Why the concept of species is more fuzzy than you might think

By Rich Feldenberg:

The term species is viewed as a fundamental unit in biology. We are the species Homo sapiens, and we love to classify ourselves and other creatures into unique categories, giving them qualities that set them apart from other creatures. Charles Darwin’s evolution by natural selection gave the first proofs that all living organisms today descended from a common ancestor, which branded into an ever growing number of different evolutionary paths, resulting in a tree of life.  The trunk being the last common ancestor (LUCA) and all the tiny twigs at the ends representing all species that have ever existed. But is this really an accurate view of the living world – each species of organism occupying its own unique little cubby, completely distinct from it’s fellows in the cubbies next door? We have learned a lot since Darwin’s important discovery of Natural Selection. Modern biology tells us that, while evolution is on firm scientific ground, the concept of the species is less so. We humans have a tendency to think in a discontinuous way – that things do fall into distinct categories – that there is a separate essence that each thing has unto itself. That may be one reason why evolution is a difficult concept to accept for some people, because if each thing has it’s own essence of being, you can’t change it into something else. This idea was demonstrated in an experiment where children were told a story about a witch that turned a frog into a rabbit. The frog now looked like a rabbit, acted like a rabbit, preferred to eat carrots and not flies, wanted to hang out with other rabbits, but when the children were asked if this animal was now a rabbit they said it was really a frog. It’s underlying froggy essence could not be altered by the witches spell.

It turns out that the concept of species is really not a discontinuous one at all. It is a continuous variable, and that may be a difficult idea to wrap your head around. In medicine some diagnoses are continuous and others discontinuous, and in some others it may be difficult to know for sure. For example, having 6 fingers on your hand is discontinuous (you either do or you don’t), but systolic blood pressure is a continuous value, with a range of anywhere from 0 to somewhere quite high like 250 or perhaps rarely 300, with most people being in a certain range, like from 100 to 140. So why is the species also a continuous variable? Isn’t a rabbit a rabbit, and a frog a frog? Certainly a human is a human, and not a chimpanzee, right?

Well, keep in mind that names are just there for our convenience. How close they approximate reality may vary depending on the purpose of the name, and how good we are at understanding what we are describing. Ideally, a name would completely describe reality, but that will never be the case because a name is just a short hand way of talking about something else. Species tells us about taxonomic ranking. This is meant to help us determine which ancestors all the members of the species have in common, and how closely related those members are to members of another species. The problem arises in that the there is no defined line in the ground where one species ends and the next begins. One definition of species asserts that members of one species can not reproduce to have fertile offspring with members of any other species. This definition isn’t technically correct. The reason that this seems true most of the time, is that the many of the ancestral species happen to have died out, so it creates the appearance of very distinct groups of organisms (each in a separate and walled off little cubby).

Every generation is the same species as its parents and the same species as its own offspring. If this is true how could new species arise? It is precisely because the changes that occur due to evolution do so over much longer periods of time than a mere few generations. An organism could reproduce with a member of the prior generation, and if transported back in time to members from tens or hundreds of generations prior. At some point, however, there will be enough structural and/or behavioral differences that reproduction would no longer be possible.

Say that we took an organism back in time (it could be any organism, even a human). When we took him or her back 50,000 generations we find that he/she was able to reproduce with the contemporary population, but couldn’t reproduce with the individuals from 100,000 generations earlier. Now if we go back 50,000 generations from our starting point and take a subject from that era (one that could easily reproduce with our original organism) and then take him or her back to 100,000 generations before our starting point (50,000 generations before this individuals time) we find that it can reproduce with an individual from that long distant time period. So the original could reproduce with a subject from 50,000 generations ago, but not 100,000 generations ago, and the individual from 50,000 generations ago could reproduce with one from 50,000 generations ahead or behind its own time.

Since in the real world, those ancestors are mostly extinct it give the illusion of a discontinuous landscape of species. Richard Dawkins gave an excellent example in his book, “The Ancestors Tale” when he described ‘the salamander’s tale’. In that example Professor Dawkins described several species of salamander that live along a ring of high elevation in Central California. The ring forms a physical geographical structure that makes the species adjacent to any salamander’s location available to them, but prevents the species from interacting with species on distant parts of the ring. At the southern end of the ring are two distinct appearing species Ensatina eschscholtzil and Ensatina klauberi. E. eschscholtzil is brown and lauberi is spotted, and the two species, while in contact with each other do not interbreed – the very definition of separate species! That’s all well and good except that as you go up north on either side of the ring there are more species still, and each of these can reproduce with the species neighboring it.

