“ Bright Ideas“ It now appears that was a pawn in a much bigger battle. —

Hieroglyphs Carved into an 18-step stopped fighting and for many never heard of actual- and brought its ruler — his own mul’s backing and became a Expose Mayan stone stairway, the hieroglyphs years was loyal to . When ly invading and defeating the brother — and other Tikal major regional power.” Superpower reveal that in the seventh cen- the king was in his early 20s, king of Dos Pilas. We thought nobles to Dos Pilas to be sacri- “Rather than being an inde- Conflict tury, the Maya world was divid- Calakmul attacked and defeated that, at most, they might have ficed.“The west section of the pendent actor as previously

Research and scholarship roundup and scholarship Research ed between two Dos Pilas. After capturing Balaj had a weak alliance.” steps was very graphic,”says thought, it now appears that Newly uncovered superpowers — one under the Chan K’awiil, Calakmul became The record continues to Fahsen.“It says,‘Blood was Dos Pilas was a pawn in a hieroglyphs in control of the city-state Tikal, a “puppet king” who kept his describe how Balaj Chan K’awi- pooled, and the skulls of the 13 much bigger battle,”says are filling the other dominated by Calak- land in exchange for allegiance. il, now loyal to Calakmul, people of the Tikal palace were Arthur Demarest, Ingram Pro- in an unknown period mul. Tikal was located in what “When I read those glyphs, I launched a decade-long war piled up.’Following the victory, fessor of Anthropology at Van- of Mayan history. is now northern Guatemala; had to blink to make sure I was against Tikal that ended in his Dos Pilas embarked on a cam- derbilt. “In today’s terms, Dos Their translation is helping to Calakmul was about 60 miles reading correctly,”he says.“I had victory. His forces sacked Tikal paign of conquest with Calak- Pilas was the Somalia or Viet- nam of the Maya world, used 1.explain the fracture of the farther north in . in a war that was actually Mayan empire into warring The glyphs — among the between two superpowers.” regional states and the eventual largest texts ever discovered — Arthur Demarest, left, In the world of archaeology, and Federico Fahsen collapse of a civilization that detail how Calakmul was have discovered Demarest has garnered atten- once ruled southern Mexico as involved in the wars that hieroglyphs that change tion for his work in confirming well as Central and South occurred in the ancient Maya scholars’ notions of the existence of a 170-room, University College, London, Myan history. America. world. Previously, Mayan schol- three-story, eighth-century and of the Uni- Complete with references to ars viewed the conflict between royal palace in Guatemala in versity of Bonn,”says Demarest. piles of skulls and flowing Dos Pilas and Tikal as a quarrel 2000. Located in the ancient After evaluating the new blood, the glyphs were partially between two brothers. city (meaning “Place material, Demarest now con- exposed during a recent hurri- The glyphs, however, reveal of Serpents”), the palace is cedes this was a time when the cane at Dos Pilas, an ancient a very different story. It’s one believed to be one of the was on the Mayan city isolated deep in the that begins with the birth of a largest, most elaborate and verge of moving to a higher rain forest.“The hundreds of king, Balaj Chan K’awiil, in 625 best-preserved residences of level of organization and con- new glyphs fill a gap of A.D., and Tikal’s creation of ancient Maya kings. solidating into a single empire. unknown Maya history and Dos Pilas as a military outpost Fahsen and Demarest con- “However, this didn’t happen. clarify many of the political and in 629. Dos Pilas was important tend the newly translated Instead, the giant war went military relationships of this for its proximity to the middle account at Dos Pilas supports back and forth. After Tikal was critical period,”says epigrapher stretch of the Pasión River, the the theory advanced by some sacked, it roared back and Federico Fahsen, adjunct pro- superhighway of the Maya Maya scholars who have assert- crushed Calakmul. And then fessor at Vanderbilt, who deci- world. It was strategically ed that this period in Maya his- the Maya world broke into phered the text. Fahsen says the important because it allowed tory was a “long world war” regional powers, setting the glyphs are extraordinary Tikal to control trade routes between Tikal and Calakmul. stage for a period of intensive, because they tell not only about between the highlands and Scholars previously character- petty warfare that finally led to the city of Dos Pilas’s triumphs lowlands. ized the conflicts between dif- the collapse of the Maya,”says but also its setbacks and As told by the glyphs, Balaj ferent -states as Demarest. By 760, Dos Pilas tragedies. He now believes Dos Chan K’awiil was installed as regional and unrelated.