Replication (Part 2)

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

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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Replication (Part 1)

In the transition from chemistry to biology, many new features had to emerge from an increasingly complex chemical system. Examples include some form of membranous enclosure to allow for appropriate concentration of reactants, thus defining the borders of a living cell; the inclusion of catalysts to allow for rapid reactions; the ability to derive energy from molecular reactions and to synthesize useful chemical end products and structural components; and many more. Most of these features, while remarkable can undoubtedly arise spontaneously given a sufficiently large pool of soluble chemicals and time.

Membrane enclosed vesicles containing rapid and complex chemical reactions that will allow for such vesicles to survive for long periods (days or longer) could be considered to be living cells. This assumes we define life in the most elementary way – an enclosed cell in which chemical reactions allow for the cell to grow to a size at which it spontaneously divides in two.

But that is not the kind of life we know. All living forms on earth are indeed composed of cells that carry out extremely complex catalyzed chemical reactions, and such cells do grow and divide. But living terrestrial cells, going all the way back to the first cell from which all modern life evolved, the Last Universal Common Ancestor (LUCA), do more than that – they evolve.

The primitive protocells that I described above cannot evolve, and they will eventually die out. The reason is that the simple division of cells, whereby a cell splits in two, is not what life does. Living cells, since before LUCA, don’t just divide – they replicate. And it’s cell replication, not cell division, that allows for evolution.

Cells replicate themselves by making close to identical copies of themselves when they divide. When one cell becomes two cells, the new cells (usually called daughter cells) are close to identical to each other and to the original (parent) cell. The new cells contain the same ingredients, catalysts, subcellular systems, and all features of the original cell. Simple division of a cell into two parts cannot do this, since there is no copying mechanism to make sure that every feature of the original cell is shared by both daughter cells. With replication, however, everything within the cell is duplicated and then equally distributed in the two new daughter cells after division.

Nothing else outside of life does this. Crystals grow in ways that replicate the starting structure, but crystals do not make copies of themselves. Neither do stars or storms, galaxies or glaciers, mountains or molecules (outside of life). Nothing does.

The ability for a single cell to make a perfect or near-perfect copy of itself is the actual beginning of life as we know it. Non-replicating cells might appear to be alive, but they cannot last beyond a short time span. To become truly alive in the sense that cells can survive and reproduce for years or millennia, evolution is essential. Evolution allows primitive cells to become more stable, more fit, more able to do what they need to do in order to survive. And evolution requires actual replication, not simply division.

To see why that is true, imagine a cell that by lucky chance has incorporated a catalyst that allows it to perform a very useful chemical reaction – say, one that generates energy. The cell now has a higher fitness (defined as the probability of survival until division). When this lucky, very fit cell does divide, the chemical catalyst it found goes into one of the daughter cells, but not the other. So one of the new cells has inherited the higher fitness of the parent, but the other has not. It isn’t hard to see that as time goes by, the more fit cell becomes more and more of a minority, and while its probability of survival might be higher than its relatives’, it’s still not very high, so eventually one of the descendants of the original lucky cell containing the new catalyst will die and that’s the end of that. No evolution has taken place.

On the other hand, if the original cell had replicated the new catalyst so that both daughter cells had inherited it, then a new population of cells with higher fitness would have developed and survived to continue to improve its fitness, leading to evolution of a strong population of living cells.

So the central question of the origin of life becomes clear:
how did accurate cell replication originate?

There are some fascinating theoretical offshoots of this question, and I have started working on them using statistical modeling. There are strong implications for the origin of life, and I will explore some of them in future posts.

 

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A Goldfish Sings a Tentative Psalm

Today’s guest post is a poem by my wife (and collaborator), Aniko Albert. There is a story behind this poem related to our relationship. After reading it, you might want to take a look at an earlier post on this blog called Tank God (dated 11/19/2015). I had first posted that piece in December 2011 on a now defunct chat site called Gather.com, where I met Aniko in 2010. Aniko had written this poem a couple of months before I posted my piece, and when she saw it, she sent me the poem. We were both struck by the coincidences in the two pieces (although my piece is more snarky, and hers is more poetic, which is sort of typical of both of us). I told her that we must be cosmically connected (yes I was already very interested in her, although at that point we hadn’t met or spoken). In the following two years we became closer, exchanging emails and texts, Skyping, and to make a long story short, at the beginning of 2014 Aniko moved across the country to live with me, and we were married that summer. The best thing that ever happened to me. So besides the beauty of the poem in its own right, I have very special feelings about it, since I have always thought it was an important part of my success in finally finding the love of my life.  

