak is a devout Jew,leaving the campaign trail each Saturday to observe the sabbath. He’s a Harvard Graduate.

The authors knew Trump would win Florida, based on the early voting. They knew how various counties reliably voted, and the panhandle was early voting heavily. They could see that blacks weren’t voting as much — down 3 – 4 % in Florida, 8% in North Carolina (apparently absolute absentee numbers by location are available long before the election, although not WHO the voters were for). So much for the theory that North Carolina was won because it was difficult for blacks to get the polls — there certainly is no obstacle for early voting.

Here’s another — why were the polls so wrong. People were afraid to say they were for Trump (particularly in liberal enclaves). One pollster (Trafalgar) figured out a way around this — they just asked people who they thought their neighbors would vote for.

On election night the media did what they authors expected, calling states for Clinton as soon as possible, and delaying calling any states for Trump for as long as possible.

Well that’s enough. Either you will grit your teeth and read it or you won’t.

A few other points — I’ve never seen the Wall Street Journal, the New York Times, the Nation and the National Review agree on anything. But they were uniformly against Trump slanting the news against him, declaring his campaign imploding at various times. Fascinating that it had no effect. The National Review put out an entire issue in January 2016 titled “Against Trump.”

So if you find a biased article against your favorite politician (assuming you have one) — relax — it no longer matters.

The book is not abstract, filled with interviews by Pollak of those attending Trump rallies (along with interview of those there to protest him).

How diverse are thy articles oh alumni magazines

College Alumni Magazines love to brag about the wonderful things their graduates are doing. The recent Jan/Feb issue of one they send to me bragged about the exploits of two of their business school alums in the sports business, one graduating in 1968 the other in 1997. They also had profiles of 7 alums receiving awards at the 2016 reunions.

I didn’t get one even though attending my 50th medical school reunion. There was a lot of congestion as Donald Trump was attending the graduation of one of his kids while running for president. Our med school classmate and Nobel Laureate addressed the graduation. He didn’t get an award either, they thought he had enough.

The issue also had room for a nice recipe for Chocolate Chip Banana Cookies.

There was also an article about the president of the school deciding what US laws the University would and wouldn’t obey, declaring the University to be a “Sanctuary”

In one of the Sherlock Holmes stories the following dialog appears

Gregory (Scotland Yard): “Is there any other point to which you would wish to draw my attention?”
Holmes: “To the curious incident of the dog in the night-time.”
Gregory: “The dog did nothing in the night-time.”
Holmes: “That was the curious incident.”

It wasn’t until I read the letters to the editor in the March/April issue, that I realized just what was curious about the Jan/Feb issue.

They failed to have an article about another graduate of the business school in 1968.

Donald Trump Wharton 1968.

The first US president from the University of Pennsylvania in its 227 years of existence.

To be fair they did have an extremely wimpy note from the editor concerning why they didn’t have an article about Trump.

Ah diversity of thought and opinion in the Ivy League

Res ipsa locquitur

It’s been over 50 years since McLuhan noted “the medium is the message”.  It’s still very true

The New York Times Parodies itself

I have a conservative friend who is becoming increasingly exercised by what he regards as the antiTrump bias of the Times. I’ve told him to calm down as the Times was turning into a parody of its former self. Today the NYT obliged by doing just that.

Here’s what so exercised my friend in today’s Times (19 Feb ’17). “For $200,000, a Chance to Whisper in Trump’s Ear”, Membership at Mar-a-Lago Gives Titans Easier Access to Political Power.” This appeared on the front page taking up the twomost right columns above the fold. All of page 13 inside is devoted to the article.

Here’s how the Times parodied itself “Around the World by Private Jet: Cultures in Transformation ” This took up the entire back page of the Style Section (New England Edition at Least) “Privately chartered Boeing 757 26 day/9 countries/50 travelers/$135,000” You will ride with 5 members of the Times staff (lilywhite) — Arthur O. Sulzberger Jr. Alan Riding, Nicholas Kristof, Elaine Sciolino and Elizabeth Bumiller. You will not have to share the air with the Times’ minority editorial contributors, Charles Blow (Black) and Ross Douhat (Conservative). They don’t appear to have a Latino.

Imagine the joy of access for the cut rate price of 135K (who said the Times didn’t care about the little man), while cruising at 35,000 feet exuding both virtue and carbon dioxide.

Here’s part of what my friend had to say about the article (unfortunately he doesn’t blog (he should ) so I can’t supply a link).

