Mark Pine

Forces on both sides of the Atlantic seem hell-bent on plunging the world into a second Great Recession in five years.

In this country, Republicans and conservatives are continuing to demand cutbacks in government spending that will take still more money out of the liquidity-strapped US economy.

At the same time, at least one of the nation’s too-big-to-fail banks appears to be rushing to repeat the reckless financial maneuvers that caused the last recession. The two billion dollar loss reported by JPMorgan resulted from speculation in synthetic credit obligations, such as credit default swaps. It seems that politicians and regulators, bought and captured by the big banks, are too beholden and timid to take appropriate action to prevent such financial abuse. That means that despite JPMorgan’s set back, other big banks will probably choose to try their luck at the same gambling game. (Yesterday, in fact, the Guardian reported, Sen. Carl Levin charged that Wall Street has made “massive lobbying” efforts to modify the “Volker rule” that prohibits such trading.)

Meanwhile in Europe, politicians are trying to impose fiscal austerity on their nations, as the Republicans are in this country. In the UK, PM David Cameron has vowed to go ahead with budget cuts that began in the middle of last year. Despite his policy — or more likely because of it — the British economy contracted during last year’s fourth quarter and this year’s first quarter. Similar strategies throughout Europe are threatening to send the continent into the second part of a double-dip recession, and Spain’s economy has already fallen into the pit.

There is danger that the austerity-induced slide of Eurozone economies could spread across the ocean to the US. Europe imports around $300 billion in goods and services from American, and a good chunk of those sales could dry up as the result a European recession. Moreover, American banks are probably exposed to European debt. Indeed, it was perhaps to hedge its exposure to European borrowers, the Guardian said, that JPMorgan may have bought those failed credit default swaps. The strategy, however, did not work and caused the huge loss. The big bank’s maneuver exemplifies the mechanism where by financial collapse on the continent could jump across the Atlantic.

I thank God I’m not likely to be affected by such financial disruptions, and my son’s family seems secure. But my daughter and her husband live in Manhattan, and he is involved with Wall Street. They would have a hard time in a second recession.

=========================================
The blog will be taking a brief vacation. It will resume in one week.

Cassandra, the Trojan woman, daughter of the King and Queen of Troy, predicted the destruction of her city. The Trojans ignored her. Jim Hansen, the NASA planet scientist, Director of the Goddard Institute for Space Studies, has predicted that catastrophic climate changes will result from the ongoing massive burning of fossil fuels and the accumulation of atmospheric carbon dioxide. Much of American society has disregarded his warning. Troy was sacked; what will happen to us?

In an op-ed in the NYT yesterday, Hansen said that extracting and burning all the oil in the Canadian oil sands would release twice the amount of carbon dioxide as has resulted from burning fossil fuels so far. In consequence, he predicted, the polar ice sheets would melt, the seas would rise 50 feet and inundate the world’s coastal cities, and “global temperatures would become intolerable.”

If most Americans took him seriously, you’d expect we would not be debating whether to build the Keystone Pipeline to bring the Canadian fuel to the US and the rest of the world. On the contrary, we would be undertaking gigantic projects to reduce fossil fuel consumption and transition the nation to renewable sources of energy. Instead, Americans have emitted a collective yawn.

Cassandra was ignored because the god Apollo put a curse on her. A beautiful woman, she had refused his advances, and though he gave her the power to foretell the future, he doomed her to prophesy in vain. But why does Hansen, a capable scientist at an accomplished federal agency, seem to be having little effect on Americans’ behavior?

Certainly, it must be our addiction to fossil fuels. So much of what we do every day for work and play depends on energy from these sources. We would have to abandon our gasoline-fueled, often luxurious and wasteful automobiles, which play such a huge role in our lives. The foods and goods we purchase in the markets would rise in price. We would have to alter our methods of heating and cooling our homes. Rather than face the prospect of such daunting alterations in our way of life, we easily listen to the voices of those who derive wealth and profit from convincing us to pay no heed and to continue consuming oil and coal.

