Resurrection

Posted on January 11, 2019 by

After I rejected the strong atheism of my upbringing, I spent many years wondering what the truth was about the existence of God. I investigated several theistic and spiritual systems. At one point I became fascinated with Jewish mysticism; I read several books on Buddhism; I listened to relatives who had delved deeply into Indian religion; I learned transcendental meditation. (I even peeked into Scientology – and I fled.)

All of this convinced me that there really was something that existed beyond the material world studied by science. I called this something “spirituality”. I began thinking that maybe the idea of “God” was the immaterial manifestation of this spiritual reality. But I was also getting the sense that if that was true, God was a very distant and unknowable entity. Both the Kabballah and the sayings of the Buddha seemed to confirm this.

I found myself standing on the shores of a sea of mystery, certain that the waters hid treasures of beauty and goodness, but with no way to see them for myself.

And then, prompted by a friend, I read the Gospels. I had read some of them before in school, but only as an exercise to reinforce my atheistic scorn at the stupidity of Christianity. Back then I was focused on the magic, the contradictions, the naiveté of the ignorant who believed in scientifically impossible events like the resurrection.

When I read the Gospels the second time, my mind was open, freed of the ideological certainty of atheism. I still saw the contradictions, but now they appeared as evidence for truth, the kind of differences one would expect in true eyewitness accounts. I still saw the magic, but now it confirmed for me my new-found conviction that science is not the only pathway to truth. And now I saw the figure of Jesus Christ, and reading His words, I realized that God must have seen me standing on the shore, staring helplessly at the waves. Jesus Christ rose from those waters and held out His hand to me.

“So you want to see God?” He asked me. “Here I am.”

The above is a poetic image, but something very similar actually happened to me, in a dream about a frightening cliff, and in another about a beautiful garden. Jesus was there in both, showing me a new reality, helping me find the gate. Jesus Christ was real, He was the incarnation of God, and He was calling me.

Well, let’s take a deep breath. I was at the time, as I had been long before and remain today, a scientist. And by most objective measures, a fairly successful one. I know that dreams are images produced by neurophysiological and psychological factors, and, like so many subjective experiences, they can be easily explained  as materialistic phenomena. So perhaps I had those dreams (and other subjective experiences) because I wanted to (as I have since been told many times).

That explanation was the one I had used as a young man to dismiss several similar experiences that I couldn’t readily make sense of at the time. But now I rejected it, as I rejected atheism as a failed worldview.

I thought of the widespread belief among scientists of the late 19th century that there wasn’t much else to learn about the physics of the universe, and the idea that the origin of life would be a simple problem of chemistry to solve. What replaced all these beliefs was not something simpler and more elegant, but theories that are far more complex and perhaps even semi-mystical, bringing into question our reliance on pure materialism as the universal truth of nature. I expect the same to happen with the current popular notion that consciousness is nothing but an illusion,

To say that dreams are just neurological impulses is like saying a Kandinsky painting is just paint and canvass, a Beethoven symphony is just sound waves, and love is just a trick of hormones. One could as easily say that the ideal gas law or the Schrödinger equation are just letters and symbols with an equal sign in the middle. And what you’re looking at now is merely the geometrical arrangement of two-dimensional symbols against a white background – “reading” is an illusion.

Which brings me back to my reading of the gospels. The figure of Jesus was powerful and produced a sense of awe in my soul. But perhaps even more important to me were the mortal characters in the story. Acts of the Apostles, which I read for the first time, brought these people into sharp focus. Peter, the man who denied Christ and abandoned him at the end, and Paul, the archenemy of the new faith, sprang off the pages as real people, not the subjects of a mythological propaganda piece. I was quite used to the stories of Soviet heroes from my childhood – they were so perfect that even as a child, I suspected that there might be just a touch of exaggeration there. But Peter was weak before he became strong; Paul was headstrong and vicious before he became virtuous (if still headstrong).

It was the resurrection of Jesus Christ that produced the transformations of these men. It was the same event that brought them together and called out to so many people of the time. It was the event that led within less than 100 years to the growth of a new religion to over a million believers – despite persecution, the murders of their leaders, and the destruction of Jerusalem, the original center of the new faith.

