Ultra-sensitive microscope reveals DNA processes

    * 14:02 15 November 2005
    * NewScientist.com news service
    * Gaia Vince

A new microscope sensitive enough to track the real-time motion of a single protein, right down to the scale of its individual atoms, has revealed how genes are copied from DNA – a process essential to life.

The novel device allows users to achieve the highest-resolution measurements ever, equivalent to the diameter of a single hydrogen atom, says Steven Block, who designed it with colleagues at Stanford University in California.

Block was able to use the microscope to track a molecule of DNA from an E.coli bacterium, settling a long-standing scientific debate about the precise method in which genetic material is copied for use.

The molecular double-helix of DNA resembles a twisted ladder consisting of two strands connected by “rungs” called bases. The bases, which are known by the abbreviations A, T, G and C, encode genetic information, and the sequence in which they appear “spell out” different genes.

Every time a new protein is made, the genetic information for that protein must first be transcribed from its DNA blueprint. The transcriber, an enzyme called RNA polymerase (RNAP), latches on to the DNA ladder and pulls a small section apart lengthwise. As it works its way down the section of DNA, RNAP copies the sequence of bases and builds a complementary strand of RNA – the first step in a new protein.

“For years, people have known that RNA is made up one base at a time,” Block says. “But that has left open the question of whether the RNAP enzyme actually climbs up the DNA ladder one rung at a time, or does it move instead in chunks – for example, does it add three bases, then jump along and add another three bases.

In order to settle the question, the researchers designed equipment that was able to very accurately monitor the movements of a single DNA molecule.

Block chemically bonded one end of the DNA length to a glass bead. The bead was just 1 micrometre across, a thousand times the length of the DNA molecule and, crucially, a billion times its volume. He then bonded the RNAP enzyme to another bead. Both beads were placed in a watery substrate on a microscope slide.

Using mirrors, he then focused two infrared laser beams down onto each bead. Because the glass bead was in water, there was a refractive (optical density) difference between the glass and water, which caused the laser to bend and focus the light so that Block knew exactly where each bead was.

But in dealing with such small objects, he could not afford any of the normal wobbles in the light that occur when the photons have to pass through different densities of air at differing temperatures. So, he encased the whole microscope in a box containing helium. Helium has a very low refractive index so, even if temperature fluctuations occurred, the effect would be too small to matter.

The group then manipulated one of the glass beads until the RNAP latched on to a rung on the DNA molecule. As the enzyme moved along the bases, it tugged the glass bead it was bonded too, moving the two beads toward each together. The RNAP jerked along the DNA, pausing between jerks to churn out RNA transcribed bases. It was by precisely measuring the lengths of the jerks that Block determined how many bases it transcribed each time.

“The RNAP climbs the DNA ladder one base pair at a time – that is probably the right answer,” he says.

“It’s a very neat system – amazing to be able see molecular details and work out how DNA is transcribed for the first time,” said Justin Molloy, who has pioneered similar work at the National Institute for Medical Research, London. “It’s pretty incredible. You would never have believed it could be possible 10 years ago.”

"You would never have believed it could be possible 10 years ago.”

Amazing what a little curiosity can bring about.

"The more we learn about the microscopic world, the less likely it seems that non-physical (or non-mathematical) principles are needed to explain its behavior."

I do think that you're jumping the gun a bit with that statement, at least as it pertains to this experiment. There are elements of this that are clearly influenced far beyond the natural situation. First, the glass beads must have some effect on the mechanics of the transcription, so who knows yet whether the one pair selection is natural or the result of taxing the net available energy beyond the limit. Second, until you can identify the exact chemical process that causes the increment of selection, it is a bit presumptive to assert that you know what is or is not needed to explain it.

" Perhaps an ID'er would suggest that a higher intelligence designed the chemical structure of RNA to do just what it does. That may or may not be, but, clearly, it's not an hypothesis of empirical science. As a consequence, prolonged examination of such a hypothesis—as if it were a scientific hypothesis—has absolutely no place in a science classroom."

I would say that if you mean only with regard to real-world biological processes such as in the above experiment, I fully agree; it's not relevant to what is being observed (or if it is relevant, there is no observable way of detecting that relevance) but the same has to be said of evolution by the same logic.

