La Cucaracha

Factoid for the day: cockroaches seem to have been morphologically stable since the Carboniferous, i.e. over the last 290 to 354 million years.

Modern cockroaches are more similar to their ancient fossil ancestors than any other extant insect - except they are a lot smaller. Some cockroaches from the Permian (about 250 million years ago) were over a foot long. Wouldn't want to step on that at night - it would go like a skateboard!

I haven't seen it in the movies, but most ships in history have had very serious cockroach problems because of the lack of predators. Captain Bligh had the Bounty doused with boiling water to deal with this. We have a cockroach problem at the South Pole's Scott Base in Antarctica for the same reason.

They were among the few creatures to make it through an ancient disaster event called the Permian-Triassic boundary, where 90% to 95% of marine species went extinct, as well as 70% of all land organisms. On an individual level, perhaps as many as 99.5% of separate organisms died as a result of the event. But cockroaches made it.

Other things that made it through and became more important as a result: mosses and worts, therapsids (where we come from), and bivalves.

Seeds from Isla Sorna:

Today's quandary -

E-mail from a highly respected medical center that wants to start a project on protein/peptide sequencing of various samples, all from previously unsequenced species. All results would be compared with the publicly available sequences to determine the relatedness to what has already been done (several hundred species), and then contributed to this same dataset so that other groups doing this sort of thing can compare with these sequences (building a library).

The catch? The samples are from a dinosaur. A T. Rex. You know, the fellow from Jurassic Park.

As I have posted before, the organic material is there in their thighbones - yes, somewhat degraded, but it is there. Note that this is not genetic sequencing - we are one level of abstraction away from the dino-DNA since these are proteins. However, this will be good enough to give a numerical level of confidence in saying T. Rex is more like a chicken than a crocodile (or otherwise).

So, readers, do I start the ball rolling on this, eventually leading to the destruction of downtown San Diego by a rampaging dinosaur?

Schweitzer, Weiner, Lowenstam, and a T-rex named Sue:

You have probably heard about the recent discovery that scientist Mary Schweitzer made: soft tissue preserved inside a dinosaur bone. It was interesting to see the media frenzy that occurred - just about every major source carried the story. The trigger, of course, being the Jurassic Park aspects of it all: after de-mineralizing a 68 million year old T. rex bone, Dr. Schweitzer found pliable material, some tubular, with dark red to brown spheres enclosed. Both the pliable tube walls and the spheres had smaller, darker central portions. The immediate interpretation by the media was veins and red blood cells with nuclei, and of course from there it was a quick jump to dino-DNA.

There are some parts to the March 25 Science article ("Soft-Tissue Vessels and Cellular Preservation in Tyrannosaurus rex," Mary H. Schweitzer, Jennifer L. Wittmeyer, John R. Horner, and Jan K. Toporski Science 307: 1952-1955; doi 10.1126/science.1108397; abstract) that the media did not choose to follow, but which I found interesting. Perhaps you will too.

My first question was 'what did her team de-mineralize the fossils with?' It turns out they used 0.5 M ethylenediaminetetraacetic acid, more commonly known as EDTA. I laughed, since EDTA is used as a food preservative, metal sequestrant and stabilizer in a lot of things we eat - check out the ingredients for many MacDonald's items (and since EDTA is used to chelate metals, it is often used in canning, as well as a poisoning antidote, and there is active debate about EDTA chelation therapy - but that's a whole 'nother subject...). In any case, it's currently thought to be safe to eat, and at the concentrations used in foods, it will not de-mineralize your bones and turn you into a quivering blob of collagen.

