You Sciency Dog You

Molina the science dog says:

Susie was a chemist, but she is no more.  What susie thought was H2O was H2SO4.

The Frequency Illusion

This week I had a good opportunity to discuss an interesting cognitive bias with one of my 4th year medical student while we were on renal rounds. The issue came up when I was examining the belly of one of my young patients, who screamed out, “your hands are cold”. One of our nurses was quick to respond, “Cold hands, warm heart”. My student looked at me then remarked that she had only recently ever heard that expression, and since then has been hearing it over and over again. This, of course, lead to a natural discussion of the cognitive bias called the Frequency Illusion, which also is known as “The Baader-Meinhof Phenomenon”. I admit we had to look up the name, as neither of us could remember what it was called. As physicians and scientists, critical thinking and rational thought are vital, and one way I teach this to my students is by discussing cognitive bias and logical fallacies. These emphasize where limitations of the human mind lie, and how to avoid common pitfalls in thinking that we are all prone towards.

The frequency illusion is one we have probably all experienced from time to time. The example above, is a not unusual. My student may have heard that phrase before, but never really registered it, or perhaps really never did hear it before recently. In any case, the true frequency of the phrase is unlikely to have suddenly increased, but only my students perception of the phrase has lead her to believe that only now is she hearing, “cold hands, warm heart” all over the place. Cognitive scientists propose that when the human mind has been given new information, it creates a bias towards that information so that we are more likely to become aware of seeing or hearing that same information again the next time it is presented. This is known as a “Recency Effect”. In reality the information has always been present at the same frequency but until recently it was part of the background noise and not in the forefront of thought.

Another example of the Frequency Illusion is one that I noticed in myself this week.  This occurred after a friend of mine posted on Facebook that he and his wife were visiting the Florida Keys for vacation. Since then I have noticed several commercials on TV advertising the Florida Keys for tourism. I had never noticed those commercials before. Now, it is possible that those commercials have only just begun to be broadcast, my friend was influenced by the commercial and decided to go to the Florida Keys, and I only started noticing the commercials because they were never on TV before this week. A more likely explanation is that I have fallen victim to the Frequency Illusion.

And yes, my hands really are cold all the time, and my heart is around 98.6 degrees Fahrenheit – so pretty warm. I guess my nurse was right after all!

Reference articles:
1. “The Baader-Meinhof pheonomonen”, How stuff works.

2. Structure of a logical argument. The Skeptics Guide to the Universe page.

3. “The Clumping Effect” Darwin’s Kidneys blogpost.

4. List of Logical Fallacies.  Wikipedia.

 

You Sciency Dog You

Molina the science dog!

Why is the pH of YouTube very stable?

It constantly buffers.

Book Review: “The Vital Question”

By Rich Feldenberg:

On this episode of Darwin’s Kidneys – first of 2016- I’ll be reviewing a book by Nick Lane called, “The Vital Question: Energy, Evolution, and the Origins of Complex Life”. This book attempts to tackle some of the toughest questions in biology today, such as how, and in what environments, life originated, how the complex eukaryotic cell evolved, how the cellular mechanisms to generate energy echo back to the days before biology, and why sexual reproduction is the way it is based constraints placed on us by our energy generating systems -the mitochondria. It is a lot of territory to cover, but Dr. Lane does an amazing job of bringing all these seemingly diverse themes together, synthesizing them into a coherent narrative that flows as easily from one topic to the next, as electrons flow down the mitochondrial respiratory chain (a central subject of the book).

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For those of you, who like me, love the topic of biological origins, this book will keep you engaged, and I had trouble putting it down, as I waiting for the next amazing revelation to be exposed. The early part of the book describes the common thread between the most essential metabolic activities of all living cells on earth -whether they are bacteria, archaea, or complex eukaryotes – and the natural geochemical activity of Alkaline Hydrothermal Vents. All life generates its energy by using proton gradients to drive the production of ATP (the energy currency of the cell). In all cells today, special pumps have evolved to pump protons (hydrogen ions) across a membrane. This creates a proton gradient (more protons on one side of the membrane than the other) which will naturally lead to those protons tending to diffuse back across the membrane. Cells use this proton gradient to run the protein ATP-synthase, to generate ATP, just like running water can be used to turn a water wheel to do work at a mill. In order to get the proton, it has to be separated from its electron, and that is done through a series of oxidation-reduction (redox) reactions, where the electron is transferred from one compound to another with each subsequent compound having a greater affinity for the electron than the last compound. It ends with the electron being transferred to oxygen (O2), which has the most affinity for the electron, converting the oxygen to water. The compounds where the electron is being transferred, are the respiratory transport chain of proteins. It is also found in plants as part of their photosynthesis machinery.

 

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This process mirrors a naturally occurring geological process found in Alkaline Hydrothermal Vents on the ocean floor. These vents are different from the “Black Smokers” that have been better popularized, as sites of chemosynthesis, where an ecology of organisms survive using the energy of the vent, and are not directly dependent on energy of the sun. The Alkaline Vents, on the other hand, are not quite so hot, but more importantly are composed of a matrix of mineral with thin walls that mimics a cell membrane. The vent fluid is more alkaline, with a pH of around 10, and the ocean water more acidic. It is thought that the ocean pH, 4.5 billion years ago might have been even more acidic that it is today with a pH of around 6. Since pH is a measure of the proton concentration, there is a natural proton gradient between vent fluid and ocean water separated by a thin mineral. The mineral also contains Iron-Sulfer complexes and other minerals that can act as redox centers, producing the electron transfer that we also still see today in our respiratory transport chain.

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Dr. Lane argues that this environment provides a very plausible explanation for how life originated and why all life uses the unusual proton gradient method to generate energy. His own research is, in part, using reactors to replicate the Alkaline Vent environment to study this theory further.
He goes on to discuss how life could then have evolved more effective cell membranes making wondering further from the vent location possible, as long as these simple organisms could begin to pump protons on their own, at this point. This movement into the new environment, and an existence independent of the Alkaline Vent, is where the split between bacteria and archaea probably occurred. He shows the evidence for this hypothesis.
A great deal of the rest of the book describes the evolution of the complex cell, by the synthesis of an archaea host cell, with a bacterial endosymbiont which went on to become the mitochondria. He also describes, in detail, the genetic evidence, as well as, that logical considerations, that suggest this occurred, it occurred only once, and how the other features of the complex cell -such as nuclear membrane developed.

