Mark Pine

The president made clear who is in charge now. Yesterday he fired the CEO of GM and ordered Chrysler to merge with Fiat. Perhaps not since Harry Truman tried to nationalize the steel companies has a president intervened so directly and forcefully in a manufacturing enterprise.

The chattering class of journalists buzzed all day, asking the obvious question. Why terminate the car company CEO while leaving the management of many financial companies in place? It does seem unfair, but while the question is worth asking, it’s premised on an erroneous assessment of what the president is trying to do.

The goal is not to punish but to maintain the viability of a significant fraction of the manufacturing capacity of the nation. GM and Chrysler must drastically revamp how they do business, and it’s both necessary and customary to change the top management when a company needs to move in a radically different direction.

The goal is different with the financial giants. In their cases, the administration seeks to maintain the flow of credit, without which economic recovery is impossible. Firing of the financial CEOs is not what is necessarily called for, since the purpose is not so much to change the direction of those companies as it is to return them to doing things right the way they used to, particularly to curtail excessive risk-taking.

To that end, government officials can directly control in the activities of financial businesses with the regulatory structures that already exist, as well as with new ones that Congress plans to enact in the coming year. It is not necessary to replace managers who are required by statute and regulation to do what the government requires.

But no such regulatory framework governs the business models of auto companies and other manufacturers, nor should one. In that situation, the government must use it’s financial control of those companies to put in place new managers who will drive the companies in the direction they must go to keep the American industry alive.

In the United States, the average person’s yearly energy consumption introduces 20 tons of CO2 into the atmosphere each year. The world per capita average is 4 tons. According to Robert Sokolow of Princeton’s Environmental Institute stabilizing global carbon emissions requires an average per person rate of emissions of 1 ton per year.

He presented this stunning information at the Summit on America’s Climate Choices at the National Academy of Sciences* (NAS) this morning.

The NAS conference comes in response to a request from Congress. The nongovernmental organization has begun a series of studies called America’s Climate Choices, designed to inform and guide the nation’s response to climate change.

Hearing Sokolow’s shocking assertion, I felt like throwing up my hands. Why bother? I wondered. How can we cut our carbon emissions so far? We each output 4 tons per year by driving or flying 10,000 miles, or by heating our homes for a year (in New Jersey’s climate). Is it futile to try?

Fortunately, Sokolow immediately showed that there are still many factors and possibilities giving good reason to hope:

The NAS panel will also examine several high-tech solutions for the future, among them:

Backyard carbon capture. If every home had a window-sized device, it could become energy neutral, pulling 20 tons per year from the atmosphere. The resulting calcium carbonate might be used in construction projects.

If it ever came to a climate emergency, artificial volcanoes could spew sulfur particles into the atmosphere to shade and cool the earth. This has happened in the past due to natural eruptions. It might be possible in a catastrophic situation, and the effect would last for only a few years.

The NAS climate panel can be an effective influence for achieving consensus on these tough issues. As a former federal physician, I attended several advisory conferences of the NAS Institute of Medicine on difficult medical questions, and each time, I was impressed by the academy’s neutrality and efforts to adhere to scientific objectivity. But it’s also clear that more than science will affect climate policy.

Also speaking this morning was James Mulva, Chairman and CEO of ConnocoPhillips, the oil giant. As a member of the industry’s Climate Action Partnership, he put forward the partnership’s position that all forms of domestic energy production must be increased to meet America’s needs and protect its businesses, including increasing off-shore drilling and expanding use of natural gas as a transition fuel.

Mulva warned that the Americans will not tolerate significant increases in energy costs and asserted that the public clearly supports expanding all sources of energy. It was obvious that he was promoting the industry’s viewpoint and the strategy behind those ubiquitous television commercials, sponsored by Exxon, Chevron, and others, that ask in sincere and urgent tones, “Will you join us?”

Still, he proclaimed that the fossil fuel companies aren’t opposed to change, and asserted that every major company is looking hard at changes in organization, efficiency and technology to reduce carbon emissions. And they are interested in expanding into low carbon and zero carbon businesses.