There was no doubt in my mind as I finished Acts that the resurrection was the central point of Christianity, that it defined who Jesus was and who we are. Because I saw myself in Peter, and even more so in Paul. Not because of the great work they did after the resurrection, but because of Peter’s weakness and Paul’s intransigence. And as I finally came to accept Christ as my Lord and Savior (the details of which, along with those of my dreams I have written about elsewhere), I saw that I and all of suffering humanity are perfectly reflected in the transformed lives of these apostles.

But how can a scientist believe in miracles? That question has been asked and answered numerous times, and I have not much wisdom to add. I rejected scientism a long time ago, even while still an atheist, so I have no problem understanding that science has limits, and that miracles, by definition, are not addressable by science. Even my father, a communist, atheist, strict materialist, and also a physical chemist, told me that the scientific method is not able to address all questions in life and nature.

Science has been my lifelong passion, but I have always been enamored of history, and while I never considered making it an official professional relationship, my attachment to the lure of historical scholarship has also been a lifelong affair. Everything I have read about the history of Christianity confirms my subjective belief in the reality of Christ’s resurrection and divinity. Again, this case has been presented by many, and I can only add that I found it convincing from the time I understood the historical reality of the first century.

I believe in the resurrection of Christ because I believe in God, and in Jesus Christ as the incarnation of God on earth, and I believe in the redemption of human beings like Peter, Paul, Mary Magdalene, myself, and you. If there was no resurrection, there would have been no Christianity, and history would have been entirely different, probably without science, hope, or moral progress. As C.S. Lewis so famously said, “I believe in Christianity as I believe that the Sun has risen, not only because I see it but because by it, I see everything else.”

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Merry Christmas to All!

Posted on December 20, 2018 by

And a happy and blessed new year. I will be back in January with new posts on various topics, including the origin of life, the question of purpose, how to be happy, and similar light stuff. And before we know it, Spring will be here. Peace and blessings.

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My Favorite Enzyme Part 3 (Final)

Posted on December 18, 2018 by

OK readers, here we go. Now that you have the basics, let’s get back to the hero of this series, my favorite enzyme, Aminoacyl tRNA Synthetase (usually referred to as aaRS, not Syzase). Remember that the task of the enzyme is to join the right tRNA with the right (cognate) amino acid. The tRNAs each carry one amino acid to the ribosome where their cargo (the amino acid) is added to the growing protein chain in the correct order. This happens because the tRNAs, using their anticodon triplets, bind in turn to the codons on the mRNA, which have been copied from the master code sheet, the DNA.

Amino acids and tRNAs cannot recognize each other because they are parts of different chemical systems, so there is no way that the correct amino acid (matching the tRNA anti codon) could ever get matched with its tRNA without help. It would be like an English-only speaker having a conversation with an Italian-only speaker. They need a translator. And the helper/translator is aaRS. That’s why I consider this enzyme to be at the heart of the entire translation process.

How does the enzyme do this? First, each enzyme has a binding site for its specific amino acid. So alanine aaRS has an alanine binding site. It also has a binding site for each of the 4 tRNAs that carry one of the 4 anticodons for alanine. Once this very large enzyme has alanine bound in one site and an alanine tRNA bound on the other site, the protein conformation (the protein’s shape) shifts in a way so that the end of the tRNA and one end of the amino acid are close. The enzyme then catalyzes a chemical reaction (requiring energy) between the two molecules, and the result is a strong chemical bond between tRNA and amino acid. The process is illustrated in the following figures.

syase2

syase3a

Imagine the interpreter saying “Mr. Smith, let me introduce Mr. Russo; Signor Russo, le presento il Signor Smith.” And the two men shake hands. Only in the chemical case they don’t let go; they are bound.

Syase3b

So the enzyme has done its job. It has taken its amino acid and matched it with the right tRNA so that the amino acid will be put in exactly the right place determined by the DNA sequence. Once this is done, the new bonded tRNA-amino acid complex can leave its binding sites, and as a tightly bound couple navigate its way to the ribosome, where the two molecules will part company, the tRNA to go back to finding another aaRS (or maybe the same one), and the amino acid to live the rest of its life as part of a protein.

