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.

*
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

You Must First Invent the Universe…

By Rich Feldenberg

This year Carl Sagan Day is being celebrated Saturday, November 14th. Sagan, who was born on November 9th, 1934 has been an inspiration to generations of scientists and science enthusiasts. Unfortunately, he passed away on December 20th, 1996 at the age of 62. Way too young, and certainly way too soon for a world that desperately needed his carefully measured dose of rationality, skepticism, and his poetic style of revealing the awe of the cosmos we inhabit together.

There are many great and inspiring Sagan quotes, or Saganisms as they’ve come to be known, but one of my favorites is, “If you want to make and apple pie from scratch, you must first invent the universe”. The meaning, of course, gets one to think deeper about where the origin for all the things we take for granted actually came from. The ingredients for an apple pie may include things like apples, flour, sugar, eggs, salt, etc. But where to these ingredients come from? To get these ingredients you must first invent a universe with laws like our own, that can lead to the formation of galaxies full of stars, which can fuse hydrogen atoms into heavier elements, which can then form planets. Some of these planets must have conditions that allow life to arise, which can evolve into things like apple trees and chickens (for the apples and eggs respectively) and for the evolution of intelligent beings that can put them together to make an apple pie. Some of the ingredients, like the salt (NaCl) and water (H2O), are relatively easy to produce, and just require the hundreds of millions of years necessary for stars to produce the heavy elements oxygen, sodium, and chloride (the hydrogen for the water was produced in the Big Bang itself). The other ingredients require billions of years in the making, for life forms and their evolution to take place. How brilliant and wonderful and simple a statement to make. Many people around the globe, that continue to honor and remember Carl make it a tradition to eat a slice of apple pie on Carl Sagan day. I know I plan to have a piece this year!

Sagan was an Astronomer, and one of the first astrobiologists. He was involved in important scientific research on the atmospheric composition of Venus and Mars. He played a major role in the Viking mission to Mars and the Voyager probes to the outer solar system. And, of course, he made communicating scientific findings to the public, and demonstrating the importance of the scientific process, a priority.

When I was growing up, the book Cosmos and the mini-series, by the same name, came out. Both were inspiring, thought provoking, and in some ways life altering, and Sagan tackled everything from Astronomy, evolution, the brain, and the importance of being skeptical of pseudoscientific claims. He had a mesmerizing way of delivering his message with intelligence and passion. The TV series was recently redone by Astrophysicist and science communicator, Neil Degrasse Tyson, who didn’t attempt to remake the original episodes, but who did an excellent job of continuing on where Sagan left off.

Sagan also wrote quite a few other excellent books. These included, “The Dragons of Eden”, “Broca’s Brain”, “The Demon Haunted World”, and “Billions and Billions”. These books really fueled my scientific curiosity growing up, as I’m sure they have done for many others who grew up to love science. After all these years, his books are still worth reading, if you haven’t done so already. He also wrote the science fiction novel, “Contact” that was made into a motion picture in 1997 with actress Jodie Foster. In the novel he attempted to show what first contact with an advanced alien species might be like.

I did have the opportunity to see Carl Sagan in person on one occasion. At the time I was a chemistry major in the mid-1980s at The University of Missouri – St. Louis. Sagan came to deliver a lecture to our university on the dangers of nuclear war and the importance of nuclear disarmament. He was a great dynamic speaker and the lecture hall was completely full. I think, at the time I was hoping he was going to talk about astronomy, but in retrospect I now understand the importance of his social concerns for our future and continued existence.

Sagan also introduced me to the concept of scientific skepticism, at a relatively early age. He was critical of how to tell the difference between science and pseudoscience (something now called the demarcation problem). He showed us that there are no beliefs that should be immune to skeptical inquiry, including religious belief. He came up with the “Baloney Detection Kit” that everyone should have in their skeptical toolbox.

Carl passed away right when the first exoplanets were just being discovered. Now we know of more than 1000 planets that circle other stars. We have made a much more thorough exploration of Mars and the moons of the outer solar system. We have strong evidence for liquid water deep under the crust of the moons Europa, Enceladus, and Ganymede. There is liquid methane on Saturn’s moon Titan. These discoveries make the possibility for life in our outer solar system a little more likely, and for life outside of our solar system very likely, by the sheer number of planets in our galaxy alone. At the same time the skeptical movement has gained momentum and is going strong. We have learned more about cognitive psychology and our innate biases and predisposition towards distortions of memory and perception. Flaws we must recognize in ourselves if we are to take the first steps to learn to become a more rational species and rise out of our superstitious past. I believe Carl would find all this fascinating and exciting. We could really use Carl’s wisdom now, but at the very least we still have him with us in the form of his writing and video.     

