An imaginary island off the coast of Costa Rica teems with make-believe dinosaurs. Millions of readers and film-goers know it asJurassic Park. Much of Utah teems with the fossilized bones andfootprints of real dinosaurs. By that token, it could claim to be called"Cretaceous Park."
On the earth's geologic calendar, the Cretaceous period began about136 million years ago and lasted 71 million years. At that endpoint intime, the dinosaurs, which had ruled the Cretaceous roost ever sinceit succeeded the Jurassic, suddenly went extinct.
Fossils are the bread and butter of paleontologists, who reconstructthe anatomy of past life forms from these petrified remains. Only anoccasional insect, entombed in ancient amber, lifts a corner of long-extinct DNA. (See BioWorld Today, June 10, 1993, p.1.)
Now a Utah microbiologist reports capturing DNA molecules frompreserved but not fossilized bone dating back to Cretaceous times.Scott Woodward's paper in the current issue of Science, dated Nov.18, describes a "DNA sequence from cretaceous period bonefragments."
A press release from Brigham Young University in Provo, whereWoodward teaches, acclaimed this publication as "the first claim ofdinosaur DNA retrieval to appear in a peer-reviewed scientificjournal."
Woodward's discovery came from a coal mine in the eastern part ofthe state. He has salvaged DNA from human remains well preservedin the hot dry soil of Egypt and Chile, and was intrigued that wet,cold peat bogs in the U.K. and Florida also yielded bodies thousandsof years old, their bones shielded from DNA-degrading oxygen.
"We know that anciently, 100 million years ago," Woodward toldBioWorld Today, "there were also peat bogs on the earth, and thoseturned into coal beds." He continued, "A couple of years ago, wefound a mammoth, buried under very wet and cold conditions, notfar from the coal mine in this story. We were able to get DNA out ofit."
So two years ago, he enlisted an engineering geologist friend, MarkBunnell (third author on the Science paper) to keep an eye out forbig bones in coal deposits. This paid off in June 1993, when Bunnellcame upon two unfossilized bone fragments 30 centimeters abovethe top of the coal bed, and about 610 meters below the surface.
Fragment one, seemingly from the limb of a large animal, measured20 by 6 by 3 centimeters (circa 7.9 by 2.4 by 1.2 inches). Fragmenttwo, perhaps from a rib, was 20 by 2 by 1 centimeters (7.9 by 0.8 by0.4 inches) in size. Neither scrap was large enough to identify thespecies of origin.
Carbon dating would have consumed too much of the material,Woodward explained. "The geology of the area is well knownbecause of the mining interests, so we dated the fragments bystratigraphy to 80 or 85 million years ago."
He added, "For the same reason, we made no plaster casts, becausewe didn't want anything to touch the bone before we got the DNAout."
That process, relying heavily on polymerase chain reaction (PCR)amplification, consumed four-fifths of the two specimens,Woodward said. It focused on resurrecting the gene sequence formitochondrial cytochrome b, a molecule with a known rate ofevolutionary mutation. He obtained positive PCR amplifications inonly nine of 494 attempts, involving over 2,880 individualamplifications.
All nine readable sequences were at least 134 base pairs long.Seeking to clarify the ancestral relationship of dinosaurs to morerecent life forms, Woodward compared his nine stretches of DNAwith all published cytochrome b databases. These included a fullrange of mammals, birds, reptiles, amphibians and insects. For goodmeasure, he also obtained from his own ancient-DNA lab at BrighamYoung partial sequences of ostrich, emu, rhea, turkey, box turtle,garter snake and alligator.
Contrary to current wisdom concerning a likely philogenetic kinshipbetween birds and dinosaurs, his bone-fragment genes were about 30percent distant in homology from all the forms of contemporary lifeon the data bases.
"It's like nothing we've ever seen before," Woodward said adding,"We're not too bothered that this particular sequence doesn't allowus to establish a philogenetic relationship to the dinosaur, because ofthe size of the fragments and the type of genes. Cytochrome b isknown to evolve at a certain rate, which probably is best at resolvingphilogenies in a much shorter time period, maybe five to 10 millionyears."
Other Genes May Help Answer Questions
He pointed out that the Cretaceous period, tens of millions of yearsago, marked "the split-off of birds, reptiles, mammals and all otheranimals. So that's the reason we'd like to look for some othersequences; maybe ribosomal genes may be a little bit better clock foranswering that [bird/dinosaur] question."