The next piece that the media did not pursue was the link to the T. rex nicknamed "Sue," the most complete T. rex ever found (~90% complete). Dr. Schweitzer's team used the same technique on specimens from several dinosaur fossils, including pieces of "Sue," to try and duplicate their results from the T. rex dug up in 2003 (and lo and behold, pliable material was found in the others, too! There were some really nasty lawsuits over the ownership of "Sue," and the fossil ended up on the auction block. The science of paleontology was at risk of losing this valuable find to a private collector, but luckily McDonald's, Disney, the Cal State system and several private individuals put up over 7 million dollars, and "Sue" ended up at the Field Museum of Natural History in Chicago as specimen FMNH-PR-2081).

I thought the pictures that the media chose to use were odd, because they didn't show off the part of the story that they emphasized in their text. Here is the picture I saw used in almost all of the media (used w/ permission of Science):


MOR-1125 endosteal tissue 

Here the arrows indicate the flexible, fibrous, even 'stretchy' material left after de-mineralization - sure, it looks like a piece of meat with gristle, but the media's main focus was the blood cells and the nuclei, and these photos certainly don't show those.

So here is a set of four pictures, also used with permission from Science, that illustrate how startlingly good the preservation is in these samples, and that you probably did not see in the paper or on TV. Schweitzer was particularly careful to avoid calling these things 'capillaries,' 'nuclei,' 'organelles,' or even 'cells.' And I will be too. More on that later.

1) This is a shot of an area about 2 mm across, showing the structure of the interior of the femur on the T. rex MOR-555, from the Museum of the Rockies, also known as the "Wankel rex" after its discoverer. I don't know how often you dine on meat with the bone in it, and if you ever pick at marrow within that, but this texture is absolutely identifiable as bone interior:

Wankel endosteal bone surface 

2) This is a photomicrograph of the Wankel rex again, showing tubular structures about 50 micrometers across, with the enclosed darker spheres. I'd love to have a medical student look at this without knowing what it was, just to hear what they said:

Wankel vessel 

3) This is a shot of a piece from "Sue," showing the same type of micro-structures:

FMNH-PR-2081 

Note that you can see darker centres to some of the red spheres in both of the above photomicrographs.

4) Here is a shot of a microstructure from the 2003 juvenile T. rex, MOR-1125, which shows internal structure, as well as thin extensions protruding from the main body:

MOR-1125 

This looks very much like an osteoblast or osteocyte, or a bone-producing cell, from any modern animal. The extensions are known as filipodia and they fit into thin channels called canaliculi that allow the cells to pass information and nutrients through the dense calcium phosphate (apatite) bone matrix (here is a slide showing osteocytes in place from a fossil theropod's toe!). While osteocytes have been seen before in fossils, we had never seen internal structure. The microstructures inside the 'osteocyte' in the picture above are interpreted as the remnants of cellular organelles. Schweitzer's team also found microstructures in the other two T. rexes and the hadrosaur Brachylophosaurus MOR-794 that looked very much like osteocytes. Immunoassay tests done against the materials from the first T. rex, MOR-1125, indicate that proteins from the original bone are highly likely to be present.

We do not know as much about what fossilization does and does not destroy as we thought we did. What Schweitzer's current work shows is that there are certain levels of physical microstructure that are preserved that we did not think were possible. Not much has yet been published about the possible preservation of the biochemical microstructure inside these things, which is where the holy grail of dino-DNA lies (but more on that later). It is slowly becoming clear that fossilization can preserve some very odd things - shapes of things certainly, like bones (even delicate ones in embryos), but also the overall shapes of soft tissues, like feathers, bananas, dinosaur heart, and even jellyfish. There are cases where fossil beetle casings and dinosaur feathers/hair (?) preserve their pigmentation, or colour.

