MD-Writer Blog

Last month’s Scientific American Mind ran an article on research showing that young adults with a variant of the enzyme MAO-A in their brains carry, on average, up to 16% more credit-card debt than those with another form of enzyme. Although that’s not a huge effect, the story is interesting because of the enzyme implicated in the study. The investigation was performed by scientists at UCSD and the London School of Economics.

Monoamine oxidase type A (MAO-A) is a central player in brain function. It metabolizes (clears) monoamine neurotransmitters, thus lowering their levels in the brain. Three of the most important and extensively studied of these neurotransmitters are norepinephrine (aka noradrenaline), dopamine and serotonin, which are involved in mood, attention, motivation, goal-directed and instinctual behaviors.

The neurotransmitters act when one activated neuron (the presynaptic neuron) secretes one of them into the synaptic cleft to stimulate or inhibit the activity of the next neuron (the postsynaptic neuron) in the neuronal pathway. After secretion the neurotransmitter is withdrawn back into the presynaptic neuron, where it is destroyed by MAO-A.

The scientists found that young adults with less credit-card debt tended more often to carry a highly active variant of the MAO-A gene. But people with a low activity variant carried more debt:

In the new study, people with one “low” MAOA gene and one “high” MAOA gene reported having credit-card debt 7.8 percent more often than did people with two “high” versions, the researchers found, even when they controlled for factors such as education and socio­economic status. For people with two “low” versions of the gene, that number jumped to 15.9 percent.

The high-activity form of MAO-A would result in lower overall levels of the neurotransmitters in the neuronal pathways utilizing them. Conversely the low-activity form would result in higher levels of the neurotransmitters.

High levels of norepinephrine and dopamine may produce impulsive, addictive and manic behavior. These neurotransmitters are closely related in chemical structure to the drugs amphetamine and cocaine. High levels may tend to promote the same sorts of behavior that these drugs do. For example, a research study in laboratory rats found that inhibition of MAO-A increased the animals’ consumption of nicotine.

In humans, inhibition of MAO-A and the resulting boost of neurotransmitter levels may often result in elevation of mood and, rarely, manic behavior. Indeed MAO inhibitors were among the first drugs approved for use as antidepressants.

I would conjecture that young adults with the genes for low-activity MAO-A and higher levels of monoamine neurotransmitters probably engage more often in impulsive and instinctually driven behavior. In pursuit of their goals, they may spend more money and use their credit cards more often, sometimes without fully considering the consequences.

VACATION: I will be on vacation next week. MD-Writer blog will resume publication of new postings on Tuesday after Labor Day.

Current education policy has moved away from No Child Left Behind, President Bush’s program, which emphasized standardized tests, to Race to the Top, President Obama’s initiative, which continues the testing but adds a focus on individual teachers and students.

Like most Americans concerned about the future of our nation and the upcoming generation of students, I’ve been troubled by our problems with education. But now I feel encouraged. I think the policymakers have finally got it right.

Last January, the president spoke about the new policy at an elementary school in Virginia. He said, “We urged states to use cutting-edge data systems to track a child’s progress throughout their academic career, and to link that child’s progress to their teachers so we know what’s working and what’s not working in the classroom.”

Perhaps in that spirit, this week the L.A. Times announced the upcoming publication of a new database tracking the performance of public school teachers in that city. The news organization analyzed seven years of students’ math and English test scores, obtained from the L.A. school system, to estimate the effectiveness of teachers. According to the article, the statistical method, called “value-added analysis,”

rates teachers based on their students’ progress on standardized tests from year to year. Each student’s performance is compared with his or her own in past years, which largely controls for outside influences often blamed for academic failure: poverty, prior learning and other factors.

Jason Felch, the reporter on the investigation, interviewed on NPR’s “All Things Considered” last evening, explained the reasons for tracking teachers and publishing the database:

Well, the big takeaway from our series and after, you know, spending a lot of time analyzing this data is that individual teachers really matter. The difference between teachers can be enormous, and which teacher a child gets is often left up to chance. So it would be difficult to have the information about which teachers are effective and which teachers are less effective and not make that public.

