Mark Pine

In 1953 at the University of Chicago, Stanley Miller fired sparks through a beaker filled with simple gases containing the raw elements of life: carbon, hydrogen, nitrogen, and oxygen. As a result, amino acids, the building blocks of protein, formed. The experiment was hailed as a giant step along the path to understand how life began on earth.

In a marvelous coincidence, 1953 was also the year that Crick and Watson proposed the correct structure of DNA in an article in the science journal Nature. Perhaps if the implications of their work had been widely understood at the time, history might have regarded Miller’s experiment as less significant.

Before the discovery of the genetic code, it seemed that proteins, formed from amino acids, must be the essential ingredients of life. Structural proteins like collagen build the bodies of living organisms, and enzymatic proteins like dehydrogenases, which transfer hydrogen ions, provide the energy and direct the chemical reactions of organisms. It would have seemed that generating the constituents of proteins would be the major step in the origin of life.

In recent years, however, focus has shifted from proteins to nucleic acids. An article in Science this month, part of an issue highlighting the origins of life, puts forward the hypothesis that RNAs, not amino acids, may have constituted the originator molecules. RNA molecules consist sugars and organic bases (compounds of carbon, nitrogen and other elements) chained together in sequences that encode genetic information.

Today we understand that nucleic acids direct the joining of amino acids to form proteins. Late last year, a Harvard research group reported that enzymes made of RNA (rather than protein) can replicate themselves, a defining capability of life. Moreover, in recent years, researchers have made progress in showing that sugars and bases, which make double-helix molecules similar to RNA, may have arisen on the pre-life earth from simpler compounds (Science, 2000).

The Harvard group has also shown that fatty acids can form globular vesicles, “protocells,” that can take up chemical precursors and hold them in proximity long enough to permit the formation of nucleic acids. (See film clip of vesicle formation.)

Life may not have begun with instantaneous flashes of spontaneous creation, such as a lightening sparking the formation of amino acids, but rather through the gradual synthesis of many different kinds of compounds—sugars, bases, lipids, etc.—eventually coming together in globs made of fatty acid, where nucleic acid-like molecules began to self-replicate.

The case for voluntarily reducing your calories grows stronger every day. Indicators that restricted-calorie diets lengthen life span began to appear decades ago from work in simpler animals—worms, fruit flies, and rodents. Rats lived up to twice as long. Then studies a few years ago of mice on diets showed the animals improved on measures of heart functioning, suggesting that limited food intake may prolong life by improving the performance of organs. Primates (monkeys, apes, etc.) fed fewer calories showed lowered levels of blood sugar and fats, improvements that may help to prevent diabetes and heart disease.

Now comes research that shows older, overweight people can improve their short-term memory by eating less. In research at the University of Muenster (Germany), reported in Science this week, 50 subjects 60 years old with BMI about 28 were randomized to one of three diets: calories reduced 30% with well-balanced nutrients, normal calories with increased unsaturated oils, or usual and unchanged diet. At the start of the experiment and three months later, all subjects took a test of short-term recall. Given 15 words, it was determined how many they could remember a half-hour later. The restricted-calorie subjects improved scores by 20%, but the two groups on the other diets showed no improvement. Moreover, it had been thought that increased intake of unsaturated oils might help memory, but that didn’t happen.

The results seem suggest that we can improve our working memory by eating less. That’s the mental faculty that gets used in daily work when, for example, we look up a phone number and then try to dial it. I don’t know about you, but I’m often bamboozled by failing to remember items on a list, things to do, or to articles take along. I sure could use some help in the recall department.

But the study has some important qualifications and caveats. The subjects were older and overweight, so that the results may have come from weight reductions toward normal rather calorie restriction, per se. Also, the subjects weren’t blinded, because they certainly knew what they were eating, and so its possible that the subjects on restricted diet tried harder on the 3-month test of recall. Lastly, only 50 people were tested, which is not a large enough number to equalize all the human variation among the groups. It’s possible that the group that tested better was different from the other two in some unknown way. The research should be repeated with larger numbers.

Still, for years a lot of different kinds of research have shown that reducing dietary calorie intake improves life span and markers of health and good functioning—in many different organisms and in many diverse investigational conditions. The results are so consistent that it’s time that we all begin to try to put these findings into practice in our lives.

It’s a story of a quest—of two quests, actually, one scientific and one personal, which join and become one. “In Search of Memory” (2008, produced and directed by the German actress Petra Seeger) traces the memorable career of physician and neuroscientist, Eric Kandel, who was awarded the 2000 Nobel Prize in Physiology/Medicine. The film aired Tuesday evening at the Carnegie Institution in Washington, DC, where Kandel and Seeger also appeared to answer questions.