Enlarging on this theme, Woodward stated that "the presumedrelationship is a fairly new idea in the last half dozen years.Dinosaurs were on earth for enough millions of years to allow a widerange of diversity to arise, probably."
His paper in Science notes that "at least 14 different dinosaur specieshave been differentiated by the tracks found in the . . . coal beds"that contained the two bone fragments.
"Very likely," he concluded, "there were groups of dinosaurs livingon the earth that were as far apart from each other as the groups ofanimals that we have living on the earth today."
But this very uniqueness, writes Science reporter Ann Gibbons in aneditorial, "cuts both ways. If Woodward does indeed have dinoDNA, many researchers think, its sequence should bear at least someresemblance to the DNA of dinosaurs' presumed modern relatives,birds or crocodiles."
One such skeptical scientist she quotes, molecular evolutionistSvante Paabo at the University of Munich, doubts that DNA couldexist in bone for 80 million years. "The jury is out until others canreproduce his results," Paabo told Gibbons.
Woodward said he has talked to "a couple of other groups" abouttrying to do just that, "but there are problems." His PCR testing, hepointed out, "has consumed four-fifths of the material, leaving onlyone-fifth for further testing." How will Woodward solve thisSolomonic perplexity of sharing those last bits of bone?
He himself has just returned to his sabbatical at the HebrewUniversity in Jerusalem, where he is looking into retrieving DNAfrom the parchment on which the Dead Sea Scrolls were written.How then to find a peer laboratory to reproduce his bone-fragmentfindings?
"E-mail stuff is amazing," Woodward replies. "It's not very difficultto keep communications going when you're halfway round theworld." If and when he concludes such a second-opinionarrangement, he said, that fact will not be announced until the newexperiments are concluded, and resulting papers published.
Two Bones Do Not A Dinosaur Make
Other scientists express doubt that those old bones are reallydinosaurian altogether. One alternative scenario: The Utah DNAsequences derive from an ancient, unknown microorganism hiddenin the bones.
While allowing that his dinosaur identification is probable ratherthan positive, Woodward marshals this evidence to support hisconviction:
"We stand by what we said in the Science paper," he declared. "Wethink that we probably have a Cretaceous period dinosaur. There area couple of assumptions that we have to make here."
Namely: "First of all, we assume we are dealing with a dinosaurbone. The evidence there is circumstantial. It's a large bone, it's 80million years old. There's evidence of dinosaurs in the area. Thereweren't very many big animals other than dinosaurs.
"Second, we also think we have ancient DNA. We think that thesequence information tells us that, because of the randomdistribution of substitutions that we see in the sequence." n
Liposome Technology's DOX-SL Gets Good Reviews
Data presented at 2nd International Congress on Drug Therapy inHIV Infection provided further evidence that Liposome TechnologyInc.'s DOX-SL is safe and effective in patients with advanced AIDS-related Kaposi's sarcoma(KS), the Menlo Park, Calif., company saidTuesday.
Liposome Technology already filed a new drug application for theproduct in the U.S. to treat Kaposi's sarcoma (KS) in AIDS patientswho cannot tolerate or who have failed conventional systemicchemotherapy. The company expects to file for DOX-SL in Europeby the end of the year for the same indication, but as a first-linetherapy.
DOX-SL is a long-circulating liposome formulation of the anticanceragent doxorubicin hydrochloride. At the meeting in Glasgow,Scotland, Simon Stewart of St. Mary's Hospital in London presenteddata from a Phase II study involving 238 patients from eightcountries.
Stewart said that at time of best response, 6.3 percent of patients hada complete response, 74.4 percent had a partial response, 18.5percent had stable disease and 0.8 percent had disease progression.
Another presentation, from a study at the University of Dusseldorf,Germany, concluded DOX-SL is a feasible candidate for long-termmaintenance therapy. A third presentation, from New YorkUniversity Medical Center, involved 11 patients with advancedepidemic KS who had stopped responding to Vestar Inc.'sDaunoXome. Five of eight evaluable patients experienced a partialresponse, and the disease stabilized in three.
Liposome Technology stock (NASDAQ:LTIZ) was up 25 cents pershare Tuesday, closing at $6.25. _ Jim Shrine
-- David N. Leff Science Editor
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