Wednesday, April 10, 2013

Of Mice and Men and the Late Lady Thatcher

This morning is a time of waiting for something to happen... 
  • Will North Korea fire a missile? Or do something else?
  • Is Congress gonna vote on gun violence?
  • Or anything?
  • Is The Rapture gonna happen this week?
  • What will Facebook and Google do next to disrupt our lives?
So to pass the time this morning I'm looking at less serious subjects.  My mind began wandering when NPR aired this story about laboratory mice and Alzheimer's research. 

Genetically Modified Rat Is Promising Model For Alzheimer's
A rat with some human genes could provide a better way to test Alzheimer's drugs.
The genetically modified rat is the first rodent model to exhibit the full range of brain changes found in Alzheimer's, researchers report in The Journal of Neuroscience. 
"It's a big step forward" for drug development, says Roderick Corriveau, a program director at the National Institute of Neurological Disorders and Stroke, or NINDS, which helped fund the work. "The closer the model is to the human condition in representing the disease, the more likely the drug will behave and cure the way it would in humans." 
In recent years, drug companies have developed several Alzheimer's drugs that seemed to work in animals, but did not help people with the disease. A lack of good animal models for Alzheimer's may be one reason for those failures, researchers say. 
For the past couple of decades, Alzheimer's researchers have relied primarily on mice that carry human gene mutations that cause people to get the disease in their 40s or 50s. Like people, these mice develop so-called amyloid plaques in their brains. 
But that's where the similarity ends. In people with Alzheimer's, after plaques appear, huge numbers of brain cells die. That's never happened in mice, despite lots of genetic tinkering, Corriveau says. 
So researchers began to consider a different rodent model: the rat. "Rats are 4 [million] to 5 million years closer evolutionarily to humans," Corriveau says, which means their brains are more like ours. 
But early efforts to insert Alzheimer's gene mutations into rats didn't work any better than with mice, he says. Then a group of scientists began studying a line of rats that are known to get some of the same health problems people do as they get older. 
"We thought that they would be sort of on the cusp of normal aging," says Terrence Town, a professor of physiology and biophysics at the University of Southern California. "And then if we added into that mix these mutant human genes that cause Alzheimer's, we might have a much better and much more full model of the human syndrome." 
Once they inserted the mutant genes, the rats began to develop plaques in their brains, just like the mice had, Town says. But unlike the mice, he says, these rats also developed so-called tangles in their brain cells, another hallmark of Alzheimer's. 
"The big shocker came when we started counting numbers of neurons in their brains," Town says. "It turns out that they lose up to about 30 or 35 percent of the neurons in brain regions that are classically associated with Alzheimer's disease." 
The rats also began to lose their ability to do mental tasks, like navigate a maze. And as the animals get older, Town says, "they perform even worse, much as you would see in a human being that would have these mutations." 
Town's lab has already begun testing some potential Alzheimer's drugs on the new rats. And Town says he's already getting calls from other scientists who want to try the new rats in their labs.
Blah, blah, blah...yadda, yadda, yadda...

Since I'm not an expert and don't pretend to be I'm able to say without worrying about repercussions:  I have been working around old people nearly a decade now, not counting a career in the cafeteria business which gave me a chance to observe thousands of the public -- often family groups -- for two or three generations. And I can assure anyone that the onset of Alzheimer's and other types of dementia is a crapshoot and nothing medical science has done thus far comes close to ameliorating or reversing the course of the disease, much less predicting who will or will not develop it.  

Next time the subject comes up make a note of the famous Nun's study described in a book published about twelve years ago. 
...Since 1986, University of Kentucky scientist David Snowdon has been studying 678 School Sisters--painstakingly researching their personal and medical histories, testing them for cognitive function and even dissecting their brains after death. Over the years, as he explains in Aging with Grace, a moving, intensely personal account of his research that arrives in bookstores this week, Snowdon and his colleagues have teased out a series of intriguing--and quite revealing--links between lifestyle and Alzheimer's. 
[...]...But Alzheimer's is not that simple. One especially telling case: Sister Bernadette (not her real name), who had shown no outward signs of Alzheimer's and whose youthful autobiography was rich with ideas and grammatical complexity, turned out at death to be riddled with the plaques and tangles of Alzheimer's..... Says Snowdon: "Lesson No. 1 in my epidemiology training is that there are hardly any diseases where one factor alone, even in infectious disease, will always cause illness.
You get that? After she died Sister Bernadette's post-mortem indicated she had Alzheimer's Disease and she obviously did not.