Eric Kandel is an Austrian born Jew, whose family fled their Viennese home to New York City in 1938, when he was 9 years old. The boy flourished in his new hometown, where he was educated, became a physician and carried out a career of scientific research on the neurophysiology of memory. But Kandel remained haunted by the experiences of Vienna. The movie shows his scientific work to understand memory following a path leading to the same distant end as his personal work recalling memories of the city of his birth.

Kandel was trained as a psychiatrist during the years when Freudian psychoanalysis held sway in the psychiatric world. His impulse to do research began with the idea of uniting psychoanalysis with neurophysiology by finding the locations of the id, ego, and superego in the human brain. It would have been an impossible task, but since psychoanalytic theory concentrated on the traumatic life-long effects of childhood memories, it was natural that Kandel would focus his research on the making of memories. His work at New York University School of Medicine and Columbia University College of Physicians and Surgeons identified the specific neuroanatomical and neurophysiological events that transform fleeting impressions into long-lasting memories. Those discoveries, he would come to realize, elucidated the mechanisms whereby his boyhood memories of Vienna remained caught in his own brain, and also in need of exploration.

The film shows his recent travels to Vienna, a city that now praises his work and lauds him as one of their own. He searches out his roots: his family’s apartments, the settings of the frightening encounters with Nazis and hostile citizens. He visits his father’s toyshop, now a delicatessen, where he is welcomed by the owner.

In the same story, interspersed with sciences of Vienna and New York, the film shows his journey through the places of memory formation in the brain. Memory traces are first lain down by connections at synapses between neurons carrying sensory impulses and neurons of the hippocampus, structure at the brain’s core. Memories are strengthened when repeated sensory inputs make the same connections over and over again, resulting in the activation of genes that cause the multiplication of synaptic connections at the same sites. Kandel did much of the work to prove this concept by the ingenious technique of experimenting the simple nervous system of the snail.

Kandel’s discovery of the mechanism of long-term memory formation in the multiplication and strengthening of synaptic connections is his great contribution to science and medicine. As shown in the movie, the discovery coincides with his contribution to understanding himself. His self-discovered knowledge has provided him the means to realize and re-experience the memories of Vienna from a position of power and accomplishment instead of persecution and fear.

Over 40% of adult Americans have diabetes or pre-diabetes.

That’s the result of a new survey by the National Institute of Diabetes and Digestive and Kidney Diseases reported online in Diabetes Care, which looked at Americans 20 years old or older. One-third of people over 65 have the disease, and the prevalence of pre-diabetes in this older group reaches a staggering three-quarters!

Diabetes is a disease that impairs the body’s ability to handle the blood sugar that gives us energy. It causes high levels of blood sugar, which damages our blood vessels and organs. Pre-diabetes involves increased blood sugar levels, too, but not yet high enough to be called diabetes.

Diabetes is slow death. That is no exaggeration. People with diabetes lose their eyesight. They gradually develop kidney failure, and many have to go to dialysis every few days to get their blood cleared of the waste compounds our bodies produce. They lose sensation in the fingers and toes and experience limb pain, especially when walking. In many people, the circulation of blood to their legs gets so bad that the tips of their toes turn black and die off, and this black death begins to spread upward. They suffer strokes and heart attacks and develop failure of the heart’s capacity to pump blood, so that everything becomes an effort. And of course, they every day have to take drugs and test their blood for sugar.

We Americans just don’t realize what so many of us are facing. We don’t eat right, many of us, and we don’t get exercise. We don’t lose weight. It IS very difficult to lose weight, but if we could all see what might happen, I think many more people could find the willpower to succeed.

Diabetes will also be deadly for our health care system. It’s not just the cost of treating the disease in so many Americans that can bankrupt us, it’s also the cost of all those other diseases that diabetes leads to, all the surgeries for our eyes, our legs, and our hearts. All the long hospital stays for strokes, recovery and rehabilitation.

I have diabetes on both sides of my family. My Dad had it when he died, and my mother’s mother did, too. Perhaps because I was a young child when she died, I starkly remember my grandmother’s debilitated condition. I never knew her except as a frail, scrawny, wrinkled woman, who had no energy. These memories, unfortunately, are not pleasant ones. My mother told me many times about my grandmother’s diabetes. I think it was the reason my mother chose to become a dietician.