I remember my fifth grade teacher. It took me years to realize that for personal reasons of her own, she actively sought to undermine my education. One day during an assembly of the students, I competed against other students answering questions on science. She arranged for my correct answer to be announced false to eliminate me from the competition and teach me a lesson.

In contrast: My high school physics teacher, who was motivated by the subject and his passion to teach. Physics and math were beautiful things to him. He wrote the equations on the blackboard in an elegant hand that expressed his love for the subjects. His enthusiasm and his conceptual clarity transferred themselves to my classmates and me.

Although, I’m not an expert in education, I’ve had some degree of educational success, graduating from an Ivy League college and a top tier medical school. I think standardized learning—measured by tests—and the learning of fundamental concepts—imparted by excellent teachers—are both important for educational success. But teachers tip the balance.

At last, the country is moving ahead on education. The first leg was the standardized learning and the tests to measure it, under President Bush’s program. Under President Obama, the second leg is the excellence of performance by teachers. The nation is stepping forward, perhaps soon to walk, eventually to run.

Researchers at Boston University School of Medicine have found that amyotrophic lateral sclerosis (ALS, Lou Gehrig’s Disease) may result from repetitive trauma to the brain. The disease characteristically begins with muscle weakness and lack of coordination. People have difficulty getting out of chairs, climbing stairs, and sometimes swallowing. Slowly, inexorably, the paralysis spreads up and down from the brain through the spinal cord, affecting almost all movements, including speech and respiration.

I witnessed the horrifying progression of the disease in my uncle, who succumbed in three or four years. He lost all motion, but he remained alert and aware throughout, since only motor functions are affected. Among my last memories of him: I was 10. He sat across the dining room table from me, trying to tell me something. He had something very important to communicate, and he tried very hard, again and again, to tell me. But his speech was so inarticulate, his voice unbroken by consonants, his tone uninflected by vowels, that I could not understand. He tried, it seemed to me, for an hour, although it was probably only a few minutes. I left him, apologizing, unable to endure more. I wonder to this day what he must have experienced, imprisoned in his skin.

The cause of the disease has always been a mystery. It is primarily genetic in only a few cases; most are sporadic. But the medical scientists studied the brains and spinal cords of 12 athletes—football players, a military veteran, a boxer and others—who had suffered multiple blows to their CNS and developed neurodegenerative diseases of the brain and spinal cord. On examination, they all had abnormal deposits of two proteins, one called tau and another called TDP-43 in their brains. But three of the 12, who had been diagnosed with ALS, also had TDP-43 in their spinal cords. Those three were the only ones of the 12 to show the protein there.

TDP-43 has also been found in the CNS of persons who suffered from the sporadic form of ALS, according to the report of the research in ScienceDaily yesterday.

In my uncle’s case, I always wondered whether his illness might have been connected to his job as a milkman. The occupation no longer exists. The delivery service worked in times when milk came in the early morning, unhomogenized and sometimes even unpasteurized, direct from local farms and plants. It faded away with refrigeration and supermarkets. But I remember, for a few years early in my life, the milkbox on the front stoop and the whiteness-filled bottles deposited each morning by the man with the truck. How many heavy crates of milk did my uncle lift day after day? How far did he walk carrying bottles? It was his right arm and right leg that first showed the telltale weaknesses.

Heavy lifting is not cerebral concussion, of course. But in an article in June, the scientists noted that repetitive injury to the CNS plays a central role in many cases degenerative CNS disease characterized by abnormal accumulations of tau protein. They said

Trauma to the central nervous system is one of the most consistent candidates for initiating the molecular cascades that result in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis.

So perhaps my uncle’s years heavy lifting and carrying, his long life of yanking on his muscles and nerves, did play a role in his disease.

Less than half of Americans accept as fact that humans descended from ape-like primates, according to a survey by the National Science Foundation in 2006. People like me wonder about these deniers of science. How do their minds work?

Not only does evolution seem self-evident, since many animals of different species are so much alike—think of wolves and dogs, tigers and cats, as well as chimps and humans—but today we understand DNA and mutations, concepts that help to explain it. So, how is it possible for reasonable people to reject evolution?