But until now, no one had thought that cellular-level physical structures might be preserved. We knew that some of the original chemicals could be preserved - I worked with Heinz Lowenstam and Joe Kirschvink while I was at Caltech, and collected 63 million year-old Cretaceous ammonites (Baculites inornatus) from Baja California that still had mother of pearl lustre in them, in the unstable aragonite form (here are examples from Japan and from South Dakota). Based on ion exchange chromatography, Weiner, Lowenstam, Taborek and Hood found that the organic matrix in the shells of 80 million year old molluscs from Tennessee (Scabrotrigonia thoracica) probably had the primary, secondary and possibly even tertiary conformations of their proteins preserved. Weiner and Lowenstam also found that the isoleucine in fossil shells was sometimes not racemized - that is, it was still all of the same chirality (handedness), when most materials will naturally devolve into a 50-50 mix of epimers. The lack of epimerization for the shell in the intervening 63 million years, when the characteristic epimerization time is about 10^5 years, is thought to be due to the stabilization of the amino acids by the bioinorganic phase of the shell matrix. Whereas dinsoaur blood had never been found, traces of hemoglobin had been seen, by Schweitzer and others.

It exactly is this 'protection' afforded by the surrounding minerals in the dense bone that contributed to the preservation in the dinosaur soft tissues - as well as the burial under anoxic conditions in sediments that apparently did not allow bacterial action, or later flow of fluids that so often severely alter biological materials. The study of all this, how living materials become fossils, is called 'taphonomy,' and obviously these latest results will have a large impact on this field. One large point in the Schweitzer article is that these types of microstructures have never been found before not because they are rare, but because we had never thought them possible, and so had never even looked.

So the question really comes down to 'exactly what level of detail is preserved in these specimens, and can we expect even better examples?'

We can probably expect to learn a good deal about cellular structure, since the morphology seems to be well preserved, whether with the original biomolecules, or with substituted materials. If original biomolecules are present, or even their degradation products, then a lot can be learned - consider that the presence of certain proteins is in fact a flag for certain DNA sequences and metabolic pathways, so there can be a lot of work done on dino-DNA by inference. And this of course will be very closely watched by folks looking at the phylogeny of the dinosaurs - are modern birds really descendants of the theropods? Were the dinosaurs warm-blooded? Proteins will play a very large part in decyphering those stories.

It turns out I have an inside track on this one, since Mary Schweitzer, the scientist who found the soft tissue in the Tyrannosaurus rex bones, is working with funding from a paleontology program I co-direct. So I picked up the phone and called her - to congratulate her, and also to get an idea of what was ahead, now that the media was paying attention. She was also amazed at the media response, and had been on the telephone pretty much continuously for the whole week.

She is working on another publication, this time looking more closely at bone sub-types and physiological function as well as chemistry - 'nuff said. I had asked her for permission to use a particularly spectacular picture that was not in the Science article for this posting, but it is being used in the new article, so I will leave it for a later date. Although we did not speak about it, I can only assume that future work by Mary and others will explore whether dinosaur fossils have the types of cells associated with bone formation and maintenance (osteoblasts and osteocytes), as well as the cells that break down bone to supply calcium when needed (osteoclasts, for making egg shells, or bones in embryos).

In an interesting aside to all this, I saw that the discovery of well-preserved materials like this is always picked up by short-time creationists (1, 2, 3), as evidence that the Earth cannot be millions of years old. It's an interesting exercise to try and refute this argument, because both sides of Occam's razor are being used: it's a simple explanation (dino bones are only thousands of years old, not millions) and yet you would have to throw away a lot of other work to accept it (all the stratigraphy and geochronology). Here's one refutation. Then again, there are also long-time creationists in the fray...

Of course when I told my nine year old son about the dinosaur marrow, he came right back with: "Did you see the special the other night on Discovery Channel where they had found a real dragon?" After probing a bit, I think he knew the dragon was not real, but the fact that dragons had been mixed with dinosaurs on the TV show made him less apt to believe in the dinosaurs themselves - an interesting effect.

Watson & Crick:

...never dreamed of this.

On August 8 last year, a group of tourists were enjoying an afternoon aboard a Chicago Architecture Foundation tour boat. The Architecture River cruise takes a 90 minute ride along the Chicago River, viewing the details of over 50 famous buildings.