Happy Carl Sagan Day. Have some Apple Pie and be sure to learn something new today!
References and other items of interest:
1. Carl Sagan Wikipedia article: https://en.wikipedia.org/wiki/Carl_Sagan
2. Article detailing the “Baloney Detection Kit”: https://www.brainpickings.org/2014/01/03/baloney-detection-kit-carl-sagan/
3. Trailer for the movie “Contact” based on the book by Carl Sagan: https://www.youtube.com/watch?v=jl7Xe80_0MY
4. The Demarkation Problem on the Rationally Speaking Blog.
http://rationallyspeaking.blogspot.com/2013/08/philosophy-of-pseudoscience.html
Also check out the excellent “Rationally Speaking” podcast. The current host is Julie Galef, and excellent skeptic and teacher of all things rational! The previous host was Massimo Piglucci and scientist and philosopher and all around brilliant guy. Well worth checking out!
5. The Rationally Speaking Podcast with Julia Galef: http://rationallyspeakingpodcast.org
6. Some great Julia Galef youtube videos on rationality: https://www.youtube.com/user/measureofdoubt
7. Massimo Piglucci’s homepage: https://platofootnote.wordpress.com/massimo-central/
8. My contemplations on the possibility of what it would take for life to evolve on Titan:
http://darwinskidneys-science.com/2015/08/05/musings-on-the-biochemistry-on-saturns-moon-titan-part-i/

What Would A Higher Level of Consciousness Look Like?

by Rich Feldenberg

As research in the neuroscience continues to advance, we are gaining more and more knowledge in regard to the sophisticated aspects of higher brain function.  Human neuroanatomy is well described, and the molecular biology leading to patterns of activity of individual brain cells up to complex neural circuits, containing astronomical numbers of brain cells, is also becoming better understood.  In addition, there is a great deal of information on patterns of human behavior, the ways people think, and the flaws and biases associated with normal human thinking based on research from the field of cognitive psychology.  One thing researcher still don’t agree about is, what is what do we mean by consciousness.  There is no single concise definition for consciousness, and there are some experts that think that this is not a well formulated or coherent question, and as such, we can never come up with a satisfactory answer or explanation for what it is or how it arises. Consciousness may not be any one particular thing, but may emerge by association of multiple brain systems.  

This reminds me a bit of the book, “Hitchhiker’s Guide to the Galaxy” by Douglas Adams, where a hyper-intelligent pan dimensional species built the supercomputer “Deep Thought”,  to find out once and for all, the answer to life, the universe, and everything, only to find after running the program for millions of years the answer was 42.  This didn’t seem like the kind of answer they were expecting.  When they asked Deep Thought what this meant the computer told them that they really didn’t ask the right question.  Our asking what consciousness is could be a little like this.  If we don’t know how to ask the question, the answer may not make a lot of sense.

Some would say that consciousness seems to be the property of being self aware of one’s own existence, to be aware of having certain ideas and thoughts, to be aware of information being received externally from one’s body through the senses, as well as, being aware of sensory information being received from within one’s own body.  

While intelligence and consciousness seem to be correlated to a large extent, these also appear to be two separate characteristics.  Intelligence is also a nebulous sort of concept, and is probably composite of many different factors.  It might be easier, in fact, to contemplate a higher level of intelligence than a higher level of consciousness.  We can all sort of imagine what it might be like to be smarter, but it seems less clear what it would mean to be more self aware.

Intelligence may be a property associated with problem solving, memory storage, memory access, and predicting future events.  It seems reasonable to conclude that if you have consciousness then there must be some level of intelligence associated with that.  If any creature or object is self aware, then there must be some degree of intelligence that goes with it, even if both the level of consciousness and intelligence are low.  It also seems reasonable to conclude that creatures with greater levels of consciousness may generally have a higher level of intelligence.  It may not follow that consciousness always has to exist with intelligence, however.  For example, it has been proposed that philosophical zombies could theoretically exist.  In other words, some entity that can think exactly like an intelligent human, respond perfectly to complex questions, solve problems, show appropriate emotions, and so on, but internally is not self aware any more than your pocket calculator when it calculates that 2+2=4.  This might apply to intelligent machines, where their very nature makes it difficult to determine if they have self awareness or not – Turing test be damned!  It could also apply to other species, both terrestrial or extraterrestrial where brain structure and nervous system are so different from us that determining the presence of consciousness could be very problematic.   