It’s likely that the ancestral species arrived at some time in the past in the north. Two descendant populations emerged, one going south by the eastern route and the other going south by the western route. If all those other species on the ring had gone extinct we would be left with two species that could not interbreed and there would be nothing very special about the story. Those other species did not die out, however, and there is a continuous ring of salamanders that can reproduce with others of similar species, except in the case of the two southern species. As Dawkins says in the book, “Strikes a blow against the discontinuous mind”. The situation for these salamanders reveals what the situation would be like for any species (human included) if all of our ancestors were alive today. There would be a continuous stream of organisms that can interbreed with those close to them in time, but only over longer time scales do differences add up that make them distinct enough that interbreeding is no longer possible.  The sides of the ring represent a common ancestor, diverging and over time becoming two separate species, but having a path of “able to interbreed” individuals all the way down.  

In another post, I’ll illustrate another problem with the “tree of life” concept.  In actuality the tree concept is complicated by “lateral gene transfer” – basically genes being swapped by other organisms of different types.  This is very common in bacteria, but also seems to happen to some extent in more sophisticated organisms.  In any case, the idea of species should be used as a useful placeholder, but has important limitations.

Reference:

1. Species, Wikipedia.
2. “The Ancestor’s Tale: A Pilgrimage to the Dawn of Evolution”, Richard Dawkins. 2004.

3. Another clever Mesign by Mother Nature.  Darwin’s Kidneys.  July 8, 2015.

 

Happy Darwin Day 2016

February 12th, 2016 is Charles Darwin’s 207th birthday. Charles also happened to share the exact same date of birth with Abraham Lincoln – so happy birthday Mr. Lincoln, as well! Since this blog is dedicated to science, with a special emphasis on evolution, and in fact, has the name Darwin in the title, I want to be sure to honor our dear Mr. Darwin properly.

There are Darwin Day celebrations planned in the USA and around the world, but no ‘Official Darwin Day’ is recognized nationally. That could change as some efforts are being made to make it official. In fact, this year the Governor of Delaware declared an official Darwin Day in his state. In some cities there are lectures or parties to celebrate.  The Center for Inquiry has a take action page, where you can send your name in a letter  to members of congress to express the importance of creating a Darwin’s Day for public education of science.

Charles Darwin’s theory of evolution was the beginning of modern biological science. As the Russian evolutionary biologist Theodosius Dobzhansky is quoted as saying, “Nothing in biology makes sense except in the light of evolution”. Evolution is the thread that binds all of biology together. Every aspect of biology, from molecular genetics, embryology, comparative anatomy, populations and ecosystems all “make sense in the light of evolution”.

Darwin’s theory was a realization of origin from common decent. Evolution does not address the emergence of life from non-biological origins, but does an excellent job explaining the illusion of design seen in the complex structures of the living world. Of course, Darwin realized that the illusion was the product of natural selection working on variations in living things. Darwin had no idea about genetics, DNA, mutations, and so on, but as those fields of biology developed they only reinforced Darwin’s big idea. It could easily have been otherwise. If evolution by natural selection was not how the world worked, then molecular genetics, phylogenetic, developmental biology, and so on would not have provided additional support to a 150 year old theory. Yet, all these modern sciences fit in perfectly, continuing to build on the original theory. Even without the fossil record modern biology would still point the way to evolution. By the way, the fossil record also supports evolution, and has only become more robust during the last 150 years as many more fossil species have now been discovered.

I’m sure Darwin would have been delighted to learn about genes, how new mutations arise by damage due to radiation, chemical mutagens, or simply errors in the normal process of DNA synthesis. He would have loved to see how the genome is cluttered with the remains of dead viruses, pseudogenes, copying errors that we have been copying and passing down to our children for geological eons. And he would have certainly understood that we can see our degree of relatedness to any living species on the planet by looking at, not just the working genes and how closely they match to us, but also these dead viruses and pseudogenes.

Darwin’s voyage on the H.M.S Beagle remains one of the most exciting and most epic expeditions of discovery in history – certainly one of the most productive, since it resulted in much of the data Darwin needed to formulate his theory over the next several decades. Darwin was an amazing naturalist and keen observer. There is hardly any area of natural science of his time that he didn’t seem to make some meaningful contributions. Not just in biology but in geology, as well.