But wait, we aren’t done. If this were the whole story, it would be amazing and exciting, but there’s more. You see, the entire process of translation really needs to be very accurate. If the wrong amino acids get attached to the wrong tRNA, the protein sequence will not be what it’s supposed to be, and the protein might not work. In fact, the entire translation process, including the work of the aaRS, is extremely accurate, with one mistake in over 10,000 trials. To reach that level of accuracy, the binding and matching I described above just won’t cut it. Many amino acids are very similar to many other amino acids (just ask a biochem grad student), and mistakes can definitely be made. A leucine might just fit into the binding site on an isoleucine aaRS, and that wouldn’t be good. And alanine is only slightly bigger than a glycine, and it would take an amazingly well engineered binding site to be able to distinguish the right from the wrong amino acid with 99.999% success.

So the enzyme has some tricks to make sure it hasn’t screwed up. Once the amino acid and tRNA are bound, the happy couple are shunted to another site on the enzyme called the editing site. This site is shaped in a way that will allow almost any amino acid and tRNA to get in, except the right ones. That particular amino acid tRNA just doesn’t fit. It’s especially good at admitting smaller amino acids while excluding the right one. So if everything is correct, the amino acid tRNA does not (cannot) bind in the editing binding site, and it breaks free from the enzyme to go on its merry way toward the ribosome. But if a mismatch or some other error had taken place, and the mistakenly bound couple does fit into the editing site, it’s cut into pieces by the action of the enzyme and never gets close to the ribosome.

So not only does my favorite enzyme recognize the proper amino acids and from 1 to 6 proper tRNAs, and not only does it provide the energy and mechanical means to link the two together, it also makes sure it got it right and deals a death blow to any erroneous products. Pretty neat, eh?

And I should mention that every cell in every living thing on this planet has the same system and has had it as far back as LUCA. In fact, we have no idea what came before and how the present universal system evolved, since it’s this system that is the biochemical key to evolution. But we can discuss this another time. For now I hope you will agree that aminoacyl tRNA Synthetase should be everyone’s favorite enzyme.

 

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My Favorite Enzyme, Part 2

Posted on December 10, 2018 by

My favorite enzyme (see previous post about enzymes in general, and why I have a favorite) has a very specific job, as all enzymes do. But my enzyme, Aminoacyl tRNA Synthetase (or Syase for convenience) has a job that is both extremely difficult and absolutely crucial to all life.

The job is to link up two chemicals that otherwise would have no chance of getting together. The sad fact is that most chemical molecules are very unreactive, and only very few sets of molecules will react with each other to form new compounds or even a complex from the two joining together. In this case, one of the molecules is an amino acid, and the other is an interesting RNA molecule called transfer RNA or tRNA. Because of the very different chemical nature of these molecules, (they belong to very different chemical families) spontaneous, uncatalyzed combination of the two would simply never happen.

As you know (or you should), there are 20 amino acids, and about 60 tRNAs, so this is an impossible job to get right for one enzyme. Luckily, it turns out my favorite enzyme is not one enzyme but a collection of 20, one for each amino acid.

To explain why there are 60 tRNAs and not 20, we need a small diversion to discuss the genetic code (and yes, it is a code!). The genetic code works  much like written language, a code we know well, does. In English, for example, meaning is assigned to words, and there are 26 letters to construct these words (which can be of any length). A word is a collection of the letter symbols in the correct order that means something different from its physical nature (which is simply a collection of shapes).

DNA operates the same way, with some important differences. First, there are only four “letters,” which are actually molecular entities, but they function as symbols. Since their importance is in their symbolism, we generally designate them by the first letter of their names, A (for adenine), C (for cytosine), G (for guanine), and T for (thymidine). The word length is constant: three letters are a code word. For example, ACC is a code word for threonine, and CAA means glutamine.