Down here on good old earth, it is easy to see that animals like chimps, dolphins, and our beloved family dog have intelligence.  Dogs for example recognize us, form social bonds with us, display emotion, recognize patterns of behavior and can anticipate future events based on past experience.  This is intelligence.  Many of us would conclude that dogs have some degree of consciousness, but of course, we can never really peer into the mind of our pet to know for sure that they are self aware.  I personally feel that philosophical zombies can’t really exist.  If something can mimic a self aware entity so perfectly, it must actually be a self aware entity.  It is just as clear that you can never prove, beyond a shadow of doubt, that anyone else really has a mind other than yourself.  Solipsism, as such, while possibly unfalsifiable, is never the most parsimonious explanation for the world around us.  It basically places us at the center of the universe, and so is by far the least likely explanation for the universe around us.   

Our brains have evolved to accept a theory of mind that allows us to view other people, besides just ourselves, as having thoughts, concerns, intentions and emotions.  This might seem a necessary requirement for a social animal, lest we forget the social insects like bees and ants.  It is certainly less clear that an ant recognizes its fellow workers as being capable of feeling pain or hunger, like it itself has evolved to perceive, but perhaps it does.  For an animal with a more complex nervous system, like a human, having a built in theory of mind is probably vital to working together towards common objectives and organizing patterns of society.  Our ancestors with this trait of understanding the mind of others, were more likely to survive due to the reproductive advantage of mutual cooperation and understanding in the group they were a part of. We must be careful, however, since these same biological circuits that evolved to give us a theory of mind often fire even when they are stimulated by patterns that have nothing to do with human behavior.  An example would be, when we as kids often feel that our toys have feelings, and could be sad if mistreated or neglected.  As adults, we often have the sense that there is unseen agency in the world.  Many primitive cultures believed there were spirits in the water, trees, sky and so on. There was a sense that other things must naturally have a mind like ourselves.  These kinds of superstitions live on today in many forms.   

So what might a higher level of consciousness look like?  It seems unlikely that consciousness is an all or none phenomenon, that it is either on or off.  We know that there are altered levels of consciousness that we are all well familiar with.  Sleep is a prime example.  During non-dream sleep we may not be aware of very much or anything at all.  People awakened from non-dream sleep often have no memory of anything or may recall only a few scattered thoughts or feelings.  During REM or dream sleep, we all know that we have a rich experience, but are usually unaware that we are dreaming, or that the events during the dream seem unusual.  Only after waking do we recognize that the dream scenario defied common sense, logic, and often the laws of physics.  The memory of the dream will usually quickly fade, unless reinforced by an active attempt to remember it.  The sleeping state, therefore, represent an altered level of consciousness.  During the dream state perceptions are altered, processing abilities are impaired, and our capacity for critical thinking is practically absent.  Lower level consciousness may be similar to having our mental processing systems and critical thinking skills shut off.  

During deep sedation or general anesthesia, our level of consciousness is artificially impaired.  Of course, this is what we want when undergoing a potentially painful or unpleasant procedure or surgery.  Most people have no awareness or concept of the passage of time when they are out during surgery.  The time under general anesthesia is essentially lost to them.  There was still brain function occurring during anesthesia, but not much higher brain function.  Even much of the crucial basal brain function is significantly impaired during general anesthesia, such as respiratory drive, making it critical that your anesthesiologist is also managing your airway and “breathing for you” by placing you on a ventilator while you are unconscious.  In many cases, the mechanism by which anesthetics alter consciousness is not well understood.

Drugs, such as anesthetics or recreational drugs that alter level of consciousness seem to be affecting certain brain areas that are necessary for maintaining consciousness.   This is also apparent with loss of consciousness that occurs with head trauma, where brain function has been disturbed in some way.  Axons stretched or sheared, neurons swollen, neurotransmitter levels in the synapses altered.   These kind of details, and many other observations of brain damaged patients, makes it clear that consciousness is a function of the brain.  There is no real evidence for a mind-body dualism that many people feel must be so.  

I tend to think of consciousness like a flashlight that is illuminating a basement filled with files and papers.  What items happen to be illuminated by the flashlight are what we are conscious of at that moment in time.  Everything else in the basement resides in our subconscious.   We may have some thought under the light in one moment, but soon the light has moved over to another item, and no longer illuminated, we lose the first thought from our conscious mind.  Some items in the basement hide in corners where we haven’t shined the light for a very long time, and possibly will never shine the light in those spots ever again.  