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The book is beautifully written, but I will say some background in biology certain helps, but his writing is clear, entertaining, and well focused.
I just finished reading, “The Vital Question” this month, but it is now in my top 10 all time favorite science books. The last Nick Lane book I read was called, “Oxygen” and was equally good. It was also about the biochemistry of energy generation in organisms. I urge you to check out, “The Vital Question”, and let me know what you think.

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References:
1. The Vital Question, by Nick Lane

2. Nick Lane webpage.

3. Darwin’s Kidney Article on Molecular Fossils (EMMAs).

4. Article on the necessity of a new word, Mesign, to help differentiate between something purposefully designed and something that has the false appearance of design being evolved by natural selection.

Happy Winter Solstice

By Rich Feldenberg:

Your Winter Solstice this year (2015) will take place on December 21st at precisely 10:49pm Central Standard Time. The Winter Solstice is a consequence of the tilt of earth’s axis in relation to the sun, and at this time each year, the Northern Hemisphere is maximally tilted away from the sun by -23.5 degrees. This results in the sun being at it’s lowest point in the sky from our earthly perspective in the Northern Hemisphere, and leads to the day with the shortest daylight hours and longest night. So, axial tilt really is the reason for the season.

It may be true that many people today are not terribly concerned about the Winter Solstice, but to our ancestors living in pre-modern societies, hoping to survive through another harsh winter, the Winter Solstice had extreme importance, and was perhaps reason for celebration. For it was now that the daylight would begin to return to the world again. The journey back to Springtime had finally begun. Imagine living in a world without electric lights, central heating, a reliable food supply, and the only the most primitive technology and medicine. Our ancestors had to use all the clues that mother nature provided to figure out what gave them the best chances to stay alive.

As Neil Degrasse Tyson pointed out in his article, “Stick in the mud astronomy”, if you place a stick in the ground you can learn a lot! You’ll find that the sun casts a shadow of the stick, and that you can trace this shadow throughout the year. If you use the stick-shadow method to observe where the sun rises each day of the year you’ll find that the sun rises in a different place through the course of the year. Follow it through for the entire 365 days of year and you will trace out a figure 8 pattern. This occurs due to the eliptical orbit of the earth around the sun. The sun will be at its lowest point on the horizon, and cast the longest shadow, on the Winter Solstice. On the Winter Solstice the sun will be directly overhead at noontime on the Tropic of Capricorn, in the Southern hemisphere. There will also be two days of the year where your stick will cast shadows in the exact opposite direction at sunrise and sunset. This is on the spring and fall equinoxes. Its possible that people have taken the time to measure the Winter Solstice in this way for thousands, if not tens of thousands of years. Why would they bother?

The monument at Stonehenge gives us some insight into the importance of the Winter Solstice to the prehistoric Neolithic people. Its huge stones are arranged to allow sunlight to pass through a certain configuration at the time of the Winter Solstice. One of its functions was to act as a celestial calendar, so the timing of the solstice could be precisely measured. Stonehenge is thought to have been built around 4000 to 5000 years ago, but there is evidence for wooden posts in the area that may have served similar functions, dating back 8000 years or more. Back in these ancient societies, farm animals were slaughtered at the Winter Solstice, so they didn’t need to be fed for the remaining winter time.

Its no coincidence that many celebrations were observed throughout the millennia by ancient peoples around the time of the Winter Solstice. The Feast of Juul was celebrated in Pre-Christian european societies, and the Juul log (Yule log) was a tradition where a large log or tree was burned to honor the god Thor. Saturnalia was observed by the Romans to honor the god Saturn. There were the traditional exchange of gifts and lighting of candles and bonfires, but it sounds as though this was also a rather unpleasant time as it typically degenerated into a period of murder, robbery, rape, vandalism, and so on, as there was no enforcement of the law during Saturnalia. Of course, in our modern society Christmas is celebrated on and around December 25th. The bible does not give a specific date for the birth of Jesus, but many scholars believe the date for Christmas celebration was chosen because of the pagan celebrations of Saturnalia and others could then more easily abandoned by switching one set of traditional celebration with a new set. The first known celebration of Christmas was in 336AD by the Roman Emperor Constantine.

Not really related to the Winter Solstice, but worth pointing out is that Sir Isaac Newton was born on December 25th 1642. Many science enthusiasts and secular humanists enjoy celebrating Newton on this day to honor his important contributions to science. Newton was a founder of modern science, inventing calculus to complete his calculations of physical motion. He is also known for his many additional contributions, including his law of gravitation, study of light and optics, improvement in telescope design, and more mathematical developments, as well. He was born on December 25th by the calendar in use at the time – the Julian calendar. The Gregorian calendar, which is our modern version, replaced the Julian calendar because it was more accurate, using the concept of the leap year to keep the seasons from drifting into other parts of the year. It’s original purpose was to prevent Easter from moving into other months as the earths rotation around the sun is not an exact 365 days. By the Gregorian calendar, Newton would have been born on January 4th, 1643. Anyway, Merry Newtonmass to my fellow science enthusiasts.

Merry Newtonmass to you good Sir!

The Winter Solstice is a reminder that we are still just inhabitants of planet earth, exposing our kinship to our cosmic environment. We have gained so much more knowledge -thanks to the ingenuity of our species – than our prehistoric ancestors had about what the earth and sun really are, how they move through space, and where we come from, but at the same time we seem to have lost the sense of oneness with the universe that our ancestors must have felt. We are riding on a spinning mass of rock as it circles a star in an enormous galaxy. The ancients knew that they were connected to the clockwork of the heavens. In our modern society we all too often forget that we also have that connection with the earth and solar system. We don’t worry as much that our families might not make it through the winter, this time. That our entire village might die of starvation, cold, or sickness. Most of us have enough food to eat, heated homes, and access to medical care. Sure, we all have new and different kinds of worries that our distant ancestors wouldn’t have understood, but they may have displayed some wisdom that we can still benefit from if we pay attention. So Happy Winter Solstice. May you and your family be happy and safe this holiday.

References:
1. Winter Solstice, The Telegraph, Dec. 20. 2015. 
2. Stonehenge Wikipedia. 

Gene Drives: so you want to change the world!

By Rich Feldenberg:
Want to change the genetic landscape of whole populations and ecosystems? Tired of having to do it the old fashioned way by genetically engineering one organism at a time? Well now there’s Gene Drive! The fast and efficient way to spread your desired genetic design! Just send $19.99 plus shipping and handling for your Gene Driver Kit today!