Nevertheless, Americans hold an overwhelmingly positive attitude toward science. According to a Pew Survey last year, 84% of us see science as having a positive effect on society. This seems paradoxical. What mental mechanisms would allow so many people to deny a core scientific theory like evolution and at the same time see science as doing much good?

Yesterday, science journalist Jay Ingram, suggested one explanation in a Scientific American podcast. Notwithstanding the well-known aphorism that you can choose your own opinions but you can’t choose your own facts, he proposed that many people actually do both.

His explanation came up in connection with the climate change debate, in order to explain why many people refuse to accept any human contribution to the phenomenon. Ingram suggested that people pay attention mostly to facts that support their beliefs but usually ignore others that don’t. Conversely they particularly scrutinize and find fault with facts that contradict their beliefs, while they accept uncritically those that confirm them.

Ingram’s proposal is supported by Pew results showing the most religious people, who attend religious services weekly or more often, question evolution more frequently than others (49% do). And conservative Republicans have the lowest rate of accepting that human activity increases global warming (21% do).

I suspect, however, that there is another reason, perhaps as significant. It is clearly expressed in an old rock ‘n’ roll song:

Don’t know much about history
Don’t know much biology
Don’t know much about a science book
Don’t know much about the french I took
But I do know that I love you
And I know that if you love me too
What a wonderful world this would be

Science and scientific knowledge are hard work, and learning them causes mental and emotional pain, even anguish at times. When you are in high school—the age group for whom Sam Cooke sung his 1958 tune—there’s little immediate payoff for making the intellectual effort to master the subjects, particularly during years when instinctual drives dominate the mind.

Many Americans who passed on science during their educational years cannot now understand its logic and reason. A significant number of us, I suspect, prefer to reject science in favor of religion or other sources of opinion, whose reasons we are able to comprehend. For this group, it’s not a matter of choosing your own facts, but rather allowing ourselves to live in the absence of facts. Ignorance—for a certain group of Americans, perhaps a substantial number of us—is indeed bliss.

This weekend, the NY Times ran a story on the Obama’s administration’s covert war on al Qaeda. But war is not the right word. What the reporters described is a clandestine Special Forces campaign.

The reporters wrote that the CIA has become a paramilitary organization, conducting attacks with missiles and other weapons, and the Pentagon has be come like the CIA, conducting spy missions. Private companies under government contract have also participated.

Such operations have played major roles in the wars Iraq and Afghanistan and in operations in Yemen. Congressional oversight has lagged, because existing legislation doesn’t apply to these special military programs, the Times reports.

I read the story with ambivalence. On the one hand, I know in my heart that if I were president, I would, like Obama, authorize any covert operation that could reasonably succeed in tracking down and eliminating Bin Laden and other terrorists.

On the other hand, I imagine and worry about the possible misuse of such capabilities by a future government of the United States. In the nightmare scenario I envision, Will Smith plays Robert Dean fleeing agents of the NSA in the 1998 movie “Enemy of the State.” Dean, an innocent bystander caught up in a rogue security operation, possesses a videotape showing a murder committed by the agents of the government.

In the most hellish scene, Smith runs and jumps from rooftop to rooftop, dashes up and down stairs, sprints down streets and through tunnels, etc., in Washington, DC, pursued by agents in helicopters, cars and on foot, all the while tracked by surveillance cameras.

Back when the movie was filmed, there were no drones. But if there were an actual Robert Dean today, he could be surveilled from on high by drones and targeted by missiles.

Ours is a nation that was founded in rebellion. The signers of the Declaration are reputed to have joined in rebellion because Benjamin Franklin told them, “We must hang together, gentlemen…else, we shall most assuredly hang separately.”

What would happen today if an unjust government misused its power against the citizenry? I don’t mean the stuff of Tea Party paranoia, which is making the rounds today on some networks on the internet. I mean suppose it really happened. What would happen if the government started using some of the awesome counterterrorism capabilities it is now developing to pursue al Qaeda on American citizens inside this nation?

I worry about that when I read a story such as this one in the Times Saturday. I applaud the aggressive pursuit of Bin Laden at the same time as I remember that the existence of al Qaeda itself is attributable to blowback from CIA clandestine operations. Could the blow one day come back to our own nation?