Perhaps a higher level of consciousness would give us the ability to hold our view over a much larger portion of our thoughts and memories at any one time, turning the flashlight into a spotlight.  Take this to the obvious extreme and we could light up the entire garage and all our previously subconscious thoughts and memories would now be in full focus at the same time.  There would be no difficulty finding any information that you possessed in your head, and you could think on multiple levels at one time.  Our internal awareness would be complete.

If being self aware is part of the conscious experience, then what would it feel like to be “more” self aware?  The Crisp and Turner, 2010 definition of self awareness is, “ a psychological state in which people are aware of their traits, feelings and behavior. Alternately, it can be defined as the realization of oneself as an individual entity.”  With this in mind a higher level of consciousness may mean that we are aware of our feelings and other traits much more often than we are now.  When we are focused on other activities, we aren’t necessarily thinking about how we are feeling, our internal states, or even that we exist at that moment.  A being with a higher level of consciousness might be much more in-tuned with those traits.  That is often the cited purpose of engaging in mindfulness exercises or meditation, so as to be more aware of your thoughts.  It doesn’t come very naturally for us most of the time.  Many times it is difficult to even describe what you’re feeling even when you do try to focus on it.  Again, take this to the absurd extreme and a being with a vastly higher level of consciousness than ourselves would never forget that they exist, what they are feeling, or any of their internal thought processes.  It would almost seem that if Artificial Intelligence (AI) is ever achieved that this kind of high level consciousness would be relatively easy to envision.  If a machine can be self aware at all, then what barrier would there be to it being more aware of all of it’s inner thoughts, identity, feelings, and memory than the average or even above average human.  Combine this with a superior intelligence, and wow, this may be the next giant leap in evolution.  

With human level consciousness, there are so many subconscious process going on behind the scenes, such as the basic instincts to survive and reproduce, that influence our day to day lives in just about every way.  Much of human behavior can be explained by these influences, even though we don’t often see this in ourselves very easily.  Perhaps having a greater awareness of all these subconsciously motivating forces could help us to be a more rational species.  Perhaps we will one day evolve from Homo sapiens to Homo rationalis (the rational ape).

The Dialogs: Is there a limit to Science?

by Rich Feldenberg

In the Dialogs the Robot from Lost in Space and Speed Racer find themselves suddenly transported to a distant location to discuss a topic of philosophy of science. This has happened on many occasions. They don’t know how they come to this place or if some intelligent being is behind it. When they return to their own worlds no one else is aware that they have even been gone.
This time Speed and the Robot suddenly appear on a beach at sunset. They are on ancient earth, in the greek islands.  The sky is ablaze with deep reds and purples as the sun is sinking beneath the sea. Waves are crashing loudly on the rocky shore and a gentle breeze is blowing. There is no one else on the island, but just 30 miles south, and out of view of our heroes, a fleet of Athenians is making a crossing as they prepare for battle.

“Hello again, Speed Racer.  In principle there are no limits to science.” Says the Robot, It’s bubble encased brain blinking red and yellow lights. “It’s methodology makes it the best tool to apply in an attempt to answer any question.”

“Good to see you again Robot.  Of course there are limits to science.” Says Speed, as he removes his white helmut and takes a step closer to the robot’s hulking metal body. “There are plenty of question it can not answer. In fact, it can’t answer the most important questions, like what is the meaning of life? What is the most ethical thing to do in a particular situation? What is love, how can you prove that you’re in love or that someone loves you? Science may be a useful tool to answer certain questions, but it completely fails in the most important areas.”

The robots accordion style arms raise into the air, claws open as its blinking red speech unit broadcasts its deep mechanical voice. “I think that if you examine both the true definition of science, as well as, the questions that you believe science can not enlighten us on you’ll find that science does, in fact, have a great deal to say and offer to us. I would also propose that if there are certain questions that science can not answer, then there is also no reason to believe that any other method of knowledge acquisition has any hope of being any more successful.”

“You’re saying that intuition, spirituality, religion, mediation, and so on, have no value? That’s ridiculous”, said Speed. Even you can’t analyze all the available data necessary for every decision you make or every insight you have. If you tried to do that you’d never even make it out the space hatch every morning. You’d be paralyzed with indecision as you scan through all the available literature, contemplate moves and counter moves, and continually update your Basyean analysis algorithm, for even the simplest choice you had to make. I dare to say that even with the processing speed of your computer brain it would take you hours to decide if you should first conduct a soil analysis, inspect the Jupiter II perimeter for danger, or see if Dr. Smith is up to no good, when you activate your circuits each morning.”