*The NAS, a nongovernmental organization, is chartered by Congress to advise the government on science. The NAS plays the role of honest broker, seeking to achieve an unbiased scientific consensus on major scientific issues affecting the nation. Experts from government, academia, and the private sector will serve on the steering committee of the climate change effort and on four focused panels, covering the magnitude of climate change, future impacts, improving climate science, and informing policy. They will issue consensus reports late this year and next to advise on policy and guide on taking action.

Marijuana has been in the news. At his Internet chat on Thursday, so many questions from viewers concerned the drug that Obama joked “I don’t know what this says about the online audience.” Only a week earlier, Attorney General Eric Holder ended the Bush Administration’s round ups of marijuana distributors. The NY Times editorialized the same day as Obama’s Internet chat that the AG’s new policy “should bring relief to people who need marijuana for health reasons,” and it added:

”There is considerable evidence that marijuana can be useful in treating pain, nausea, weight loss and other symptoms associated with chemotherapy and H.I.V. and other illnesses.”

Several states are even considering taxing marijuana sales as a source of needed new revenue.

Adding the imprimatur and legitimacy of the authoritative journal of the AMA to the debate, the magazine published an article on endocannabinoid signaling the same day as Holder’s policy announcement. Endocannabinoids are the natural internal brain neurotransmitters that affect the same receptors as marijuana’s active ingredient, tetrahydrocannabinol (THC), which is the chemical thought to reduce the symtoms of pain an nausea.

The authors from Rockefeller University in NY noted that the endocannabinoid blocking drugs rimonabant and otenabant have been suspended from marketing and testing because the drugs were causing depression, probably by blocking these receptors. For centuries, they added, cannabis has been self-administered to elevate mood, so it wasn’t surprising that the drugs, which had been intended to treat obesity, were causing that depression as a side effect.

Conversely, treatment with antidepressants increases the number of cannabinoid receptors in the hippocampus and limbic system of the brain, regions involved in depression. They suggested that new drugs to enhance endocannabinoid neurotransmission would provide a new option for treating this very common and debilitating mental illness.

The war of the drug cartels in Mexico has also filled the news in recent days and weeks. And people everywhere are asking whether the decades-long War on Drugs really makes sense. In my view, this is a valid question. Obama’s joking aside, regulating and taxing marijuana, at least, would provide safe, legal sources of a drug that is long known to ameliorate some instances of depression. And it would reduce the profitability and violence connected with smuggling drugs across the Mexican border.

Alzheimer’s Disease (AD) develops silently for perhaps the first 10 or 20 years. There’s no way to know whether you’ve got it or not. Was that slip of the memory—you forgot where you put your keys, but you had them in your hand a few minutes ago—a typical “senior moment” or was it an early sign of something much worse? There’s been no way to know.

Up till now, the only way to diagnose AD for certain has been the autopsy. But that may be changing. The National Institute on Aging (NIA) reported last week that harbingers of the disease might be found in the levels of two proteins in the cerebrospinal fluid (CSF), the liquid environment of the brain and spinal cord.

The pathological changes in the brain in AD consist of plaque-like accumulations of the protein beta-amyloid and tangles of nerve fibers containing another protein tau. Researchers funded by the NIA collected CSF from over 400 older people being tracked as part of the Alzheimer’s Disease Neuroimaging Initiative. Some of these subjects had normal cognitive function, some had mild cognitive impairment (MCI)—a condition that often precedes AD—and some had early AD. They tested protein levels twice, one year apart, in each subject. The levels of the proteins in the subjects’ CSF were compared with those of 52 normal controls and 56 people who later died of autopsy-confirmed AD.

Subjects with early AD had lower levels of beta-amyloid than subjects with MCI, who had lower levels than normal subjects and controls. The reverse was true of tau protein. AD subjects had higher levels than MCI subjects, whose levels were higher than normals. Subjects who had a known genetic risk factor for AD (the APOE-e-4 gene) had high tau, low beta amyloid and were more likely to have MCI. There were 37 subjects with MCI who were diagnosed with AD at the time of the second test a year later. These subjects had CSF protein levels similar to the group already diagnosed with AD. So levels of low beta amyloid and high tau seem to be pointing to Alzheimer pathology.