The Heartland Institute has made news recently by sponsoring ads that caricature climate scientists like Hansen as Unabombers. The institute also publishes a report titled “Climate Change Reconsidered,” which asserts that human-caused greenhouse gas emissions “are not playing a substantial role” in climate change. A loose association of politically conservative interests, Heartland has received funding from the oil refiner company, Koch Industries, and probably from other fossil fuel companies as well.

Exxon-Mobil, the world’s largest oil company, has also worked to “deceive the public about the reality of global warming,” the Union of Concerned Scientists charges (pdf). It has backed and promoted scientific spokespersons, who try to “persuade the media and the public that there is still serious debate among scientists that burning fossil fuels has contributed to global warming and that human-caused warming will have serious consequences.” The oil company and its allies in the climate debate appear to have succeeded to an astonishing extent in minimizing public concern.

What can be done to get the nation to pay attention and see the need to make substantive changes? In my view, reputable scientists must make use of events like Hurricane Katrina, the most destructive hurricane in US history, the tornado devastation of last spring, and the predicted severe tornado weather forecast for this year.

Climate scientists have been scientifically and appropriately cautious in their statements until now. They avoid attributing any one event or any one season to warming atmospheric temperatures, because of the unavoidable uncertainties involved. But as Hansen and other climate scientists have said repeatedly, there is no longer any real debate about global warming among the large majority of scientists.

It’s time for the scientists to stop being so reticent. The only way to get the public and the politicians to listen and take action is to make use of these catastrophic weather events to scare people. When Americans get frightened, they will change as they need to. They will demand that the president and Congress pass laws to reduce carbon emissions, and they will accept the unavoidable changes that will follow. That is what needs to happen.

I have supported marriage equality for gays and lesbians for years, and I’m pleased that the president announced his support for it publicly yesterday. But this isn’t the first time he’s done so, and it’s implausible that Barack Obama has evolved on this issue in recent years. What has evolved is his understanding of what the country is prepared to accept in a president.

Obama first declared support for marriage equality in 1996, Fox News reported yesterday. He did so in response to a questionnaire during his campaign for the Illinois state senate. That is and always has been his true belief, in my view. I find it inconceivable that a man whose white mother married his black father and who changed the course of American history by becoming the first black President of the United States, could feel anything but full support for the rights of gay and lesbian people to marry.

On the other hand, Obama quickly retreated from his first declaration of support. Two years later, he was “undecided” on the issue during a second bid for the Illinois senate in 1998. By 2004 he had anchored his position to support for the less controversial notions of domestic partnership and civil unions. It was the stance he publicly maintained until yesterday. During those years, Obama apparently had decided not to get ahead of the electorate.

But the president, a political genius, always has his nose to the wind and his ear to the ground. He knows that opinion polls have shown steadily rising support for marriage equality. Surveys by Gallup, the Washington Post-ABC News, Pew Research, and the NY Times now have support among Americans exceeding opposition, a reversal of a previously negative plurality that has occurred since the last presidential election. Obama senses that the time is now ripe.

The main risk for the president is that voters in several swing states important to his re-election — Ohio, Pennsylvania, Virginia, and Iowa — still predominately oppose gay/lesbian marriage, as do most African-American voters, whose overwhelming support bolstered him in 2008.

Still, I think the president has little to lose by coming out in favor of marriage equality. Few of his supporters will change their minds and vote against him because of this. In declaring this stance, he assumes a morally correct attitude, makes a historic statement, and places himself on the right side of history. … And, as a plus, he forces Mitt Romney to go on the defensive between now and November by having to maintain and justify his opposition in the face of repeated questions on the issue from the press, as well as charges and criticism from gays, lesbians, and their supporters.

The food industry is still behaving very badly, producing and marketing unhealthy foods to children in unpardonable amounts.