The robot rotated its torso slightly “Negative, as usual Speed Racer, you’ve made many false assumptions, which lead you to your illogical conclusions. First, science is simply the most reliable method that you humans, or machines like myself, have to answers questions. Science is not a perfect system, but has a number of qualities that make it extremely useful and unique. It is a self correcting system so that any conclusions from a particular experiment may be updated by new data from additional experiments. It uses statistical methodology to come to conclusions that may be very different than “common sense” intuitions would predict. It’s experiments or observations can be designed to minimize the potential bias that are inherent in both the human and the machine mind.”

“But that still doesn’t mean it can answer any question.” Speed looked out onto the darkening horizon. The stars were beginning to appear in the sky and it was getting a little cooler now. “It has important limits. I might not expect a machine to understand that, but most humans realize that there are other ways of knowing. Science is limited to naturalistic investigations and explanations. If there are phenomenon outside of nature then science will always be blind to it.”

“While human intuition and meditation and prayer may result in some eventual decision making process, there is no reason to believe that any special knowledge is delivered via these methods. Take intuition as an example”, said the robot as it’s high frequency sensors were rotating near the head. It’s blinking lights now seemed quite bright as the fading sun became lost below the ancient greek sea . “It’s clear that humans have intuition about certain things. It’s likely that over the course of evolution Homo sapiens has evolved the ability to have insight into certain common situations. Intuition might give a human the feeling that there is some danger in this place, and that it would be best to leave. This could easily be an evolved trait to promote survival, and those humans that didn’t feel a sense of dread or doom in a particular situation may have been less likely to pass on their genes to subsequent generations if they were eaten by saber tooth tigers or killed by neighboring tribes because they didn’t pick up on subtle unconscious clues that their immediate environment was unsafe. Those systems built into your neural networks are nothing more than survival circuits and were never evolved to produce accurate information about the world. They only have to be correct often enough to enhance survival, but in no way need to be highly accurate, and can be prone to a high false positive rate. Even the software engineers that designed my computer brain, and other AI even more sophisticated than myself recognized the importance of building in a set of heuristics to prevent a robot from harm and damage without involvement of higher brain circuits. “

Speed took a few steps toward the water. “Look Robot, I appreciate that science has taught us about black holes in the center of galaxies, and quarks in protons and neutrons, and gives us the knowledge to build interstellar ships like the Jupiter II to travel to the stars, or to design the Mach 5 to win races, but it can’t tell us about meaning or purpose or the right way to live your life. You have to find the answer to those questions through other means.”

“In many situations there may be insufficient data to draw firm conclusions”, said the robot, “and in all cases science is clear that it’s conclusions are non absolute but simply the closest approximation to truth that we can come to at the time. Asking, “what is the meaning of life”, may be an empty and futile question, since it is quite reasonable to conclude that there is no objective meaning – that the question itself is meaningless. And in this way one does reach the limit of science, in the sense that science can not answer a question that has no answer. Many philosophers would conclude that we have to create our own purpose for our life, and that this self-created purpose can be very fulfilling and give our temporary existence a great deal of meaning.”

“What about things that we know are real but can’t be studied in a lab like love?” Speed put his hand over his heart. “How can science prove that Trixie loves me? I don’t need to be put in an fMRI scanner to know. I know that she does but there is no test that can show something so important and invisible as love.”

“Love is a human emotion”, the robot said. “There is sufficient evidence to conclude that it is also present to some extent in other complex animals, especially higher mammals. While I don’t have that emotion built into my AI circuitry, there is clear scientific evidence that love does exist as a property of the central nervous system of certain animals, like humans. There is no evidence, however, that love exists outside of these systems. In other words, there is no proof that love is a force in space or would exist if there were no life or intelligent beings in the universe. Emotions, like love can be studied in the lab. Their effects on human behavior can be observed, measured, classified, and understood, in terms of underlying mechanisms. Based on that understanding, predictions can be made as to effects on future behavior or activities of those afflicted by such emotions. You can’t “know” that Trixie loves you, but you can have a high degree of confidence that she does based on experience and observation. An independent observer, such as myself, might come to a similar conclusion based on a careful inspection of facial expression, body language, speech patterns, and so on. The level of confidence might be improved further if I did indeed scan Trixie’s brain to examine blood flow patterns and oxygen consumption in specific parts of the brain while she was looking, thinking about, and interacting with you.”