So, why three, and not four or two? Well, two-letter words would allow for 16 permutations, not enough for the 20 amino acids. Four letters would give far more possibilities than needed and would cause confusion and chaos. So three letters, which gives 64 possible arrangements, is what we have. What this means is that there are synonyms, more than one word (or codon in Biologese) for each amino acid. Thus ACA, ACG and ACT also mean threonine, and CAG also codes for glutamine. Some amino acids have as many as 6 synonyms.

I am not going to discuss the details of how the proteins are built on the ribosome (see Figure 1 and online videos), but I need to tell you that the key step in making the right protein (meaning having the right amino acids in the right order) is for each tRNA/amino acid complex to bind to the codon copied from the DNA onto a long RNA strand called messenger RNA (mRNA). Now, if you read the post on how to be a molecular biologist, you will remember that the secret is that A always and only binds to T, and C only and always to G (even though this not actually true, but see the post if you forgot why).

Syase 1

Figure 1.

The point is that the tRNA for each amino acid contains a three-letter sequence designed to perfectly bind to the codon. That sequence is the complementary sequence of the codon, called the anticodon. So for the codon ACC, the anticodon is UGG. And for CAA, the anticodon is GUU. (One little detail, in RNA we use U instead of T. Doesn’t matter why.)

Now, since there are anywhere from 1 to 6 different codons for each amino acid, there are from 1 to 6 different tRNAs for each amino acid, each with its own anticodon. And each of the 20 Sysases must be able to attach its specific amino acid to each of the different (up to 6) tRNAs that have the correct anticodon.

I should apologize for oversimplifying this whole thing. The reality is far more complicated, and you will notice that I haven’t even gotten to describe what it is that my favorite enzyme actually does. But I thought it was important to set the stage, as it were, and explain what the task it must do entails. Now that we have that all straight, I should (hopefully) get to how Syzase does its job (and if you think this is hard for you to understand, imagine how a poor senseless molecule feels!) in the very next post. I promise (sort of).

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My Favorite Enzyme

Posted on December 4, 2018 by

All enzymes are great. So by saying I have a favorite, I don’t mean to denigrate the others in any way. All enzymes are just great at what they do, and most of them simply couldn’t possibly do their jobs better than they are doing them.

Having said that, I do indeed have a favorite, and I will explain why. But first, you might be asking: what is an enzyme? Enzymes are proteins, meaning they are strings of amino acids linked in long chains. More specifically, enzymes are proteins that function as catalysts. And you know what a catalyst is, right? A catalyst is a chemical that makes a chemical reaction go faster than it would go otherwise but isn’t part of the reaction itself, so it doesn’t get used up.

Enzymes are the best catalysts known. Lots of metals can act as catalysts for chemical reactions used to make stuff, and cars have a catalytic converter that helps eliminate air pollution. But enzymes are thousands of times more efficient and more specific than any other kind of catalyst. Life could not exist at all without enzymes (or some kind of catalyst), because the chemical reactions that make life work must go on very rapidly, and without catalysis, those reactions could take hours or weeks.

Enzymes work so well as catalysts because they are large molecules that are perfectly shaped to bind to the molecules that need to react, and then they encourage, simulate, and… well, catalyze the reactions by moving the reactants closer together; by using some of the chemical properties of their amino acids; by providing energy to some reactions; and by making sure only the exactly correct chemicals react with each other (and not some closely similar chemicals).

Enzymes are so close to being perfect at their job because it’s the enzymes (mostly) that are the targets of natural selection and evolution, so after a couple of billion years of trial and error, most enzymes have become really good at what they do.

And that brings me to my favorite enzyme. My favorite enzyme has a terrible name, so let’s call it Syzase, as a nickname. Its real name is Aminoacyl tRNA Synthetase, so you see why I prefer Syzase.

Syzase is the most important enzyme in the most important biological process in evolution – and in life in general. The process is called protein synthesis or translation, and it’s the way that proteins (including all the enzymes, including Syzase itself) are synthesized. You might have already learned that the exact sequence of the amino acids in a protein (which is the critical feature that allows them to act as very specific catalysts for specific reactions) is determined by the sequence of the nucleotide bases in a gene made of DNA.

