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.

Entropy as an engine of life’s origins

by Rich Feldenberg:

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

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

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

 

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

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

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

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

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

 

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

 

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.