Spit and adenosine triphosphate

How is it you can drink saliva all day long and never run out of the stuff?

Sorry to put the image of spit-drinking in your mind, but you’re doing it right now, am I right? And the more you think about it, the more you do it. Before today is over, you’ll have swallowed more than one vice-president of the stuff. Here’s how I figure it: a healthy human (that’s you) consumes something like a liter of spit per day. That would fill up a typical pitcher, and John Nance Garner, who was vice president under Franklin Roosevelt, once remarked that his job was “not worth a pitcher of warm spit.” So the vice-president, as a unit of saliva volume, is therefore less than your daily output. This reminds me of the names of champagne bottle sizes. The larger sizes are named after rulers of Israel and Babylon. So a double magnum, or three liters of champagne, is known as a Jeroboam (the first king of northern Israel). By extension we might measure salivary volume in terms various legislative occupations. How much is a Speaker of spit? Or a House Minority Whip of spit?

But I digress.

My point is that your body is a collection of remarkably dynamic processes that give the illusion of stasis. And the thing that got me started on this line of thought was this sentence:

In order to provide energy to sustain our lives, every day, each one us produces a quantity of ATP by this mechanism that is approximately equal to our body weights.

Yikes! That’s an astonishing amount of flux for one single molecule. Do you want to see how (most of) this ATP is made? Look at this.

The quote and the image come to us courtesy of the Mitochondrial Biology Unit at Cambridge University. We’ve known for a long time where the ATP was being synthesized. But now we know the shape of all the insane molecules that do that work. The ATP mill you’re looking at here isn’t something exotic. Your body has enough of them to pump out a pound of ATP every ten minutes or so, one molecule at a time. And that is a spitload of ATP.

Molecular biology cinema

Hey, so I totally scooped the New York Times with my post last week about animation and molecular biology. Only two days ago they came out with this article: Molecular Animation – Where Cinema and Biology Meet. I’m sure they were peeved about my piece, and they probably rushed theirs into production as a result, but it’s a nice article.

It’s accompanied by this video, which I would embed here, but it appears they don’t permit that.

Cell Size and Scale

In a Zoomable User Interface (ZUI), you can move up and down the scale of a spatial dimension easily. This feels very natural when you’re zooming through something that you have some physical intuition about, like a picture of the inauguration, or a map of the planet. It can be very disorienting when you’re zooming through an abstract space.

Here’s an especially nice example of where it can work well: Cell Size and Scale.

It’s always eye-opening to see how tiny cells are, and then to see how tiny (most) bacteria are relative to eukaryotic cells. Consider: you couldn’t cram one of your chromosomes into an empty E. coli shell if you used a spatula and two shoehorns. I don’t know if I’m more impressed with my size or E. coli’s minuteness.

Evolution and geology

I just finished reading Sean Carroll’s book The Making of the Fittest. Subtitled “DNA and the Ultimate Forensic Record of Evolution”, it’s the follow-on book to Endless Forms Most Beautiful. In this book Carroll devotes several chapters to demonstrating how, against our natural intuition, there really is enough time (given a few hundred million years) for DNA to mutate bit by bit and still make amazing new structures like eyeballs, wings, and that pink dangly thing that hangs at the back of your mouth.

Carroll also points out that while almost everything is in flux, genetically speaking, there are some stretches of DNA so crucial to life that they never change. Which is to say, they can’t change because any variation would be fatal. Here, for example, is a six amino acid stretch that has been found in every single living thing: KNMITG. It’s an immortal sequence, unvarying across more than a billion years.

The last chapter deals with the controversies associated with teaching evolutionary theory in public schools. This is well-traveled ground, but it got me thinking about how much the opponents of evolution focus on man, monkeys, and biology class. But shouldn’t they be attacking geology too? Some of them do, insisting, for example, that the Grand Canyon formed during Noah’s flood. But it seems that a serious and consistent creationist ought to stick those little “this is only a theory” labels in every science book on the shelf. The astronomy book, the geology book, the physics book, they should all be thrown out the window along with The Origin of Species. Why is poor old Darwin always taking the heat?

Funny gene names

Do you suppose, if your house was knocked over by Hurricane Fifi, that you might feel more slighted than if the same damage had been done by a storm with a more muscular name? Generals have long understood the value of giving their military operations intimidating names like Rolling Thunder and Urgent Fury. If you have a rare disease, it can be a source of perverse comfort to know that it is named after a pair of stern and bespectacled Old World doctors like Creutzfeldt and Jakob or Kugelberger and Welander.

But geneticists and molecular biologists have a couple of strikes against them when it comes to naming genes. First of all, they tend to name genes for what happens when the gene doesn’t work, which ends up making a critical functionality sound like a problem. Thus eyeless helps make eyes. The other problem is that it never occurred to them that the silly inside-joke names they gave to their fruitfly genes would have such straightforward parallels in humans. As it says in the NY Times article ‘Sonic Hedgehog’ Sounded Funny, at First:

It’s a cute name when you have stupid flies and you call it a ‘turnip.’ … When it’s linked to development in humans, it’s not so cute any more.

