It’s all about shape

If there’s one phrase that has framed virtually all my education in biology the best, it would be “It’s all about shape.”

Probably the easiest way to think about this is with an analogy of a key and a keyhole. That’s how biological and chemical interactions occur – one thing fits into another. And so that’s the case with what researchers have done with the restoration of the activity of a particular enzyme.

The enzyme, called ALDH2, plays an important role in metabolizing alcohol and other toxins, including those created by a lack of oxygen in the wake of a heart attack. It also is involved in the metabolism of nitroglycerin, which is used to prevent chest pain (angina) caused by restricted blood flow and oxygen to the heart.

The problem is that a lot of people have a mutation in the gene which codes for this enzyme. This presents a couple of options. One is gene therapy where, in effect, a small piece of the genome (just a single gene) is altered, usually using an adeno-associated virus to introduce the correct DNA sequence into a nucleus (as happened with the spider monkeys recently cured of color blindness). This presents some problems because there isn’t a one-to-one correspondence with genes and proteins or enzymes. Alternative splicing means that a single gene can code for several different proteins. Sure, a correction may be just right for making one correct protein, but it may not also be correct for other proteins. This can result in serious side effects (though it didn’t in the spider monkeys). There are other reasons gene therapy can go awry, too, so it isn’t necessarily the best choice, however promising the field is for curing innumerable afflictions.

Then there’s the option these researchers took. Instead of messing around with anything to do with the genome, they looked at the proteome. Specifically, they looked at the enzyme ALDH2. Its mutated form doesn’t perform very well. It still works because it maintains some of its shape, but its active site does not comport to the appropriate substrates of the other molecules its trying to act upon as well as it should. So in effect, researchers took a compound (Alda-1) and injected into test subjects. In turn, this compound altered the shape of ALDH2, putting it back in proper working form.

“Because of the mutation in the gene, parts of the protein structure become loose and floppy. Alda-1 reactivates the enzyme by propping up those parts of the structure so they regain normal function,” said Dr. Hurley, director of the Center for Structural Biology on the Indiana University-Purdue University Indianapolis campus.

It’s an elegantly simple idea with a complex execution.

Incidentally, this all can be related to evolution in that if an enzyme has a given shape which catalyzes something even a little, it can be sculpted by natural selection to better catalyze that reaction, eventually getting to a relative optimum in shape.

Ted Olson

Ted Olson is one of the lawyers arguing in federal court that same-sex marriage is a right for all consenting adults. He’s long been in the middle of conservative circles, including Reagan’s administration. He has recently written a piece of Newsweek in which he makes the conservative case for gay marriage.

This procreation argument cannot be taken seriously. We do not inquire whether heterosexual couples intend to bear children, or have the capacity to have children, before we allow them to marry. We permit marriage by the elderly, by prison inmates, and by persons who have no intention of having children. What’s more, it is pernicious to think marriage should be limited to heterosexuals because of the state’s desire to promote procreation. We would surely not accept as constitutional a ban on marriage if a state were to decide, as China has done, to discourage procreation.

His final line is especially compelling. Of course, the procreation argument has long been a failure given all the people who don’t procreate, not to mention the fact that the government says nothing encouraging to the point anyway, but the comparison with China is the final nail in this long buried coffin. Give it a thought. What if, say, Montana offered tax breaks for specifically for couples with only one child? Or if Washington added a special tax for every child a couple has but the first? Would, then, a ban on marriage be acceptable? Of course not. Clearly, procreation is not the overriding factor here. It’s a lie when claimed otherwise.

Another argument, vaguer and even less persuasive, is that gay marriage somehow does harm to heterosexual marriage. I have yet to meet anyone who can explain to me what this means. In what way would allowing same-sex partners to marry diminish the marriages of heterosexual couples? Tellingly, when the judge in our case asked our opponent to identify the ways in which same-sex marriage would harm heterosexual marriage, to his credit he answered honestly: he could not think of any.

It’s obvious why he couldn’t think of any. Aside from the fact that same-sex marriage doesn’t harm heterosexual marriage, this isn’t actually an argument at all. It’s pure political rhetoric. It’s useless.

And, while our Constitution guarantees the freedom to exercise our individual religious convictions, it equally prohibits us from forcing our beliefs on others. I do not believe that our society can ever live up to the promise of equality, and the fundamental rights to life, liberty, and the pursuit of happiness, until we stop invidious discrimination on the basis of sexual orientation.