The comment is by Kelly Brownell, director of Yale University’s Rudd Center for Food Policy and Obesity. She was quoted yesterday in an LA Times article on the developing effort to deal with the obesity epidemic that plagues the nation.

Good luck with getting the food industry to change its ways.

Yesterday, the Institute of Medicine of the National Academies of Sciences issued a report on ways to reduce “the weight of the nation.” The report coincides with the CDC’s publication of an article (pdf) in the American Journal of Preventive Medicine that projected that almost 40% of Americans will be obese in 2025, if current trends continue.

One of the main components of the effort to get Americans to lower their weights, the IOM recommends, should be teaching school children to choose healthier, more nutritious food. In my view, that’s an excellent strategy, and if it is successful, during the next few decades the national waistline will shrink.

However, the notion that the food industry will help substantially in this effort is pie-in-the-sky. Perhaps food companies, under pressure from the government and health organizations, might start offering a few lower calorie, more nutritious options for snacks, while they continue to promote and sell high-fat, high-sugar fare. But the hope that they will play a part in leading this effort is vain. The food companies will have to be dragged along in response to the food demands of the American people.

That’s why most of the effort and money to slim Americans should go toward the strategy that the IOM listed last among its five groups of recommendations (pdf): Making schools a national focal point for obesity prevention.

Children must be inculcated with good nutrition information and advice from the very youngest ages. They must be taught which foods are good for you and which foods aren’t and should be eaten only in very small amounts. They must be taught daily, with information and exercises, that good food and physical activity, especially aerobic activity, is vital for health.

One other IOM recommendation is as important as that concerning schools: Establishing physical activity standards for child care centers, so that this effort to teach children can begin as soon as they understand what food is and that there are different types of food. These concepts and the behaviors must be drilled in to the kids as soon as possible, or they won’t take.

Other IOM recommendations will flow from these, such as improving neighborhoods so that they offer places to be active in a healthful way, adding community programs for physical activity, making more healthy food available and affordable, marketing strategies targeting food purchases, and getting doctors and health professionals to emphasize good nutrition in their practices. These and all the other recommendations are helpful and important, but their implementation will follow if Americans are taught from the youngest age to demand good food and to seek out opportunities for physical activity.

I had the good fortune of having a mother who was a dietician. From the time I was very young, she taught me about nutrition. Despite the fact that a genetic disposition toward obesity ran very strongly in her family (and, of course, in me), I’ve always eaten a lot of healthful food — vegetables and fruits especially. Now in the latter part of my seventh decade, I have managed to keep my weight in check. Although, I failed in this effort many times, I always came back to it. In large part, I believe, because I eat good food and keep active, I’ve maintained good health. … At least so far, anyway.

Obesity in America — the portion of the U.S. population with BMI ≥ 30 or more than 30 pounds overweight — has more than doubled since the 1990, the CDC reported yesterday. In an article (pdf) in the American Journal of Preventive Medicine, researchers at the disease control agency projected that by 2025 the proportion of obese Americans will hit 40% and almost 10% will be severely obese.

About 13% of Americans were obese two decades ago. Today almost 29% are. Even more worrisome, severe obesity — BMI ≥ 40, about 100 pounds overweight — has quadrupled, rising from less than 1% to more than 4%. To compile the findings, the researchers analyzed data drawn primarily from the Behavioral Risk Factor Surveillance System (BRFSS), an on-going, state-based telephone survey of health conditions and risky behaviors begun in 1984.

The analysis shows that not very much in the socioeconomic milieu of the nation has dramatically changed in those years that might explain the dramatic rise in body mass. One change, however, has been striking. The CDC found that the number of restaurants per 10,000 people has jumped by more than one-third, from about 14 to almost 23. Evidently more of us are eating more often at restaurants rather than eating at home or bringing lunch to work.

Compared to women, men are slightly more likely (by 10%) to be obese, but men are substantially less likely (by 36%) to be severely obese. Men who have married are obese about one-third more often than never-married men, but there is no difference in women’s rates of obese in regard to marital history. Blacks are nearly twice as likely as whites (by 85% – 89%) to be obese or severely obese, an ethnic disparity not found among Hispanics.