If the “Fake Advertisement” in the paragraph above, made it sound as though the Gene Drive concept is some crazy kind of internet scam that is to good to be true, actually nothing could be further from the truth. Well no, you can’t just send in money for a gene drive kit yet, but it turns out that gene drives are real, they’re awesome, they’re controversial, and they can in principle, change the gene pool of an entire population of an organism. In fact, this method of gene editing is so new that very few experiments have even been done, and its founder, Kevin Esvelt, feels that the technology is so powerful that he wants to put a halt on experimentation until society can come together and discuss whether we collectively feel this is an area of science we should pursue, not just one that we can pursue. To understand gene drives we first have to remind ourselves of how the CRISPR-Cas9 system works, which I reviewed in an earlier Darwin’s Kidney post.

Briefly, the CRISPR-Cas9 system is a new and powerful gene editing technique that can be used in living organisms. This system is found naturally in many bacteria, as part of their immune defense mechanism against viral attack. There are two major parts to the system. The first is a guide RNA and the second is the Cas9 enzyme. The guide RNA is a small strand of RNA (somewhere around 20-40 base pairs in length). When the guide RNA finds a perfect base pair match with a DNA strand somewhere in the cell, the Cas9 enzyme cuts that piece of DNA. In the case of bacteria, this allows the them to match one of their guide RNAs to a sequence of DNA from an invading virus, then cut the viral DNA, which disables the virus from taking over the bacterial cell. The guide RNA came from a previous viral attack that the bacteria survived, and when the bacterial enzymes chopped up the invaders DNA into small bits, some was incorporated into CRISPR so that exposure to that same virus the next time would quickly result in recognition by the bacteria – an immune system! In the last few years scientists have discovered how to make guide RNA for any desired gene, and along with the Cas9 enzyme, can then “snip out” the gene or any piece of DNA in question. This can be used to silence genes, or can also be used to replace genes if the cell has access to a DNA sequence that can fill the gap left by the Cas9 enzyme. This may turn out to be a great way to cure genetic diseases through gene therapy.

Gene drive systems, take this concept a step further. Gene drives rely on the gene editing to take place in germ line cells versus somatic cells. Germ-line cells are the cells that will become egg or sperm, and will be used to create new organisms through sexual reproduction. Somatic cells are all the other body cells, such as skin, kidney, brain, pancreas, etc. If a gene is edited in a somatic cell, that change will effect the organism in whom the change was made, but would not be passed down to the next generation.

As an example, lets say you want to be able to provide gene therapy for a genetic disease such as Nephrogenic Diabetes Insipidus (NDI). This disorder is X-linked, meaning that the gene is on the X chromosme. Since males have an X and Y chromosome, with the X coming from their mother and the Y coming from their father, if the mother’s X chromosome has the mutant gene for NDI they will have inherited the disease, which leads to the kidneys inability to regulate water loss. People with this disorder can die of dehydration because even when dehydrated they continue to produce too much urine. A female, having two X chromosomes, one from her mother and the other from her father, might be a carrier for NDI if her mother’s X had the mutant NDI gene, but she still wouldn’t develop the actual disease since her normal NDI gene from her father’s X chromosome will compensate.

In principle you could use the CRISPR system to edit the defect gene, so that the male patient with NDI can now regulate water loss through the kidneys normally. There is still no way to really do this yet. You would need to deliver the CRISPR-Cas9 system, to the appropriate kidney cells of the affected individual. At the present time, a way to target and deliver the system is still not available, but if it could be delivered to the kidney cells it would excise the defective DNA. The cells own repair mechanisms will then look for a replacement to fix the DNA break made by the CRISPR-Cas9. If the normal gene was also delivered to the cell it will be incorporated into the place where CRISPR-Cas9 made the break. This will result in having removed the defective disease causing gene and replaced it with the normal healthy gene, and should therefore cure the disease – Nephrogenic Diabetes Insipidus kidney disease in our example. However, even if this could really work – its never been tried yet for this disease – but was unsuccessfully attempted for Hemophilia, the cured individual would still be able to pass the disease on to their children. The reason is that only the kidney cells were altered, and not the germ-line cells.

Gene drives, on the other hand, effects the germ-line, but they have an even bigger, more ingenious twist to their potential to alter future generations. With gene drives, in addition to supplying the new gene, the genetic code for more CRISPR-Cas9 is also inserted into the target genome. So here is how it might work. Let simplify the example by calling the two alleles of the gene (one allele comes from mom and the other from dad) as Normal and Engineered. It could be any gene in the genome that you’re interested in, such as the gene for making insulin or for making neurotransmitters in the brain, or transcription factors that tell more genes what to do. In this example we want the Engineered gene to take over because it has some trait we have engineered for it that we find desirable. It could be to fix a defective gene or it could be to give the organism some new property. We’ll get to some examples of new properties shortly.

 

The first step might need to take place in the lab when the organism at its earliest stage, the fertilized egg. You place the CRISPR-Cas9 into the fertilized egg with guide RNA that recognizes the Normal gene. You also place the Engineered gene in the cell to replace the Normal gene once Cas9 has cut it. The cell will now have the Engineered gene as part of its entire genome. This will effect both somatic cells and germ-line cells since the fertilized egg will continue its job of dividing into more and more cells, which will eventually become all the cells of the body. Eventually this organism will develop into an adult and find a mate to produce more offspring. The offspring will have an approximately 50% chance that the Engineered gene will be passed on to the the next generation. That is because each offspring will get one copy of Engineered gene from our genetically modified organism and the other gene from its mate, which would carry the Normal gene version since it was never modified. So this is where the special ingenious twist comes in!

Not only does the gene you inserted into the fertilized egg contain the DNA of your engineered gene, but it contains the DNA for making a CRISPR-Cas9 system, as well. This CRISPR-Cas9 is hidden somewhere in the middle of your Engineered gene so that the cells DNA repair enzymes don’t recognize it as being novel to the cell. They only recognize the ends that need to fit in the space that Cas9 cut out. So in this way, the gene we pasted into the genome is Engineered-CRISPR-Cas9. Now when the cell transcribes that gene the CRISPR-Cas9 is also transcribed which leads to a guide RNA and a working Cas9 enzyme. The guide RNA will then match to the Normal gene and Cas9 will cut it. This is important because when the genetically modified organism mates with a wild type organism the offspring will have one Normal gene from the wild type and one Engineered-CRISPR-Cas9 gene from the genetically modified organism. CRISPR-Cas9 then gets transcribed, seeks out the Normal gene, and replaces it with the Engineered-CRISPR-Cas9 gene, so the offspring actually ends up with two copies of the Engineered-CRISPR-Cas9 gene. In this way the rate of transfer of the Engineered gene, to successive generations, goes from 50% to 100%. The Engineered-CRISPR-Cas9 gene effectively edits every other allele that matches its guide RNA, turning it into the Engineered gene. Now the gene can spread rapidly through a population because the odds are always in favor of this gene being passed down to all offspring. See the excellent Mosquito chart in the following article I’ve linked to in order to get a visual on how the inheritance would be effected.

