Why does God hate people who have heart attacks?

Consider Hypoxia Inducible Factor, or HIF.

HIF is one of a class of proteins known as Transcription Factors which are, basically, the on/off switches for genes. In general, they bind to a specific sequence in the beginning of a gene (although, sometimes, they also bind to the end, or somewhere in the middle as well), and initiate transcription of the gene into RNA. Usually, this mRNA is subsequently translated into a polypeptide.

HIF in particular modulates the expression of hundreds of genes in every tissue. It's basically exactly what its name sounds like. It activates during times when a tissue is oxygen-scarce and initiates a series of potentially helpful responses. Among others, it initiates proliferation of capillary beds, it modulates metabolism so that less oxygen is used, and in some tissues, drives the production of red blood cells (one of the genes which is most strongly driven by HIF is erythropoietin). Then, once oxygen tension is restored, it inactivates and disappears.

As you might guess, the activity of HIF is virtually always temporary. It activates during exercise, or times when you're breathing a thin atmosphere.

In the heart, one of the genes that HIF down-regulates, or partly turns off is called SERCA. The SR/ER calcium-dependent ATP-ase. SERCA is basically an ion pump which, at the end of every contractile cycle, pumps calcium ions into a small "bag" inside every muscle cell. The overwhelming majority of the calcium ions used in cardiac contraction come from this bag. Without this calcium, contraction doesn't happen, and the strength of contraction is approximately proportional to how much calcium is contained in this bag. This, effectively, makes SERCA a "gatekeeper" protein for energy use in the heart. One of the effects of adrenaline on the heart, for instance, is to make SERCA work harder, thereby pumping more calcium ions into the reservoir.

SERCA also happens to be one of genes which is most strongly downregulated by the action of HIF. Because it is so tightly linked to energy use, it's a perfect target if the goal is to conserve energy for a brief period of time.

In most cases where Hypoxia Inducible Factor is active in the heart, this is a very, very good thing. HIF turns on for a few hours, limits the energy consumption of the heart until oxygen delivery is restored, then shuts off, and SERCA returns. In the short term, this extends the "buffer zone" in which the heart can restore oxygen tension.

In a heart attack, this is a very, very bad thing.

When an artery is occluded, HIF has no way of knowing whether the oxygen shortage is because of a blockage, or because you went for a long jog. In either case, it does exactly the same thing. It forms new capillaries. It reduces your dependence on aerobic metabolism, and it drops SERCA in order to reduce energy demands. And if you'd been out jogging, rather than suffering a heart attack, all this probably would help. In the case where an artery is occluded, especially if it's occluded far from the hypoxic tissue, growing new capillaries will do nothing to increase oxygen delivery to the heart. As a result, there's nothing to shut HIF off. It keeps working and working, trying to restore oxygen tension.

Then things start to get bad.

As hypoxia deepens, HIF effectively shuts off the production of SERCA protein, and it basically vanishes. At this point, for all practical purposes, the heart could no longer contract, even if blood flow were restored. Basically, HIF takes a bad situation, and makes it much, much worse.

There's a very simple explanation in evolutionary terms why such a detrimental mechanism would evolve. Heart attacks are, for all practical purposes, invisible to natural selection. In all but a few rare cases, heart attacks occur long after humans reach reproductive maturity. Since natural selection can only select factors which will enhance or decrease the probability that a given organism will reproduce, heart attacks are basically impossible for natural selection to act upon. However, a mechanism which allows human beings to run longer, climb higher, and survive temporarily hypoxic environments would have an obvious selection benefit. In laymans terms, natural selection would select for the benefits of HIF action, and completely ignore the detriment.

But, for the sake of argument, let's posit that an all-powerful, all-knowing, intelligent entity built the HIF pathway all at once. It is basically impossible to escape the conclusion that God deliberately designed this pathway to kill people who have heart attacks. Remember, when God put this pathway together, She knew that this mechanism would be detrimental to the millions who suffer from myocardial infarctions every year (since She's all-knowing, and all), and She built it anyway. She designed a process which would dramatically increase human suffering down the road.

So, I feel it's worth asking: why does God hate people who have heart attacks?