I came across a link to the Times article because of an entertaining blog post from the bioinformaticist Nick Saunders: What’s in a (gene) name? . You never know when a name is going to matter.

The year of the personal genome

Want to buy a slightly used genome?

Back in 2000, Craig Venter and Francis Collins (and Bill Clinton) announced the completion of “the” human genome. Not to take anything away from that achievement, but genomes are just as varied as humans. Whose genome was the human genome? Or to come at it from another direction: if they popped that first draft genome into a baby printer, who would it come out looking like? The Celera version would probably look an awful lot like Craig Venter, because he just couldn’t stop himself from secretly “volunteering” his own DNA to the project.

More recently, Venter gave up any pretense of secrecy and published the most thorough human genome to date: both sets of 23 chromosomes for… Craig Venter. And not only that, it’s published on PLoS Biology, so you can go inspect every nucleotide. Or you can just print out this poster for your room. Think of it as a pin-up for the bio-geek set (I see London, I see France, I see someone’s 16 base pair non-genic heterozygous indel).

So old Craig gets to see all of his genes. Do you want to see yours? If so, you’re in luck, because, as noted in Technology Review, several new companies have set up to service your genomic needs. While you can’t get the royal (i.e. accurate and thorough) treatment that Venter and James Watson get, you can do pretty well.

23andMe, DeCodeMe, and Navigenics all will take something like $1000 from you and send you a bunch of genomic data. As many have observed, the exact value of the data is a sketchy. You may learn some things that will do little more than make you anxious.

Even so, I suspect these services will be a commercial success. There is a desire to know what cards you’ve been dealt that somehow trumps any rational medical value. When it really comes down to it, knowing about your personal DNA is almost more of an aesthetic experience than anything else. So it makes sense that there’s a company that can turn your DNA into art. That may be the most reasonable thing to do with your genes, at least for now. Hang them in your living room.

The best proof I’ve seen that biology is going mainstream is this ad for a PCR machine. Check out the insanely high production values on this video that’s peddling a piece of lab equipment for the white coat crowd. Amazing.

Cellular pornography

We live in some kind of golden age of microscopy. In the old days, people relied on stains that made cells look like this.


Useful, but not too pretty. It kills the cells too, but more to the point, no matter how useful it is, a picture like this is never going to land you on the cover of Science or secure your next grant. Not anymore. Why? Because the bar has gone way way up. This is what cellular imaging looks like now.


Va-va-va-voom! It’s like some kind of crazy Post-Impressionist fruit bowl on black velvet. That picture has my vote in the 2008 presidential election.

If you want to see some racy, juicy-looking cellular images, look at the winners of the latest Olympus BioScapes Digital Imaging Competition. The honorable mentions are just as good. Look, for example, at this brainbow image and keep in mind that individual brain cells have been genetically induced to color themselves distinctly. Not only are they able to live in this state, you simply couldn’t get this kind of cell-by-cell contrast with the old heavy-handed staining approach. As a result, you can draw maps of the interconnections of individual brain cells.

I know the colors are all pumped up with computer graphics, but still, look at those pictures. I am simultaneously impressed with the image-making capability and the thing being imaged. Leeuwenhoek would be proud.

Grove: I can Moore’s Law. Why can’t you?

I came across this Andy Grove interview in Newsweek in which he is complaining bitterly about the pharmaceutical industry. The piece begins with the statement that during the time that former CEO Grove spent at Intel, “the number of transistors on a chip went from about 1,000 to almost 10 billion.” And I thought to myself: Uh-oh. You don’t suppose he’s going to compare semiconductor manufacture to the molecular biology of pharmaceuticals?

Yes he is. It happens that he suffers from Parkinson’s disease, and he’s baffled and angered that no new therapies have been launched in the last ten years. He goes on from there to point out the many ways that the drug industry is stupider than the chip industry. All that’s missing is a man-on-the-moon quote, as in: “This country can put a man on the moon, but gosh darn it, we still can’t cure genital herpes” etc. etc. What we need is more managerial kick-ass and less regulatory kiss-ass. And so on.

One of the nice things about living in the Age of Blogs is that I immediately knew that bio-pharma insider Derek Lowe, over at In the Pipeline, would have something fun to say about this. He did: Andy Grove: Rich, Famous, Smart and Wrong. Lowe embellishes the obvious. Grove is being manifestly unfair for a variety of reasons. Pentium bugs, for example, are embarrassing but not lethal. Nevertheless, there is something useful in having an outsider beat up your industry. At the very least it prevents you from being complacent. And I happen to think that in the last paragraph of the Newsweek piece, Grove hits on an important point that Lowe chooses not to rebut:

The peer review system in grant making and in academic advancement has the major disadvantage of creating conformity of thoughts and values. It’s a modern equivalent of a Middle Ages guild, where you have to sing a particular way to get grants, promotions and tenure.