A Goldfish Sings a Tentative Psalm

By Aniko Albert

 

The perfection of the universe is written around me:

bounded yet infinite space.

Light bounces back and forth

reflecting and refracting

in every direction

defining its liquid geometry.

I sway with the perfect cadence of its smooth substance,

I dance with the caressing currents of its fine-tuned laws,

I’m one with its still, self-enclosed beauty.

I lack nothing: colorful manna falls in its appointed time,

Brine shrimp and worms in their seasons.

Down I go to bury my nose in sand,

to lay in cool green glades of leaves.

Up I glide to the shining flat boundary,

where the gate to nothingness is open,

a soft, rippling surface my fin can break without effort.

I play at jumping into it, just for the thrill,

to shudder at the feel of vacuum on my skin,

to feel the sting of emptiness in my gills.

I draw a circle up there, and laugh on my way down

as the nature of things pulls me back where I belong.

On other days, when I feel like it,

I race along the curved boundary,

brushing its closed hard brilliance with my tail,

thinking about its mysteries.

Some say those images on it are illusions,

tricks of the light as its rays hit our eyes,

paradoxes we can expect at the edges of reality.

Some propose that they are our dreams,

perverse projections from our minds,

things to write poems in the sand about but not take too seriously.

But there are those who think the shadows are real:

that there’s a world on the other side,

like ours, but different,

where strange misshapen beings

with clumsy columns for fins and tails

lumber along their illogically curved paths,

obeying a force unknown to us.

Eli the Black stops me on some days

as I make my rounds,

taps an antenna against the boundary,

curls the others into a frown of gravity

and tells me his theory.

The clumsy shadow creatures, he says, are

no myth

or mirage,

but the very reason we’re here.

They’re the creators of our world,

the designers of its beauty,

the refreshers of its substance.

They provide the flakes and the worms,

they remove what’s dirty and bad

and restore goodness.

I like the story. Some days I almost believe it.

But remember the source: Eli is a Shelled One.

They are half strange themselves, aren’t they?

They spend much of their time stuck to the boundary,

Not knowing the beauties the rest of us share in.

They eat dirt,

and crawl around ungracefully

with those heavy burdens on their backs

whenever they’re not hiding those devilish faces they have.

No wonder they like to make up stories.

I smile at Eli,

the light,

the coolness,

and keep swimming.

 

 

 

 

 

 

 

 

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The Right Thing

People talk about morality a lot. Some say there are moral facts, others that moral codes are subjective and depend on culture. I have read the argument that human moral instincts are the product of evolution, or simply the collective experience of what works. Others claim that morality is of divine origin and part of the imago Dei, the image of God, in which humans were created.

This is a tough subject, almost as tough as the question of evil. And it’s primarily a problem in philosophy, although some folks have tried to make it all about science. (Of course, these are the same folks who make everything all about science.) Because it’s so hard to figure anything out about the nature of good and evil, I generally stay away from the subject. But I do have some ideas on the matter, and while probably naïve and way under the standard for philosophical discourse (I am, after all, only a mere scientist), I thought this blog would be a great place to express them – since, well, why not?

So what is my view of morality? In a nutshell, I believe that all of the statements in the first paragraph above are correct. There are moral facts and morality also depends on culture. Evolution plays a role in how people behave, and we do learn to do better on practical, empirical experience. And morality is a central aspect of our God-given human nature. The idea that any of these statements are mutually exclusive with any of the others is an example of the kind of philosophical absolutism that has become (or maybe has always been) so popular: if human nature derives from genes, then culture has no role, and vice versa. The truth, of course, is that both play a role. Another example of modern absolutism is the idea that since science tells us a lot about the world, only science can tell us anything true about everything.