If low levels of beta-amyloid are, in fact, associated with increased risk of developing AD, the researches suspect it may be due to the deposition of the protein in the plaques, which would take it out of circulation and reduce its levels in the fluid. If this is true, it may point to a possible therapy for the disease, if some way can be found to diminish the deposition of the protein or break up the plaques.

All tests for disease make errors. A test for AD based on CSF levels of beta amyloid and tau protein would have to be evaluated for rates of false positive and false negative results. The preliminary indication from the work done so far in the NIA groups suggests that it may be 85-90% accurate in pointing to AD pathology. But before such a test could become available in medical practice, it would have to be assessed more rigorously. Unfortunately, since AD is a disease that develops slowly, this might require quite a few more years.

The Senate Republicans held a brief news conference yesterday. It was related to the issue of whether to use the budget reconciliation process to pass health care legislation, something that the Democrats may want to do to avoid filibusters. But the GOP Senators used the occasion to hurl their usual accusations at the Democrats. I think they ought think about what they’re saying.

Judd Greg (R-N.H.) accused the administration of steering the country “hard left.” And Mitch McConnell (R-Ky.), the minority leader, backed him up. They both complained that Obama’s budget would lead the country to disaster.

But suppose it doesn’t?

Suppose we climb out of this recession. Suppose we enact universal health care. Suppose we make good progress on energy and education. What will the nation think then? The Repubs repeatedly insist that the United States is a “center-right” nation, politically. Well maybe it has been … since Ronald Reagan, anyway.

But now American’s seem to want the government to take action. They seem to be hoping that the huge problems we face, like health care, climate change, education failures, and the recession, of course, all require government action. Is the nation a center-right nation right now?

I think American’s mainly want what works, and they want government to be effective. So let the Republicans hurl labels like “hard left,” “liberal,” even “socialist” at the Democrats. They may just succeed in convincing Americans that these intended invectives really refer to some good ideas.

A news story in 2004 in the NY Times made it sound too good to be true:

“People who take it say it keeps them awake for hours or even days. It has been described as a nap in the form of a pill, making most users feel refreshed and alert but still able to go to bed when they are ready. And because its side effects are rarely worse than a mild headache or slight nausea, experts fear that it has rapidly become a tempting pick-me-up to a nation that battles sleep with more than 100 million cups of coffee a day.”

The buzz was that it didn’t work like the old-line stimulant drugs and didn’t have much potential for abuse. The article continued:

“Researchers know that modafinil is distinctly different from conventional stimulants, which ramp up arousal and set off a flurry of activity throughout the brain. Such stimulants, like cocaine and amphetamines, for example, produce wakefulness but also produce a high and can lead to dependence. Modafinil appears to steer clear of those side effects by aiming at specific structures and chemicals.”

I wonder whether the reporter might have been smoking something.

A report a week ago in the AMA journal has demolished these claims. The researchers at the National Institute on Drug Abuse (NIDA) used PET scans of the brains of subjects taking modafinil (Provigil) or a placebo, and they showed that the drug affects the same receptors and pathways as do methylphenidate (Ritalin) and cocaine. All the drugs affect dopamine, the wakefulness-inducing neurotransmitter that’s active at the reward and reinforcement center of the brain (the nucleus accumbens).

The authors concluded:

“Because drugs that increase dopamine in the nucleus accumbens have the potential for abuse, and considering the increasing use of modafinil, these results highlight the need for heightened awareness for potential abuse of and dependence on modafinil in vulnerable populations.”

The Washington Post carried the story of the NIDA findings last week, but The Times did not and still asserts on its health guide page that “It has much less abuse potential than other stimulants.”

To be fair to The Times, the NIDA authors did say that modafinil is “much less potent as a reinforcer than stimulant drugs, and reports of modafinil abuse are rare.”

Nevertheless, the FDA medical officer, who reviewed and approved the new drug application in 1997, found that subjects taking the drug reported liking its subjective effect as much as that of methylphenidate, and the female subjects liked the effect more than methylphenidate. He concluded that “its dependence capacity is equivalent to that of CNS stimulants.”