Obesity rates vary dramatically with household income. Among the very poor, families with annual incomes less than $10,000, obesity occurs one-third more frequently than among families with incomes of $50,000 or more, and severe obesity occurs more than twice as often. Rates of obesity and severe obesity decline steadily as household income rises. Obesity rates are also elevated to a small degree (by 11% – 13%) among people with less than a high school education .

Despite the inverse association between obesity and household income, the CDC discovered that the condition is not more common in states where groceries are priced more expensively in comparison to the prices of other goods. Severe obesity, however, is 39% more common in high-grocery-price states. In contrast, both obesity and severe obesity were found much more often in states where healthy foods are more expensive relative to less healthy foods. This finding may help to explain the marked relationship between obesity and family income, since it suggests that low-income families buy less healthy foods.

Obesity is also more common in households with internet access.

As quickly and dramatically as obesity prevalence appears to be rising, the CDC’s projections are actually lower than they might have been. Rather than extrapolating the increases linearly from past trends, the researchers used a logarithmic model that assumes the increases are slowing down. This has occurred in some subgroups of the U.S. population. Nevertheless, the authors said, “the study still forecasts a 33% increase in the prevalence of obesity over the next 2 decades.”

The projections for severe obesity are even more dire. The results of the study forecast that the distribution of BMI in the U.S. population is in process of skewing toward the heavier end (the right side) of the curve. Severe obesity correlates strongly with adverse health risks, and the association between excess weight and adverse health outcomes rises more quickly than a simple linear trend. The authors wrote:

Those with a BMI higher than 40 are at much greater risk for diabetes and other medical conditions than those with a BMI between 30 and 35. They also have a much shorter life expectancy and generate greater lifetime medical costs, suggesting that future healthcare costs may continue to increase even if obesity prevalence levels off.

For much of my life, I yo-yo’d between obesity and normal-range weight. When successful in keeping my weight within bounds, I achieved that goal with a combination of diet and exercise. Upon turning age 60, I decided it was time to get serious, and in the last several years I’ve maintained a BMI between 25 and 30.

I use a spreadsheet to note all the food I eat. Initially irksome, it has become automatic to keep the record, and as computers and tablets have become smaller, it has become easier to carry it around. The sheet stores nutritional information, including calories, for all the foods I usually eat, and it calculates a running calorie total during the day. I’ve found I can maintain weight by eating 2400 calories or fewer per day, exclusive of at least 400 calories I expend in aerobic exercise. It has worked for me.

Did USA Today open a can of worms? The nation’s most widely read newspaper proposed in an editorial yesterday that the FDA should make more prescription medications available “over the counter.” In opposition to the idea, the president of AMA authored an opinion piece, which USA Today published alongside the editorial. The point-counterpoint follows up on a notice the FDA put out in March that the drug regulatory agency is considering expanding its “definition” of nonprescription drugs. If it does so, consumers would be able to buy either on their own or with the guidance of a drug-store pharmacist many medications now available only with a doctor’s prescription.

USA Today argued that making more medications available OTC would lower their costs and increase access to them. Many patients don’t get the drugs they need or stop taking them too soon, it said, and many patients can’t or don’t go to the trouble of getting their prescriptions filled. “Easier access could help them save money” … and presumably raise the number of patients who would get all the medicines they need.

On the contrary, substantially increasing the number of OTC drugs would result in more problems than benefits, the AMA said. It would lead to many patients trying to diagnose themselves and manage their own chronic medical conditions. And it wouldn’t reduce the costs for patients, because they would have to pay on their own the entire cost of the medicines they would purchase OTC.

Among its primary reasons for opening the debate, the FDA cited the concerns about cost and access that USA Today raised, which affect 20% of patients, the agency said. To ensure that nonprescription drugs would still be used safely and appropriately, the FDA made clear that before getting some types drug, a patient “might have to talk with a pharmacist, or need to have a diagnostic test.” In other cases, a patient “might have to visit a physician to obtain the original prescription, but not to get refills.”