--Drew

An open Letter to Ray Comfort

Dear Ray,

I think you probably already have guessed that I accept evolution. It has nothing to do with my belief or non-belief in God (as you have repeatedly implied). I have no opinion on whether God exists one way or the other. Evolution is, put simply, the best explanation we have for the pattern of the diversity of life on this planet. I have spent years studying molecular biology and bioinformatics and not one piece of evidence has arisen to make me reconsider the possibility that evolution works.

In all that time, another consistency has been observed: I have yet to find one single person (yourself included) who claims that evolution is impossible, and that actually has a correct argument. And just to be absolutely, 100% clear, let me explain what I mean when I use the words "correct argument." Every single pseudoscientific argument I have ever heard you make would be wrong even if evolution turns out to be wrong. A lie is a lie.

In fact, I'll go a step further: my experience suggests that most people who actively deny the theory of evolution don't actually understand it. And without exception, all those who actually do won't be able to give any solid scientific reasons for their rejection; they just choose not to believe in it, and trust that someday some fatal flaw will be found.

Imagine how frustrating that must be. Imagine that every day, you were meeting people who were constantly telling you that they don't believe the bible because it talks about Jesus walking around New York City, a city that didn't exist when Jesus supposedly walked. It's pretty much the same thing. Someone gives you an argument against something you understand in great detail that even the most cursory examination of the documents in question could prove to be false, and presents that as if it were a valid indictment of what you accept and believe. Tell me honestly that you wouldn't find that to be frustrating after a while.

You want me to see the impossibility of evolution? Show me that the successful attempts by scientists to evolve forms of HIV without the V1 and V3 variable loops didn't work. Show me that cancer cells don't evolve new pumps to pump chemotherapeutic drugs out, thereby developing resistance to the drugs. Show me that evolution-based bioinformatic programs like rVista don't work, which they would not, if the principles they were based upon were unsound. Show me that we have more ERVs in common with an elephant than a monkey, or more in common with a monkey than a chimpanzee. Or show me that all animals have different genetic codes (ie: the same genetic code in one metazoan produces a completely different amino acid sequence in another). Show me that DNA can't mutate, or that any mammal, anywhere on the planet doesn't have its embryonic development ass-first. Show that genes are not passed from parent to offspring, or that, as creationists have often contended but never supported in any way whatsoever, there is no mutation that confers a benefit upon the organism which possesses it. And this is only the barest scratch of the surface. I could write an absurdly long post consisting only of observations which could potentially disprove the theory of evolution.

So Ray, show me the cheddar. If you have something that will outweigh all of that, and prove the impossibility of evolution I see with my own eyes and touch with my own hands every day, please, present it. I guarantee you that you will be showered with praise and prizes, as you will have made the greatest single breakthrough in science in the last half century (at least).

There's one catch though: the argument actually has to be true and correct. Sure, it means a lot of work. Years, certainly, possibly decades worth of work, but if disproving evolution were that easy, someone would have done it by now.

Until you do...well, imagine a man. This man is standing in the middle of an airport, with hundreds of planes flying overhead. He is currently talking to a group of aerospace engineers, some of whom have worked on designing actual spacecraft. And he is proudly announcing to them that his simple "common sense" argument neatly proves that heavier-than air aircraft are impossible.

Unless you can provide the evidence, Ray...you are that man.

So why are we so frustrated?

Well, to start with, it is pretty obvious, so obvious that you acknowledge it yourself, that you don't understand biochemistry and genetics too well.

Now, I cannot emphasize this enough: this is not intended to be an insult. Both of those are rather complicated subjects and require a lot of study to even develop a rudimentary understanding. I mean, to understand basic biochemistry, you need to spend at least a year of concentrated study on it and it alone. Before you even get to that point, you need at least a year of organic chemistry, and a year of basic chemistry before that. You should also understand mathematics to the point where you're comfortable with basic calculus as well. Finally, the picture won't be complete unless you take at least some physical chemistry.

That's just biochemistry. To get a good enough understanding of genetics, in addition to the aforementioned courses necessary to understand biochemistry, you need a solid grounding in molecular genetics and inheritance (a solid year each), and at least another year of population genetics to get an understanding of how all of the above applies to evolution. You should also get a decent understanding of chemical thermodynamics and nonlinear dynamics. A grasp of physical chemistry would also be a plus. This is not a matter of intelligence, there simply are that many facts to keep in mind.

