The science magazine Discover has covered the research of SMU vertebrate paleontologist Louis L. Jacobs and the infamous Bone Wars of the late 1800s.
In a post on Discover’s “80 beats” blog, the magazine reprinted the translation of a poem written by frontier naturalist and fossil hunter Jacob Boll.
Jacobs came across the poem at the American Museum of Natural History on a label on the back of Eryops specimen No. AMNH 4183.
SMU biology professor Pia Vogel translated the poem. Vogel and Jacobs worked with SMU English professor John M. Lewis to retain the essence of the poem in English.
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To book a live or taped interview with Louis Jacobs in the SMU News Broadcast Studio call News and Communications at 214-768-7650 or email news@smu.edu. (Photo: Octavio Mateus)
The Bone Wars was a flurry of fossil speculation across the American West that escalated into a high-profile national feud. Drawn into the spectacle were two scientists from the Lone Star State, geologist Robert T. Hill, now acclaimed as the Father of Texas Geology, and Boll, who made many of the state’s earliest fossil discoveries.
Hill and Boll had supporting roles in the Bone Wars through their work for one of the feud’s antagonists, Edward Drinker Cope, according to Jacobs’ new study.
Currently his field projects include work in Mongolia and Angola. His book, “Lone Star Dinosaurs” (1999, Texas A&M University Press) was the basis of an exhibit at the Fort Worth Museum of Science and History that traveled the state. He consulted on the new exhibit, Mysteries of the Texas Dinosaurs, which opened in 2009.
Discover
This poem in praise of the Permian amphibian Eryops was scrawled on the back of a label now in the American Museum of Natural History by Jacob Boll, a Swiss-German fossil hunter involved in a tumultuous 19th-century paleontology feud.
Graduate students and post-docs do a lot of important work in science these days, in the names of their more eminent supervisors, and there was a similar set-up in the early days of American paleontology. Many of the fossils named by and attributed to E.D. Cope and O.C. Marsh, archenemies and the era’s most prominent paleontologists, were collected in the field by hired hunters like Boll and his contemporary Robert T. Hill, who both worked for Cope.
Paleontologists sifting through papers in the library of Southern Methodist University recently came across letters between Hill and Cope and, while examining specimens at AMNH, happened on Boll’s little poem.
SMU is a nationally ranked private university in Dallas founded 100 years ago. Today, SMU enrolls nearly 11,000 students who benefit from the academic opportunities and international reach of seven degree-granting schools. For more information, www.smu.edu.
SMU has an uplink facility located on campus for live TV, radio, or online interviews. To speak with an SMU expert or book an SMU guest in the studio, call SMU News & Communications at 214-768-7650.
Jason Heid, an editor with D Magazine’s popular Frontburner blog, covered the research of SMU vertebrate paleontologist Louis L. Jacobs and the infamous Bone Wars of the late 1800s.
The Bone Wars refers to a flurry of fossil speculation across the American West that escalated into a high-profile national feud. Drawn into the spectacle were two scientists from the Lone Star State, geologist Robert T. Hill, now acclaimed as the Father of Texas Geology, and naturalist Jacob Boll, who made many of the state’s earliest fossil discoveries.
Hill and Boll had supporting roles in the Bone Wars through their work for one of the feud’s antagonists, Edward Drinker Cope, according to Jacobs’ new study.
Currently his field projects include work in Mongolia and Angola. His book, “Lone Star Dinosaurs” (1999, Texas A&M University Press) was the basis of an exhibit at the Fort Worth Museum of Science and History that traveled the state. He consulted on the new exhibit, Mysteries of the Texas Dinosaurs, which opened in 2009.
Jacobs co-leads Projecto PaleoAngola, a collaborative international scientific research program focused on the ancient life of Angola.
Besides the discovery of the first dinosaur of Angola, the team has uncovered mosasaurs, plesiosaurs, turtles and other Cretaceous marine animals, but the aim is also to create a strong and lasting institutional and scientific collaboration that has a multiplier effect in Angolan academia.
In the laboratory, Jacobs’ research utilizes advanced imaging and stable isotope techniques to investigate paleoenvironmental, biogeographic and phylogenetic issues of the Mesozoic and Cenozoic eras.