So the DNA sequence determines the amino acid sequence. That seems fine, unless you happen to know some chemistry. Because, chemically, there is no way that the nucleotides in DNA can interact with amino acids to produce a protein with a specific sequence. Amino acid chemistry and nucleic acid chemistry just don’t go together.

So how does it happen? The answer is why I love Syase. The code in the DNA sequence needs to be translated into amino acid chemistry. Translation is in fact the name of the process, and it’s probably the most complex chemical process in the universe. And my favorite enzyme, Aminoacyl tRNA Synthetase, is at the very center of the process and might even be considered the actual translator, the chemical entity that speaks two languages, nucleotidese and amino acidese, and can translate each into the other.

But this post is getting too long, so I will post the amazing details of how my beautiful, favorite enzyme does its job so spectacularly well in the next post (coming very soon, I promise).

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Replication (Part 2)

Posted on November 14, 2018 by

In a recent post I said that the replication of cells is required for evolution and the origin of modern life as we know it. While it’s true that the daughter cells of a parent dividing cell end up containing all the elements and features of the parent (assuming replication accuracy is very high, as it is in all life forms), the fact is that cells don’t actually replicate all of their components. In other words, each protein doesn’t produce a faithful copy of itself, and neither do membranes, filaments, flagella, or ribosomes. There is only one component of living cells that is replicated with high accuracy, and that is the DNA molecule. The reason that works is that DNA is not only capable of being copied almost exactly, it is also the part of the cell that is responsible for guiding the production of all the other components of the cell – all the proteins, enzymes, membranes, and cell organelles. (One exception is the energy-producing mitochondria in eukaryotes, but we won’t go there now). This means that if the DNA of the parent cell is faithfully copied, then the entire cell will be faithfully copied in the two daughter cells.

There is a scientific consensus that the modern life system of DNA replication and DNA control of the synthesis of all subsequent cellular components is so complex that it could not have been present in very early life forms. The idea that earlier life forms might have used RNA (similar to DNA) as the original replicating molecule has become known as RNA world. This RNA world is proposed to have predated our current DNA world (along with LUCA, the last universal common ancestor of all life today).

RNA can probably be copied (although the details of how this happens are not yet completely worked out. See previous post). In addition, RNA can act as a catalyst, so all the protein enzymes present in modern cells might not be needed. How RNA world turned into DNA world is a question that has not yet even been addressed.

Aside from the existence of some kind of replicator molecule like DNA or RNA (there are one or two other possible candidates), there is no known possible mechanism for a cell to replicate itself into two daughter cells that are just like the parent. This is the reason that replicator-first proponents insist that cells that have plenty of metabolism but no replicators could never evolve to produce anything like the life we know.

But even if primitive early cells had replicators that were able to manage the production of an accurate copy of the parent cell phenotype (meaning all the components and characteristics of the cell), there is a potential problem that has only rarely been addressed. That problem can be stated simply: How did the accuracy of replication become so high?

One would expect lots of errors in primitive replication systems, no matter what chemical composition they had. It’s likely that replication became more accurate over time thanks to the only biological process we know that makes things better over time – evolution. But wait, if accurate replication is required for evolution, and evolution is required for accurate replication…? We have a problem.

And that is the problem I have been working on. I will present some preliminary results in Part 3. Stay tuned.

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How to Be a Molecular Biologist

Posted on November 8, 2018 by

It’s easy. All you need to know about molecular biology is that it’s all about DNA. And you don’t need to know what that stands for, or anything else about DNA except this. It’s a really long molecule, like a chain with millions of links. Actually make that a double chain. And there are 4 different kinds of links that go by 4 different letters. Those letters are A, C, G, and T, and it doesn’t matter where they come from either. And now here is the secret to all of molecular biology: the A link on one chain always pairs up with a T link on the other chain. Always. You will not find an A opposite another A, or a C or G. Only T. Got that? You can remember it if you just think of the most important symbol these days: @. Which of course stands for “at” or in Molecular Biologese AT.