This, in truth, is the central argument against same-sex marriage. It isn’t always front and center per se; it’s often the other dishonest arguments that get put forth. But the reality is that the religious want to impose their beliefs on everyone without justification. That is part of the fundamental evil religion has always cultivated: We’re right and you’re wrong and we know it. We just know it.

These decisions have generated controversy, of course, but they are decisions of the nation’s highest court on which our clients are entitled to rely. If all citizens have a constitutional right to marry, if state laws that withdraw legal protections of gays and lesbians as a class are unconstitutional, and if private, intimate sexual conduct between persons of the same sex is protected by the Constitution, there is very little left on which opponents of same-sex marriage can rely. As Justice Antonin Scalia, who dissented in the Lawrence case, pointed out, “[W]hat [remaining] justification could there possibly be for denying the benefits of marriage to homosexual couples exercising ‘[t]he liberty protected by the Constitution’?” He is right, of course. One might agree or not with these decisions, but even Justice Scalia has acknowledged that they lead in only one direction.

Of course, it’s unlikely Scalia will abide by his own conclusion, instead making a purely political decision, when this case makes it to the Supreme Court. But, for once, he is right. There is no longer any valid legal argument* standing in the way of equality for same-sex couples.

*Key word legal. As for valid arguments based upon reason, understanding, and rationality, they’ve never actually existed.

The stupid political crap over Reid

Sen. Harry Reid recently was quoted as saying Obama’s electability comes in part from being relatively “light-skinned” and having no “Negro dialect, unless he wanted to have one”. Naturally, the political spin machines are going crazy.

One thing missing from all this is that Reid was right. His terminology was dumb, but the essence of what he was saying was correct. Obama’s skin tone and lack of identifiable accent have helped him. If he talked like Gary Coleman from back in the day, he would have been rejected rather promptly. Something similar can be said of accents from the deep south. There’s the on-the-border Fred Thompson accent that gets a pass, but the slack-jawed yokel accent would be unacceptable. Granted, that’s more a caricature than anything, but there are associations people make the more a person has an accent. How many politicians are there in England with thick cockney accents?

All that aside, this whole fiasco is being compared with the past political transgressions of Republican leaders. Trent Lott, for instance, said the country would have been better had Strong Thurmond been elected in ’48. He probably should have realized that Thurmond ran on a segregation platform, but there shouldn’t have been too much to say about his comments. It’s obvious he was trying to be nice to an old man on his birthday. Honestly, if Lott really is a racist, I think he would be either far more careful with his wording in all situations or he would have been found out much, much earlier.

Then there’s the case of Georgia Republican Rep. Lynn Westmoreland who said Obama was “uppity” during the last presidential campaign. He was roasted because the term has been used to trivialize blacks whenever they’ve argued for civil rights (sort of like “militant” gets applied to atheists who dare speak an ill word toward religion). Of course, Westmoreland claimed he had no idea what the racial connotations were of the word. I find this credible. Plenty of people didn’t know anything of the word (myself included). What’s more, it fit in with the political rhetoric of Obama being an elitist. But no one cares about truth when politics are involved.

So now there’s Reid. The GOP is calling for his resignation and just won’t shut the hell up. The talk shows are whining about Democratic hypocrisy in light of reactions to similar past Republican missteps. Okay, there’s a point there. The Democrats did put up a big political stink over a number of trivial issues. They’re politicians; we should expect as much. But don’t the Republicans agree that those past issues really were trivial? Don’t they agree (especially on the talk shows) that Lott et al shouldn’t have faced the sort of criticism they did? So why is it that two wrongs make a right? Their argument is essentially that Democrats should not be hypocrites by demonstrating that they can do something wrong once again. It’s entirely stupid and only politically motivated.

But if any Republican is interested in why more people may care about this sort of thing when they say it over when a Democrat says it, it’s obvious. The Republican party does not support policies which tend to favor minorities. There’s a strong feeling that George Bush and other Republicans really, in fact, don’t care about black people. Furthermore, Republicans aren’t necessarily going to be racists, but racists are likely to be Republicans. That’s why Democrats get more slack. They’ve tended to earn it by not having the same history as Republicans (more specifically, liberal trends don’t have the same track record as conservative trends, and Republicans are conservative and Democrats are (relatively) liberal, by and large).