When I turned 60, I vowed to prevent that kind of thing from happening to me. Through all my adult life, I’ve exercised regularly. That has helped. But by the time I reached my seventh decade, I was still 30% overweight. So each day I wrote down everything I ate, along with the calories. That’s all I did. I kept track of everything. I began using a spreadsheet on the computer, and since I eat many of the same kinds of food day after day, it became easier to keep track by just copying and pasting. I have a daily diet record that goes back to 2005.

That was what it took. Just seeing the numbers add up—over time, day after day—I slowly began to adjust my food and calorie intake. Gradually, my daily intake and weight came down. Since I began keeping records, I’ve lost 40 lbs. My last fasting blood sugar was 86. Of course, I’m a retired physician. I know what the deal is. I wish everybody did.

In the NY Times today, reporter Steve Lohr drew useful comparisons between FDR’s plans in the first years of the Great Depression and those of President Obama. But though he wrote that the economic collapse of the 1930s was “deeper and more ominous,” you wouldn’t know that from listening to callers on the C-SPAN show this morning. People are really hurting now. Many callers were out of work, with little hope for jobs after months of searching. Some spoke of not knowing where any money would come from. One distraught woman said she had just spent $600 on heating and had no money left, but then she chose to end her call to avoid losing it completely. Perhaps we’re not in a depression, but for many people it seems like we are.

Many economists agree that Roosevelt’s spending programs didn’t replace enough of the private-sector economic activity lost to the Depression. According to Lohr, New Deal programs totaled only $200 billion in today’s money. Keynes wanted FDR to spend more. Similarly, economists say Obama’s current plan for $825 billion isn’t enough to replace trillions of dollars in lost economic activity due to the current recession.

While most Democrats in Congress favor moving the spending package forward quickly, many Republicans are trying to reduce its size and slow it down. One valid issue the Republicans raise is to question who will buy all the Treasury debt issued to finance it. Other than that, they try to make the case that much of the planned spending is not directly related to combating the recession. They seem to fear that Obama really will launch lots of New-Deal-like of programs, while they offer as solutions only their usual tax-cuts-solve-all-problems recommendations.

Almost all economists agree, as Lohr explained, recovery from the Depression “arrived only with the buildup for World War II.” But was war-related spending directly related to combating the Depression? Far from it, it was intended to fight wars. The lesson, therefore, is that it doesn’t matter what the spending is for, except that it replaces the economic activity lost to the downturn.

Obama and the Democrats are right to propose spending on many different things. The Republicans criticize spending on contraceptives. Do they think drug companies don’t employ people? They criticize spending on the National Mall. Do they think that landscapers don’t work and feed their families? Of course, we shouldn’t waste money, but let’s not worry exactly where it all goes as long as the programs will provide jobs and target improvements to our country.

Sort of, anyway. But it’s not about finding a mate … although, if you’re a man, having a longer ring finger may mean you’re more likely to win a certain kind of woman.

Scientists at the University of Cambridge (UK) reported this month that men working as day traders at a London exchange , who had relatively long ring fingers in comparison to index fingers, made an average of six times as much profit as their short-ring-finger colleagues. The lead scientist, John Coates, a cognition researcher and former Wall Street trader, had previously measured testosterone levels twice a day among a group of London traders. He reported last April that elevated levels of the hormone, especially in the morning, correlated with more profitable days.

It’s long been known that innate testosterone level correlates with the relative lengths of index finger and ring finger. This is true in both men and women. The length ratio (2D:4D) is a sex-related trait, lower in men than women and determined largely by in-utero levels of testosterone during the first trimester of gestation. Testosterone levels and the finger-length ratio are also correlated with risky behavior. So on a hunch, Coates checked the finger-length ratios of his group of day traders and found the impressive six-fold profit difference between the traders with low and high ratios (Science, Jan. 16). “I almost fell off my chair,” he told Science magazine. “I could not believe what I was seeing.”

Some details of these differences may be found online in a 2008 paper from Case Western Reserve University that looked at men and women in a financial gambling experiment. The researchers measured lengths of the second and fourth digits from the crease closest to the base of the finger to the central point of each fingertip. They also used the experimental situation to test for risk taking behavior. As expected women showed less risky behavior than men, and the 2D:4D ratio decreased as the subjects’ behavior grew riskier. The researchers’ finger-ratio measurements were in line with averages reported in the scientific literature. The average ratios for females range from .96-.99 while male average ratios range from .93-.97.

Naturally, I had to measure my own ratio. Surprisingly (because I had never thought of myself as much of a risk taker) I found the average of my two hands was 0.94, which seems to fall toward the low (risky) end, even for a man. But I think it did teach me something about myself that I didn’t consider before. Next time I buy stock, I’ll think about it.