Speed circled around the robot as the robot rotated its body without moving its legs. “Well, lets say that for the sake of argument “, continued Speed, “there are ghosts. You know, some kind of spirit with an intelligence of some kind that can haunt a house or drive an invisible ghost race car. Science could never find that because it is only designed to look for natural causes, and the scientists themselves would never believe in ghosts so wouldn’t design an experiment to test for it. You have to admit that is true.”

The robot answered. “Speed Racer, if there is another type of reality that exists, that has some form of interaction with the natural world then that is a scientific claim. Whether that claim involves ghosts, spirits, ESP, angels, miracles, or so on. If it affects this world it can be studied in some way by the scientific method. While extraordinary claims require extraordinary evidence, to quote Carl Sagan, scientists follow the data. If there was sufficient and reproducible effects that could best be explained by ghosts, then that hypothesis would have to be seriously considered. So far, that type of evidence has never been reliably demonstrated which leads scientists to conclude that any supernatural phenomenon seems highly unlikely. It can never be fully ruled out since additional evidence might surface at anytime and in science one is always open to new evidence.”

“So you are saying that science has no limits?” Speed said, squinting into the robots bubble head.

“Not necessarily”, replied the robot. “There may be physical limits that science will never be able to penetrate. If quantum uncertainty is built into the very fabric of space-time we will never have a full understanding of the quantum state of an object. In other words we can’t know both an electron’s position and momentum with full certainty. We may never be able to probe matter at the smallest Planck scales since that may take more energy than is available in the entire observable universe. It is also possible that our minds might have a certain limit in which we simply can not understand anymore beyond a particular point. Some of those limits could also be imposed by physical limits so that even the best designed computer brain might never be made intelligent enough to grasp the most fundamental truths of the universe. Your pet chimp Chim Chim can never be taught to understand calculus because it’s brain is just too simple, but there may be no plausible brain that could fully comprehend all aspects of nature.”

Speed looked down at his feet. “Even I had trouble with calculus. Trixie had to tutor me through it. I see what you’re saying Robot. I’ll consider your points. I feel like we’re being pulled back to our worlds again. I’m in the middle of a big race and the Car Acrobatic Team was trying to finish me off. I’m sure I’ll see you again.”

“Good luck in your race Speed Racer”, said the machine. “I was in the middle of searching for Penny Robinson who is lost on the planet we are stranded on. I must help find her. Until we meet next time, Speed Racer.”

EMMA knows the secrets of your past – but will she tell?:

How molecular relics in your cells tell the story of our common origins.
By Rich Feldenberg

In “Emma”, Jane Austin’s classic Novel, Emma Woodworth is described as handsome, clever, and rich. She takes to matchmaking, perhaps overestimating her abilities, and in doing so a variety of humorous and near disastrous calamities ensue. Of course, all ends well for Emma and her friends in the Novel. In this article we will examine a different sort of EMMA, but there may be some analogy to be found that even the brilliant Ms. Austin could not have foreseen. EMMAs is my acronym for Evolutionarily Modified Molecular Artifacts. I have used it in place of what has previously been referred to by some as molecular fossils. Fossil has the implication of something long dead, now extinct, and not seen in the world for many ages. Besides not being precisely what is meant by molecular fossil, when used by molecular biologists or astrobiologists, molecular fossil already has another meaning when referring to molecular or chemical remnants of past life. EMMAs may be a more appropriate term since it refers to molecular parts of still living systems that still display some resemblance to their more ancient and primitive forms. In this article we’ll explore a few examples of EMMAs and see what they can tell us about our distant past and the origin of life on earth. Austin’s Emma says “seldom, very seldom does complete truth belong to any human disclosure; seldom can it happen that something is not a little disguised or a little mistaken”. It is the nature of Evolutionarily Modified Molecular Artifacts, that their true nature is more than a little disguised and has traditionally been more than just a little mistaken. Lets look at the evidence that these living artifacts may give us a glimpse at a truth about our distant past, where we came from, and our common origins with our fellow living inhabitants on planet earth.