It should be pointed out that this is only effective for organism that reproduce sexually. Asexually reproducing organisms (such as bacteria) won’t be influenced by this mechanism. For organism that have short generation time this is ideal. One proposed problem that gene drives might be able to solve would be in the fight against malaria. Malaria kills millions of people each year (see Darwin’s Kidneys article: Diseases with an Upside). If mosquitos were released into the wild, that were engineered to have a malaria resistant gene and also the CRISPR-Cas9 system, then that gene would spread rapidly throughout the mosquito population. The result would be malaria resistant mosquitos and possibly an end to suffering and death in many parts of the world due to this parasitic infection.

There’s no guarantee, however, that the malaria organism – Plasmodium – would not find a way to evolve around the mosquito’s malaria resistance given enough time. There is also no guarantee that the malaria resistant gene might not somehow decrease the “genetic fitness” of the mosquito making them less likely to survive and reproduce. Mosquitos would be an ideal organism for this type of engineering, however, since they have a rapid generation time, so within several years to decades a gene system of this type could theoretically pass to all members of the population. Humans, on the other hand, reproduce slowly so a gene drive in humans would probably take hundreds of years to spread through the population. Still, you could imagine an attempt to eliminate many genetic diseases completely from existence by using gene drives that over the course of centuries might be effective. One could also imagine the ability to produce a civilization of future generations of humans that are more intelligent, more rational, less violent, more empathetic, and so on, if the genes involved in producing those traits could be identified. It is harder to imagine, however, that society as a whole would ever agree to such a mass alteration of the human genome – creating something beyond human – by directing human evolution in a desired direction. Its too early to know if such changes to the human genome could even be done safely without creating damaging consequence that are impossible to predict. I’m not necessarily advocating for changing the human race for the better, but more just advocating for discussion of the potential positive and negative effects might result from such grandiose dreams.

Because the implications for gene drives are so powerful and large scale, there is currently a call for a hold on research until the ethical considerations can be more fully considered. I think this seems wise at our current state of understanding. Changing an ecosystem could have unforeseen consequences. There may be ways to alter some behavior in organisms with gene drives that would not necessarily eliminate those organisms from the ecosystem – and so may have a mild impact on the ecosystem as a whole. For example, one could engineer a pest to dislike the taste of a crop that it normally damages, and therefore protect the crop without the need for as much pesticide use. The pest is now no longer a pest, but remains in the ecosystem where it can feed on other plants and remain part of the normal food chain for other organisms. Could gene drives be used to engineer plants to more efficiently remove CO2 from the atmosphere, and combat global warming while increasing crop yields?

Gene drives are an exciting new method of changing the genetic makeup of populations of organisms. Whether they will be used to prevent diseases like malaria from killing so many or making crops less prone towards pests and therefore reducing the amount of insecticides released into the environment, is up to society at large to decide if we are ready to pursue such far reaching technology. My hope is that we may find ways to safely use gene drives to improve life on planet earth for ourselves and our fellow species.

References:
1. “Genetically Engineering Almost Anything” by Tim De Chant and Eleanor Nelson, Nova Next. July 17, 2014.
http://www.pbs.org/wgbh/nova/next/evolution/crispr-gene-drives/
2. “Gene Drives and CRISPR could revolutionize ecosystem management”, by Kevin Esvelt, George Church, and Jeantine Lunshof; Scientific American Blog. July 17, 2014.
http://blogs.scientificamerican.com/guest-blog/gene-drives-and-crispr-could-revolutionize-ecosystem-management/
3. Gene Drive Wikipedia: https://en.wikipedia.org/wiki/Gene_drive
4. “Gene editing in Humans”; Neurologica blog by Steven Novella; Nov. 19, 2015
http://theness.com/neurologicablog/index.php/gene-editing-humans/
5. “CRISPR: what’s the big deal?”, Darwin’s Kidney blog by Rich Feldenberg. Nov. 28, 2015.
http://darwinskidneys-science.com/2015/11/28/crispr-whats-the-big-deal/
6. “Can we genetically engineer Rubisco to feed the world?”; Darwin’s Kidney blog by Rich Feldenberg.
July 22, 2015.
http://darwinskidneys-science.com/2015/11/28/crispr-whats-the-big-deal/
7. “Diseases with an upside”; Darwin’s Kidney blog by Rich Feldenberg. July 29, 2015.
http://darwinskidneys-science.com/2015/07/29/diseases-with-an-upside/
8. “Live at the NESS: New Dilemmas in Bioethics”; The Rationally Speaking Podcast. April 24, 2011.
With Massimo Pigliucci and Julia Galef as hosts.
http://rationallyspeakingpodcast.org/show/rs33-live-at-necss-new-dilemmas-in-bioethics.html

9. “Sculpting Evolution”; website of Kevin Esvelt, PhD.  Founder of gene drives.   http://www.sculptingevolution.org/kevin-m-esvelt

 

 

 

Entropy as an engine of life’s origins

by Rich Feldenberg:

In our last Darwin’s Kidneys post we discussed the basic concept behind the second law of thermodynamics, which requires that entropy increase for every irreversible process. Entropy can be thought of as the amount of disorder in a system, so this law is essentially saying that there is an increase in the total amount of disorder that accompanies every physical process. We discussed why this law – which is thought to always hold true throughout time and space – does not prohibit the development of complex structure or the evolution of life, but it might also be true that the second law is a driving force behind the evolution of complexity in both living and non-living systems.

In this article I would like to continue our thermodynamic discussion, but introducing an interesting, although somewhat unproven and controversial offshoot of this scientific principle, which attempts to show that self organization of atoms and molecules is actually a consequence of second law dynamics. It’s founder and major proponent is a young physics professor at MIT, named Jeremy England. He has been attempting to show through a rigorous mathematical approach, that complexity arises naturally in physical systems as these systems move towards more efficient mechanisms to disperse energy – increase disorder in their surroundings. These systems become more efficient at increasing universal disorder, by becoming themselves more ordered. This work has potentially broad implications helping us understand how living systems might have arisen naturally from non-living systems, even before those systems were self-replicating and capable of Darwinian evolution.