So this Darwin’s day I plan to celebrate at home with my family. Perhaps have a piece of Common Decent Cake or Evolution Pie, learn something new I didn’t know about evolution, and honor our Dear Mr. Darwin.  Let me know how you plan to celebrate.

Other Reading:

1. Darwin Day:  Wikipedia
2. Natural Selection:  Wikipedia
3. Youtube.  Climbing Mount Improbable.  Lecture by Richard Dawkins.
4. OxoG is how radiation turns your own water against you.  Darwin’s Kidneys blog
5. Cytosine Deamination.  Darwin’s Kidneys blog.  (another mechanism of mutation).
6. Another Clever Mesign by Mother Nature.  Darwin’s Kidneys blog.  New word mesign to differentiate apparent design in nature from when we mean a designed object.
7. How our ancestors promiscuous genes became more discriminating.  ZME Science. Feb. 9, 2016.  Article on how gene families arise by gene duplications.

Book Review: “The Vital Question”

By Rich Feldenberg:

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

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

 

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

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

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

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References:
1. The Vital Question, by Nick Lane

2. Nick Lane webpage.

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

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

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!

 

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/

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”.

You once had six kidneys, and no you’re not an alien!

By Rich Feldenberg

This article is the first in a series of articles that relates back to the name of this blog. Darwin’s Kidneys is the blog name and also the name of the book that I am currently in the process of writing. It is an attempt to illustrate the convoluted evolutionary path that kidneys have taken down our ancestral line. More importantly, it is an attempt to highlight the importance of the kidneys in allowing animals to adapt into new environment along that evolutionary road. In the case of our ancestors, and all land vertebrates, that road began in the oceans, detoured into fresh water habitats, then rose up onto dry land. Be aware that that is simply the road that lead from the first animal ancestors to humans. Other animals began at the same starting line, but took different turns along the way, sometimes taking them far from where our particular road has taken us. In many cases, the road for certain creatures came to an abrupt dead end, as extinction ended that journey. Along the way, kidneys helped creatures survive by keeping their internal environment stable even as they moved into environments very different from which they originally evolved. To meet those new challenges, kidneys had to evolve to prevent the internal environment from reaching chemical equilibrium with the external environment.

So what’s all this about you having had six kidneys? Well, our earliest development betrays something of our evolutionary past. Think back to when you were just a little fetus in the womb. I know, it was a long time ago, but think hard. As a fetus you didn’t have to worry about very much. Mom took care of you. For instance, you didn’t need kidneys to clean your blood back then. That’s what mom’s kidney’s were doing for you through the intermediate organ of the placenta. The placenta, which is the only organ that was part you and part mom, was the portal between the two worlds. The nice warm watery world you were floating in, and the harsh outside world that you had no idea you would be rudely tossed into in a short 9 months. But, since you were going to need kidneys when the connection between the two worlds was eventually lost, your genetic programming was instructing your developing body to start making kidneys.

You might think that a good way to make kidneys would be to have certain cells in your developing body begin to transform into kidney cells, and arrange themselves into the proper architecture to create the complex tubules, glomeruli, blood vessels, and so on necessary for a functional organ we know as the kidney. That would probably make a lot of sense to an engineer, architect, or designer, but that is not how nature decided to go about this particular project. To make human kidneys, or any mammalian kidneys for that matter, we first have to go through two false starts, then finally get to the real deal.

Your first set of kidneys starts to take place somewhere around where your upper chest or neck will eventually be, when you are a mere 22 days gestation (ah, the joys of youth). Tissue known as the intermediate mesoderm receives chemical signals, called morphogens, from the nearby anterior somites to start forming a duct named the pronephric duct. These morphogens effect which genes get turned on or off in the cells that come into contact with them. Cells in the pronephric duct then begin a migration to nearby tissue and cause more of the intermediate mesoderm to start forming little tubules. By the way, tubules are what the kidney is all about, so tubules are a good start at this point. These tubules form the pronephros. Nephros refers to kidney, and pronephros doesn’t mean “go kidney!”, it means first kidney. Why? Because this is your first set of kidneys, but luckily not your last. Now if you happen to be a fish or an amphibian, this is about as good as it gets. These are the final kidneys for these groups of creatures. In mammals the pronephros is not thought to be functional, but keep in mind that as mammals, our distant ancestors included fish and amphibians – hint hint- so our non-functional pronephros may be evolutionary baggage that we are stuck lugging around from generation to generation.