Vaccination usually involves injecting someone with a dead or weakened microbe for the purpose stimulating the development of immunity. A similar thing happens when a malaria-infected mosquito bites a human. The mosquito injects a form of the malaria parasite, called a sporozoite, into the person’s blood stream. Only, the human usually doesn’t become immune but sick with malaria.

Suppose there were a way to weaken the malaria parasite after a mosquito bite, so that instead of becoming sick, a person developed immunity. Scientists in Germany, the U.K. and Kenya may have discovered how to do just that. If they are correct, it may be possible to transform mosquitoes from vectors of the disease to vectors of the vaccination.

In an article last month in Science, the medical researchers reported injecting mice with sporozoites of a malaria species that mice are susceptible to. As described yesterday in a broadcast email from ScienceDaily, the scientists then administered the antibiotics clindamycin or azithromycin to the mice for three days. Instead of becoming sick, the rodents developed strong, long-lasting immunity to the parasite.

The methodology worked because of the life cycle of the malaria parasite, Plasmodium. The microbe goes two stages: a stage of sexual reproduction in the insect, which produces the sporozoites, and a stage of asexual reproduction in a human or other mammal, which produces so-called merozoites and causes the disease.

After entering the blood through a mosquito bite, the sporozoites go to the liver, where they mature into merozoites. These forms then leave the liver to infect red blood cells in the bloodstream. About two weeks after the mosquito bite, the infected red cells burst, releasing thousands of merozoites, which in turn infect more red cells. This coincides with the chills, high fever, sweats, headache, nausea and vomiting that characterize the disease. Some of the merozoites created in this stage change back to the sexual form by becoming male and female gametes. A mosquito biting at this time and sucking a blood meal ingests the gametes and the cycle begins again.

In giving the antibiotics to the mice after injecting them with the sporozoites, the scientists interrupted the cycle at the point when the parasite exits the liver. The antibiotics prevented the parasite from invading new cells by destroying an organelle it needs to do so. The parasites were thus forced to remain in the livers of the mice but were unable to invade their blood and cause the disease. But while they remained in the liver, the white cells of the mice were exposed to many of the parasite’s antigens, and the animals developed robust immunity, much as occurs in response to an effective vaccine.

The scientists hope to test their strategy in humans by providing the antibiotics, which are relatively inexpensive, to people in regions where malaria is endemic. Dr. Steffan Borrmann, one of the researchers, said:

The periodic, prophylactic administration of antibiotics to people in malaria regions has the potential to be used as a “needle-free,” natural vaccination.

Until now, efforts to develop a malaria vaccine of the usual kind have not succeeded. On its website, the National Institute of Allergy and Infectious Disease explains, “The complexity of the Plasmodium parasite and the lack of understanding of critical processes, such as host immune protection and disease pathogenesis, have hampered vaccine development efforts.”

If “natural vaccination” for malaria proves effective, would it be possible to use similar strategies to promote immunity to other vector-born diseases by giving prophylactic antibiotics to people in endemic regions?

A new test to diagnose Alzheimer’s disease (AD) at an early stage may be at hand. Until now, the definite diagnosis of this most common form of dementia required an autopsy to demonstrate plaques of amyloid-ß protein and tangles of tau protein in the brains of deceased patients. A test that would diagnose the disease before death would permit trials of drugs on living patients who test positive, a critical requirement for development treatments. The ability to diagnose early may also be a critical requirement for developing effective treatments of AD-associated brain degeneration, ones that can be administered before irreversible brain damage has occurred.

The new test assays the levels of amyloid-ß and tau in the cerebrospinal fluid (CSF), the liquid that surrounds and bathes the brain and the spinal cord, supplies these organs with nutrients and removes their waste products. The research by scientists in Europe and America, reported this week in the Archives of Neurology, found that amyloid-ß was reduced and tau was elevated in the CSF of the AD patients.

A report by Gina Kolata in the NY Times on Monday suggested that the test “can be 100 percent accurate in identifying patients with significant memory loss who are on their way to developing Alzheimer’s disease.” But although it may turn out to be highly accurate, the reporter’s assertion of perfect accuracy may have conveyed an erroneous impression.