But let’s get back to morality. Most humans agree with and generally follow certain moral principles, such as “it’s wrong to harm children,” and “it’s wrong to cause death or pain to another human being.” But for many other issues of moral behavior –and, in fact, for even these basic ones – different cultures can have different codes. By different cultures, I mean both different parts of the world and the same part of the world at different time periods. Causing the death of human beings used to be far more tolerated in most cultures than it is today. The death penalty was accepted as a just punishment for murder, theft, vandalism, some forms of sexual misconduct, etc. in cultures from Asia to the Middle East to Western Europe a mere 500 years ago. Slavery, a practice we all find repugnant today, was wide-spread in the ancient world and deemed not only acceptable but necessary for a functioning society. The abolition of slavery in the Mediterranean world would have been as impossible to conceive of as the enforcement of a fully vegan diet in the Western US (although no doubt some people feel the two are morally equivalent).

Did we get our moral standards from the evolution of the human brain? Or have moral values simply kept pace with the growing recognition that certain ways of acting make our lives better? As I said above, both are true to some extent. Like other primates, we are social, and genetically based instincts that act in ways that do not disrupt but reinforce group success are likely inherited from our primate forebears. And yes, it’s probably true that people have come to see that some ways of behaving toward our fellow creatures don’t really work that well. Early historical moral codes like the ten commandments are probably based on such experiences in agrarian, civilized societies.

But none of these things tell the whole story about morality and the role it plays in human interactions.  The concept of right and wrong is uniquely human. As C.S. Lewis so eloquently pointed out, arguments between people are almost always about whether somebody did or said something “wrong.” This assumes that there exists a right and a wrong. When accused of being “bad,” only a psychopath would say, “yeah, so what?” Everyone else will answer either “No, I didn’t do that,” or “Well, I did that, but I had a good excuse.” Some might argue “I did it, but it isn’t wrong to do that”. But in every case, there is tacit agreement that there is such a thing as “wrong.”

Where did humans get this idea that something exists that is morally right or not? Not from evolution. While other animals do good things or bad things, they are not aware of the existence of good or evil. They simply do what they do. They can be trained, of course, but that is a function of human definitions of good and evil, not theirs. The fact that many mammals care for their young, protect their mates, and do other things that we consider to be morally right is not relevant to the question of right and wrong.

Animals don’t do these things from a learned moral code, or because they were born with a human-like understanding of the concept of good and evil. All the individuals of a species will exhibit the same behavior, a sure sign that this is a built in, programmed result of an evolutionary based instinct or biologically determined response. The fact that human morality is largely culturally based, and not universal in time or across cultures argues strongly against a biological evolutionary mechanism. Of course, kindness toward kin and care of offspring, are not only considered moral, but are also likely originated from evolution. But how to care for one’s offspring, is not.

So where did that come from? And when did that start? We don’t know, but human beings as a species are about 250,000 years old, and there is no evidence that the human brain includes any particular genetic polymorphism linked to a concept of right and wrong. In fact, one would be hard pressed to imagine what sort of protein (which is the product of genes, after all) might have as its function making us recognize that it’s possible to be bad or good. Perhaps the answer is that morality, like so many amazingly complex non-material thought processes from mathematics and humor to sexual proclivities and literary creativity, arises from the billions of neural interactions in that incredibly complex organ, the human brain. Maybe. But that isn’t really an answer, is it? It’s a confession of ignorance.

Francis Collins tells us that one of the most compelling arguments that led him to accept Christianity was what he called the moral law. By this he means not just that people have a sense of morality, but that sometimes that moral sense can take such radical forms, as in extreme cases of self-sacrifice or altruism, that it defies logic, common sense, and a host of biological imperatives. The moral law says that we know what is right and what is wrong, and we often do the latter, for which we feel another uniquely human trait: guilt.

As a Christian, I agree with Lewis and Collins, and I see the concept of morality as something given to human beings by our Creator. The Bible presents the creation of Adam as God’s breath bringing to life of a creature made of clay.  But the moment when Adam and Eve became fully human, as we are today, was when they learned of good and evil, and in that moment also knew they had sinned.

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How I spent my summer vacation

Hello to my readers, and welcome back to the Book of Works. It has been a long, sometimes relaxing and sometime productive summer. In July, I went to the ASA annual meeting near Boston, where I gave a talk and moderated two sessions, but of course the best part (as it is with all conferences) was getting to spend some time with so many friends and colleagues in the science and Christian faith community. The highest point was hearing the talk by Francis Collins and then attending the informal sing-along he led. He is a remarkable man in so many ways.