In a related finding, a study at the University of Nottingham of patients with knee joint arthritis found that women with shorter 2D:4D ratios were significantly more likely to suffer osteoarthritis of that joint (i.e., wearing down of knee cartilage along with pain). The Nottingham researchers didn’t speculate as to cause of the difference, but I wonder whether joint injury might be more common among women who are more physically vigorous due to higher innate levels of testosterone.

As one of its most important appointments, the Obama administration may choose a new commissioner for the Food and Drug Administration, an agency which has been troubled in recent years. The prestigious Journal of the American Medical Association and the New England Journal of Medicine have criticized the FDA for failing to act effectively when adverse drug reactions are discovered following the approval and marketing of new drugs. Several highly publicized drug recalls during the past decade have reduced confidence in the agency’s ability to regulate pharmaceuticals. Problems with inspecting and regulating the purity of imported and domestic foodstuffs have weakened the public faith in our food supply. Recently a group of medical science reviewers at the FDA protested agency policies that they said were thwarting their work to ensure the safety of medical devices.

It’s widely believed that the agency needs a major overhaul to improve its vital work. I favor Steven Nissen, MD, a renowned cardiologist of the famous Cleveland Clinic, for the post of commissioner.

For years, Dr. Nissen has strongly advocated the use of rigorous medical science to accurately evaluate questions of drug safety and efficacy and to effectively regulate new drug approvals and post-approval adverse drug reactions. He was one of the first independent clinical scientists to show the elevated risk of cardiovascular thrombosis associated with the drug Vioxx, which was finally withdrawn from the market by Merck and the FDA, but only after several more years. Nissen also authored papers on cardiovascular safety concerns associated with Avandia, a drug for diabetes, and he has questioned the FDA’s approval of the cholesterol drug, Zetia, a drug combination that many medical scientists think problematic.

Nissen clearly is a medical man who wants to the FDA work more effectively to promote and protect public health. He recently wrote a letter to the journal Nature recommending changes to reinvigorate the agency. Among his proposals are these:

(1) The commissioner should serve a fixed term of six years to reduce political influence.
(2) The new administration should re-evaluate the use of user fees to fund the agency. These payments are made by pharmaceutical companies for the agency to examine their own applications to approve new drugs.
(3) The FDA should make publicly available all clinical investigation data on drug safety and effectiveness.
(4) The agency should develop better methods than voluntary reporting of adverse drug reactions to monitor drug safety after approvals.
(5) The FDA should tighten standards for approval of drugs and devices and medical product advertising.
(6) The agency needs stronger enforcement capabilities, especially to conduct more frequent and thorough inspections of food and medical product suppliers.

These are all excellent recommendations, which sorely need to be implemented soon. Nissen appears to be the man for the time and the need. I hope President Obama and Secretary Daschle choose him for the job.

Many Americans are concerned that closing Guantanamo will result in terrorists being set loose on our nation and the world. Nothing in Obama’s order to close the prison suggests that will happen. Although the Bush administration said that in the past released prisoners have joined with Al Qaeda or other terrorist groups, it was they who brought it about.

Obama’s order is about seeking a different, more effective solution to the problem of the Guantanamo prisoners. It is about eliminating a present danger to the United States. Guantanamo has harmed our nation and continues to harm us, because its existence has been a rallying cry and a recruiting tool for terrorist organizations, and a source of trouble for American diplomacy and foreign policy. Our president’s action joins two important goals: It improves America’s standing in the eyes of the citizens of the world (including Arabs and Muslims), and it brings our country back into sync with our own professed ideals.

In eliminating the present dangers to America that the existence of Guantanamo presents, Obama’s order also seeks to reduce potential future threats from the prisoners. The order specifies one year to examine the prisoners and determine who is a threat and who is not. It also requires that appropriate means for dealing with them be found or devised. Under the order, any crimes committed by these men will be tried in lawful courts and sentences carried out. Since threats and actions to harm us constitute crimes, it should be possible to lock up the guilty ones in maximum-security prisons. Surely a country like ours has means to create secure prisons for those Guantanamo prisoners who have been found guilty of dangerous activities.

There will always remain a risk that those prisoners not found guilty might try to harm us in the future. But we should not perpetuate the ongoing danger that Guantanamo presents to us in order to avoid the future possibility one of them might someday try to harm us and succeed in doing so.

Several weeks ago, I posted on an article in Science magazine about a claim that an fMRI experiment in human subjects cast doubt on the concept of free will Will the Case Remain Open for Free Will?.