There are a number of critical biological molecules that are common to all life forms on earth today, and that have some unusual properties suggesting a common origin arising from more primitive precursor molecules. With this in mind, we’ll look at the common molecule ATP and the coenzymes NAD, and Acetyl Coenzyme-A, and finally the catalytic site of the protein synthesizing ribosome, which is perhaps the most fundamental molecular machine of any living cell. We’ll see that these examples also hint at a previous and now lost stage of life known as the RNA world, that preceded the Last Universal Common Ancestor (LUCA) of all living things on our planet today. To continue to stretch our Jane Austin analogy just a little further, we might imagine that the RNA world played matchmaker, in world long lost in deep time, and successfully paired DNA and protein, the two major biomolecules of life in our modern world. EMMAs demonstrate the remnants of that world before the matchmaking. Over evolutionary time they have been mesigned in their original forms, and re-mesigned into their current disguised forms. Like children who can not imagine a world before they were born, or before their parents existed, we too have a difficult time looking past the DNA/protein paradigm and into the RNA world.

Just like any good Austin Novel there are many interesting and complex characters. Some of the important players in our story of life on earth include molecules that contain pieces of ribonucleic acids (RNA). The first we’ll meet a key character known as adenine triphosphate (ATP). We will then be introduced to several of the coenzymes – small organic molecules that are necessary for the function of larger enzyme complexes. An finally we’ll become acquainted with one of the classic characters on life’s busy stage, the active site of the ribosome, which catalyzes one of the most fundamental reaction of the cell – the peptide bond to build protein. As stated above, each one of these molecules contains an RNA component, even though none of them are used to store or transfer genetic information. They are all involved in important biochemical reactions that have traditionally been thought to be performed only by protein enzymes. As we will see, the catalytic site of the ribosome relies on RNA exclusively to catalyze it’s fundamental reaction, and is therefore a ribozyme (RNA enzyme). These examples, and many others that we won’t describe today, appear to provide evidence of a long lost RNA world, with protein eventually evolving around the RNA core to assist and improve its biochemical efficiency.

First let’s look at the simple ATP molecule, which is well known to serve as the energy currency of the cell. It functions to power chemical reactions by transferring energy from its high energy phosphate bonds. It contains the base adenine, bound to the pentose sugar ribose. Ribose is the same sugar used in RNA (ribonucleic acid). The sugar ribose differs from the sugar deoxyribose (the sugar of DNA) only in the presence of a hydroxyl (OH) group at the 2-prime carbon. DNA does not contain this 2-prime hydroxyl group.

ATP is produced by the metabolic processes of glycolysis, the Kreb’s cycle, oxidative respiration, and by light powered photosynthesis, but is used in a multitude of reactions to provide the energy necessary to drive those reactions in the desired direction. Why should it be necessary that this energy storage molecule is a nucleotide? Could this be a hint that it’s important role began at a time when RNA played a much more central role in biology than it does today? Is the adenine now just a left over of the original mesign?

ATP – the energy currency of the cell.

Let me now introduce you to the charming NAD. Nicotinamide Adenine Dinucleotide(NAD) is a coenzyme that is composed of two ribose containing nucleotides linked together by a diphosphate connector. One of the nucleotides is adenine, just like that found in RNA, and the other nucleotide contains the non-RNA base nicotinamide. Being a dinucleotide, again should make us appreciate this coenzyme’s primitive origins.

Nicotinamide Adenine Dinucleotide (NAD)
The Adenine base is on the bottom half and the Nicotinamide is on the top half.

Nicotinamide is converted from nicotinic acid to its amide form. Nicotinic acid is also known as the vitamin niacin. The name was changed to niacin due the concern that people would confuse the nicotinic acid with nicotine and falsely believe that nicotine had nutritional health benefits. Nicotinic acid and nicotine are chemically distinct molecules, although they both share a pyridine ring structure- which is an aromatic heterocyclic ring with nitrogen at position 1 (see below). Both nicotinic acid and nicotine have their own distinct biological effects. Of course, nicotine is produced by the tobacco plant, but is not produced by animal cells. Nicotinic acid is found in all living cells, whether they are animal, plant, or single celled bacteria.

Chemical similarities between Nicotinamide (part of NAD) on the left, Nicotinic acid (Niacin) in the middle, and Nicotine (harmful carcinogen) on the right.

Nicotinamide Adenine Dinucleotide (NAD) is necessary for the operations of a wide variety of enzymes in all cells. The NAD molecule can be in either an oxidized form (NAD+) or a reduced form (NADH), and is therefore an important component of many oxidation-reduction reactions in the cell. It can transport electrons in its NADH form, or take them away in its NAD+ form. Since cell metabolism is, in large part, the process of extracting energy from biomolecules like sugars and fatty acids – in other words oxidizing these molecules in a slow and controlled way – NAD is important for the function of many enzymes found along these these metabolic pathways in the cytosol and mitochondria in eukaryotic cells. In the mitochondria NADH becomes oxidized, as electrons flow down the electron transport chain. The resulting H+ (proton) is pumped across the cellular membrane, creating a proton electrochemical gradient, which then is used to produce ATP – to be used to power other non-spontaneously occurring chemical reactions.

