Some musings on health Care

One often but not always learns best by comparisons with others. For example, in every other civilized industrialized country in this world, health care is a right, not a privilege, and is provided by the government to everyone in that country, even to visitors. By this reasoning, I came to the conclusion years ago (especially in the last 8 years) that our country must not be civilized, at least from this point of view. But then Obama was elected and I saw some hope on the horizon. I must admit that he has not been perfect. He appears to have been swayed too much by the intelligence agencies and military in such policies as continuing warrantless wiretapping of American citizens, in not prosecuting people at the top who broke the law in the previous administration, in not releasing the latest torture photos, in not pushing for gun control, in not yet completely leaving Iraq, and more recently, in not pushing for Medicare for everyone as the solution to health care reform. But in most other areas, he has been great and has returned our country to the status of an almost civilized country.

The Health Care controversy has once again made me have some doubt about the level of civilization in our country. Why on earth would anyone be against providing health care for everyone and stopping the predatory practices of the health insurance companies who now rule our medical lives? It can not be the shouted out argument that government should not run health care or even pay for it, since the popular Medicare program is government run and is very efficient and successful. Even those opposing health care reforms would not give up Medicare and also would not return those checks from Social Security they receive each month when they turn 65. So why is this occurring? The only reason I can think of is that this reform would hurt the profits of the giant health care insurance companies so they are paying huge sums of money to prevent this. This money is spent both in advertising to sway public opinion and in "campaign contributions" to the very members of Congress and the Senate who will have to vote on this type of bill. To connect the company money with opposition to reform implies that these politicians will be swayed (i.e. bribed) by the contributions to vote however the companies desire, but this unfortunately appears to be the case. There can be no other reason. And the politicians do not have to worry about health care since they are covered by a government financed program and will be covered their whole lives (I believe).

Oh, and I forgot that another reason is that the opposition political party (i.e. Republican Party) appears to want to damage the Obama administration by any means, even it involves damaging the health of their constituents. This is political suicide, but nevertheless the result may prove to be an absence of health care reform in the near future. I truly hope not. I like living in a civilized country.

The lights in the sky are stars

"Seeing the blindness and misery of man, and looking over the muteness of the entire universe, and man without any light, abandoned and alone in this corner of the universe, without knowing who placed him there, what he has come to do, what will happen to him when he dies, incapable of knowing anything at all, I am seized with fear, like a man who has been carried in his sleep onto a desert island and who wakes up without knowing where he is, without any means of escape." Blaise Pascal - Pensees

Any time I feel cocky and start thinking what a great teacher and scientist I am, I look up to the stars and realize that we and the entire earth we live on are simply a tiny, tiny, tiny blip in the Universe. The light actually left the stars years or even thousands of years ago and just now arrived here. And the panorama of stars one sees (if one is lucky enough not to live in Los Angeles) does not really exist, but represents slices of history, with each star releasing its light at different times in the past, with some probably not even existing anymore. And the light from the billions of stars in the billions of galaxies was emitted millions to billions of years ago and has endured the most incredible trip one could imagine to get to us here on earth. Sometimes this is too just much to comprehend, so I start out by trying to visualize distances. I start with the understandable - the distance from here to the other side of my yard, then from my city to another city and from my country to another country. I understand this because I have walked across the yard and have stared out the small window of an airplane flying several miles above the earth for 10 hours. Looking at my flight from here to London on a globe gives me a feeling for the size of the earth. To get to the moon, it would take my jet plane around 16 days since it is around 30 earth-diameters distant; it even took the Apollo astronauts 3-4 days with a much bigger jet plane. I can see the moon and can easily grasp this distance with some stretching of the imagination and can even imagine that I see the lunar lander left behind when the astronauts departed. But then things get a little hairy. Light from the nearest non-sun star, Proxima Centauri, which I can easily see with my 10 inch telescope, took 4.2 years to reach me, and light travels really fast - around 670 million miles per hour. Now I am struggling with the concept, but worse is yet to come. Light from our closest neighboring galaxy, Andromeda, took 2.5 million light years to arrive here, and light from the farthest object yet observed, a stellar explosion that released an immense amount of gamma-rays, took 13 billion years to arrive here. Now it is just numbers, but numbers do have meaning and the meaning is that I myself am meaningless in the immensity of it all and am properly chastened.