Other important voices in the debate, one has to assume, are those of trade and professional associations that have large financial interests in the outcome. Obviously, the pharmaceutical industry, with its huge television advertising operations, would favor selling more of their products directly to patients. The pharmacists and the drug stores also have an interest in taking on some of the functions now carried out by physicians and clinics — and in receiving more of the associated revenue stream.

The main problem with the proposal, in my view, is that all medications have the potential to cause considerable harm. Blood pressure medications and asthma drugs, for example, which are among those that USA Today urges be considered as OTC drugs, can cause serious and even fatal adverse reactions, if taken improperly. The FDA describes a number of ways that such risks could be reduced: Pharmacists could be required to oversee and guide the use of potentially dangerous drugs. Websites could help consumers diagnose themselves and choose appropriate medications. But whatever systems are put in place, they will work only if consumers are careful and responsible in carrying out the new functions and making the new judgments that the proposal would require of them.

Inevitably, some people will make mistakes and act irresponsibly, and the main question is how many will do so. How many people taking blood pressure drugs will dangerously drop their pressure, perhaps while driving; how many will develop arrhythmias by accidently overdosing on asthma meds? I’m reminded of one elderly gentleman I knew. Nearing ninety, he suffered from hypertension, diabetes and mild dementia. Inadequately supervised regarding his blood pressure medicine, he took too many diuretic pills and was hospitalized for dehydration.

Before expanding access nationwide to a large number medications, it would make sense, I think, to perform limited field tests of just a few drugs in a several test markets, in order to determine how well increased OTC availability would work. OTC access to several potentially dangerous medications could tried in small metropolitan areas. Doctors, clinics, hospitals, pharmacists, etc., would be notified of the testing program and would be asked to report any patients who experienced serious adverse reactions as the result of trying to diagnose themselves and manage their own treatment.



Implementing and carrying out such a testing program would require new regulations, several years, and the budget to do so, but it could provide a rational, empirical basis for deciding whether, how fast and how far to move forward with proposals for increasing OTC access to many drugs.

In the consciousness section of this blog, I’ve often tried to make the argument that consciousness is the immaterial aspect of material existence. The notion is based on the particle/wave function duality principle of quantum mechanics. The principle asserts that all things that exist have two alternative aspects, a material form as a collection of particles, and an immaterial form as a wave function. In my view, this immaterial, wave-function form of all things is consciousness. Consciousness is more than just a capability of the human brain, it is a fundamental property of universe.

Until now my reasoning has been almost entirely abstract. Generally, I’ve not considered the results of scientific observations or experiments. Last Sunday, however, the NYT ran an op-ed piece titled, “If Peas Can Talk, Should We Eat Them?” The article, written by Michael Marder, a professor of philosophy at the University of the Basque Country, did not imply that peas and other plants possess conscious, but it did describe plants in terms that evoke this capability:

Imagine a being capable of processing, remembering and sharing information — a being with potentialities proper to it and inhabiting a world of its own. Given this brief description, most of us will think of a human person, some will associate it with an animal, and virtually no one’s imagination will conjure up a plant.

Marder discussed experimental findings on pea plants made by a team of scientists at the Blaustein Institute for Desert Research at Ben-Gurion University in Israel. Published in the peer-reviewed journal PLoS One, the results indicated that pea plants subjected to drought conditions communicated their stress to other pea plants.

The experiment utilized groups of about 17 pea plants grown in two rows. All the plants had their main root split into two roots. One plant at the center was subjected to osmotic stress due to mannitol, an osmotically active sugar-alcohol compound, experimentally applied to the soil around its roots. The researchers assessed plant stress using a recognized index, stomatal aperture diameter.

