Suspended animation

In the April 22 issue of Science, a group from the Fred Hutchinson Cancer Center reports that a state of suspended animation can be achieved in (nonhibernating) mice when administered hydrogen sulfide (H2S). H2S is a reversible inhibitor of oxidative phosporylation. It is known that this induces hibernation in some animals.

When the mice were exposed to 80 ppm of H2S, their oxygen consumption dropped by 50% in the first 5 minutes. After 6 hours, their metabolic rate dropped by 90% and the core body temperature reached 15 degrees Celsius where the ambient temperature was 13 degrees. When the mice were returned to room air and temperature, their metabolic rate and body temperature returned to normal.

If this works in humans, we may now have a means of reducing metabolic demand after traumatic injury or surgery. H2S may become a standard part of the repertoire of paramedics. I won't bother to dwell on the space travel implications.

Hydrogen sulfide is the gas emitted by volcanos and geysers responsible for the rotten egg smell. It is usually considered toxic but now you know that if you see someone looking lifeless at the edge of a volcano, make sure to pull them out because they may note be dead but just be in a state of suspended animation.

Mathematical Biology

I am the first to admit that I'm not sure how much mathematics and theory has contributed to biology. Certainly the buzz is there. With the reams of data generated by the human genome project, biologists are begining to realize that they could use some help to understand all of this new data. The result has been a surge of available grant money and a flood of physicists, computer scientists and mathematicians into the field. (For the record, I made the jump over ten years ago when it was less fashionable.) I think it's safe to say that the jury is still out on whether or not the hype has been justified.

However, there has been one instance where mathematics has made a major difference and that is in the development of the triple cocktail treatment for HIV-AIDS. HIV is a particularly insidious virus because it attacks CD4 T cells of the immune system. However, it is rather slow acting. So often, when a person is infected with HIV, their virus load will remain low and CD4 counts will remain relatively high for a long period of time. Then, suddenly, the CD4 count will plummet and they will lapse into fully developed AIDS. It was first assumed that the virus replicated slowly and then accelerated at some point.

In the early 90's, David Ho and his group were testing treatments for HIV infection and decided that mathematically modeling the virus dynamics may give clues as to what was really happening. So they called in Los Alamos biological physicists Alan Perelson and Avidan Neumann (who is currently visiting our lab at NIH) to see if anything could be inferred about the virus. They used simple models of just a few ordinary differential equations to fit to the virus load during perturbation experiments where a potent protease inhibitor was administered.

Their simple model showed that the virus was far more active than previously believed. During the quiet phase where virus loads were low, the virus was actually replicating very rapidly but the immune system was running at high speed to compensate. Full blown AIDS developed when the immune system wore out and could no longer keep up with the virus. The implication was that any anti-viral treatment that targeted a single specific mechanism would fail because the virus would quickly evolve a defense. Thus the triple cocktail was invented. The virus would then need to evolve three separate defenses and this was difficult enough to keep it at bay. The results were published in two deservedly celebrated papers - the first in Nature in 1995 and the second in Science in 1996. I think their achievement represents the best example of how theoretical ideas can be useful in biology.

A new new world order

An excerpt from Thomas Friedman's book "The World Is Flat: A Brief History of the Twenty-First Century" appeared in last Sunday's New York Times magazine. The premise is that the information age has truly arrived and now people all over the world can compete on equal terms. Steve Hsu summarizes the idea in his blog. The tone of Friedman's excerpt and Hsu's posts is that the Chinese, the Indians, and the Russians are coming and we better get ready for the new competition. America's dominance over the world is beginning to decline and if we don't recognize it now our standard of living will fall with it as our wealth starts to diffuse across the globe.

I certainly believe this is happening and it is unavoidable. Improving our educational system or motivating our citizens won't solve the real problem and that is the US only constitutes five percent of the world's population and if life were fair, it should have only five percent of the wealth. Even given that life is not fair, having only five percent of the world's population means that we only have five percent of the brightest, most innovative, and most energetic people to create the wealth for the future. Eventually, things will equalize. It's a battle we just can't win.

So what should we do? One solution is to bring the rest of the world up to our economic level. Unfortunately, I don't think a world where everyone lives like an American is sustainable. See my estimate of energy use from a previous post. A possible scenario is that as the world catches up and begins to compete for scarcer and scarcer resources, the pecking order will be sorted out through military means. I truly hope we are sane enough to avoid that fate. My deluded, quasi-utopian vision, is that we all scale back and share. The pessimistic nihilist in me says that won't happen in my lifetime.

The North Pole

The earth's magnetic field is generated by the motion of molten iron in the earth's core. The combination of convection and coriolis forces generates the right set of currents to establish a dipole field with the north and south poles approximately in line with the rotational north and south poles. We partially owe our existence to this magnetic field because it provides a shield against charged particles from the solar wind. Without it, we would be subject to ionizing radiation and may also lose our atmosphere.