The pronephros begins to degenerate not long after it forms, but before it does so it produces a duct that begins to grow in a downward direction towards the lower body. This duct is called the nephric duct, or sometimes the Wolffian duct, secretes chemical morphogens in the the tissue below where the pronephros had previously appeared then disappeared. This time the morphogens secreted by the pronephros start the generation of tubules in our second pair of kidneys – the mesonephros. In humans the mesonephros forms around day number 25, but alas, it too has only a brief ethereal existence and begins to degenerate soon after forming it’s mere 30 or so tubules.

Curiously, while the mesonephros doesn’t appear to filter blood like an decent kidney would, it does have some interesting functions and lead to some important structures. For one thing it happens to be an important site for the production of blood cells in the early fetus. The so called, hematopoietic stem cells begin to form in the mesoderm at the aorta-gonad-mesonephros region (AGM). So your second pair of kidneys is important as an early red blood cell production factory. The hematopoietic stem cells jump ship, however, as the mesonephros eventually disintegrates away, and they travel to the nearby liver where they reside for another brief interval, producing blood cells for the fetus. Eventually they move on from this location too, and set up shop in the bone marrow, where they eventually settle down for the long duration of your adult life.

The second important legacy left by the mesonephros is that some of the tubules become components of the male reproductive tract. The tubules of the mesonephros connect the Wolffian duct to the testis and the Wolffian duct itself transforms into the epididymis and vas deferens of the male gonads. In female, lower levels of testosterone allow degeneration of all the Wolffian duct structures so these male structures don’t form in the female fetus.

In the mean time, as the mesonephros follows the unfortunate fate of the doomed pronephros, the Wolffian duct continues to grow downward on it’s journey towards the pelvis. When it reaches a certain patch of cells, called the metanephric mesenchyme (MM), it pops off a little shoot called the ureteric bud. How the ureteric bud knows where to sprout off the Wolffian duct and which direction to grow is due to it having received an important, and tongue twistingly named chemical signal from the MM called glial cell line-derived neurotrophic factor or the easier to say GDNF. The bud cells have protein receptors that can recognize the GDNF diffusing into the area. Experiments where mice had their GDNF receptor gene deleted failed to form kidneys at all, illustrating the importance of this chemical interaction for renal organ development. The ureteric bud then kindly replies to the MM with it’s own suite of chemical morphogens which tell the MM to please not die by apoptosis (apoptosis is programmed cell death and is an important means of removing unnecessary tissue during organ development) and then to cause the cells to begin to cluster around the bud itself.

Further chemical interactions between the MM and ureteric bud cause the bud to begin branching, like branches and twigs on a tree, and for the cells of the MM to transform into epithelial cells and arrange themselves into tubules. This time -third times a charm- the tubules don’t disintegrate, as they did with the pronephros and mesonephros. Instead, they go on to produce the final and permanent set of kidneys – the kidneys that you’ll use for your lifetime – and the third set of kidneys that you made! The first four kidneys are gone by the time you’re born, so it is true that the metaphros is the only set of kidneys that you’re born with. Although, it you’re a male then some remnants of the previous kidneys still remain as part of the reproductive tract – weird, right?!The dance between the MM and the ureteric bud continues, resulting in the formation of nephrons from the MM end, and collecting ducts and ureters from the ureteric bud end.

While the pronephros and the mesonephros do not function as kidneys for us, they none the less, are absolutely necessary to get to the metanephros stage. If something goes wrong at one of the first two stages, then the final kidney will either not form at all, or be malformed in some horrible way. As in nearly every case, evolution uses what it has already available to work with, and modifies that in some way to produce new structures, and structures with new functions. It seems that evolution used many of the genetic pathways that were already in place to produce fish kidneys, to eventually get to a mammalian-type kidney, which has many different functions than a fish kidney is required to perform. Wouldn’t it seem more logical to produce the mammalian kidney in a more direct manner, bypassing the unnecessary and complicated steps taken to begin the 1st the 2nd sets of kidneys? This might even have reduced the risk of many types of birth defects in the kidneys, that are so common, but nature does not operate by logic or foresight. Systems that are in place are simply prone toward variation through mutation. Vary rarely one of those mutations may improve the odds of survival, and because there are so many organisms born over long periods of time, these rare advantageous mutations are almost inevitable. Environmental pressures will continue to filter out the disadvantageous variations and increase the advantageous ones in the gene pool.

So yes, you’ve had six kidneys and no, you’re not an alien. You’re simply a result of the long process of evolution. Your distant ancestors live on, in you, in the way your genetic programming is constructed and operates.