The pharmaceutical industrial complex has excelled at peddling medicine much better than curing disease. But that is consistent with their business model -- if a little is good then more is better, especially for shareholders, so the more we sell the better it is for everybody. Besides, the heavy lifting in research is done mostly by NIH and academic institutions (see above -- University of Kentucky in that case) paid for mostly by grants and tax money. The R&D divisions of for-profit drug companies are more concerned with crafting the legal details having to do with patent awards than any serious medical advances. But I digress.
Do your own search for patent evergreening and see what comes up. 

I was discussing laboratory mice and rats.

The first rat story kept playing with my mind. 
Another rat story at 3Quarks Daily seven or eight years ago reminded me of yet another story by Art Buchwald.
I heard on NPR that today is the birthday of Art Buchwald who turns eighty today. Years ago he had a radio spot for reading his columns, one of which was a crazy account of a friend of his who was going to revolutionize science by breeding a line of super-rats to be used in laboratory experiments. His reasoning was simple: Every experiment that involved testing with rats based its conclusions on statistics -- how many rats died and how many survived? The plan was to go round to the labs and collect the survivors of all these experiments, the durable "super rats" that were able to resist the disease or drug or situation that had killed off the others. By breeding a new and stronger species of lab animal it would then be possible to repeat the experiments with different conclusions because fewer of the subjects would die! The result would be freedom from ominous threats that we otherwise face because so many rats die from this or that drug or disease. Very reassuring, he reasoned!
 Again, my observations about dementia and Alzheimer's have not been shaken by any of the new designer drugs on the market. I have seen people taking Namenda and Aricept, the biggest names marketed for the disease, and none appear different from others on the group once called tranquilizers, a descriptive word no longer fashionable.  If and when my day comes, let it be known that "happy pills" will be just fine with me. Generic, thank you. No need to throw good money after bad. And in my case, if cutting the pills in half works just as well, that's even better.

(Never mind millions of others without insurance, education or other benefits who self-medicate with alcohol or bootleg pain-killers. We're not allowed to bring them up when discussing medical problems in serious conversation.)


(Get ready for a leap, now.)

Speaking for Alzheimer's, it's time to remember Margaret Thatcher who finally checked out Monday, having spent her final years in a demented decline. I will be glad to see another big news story if for no other reason to stop the avalanche of recollections of the Iron Lady cluttering up air time, column-inches, Twitter messages and Facebook infographics. 

Since this blogpost is my contribution to that collection I am including two references, both of which concern what happens after Alzheimer's (or dementia, if you prefer) runs it's course. In the end we all die. Again Art Buchwald left behind some delightful stories set in the afterlife. 
Roger's Story

My name is Roger Folger, I'm sixty-one years old, and I'm a widower. My wife, Stella, went to Heaven two years ago at the age of fifty-nine, mainly, Dr. Rappaport said, from consuming a pack of cigarettes a day. 
I was married to Stella for thirty-eight years and like most marriages, some of it was good and some of it was not perfect. I'm afraid she might say the same thing or something different.
What I didn't expect is that she would go to Heaven before me. I was crazy enough to think I could decide who died first. But it was Stella who made the decisions in the family, including this one. She was the strong one in the family and everyone had to follow her. She decided where we went on vacation, what movie we were going to see, when we went out for dinner and when we stayed home. The kids called her "Mrs. McNamara, the leader of the band."
In my immediate family Stella left behind my forty-year-old son, Timmy, who works with poor kids in the Bronx, and my thirty-eight-year-old daughter, Sarah, who can be a bit of a problem. Sarah still lives at home with me and my mother, Mimi, who drove Stella crazy throughout our marriage.

