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.

The Best of Times

This is my final web alert in a continuous series, mainly due to having culled most of the interesting protist sites. But since the web is dynamic and always changing, I am sure that new valuable sites will appear and I hope to present web alerts sporadically when appropriate. However, since this is the song of my swan, I would like to request your indulgence (and that of our fearless Editor-in-Chief) for a little philosophical waxing and waning. I started this series with an article entitled “Protists on the Web” in which I stated that the web was a true revolution in communication. Today I am convinced that this was an understatement and that the web is perhaps the next step in the evolution of our species. It represents the beginning of instant and continuous communication between all humans, which in a way is the annealing of our species into a super-organism. Of course this simplified system that exists today is limited to one way communication and is barely interactive but it will evolve into totally interactive, totally encompassing communication. Every person will have instant access, perhaps through chip implants, to all accumulated human knowledge, and be able to add their intellectual and even emotional and political contributions to this pool with ease. At this time we can not even conceive of such a system but the beginnings are there and cannot be impeded. The question of whether this is a good thing is an important one and ethical concerns should help steer the technology and avoid dangerous avenues. But the history of our species shows that change can not be stopped and will ooze out of all walls put up to block it. Ethical concerns should help avoid the dark scenarios in which dictatorial governments by means of this technology have complete knowledge of the location, genetic composition, speech and perhaps even thoughts of its subjects. But the light scenarios are more compelling and marvelous to think about. I do have however one overriding fear and that is that our species may destroy itself together with this marvelous communication system, and that would be a real shame. Malthus was right and any species, be it protist or human, cannot increase exponentially with limited resources of food, water and energy. Too many people inhabit this earth already and it is getting worse. This is the underlying reason for all human problems, including famines, wars and terrorism. We have intentionally and inadvertently initiated the most massive extinction of species in evolutionary history and have again, intentionally and inadvertently, made macro changes in the earth’s various normally self-regulating systems such as climate and atmospheric composition. I don’t want to end this musing on such a dark note. Let me instead discuss why I am in this crazy business. Imagine (my mother would say), grown men spending all their time studying little creatures that no one can see! I would respond, if she were here, that this is the best of times – grown men (and women) are paid by society to simply discover new knowledge about the world, its creatures and the universe in which we live. This is truly the best of times.

From Protist (2002) 153, 365.

Death of the "ologies"

It is my sad duty to report on the death of one of academics’ most cherished institutions – the “ologies”. Way back before we knew so much and understood so little, Universities compartmentalized knowledge by the addition of the Greek logos, meaning the 'study of', 'specialty in' or 'art of' a given field to the end of the word. I did a Google search on “ologies” and the winner (http://phrontistery.info/sciences.html) had 633 different fields with this suffix. There is also an entire book on this subject called ”Ologies and Isms : A Dictionary of Word Beginnings and Endings” by Michael Quinion for those who want to delve further. The purist should note that the “o” is superfluous, with the true suffix being “logy”, which had led to a few “alogies” as pretenders to the “logy” throne.
This compartmentalization was quite successful and led to the creation of many departments of “-logies”, each with a separate supposed set of goals that survive to this day in all major centers of higher learning. It also led to the creation of innumerable tenure-level jobs for Chairs, Directors, Deans and the like, each with their own fiefdom of administrators and budgets and also a few researchers or professors.
Generalizations and attacks on the status quo are dangerous and lead to shrill counter attacks by those affected, but I feel it is clear that the growth of modern science has led to the death of this venerable institution. Let me illustrate this in the field I am familiar with – modern biological research. Yes there are still Departments of Biology, Physiology and even Botany, Zoology and Protistology, but everyone in these Departments is doing the same thing and this has nothing to do with the ”ology” that pays their salary. They are studying interesting problems from every point of view at every possible level. The Protistologist, say, is interested in the motility of a particular protist. He or she however is interested in not only the molecular mechanisms involved down to the level of the molecules and energetics, but also the comparative aspects of motility in other related protists and even metazoans, the evolution and origin of this mechanism (and the cell itself), the morphological aspects, the natural history of this phenomenon, and even the role of this phenomenon in eco-communities of cells, and from a selfish anthropomorphic point of view, the possible biomedical significance, including the immunological aspect and interaction with the host if they are parasites. Each aspect of this study could be called by a different “ology” and therefore the existing nomenclature fails to communicate the existing reality.
One sign of the death throes of the “ologies” is the desire of almost all University Departments in the Life Sciences to include the word, Molecular, in their title. At my University, UCLA, it began with the creation of an interdepartmental Institute of Molecular Biology almost 42 years ago. Then the powerful techniques of molecular biology diffused to the existing “ology” Departments and there was a recurring scramble to rename the existing Departments and to wage the turf battles with the Institute that resulted. Even clinical Departments in the UCLA School of Medicine began hiring basic researchers who used recombinant DNA techniques and the great name change race was on. The final result as of today is that the venerable Molecular Biology Institute is a place where one eats a free lunch on Tuesdays while listening to seminars, and every Department is the same with a heterogeneous group of people all using every possible research technique ranging from molecular to organismal to ecological to study basic problems in the life sciences and biomedicine. But they still advertise themselves as different, claim to have specific goals and still teach courses with different names, but this is like whistling into the winds of change.
Another sign of the death throes is the emergence of entirely new fields derived from amalgamation of existing fields and exhibiting new “emerging properties”, such as, for example, Systems Biology or Astrobiology and the Search for Extraterrestrial Life. I myself find that I utilize examples in my courses of, for example, the discovery of dark matter and dark energy in the Universe from Astronomy as metaphors for the discovery of the World of Small RNAs in Biology.
I make no value judgment on this paradigm-changing change in academic organization, except to say that it makes life much more interesting but at the same time more confusing. Politicians, Universities, students and even faculty like compartments and get disoriented when faced with the chaos of real life. But perhaps the death of the “ologies” may lead to a deeper appreciation of the true goals of modern science and academics – an answer to the really big questions of what life is, where it came from and how it works, who we are and where we came from, and what is existence and the nature of things.