The entropy of a closed system will always increase over time, but an open system allows an influx of energy so that the entropy of part of that system can decrease as the entropy of it’s surroundings increases. The geochemical environment of the early earth could be considered an open system because there was intense energy continuously entering into the system from the sun. Plants are extremely efficient at using that energetic sunlight to maximize the disorder of their surroundings. This is somewhat like looking at the problem upside down from our usual way of thinking. We normally think of plants evolving to use sunlight more effectively to become more complex, and as a natural consequence they create a larger entropy to the environment. England’s way of looking at the plant might be to say that second law demands that entropy will increase with time and the highly energetic sunlight will affect the system so that complexity will arise that will move towards maximum entropy generation. Those more effective entropy generators will necessarily be more complex systems, tending toward self-assembly and reproduction, and in some cases, eventually what we would recognize as living things. Living systems are very good at dissipating its energy.

 

For these kind of processes to occur a system has to be out of thermodynamic equilibrium. At equilibrium there is no net energy transfer, but a system out of equilibrium has a net movement of energy – the influx of sunlight, for example. At some distant time in the future, the entropy of the entire universe will be high (the universe being a closed system), and at that point all areas of the universe will be in thermodynamic equilibrium, and complexity, organization, and life will cease to exist. Fortunately, it is likely to be a very long time before that fate befalls our universe.

England’s thermodynamic dissipative process might explain organized non-living structures we see everywhere in the world, from the formation of snowflakes and sand dunes, to planetary rings and spiral galaxies. These structures preferentially form to better disperse energy into more disordered and less usable forms – a consequence of thermodynamic’s second law. In this way, life itself is just one form of a more broad variation on this theme. Self organizing structures may have formed to raise entropy maximally, and in doing so lead to the first self-replicators. Once you have replicators, a Darwinian evolution by natural selection can take over to increase complexity further.

Not all researchers believe that Dr. England’s theory will pan out as a solution to the origin of life, but it seems that there are more than a few that have been impressed with the theory and its results so far. I have read two of England’s original journal articles, and unfortunately that math of the statistical mechanics was beyond me. From what other researchers have said, however, the equations used are valid, it is their interpretation for self assembly and origins of life, that is still unclear.

Professor England is himself and interesting individual. In his early 30s and approaching the origin of life field from a fresh perspective, England earned his PhD in physics at Stanford University in 2009, and is now an Assistant Professor of Physics at the Massachusetts Institute of Technology with his own research lab. In 2011 he was named as “one of the 30 under 30 rising stars in science”, by Forbes magazine. One thing that I found particularly fascinating is that although England is attempting to crack the tough nut of the origins of life, using sound science and mathematical modeling, he is a devout Orthodox Jew. He speaks somewhat to his faith and how he reconciles faith with his naturalistic scientific approach to answer this basic fundamental question, of interest to both science and religion, in his podcast interview that I linked to below. Faith and high level scientific inquiry may be a good topic for another time.

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I look forward to following Dr. England’s future work, and watching if others pick up on it and extend it further. If England is right, then far from The Second Law of Thermodynamics being a repressor of complexity, it may more accurately be a driving engine of the spontaneous production of organization and complex systems.

 

References:
1. “Statistical physics of self-replication”, Jeremy L. England; The Journal of Chemical Physics. 139, 121923 (2013).
2. “Dissipative adaptation in driven self-assembly”, J.L. England; Nat Nanotechnol. 10(11):919-23, Nov 4, 2015.
3. “The New Physics Theory of Life”. Quanta Magazine. January 22, 2014.
https://www.quantamagazine.org/20140122-a-new-physics-theory-of-life/
4. “Origins of Life: A Means to a Thermodynamically Favorable End?” Yale Scientific. July 1, 2014.
http://www.yalescientific.org/2014/07/origins-of-life-a-means-to-a-thermodynamically-favorable-end/
5. The 7th Avenue Project (Podcast). “Biophysicist Jeremy England: A New Theory of Life”. May 3, 2015.
http://7thavenueproject.com/post/118064180870/biophysicist-jeremy-england-new-theory-of-life
6. “How can we be so complex if the second law of thermodynamics is true?” Darwin’s Kidneys. Dec. 4, 2015.
http://darwinskidneys-science.com/2015/12/04/how-can-we-be-so-complex-if-the-second-law-of-thermodynamics-is-true/

 

How can we be so complex if the second law of thermodynamics is true?

By Rich Feldenberg:

There is no doubt that physics is a difficult subject to master, but there seem to be particular areas of physics that are commonly misunderstood and misapplied by the general public. One such area is quantum mechanics – a field within, so called, modern physics – where complex mathematical structures provides hints of the underlying nature of the universe that are completely counter intuitive to our “common sense” notions of how things should be. Another area of physics that falls into this category of being frequently misunderstood is thermodynamics – specifically the second law of thermodynamics – a field coming out of classical physics that deals with the notion of changes in entropy of physical systems. This article will focus on that second area – the second law of thermodynamics.

 

Thermodynamics originated in the 17th century, as a way to understand heat, energy, and work. Over time there came to be four laws of thermodynamics described and labeled as laws zero through three. The zeroth law relates the fact that if object A is in thermodynamic equilibrium with both objects B and C (meaning that there is no net heat exchange between them), then it follows that B and C are also in thermodynamic equilibrium with each other. Maxwell concluded from this observation that, “all heat is of the same kind”. We understand this effect when we take a temperature measurement with a thermometer. Once the thermometer is in thermodynamic equilibrium with the object of interest (there is no net heat exchange) the temperature of the thermometer will give you the temperature of the object being measured. A perfect thermometer will not change the temperature of the object in question.

 

The first law of thermodynamics is a conservation law, and simply put says that energy is a conserved property. The energy in a closed system is fixed, or constant, and while the energy can change form (i.e.. Could change from thermal to mechanical, kinetic, electromagnetic, gravitational, or so on) the amount of energy stays entirely the same, always and forever. The only processes that are allowable are those in which the total energy of a closed system is constant. This law lets us know which process can occur. If a process would require a change in the total energy of a closed system, then that process is forbidden by nature.

 

The third law of thermodynamics provides us with the simple statement that ‘the entropy of a perfect crystal at absolute zero temperature is zero’.   We’ll define entropy in a moment, once we get to the second law of thermodynamics, but we’ll just remark that absolute zero is the lowest temperature theoretically possible, and that if you ignore the effects of quantum mechanics where neither the momentum and position of a particle can both be known with perfect precision then in a classical system an object is in its lowest energy state at absolute zero, thereby removing any disorder in the system. This law also indirectly implies that it can never be possible to reach absolute zero through any means.