* * *

Do I miss Stella? The answer is very much. I'm very lonely without her. The only thing that makes it at all livable is that I talk to her every night. I know it sounds crazy, but we converse without any problem, she in Heaven, I in my bedroom. We've been doing it ever since she passed away. How it got started is that a week after she was buried I went to the cemetery to put flowers on her grave and said how much I missed her. All of a sudden I heard her voice. 
"Roger! It's me and the Divine Telephone Service—and it's free?"
"Stella! Does this mean we can talk to each other every day?"
"Of course. I've got a Princess phone right in my room."
I was thrilled. It was almost like being married again.
So all of a sudden we were right back to our chats, and our disagreements. With us it's not always "I love you" and "Wish you were here." 
For example, one night a few weeks ago Stella told me Mrs. Gittleson, who lived on 63rd Road, passed away. Mrs. Gittleson told Stella that I had become the Don Juan of Forest Hills and had been dating a different lady every week. 
This got me very angry and I told Stella that Mrs. Gittleson was a bitch on Earth and she's a bitch now. I also asked what she was doing in Heaven in the first place.
Stella said, "You shouldn't talk that way about the dead." 
I didn't want to defend myself but I felt I had to. I explained to Stella that I didn't go out with any one woman because I didn't want to get into a serious relationship. As a matter of fact, I didn't know what I wanted. I took one lady to the movies, another to the theater, one to dinner and someone else to watch the Mets. 
But I didn't shimmy between the sheets with any of them. 
Of course, Stella wanted to know if I desired to. I said that I didn't and neither did they.
Before we go any further, let me say that I'm not a swinger. You could call me an average person who would have remained a loyal husband if his wife hadn't died. 
I was born and raised in Montclair, New Jersey, the only son of a domineering mother and a drunk father. My mother tried to remain in complete charge of my life, even after I got married. My father was a certifiable alcoholic and our basement was piled high with empty liquor bottles. He insisted on saving every empty bottle of liquor he consumed. He said each bottle reminded him of a memorable time he had without my mother. 
My mother came from Hungarian stock. My grandparents were from Budapest. They settled in the Bronx, where my grandfather worked for a tailor. My grandmother was even more outspoken than my mother. Every time someone did something she didn't like, she put a curse on them. My mother explained to me that even if it wasn't a real curse, it was enough of one to frighten the other person, so it served its purpose. Everyone called my grandmother "Big Mimi" and my mother "Little Mimi." 
As the only child, I was Little Mimi's pride and joy. To make sure I didn't do anything wrong, she searched my room once a week. One time she found a Trojan rubber at the bottom of a drawer. I told her I was just keeping it for a latex experiment in chemistry class, but she was furious and spanked my bottom as hard as she could. 
My father died when I was ten years old. I guess I was sorry to see him go, but he wasn't much of a father. Because of his inebriation I could never understand a word he said. 
Mimi went through a grieving process when he died, but it didn't last very long. In fact, within six months she confessed to me that she had made a mistake when she married him. She told me that my father wasn't what she'd bargained for and if she had to do it all over, she would never marry anyone unless he drove a new Pontiac. 
My school life was no better or worse than anyone else's who grew up in Montclair. Mimi had a job as a nurse and I was left alone to amuse myself. 
My best friend was Twoey McGowan and he's still my best friend today. Twoey is Irish and has red hair and freckles all over. He told me he got the name Twoey because he was the second one born in his family. He didn't mind the name but no one ever spelled it right.
Twoey and I were inseparable. We went downtown every day hoping to find stuff that might have fallen out of someone's shopping bag. We'd go into a Montgomery Ward's and he'd start screaming and holding his groin. While he had everyone's attention, I'd grab whatever was on the counter. It never failed. 
At thirteen Twoey also told me how to French-kiss. He said French-kissing was God's way of telling women they should have children. 
Sex was constantly on our minds. We once went up to Twoey's apartment and watched through a window across the street while a young woman disrobed to take a bath. She had flaming blonde hair and great, round breasts. The next night we looked again, and a male the size of a grizzly bear was in the room, scratching his hairy stomach. He suddenly saw us and started yelling and flailing his arms around. We jumped down and pulled the blinds closed, hoping Mimi hadn't heard him. 
While somewhat mischievous, I was good in school and got A's most of the time. Mimi wouldn't accept anything less. Early on I told her I wanted to be a scientist. She said that was a mistake because scientists, unlike lawyers, couldn't charge by the hour. But she didn't fight me when the A's rolled in. 
Twoey, on the other hand, earned C's and D's. He said it didn't bother him because he was going to become a builder when he grew up, and you didn't need good grades to build houses.