Back in the early 18th Century William Congreve wrote:

” Heaven has no rage like love to hatred turned
Nor hell a fury like a woman scorned”

You would think he was talking about the venerable “Gray LADY”, aka New York Times. Indeed the paper has jettisoned any pretense of professional journalistic ethics – any pretense of journalism purpose. A week after the election, after flagrantly shilling for Clinton and smearing Trump in previous months, the editor of the Times issued in writing to the papers readers an apology of sorts by admitting the paper had lost its way and promised to return to reporting news. Evidently atonement to its readers is in the words not the performance. The Gray Lady is profoundly stunned by the rejection by most of the country of the paper’s vision of how the world should be.

—-

Since the election the scorned and enraged Gray Lady has fill page after page , day after day , with disgrace as represented by the article below. The paper has flooded us with conjecture about things that have not happened and gossip of any sort that could denigrate and damage Trump.

The relentless attacks on Trump and his playing golf with dangerous cohorts etc is in marked contrast to how it suppressed any conjecture about Obama’s rise through the notoriously crooked Chicago political machine. Not a whisper of how he was dependent on other graduates of the Chicago cesspool, such as Axelrod and Jarrett. There was dismissal of Obama’s friendship with Ayers, a principal in a murderous urban terrorist group.

The august “paper of record” never conjectured how Obama could spent 20 years listening to Rev. Wright vicious racist rants and kept listening to them, but later said he hardly knew the man.

One final thought — could this be fake news, an ad bought by the Koch brothers to embarrass the Times. Possible, but unlikely.

It all depends on whose ox is being gored

The following article appeared in the New York Times 19 October 2016. The following paragraph begins a direct, continuous, unedited quote from the start of the article. Subsequently, the article discusses other matters brought up in the debate — here’s the link for the whole thing — https://www.nytimes.com/2016/10/20/us/politics/presidential-debate.html?_r=0. The times they are a’changin’ aren’t they?

“In a remarkable statement that seemed to cast doubt on American democracy, Donald J. Trump said Wednesday that he might not accept the results of next month’s election if he felt it was rigged against him — a stand that Hillary Clinton blasted as “horrifying” at their final and caustic debate on Wednesday.

Mr. Trump, under enormous pressure to halt Mrs. Clinton’s steady rise in opinion polls, came across as repeatedly frustrated as he tried to rally conservative voters with hard-line stands on illegal immigration and abortion rights. But he kept finding himself drawn onto perilous political territory by Mrs. Clinton and the debate’s moderator, Chris Wallace.

He sputtered when Mrs. Clinton charged that he would be “a puppet” of President Vladimir V. Putin of Russia if elected. He lashed out repeatedly, saying that “she’s been proven to be a liar on so many different ways” and that “she’s guilty of a very, very serious crime” over her State Department email practices. And by the end of the debate, when Mrs. Clinton needled him over Social Security, Mr. Trump snapped and said, “Such a nasty woman.”

Mrs. Clinton was repeatedly forced to defend her long service in government, which Mr. Trump charged had yielded no real accomplishments. But she was rarely rattled, and made a determined effort to rise above Mr. Trump’s taunts while making overtures to undecided voters.

She particularly sought to appeal to Republicans and independents who have doubts about Mr. Trump, arguing that she was not an opponent of the Second Amendment as he claimed, and promising to be tougher and shrewder on national security than Mr. Trump.

But it was Mr. Trump’s remark about the election results that stood out, even in a race that has been full of astonishing moments.

Every losing presidential candidate in modern times has accepted the will of the voters, even in extraordinarily close races, such as when John F. Kennedy narrowly defeated Richard M. Nixon in 1960 and George W. Bush beat Al Gore in Florida to win the presidency in 2000.

Mr. Trump insisted, without offering evidence, that the general election has been rigged against him, and he twice refused to say that he would accept its result.

“I will look at it at the time,” Mr. Trump said. “I will keep you in suspense.”

“That’s horrifying,” Mrs. Clinton replied. “Let’s be clear about what he is saying and what that means. He is denigrating — he is talking down our democracy. And I am appalled that someone who is the nominee of one of our two major parties would take that position.”

Mrs. Clinton then ticked off the number of times he had deemed a system rigged when he suffered a setback, noting he had even called the Emmy Awards fixed when his show, “The Apprentice,’’ was passed over.

“It’s funny, but it’s also really troubling,” she said. “That is not the way our democracy works.”