Now you might ask if A and T are always so bound up with each other, what about C and G? What do you think they are doing? Take a guess. YES, they have a thing going also, what else would they be doing? So, since A and T are always matched, so are C and G. And that, boy and girls, is all there is to molecular biology. Let’s review:

1.The A on one strand (chain) of  DNA always and only bonds to a T on the other strand.

2 The C on one strand of DNA always and only bonds to a G on the other strand.

That’s it. The rest is details. Once you know the two statements above, its easy to understand how DNA replicates, what a gene is and how it works, how genes make proteins, what a mutation is, how evolution works, and why identical twins are clones, but everybody else is genetically unique. Pretty simple, eh?

Of course, we know where the Devil lives, right? Right. Those pesky details. And there are lots of them. The peskiest of all the details in biology, the thing that drives biology grad students insane, is this: biology (and that includes molecular biology) is full of lies.

That isn’t a value judgement, or an expression of hostility – it’s the truth. Almost every statement in biology is a lie. Or more precisely, it isn’t true. This is not the case in physics or chemistry. We can say that force is equal to mass times acceleration and that is true all the time, everywhere. The volume of a gas depends on its volume and  temperature. Fact. No wiggle room.

In biology there are no such statements. Nothing you can say in biology is always true. Not even what I just told you about A and T always pairing up is true. Sometime A will form a bond with a G or a C, or even (gasp) another A. Yes, it happens, and so when I said always and only, I lied. I am after all a biologist, and we all lie all the time. (Actually, that isn’t true either.)

So how could I dare to say something that isn’t true? How can I say that A only bonds with T, when in fact sometimes it doesn’t? Shameful, I admit. So let’s rephrase. Under the vast majority of normal circumstances, A does only pair with T. But sometimes circumstances in biology are not normal. And mistakes are made. When that happens, and an A matches up with a G, or a T finds itself opposite a C, we have something called a mutation. In fact that is the definition of one kind of mutation. (In biology there are always several different kinds of everything).

Are mutations good or bad? Ha ha, what a question. Clearly if you asked that, you are not a biologist. Nothing is good or bad in biology = everything depends on something else. Mutations can be very bad; they  can lead to diseases like cancer or genetic diseases like cystic fibrosis or to increased susceptibility to a host of diseases. A mutation can make you stupider or shorter or uglier than you would otherwise be. Of course, it could also make you smarter, taller or prettier. Mutations are also essential for evolution – if there were no mutations we would still be very primitive bacteria and wouldn’t be having this conversation.

Speaking of evolution, some people sometimes ask why evolution is still a theory and not a law. A law is a statement of a scientific truth in mathematical terms. Laws can have exceptions, sometimes, but laws don’t do well in biology (there are a total of maybe three biological laws), because the number of exceptions to anything we might say about how biology works are too many to be dealt with. Too many lies, in other words. So, while a lot of people have come up with a lot (thousands, actually) of mathematical laws of evolution, none of these are all-encompassing, because none of them fit all of the various and diverse situations that apply to evolution.

Getting back to molecular biology, let’s take a look at how the basic fact of AT and GC base pairing (I might not have mentioned this. but those links named A, C, G, and T are actually called “bases”) works. When a cell is ready to divide into two cells, the DNA double strand (which is  wound around into a helix) separates into two individual strands. And then each A on one strand attracts a T, each C attracts a G, and a new strand  is built up with all the correct matching bases. Since this happens to both of the original strands, what we end up with is two double strands, each of which is identical to the original double strand. Pretty neat, eh?

When James Watson and Francis Crick solved the puzzle of the DNA structure in 1953, they realized right away that the obligatory base pairing and the double helix solved the biochemical mystery of how DNA replicates to form two perfect copies of itself. Thus the basis of inheritance was discovered.

There is more. (A lot more, actually.) The genetic code, which is the way the genes (DNA) make all the characteristics of the cell, called the phenotype (the proteins), also relies on base pairing. But that is a very long and complex story that we should save for later. For now, just practice saying AT… AT… AT. And maybe also practice a little bit of lying, if it doesn’t already come naturally. And you will be on your way to becoming a real  molecular biologist.

 

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