However, on this day, the tourists got more than they expected. As the boat passed under the Kinzie Street bridge, a passing tour bus emptied its bathroom waste tanks through the grating onto the helplessly upturned faces below. One hundred nine people, including several children and an infant, were showered with, um... sludge.

Surveillance cameras indicated a bus with characteristic markings was the only one to cross within 15 minutes of the incident, and descriptions from those passengers who could still see narrowed down the the bus to one chartered by the Dave Matthews Band.

The band was of course highly concerned, stated they were not on board at the time, that they trusted their long-time driver, and that they stood by his statement that he had nothing to do with the incident. In a public statement, the band members offered their DNA to prove that the offending items were not their droppings. The band later offered a $100,000 settlement for the passengers before results of the DNA test were divulged.

The case comes up before a judge next Friday, January 14th. There is no statement yet from the Illinois Attorney General's office regarding the results of the DNA test.

Moral - always be careful where you s#!t (or speak). Someone may carry it away and throw it for you. And it carries your characteristic stink, wherever it ends up.

A. Chu:

Scematic of a T4 bacteriophage (Purdue) 

I knew that in the end, the proteins that make up the organelles, walls, and other structures in cells and viruses had to have a physical movement involved when they changed conformations. What I wasn't prepared for was how darned mechanical those motions might appear in some cases.

Recent work by a group from Purdue University and the Shemyachin-Ovchinnikov Institute combined data from many X-ray crytallography and cryo-electron microscopy experiments to get a step-by-step picture of how a T4 phage (virus) infects an E. coli bacteria. This combination of data allowed the group to make a simulated video of the protein conformational changes as the phage attacks a bacterium.

?The video (large 20.7MB Quicktime, small Quicktime, large MP4, small MP4, large DivX) is quite amazing - watch for the unfolding short tail fibers, the simultaneous change in the baseplate (the kernel of the Purdue/Shemyachin-Ovchinnikov group's work), and then the eerie coiling of the tail sheath proteins. It's very gear-like as the tail tube drills through the cell wall. The deposited lysozyme (in green) then digests the peptidoglycan (in blue) and the tube can then inject the viral DNA into the bacterium.

I wonder how much of this is from actual data, how much is from animation texture mapping, and how much is "in-betweening."

The long-term driver behind this research is not only to study how T4 attacks E. coli, but to understand how each of the proteins contributes to the activity, possibly modify some of them so that T4 can attack other pathogens, and in the very long run, learn how to make nano-machines that can carry out particular actions (contract, drill, rotate, etc.)

Hang on - I have a tingle in my nose.... perhaps H7N2 avian flu?

Father William:

Apparently, if you have the C150T mutation in your mitochondrial DNA, you stand a good chance of getting old. Very old.

Seventeen percent of a group of 52 Italians between 99 and 106 have it, while only 3.4% of 117 people under 99 had it. That's statistically significant, but we still don't understand how the mutation appears (is it inherited or is it a mutation that occurred after conception) or how this affects lifespan (does it contribute to accelerated replication?).

Here's the link to the PNAS 100 (3) 1116-1121 Feb 4 2003 abstract.

What I always found intriguing about mitochondria (wow, there's a cocktail conversation stopper...) is that they use a prokaryote coding scheme, and replicate completely independently of the surrounding (eukaryote) cell. What this probably means is that at some distant point in eukaryote ancestry we had a commensal relationship with a prokaryote, which slowly lost its independence and identity.

Flash to a future actuarial table: "...mtDNA/C150T: Yes/No..."

Flash to a future breakfast cereal advert: "...New! Loaded with mito-DNA enhancing minerals!"

Thurmond, Hepburn:

I have to admit that I was more affected by the news of Katherine Hepburn's passing than that of Strom Thurmond. But that's a sign of how much exposure I had to them -- I saw Hepburn a lot more than Thurmond because of her movies. What if Strom had acted in "African Queen" -- would I remember him as fondly? How about Strom Thurmond in "Guess Who's Coming to Dinner?" Hmm. And as a male, I have to say that she was definitely more attractive than the late honored Senator.