Stella's Story
I'm Stella, the deceased. I'm in Heaven just like the song says. I'm happy here, though it doesn't mean I wouldn't be happier on Earth. My family and friends are there and I miss them very much. 
So what is Heaven like? The only thing I can compare it to is the Ritz-Carlton in Florida. Roger and I celebrated our 25th Anniversary there, in a suite overlooking the Gulf of Mexico. Up here almost everyone has a suite with an ocean view. The lobby is decorated with the finest French and English furniture and has art to die for. They have everything from Leonardo da Vinci to Norman Rockwell. 
Our Heaven is managed by Moses and St. Peter is the assistant manager. No one ever sees God. Like all Ritz-Carltons, the manager hangs out behind a closed door in the back. 
You have to follow certain rules. You have to keep the noise down, which makes life difficult for people from New York. You're not supposed to cry or complain and, above all, you have to love your neighbor even if you're not certain about her. Some people can't take the lack of conflict so there is a free shuttle bus that runs on the hour and will take them to you-know-where. 
The lobby is covered in gold. Two angels manage the reception desk and check you in when you first arrive. The concierge is Mary Magdalene and her friendly staff is there to take care of all your needs, and the bellman will do anything for you but he won't take tips. You are not permitted to tip here at all, which is how you know this is truly Heaven. 
What makes it especially relaxing is that you can order up a massage anytime you want, so you're always relaxed in the evening when Mozart gives a recital. 
Roger once asked if I had enough to do in Heaven. 
I told him everything is available. There are cooking lessons with the greatest chefs in the world. You can either get tailored clothes or Ralph Lauren off the rack for free. We have lectures by everyone from Maimonides to Winston Churchill. My favorite speaker is Franklin D. Roosevelt. When he tells us how we got involved in World War II, it's riveting. Everyone loves to listen to Eleanor too. When the Roosevelts come over from wherever they're staying in Heaven, it's standing room only. 
You can have room service here anytime you want and you can order up everything you desire, including chocolate fudge sundaes and crepes suzette—without getting fat. 
I have a beautiful living room with Louis the XIVth furniture, where I can entertain my friends, and a lovely bedroom with a Marie Antoinette bed. 
Roger asked me if we have television. 
"No," I said, "Moses won't allow it. It's full of violence and wife-beating. He told us, `If you want television, go to Hades.'" 
We can see movies like Casablanca, Gone With the Wind and the Marx Brothers, but Moses won't allow gangster movies with James Cagney or Edward G. Robinson. He also won't show The Godfather because he says it portrays human beings in a very bad light. 
One of the things available to us is concerts by the greatest musicians who ever lived. I saw Beethoven sitting in a box the other night while Leonard Bernstein was conducting the Ninth Symphony. He seemed to approve. And people who are interested in art can take courses from Michelangelo and Andy Warhol. 
You're probably wondering if there's anyone up here who shouldn't be here. Some of us think so, but we don't want to say anything because it might get back to Moses that we're criticizing the clientele. I heard there was some discussion over whether Picasso should have come to Heaven since he had such a wild life on Earth, but it was decided he was such a genius that, if rejected, he would wind up painting for the Devil. So he's around here too. 
Moses encourages people to get involved in sports too. We have an Olympic-sized swimming pool, a soccer field, a basketball court and a completely furnished gym. We don't compete because this causes ill feelings. Everyone competes against himself. There is a salon where you can play bridge, a ski lift outside the door, a bridle path, a bowling alley and a spa. You can also play golf where the course is designed so that you never hit a bad shot. There are also tennis courts and croquet greens. If you ask for a sport and they don't have it, they'll get it for you. 
What makes Heaven really Heaven for women is that they don't have to dust or vacuum or do the dishes. Roger asked me who did those chores and I told him nothing ever gets dirty.
"Is there a temple up there?" he once asked me. 
I told him there's any house of worship you could ask for. But there is a rule which is strictly observed. No one can make fun of anybody else's religion. You can worship any God you want but you can't interfere with somebody else's beliefs. If you do, they will kick you out.
"Is this Moses' rule?" 
"It's God's. He really has a thing about everyone claiming their religion is the only one. He gave Moses strict instructions that if anyone tried to cause trouble, he's to pull the trap door." 
"So being Jewish doesn't make you any better or any worse than anybody else?" 
"Right, but you can practice any religion. They even have a kosher kitchen if you want. The thing is Catholics, Jews, Protestants, Muslims, Buddhists and Hindus get along just fine. Besides, when everything is great, there's no reason to think that one of the other religions is going to hurt you."
* * *