Ball and Stick chemical model of NAD

The coenzyme known as Acetyl-CoenzymeA , like NAD, also contains the nucleotide adenine. Connected to it is a molecule with a thiol group (SH) at its end. This molecule participates in important chemical reactions that require the transfer of an acetyl group (a methyl bonded to a carbonyl – see below).

         acetyl group

Many steps in key chemical pathways involve acetyl transfers to build or break down molecules. The sulfur group in Coenzyme A can chemically attack the acetyl group of another molecule, remove it from that molecule, and thereby take it for use in a multitude of biochemical reactions. In the process Coenzyme A becomes Acetyl Coenzyme A, and can be recycled back to Coenzyme A once it released the acetyl group at the right time and place. It is an important part of enzymes involved in glycolysis and the Krebs cycle – both chains of reactions that break down glucose to create ATP. Gene expression can also be regulated by acetylation of histone protein, telling the cell which genes to transcribe and which need to remain silent in a given cell type. It is also used to create the neurotransmitter acetyl-choline from choline.

Conenzyme A. To become Acetyl-Coenzyme A, an acetyl functional group is attached to the thiol group at the far left end of the molecule. In this way, Acetyl-Coenzyme A can transport a carbon atom to be used in other chemical reactions.

Our true hero is the ribosome, the site of protein synthesis, and common to all modern cell types, although, the molecular structure differs enough between prokaryotes (single celled organisms like bacteria and archaea) and eukaryotes (more sophisticated cell types like that seen in animal or plant cells) that these differences can be exploited by certain antibiotics which target prokaryotic ribosomes, but leave the eukaryotic ribosomes unharmed. Even the mitochondria found in animal and plant cells have their own ribosomes that resemble prokaryotic ribosomes more than eukaryotic ribosome found in the cytoplasm of those same cells. The production of protein is perhaps the most primitive and basic metabolic function of all living cells. It came as a huge surprise to scientists when they learned that the active site of the ribosome (where the peptide bonding reaction takes place – the peptidyl transferase reaction) is composed only of RNA and no protein at all. Additional structural studies have confirmed that it is the RNA that catalyzes this basic cell reaction.

This would seem to support the notion that RNA played the major role in the biochemistry of the most primitive life forms. Ribosomes today are complex molecules, made of multiple components, some of which are ribosomal RNA and other parts are protein – it is therefore a ribonucleoprotein. The protein portions seem to assist the ribosome in doing its job more efficiently.

The examples given above reveal the important role that RNA molecules play in cellular biochemistry. The fact that some of the basic process of life rely on these RNA containing molecules lends support for the RNA world hypothesis. Except for the ribosome where the actual catalytic site is still a ribozyme, the other examples don’t use the RNA portion for the vital catalytic role, but may possibly have done so in the distant past. The presence of the RNA still retained in the coenzyme may offer proof that it is a molecular fossil – or as I prefer an Evolutionarily Modified Molecular Artifact (EMMA). To paraphrase Jane Austin, when referring to the RNA that lays hidden at the core of many of our most rudimentary metabolic processes, which may have served a grander role in a far distant past, and which now has relinquished it’s primary role for one of a more modest, behind the scenes assistant, “The sweetest and best of all molecules, faultless in spite of all her faults”. In future articles we can examine some other examples of EMMAs, such as additional types or ribozymes and riboswitches.

References:

1. Article on Mesign in Nature (also linked to within this article):
http://darwinskidneys-science.com/2015/07/08/another-clever-mesign-brought-to-you-by-mother-nature/

2. Nicotinamide Adenine Dinucleotide (NAD) Wiki article.
https://en.m.wikipedia.org/wiki/Nicotinamide_adenine_dinucleotide

3. Acetyl Coenzyme A Wikipedia article.
https://en.m.wikipedia.org/wiki/Acetyl-CoA

4. “The RNA World” Gesteland, Cech, and Atkins. Second Edition, Cold Spring Harbor Laboratory Press. 1999.

5. “Molecular Biology of the Gene” Watson, Hopkins, Roberts, Steitz, Weiner. Fourth Edition, 1987.

6. Life as we don’t know it.   “Musings on the Biochemistry of Saturn’s Moon Titan”.