On one side, one of the central plant’s roots penetrated into soil that was continuous with and “shared” by one of its immediate neighbors. One of the neighbor’s roots also penetrated into soil shared with its immediate neighbor further down the row. Each plant was grown so as to form a chain of root links along the row. On the other side, the plants were set up with similar root links. However, the central, stressed plant’s other root did not penetrate into or share soil with its immediate neighbor on that side. The arrangement is illustrated in this diagram.

The set up allowed the central, osmotically-stressed plant to communicate with plants on the first side through the soil with soluble factors secreted by its roots. The plants on the second side were cut off from such communication. The authors wrote:

Fifteen minutes after mannitol injection, the stressed plant and its two nearest SHARED neighbours closed their stomata by 39% compared to their water controls, while SHARED target neighbours positioned further away from the [central] plant maintained increasingly opened stomata. Sixty minutes after the mannitol injection, the width of the stomata of all the SHARED plants was drastically reduced to a similar extent.”

In contrast, the plants in the “unshared” soil containers experienced no similar stomatal closure. Discussing the findings, the scientists said:

The results suggest that unstressed plants are able to “eavesdrop” on their osmotically-stressed neighbours and respond in ways that might prepare them for subsequent stress. … The results also demonstrate a novel feature of plant-plant communication: elicited by their stressed neighbours, unstressed plants not only exhibit stress response but also emit stress cues that are perceived by additional unstressed plants. Although not directly demonstrated, recent evidence suggests that the described chain-communication might exist and play an adaptive role in other plant systems.

In their conclusions, the authors did not suggest in any way that the communication they demonstrated among plants demonstrates that plants are conscious. Rather, they said, the findings point to “a simpler type of networking” than the “advanced coordinated networking of the types found in social birds and mammals.” Their study, however, provides evidence that communication may be a capability of many types of plants.

In the piece in the Times, however, Marder discussed this experiment and wrote this:

In 1973, the publication of “The Secret Life of Plants,” by Peter Tompkins and Christopher Bird, which portrayed vegetal life as exquisitely sensitive, responsive and in some respects comparable to human life, was generally regarded as pseudoscience. … But today, new, hard scientific data appears to be buttressing the book’s fundamental idea that plants are more complex organisms than previously thought.

In my view, the phenomenon that is observed objectively from the outside as communication among pea plants has an internal perceptible aspect. From the inside, I believe, it is perceived as consciousness — though a much simpler form of consciousness than human consciousness. Marder, I suspect, would not be unsympathetic to this idea.

Yesterday’s post focused on the antidepressant drug Prozac, one of the best-selling drugs of all time. Because Prozac boosts levels of serotonin within the synapses between neurons, the drug’s efficacy in the treatment of depression was main justification for the serotonin hypothesis that the neurotransmitter plays an important role in major depressive disorder.

But how do we know that antidepressants, like Prozac, work? At least one prominent psychologist, Irving Kirsch of Harvard Medical School, has expressed doubts that they do.

As with other medications, the effectiveness of antidepressant medications is evaluated by the Food and Drug Administration, which reviews the results of clinical trials of the drugs. The studies, which are usually carried out by the company that wishes to sell the medication, compare its effects on depressed patients to those of a placebo, a pharmacologically inactive pill. An antidepressant receives FDA approval if the patients taking it improve significantly more than those getting the placebo treatment. (Of course, the drug must also be proved safe — which means that during the trials, the drug doesn’t cause significantly more serious adverse effects that the placebo does.)

Surprisingly, the real medications aren’t always more effective than the placebos. In fact, if Kirsch is right, antidepressants don’t work any better than the placebos most of the time. The well-recognized reason for this is that placebos can exert antidepressant effects, too. Here’s a nice video on the subject of “placebo power.” It makes the point that placebos can mimic the effects of just about any kind of medicine.

UCLA investigators decided to examine the antidepressant efficacy of placebos by looking at their actions in the the brains of patients. They reported their results last month in the journal European Neuropsychopharmacology. Their work was reviewed a few days later in ScienceDaily.