Some of the comments on Lowe’s blog pick up on this, but most just pile on the anti-Grove bandwagon (see the Newsweeks comments for a remarkable contrast). Clearly Grove has touched a nerve, but the fact that this discussion is happening at all indicates something fun is happening. Like it or not, pharmaceutical research is being dragged out into the sunlight. The public, including former CEOs of Fortune 500 companies, has some foolish misconceptions to get past. But they’ll also bring some fresh air with them.

A letter to the American Chestnut Foundation

One of the last healthy American chestnut trees

Among the last of a proud breed, this Castanea dentata, or American chestnut, stands alone in a Kentucky field. It is one of the very few mature flowering chestnuts that has so far eluded the fungal disease known as chestnut blight. What you see in the picture is a tree so valuable that it is hand-pollinated by a botanist in a cherry picker. The botanist in the bucket is doing what he can to resurrect the old tree for posterity. I wish him luck.

When it comes to endangered species, the American chestnut is the botanical version of charismatic megafauna. Charismatic megafauna, those large and tragic beautiful animals like lions and gorillas, are the spokesmodels of extinction threat. The Tecopa pupfish can leave the stage unnoticed, but we can’t help but empathize with the plight of the Siberian tiger. Equally tragic and majestic is the mighty American chestnut. Call it charismatic megaflora. At one time it dominated the old-growth forest canopy in the Appalachians. And in a single generation it was gone. Or very nearly so.

The American Chestnut Foundation is dedicated to bringing back a blight-resistant version of the chestnut. As part of their campaign, ACF publications director Jeanne Coleman asked for letters from people who grew up in the shadow of the old chestnuts, people who can testify to what the trees looked like in their prime. My father is one of those people. And he sent Jeanne Coleman a letter. But Jeanne Coleman never wrote back.

So, as a public service on behalf of my father and his trees, I am posting the letter.

American Chestnut Foundation
P. O. Box 4044 Bennington, VT 05201

Dear Ms. Coleman,

In the late 1920’s and the early 1930’s I lived in a village, Crozet, at the foot of the mountains north of Charlottesville, Va. The mountains were beautifully green with great chestnut trees that marked our seasons.

In the autumn we waited for the excitement of the first frost and opening of the bur. Trips up the mountain brought home baskets of chestnuts that had that distinctive sweet firmness that lingers in memory. The fun and the flavor mingled.

This was especially true with the smaller chinquapins. I could collect a pocket full on my way to school and have a days worth of good eating as well as a supply of missiles that bedeviled the girls.

Of course those days preceded anyone’s idea of air conditioning other than a breeze through an open window. I would sleep with my head close to the window and enjoyed the panorama of the mountain. It was a great shock to see a line of brown moving day by day across the mountain. The concept of the blight was difficult for a boy to grasp and it took a considerable period of time for me to understand the inexorable march of destruction I was witnessing. I could not believe our chestnut trees would not come back.

My feelings were mixed in a way that a boy has difficulty expressing. They were a mixture of disbelief and vague grief that persist to this day. Mixed with this of course was that gift of the human spirit, hope.

I celebrate the persistent energy of the American Chestnut Foundation. I anticipate the day when my nostalgia blends into warm pleasure at your success—and the blacksmith can enjoy the shade.

Very truly yours,
Marcus M. Gulley, MD

As a footnote to this letter, I observe that the ACF describes in their FAQ two weevils that attack the chestnut. They are known as the “lesser” and the “greater”. To think, with that setup, that they attempt no joke about the lesser of two weevils… Oh the humanity! First they scorn my father’s letter, and then they forbear to use a perfect weevil-related punchline. Truly they are squandering riches.

Ignite Boston and bioscreencast.com

I gave a talk at the second O’Reilly Ignite Boston event tonight, and I was lucky enough to meet Hari Jayaram who was also there to present. Hari is a crystallographer at Brandeis with several Protein Data Bank entries under his belt, including the notorious coronavirus nucleocapsid of SARS fame. Along with several other friends, he is busy creating bioscreencast.com. The site was the topic of his talk. Like JoVE and SciVee, bioscreencast aims to remedy the dreadful dearth of practical advice and information faced by working biologists. For example, how do you use BLAST at NCBI to look for homologous proteins? You could waste a lot of time screwing around on the site, or you could just let Hari tell you.

The Navy discovered that kids who spent a lot of time playing flight simulator games were better prepared to learn to fly. I wonder if, in a few years, freshman biology students will arrive on campus knowing all their protocols by heart because they spent so many hours watching bioscreencast.com videos and paging through OpenWetWare.