Jacobs is featured by National Geographic on its Explorers web site, which acknowledges the work of the world’s scientists whose research is made possible in part through funding from National Geographic.
By Jason Heid
Frontburner
SMU paleontologist Louis Jacobs has been studying the role of two Texas fossil collectors in the 19th century Bone Wars, which played out across the American frontier as rivals competed fiercely to uncover new fossils (and thus discover new extinct species.) In doing so he found a poem written by one of the men, Dallas naturalist Jacob Boll, whose Swiss family was among those that founded the utopian La Reunion colony here.
During a break in his field labors, Boll’s fascination with ancient bones prompted him to write in his native German an ode to fossils. Jacobs found the poem in the American Museum of Natural History on a label on the back of Eryops specimen No. AMNH 4183.
SMU biology professor Pia Vogel translated the poem. Vogel and Jacobs worked with SMU English professor John M. Lewis to retain the essence of the poem in English.
Treasure trove of archived letters discovered at SMU; Permian hunter’s German ode to a fossil is translated into English
In the late 1800s, a flurry of fossil speculation across the American West escalated into a high-profile national feud called the Bone Wars.
Drawn into the spectacle were two scientists from the Lone Star State, geologist Robert T. Hill, now acclaimed as the Father of Texas Geology, and naturalist Jacob Boll, who made many of the state’s earliest fossil discoveries.
Hill and Boll had supporting roles in the Bone Wars through their work for one of the feud’s antagonists, Edward Drinker Cope, according to a new study by vertebrate paleontologist Louis L. Jacobs, Southern Methodist University, Dallas.
The study by Jacobs expands knowledge about Cope’s work with Hill and Boll.
It also unveils new details about the Bone Wars in Texas that Jacobs deciphered from 13 letters written by Cope to Hill. Jacobs discovered the letters in an archive of Hill’s papers at SMU’s DeGolyer Library. The letters span seven years, from 1887 to 1894.
Hill, who worked for the U.S. Geological Survey, not only provided Cope with fossils of interest but also shared geological information about fossil locales.
Boll, who was a paid collector for Cope — as was the practice at the time — supplied the well-known paleontologist with many fossils from Texas. More than 30 of the taxa ultimately named by Cope were fossils collected by Boll.
“Fossils collected by Boll and studied by Cope have become some of the most significant icons in paleontology,” said Jacobs, an SMU professor of earth sciences and president of SMU’s Institute for the Study of Earth and Man.
The survey party of USGS geologist Robert T. Hill explored Texas during the 1800s to report on the geology and resources to open the West to agriculture. (Credit: USGS)
Rush to find fossils explodes during opening of the American West
Jacobs describes the late 1800s as a period of intense fossil collecting. The Bone Wars were financed and driven by Cope and his archenemy, Othniel Charles Marsh. The two were giants of paleontology whose public feud brought the discovery of dinosaur fossils to the forefront of the American psyche.
Cope, from Philadelphia, and Marsh, from Yale University, began their scientific quests as a friendly endeavor to discover fossils. They each prospected the American frontier and also hired collectors to supply them with specimens. Cope and Marsh identified and named hundreds of discoveries, publishing their results in scientific journals.
Over the course of nearly three decades, however, their competition evolved into a costly, self-destructive, vicious all-out war to see who could outdo the other. Despite their aggressive and sometimes unethical tactics to outwit one another and steal each other’s hired collectors, Cope and Marsh made major contributions to the field of paleontology, Jacobs said.
Hill first to identify and map the Cretaceous geology in North Texas
Born in 1858, Hill was a teenager when he left Tennessee as an orphan and arrived on the Texas frontier in 1874, says Jacobs’ study. Hill settled in Comanche, southwest of Fort Worth, where he went to work for his brother’s newspaper, the Chief. After earning a Bachelor of Science in geology from Cornell, Hill was hired as a field geologist for the USGS.