 

We won’t comment further on thermodynamic laws zero, one, or three in this article, but will move onto the second law of thermodynamics. The second law governs which types of process are spontaneous – will occur without the input of energy from the outside. The second law states that the entropy of a system as a whole, must increase for any spontaneous or irreversible process. For a reversible process the entropy could remain constant, which is also allowed by the second law. Entropy (given the symbol: S ) can be described as the amount of disorder in a system. For a system to increase its entropy, the system must become more disordered. This is not to say that certain subparts within the system might not become more orderly (i.e. Decrease their entropy), but they would do so at the expense of the system as a whole, which if you added all the contributions to ‘change in entropy’ together (the pluses and the minuses) you would find that the sum is always a plus (entropy has increased). This does not prohibit complex, and very ordered, systems to develop, but they do so because they are increasing entropy even more is some other part of the universe.

 

If the second law really forbid anything becoming more ordered or complex then we would be breaking the second law of thermodynamics every time you made your bed, cleaned the living room, baked a cake, or put together a lego model. When we use a refrigerator to cool the temperature in the freezer we are decreasing the entropy inside the fridge. Even the ancients were skilled at producing order when they built the pyramids out of clay and stone, mined and separated metal ore from the earth, and grew crops. To the uninitiated, all these things, at least on the surface, would seem to break the second law of thermodynamics. But, we know the second law can not be broken, at least no one has ever seen an example of an exception to the rule yet.

 

As impressive as these examples of technology to increase complexity are, they pale in comparison to the complexity of a living system. Look at how complex, orderly, and precisely organized is a living cell. Even a lowly bacteria is a little pocket of highly organized molecular structures, far out of thermal and chemical equilibrium with its environment (one requirement for life, even if not a complete definition). The cell has a very improbable structure, based on random chance alone – that the atoms of the cell would randomly assemble based on thermal motion into the complex set of protein, nucleic acids, and so forth – but we’ll see that it was not random chance that lead to living cells. A cell functions as a living thing precisely because its entropy is so low. So how could such a thing exist in a universe where the second law of thermodynamics is in effect? If entropy (disorder) has to increase, then how can there be even the simplest of cell types?

 

Well, the complex and organized structure of the living cell, can be generated when it creates an even greater amount of disorder in its surroundings. The heat generated by metabolism is transferred to the surroundings where it loses its potential to do useful work. The power supplied by the sun to run nearly all ecosystems, provides energy that can be harnessed by living things to keep their entropy low, and stay far from equilibrium with their surroundings. If the sun went out, that supply of energy would be cut off, and without a continuous supply of renewed energy being delivered, entropy of the ecosystem would certainly increase as organism die, losing order as their molecular parts are dispersed. The sun itself, the power supply, has a low entropy due to its dense structure of hydrogen, and is increasing the entropy of the universe as it fuses hydrogen to helium, releasing less orderly radiation and neutrinos out into space. It’s taking a nice condensed ball of hydrogen gas and producing a sea of radiation spreading out in all direction in space – in other words, it’s making a real mess of things! The entropy of the universe is ever increasing, as a consequence all the processes, both living and non-living, that the universe is so good at performing.

 

The total amount of energy in the universe remains unchanged throughout time (first law), but that energy becomes less and less usable due to the increasing entropy (second law).   The quality of that energy (how useful it is at doing work) does change, and the quality of universal energy is worsening as time goes on. In fact, it is entropy which seems to provide some sense of which way time is flowing, what some call an arrow of time. The difference between past and future is not the amount of energy in the universe (which is constant) but in which direction the disorder is higher. The past, always more ordered and the future always more disordered. This increasing disorder is a natural consequence of the number of micro-states a system has. What we mean by this is simply that, if you imagine say a container filled with helium gas (this is our closed system) each helium atom can occupy any particular point in the box, so long as there is not already another helium atom taking that spot. Even in a small box, there could be a very large number of helium atoms – atoms being so tiny, and a mere 4 grams of helium would contain 6.02×10^23 atoms – a truly astronomical number. If you consider where each helium atom is in the box at some given time, that is one micro-state. The atoms will have some thermal energy and will be moving in random directions, bouncing off the walls of the box and off each other, so at some other time each atom will be in some new location. This would be a new and completely different micro-state, but it is likely that both micro-state will look essentially indistinguishable – both appear to us just as completely random mix of helium atoms. That is they will have basically the same macro-state because there would be no way to tell the different micro-states.

 

Now a micro-state could appear different, however, if all the helium atoms suddenly moved to one corner of the box and left the remains areas an empty vacuum, or if they all huddled together into the shape of a little arrow in the middle of the box. There is nothing saying that such micro-states are impossible, it is just that with the huge number of micro-states available, those with random appearing properties will far out number the few states with non-random appearing properties. The non-random appearing states really are just random, but they are going to be very unlikely to occur, just by statistics alone. There will be many many micro-states where all the atoms look randomly distributed in space, and in comparison, really few micro-states where the atoms look non-randomly spaced. It’s just a statistical argument, nothing more.

 

So how can order be increased (entropy decreased) so that things like living things can be alive, evolution can take place, and so forth? We could force all the atoms in our box to reside in one small corner, but it would involve work being done on the system. This would lead to an increase in entropy somewhere else.   For example, we could have a piston in the box, and push the piston down causing the helium atoms to move closer to the corner, making the gas more dense, and decreasing the entropy in the box. In order to do this energy has to be supplied to the piston. This will mean that some of the energy used to drive the piston must be wasted as heat (it is thermodynamically impossible for the energy efficiency of the piston, or any machine, to be 100%) and leading to increased entropy.

 

Living systems are able to harness energy from their environment to remain in their low entropy ‘alive’ state. That energy may come directly from the sun to run the process of photosynthesis, or could be chemical energy derived from high energy chemical bonds in biomolecules consumed by animals, for instance. As stated before, the low entropy state of the living system remains highly ordered at the expense of an even greater increase in entropy of the universe.

 

Creationists have been known to invoke the second law of thermodynamics as a way to show that evolution breaks the laws of physics, but this only really reveals the creationists lack of understanding of the second law. One consequence of evolution is that over geological time the complexity of organisms has increased. That is not the “goal” of evolution, who’s only objective is to pass genes on to the next generation, but in the process of producing more efficient gene passing devices (i.e. Organisms that survive and reproduce more effectively in their environment) some will have proceeded down a road of increased complexity (keep in mind that many remain simple if they can find other ways of remaining good reproducers, in fact, some may even regress as parasitic worms have which no longer need much more than a gut and reproductive tract to be successful).   The second law does not forbid evolution or the evolution of increasing complexity. Organisms in the process of survival, reproduction, natural selection are simply taking the energy stored from sunlight and using in a multitude of different ways. The universe at large pays the price for all the things living things do, including evolving, by increasing its overall entropy.