Information about the drug’s pharmacology and metabolism suggests that it might work as a partial agonist-antagonist in the brain. This means that the drug might activate and at the same time block the receptors involved with its stimulant actions. Apparently it binds tightly to the receptors and has a long half-life.

For a couple years in my career, I was involved with a research project at NIDA on the drug buprenorphine, a partial agonist-antagonist at opiate receptors in the brain. Although buprenorphine is less rewarding than morphine or heroin, there was never any question that it is a reinforcing and addictive substance. That’s clearly true of modafinil as well.

Although he is Treasury Secretary for all the citizens of the United States, Geithner continues to act and speak as though our whole nation lives on Wall Street. Yesterday, the Wall Street Journal published his explanation and justification for his recovery program. He spoke to the financiers and the traders, but he didn’t speak to us, the ordinary people of this country, who don’t read the WSJ.

When he has spoken to us all on a TV news program, he has shown that he doesn’t seem to understand us and communicate well. In contrast to the president, who is the same age, Geithner seems an upstart whiz kid who thinks, speaks, and acts technically but not personably and not reassuringly.

Paul Krugman wrote today in the NY Times that Geithner’s policies cater to the financial crowd, not the ordinary people. Chief of of the NY fed under Bush, his work with former Secretary Paulson showed unnecessary deference to the interests and impulses of the financial crowd. And yet that bunch seem to have deserted him. Although he gave them some of what they wanted, he didn’t give them clarity or certainty that they would not suffer losses. I think they really wanted to be bailed out completely. Athough they got billions and trillions, some of the money came with a few strings attached—more recently, anyway.

Geithner and Paulson gave over a hundred billion to AIG, and we’ve learned that the biggest largest chunks of that went to Goldman-Sachs and other Wall Street firms, without any strings. And Geithner fought against executive pay restrictions and government control over the money he doled out. Then recently he got blindsided by public reaction to the AIG pay bonuses. It’s not surprising that he was surprised, since his vision has been limited to the world of Wall Street, and of course they wouldn’t object to the bonuses.

On C-SPAN Washington Journal this morning, I heard a brief replay of an interview given by Austan Goolsbee, a long-time economic adviser to Obama. I do not know much about him, but the little I know suggests that his economic view is much broader than Geithner’s. I thought he spoke well, knowledgeably and reassuringly, with as sense of experience and gravitas—not like a whiz kid. I said to myself that if the president needs someone to do the economic explaining to the country, this is the man who should be doing it.

Electrical deep brain stimulation (DBS). It’s been tried—and shown surprisingly helpful—in several severe brain disorders: Parkinson’s disease, essential tremor, obsessive-compulsive disorder, major depression, memory disorders, and a number of others. The results in Parkinson’s have been impressive. A randomized controlled trial reported in January showed DBS significantly better than the best medical therapy. The treatment implants electrodes in the basal ganglia deep within the brain.

Why it works is not known. But a report in yesterday’s issue of Science magazine suggests a intriguing possibility. It’s not just in the basal ganglia that Parkinson’s happens, but in the neural circuitry connecting the ganglia to the motor cortex.

Parkinson’s disease results from loss of neurons in the substantia nigra (SN) of the brain stem that project upward to the basal ganglia (BG) in the core of the brain. The neurons release the neurotransmitter dopamine from the synaptic terminals of their axons onto the neurons in the BG. In the absence of dopamine, the BG neurons fail to work properly, resulting in muscular rigidity and tremors. Medical treatment replaces dopamine chemically, or inhibits the break down of the neurotransmitter. And scientists have guessed that DBS must substitute somehow for the effects of dopamine in the BG.

But the Science article points to another possibility. The researchers used an ingenious and promising technique to activate genes in cells targeted by laser light. This allowed them to turn neuron firing on or off, depending on the cells that were being targeted. Working with Parkinsonian rats and mice, they excited and inhibited neurons firing in the SN. Unexpectedly that had no effect on the disease. But when they performed similar manipulation of neuron firing in the motor cortex, the mice showed considerable improvement. Although the axons of motor cortex neurons also project into the BG, it had been thought that the projections from the SN are involved in the disease.