What is it about high cheekbones? Is it simply a fashion of the times that defines what beauty is, or is it truly engraved in our DNA, and what we perceive as a good match? And how is intellect interfering with all of this?

There are some great studies out there in cognitive science that look at how we perceive different faces, and although a lot of it seems like it is to do with how we perceive different expressions, I think the tools are there to do some interesting research on perceptions of attractiveness. Is it based on where you were brought up? Is it based on exposure to media? Is it based on race, culture, and/or ethnicity? How similar are the features on finds attractive to one's parents? etc. etc.

Off to write a grant... oh damn it, I can't. I work for the people that fund the grants. Sheesh.

Venter and Smith:

I was very surprised that the founding of this organization did not receive wider notice:
 
" IBEA?Institute for Biological Energy Alternatives

Institute for Biological Energy Alternatives (IBEA) is a research-based institution dedicated to exploring solutions for carbon sequestration using microbes, microbial pathways, and plants. For example, genomics could be applied to enhance the ability of terrestrial and oceanic microbial communities to remove carbon from the atmosphere. IBEA will develop and use microbial pathways and microbial metabolism to produce fuels with higher energy content in an environmentally sound fashion. IBEA will undertake genome engineering to better understand the evolution of cellular life and how these cell components function together in a living system."

Craig Venter and his colleagues are planning to engineer an organism from the bottom up. Not to modify an existing organism, but make a new, man-made organism.

Now, before you go haywire and worry about a rogue bacterium or some such, we are assured that because of extensive work on what exactly a microbe can and can't live without, they will be able to make something that, say, eats oil spills, but can't live where spills don't exist. Other parts of the 501 (c) (3) empire that he is building deal with the PR aspects - looking at the ethics of the whole thing, and convincing the public.

At present, they have been able to get a drastically reduced genome to reproduce, but as far as packaging the genome in a working cell, and assigning it a very specific task... that remains in the future.

This technology is certainly of great interest to the newly-formed Department of Homeland Security. Not only in terms of how it could be mis-used, but in the immense potential it shows for dealing with current threats. A specifically-engineered virus could be used to mitigate an anthrax or botulinum attack. Other engineered bacteria might be able to catalyze the breakdown of nerve agents, either defensively during the dispersal itself, or later during victim treatment and site clean-up phases.

Remember, this type of engineering has allowed us to move from using pig insulin for diabetics, produced by processing millions of pounds of pork pancreas, to the production of human analog insulin using non-pathogenic E. coli bacteria.

Venter envisions many more uses for these techniques, using recombinant DNA (rDNA) to both insert and extract sections of DNA that are useful or inert in the target organism. The NIH has guidelines for using rDNA, and Venter's IBEA group will have set up an external committee that monitors his projects.

Stay tuned for the next best thing in bug-nology.

Watson & Crick (& Wilkins & Franklin):

General Tommy Franks' responses to a set of questions about whether the crater in Baghdad was being tested for Saddam Hussein's DNA was very interesting. Yes, the crater is being tested. And yes (emphatic yes), the U.S. does have a DNA sample against which to compare traces.

Hmm. That means that at some point, they got a sample from a hairbrush, a toothbrush, or a fedora. And either they got it from one of the recently entered palaces, or they have had it for a long time. I suspect the latter, because they would be much more controlled circumstances, and probably while Saddam Hussein was on travel. It also means there is probably a whole set of DNA samples that belong to other world leaders in some "mojo vault."

GATTACA. And so it begins.

Watson & Crick:

Gee, was it any surprise that there was no access given to Eve's DNA? Speaking of DNA, I have a swab of my child's squamous epithelials in my freezer, and so should every parent. Having just seen "Minority Report" last night, I was glad I had taken that sample several years ago. Hmm... time to renew that swab.