 

We know that the entropy in the universe today is more than it was yesterday, and less than it will be tomorrow. If we extend this line of reasoning to the universal extremes then it stands to reason that entropy was at its minimum at the beginnings of the universe and will be at its maximum at the end of the universe (if there is such a thing). The Big Bang was a very orderly state when you consider that all energy was packed into a tiny subatomic space. What about our cosmic destiny? Most cosmologist believe the evidence shows that the universe will continue to expand forever, and entropy will eventually reach a maximum. At that point there will be no further processes or reactions (whether chemical or nuclear) that will occur. This is called the ‘heat death’ of the universe, as there can be no net heat transfer, and hence no way to increase entropy further. When this happens there will be no more stars or living things, just a sea of ever diluted radiation, as space-time continues to expand.

 

The second law is fundamental to our understanding of how things work. It also explains why some things can never be possible – like perpetual motion machines which never lose heat energy to their surroundings – impossible! It makes sense when you begin to understand it as a consequence of what is happening on a microscopic scale. It is certainly not an argument against complexity arising, but it does tell us that all complex systems have a universal cost that has to be paid.   As long as we have a ready source of incoming power – the sun in our case – things can continue to remain ordered for billions of years. That’s good news for us who have no choice but to obey the law!

 

CRISPR: what’s the big deal?

By Rich Feldenberg:
In the last couple years there have been a growing number of mainstream media stories (like this recent CNN article) highlighting a new molecular biology technique that is revolutionizing the way scientists conduct genetic experiments, and may soon make the holy grail of medicine (gene therapy) possible. It certainly seems far from usual for the media to be overly concerned with a technical method of scientific investigation, but CRISPR has caught the attention of scientist and non-scientist alike due to its huge potential to change the research landscape. This article will discuss what CRISPR is all about, what it does in nature, how scientists are using it in the lab in place of older more traditional techniques, and what its future potential might be to cure diseases that are now incurable.

CRISPR (pronounced like Crisper) is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. Yeah, CRISPR is much more fun to say. It is a naturally occurring segment of DNA found in many prokaryotes. Prokaryotes are single celled organisms that lack a nucleus and other internal structures that more advanced eukaryotic cells contain. The prokaryotes include bacteria and archaea, and CRISPR has been found to occur in about 40% of bacteria and 90% of archaea sequenced so far.

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The CRISPR DNA is organized in a particular way. It is made of short lengths of repeating DNA basepairs that are separated by regions of seemingly random DNA, known as spacers. Both the repeating regions and the spacer regions are on the order of 24-48 base pairs in length. These repeating structures were first discovered in the DNA of E.coli (a common bacteria found in the intestines of humans) back in 1987, but their function was not known at that time. It was not until 2005 that their function began to become understood, thanks to bioinformatics. Bioinformatics is a computational biological approach to problems in molecular genetics. Using computer programs to search and compare genetic databases, it was found that the spacer portions of CRISPR exactly matched portions of DNA from bacteria infecting viruses and plasmids. That lead to the realization that CRISPR serves as a kind of immune system for prokaryotic cells.

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Basically what happens is that when a virus infects a bacterial cell, the cells first line of defense includes nucleases (enzymes that cut up DNA) that are released in an attempt to destroy the invaders genetic code. The majority of cells infected will not survive, but in the rare chance that it does survives the viral attack, nucleases then cut up the virus DNA into small parts, some of which become the spacer segments in the CRISPER complex of the bacterial DNA. Next time that the same type of virus infects the bacteria, the bacteria can quickly identify it based on the DNA match between its CRISPR spacer segment and the viral DNA. Enzymes called Cas (for CRISPR associated) are nucleases that will associate with the spacer sequence. They cut the viral DNA at the specific place where the match occurs. This increases the chance for the bacteria to survive the viral attack and confers a kind of immunity to the cell.

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It has been shown that bacteria that contain CRISPR are much more resistant to virus that have DNA sequences contained in their CRISPR spacers, and if those spacers are removed from their CRISPR segments, they lose that resistance. There are certain Cas enzymes that can continue to add new spacers each time they are attacked with new kinds of viruses, and if these types of Cas enzymes are defective or absent, the bacteria can still defend against attack with familiar viruses but are unable to acquire immunity to new ones.

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This certainly seems like good new for bacteria, which are continuously under attack by viruses day in and day out. In fact, it has been estimated that viruses kill 40% of the bacteria in the oceans each and every day. It didn’t take long for scientists to realize that CRISPR could provide an amazing and precise genetic tool. Since the spacer sequence can recognize very specific regions of target DNA and Cas9 (the particular Cas enzyme that is attached to the spacer) can then carry out a seek and destroy mission of the target DNA. It is like the delete key in a word processor program.
It was found that the target DNA didn’t have to be just viral DNA for the process to work. If DNA from a bacteria, animal, plant, fungus, or apparently any organism was inserted into the spacer sequence of CRISPR-Cas9 complex, then a genetic modification could be easily made to that organism. Using CRISPR, genes can be easily and cheaply edited. This system has set in motion a new revolution in molecular biology that has not been seen since PCR (polymerase chain reaction), a technique to amplify DNA was first introduced in the 1980s.

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So what can CRISPR really do in the lab? It can be used to delete specific genes or segments of genes. All you need is a copy of the basepairs that correspond to where you want your deletion in the target organism, and with that and your Cas9 it will find the correct place on the DNA and then cut the DNA at the precise location. In that way you can remove a gene. You can also insert a gene as well. This is done in a similar manner. You have your target DNA picked out and inserted into your CRISPR system, but in addition you need the gene, or segment of DNA you want to insert placed into the cell, as well. The cell’s own repair mechanism will detect the damaged DNA and attempt to repair the break with the added gene. In this way it acts like the cut and paste function of your word processor.
By removing the DNA from the target you are making an irreversible change to the genome of that organism, but it is also possible to use CRISPR to make reversible changes too. This is done by using a defective Cas9 enzyme. The spacer DNA sequence will still seek out and find the desired region of genome, but due to defective Cas9 the DNA will not be cut out. The spacer sequence will still attach to the DNA and block transcription, so is effectively turning off that gene.