In related research, reported in the same issue of Science, scientists showed that electrical stimulation of the spinal cord of rats and mice improved Parkinson’s symptoms. While stimulating, they monitored neural activity in the BG and MC and showed that before stimulation, the Parkinsonian animals had low-frequency synchronized oscillations of firing rates in the two regions, but during stimulation the synchronicity and the oscillations were reduced.

This suggests that the Parkinson abnormality may involve an inappropriate periodicity and synchronization of communication between neurons in the BG and MC. The work also points to the use of spinal cord stimulation as another form of electrical stimulation that may improve Parkinson’s. If it works, it would be a much less difficult and risky way to treat the disease than simulation deep in the brain.

The findings bring into focus the notion that some medical disorders, particularly those that show periodic pathologic signs—like the tremor of Parkinson’s—may not be disorders at all, but too much order. One of the most well researched examples of this kind of thing happens in diseases of heart rhythm.

The rhythm of the healthy heart is chaotic. It is unpredictable and shows no clear periodicity in its rate of beats per minute, even though the rate does have a determinable mean and variance. If you examine a tracing of heart rate over time, it shows no simple waveform. In contrast, the rate of a diseased heart, such as one in congestive heart failure, shows obvious wavy oscillations with easily determinable period. An excellent review of the chaotic rhythm of the healthy heart can be found here.

It makes sense when you think about it. In order to deal with changing circumstances and needs, an organ of the body has to be able to respond as flexibly as possible. If it’s tied to an invariant rhythm of response, that flexibility is impaired. This is especially true in the case of the heart and nervous system, which must deal with rapidly changing conditions of great diversity.

Another way of putting this is that as response patterns become more regular and less complex, the amount of information they can contain decreases. The healthiest organs are those whose response patterns can carry the most information.

Will it turn out that Parkinson’s disease and other brain disorders are not really disorders at all but excessive degrees or orderliness? I think that this is very likely. I once studied the speech patterns of autistic children. The overwhelmingly impression was that they speak repetitively, saying the same things over and over, even though the situations vary. This may be said of all mental illnesses, I think—that they are characterized by inflexible, repetitive behaviors that do not respond to changes in circumstances.

Something is wrong with AIG.

Of course, we know that. The hedge fund unit, AIG Financial Products, sold billions of dollars of credit default swaps—insurance bought by investors to secure their mortgage-backed securities. AIG’s fast traders, who earned commissions on their deals selling the swaps, made out like bandits, collecting huge paychecks until the housing price bubble burst.

The massive losses incurred by the AIG FP unit damaged the ability of the company’s other normal insurance businesses to hold on to financial reserves sufficient to pay customers on insurance claims. So the government stepped in with the funds to keep the normal businesses afloat and their customers in secure insurance policies.

But AIG’s new chairman Edward Libby approved $165 million in bonus money going to those same fast traders, who destroyed the company and might have succeeded in destroying our economy. It’s all the rage now to decry the corporate unfairness, greed, and even immorality of the company’s action. And the fury has reached such intensity that it threatens our government’s ability to intervene with more money to bolster the economy, as it will soon have to do again.

So here is a company at the eye of the financial storm, which has imperiled our economy more than any other corporate entity, and now more actions by that same company threaten to destroy the power of our government to save us from further disaster.

If such a company could go for psychotherapy, the therapist might wonder about an unconscious death wish in the patient.

Because it’s getting even worse. The NY Times reported yesterday that AIG is SUING the government (the same government—our government) that has rescued it from insolvency and now owns 80% of it. So: the company first handed the government a financial cannon to blast it, then it said “Go ahead and shoot me!” and with this latest action, it is saying “I dare you, I double dare you, go ahead and shoot.”

What is it about this company? If you believe, as I do, that companies have “personalities,” I think we have to look at the person of Maurice R. (Hank) Greenberg, AIG’s chairman until 2005, when he resigned under a cloud of lawsuits and allegations of accounting fraud. The culture of a company—its character—mimics that of its leader, particularly a brilliant, charismatic one like Greenberg. The Times reviewed a biography of Greenberg, Fallen Giant by Ron Shelp, who worked at AIG. The review begins, “All Hank Greenberg ever wanted was ‘an unfair advantage.’”