I hate to say this but not everyone in Heaven is an angel. As a matter of fact, not every angel in Heaven is an angel. There is one angel named Prudin who is a real pain in the neck. She's into everybody's business and is constantly reporting misdemeanors to Moses. He doesn't like the idea, but angels have a different status than the rest of us. They can't be kicked out and they can only be punished by God. 
Rumor has it that Prudin was up for sainthood but when her name came up in the Vatican, she was unanimously voted down because no matter what she did for the poor she wanted everyone to know about it. 
They say that when Prudin asked a friend in Rome, "Was I blackballed by one priest or two?" the friend said, "Have you ever seen caviar?" 
I don't know if she's bitter because she didn't make sainthood or if she's just a troublemaker.
I know. That has nothing to do with Lady Thatcher. I just needed to toss that in for comic relief. In the case of Lady Thatcher's passing, it's like that of Ronald Reagan or Joseph McCarthy -- you need to  laugh to keep from crying   be serious to keep from appearing too relieved.  Here are a couple of retrospectives that caught my eye.

Margaret Thatcher will be remembered, but Thatcherism is long gone
From yesterday's Globe and Mail a remembrance that ends with this...
At first, she balked: “Must I do all this international stuff?” That, according to former minister Alan Clark, was what she groaned in 1979. She soon made up for it, and did a lot of international stuff. 
Most of it was designed to prevent or delay the great changes that soon would transform and vastly improve the world. And most of this was done to preserve Britain’s moment of fleeting power in the world. 
She worked hard to prevent the Berlin Wall from coming down and aggressively opposed German unification, telling her ministers in the midst of the 1989 uprisings not to support them. “We know perfectly well what the Germans are like and what dictators can do and how national character basically doesn’t change.” Her reason was simple: A free, post-Communist Germany would become a European voice to rival Britain’s. 
She fought hard against nuclear disarmament, to the point of opposing Mr. Reagan’s Strategic Defense Initiative because she feared it could render nuclear weapons obsolete – thus making Britain, as a nuclear power, less influential. 
She lobbied hard against ending racial segregation in South Africa, denouncing sanctions and boycotts as “patronizing” to the apartheid regime, not because she was a racist (she wasn’t) but because she saw the maintenance of racist policies as crucial to maintaining Britain’s economic power in its former colony. 
Luckily for the world, her foreign policies were generally failures. There was one exception, the one that U.S. secretary of state Alexander Haig described as “a Gilbert and Sullivan battle over a sheep pasture between a choleric old John Bull and a comic dictator in a gaudy uniform.” The Falklands War also had no meaning beyond Mrs. Thatcher’s term, or even beyond 1983 (although, quite by accident, it precipitated the end of Argentina’s military dictatorship). 
But it created the worldwide image of a triumphant, headstrong, unstoppable, stalwart Margaret Thatcher. And that image, more than any of the accidents of fate that lay behind her success, has remained. Thatcherism has vanished, Cheshire-like, leaving only the memory of a beaming face beneath a bold coiffure.
And finally, this infographic via my friend Steve Hynd who shared it on Facebook. 
For Scots the passing of Margaret Thatcher is a case of Good-bye and Good-riddance. 

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