Mrs. Clinton also accused Mr. Trump of extreme coziness with Mr. Putin, criticizing him for failing to condemn Russian espionage against her campaign’s internal email.

When Mr. Trump responded that Mr. Putin had “no respect” for Mrs. Clinton, she shot back, in one of the toughest lines of the night: “That’s because he’d rather have a puppet as president of the United States.”

“No puppet, no puppet,” Mr. Trump sputtered. “You’re the puppet.” He quickly recovered and said, “She has been outsmarted and outplayed worse than anybody I’ve ever seen in any government, whatsoever.”

There’s more — but the above is a direct continuous unedited quote from the article

One good thing about Trump’s election (maybe two)

Two comments on the election then back to some neuropharmacology and neuropsychiatry which will likely affect many of you (because of some state ballot initiatives).

First: Over the years I’ve thought the mainstream press has become increasingly biased toward the left (not on the editorial page which is fine) but in supposedly objective reporting. Here are just two post election examples

#1 Front page of the New York Times 9 Nov — the first sentence from something they characterize as ‘News Analysis’

““Donald John Trump was elected the 45th president of the United States on Tuesday in a stunning culmination of an explosive, populist and polarizing campaign that took relentless aim at the institutions and long-held ideals of American democracy.”

#2 Front page of the New York Times 10 Nov — more ‘News Analysis’ — Here’s the lead “Populist Fury may Backfire”. Don’t they wish.

I’ll never complain about this sort of thing again (well at least not for four years). Why? Because I’ve been reading the Wall Street Journal, The New York Times, The Nation and the National Review for probably 50 years, and Trump as the antiChrist is the first thing I’ve ever seen all four agree on. This biased coverage simply no longer matters. If it did, Trump would have lost and lost big. This just confirms the marked loss of credibility that the mainstream media has suffered.  People aren’t as dumb as the elites think they are.

Second: Political correctness and attempts to control speech so as not to offend lost big. That’s very good for us all right and left (although the impetus for speech control has switched to the left from the right over the past 56 years) — see https://luysii.wordpress.com/2015/11/22/from-banned-in-boston-to-banned-in-berkeley-in-55-years/

What do the state ballot initiatives have to do with neuropharmacology? Just this. Voters in California, Massachusetts and Nevada approved recreational marijuana initiatives Tuesday night, and several other states passed medical marijuana provisions.

I don’t think this is good. One of the arguments in its favor is that marihuana isn’t as bad as alcohol, which may be true, but if marihuana isn’t all good why add it to the mix? We don’t have a good handle on marihuana use, but it is likely to increase if it’s legal.

Why do I think this is bad (particularly for adolescents)? It is likely that inhibiting synaptic feedback isn’t a good thing for a brain which is pruning a lot of them (which happens in normal adolescence as the thickness of the cerebral cortex shrinks).

There have been many explanations for the decline in College Board Scores over the years. This has led to their normalization (so all our children are above average). If you’re a correlation equals causation fan, plot the decline vs. time of atmospheric lead. It is similar to the board scores decline. Or you can plot 1/adolescent marihuana use vs. time and get a similar curve. The problem, of course, is that we have no accurate figures for use.

Here’s the science — it’s an old post, but little has happened since it was written to change the science behind it

Why marihuana scares me

There’s an editorial in the current Science concerning how very little we know about the effects of marihuana on the developing adolescent brain [ Science vol. 344 p. 557 ’14 ]. We know all sorts of wonderful neuropharmacology and neurophysiology about delta-9 tetrahydrocannabinol (d9-THC) — http://en.wikipedia.org/wiki/Tetrahydrocannabinol The point of the authors (the current head of the Amnerican Psychiatric Association, and the first director of the National (US) Institute of Drug Abuse), is that there are no significant studies of what happens to adolescent humans (as opposed to rodents) taking the stuff.

Marihuana would the first mind-alteraing substance NOT to have serious side effects in a subpopulation of people using the drug — or just about any drug in medical use for that matter.

Any organic chemist looking at the structure of d9-THC (see the link) has to be impressed with what a lipid it is — 21 carbons, only 1 hydroxyl group, and an ether moiety. Everything else is hydrogen. Like most neuroactive drugs produced by plants, it is quite potent. A joint has only 9 milliGrams, and smoking undoubtedly destroys some of it. Consider alcohol, another lipid soluble drug. A 12 ounce beer with 3.2% alcohol content has 12 * 28.3 *.032 10.8 grams of alcohol — molecular mass 62 grams — so the dose is 11/62 moles. To get drunk you need more than one beer. Compare that to a dose of .009/300 moles of d9-THC.