The scientists studied human subjects in a functional MRI scanner, which recorded their ongoing brain activity as they made a choice to press a button either on their right or left. The scan showed an activity pattern that correlated with the choice about 60% of the time, significantly better than chance. But the pattern was observed about 10 sec. before the time that the subjects reported consciously making the decision. The scientists claimed the finding was evidence against free will, since it implied that the earlier brain activity predicted the choice about 10 sec. before the subjects made (what they believed was) their conscious free will decision.

Previously, I wrote that the scientists did not consider the possibility of delay between an earlier tentative or preparatory decision and a later confirmatory decision to report to the investigators and carry it out. In this connection, an article online in Science yesterday Brain’s Arteries Have a Mind of Their Own describes an experiment using electrodes in the visual cortices of monkeys. The animals were trained “to monitor a tiny light … when the light turned red, as it did at regular, predictable intervals.” If the monkeys directed their gaze to the light when it changed color, they would earn a reward.

The electrodes picked up only a little neural activity when the red color actually appeared, an amount consistent with the tiny size of the light. But measurements of blood flow in the same region showed significant increases peaking a few seconds before the light changed color. According to the article, “the findings indicate that the flow of oxygenated blood to a particular brain region doesn’t just increase in response to neural activity but can actually anticipate an expected task.”

Functional MRI scans measure blood flow, and scientists using these scans to study brain activity assume that blood flow correlates with neural activity. This result in monkeys, however, calls into question conclusions based on increased fMRI activity preceding the making of a decision. In this case, when the monkeys actually observed the light, little neural activity occurred. But significant changes of blood flow occurred seconds earlier in preparation for the event.

Experiments in monkeys cannot resolve questions about the human exercise of free will. But this investigation does suggest that the fMRI scans of subjects choosing to press a button may not have been showing a reflexive decision made before the time of a perceived, illusory free-will decision. Rather the scans may have been picking up blood flow changes happening in an anticipatory or preparatory stage of a free will decision that was completed some seconds later.

In the past couple of decades a number of investigators have reported similar findings in human studies of brain activity, where the activity precedes the time that subjects are conscious of making a free-will decision. The first such studies were done with EEGs and showed a particular electrical potential wave, which correlated with the subjects’ decision but which preceded the time that the subjects reported making the decision. All these investigations, it seems to me, have the same problem of not taking into account the possibility of a delay between earlier and later parts of a decision process.

The exercise of conscious free will is not likely to be an instantaneous all or none process. More likely, conscious free-will decisions involve more than a single decision —perhaps the earlier and later stages of a decision process—including anticipatory or preparatory activity that precedes actually carrying it out. In several experiments, as in the one reported recently in Science, it seems that the delay may involve time between an earlier tentative decision and a later confirmation that includes the decision to report to the investigators.

If this turns out to be the case, the occurrence of anticipatory or preparatory stages, which are seen on MRI scans or EEGs and which correlate with later decisions, would not rule out the possibility that the decisions are exercises of free will.

The odds are against him. No president since LBJ—perhaps since FDR—has succeeded in harnessing the full power of the federal government in the service widespread economic prosperity. Will BHO achieve it?

Entrenched and powerful interests will work just as hard to oppose him.

Financiers, who cut secret deals in unwatched rooms, manipulating markets, cracking into fiscal fissures, and reaping vast profits, are continuing to do their business. The unregulated hedge funds will go on resisting regulations and reporting. Through their moneyed lobbyists they will continue their contributions and claims that their valuable services create prosperity.

Health industry companies—insurers, providers, and health product producers—will hustle to protect their prices and profits. In the halls of Congress and in ads on TV they will brand proposals for universal coverage socialism. They will try to scare us about change. And if changes become inexorable, they will seek protect their revenues by enacting requirements that the government underwrite whatever they bring to market.

Energy companies will advertise all their products as green and good for the environment. Producers of fossil fuel will say there is no substitute. Alternative energy businesses will assert they have the answer. All of them will resist accurate assessments of the value of their products and regulations to ensure energy efficiency.

Companies of all kinds will try to cash in on the flood of government funds for infrastructure and commit the government to cost plus contracts that keep the money flowing. They will curry favor with legislatures and kickback on their revenues.

The barriers to progress are all high, wide and entrenched. Obama has promised that “those of us who manage the public’s dollars will be held to account, to spend wisely, reform bad habits, and do our business in the light of day.” Openness, transparency, and widely available information will be the only way it will all work. But even if Obama can achieve accountability, he will have to campaign to counter opposition and constantly strive to sustain public support.