I'm not, for the record, saying that you can't do it, just that you haven't. There's absolutely nothing inherently wrong with that, until you come up to someone who actually has put in the time and effort to learn all the things you haven't, and present them with a bogus argument that seems to oh-so-neatly debunk evolution, then slyly imply that they've wasted the last decade of their lives pursuing a theory that a four-year-old could see is worthless. When that argument happens to be completely without merit, as it pretty much always is, I imagine you can see why that would be frustrating.

But here you are, a person who has only some cursory knowledge of these areas. You see an argument, based on them, which claims to completely invalidate evolution. You can understand the argument, and as far as you can see, it seems to be correct.

Now, here's the $64,000 question: did it occur to you to ask yourself: "If I can understand this argument, with my very limited knowledge and understanding of biochemistry and genetics, how comes that all those people who spent a decade in school to learn those subjects, and understand these very complex subjects can't comprehend it? If it's so simple and so true, why can't they accept it?"

In short, did you ever even consider the possibility that it's actually you (and whoever fed you this oh-so-tidy disproof of evolution), and not the scientists who are wrong?

Scientists rarely accept things without checking unless they don't really care about the answer one way or the other. It's actually one of the first lessons you learn as a scientist: distrust other people's data at least twice as much as you distrust your own. Occasionally, someone will manage to pull a hoax off, some distinguished professor will manage to coast for a while on his reputation (setting aside, for the moment, that he or she generally has to make a reputation first, which always involves putting out some real work first)...but sooner or later, someone catches up with them. And the bigger the scam, the more difficult it is to hide. Every single hoax that you are oh-so-fond of trotting out and presenting as if they were somehow an indictment of the entire scientific process was found by the very scientific process, and the very scientists that they are trying oh-so-hard to indict.

In short, if evolution were wrong, it would not be accepted by scientists. Even censorship and peer pressure wouldn't be able to keep a lid on it very long. There would be uproar; there would be groups of scientists organizing themselves (and getting tons of money from religious organizations) against the "evolutionist establishment". There would be dozens of new antievolution biology journals popping up, publishing papers that show evidence of creation.

In communist countries, if you questioned the official party line, you risked jailtime, being beaten up, or just vanishing into thin air. Still (and I speak from personal experience here), at least 10% of the people in power structures opposed the establishment as best as they could. Even if you accept the most horrible horror stories about evilutionist conspiracies, you don't have anything even remotely close to this in science...and yet 99.9% of the people in the field --people who have the strongest understanding of the complexities and intricacies of the theory-- accept evolution. How is that possible? Wouldn't at least 10% resist? 5%? If evolution is so obviously wrong, why are they all supporting it?

So when you encounter the next piece of evidence that seems to oh so neatly debunk evolution - ask yourself, is it actually correct? And instead of approaching a scientist and saying "hey, this proves evolution is impossible", approach one and say "hey, I found this, is this actually true"?

You will save yourself a lot of embarrassment that way. Whether you believe it or not, most of us scientists actually know what we are doing. After all, the average life expectancy has been extended a bare minimum of 30-40 years since the early 20th century. This is largely a consequence of research performed by the very "Darwinist" scientists you claim lack even the most basic of investigative skills.

In general, the answer to just about any question you have will almost certainly be "no, that is not a problem for evolution, and your understanding of how the process works isn't correct," and in many cases, the person in question will probably be willing to explain your error to you, as many scientists are first and foremost educators, and maybe they'll succeed. But that won't teach you genetics; it will teach you that this particular argument isn't right, which won't prevent you from making some very similar errors in the future.

So, you have two broad options. First, you can trust that we know what we're talking about. The other is to check for yourself. If you choose the second one, however, you must be prepared to put in the work. I'd strongly recommend Lewin's Gene (currently in its ninth edition) along with Daniel Hartl's Essential Genetics. Both are very readable textbooks which cover their respective subjects well but at the end of the day, the chances are, you'll have to go and take classes for a few years. At the end of those years, you might have enough of an understanding of evolution to grasp why the argument you presented which oh-so-neatly debunks evolution is bogus without having someone else explain it to you.