Oh? Are you God, then? Are the folks who produce my son's insulin, God? [blah blah blah]

Either you did not read the post, or you dishonestly (yes, that word) forgot to include the very next sentence. Let me help you with that: it was "Of course not."

So the full phrase, is: Oh? Are you God, then? Are the folks who produce my son's insulin, God? Of course not. (emphasis mine)

The extra sentence rather changes the meaning of my comment, doesn't it? Unfortunately, your history on this thread leads me to suggest once again that you did not make an honest mistake in your selection of quotes.

Oh, for pete's sake...

Anyone interested in actually understanding the context of the comment should go back and read the conversation from which my comment came. It was a discussion about whether "supernatural" is a necessary part of an ID hypothesis -- which it clearly is not. The context of my comment is important to its interpretation. Your failure to include (or perhaps even to understand) the context led you to make an irrelevant but typically uncivil response.

This comment was made in a post ADDRESSED TO YOU, and you HAVE ALREADY RESPONDED TO IT, so you can hardly pretend that you didn't see it. [snippet moved for clarity of presentation]

Alas, I confess that I responded to a different (and obnoxious) part of your post, and never got beyond that. Truly I had not seen those particular comments before now. My apologies. So we'll address them now.

Yawn -- yet another dishonest straw man. Look, son, no one has ever denied that "intelligent design" as a *process* works. That would be immensely stupid, which is a) why no one ever makes that claim, and b) why it's immensely stupid *and* dishonest for you to try to imply that we ever had.

OK, so it works as a process, and it would be "immensely stupid" to dismiss it as a process, and, as we've since seen, this point is crucial in showing that "supernatural" is not a necessary ingredient in an ID hypothesis ... but for some reason it's an invalid hypothesis? That is a discussion I've been attempting to have with you on this thread, so the fact that I didn't respond to this particular iteration is not important.

Instead, as we are quite clear to anyone with working reading comprehension (admittedly, this leaves out a lot of "IDers"), is that the "Intelligent Design postulate" (as held by the Intelligent Design movement) which hypothesizes that there was "design" in the formation of life as we know it is, in its current state, utterly unscientific and untestable.

Three points on this.

First, if your selection of quotes is not actively dishonest, then one must conclude that your own reading comprehension is substandard at best. Either way you should leave out the insults, lest you be branded a hypocrite.

Second, you and I discussed a specific claim made by Behe, and I suggested a test by which that particular claim could be falsified. "Falsifiable tests" is the one consistent claim made by ID opponents, and I've suggested one. Clearly that specific claim is not "untestable," at least in the abstract.

Finally, in our discussion of that test, a very interesting question came up: has the claim that flagella evolved ever been tested? Perhaps such a test has been done -- but you seem not to have actually heard of one, and neither have I.

For some reason, whenever we talk about THAT movement and its positions, *YOU* want to keep blathering on about the fact that people can design things.

I've never denied that people such as the fellow you quoted exist. I don't agree with them, so I've also never expended any effort defending their wilder claims. If you go back on this thread, you'll notice that I generally try to limit my remarks to looking at the scientific basis of your position, and I try to push in the other direction to see if there's any rational reason to oppose an ID hypothesis on logical or scientific grounds. To date I have learned that you, personally, are not able to present a consistent, logical objection to an ID hypothesis, but that you are very good at insults, derision, and the dishonest use of quotes. I cannot help thinking that your unpleasant approach to what could be a civil discussion is due at least in part to personal biases, and not a pure and simple devotion to science.

"On the contrary, it is scientifically accurate to say all matter is ordered and genrrally behaves consistently with established physical laws. It may also be scientifically accurate to say God is responsible for it all. Science is free to explore the matter. Brain-tied ideologues are not.

For some definition of science perhaps, but not the definition scientists use. The supernatural, or God in your parlance, is untestable, unverifiable, unfalsifiable, and is therefore not science. If you want to believe in God and his hand in the creation of the universe and natural laws that fine, but it is not science. Because of the way science is done, there needs to be a way to rule out some hypotheses otherwise all hypotheses, no matter how loony (I'm not talking about religion here), have the same value. If you truly believe there is a way to scientifically investigate nature while not testing your hypotheses, please explain the methodology.

Making the assumption that everything is the result of God's design may be a valid world view but it is not science.

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