Hill is noted for being the first to identify and map the distinct rock formations in North Texas that correspond to the Earth’s Cretaceous geologic period from 146 million years ago to 65 million years ago, Jacobs said. For much of the Cretaceous, a shallow sea cut North America in half from the Arctic to the Gulf of Mexico. Dinosaurs roamed the coastal shoreline and huge reptiles swam the waters, an environment that preserved plants and animals as fossils for posterity millions of years later.
Through his reading of the letters, Jacobs found that Cope disagreed with the way Hill named the Cretaceous rock units, and told him so. Cope counseled Hill: “You mustn’t mind criticism. We all get it and get used to it; but it isn’t comfortable at first.”
In subsequent letters, said Jacobs, it’s apparent Hill had changed his approach, for which Cope offered him high praise: “I wish to say definitely that your discovery of the lower Cretaceous series in this country is the most important addition to our geology that has been heard for a long time.”
Hill contributed one of 1,000 species of backboned animals named by Cope
Jacobs’ research found that numerous letters reveal that Cope was persistent in trying to buy a Cretaceous fish fossil that Hill had collected. In various letters, Cope expresses a desire to view the fossil, each time stating his request in a different way. Hill ultimately sold Cope the fossil for $15. Cope named the specimen Macrepistius arenatus. It is housed at the American Museum of Natural History in New York City.
Hill’s fish specimen was one of 1,000 species of backboned animals, from fish to dinosaurs, that Cope described and named in his lifetime.
Also evident in the correspondence is a glimpse into the battle intrigue between Cope and Marsh, Jacobs said. In one letter, Cope angles to learn from Hill details about a new director of the USGS, to judge whether “our ? friend O.C.M.” would have an advantage.
Cope wrote to Hill, “Possibly you can find out how the land lies?”
Cope’s other Texas connection was through Jacob Boll
Boll was a much larger supplier to Cope and ultimately made significant contributions to the field of paleontology. Boll “is mentioned, usually in passing, in virtually every history of the subject,” according to Jacobs.
Born in 1828 in Switzerland, Boll was the first to discover vertebrate fossils in the Permian red beds along the drainages of the Wichita and Red rivers and their tributaries.
“The discoveries opened up an entirely new chapter in vertebrate evolution some 280 million years old,” Jacobs said. “Boll’s finds include some of the oldest close relatives of mammals whose evolution eventually led to humans.”
Boll belonged to one of the Swiss families that founded the mid-19th century utopian society La Reunion in Dallas, Jacobs said. Boll made Dallas his home sometime after 1874. He died in the field in the Permian red beds in 1880 from a snake bite.
At least one scholar has asserted that Cope — to keep the identity of his collectors secret from Marsh — never credited Boll for the Texan’s many fossil discoveries. Jacobs, however, found evidence that in 1878 Cope, in fact, did acknowledge Boll’s contribution, at least for the big-headed, semi-acquatic amphibian Eryops. Cope wrote that the fossil was “found … by my friend Jacob Boll.”
Boll’s fossil fascination erupted into a poem for Eryops
During a break in his field labors, Boll’s fascination with ancient bones prompted him to write in his native German an ode to fossils. Jacobs came across the poem in the American Museum of Natural History on a label on the back of Eryops specimen No. AMNH 4183.
SMU biology professor Pia Vogel translated the poem. Vogel and Jacobs worked with SMU English professor John M. Lewis to retain the essence of the poem in English.
“Now you will with some few others
Trek to the professor’s seat.
Awakened through his careful thought,
Be reassembled from your fragments,
To tell to others yet to come
From the sculpting of your teeth
How you lived and disappeared,
Name you he will, and what he found.”
While Hill and Boll were linked by their relationship to Cope, it isn’t known whether the two of them ever met, according to Jacobs.
”Hill and Boll both made major contributions to frontier science at an important time in American history,” Jacobs said. “They may have been nearly forgotten, but their lives have influenced much that came later.” — Margaret Allen
Powerful discovery tool is at work screening millions of drugs in the search to reverse chemotherapy drug resistance in cancer
A picture is worth 1,000 words when it comes to understanding how things work, but 3D moving pictures are even better. That’s especially true for scientists trying to stop cancer by better understanding the proteins that make some chemotherapies unsuccessful.