Well, there is a third option: to believe that you understand it better then we do without having to study it, and therefore reject everything we say out of hand. But I'm kinda hoping you are too honest to do something like that.

Sincerely,
Drew

What would Hitler do?

By far, one of the most egregious claims made by creationists is that somehow the theory of evolution is responsible for the Holocaust.

Now for the purposes of this discussion, I will set aside two undeniable facts:

1) the claim is pure, unadulterated, bullshit.

and

2) it would have no effect whatsoever if Hitler had quoted Darwin in every third sentence of Mein Kampf. One very evil person's opinions do not, in themselves, constitute an argument against any given position.

I'm going to set both of these aside for the moment and ask something a little more fundamental: if, indeed, Hitler were motivated purely by Darwin's theory of evolution, does the Holocaust even make sense?

Of course, one could posit that Hitler's approach is based upon a misunderstanding of the theory of evolution, but that can hardly be blamed on the theory. So, in the interest of full disclosure, in this little thought-experiment, I will make one assumption which I'm sure will be considered reasonable: Hitler actually understood the theory of evolution beyond the typical creationist straw-man versions of it. In other words, he understood what the theory of evolution actually says, rather than what creationists say it says.

So, if one was a dictator, motivated purely by an understanding of evolution, what would one do? In short, how, as a maniacal dictator, would one go about maximizing one's evolutionary potential? Well, in order to do that, one needs to first look at nature and ask what the most successful organism on the planet is, and see if there is any way we can mimic its behaviour.

Creationists are fond of claiming that human beings are the pinnacle of evolution. We're the most successful species on the planet, according to their version of evolution. This is, by any standard pertinent to what evolution actually says, false.

By any standard pertinent to evolution, the lowly e. coli bacteria is among the most successful organisms on the planet. Bacteria in general (and yes, I know, I'm talking about a whole kingdom here, rather than a species) are now, and always have been, the dominant organisms on this planet. They kick the asses of the entire animal kingdom in terms of reproductive rate, adaptability, and number of individuals, biomass, and environments exploited. By these standards, the only standards pertinent to evolution, all of the eukaryotic branches of the tree of life combined (that includes plants, animals, sponges, anything multicellular, and absolutely every living thing you can possibly see without a microscope) cannot even come close to matching the success of the e. coli species of bacteria alone.

A dictator, familiar with what the theory of evolution actually says would know this. Such a dictator would also know that it is beyond our technical capabilities to cause the human race to revert to the prokaryotic stage.

So, given this limitation, what is a dictator to do?

Well, short of reducing the human generational time to a matter of hours, rather than years (also beyond our capabilities), the next best option would be to increase the level of biological diversity as high as you possibly can. Actually, the most sure-fire way of guaranteeing a population's extinction would be to reduce the gene pool of your populus. Since extinct populations generally don't evolve any further, it seems unlikely that a dictator familiar with what the theory of evolution actually says would take this course of action. Put simply, if Hitler were actually motivated by the theory of evolution, the absolute last thing he would ever, ever want to do is create a "master race." In fact, were he motivated by what the theory of evolution actually says, he would know a "master race" of any kind; whether black, white, fuchsia, mauve or green; should be avoided at all costs.

There are any number of ways in which the genetic diversity of a population can be maximized, and while none of them are particularly palatable options, they're certainly not what Hitler did.

First off, some form of breeding program is a must. Not to breed out specific characteristics, mind you, the way that you do with dogs. The objective here would be to create the human equivalent of a mutt. Women will have to be required to produce offspring with different men of different ethnic backgrounds. This breeding program will have to go on for generations. After 6-10 generations or so (when we're breeding mice, we generally go with 6), it will be virtually impossible to tell that you have "races" at all in your population.

Next, from any country you conquer, the population which survives the conquering process will have to be included in the above-described breeding program. For example, it would be to your benefit to make sure that the gene for sickle-cell anemia exists somewhere in your population, as this has as a benefit a near-immunity to malaria. This gene exists almost exclusively in African populations. There's also a family in Greece which has a mutation which allows them to more efficiently process low-density lipoproteins. As a consequence, they have no family history of heart attacks. In tibet, a population has a gene which allows them to survive better at higher altitudes. Since none of these exist inherently in Germany, and very few exist in the caucasian races, limiting your genetic diversity to one race is, frankly, stupid.