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These sorts of techniques can be used to make “knock out” organisms – organisms that lack a particular gene. Knock out mice, for example, are an indispensable tool for understanding how certain genes function in a whole creature, and how mutations in those genes lead to certain diseases. Genes can also be turned on by CRISPR by combining the CRISPR complex with a promotor – a regulatory element that tells the cell to begin transcribing a particular gene.

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This is now allowing labs around the world to investigate disease causing mutations, including cancer biology, at a much faster rate. The techniques are considered relatively easy to use and master, and much less expensive than traditional molecular techniques to achieve similar results.
CRISPR has already been discussed as a potential therapeutic medical intervention, although, the ethics of genetic engineering are still being hotly debated. There was a attempt to use CRISPR to cure the disease hemophilia by a group of Chinese researchers, although they were not successful it is likely only a matter of time before progress along these lines would make similar trials more effective. Right now it is considered by most to be too new of a therapy for clinical medicine, and even if it could be done, some consider tampering with the human genetic code too dangerous. This might especially be true for genetic alterations that would be passed on to subsequent generations beyond the individual being treated. Some worry that it will go beyond just curing disease, and be used by the wealthy to create “designer babies”. Perhaps couples that want taller, stronger, or smarter children would be able to engineer their children to be so. Would that create an even wider divide between the haves and the have nots? These are certainly questions that should be addressed and discussed, but I do hope that fear won’t prevent this technology from reaching it full potential to treat genetic disease.

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Would it really be so bad to have future generations of humans that are more disease resistant (perhaps less prone not only to heart disease, diabetes, and Alzheimers, but less prone towards depression, addiction, or apathy)? What about a future of humans that are more intelligent, more rational, less violent, more compassionate and empathic? Only by being properly informed can we make the best decisions as a society about how to best use such technology.

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References and other reading:
1. CRISPR wikipedia article: https://en.m.wikipedia.org/wiki/CRISPR
2. CRISPR interference wikipedia article: https://en.m.wikipedia.org/wiki/CRISPR_interference
3. “CRISPR/Cas9-mediated gene editing in human triproneulcear zygotes”; Protein & Cell; May 2015, Vol6, Issue 5, pp 363-372. http://link.springer.com/article/10.1007/s13238-015-0153-5
4. “Molecular Biology of the Gene”; 7th Edition, James D. Watson, Cold Spring Harbor Laboratory Press; 2014. Pages 706-712.
5. http://www.geneticliteracyproject.org/2015/06/25/ethical-and-regulatory-reflections-on-crispr-gene-editing-revolution/
6. http://www.nature.com/news/ethics-of-embryo-editing-divides-scientists-1.17131
7. http://www.cnn.com/2015/10/30/health/pioneers-crispr-dna-genome-editing/
8. Neurologica blog article on CRISPR: http://theness.com/neurologicablog/index.php/gene-editing-humans/
9. “Is Bad Luck Really a Diagnosis?”, Darwin’s Kidneys blog: http://darwinskidneys-science.com/2015/06/14/112/

The Clumping Effect

by Rich Feldenberg

Cognitive biases permeate our thinking process, leading us to false conclusion and beliefs. Aristotle called humans, “The Rational Animal”, but it has been pointed out before that we are much more rationalizing than rational. We have a strong tendency to hold onto our notions, defending them with faulty logic and weak arguments, because we wish them to be true. Motivational reasoning and emotional argument is common to see in even very intelligent and educated individuals. Daniel Kahneman helped to define the idea of cognitive bias, and popularized it in his book, “Thinking Fast and Slow”. Over the decades the ways in which evolution has mesigned the human mind to fail the litmus test of reality testing has been more fully explored, and the list of cognitive biases, logical fallacies, and faulty brain circuits continues to grow ever longer.
I would like to introduce what I believe is a new, and as yet, unidentified type of cognitive bias the I’m labeling as “The Clumping Effect”. I have noticed this effect in myself over the last few years, and although I have not done a statistical analysis of the effect, feel it can be nothing more than a cognitive bias. The effect occurs when I am on the trail, either on my bike or running. The nature of the effect is this: If there is a stretch of trail with few runners, walkers, and cyclists, I notice that if there are two other people on the trail that are separated from each other at time 1 (when I notice them), then the three of us all converge at the same spot (time 2). In other words, if I’m on my bike I don’t just pass the first person and then later the second person, we all happen to be along the same point of the path together at time 2.
This effect can occur if all three subjects are moving in the same direction, or if two or moving in the same direction and one in the opposite direction, but all subjects must be moving at different velocities. In this definition I’m using the term velocity in its true physical sense (speed and direction), because you could for instance, have two bikes moving at the same speed, but opposite direction. Place a runner in-between the bikes and the Clumping Effect demands that the three will pass each other at the same point.
I notice this because it is somewhat annoying to be a cyclist, moving at a good clip on an empty trail, then have to be cautious about avoiding a collision when the lone spot of the trail is suddenly at full capacity. And, that I believe is the underlying reason for the Clumping Effect. It is those instances that stand out in my mind, whereas the many times that I pass one athlete then the other doesn’t really register as an event at all. We remember the hits and forget the misses, as any good skeptic knows.
I would be interested to know if anyone else has ever experienced a similar effect. I may also decide to do an experiment to measure the incidence of “hits” in comparison to “misses” on my typical trail. I’m curious to know do ‘hits to misses’ happen at a rate of 1:100 for example. How often does it have to happen that it stands out in my mind as something that “always happens”. Also, what proportion of users of the trail also notice the effect? I could send out a survey to local running and cycling groups?

References and other sources of good info:
1. Cognitive Biases Wikipedia article: https://en.wikipedia.org/wiki/Cognitive_bias
2. Daniel Kahneman Wikipedia article: https://en.wikipedia.org/wiki/Daniel_Kahneman
3. “Thinking Fast and Slow” by Daniel Kahneman. I really recommend this book.
https://itunes.apple.com/us/book/thinking-fast-and-slow/id443149884?mt=11
4. “The Skeptics Guide to the Universe (SGU)” podcast. Great free source of information on how to think logically.
http://www.theskepticsguide.org
5. “Neurological” Blog by Dr. Steven Novella. Also filled with great information on skeptical and logical thinking.
http://theness.com/neurologicablog/
6. “The Rationally Speaking Podcast”, host Julia Galef.
http://rationallyspeakingpodcast.org
7. SGUs guide to argument and logical fallacies: http://www.theskepticsguide.org/resources/logical-fallacies