As we’ve found out — d9-THC is so potent because it binds to receptors for it. Unlike ethanol which can be a product of intermediary metabolism, there aren’t enzymes specifically devoted to breaking down d9-THC. In contrast, fatty acid amide hydrolase (FAAH) is devoted to breaking down anandamide, one of the endogenous compounds d9-THC is mimicking.

What really concerns me about this class of drugs, is how long they must hang around. Teaching neuropharmacology in the 70s and 80s was great fun. Every year a new receptor for neurotransmitters seemed to be found. In some cases mind benders bound to them (e.g. LSD and a serotonin receptor). In other cases the endogenous transmitters being mimicked by a plant substance were found (the endogenous opiates and their receptors). Years passed, but the receptor for d9-thc wasn’t found. The reason it wasn’t is exactly why I’m scared of the drug.

How were the various receptors for mind benders found? You throw a radioactively labelled drug (say morphine) at a brain homogenate, and purify what it is binding to. That’s how the opiate receptors etc. etc. were found. Why did it take so long to find the cannabinoid receptors? Because they bind strongly to all the fats in the brain being so incredibly lipid soluble. So the vast majority of stuff bound wasn’t protein at all, but fat. The brain has the highest percentage of fat of any organ in the body — 60%, unless you considered dispersed fatty tissue an organ (which it actually is from an endocrine point of view).

This has to mean that the stuff hangs around for a long time, without any specific enzymes to clear it.

It’s obvious to all that cognitive capacity changes from childhood to adult life. All sorts of studies with large numbers of people have done serial MRIs children and adolescents as the develop and age. Here are a few references to get you started [ Neuron vol. 72 pp. 873 – 884, 11, Proc. Natl. Acad. Sci. vol. 107 pp. 16988 – 16993 ’10, vol. 111 pp. 6774 -= 6779 ’14 ]. If you don’t know the answer, think about the change thickness of the cerebral cortex from age 9 to 20. Surprisingly, it get thinner, not thicker. The effect happens later in the association areas thought to be important in higher cognitive function, than the primary motor or sensory areas. Paradoxical isn’t it? Based on animal work this is thought to be due pruning of synapses.

So throw a long-lasting retrograde neurotransmitter mimic like d9-THC at the dynamically changing adolescent brain and hope for the best. That’s what the cited editorialists are concerned about. We simply don’t know and we should.

Addendum 11 Nov ’16:  From an emerita nonscientific professor friend of my wife. “Much of the chemistry/pharmacology etc. is way beyond me, but I did get the drift of the conversation about marihuana and am glad to now have even a simplified concept of what it does to the brain. Having spent the last 20 years working with undergraduate and graduate students, I’ve seen first hand the decline in cognitive ability.” 

Scary ! ! ! !

Having been in Cambridge when Leary was just getting started in the early 60’s, I must say that the idea of tune in turn on and drop out never appealed to me. Most of the heavy marihuana users I’ve known (and treated for other things) were happy, but rather vague and frankly rather dull.

Unfortunately as a neurologist, I had to evaluate physician colleagues who got in trouble with drugs (mostly with alcohol). One very intelligent polydrug user MD, put it to me this way — “The problem is that you like reality, and I don’t”.

Trump

Too late to start an enormous post on huntingtin, the protein mutated in Huntington’s chorea. Coming soon. Sorry. But consider this: If Trump wins the presidency it will be a remarkable demonstration of the the lack of power of the press. When have the following agreed on an issue — New York Times, Wall Street Journal, National Review, The Nation, Weekly Standard, etc. etc. They all hate Trump editorially and by their selection of articles and phraseology. I’ve never seen anything like it.

Remarkable times. There is tremendous dissatisfaction with the way things are going. Bernie taps into it as well.

If a Harvard professor said it, it can’t be wrong

Harvard professors are always right, so here’s a quote from one about immigrants.

” It may be doubted, as a gen­eral rule, whether the young Irish-American is a better or safer citizen than his parent from Cork. He can read, but he reads nothing but sensation stories and scandalous picture-papers, which fill him with preposterous notions and would enfeeble a stronger brain than his and debauch a sounder conscience. He is generally less industrious than his sire, and equally careless of the public good.”

This is Francis Parkman (Harvard 1844) Professor of Horticulture at Harvard writing in 1878.

Got that Donald !