A modest proposal

I have a suggestion for the siting of a large solar power plant in the Mojave desert: Use the Owens Lake bed, which is a 200 sq mile dry lake between Olancha and Lone Pine in California which was created by the removal of water for Los Angeles through the construction of the LA Aqueduct. It is one of the worst environmental disasters in the United States and contributes around 8% of the country’s total particulate matter pollution. Although Los Angeles is legally obligated to solve this problem, nothing in reality will ever be accomplished as long as a growing city of 10 million people requires water. Totally covering this lake with a solar plant could probably solve two problems at the same time - It would solve the dust pollution problem by covering the dry lake bed with the necessary solar energy equipment and would provide a site for solar plant siting which is already environmentally damaged and therefore would not cause any environmental opposition. This would avoid having to site new solar plants on environmentally sensitive areas of the Mojave desert as is currently planned.

And in the near future another such site will unfortunately become available by the inevitable drying of the Salton Sea.

Postscript added on Aug. 17.
I don't want to brag but I just read a news article about covering the Owens dry lake with solar collectors (http://abclocal.go.com/kabc/story?section=news/state&id=6966498). In addition to the above Blog posting, I had written the Department of Energy and also a solar company that plans to open a large solar plant in the Mojave desert (with no responses of course). In any case, I am sure that this idea was so obvious that it occurred to many people previously.

Science is a hard mistress

To do research is to have a series of incredible highs interspersed with often as many daunting lows. The highs arise from those infrequent discoveries that come after months if not years of grueling work in the lab when things suddenly fit together and a door to the future opens. The lows come from those times when you realize that the data you have obtained with all that work just do not fit your favorite hypothesis and you must reject it. It seems paradoxical but the lows are what it is all about. Unlike any other field of human endeavor, scientific research demands a basic humility in the face of facts, a humility that flies in the face of human nature. Everyone wants to be respected and even famous and to reach a position of power and influence, and these human desires often lead to the avoidance of inconvenient facts either consciously or subconsciously. The researcher however must look at the data and interpret them in terms of the best model even if it means rejecting your own hypothesis.
I myself have experienced both types of emotions in my research career. The high came in 1990 when we suddenly realized that we could explain the extremely enigmatic and even disturbing phenomenon of uridine insertion/deletion RNA editing in trypanosomes that was causing serious scientists to speculate that the genetic dogma of information flow from DNA to RNA to protein was incomplete. We and others had found that multiple transcripts of the maxicircle mitochondrial DNA in trypanosome mitochondria could not be translated due to the absence of open reading frames, and that these transcripts were somehow corrected after transcription by the insertion and occasional deletion of uridine residues at specific sites thereby eliminating the encoded frame shifts and producing mRNAs with open reading frames that encoded conserved mitochondrial proteins. Initially the phenomenon was thought to involve a few U’s at a few sites, but soon it blossomed into cases of hundreds of U’s at hundreds of sites, in essence creating genes de novo.
The overriding question was where did the information come from that told the U’s to be inserted and deleted at these precise sites. The information did not appear to be encoded anywhere in the mitochondrial genome, which was in itself quite bizarre in that it consisted of around 50 maxicircles catenated with thousands of minicircles into a single giant network of DNA. Not giving up on the central dogma we were looking for RNAs that could base pair with mature edited sequences and thereby provide the information by this well tested mechanism. We speculated that perhaps the reason no one had seen this sequence information was that it was in short segments. Having asked our friendly lab computer to search for short sequences anywhere in the maxicircle genome that could base pair with the mature edited sequences and thereby encode the insertions and deletions of U’s, it was at first disappointing that there were no such antisense sequences. But a closer examination of the results showed that the mismatches were always transitions and suddenly we realized that if we took off our Watson Crick blindfolds and simply allowed G-U base pairs in addition to G-C and A-U base pairs, the computer was telling us that there were short complementary sequences in the maxicircle DNA that could encode the editing information. A few days later we obtained some direct evidence for the existence of a novel class of small RNAs with these sequences (and also with 3’ non-encoded oligo U tails!) and we named them “guide RNAs”.
The next high came when we (i.e Nancy Sturm, my graduate student) realized that the thousands of minicircles also actually encoded the majority of guide RNAs and that this was finally the long sought after solution to the genetic function of minicircles. Suddenly we had two mitochondrial genomes in the same cell, one with cryptogenes and another one with complementary guide RNA genes. Immediately this discovery led to a mechanism in which the gRNAs formed an anchor duplex with the pre-edited mRNA just downstream of the editing site and recruited a cadre of specific enzymes to the editing site. We proposed a nuclease that cleaved the pre-edited mRNA at the editing site, a 3’ terminal uridylyltransferase that added U’s or an 3’-5’ U-specific exonuclease that deleted U’s, and finally an RNA ligase that religated the cleavage fragments. Like all good models it was very satisfying since it explained a number of previous observations such as the 3’ – 5’ polarity of editing. This was a definite high in the life of my lab.
But my Swiss postdoc, Beat Blum, had the habit of thinking too much and soon came up with another model - in which the U’s were transferred from the known 3’ oligo U tail of the gRNAs to the editing sites by a transesterification mechanism such as employed in RNA splicing. This model had an easily testable prediction – that there were chimeric intermediates in which the 3’ end of the gRNA was covalently linked to the mRNA 3’ cleavage fragment at an editing site. When this was rapidly confirmed, the lab entered another high, albeit with a low level of anxiety and chagrin that we had just proposed another seemingly viable model and now were saying that this was wrong. The transesterification model became the flavor of the week and even the Nobel laureate, Tom Cech, independently proposed an identical hypothesis. The new vistas opened were awesome: Editing was now a type of RNA splicing and was a very ancient phenomenon indeed!
But then evidence slowly accumulated drip by drip that the chimeric intermediates were artifacts of cleavage ligation and that our original theory was correct and not the awesome transesterification model. Again a beautiful theory crashed on the hard rocks of inconvenient facts, but the inevitable low was tempered by the high that remained from the fact that our original model was indeed correct.
A few years have passed since those exciting days but the memories linger.