From Protist (2006) 157, 361

Who am I?

I introduce a discussion of parasitism and symbiosis in my undergraduate course by asking some poor student happening to be sitting in the first row — ‘‘Who are you?’’. She answers of course — ‘‘I am so and so.’’ I then persist with ‘‘What do you mean by ‘‘I’’?’’ and the student begins to give me a quizzical look, perhaps starting to realize that I am actually asking one of the most important and profound questions of the human experience. We then jointly attempt to define more precisely the nature of ‘‘I’’ — a body with arms, legs and head that respond to one’s wishes, or is it a brain in this body that has inputs from the senses and somehow has long term and short term memories, or is it the actual possibly holographic memories and thoughts themselves which represent the ultimate emerging character of complex neocortical neuronal activity. I then ask what about the bacteria in her gut, hundreds of species representing over 1 kg of biotic material, or the mites (Demodex folliculorum ) inhabiting her eye lash follicules, or the Toxoplasma bradyzoites hibernating within cysts in her brain (if she has eaten steak tartare frequently). These organisms are certainly part of her body and some are even essential for her normal development and physiology. Are they included within the ‘‘I’’? And if we delve even deeper into her cells, are the nuclei in the billion of cells or the subcellular organelles part of ‘‘I’’? It gets even murkier if we remember that the mitochondrion evolved from endosymbiotic purple non-sulfur bacteria and perhaps the nucleus evolved from archaeobacteria. Does my student’s ‘‘I’’ include these evolutionary memories? Or is the ‘‘I’’ her nuclear genetic information which in fact is full of evolutionary remnants of lateral gene transfer events as well? Or are her DNA sequences merely an operational and trivial forensic defnition of self? This is the stuff of plays (e.g. ‘‘On Ego’’ by Paul Brooks currently in the Soho Theater in London) but is it in the realm of science? I believe so since we are indeed the sum of a multitude of symbiotic relationships, both commensual, mutalistic and parasitic in nature, between our own cells and many eubacterial, archael and even metazoan creatures that inhabit our universe of self. My students and I never really reach any conclusion about the definition of ‘‘I’’, but the discussion certainly illuminates the nature of symbiotic relationships between organisms and leads directly to a discussion of those relationships which have not yet reached an evolutionary equilibrium and are termed ‘‘parasitic’’. I myself feel gratifed if I have merely stimulated some of those reverberating neuronal circuits of my students and made them stop and think whenever they say ‘‘I am so and so.’’ Such are the small but poignant rewards of teaching.


From Protist (2006) 157, 89.