Neither Mars nor Venus has a significant magnetic field and we're not fully sure why. Mars once had a thick atmosphere of CO2 that may have been blown away by the solar wind. It could be that the molten iron has solidified or that the pattern of flow no longer supports a magnetic field. In any case, I think the lack of a field on Mars should make us less secure that we'll always have ours.

The earth's dipole flips every 250,000 years on average. We're not exactly sure why but some recent magnetohydrodynamic simulations of the geodynamo have shown examples of field reversals due to instabilities in the turbulent flow. It's been 780,000 years since the last reversal so we may be due for another one soon. It will take approximately 4,000 to 10,000 years for a reversal to take place. During the transition, the magnetic field may lose its intensity as well as its dipole structure which may have implications for life on the earth.

Another consequence of the turbulent geodynamic flow is that the north pole is in constant motion. It usually moves about ten kilometres a year but recently it has been moving forty! If it keeps moving at this rate, in about fifty years it will leave Canada and reach Siberia. This increased speed of drift of the north pole may be nothing more than natural random variations but it definitely makes me worry just a little.

Engineers in Government

Ever wonder why science and engineering policy doesn't make much sense. Here's an article from this month's Technology Review that may give a reason why.

Engineers and Political Power
by Ed Tenner, April 2005

In the united states, engineers don’t rule. According to a Congressional Quarterly survey of the 109th Congress, there are just four engineers in the House and one in the Senate. When the engineering specialties in the 2004–2005 Statistical Abstract of the United States are combined, there are 2.12 million engineers in the U.S. versus 952,000 lawyers and 819,000 doctors; yet 10 physicians now sit in the House and two in the Senate, and CQ lists 160 representatives and 58 senators with legal backgrounds.

One explanation for those discrepancies is that rapid technological change makes it hard for engineers to return from political office to professional life. In a 1992 interview with Technology Review, John H. Sununu, President George H. W. Bush’s chief of staff, acknowledged that as a consulting mechanical engineer, he was lagging ten years behind the field. Physicians, however, face equally great problems keeping up with the latest research, and by entering public service, they often forgo even greater potential income.

Another theory is that engineers are self-selected for social distance. Sylvia Kraemer is an intellectual historian who became a senior NASA official and interviewed 51 colleagues for her insightful study NASA Engineers and the Age of Apollo. She found that lab engineers and those promoted into management endorsed the reputation of awkwardness. A manager declared that most engineers "wouldn’t recognize an emotion if it hit them in the face." One rocket engineer flatly acknowledged, "I related to things."

This is an old American stereotype. In The Engineers and the Price System, the maverick economist Thorstein Veblen, championing what was later called technocracy, wrote that the public considered engineers a "somewhat fantastic brotherhood of overspecialized cranks, not to be trusted out of sight except under the restraining hand of safe and sane businessmen." He added, "Nor are the technicians themselves in the habit of taking a greatly different view of their own case."

But in many other cultures, especially in Eastern Europe, Asia, and the Middle East, engineers have been in the thick of power. The’ve been prominent in Marxist movements, such as the brief Hungarian Communist revolution of 1919. They became influential enough in the early Soviet Union that Stalin directed one of his first purges against them. Later, scientists and engineers were put to work in the gulags’ special research prisons, the sharashkas. After Stalin’s death, engineering degrees became desirable credentials for the politically ambitious. As the historian Kendall Bailes wrote in 1974, "What lawyers and businessmen are in the American political system—the major professional groups from which most politicians and policymakers are recruited—men with engineering backgrounds have become to a large extent in the Soviet Union."

In 2004, almost all two dozen members of China’s ruling Politburo had engineering degrees, including all nine members of the Politburo’s Standing Committee. In the Middle East, prominent engineers fill the political spectrum, from former president Süleyman Demirel of Turkey to the members of the Society of Muslim Engineers, pillars of the ayatollahs’ Iran, to the late secular nationalist Yasser Arafat. In many countries, engineering appeals -to the civic minded. On the other hand, disaffected young men recruited in European engineering schools were prominent among the September 11 hijackers. As R. Scott Appleby and Martin E. Marty observe in Foreign Affairs, "fundamentalists tend to read scriptures [as] engineers read blueprints—as a prosaic set of instructions and specifications." Civil engineer Osama bin Laden surely did.

Globally, then, the unpolitical Anglo-American nerd is the exception. The argument that gained credence in 19th-century France and was echoed in other regimes is that a state must be guided by a scientific and technological elite. Two forces kept that notion from taking hold in the United States. The first was American suspicion of central government. The second was industry’s appetite for engineers; at the turn of the 20th century, U.S. companies fearing manpower shortages resisted attempts to make elite postgraduate degrees the norm for engineers, as they were becoming for lawyers, doctors, and executives. So engineers in this country continue to design and implement everything but our laws.