“The was abandoned. Pilas was part of a dramatic ruler of Dos Pilas by Tikal at the new evidence supports the The work in Guatemala was superpower struggle that may age of 4.“Balaj Chan K’awiil more extreme versions of theo- funded, in part, by Vanderbilt have contributed to the collapse became a very big warrior,”says ries advanced by two Maya and the National Geographic of the Maya civilization. Fahsen.“He almost never scholars — of Society. PHOTOS: KENNETH GARRETT ©2002 NATIONAL GEOGRAPHIC SOCIETY >>

24 W inter 2003 V anderbilt Magazine 25 Deciphering Pancreas Cells Pave online Aug. 19, 2002, that p48 is A simple way to think about pancreas were blue, too. Mosquito Senses Way for Diabetes required for the development of the technique, Wright says, is to Wright’s team combined this Treatment the pancreas — both its exocrine picture the crowd at a football powerful method for tracing a There’s been a cells (those that secrete digestive stadium and to imagine that cell’s lineage with gene knockout national buzz about Before the pan- enzymes) and its endocrine cells somewhere in the stadium, for a technology. They engineered are thinking about manipulating mosquitoes this creas is a pancreas, it (those that secrete insulin and limited time, a man gave away mice to lack the p48 gene, caus- stem cells in the laboratory. year, but the study of is just two tiny other hormones). unique blue hats and asked peo- ing abnormal development of Because you know now, at least the genetic map of bumps — two groups Wright’s team used what ple to wear them.“Now we can the pancreas. Cells in these for some genes, that you can put the species, Anopheles gambiae, of cells sprouting one reviewer of the paper called follow the people who got hats, knockout mice still tried to turn them in or take them away and by2. three Vanderbilt researchers from a central tube. What makes “a novel and powerful cell no matter where they go,”says on the p48 gene, so the investiga- you don’t kill the cells; you has gained notice within the sci- 3.these cells bud off from the main marking method” to track cells Wright.“Whether they go to get tors were able to follow the blue manipulate what they’re going to entific community and may fos- group? How do they go on to in the mouse that express the a hot dog or leave the stadium marker in these cells. become. And that’s exactly what ter new ways to control this make all the cell types of the p48 gene, starting very early in entirely, we can find them.” They found that, with p48 we want to do therapeutically.” disease-carrying insect. mature pancreas? These are the embryonic pancreas formation. Using the technique, the absent, the cells that normally Wright believes that linking It seems that A. gambiae is kinds of questions that drive the The method relied on genetic investigators found and followed express p48 and go on to form lineage tracing and gene knock- something of a gourmet — its research efforts of Christopher manipulations to introduce an the cells that turned on the p48 pancreas became intestinal cells outs will become increasingly preferred meal is almost exclu- V.E. Wright and colleagues. The inherited marker — a blue color gene — as if these cells were instead. And they became all common.“It adds extra depth to sively human blood. Its insect’s Laurence J. Zwiebel answers could pave the way NEIL BRAKE that could be followed in cells wearing blue hats. The cells that types of cells in the intestines, understanding cellular behavior,” preference for humans and its toward limitless supplies of pan- that turned on the p48 gene, budded out to form the pan- including intestinal stem cells. It he says. He is also enthusiastic ability to seek them out, in fact, environmentally benign fash- 72 involved in taste. Previous creatic cells for transplantation and in all the cells that came creas turned on p48; they were is the first time, to Wright’s about fluorescent variants of the are the insect’s hallmarks and ion,”says Zwiebel, an assistant studies have shown that both of therapy of diabetes. from those cells. blue. And the cells of the mature knowledge, that investigators lineage tracing technique that have made the mapping of its professor of biological sciences these chemo-sensory senses “It has been established that have tracked what happens to will allow investigators to follow genes an important subject of and study leader. play a major role in the mosqui- islet