The researchers found that the statistical distribution of amyloid-ß levels was bimodal, i.e., there were two clearly defined peaks, indicating that CSF amyloid-ß level probably reflects a single disease process affecting the patients suffering from AD.

The scientists tested the test in three distinct populations of patients with similar encouraging results. In one carefully selected group, in whom the diagnosis of AD had been made made clinically based on signs of dementia, levels of amyloid-ß were found to indicate AD in all the patients. But in a different group of patients diagnosed after death with autopsies, which is the most accurate method, 94% of the patients with AD had levels of amyloid-ß consistent with the post-mortem findings.

It’s important to bear in mind that the results reported this week came from retrospective studies. Patient-derived data from existing databases of patients, rather than the patients themselves, were the subjects of the analyses. With the outcomes (AD present or absent) known, the scientists “looked back” to the results of previous CSF tests.

A definitive study of the accuracy of the test would have to be done prospectively. Patients whose diagnoses are not known would be followed forward in time until their diagnoses became evident. The results of prospective studies—unavoidably among less carefully selected patients—often turn out less impressive than those of retrospective ones.

The new test would require patients to undergo a spinal tap to obtain CSF for the assay. Some patients and even some doctors might be discouraged by the prospect of the procedure. They need not be. The spinal tap is a fairly routine test, probably done thousands of times a day. It is safe and doesn’t usually cause severe or significant side effects.

Google, the company that some time ago evidently changed its motto to “Do evil,” is teaming up with handmaiden Verizon to influence FCC regulations regarding net neutrality. Their apparent goal is to insinuate preferential treatment into the internet by persuading the commission to establish exceptions to such regulations. The effect would be to create a premium, high-performance tier of internet transmission that would be available at higher cost. What is now a level field and neutral network could become, in part, a telecommunications system that charges extra for enhanced content, more bandwidth and higher speed.

“As Google has gotten bigger and entered new lines of business, it has revised some of its principles — and it is drawing criticism from start-ups and public interest groups along the way,” the Washington Post reported yesterday.

Google and Verizon agreed that telecommunications companies could charge consumers for the quality of the content coming through their networks and even block access to certain content. For example, Verizon could transmit Google’s search engine but block Microsoft’s Bing, the Post said.

The NY Times, however, reported that the two internet giants had proposed that blocking any ordinary internet content would be prohibited. But new services providing enhanced content would be exceptions to the requirements of net neutrality. Such premium content and services would be allowed to transmit via high bandwidth channels, with premium prices set for access to them. For example, the Times said

the Metropolitan Opera might decide to stream its performances in 3-D through such a service because it would otherwise require too much bandwidth.

Support for exceptions to net neutrality may be building in Congress, even among Democrats, who might be expected to try to protect ordinary internet users from higher charges. On Monday, Chris Van Hollen, a Maryland Congressman and chairman of the Democratic Congressional Campaign Committee, wrote in an email response to an inquiry on net neutrality,

I believe that this vast new frontier [the internet] must also have the careful watch of regulators to ensure that no collusion or anti-competitive practices take place and that those who control the distribution channels do not attempt to unduly influence the content. I will continue to support measures to allow fair-use of the internet….

Absent—conspicuously so, in my view—from Van Hollen’s response was any use of the term “net neutrality” or any statement of support for that concept. Instead the Congressman used the phrases “unduly influence” and “fair-use of the internet.” But what constitutes undue influence and fair use? Responsible for raising contributions for Democratic campaigns, I suspect Van Hollen may have agreed with Verizon, Google and other huge companies to try to drill holes in regulatory walls protecting internet neutrality.

If that happens, large corporations and their legal staffs could breed corporate mice to squeeze through the holes in the regulatory walls and then grow to guerilla size. If permitted to exist and grow, these entities would transmit enhanced content and would surely diminish the visibility, audience and influence of ordinary content providers.

The internet would not remain the open, innovative space for new creators of content to work in at minimal initial cost.