From Protist (2009) In press.

My personal epiphany

I will never forget the first time as a PhD student I did a growth curve on Leishmania cells in culture. As I began to plot the data I found that the number of cells increased at around 9 h doubling time and then began to slow down and finally level off and actually decrease as the cells died. When I plotted the number on a semilog scale against time, I suddenly realized what was meant by ‘‘exponential growth’’ and why Malthus had concern. This was a true epiphany for me as I ran through simple calculations showing what would happen if the cell growth did not slow down and continued doubling every 9 h. The numbers of cells and the space they would occupy blasted my mind when I tried to compare the Leishmania cells with larger animals and with humans. In the case of Leishmania the natural slow down, whether it be caused by nutrient deprivation or more exotic physiological reasons, is what has saved the world from being covered with Leishmania. In the case of humans, it remains to be seen what causes will slow down the exponential growth. The two alternatives are to decrease the rate of increase, i.e. the number of offspring per family until this rate equals the death rate. Or to experience a catastrophe such as a major rapid die off from a disease, a nuclear holocaust or a world-wide famine (‘‘famine, distress, havoc and dismay’’ in the words of Malthus) or a slower die off from the degradation of life produced by the loss of an essential resource required for modern civilization such as oil. Why do I bring up this ancient epiphany (that I am sure each person at one time experiences) in the pages of this journal? My main reason is that this journal exists within a civilization and culture and even scientists doing research on protists must be cognizant of possible oncoming doom. There is great concern recently about climatic warming and how human activities have contributed to this phenomenon by increasing greenhouse gases in the atmosphere. The appearance of a huge hole in the life-preserving ozone layer in the atmosphere over Antarctica is another recent concern since this may allow UV irradiation to affect phytoplankton in the ocean at the base of the world’s food chain. Failures of most of the world’s fisheries have occurred. Species are being extinguished due to habitat encroachment by humans at a rate greater than during any of the major extinctions seen in the fossil record. The price of oil is rising rapidly and may skyrocket as supplies are depleted in the near future. The supply of clean water is running out in many places. The common theme underlying all these dramatic events and those yet to come is exponential growth of the human population. Yet no one talks about this and religions and governments, at least in the United States and apparently elsewhere also, actually almost forbid any rational discussion. Yes climatic warming is occurring and will cause major disasters, but even if we decrease the emissions of CO2 into the atmosphere, the real underlying problem will not be touched — exponential growth. Sure one can simply ignore this and live from day to day studying our protists and let our children and grandchildren find a solution (or suffer the catastrophe). But I myself feel we should take a lesson from the Leishmania cells growing in culture and somehow decrease our growth rate.