The rest of the summer was busy with writing, teaching, and sending the last kid off to college. Finally, two weeks ago, my wife and I took off for our first-ever duo vacation. It was a somewhat unusual agenda I had planned. One of our goals was to carry clothes and other essentials to my stepson in Cambridge, so we drove. Along the way we stayed at places I had lived in or had once had family from. Nyack, NY and Winthrop, Mass were two of these places. Then from the Boston area we drove up to the mid-coast of Maine, where I used to spend the entire month of August during my first marriage in the 1980s.

I don’t usually post personal stuff on this blog, but I am going to make an exception and talk about a year that was pivotal in my life story. It was 1992, I was about to turn 45, and at a crossroads both in my marriage and in my professional scientific career. I considered myself an agnostic – I wasn’t sure about God, but I did think that there might be something beyond the materialistic view I used to have of the world. Something spiritual, something not quite explainable. But I wasn’t sure.

Near the end of our family sojourn in a cabin on the coast, I took my small (12 ft) outboard-powered boat out for a solo ride. For some reason, and for the first time, I ventured pretty far out from shore, past the islands that usually marked my limit of exploration and into a broad channel in the open Atlantic Ocean. All of a sudden I saw a dark and ominous shadow in the water right next to the boat. It was bigger than the boat and moving fast. I was terrified when, a few seconds later, I saw another one on the other side of the boat. Then one of the shadows rose and broke the surface. It was a dolphin. I slowed the boat down and began to relax. The pair of dolphins were not just playing – they were swimming next to me, then crossing in front of the boat, and soon I realized they were guiding me. They were aware I was too far out for such a small boat and were leading me back toward the shore. I followed them. Heading back in, with my wonderful escort, I began to feel not only calm but a sense of gratitude and love for these creatures of nature. After a short while, when I was back where I belonged, they disappeared, and I returned to shore in a state of wonder.

The spiritual sense that I felt from that experience on the sea stayed with me. My life changed, radically, in every way. I left my terrible marriage, moved to Italy, changed my research direction, started attending church, and so on.

A week ago, my wife and I were in Camden, Maine, not far from where I used to vacation two and a half decades ago. We signed on for a two-hour scenic cruise on a schooner. As we sailed out into the ocean, the day was gorgeous and the views spectacular. And then somebody pointed sternward. The captain turned and announced, “We are very lucky. folks. We have company.” I looked out just past the stern and there they were: two dolphins, breaking the water in plain view and putting on a small show for the passengers. But I know better. They were there for me. I had been gone for 26 years, and now I was back, a different man, and they were there once again, to give me a sign. I took it as a sign of encouragement and of affirmation.

I am still a spiritual person, but now I know that God is the source of that spiritual power. And I know that God has shown me signs of mercy and hope my whole life, even when I scorned His existence. I don’t know if I have made the right choices or lived according to His will, but I am hopeful that this sign of His favor might mean my path has not been in vain.

Thanks to all for your patience in reading this very personal account, and for your continued support of this blog. Praise God, from whom all blessings flow.

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Vacation

At this beginning of July, I want to take an opportunity to thank all those who read and comment on this blog. It has been a great three years, and I have learned a lot and enjoyed all the interactions resulting from the blog.

No, I am not ending the blog. But I am going to take a needed blog vacation for the summer. As my retirement (coincident with starting this blog) enters its 3rd year,  I have grown progressively busier. Here is a sample of what I will be doing in July:

As Editor-in-Chief, I will be finalizing the Summer issue of God and Nature, with some great content, including nine essays on two focus topics (authors include Gareth Jones, Kevin Arnold, Jim Peterson), two poems, a great photoessay by Tom Oord, and an interview. The goal is to get everything done and published by the middle of the month.

Right after that, my wife and I have committed to doing a week of Vacation Bible School at our church with a class of science experiments for kids. We did it last year, and it was great, but it takes a lot of time and effort to make sure everything works.

And then at the end of the month I am off to Boston for the annual ASA meeting, where I am presenting a paper, moderating two sessions, reporting to the Executive Council, and of course meeting and greeting many friends and colleagues.

August is a bit less intense, and my wife and I will go on a real vacation to Maine and Long Island.

So I will be back here in September, hopefully rested, and with something to say. Meanwhile, may God bless all of you, and may the summer bring you joy and happiness along with whatever else it may bring.

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