Like I said, this will likely have to carry on for many generations, so you'll also probably have to do something about that whole "mortality" thing.

Now, we can argue about the ethics of this approach, and I agree, I'm not terribly keen on it myself. However, I think that there's one thing we can all agree on:

It's not what Hitler did.

The retroviruses that are Endogenous

A blogger, SA Smith, phrased it in a way that, frankly, is hard for me to improve upon, so I'll just quote her:

If Darwin and Wallace had decided to open a resort in Cuba instead of going into science -- if every fossil were still hidden, then the second we found ERVs, common descent would have smacked us in the head like a sack full of doorknobs.

So, what are endogenous retroviruses (ERVs), and why is Ms. Smith so convinced that they are such powerful evidence in favor of common ancestry?

Let's start with the basics, shall we?

A retrovirus is pretty much what it sounds like. It's a virus that works backwards. Most viruses contain a double strand of DNA, locked within a protein coat, which is dumped into the cell. This double strand of DNA hijacks the cell's machinery and uses it to churn out more copies of itself. The DNA from the virus produces mRNA, the mRNA migrates to the cell's ribosomes and produces more proteins, and the DNA churns out more copies of itself. This is a massive oversimplification, and it doesn't apply to all DNA-based viruses, but for the purposes of this discussion, it's sufficient.

A retrovirus does this backwards. A retrovirus is a protein coat which contains single strands of RNA. Using an enzyme called Reverse transcriptase (also, pretty much, exactly what it sounds like), the RNA in the virus is reverse-transcribed into DNA which is then inserted in the genome of the cell they're attacking. That DNA then pumps out tons of copies of the virus, which then move on to infect other cells.

Now, these retroviruses have a very distinct genome of their own. As distinctive as a fingerprint, maybe even more so. In addition, they have a giant molecular flashing neon sign which says HERE IS WHERE A RETROVIRUS WAS INSERTED. Not literally. It's called the Long Terminal Repeat, or LTR, it's a specific type of sequence which has only ever been found in the genes encoded by retroviruses. Sandwiched between these two LTRs are the genes for the proteins that make up the virus. In other words, once a retrovirus has inserted itself into its host genome, it's easy to find, and the gene sequence in between those LTR signposts is easy to identify, and is so specific that a single virus can be identified within the genome.

Okay, so what?

Well, sometimes, not often, but sometimes, a retrovirus inserts itself into a germ cell, reverse-transcribes itself onto the genome of that germ cell, and becomes inactive. At this point, we call the retrovirus endogenous. This doesn't happen often, but it happens often enough that it's estimated that approximately 8% of the human genome is made up of remnants of ERVs, and because we have this giant molecular neon sign hanging on either side of them, they're pretty easy to nail down. So this ERV, newly dumped into a germ cell, gets passed from parent to child, and from that child to his or her children and so on. They get dumped into the genome at random points, but once they're there, they can stay in the genome, in pretty much the same place, for millions of years.

Every vertebrate species we've every looked at has ERVs, conserved so neatly that we can trace them back through the animal's ancestry, literally playing connect-the-dots by finding common ERVs between humans. Buried within the very molecules that make us, we have tiny molecular fossils which can be followed back millions of years.

So, let's look at the creationist viewpoint, and what this viewpoint would predict for ERVs. If all animals on earth were specially created, pretty much in their current form, then you'd expect all animals, including humans, to have completely different ERVs in completely different points of their respective genomes. In other words, we'd expect no commonality in the ERVs, either in location, or in species of ERV. If you looked at the human genome and found an ERV, then looked at the same locus in the Chimp genome, you would expect never to find the same ERV. The same applies for humans and Gorillas, and Humans and Orangutans. There should be absolutely no commonality between ERVs of different species.

However, if common descent is correct. If all animals share a common ancestor, then we should find commonalities between ERVs in a very specific, predictable pattern. Namely, animals which are more closely related should have more common ERVs than animals which are more distantly related. Humans should have a lot of ERVs in common with Chimpanzees, a few in common with other primates, and almost none at all with elephants. If we had none in common with Chimpanzees, or a lot in common with elephants, evolution (certainly the common ancestry of humans) would be disproved on the spot.