The prevalence of obesity in America has risen to 34% of the adult population, the CDC announced last week. An adult is considered obesity if his or her BMI, which is calculated from height and weight, is greater than 30. The public health agency tracks the nation’s average BMI with telephone surveys asking people to report height and weight. Since the respondents often underestimate their weight and overestimate their height, the agency corrects the raw data to compute the actual rate of obesity. Referring to its full report, the CDC said on its website:

The data show a 1.1 percentage point increase—an additional 2.4 million people—in the self-reported prevalence of obesity between 2007 and 2009 among adults aged 18 and over. The report also notes the medical costs associated with obesity are high. In 2008 dollars, medical costs associated with obesity were estimated at $147 billion. People who are obese had medical costs that were $1,429 higher than those of normal weight.

In 2005, the NIH warned that rising obesity rates could reduce Americans’ life spans by as much as 5 years, on average. The health research institute based the projection on a report in the New England Journal of Medicine that estimated a 5-20 year reduction in longevity among the severely obese portion of the U.S. population. The problem could have an especially large impact on young people. The article said,

If the prevalence of obesity continues to rise, especially at younger ages, the negative effect on health and longevity in the coming decades could be much worse. It is not possible to predict exactly when obesity among the young will have its largest negative effect on life expectancy. However, in the absence of successful interventions, it seems likely that it will be in the first half of this century, when at-risk populations reach the ages of greatest vulnerability.

Yesterday, the NY Times reported that more girls are developing breast enlargement at the age of 7 or 8, and “increased rates of obesity are thought to play a major role, because body fat can produce sex hormones.” The article was based on research by physicians at Cincinnati Children’s Hospital Medical Center, who found that overweight girls were more likely to develop breasts. At that young age, girls may be unprepared to deal with the emotional and interpersonal challenges of elevated hormones and sexual development.

There can be little doubt that the diet of Americans, who consume large amounts of high-fat, high sugar foods, is one of the main causes of the epidemic of obesity. And the U.S. food industry has contributed mightily to the problem by selling and advertising many food products with high-fat, high-sugar content, in order to boost sales.

We Americans should at the very least, as national policy, restrict the advertising of these high-calorie food products to children via TV and the internet. And parents should teach their children to eat healthfully.

When I was a schoolchild, my teachers taught that America was first settled by Pilgrims, who sought to worship God in the manner they chose. Practicing their religion was so important that they crossed the treacherous expanse of the Atlantic in the little Mayflower, to begin new lives in the wilderness, thousands of miles from the civilization of their births. My teachers’ point was that freedom of religion is one of the original and central founding principles of our American nation—one worth facing great hardship and sacrifice, including loss of life.

Why is it that so many Americans don’t seem to understand that?

The Anti-Defamation League—of ALL groups—has joined a cacophonous chorus of opposition to the ground zero mosque. According to the statement of purpose on its website, the association is dedicated to “to secure justice and fair treatment to all.” But not including Muslims, apparently. After considering “the anguish of the families and friends of those who were killed on September 11, 2001″, the organization declared:

Proponents of the Islamic Center may have every right to build at this site, and may even have chosen the site to send a positive message about Islam. … But ultimately this is not a question of rights, but a question of what is right.

ADL fights discrimination against Jews, but it apparently doesn’t see a contradiction in supporting discrimination against Muslims. How would ADL react if the religious center were synagogue, I wonder. Would it claim it isn’t “a question of rights?”

But Fox News and its commentators are sounding the sourest notes. A story on the politics of the mosque showed a picture of a demonstrator with a sign equating building the house of worship at that site with glorifying the murders of the three thousand 9/11 victims. It’s clear from the text that Fox News accepts that view and is trying to demagogue it.

Didn’t these people take any American history? We learned about the Pilgrims in elementary school.

Freedom of religion is part of the first of the amendments for a reason. That’s how important the founding fathers thought it was. Since there would be no objections to a church or a synagogue, there should be none to a mosque. That’s how America works, or is supposed to, anyway.

The hullabaloo shows how many Americans, including some of the most fiercely patriotic, have failed to take to heart the history of our country and what the founders intended.

The First Amendment of the Bill of Rights requires that government not favor or discriminate against any establishment of religion. As Americans, we should all uphold that principle, and we should avoid demonizing any single religion and denying its followers their rights because of what a few of them have done.