The insurance business is a Janus-faced kind of enterprise. Like barkers at a carnival midway, its salesmen practice the appearance of befriending their customers and seek an advantage over them at the same time. AIG began as an adventurous endeavor, selling American insurance in China. One imagines that the premiums it charged the Chinese clients were probably way out of line with the risks the company accepted and the likelihood that it would have to pay out. The biography recounts an incident when Greenberg “lobbied for China’s admission into the World Trade Organization in 2001 — then maneuvered for a delay, at the last moment, until the Chinese agreed to let A.I.G. operate freely on Chinese soil.”

The recent lawsuit by AIG against the government asks for return of $306 million in tax payments related to deals made by the FP unit and also to deals involving “A.I.G. offshore entities whose function centers on executive compensation and include C. V. Starr & Company, a closely held concern controlled by Maurice R. Greenberg,” according to The Times article. So is Greenberg behind this lawsuit, too?

In the theory of psychotherapy there’s an idea that aggression directed outward can sometimes turn inward against the self. And Greenberg is clearly a very aggressive man. Are he and his former company now the objects of their own aggression, which once built the company into a global giant? Is it the same death and disaster that AIG and its former chairman insured against that they are now unconsciously seeking? As a kind of self-punishment? That could take us all down with them?

That’s the conclusion from a huge study of prostate screening done as part of a massive investigation of cancer screening as a preventive medicine intervention. Done by the National Cancer Institute and reported this week in the New England Journal of Medicine, the research is an ongoing examination of the utility of screening tests in cancers of the prostate, lung, colon, and ovary.

The prostate study involved 77,000 men. Those who had annual screening for prostate cancer with either PSA blood tests or manual rectal exams died from the cancer no less often (in fact, a bit more often) than men who had usual care by their physicians. In the annual care cohort, about half the group, 85% of the men had annual tests or exams, while less than 50% of the usual-care group had them. The screening tests used standard procedures and criteria for referral. After seven years (and continuing to ten years at this time), about 20% more cancers were detected in the screening cohort, but 50 (0.13%) deaths from prostate cancer occurred in them, while 44 (0.11%) deaths happened in the routine care group. The difference wasn’t significant.

Even more problematic were the numbers of men who died from other causes—312 (0.81%) in the screening group and 225 (0.59%) in the controls. According to the article, the excess in the screened men probably resulted from cancer treatment.

A major issue with all screening tests is that the overwhelming majority of those screened do not have the disease being screened for. But since all screening tests have a false positive rate, usually between 1 and 5%, this means that most people who test positive do not have the disease, and they get unneeded follow-up exams and perhaps unnecessary treatment, with additional cost and sometimes adverse effects.

Even when the screening test does detect real disease, in this case prostate cancer, it doesn’t mean that every case is the same. Some cancers are not aggressive and others simply disappear. Without screening most patients who didn’t have dangerous disease might not have been discovered, and they would have happily lived on. So screening tests also have the unfortunate effect of subjecting such patients to worry and treatment that they wouldn’t have needed.

Prostate cancer is a particular case in point. Annual prostate screening has become widespread. But this cancer often develops slowly, and men with the disease sometimes die from other causes before the cancer takes its toll. Thus the current recommendation of the U.S. Preventive Services Task Force is not to screen all men over 75.

And to make everything just a bit more complicated than it already is, the same issue of the NEJM reported a European prostate screening study that did show a preventive effect on death from prostate cancer. The screening in this case occurred every four years rather than annually, and it used a lower PSA level to refer men to treatment. Still, the results showed a significant, but not particularly impressive, 20% reduction in death rate and a number of 48 men referred for treatment for each death prevented.

I get a PSA and manual exam almost every year. And if you’re a man like me, you find it reassuring when your exams are negative. But the good feeling may be illusory. The best thing may simply be not to worry. There are lots of ways to get deathly ill and almost all of us deal with that harsh reality but just not thinking about it.