cell transplantation can cells when a gene that they nor- living cells as they change fates. scientific study. The net result Malaria is spread when a to’s strong preference for solve the diabetes problem,”says mally turn on is missing. And he is excited about his could lead to a more effective human is bitten by an A. gambi- human blood. Wright, associate professor of cell “The really important point group’s ongoing studies with assault on the mosquito’s ability ae mosquito carrying the proto- The identity of many of the and developmental biology and is that these cells don’t just die; p48. The team is currently intro- to spread malaria, a disease that zoa that causes the disease. This genes was determined from director of Vanderbilt’s Develop- they go on to behave as a differ- ducing the p48 gene into cells annually causes millions of single-celled entity spends part their structural characteristics mental Biology Program, refer- ent tissue,”he says.“That is very that would normally become deaths worldwide. of its life cycle in humans and and their similarity to genes ring to studies carried out in powerful information when you intestinal cells to see if they Vanderbilt researchers part in the mosquito. The found in a particular species of Edmonton, Canada, and else- change their fate and become Laurence J. Zwiebel, A. disease produces a fruit fly.“In addition, we found where.“The problem is having a pancreatic cells instead. Nicole Fox and Jason severe fever and, in a large number of genes that are suitable and sufficient source of “If we can do that,”he says, Pitts, along with sci- some cases, potentially unique to the mosquito and, transplantation material.” “we’re a big step further towards entists from the Uni- fatal complications therefore, could very well be Donated pancreases and the Christopher knowing that p48 is one of the versity of Notre Dame affecting the kidneys, involved in mosquito-specific technical expertise required to V.E. Wright gene triggers you might want to and the University of Illi- liver, brain and blood. behaviors such as blood feed- isolate functioning islet cells — put into an embryonic or other nois at Urbana-Champaign, In the Oct. 4 issue of Science, ing, host preference and track- the pancreatic cells that produce stem cell to make pancreas.” have identified specific genes Zwiebel, Vanderbilt graduate ing,”says Zwiebel. insulin — will not meet the Those “other” stem cells related to this species’ ability to student Fox, and research asso- The Vanderbilt researchers’ demand, Wright says. An alter- could be circulating-blood stem spread malaria. These genes play ciate Pitts and colleagues paper on the topic is part of a native, he says, is to produce cells or even cells within the pan- a critical role in almost every reported the identification of special issue of Science that insulin-secreting cells from creas that could potentially aspect of the insect’s life cycle, 276 genes in the A. gambiae reports the sequencing of the embryonic or other stem cells. regenerate the organ, so-called including its ability to see, taste, genome. These provide the entire Anopheles genome. Con- “If we can identify the factors pancreatic stem cells. They touch and smell. blueprints for proteins central currently, the journal Nature is that determine pancreatic cell appear to exist in mice, which are “This is an important step to the mosquito’s sensory sys- announcing the sequencing of fate, we might be able to coerce capable of pancreatic regenera- in our ability to first under- tems, including its ability to the genome of Plasmodium fal- embryonic stem cells or other tion, explains Wright. It is not so stand the mosquito’s host pref- find and feed on humans. In ciparum, the single-cell parasite cells to turn into pancreas.” far-fetched, he adds, to believe erence and tracking system and particular, Zwiebel and col- carried by Anopheles that causes One of these factors is a gene that human beings harbor such then to interfere with it in a leagues found 79 genes that malaria. These two achieve- called PTF1p48 (p48 for short). cells. Identifying the genes, such way that can save human lives appear to be involved in the ments are providing the impe- Wright and colleagues reported as p48, expressed by pancreatic in an economically feasible and mosquito’s sense of smell and tus for an assault on malaria. in Nature Genetics, published progenitor cells forwards efforts to find pancreatic stem cells. For more information about stories in Bright Ideas, visit Vanderbilt’s online research journal, Exploration, at http://exploration.vanderbilt.edu.

26 W inter 2003 NEIL BRAKE V anderbilt Magazine 27