The researchers gave 89 depressed persons either a real antidepressant pill or similar looking placebo pill for 8 weeks, and they checked the subjects’ brain activity with EEGs. Among the people who got the placebos, the pills induced alterations in brain activity that depended on whether or not the subjects had ever previously been treated with an antidepressant drug.

The results indicate that the placebo-treated subjects who had never previously taken antidepressants showed increased brain activity in the prefrontal cortex of their brains, which is the executive region that makes decisions and determines behavior. In contrast, those who had previously been treated experienced reductions of prefrontal activity. The latter effect is the one that real antidepressant drugs exert in the brain.

The previously treated subjects who got the placebos voluntarily readjusted the activity of their brains to mimic that which they had previously experienced during antidepressant therapy. However, the subjects who hadn’t ever been treated before, increased their executive-function brain activity.

Perhaps the previously untreated subjects were trying to decide how to behave while “under the influence” of a pill that was having no real pharmacological effect on them. Perhaps they were trying to remember past experiences of different medicines to see whether any previous drug felt like the one they were now taking. On the other hand, the previously treated subjects appear to have been settling themselves in to experiencing a repetition of the same kind of experience.

I think the findings point to an important factor in the power of placebos. It seems that placebos work, at least in part, by activating expectations that a past experience will be repeated.

Writing in the NY Times Magazine last month, Siddartha Mukherjee, a Columbia University oncologist and occasional contributor to the Times of articles on medicine, tried to figure out how Prozac and other antidepressants improve the mood of sufferers of depression. It’s a complex subject involving neurotransmitters and regions of the brain. Mukherjee seemed to struggle to connect the known effects of antidepressant drugs in the brain to the emotions of depressed patients. “For decades, a central theory in psychiatry has been that antidepressants worked by raising serotonin levels in the brain.” he explains. But that formulation goes beyond what the experts in the field have thought, if I remember correctly.

Ever since the serotonin-selective reuptake inhibitors (SSRI antidepressants) appeared on the scene, beginning with Prozac in the late 1980s, a major theory of depression was that it is caused by a chemical imbalance in the brain that is corrected by revving up the activity of “serotonergic” neuronal pathways. It was a refinement of a more general hypothesis, which proposes that depression is related to abnormal levels of activity of one or more of several neurotransmitters. There are the monoamine neurotransmitters — serotonin, norepinephrine, and dopamine, so called because they have a single amino group in their chemical structures — and also acetylcholine, which has a very different chemical structure.

In 1986, when I began examining Eli Lilly’s New Drug Application for Prozac, the leading theories of depression implicated alterations of activity of levels of any or all of these neurotransmitters. The most widely used antidepressant drugs at that time were known as the tricyclic drugs because of their three-ring chemical structures. Imipramine (Tofranil), amitriptyline (Elavil), and a number of others affected the activity levels of many different neurotransmitters in the CNS.

Once Prozac, which mostly affected the activity level of serotonin, hit the market, the serotonin theory gained prominence. Many other SSRI drugs followed it into use, including Paxil, Zoloft, Sinequan, and others. There are now three dozen antidepressant drugs on the market, including the SSRIs, the tricyclics, and the oldest class of medicines, the MAO inhibitors. These drugs affect all the monoamines and acetylcholine, to varying degrees.

The reason for the ascendancy of the serotonin hypothesis, oddly enough, probably has nothing to do with antidepressant efficacy. Prozac was the first SSRI drug and it quickly became the most widely used drug in the world. But this was mainly because it is much safer than the other types of antidepressants that were available then. The MAO inhibitors can cause severe hypertensive crises, and patients taking them must adhere to strict diets. The tricyclic drugs have major effects on heart rhythm and can be cardiotoxic. Both classes of drug are especially dangerous when taken in overdose — obviously a real risk, since they are prescribed to depressed and often suicidal patients.