From Protist (2007) 158, 3.

Musings on the real problems

I realize that Protist is a journal for the science of protozoa, not for musings on the future of humanity (and of protistologists!), but please give me leave to attempt to articulate my thoughts. We too often get flustered and concerned about current problems, be they personal or international, and leave festering in the dark corners of our minds the real problems. I agree that the loss of my (and others) retirements savings invested in stocks is serious and close to a personal and even international calamity. I agree that the election of an intelligent, rational and less bellicose American President is important and serious. I agree that anti-intellectualism and the rise of religious fundamentalism has been and is a serious and distressing and recurring problem in all societies. I agree that the continued existence of thousands of horrible nuclear weapons by multiple countries is a serious and perhaps fatal problem.
But the certainty of the universal devastation which will be, and amazingly, is already starting to be being reeked by human-caused climate change throughout this world of ours is to my mind the most serious and consequential problem that Homo sapiens has ever faced. The various scenarios modeled by the most eminent climatologists are frightening and bode ill for civilization as we know it now. The certainty of rises in ocean levels which will inundate island nations and flood costal cities world-wide, combined with the certainty of changes in weather patterns and sources of water have extreme consequential predictions. These changes will produce starvation, increase disease and cause massive emigration of millions upon millions of people world-wide. The eventual pressure on highly industrialized countries to decide whether to accept the massive immigration of poor starving people or to build Berlin-walls to keep them out and try to preserve their own devastated infrastructures and crumbling economic frameworks produced by the loss of major cities will be one of the most important ethical and moral decisions ever made. But the walls will be to no avail and this influx and the destruction of societies will forever change the industrialized societies in irreversible ways. An immediate result will be the use of military power to either obtain newly fertile regions for agriculture or to fight against the movements of peoples. The resulting wars will devastate more counties and weapons that were created never to be used perhaps will finally be used. Finally the economic and social framework and the very fabric of modern societies will collapse. The further consequences can not even be imagined by my feeble imagination.
Of course it is clear to anyone who can think rationally that the ultimate underlying cause of these horrible scenarios is overpopulation, which appears for multiple fundamental reasons to be impossible for the human species to change. But there are of course more immediate causes that actually can be remediated somewhat. A mandated world-wide severe decrease in the output of carbon dioxide from burning of fossil fuels would by all the models begin to decrease the rate of change, but this also appears to be beyond the abilities of humans (if our leaders and politicians are indeed human).
I myself will probably not experience the worst of this but our children and their children certainly will. Perhaps our species’ evolutionary time span has been reached, but I truly hope not. The intelligence, ingenuity and resourcefulness of humans will perhaps reverse these trends and leave the protistologists a little more time to study our little beasties.

From Protist (2009) 160, 1.

What is Science and Why do I do It?

Every once in a while I try to step back from the ongoing little emergencies and exigencies of lab research and think about the meaning of it all. Why is it at all important to learn exactly how a biological phenomenon occurs and has evolved, how molecules interact, what are the rules that govern the behavior of matter at all levels, how our universe evolved and even how mathematical truths exist. Any why does Society pay us and (sometimes even respect us) to try to learn these things? The second question is easier to answer, especially for biomedical research. Clearly humans desire long healthy, happy lives and human societies want to perpetrate themselves and this knowledge may aid in achieving these desires. The first question however is difficult and has no easy answers or perhaps any answers at all. I myself feel that knowledge and understanding of the world around us has an inherent worth beyond that of the welfare and happiness of individual humans and groups of humans, although it indeed may prove incredibly important for the very survival of our species, without which knowledge in any sense is meaningless. Knowledge is also self gratifying and pragmatically useful for future behavior but that is hardly the real reason to do research. But what is this “inherent worth” of knowledge? I equate it with the sense of wonder and beauty that one feels when one finally understands how recalcitrant facts fit into conceptual frameworks and new facts are then predicted. This sense of wonder must be tempered by the realization that the theories almost certainly will change and the “facts” reinterpreted, but for that small period of one’s life the wonder and beauty of it all glistens and all striving and daily routines are subsumed. It may sound presumptuous, but that is why I do Science.

From Protist (2008) 159, 3.