In other words, we can place these two predictions side by side and see how they match up with the available data. Is there no pattern whatsoever to ERVs in different animal species, or do we see this pattern predicted by common descent?

Well, guess what, the experiment has been done for humans and the other great apes eight years ago (Gene 2000 Apr 18;247(1-2):265-77). Sure enough, we share ERVs in common with all of the other great apes, and exactly as the theory of evolution predicts, we have more in common with chimpanzees, our closest living relative, than any of the others.

And it doesn't just work for humans. Other vertebrates have had their phylogenies worked out, and their relationship with other vertebrates and their ancestries worked. Time and time again, we can use ERVs to trace the lineage through a single species (for humans, for example, there are even a couple of ERVs which appear in some humans, but not all of them, indicating an extremely recent addition to the human genome), or between species. And that phylogeny can be laid neatly over the nested hierarchy that we've already constructed. This is easy to explain by a common ancestry. Actually, it's kinda hard to explain it any other way, but I'm willing to let the creationists try.

So by all means, what's the creationist explanation for Endogenous Retroviruses, and what evidence can you bring to bear to support that explanation?

Please allow me to introduce myself...

I think it's worth explaining where I got the title for this blog. Something, historically, that scientists have not done well is making what we do cool. We're just not that good at explaining what we do to the proportion of the population that doesn't read scientific journals every day. It's hard for us to connect with the layman and explain to them why what we do is interesting, and perhaps more importantly, why it's important.

One of the great exceptions to that rule is the late, dearly missed, Carl Sagan. Sagan was one of the great popularizers of science. He had a gift to reach out to audiences of all faiths and backgrounds and talk about the wonder he felt when he looked at the universe.

One of my favorite quotes of his is this one:

How is it that hardly any major religion has looked at science and concluded, 'This is better than we thought! The Universe is much bigger than our prophets said, grander, more subtle, more elegant?' Instead they say, 'No, no, no! My god is a little god, and I want him to stay that way'

As he did so often, Sagan summarized what I have always felt about the way creationists approach the universe in one two sentences. Worse than that, creationists seem to feel that because I accept the theory of evolution I either view mankind as a worthless animal, or I view life as meaningless.

Respectfully, if people truly believe that that's what evolution says, they're full of shit.

The number of individual beings which could be standing here in your place vastly outnumber all the grains of sand, on all the beaches, in all the world. You're the inheritor of a genetic legacy which stretches back 3.8 billion years through the eons, and which has circled the center of our galaxy about 20 times. You're the endpoint of billions of generations of births, competitions, wars and deaths, the only possible sequence of hereditary combinations that can possibly result in you. Your forbears have survived arguably the single greatest ecological catastrophe ever to hit the planet, when the earliest plants started poisoning the atmosphere with oxygen. Yet, your ancestors learned to use this poisonous gas to produce energy in a way that had never been attempted before; an evolutionary triumph which paved the way for the first multicellular life. Your genetic line has survived floods, freezes and meteor impacts from the skies themselves, preserving this single genetic line through the eons to lend ultimately to you. This is a legacy you share with every living thing on earth, from the largest creature ever to have lived; the blue whale, to the lowlies prion. You share this legacy with the blades of grass between your toes and the trees that gave you shade. You are a thread in a huge, amazing, incredibly diverse tapestry of living things; some of whom have clawed their way our of the seas to survive on land, some of whom remained in the ocean and a few of whom stood on land for a few million years, ultimately said "well, screw this" and marched back into the sea. Once we add cosmology into the mix, not only does this legacy stretch to everything living, but to the non living as well. You share your origins with the stars and planets. The asteroids which hang in space, all the way down to the loneliest hydrogen atom in deep space. All the parts that make you stretch back through the eons and have borne witness to the very birth of the universe. They have seen the birth and death of stars, supernovae, black holes and pulsars. They've seen planets torn to pieces and solar systems form. They've seen galaxies coalesce and skies darken.

The universe is much more grand, more amazing, more beautiful, more elegant and more subtle than has ever been written in any holy book, and you are here, against nigh-incalculable odds to see it all. Just consider that for a moment.

If acceptance of the theory of evolution, or of cosmology, is a sign of low self-esteem, what the hell are the standards for a high one!?