But most of the adverse effects associated with Prozac and other SSRIs, though unpleasant, are substantially less dangerous. They include nausea, vomiting, anxiety, insomnia, altered appetite, weight loss and weight gain. The most serious prominent adverse effects include rashes, which sometimes can be very severe, and around 2000, it was discovered that SSRIs may actually worsen suicidal ideation, particularly among children, adolescents and young adults.

I don’t think it was ever true that the cause of depression was seriously attributed to low serotonin levels, as Mukherjee suggests, except perhaps by members of the lay public. It was clear since the SSRIs were first synthesized in the 1970s that the drugs acted in the CNS to boost serotonin activity levels within hours, but their antidepressant effects took weeks to develop. Something else had to be at work.

Mukherjee also makes the point that the efficacy of antidepressants is often marginal. They appear to ameliorate depression the most in the most severely depressed patients, he says. When I reviewed the placebo-controlled clinical trials of Prozac in the original NDA, I was not so much impressed that the drug boosted mood better than the placebo, since most patients taking either the active drug or the “sugar pill” responded with similar degrees of improvement.

Prozac, however, alleviated depression faster than the placebo. Thus, by the time of the pre-planned ending of the blinded portion of the clinical trials at 6 weeks, the patients in the Prozac group were, on average, significantly less depressed than those in the placebo group. Since, for most patients, depression usually follows a waxing and waning time course, the placebo patients eventually improved, too.

Recent theories of the actions of antidepressants focus on their effect in stimulating the growth of new neurons in the hippocampus of the brain, a phenomenon that has a time course of a few weeks, similar to the onset of antidepressant effect. Mukherjee puts it this way: “Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits.”

That theory remains unconfirmed, but perhaps the formation of new neurons does play a necessary role in antidepressant activity. Maybe it is as simple as their replacing neurons that malfunction as a result of getting worn out or diseased. What, if anything, can be concluded beyond the bare fact that the process of neurogenesis has a time course similar to antidepressant action is unclear.

If you have immigrants in your family tree, if you have faced prejudice or discrimination, if you have misunderstood what to do or say in an unfamiliar situation — in other words, if you are just about anyone — your heart will open to Monsieur Lahzar. The movie of the same title, the best Canadian film of the 2011 Toronto International Film Festival, was nominated for an Oscar this year. It didn’t win only because it faced stiff competition.

Lahzar is a refugee to Canada from Algeria. The movie follows him through his first year taking over a class of pre-adolescent pupils at a Montreal public school. Their previous teacher has just hanged herself from the beams of the classroom. It is a difficult situation. Grief pervades the film, and the mood deepens even more, as we learn of the nature of the tragedy from which Lahzar fled his native land. We watch his missteps and his efforts to learn to guide his young and vulnerable charges, and himself as well, through the work of mourning.

But the movie is anything but maudlin, and the school children are not at all dismal or bleak. Tender though their feelings are, they nonetheless show the irrepressible brightness and liveliness of youth, and they infuse their teacher with it. Old-school and a bit too correct, Lahzar must learn to deal with the children’s guilt, as well as the nowadays easygoing educational style. As he remarks one day to the class, he and they are both learning, growing and starting lives.

He must also pass the tests and overcome the obstacles of Canada’s immigration system. The school principle, an unsentimental but not unkind woman, helps to keep things on course. She is put in the position of dealing with certain unpleasant certain facts, which she eventually learns about Lahzar’s background, but she proves to be his friend.

The acting and the direction are entirely without pretension. Mohamed Fellag, as Monsieur Lahzar, plays his role modestly, underplaying his feelings and in so doing conveying them powerfully. Sophie Nélisse, a lovely, adorable girl, and the tragically-countenanced, Émilien Néron, play the two children who witnessed their former teacher’s body suspended from a rope. Under the sensitive direction of Phillippe Falardeau, who also wrote the script, the children seem nonetheless just children. The most remarkable thing about the movie is its skillful it avoidance of all excess and mawkishness in every aspect of this simple, touching story.