Researchers for decades have had to rely at best on static images of the key proteins related to recurring cancers.
Now SMU biochemist John G. Wise at Southern Methodist University, Dallas, has brought to life in a moving 3D computer model the structure of human P-glycoprotein, which is thought to contribute to the failure of chemotherapy in many recurring cancers.
“This is a very different approach than has been used historically in the field of protein structure biochemistry,” Wise said. “Historically, proteins are very often viewed as static images, even though we know that in reality these proteins move and are dynamic.”
The model is a powerful new discovery tool, says Wise, particularly when combined with high-performance supercomputing. The dynamic 3D model already has made it possible for Wise to virtually screen more than 8 million potential drug compounds in the quest to find one that will help stop chemotherapy failure. (Youtube video)(Flickr images)
So far, the supercomputer search has turned up a few hundred drugs that show promise, and Wise and SMU biochemist Pia Vogel have begun testing some of those compounds in their wet lab at SMU.
“We’ve seen that running the compounds through the computational model is an effective way to rapidly and economically screen massive numbers of compounds to find a small number that can then be tested in the wet lab.”
The research is funded by the National Institute of General Medical Sciences, National Institutes of Health.
Seeking new drugs that would allow chemotherapeutic compounds to enter and destroy cancer cells Since the 1970s it has been known that the so-called multidrug resistance protein, P-gp, is most likely responsible for the failure of many chemotherapy drugs. P-gp is nature’s way of pumping toxins from a cell, but if cancer cells express more P-gp than cells normally would, the chemotherapy is no longer effective because the protein considers it a toxin and pumps it out before it can destroy the cancer.
“We’re looking for small molecules that will temporarily inhibit the pump; a new drug that could be co-administered with the chemotherapeutic and that stops the sump pump in the cancer cell so that the cancer chemotherapy can remain in the cell and kill the cancer,” Wise said.
High-performance computer enables millions of digital screenings Wise has run about 10.5 million computational hours since August 2009 and has screened roughly 8 million potential drugs against different protein structures.
SMU biochemists Pia Vogel and John Wise have paired a moving 3D computer model of a key human protein together with the SMU supercomputer to search for potential drugs to stop chemotherapy failure. (Image: Hillsman Jackson, SMU)
“We are currently screening about 40,000 compounds per day on SMU’s High Performance Computer,” Wise said.
“We found a couple hundred compounds that were interesting, and so far we chose about 30 of those to screen in the lab,” Vogel said. “From those, we found a handful of compounds that do inhibit the protein. We were thrilled. Now we’re going back into the models and looking for other compounds that might be able to throw a stick in the pump’s mechanism.”
Massive increases in computational power in recent years have made the screening research possible, Wise said. “Ten years ago you couldn’t have docked 8 million compounds — there just wasn’t enough computational power.”
Human P-gp: “We don’t know what it looks like exactly.” Every organism has a version of P-gp. Its structure has been previously determined for some organisms — mostly bacteria, but also in mice — by studying the arrangement of atoms within protein crystals. However, the exact structure of the human enzyme remains unclear. Wise deduced the structure of human P-gp by relying on evolutionary relationships and scientific understanding of how proteins are put together. He then used computer programs to model the protein in a way that brings the static picture of the human pump to life in the computer. (Youtube: Moving model)
To develop the model, Wise used freely available simulation software developed by researchers at the University of Illinois, the National Institutes of Health and the Scripps Research Institute. Wise and Vogel use compounds from ZINC, a free database of more than 21 million commercially available compounds for virtual screening. ZINC is provided by the Department of Pharmaceutical Chemistry at the University of California, San Francisco.
“We can physically build these molecules in the computer, in silico, and computationally we can model a variety of conditions: We can raise the temperature to 37 degrees Centigrade, we can have the right salts and all the right conditions, just like in a wet-lab experiment. We can watch them thermally move and we can watch them relax,” Wise said. “The software is good enough that the model will move according to the laws of physics and the principles of biochemistry. In this way we can see how these compounds interact with the protein in a dynamic way, not just in a snapshot way.”
Even with the 3D dynamic model and a supercomputer, the odds are stiff Theoretically, if a drug can be found that temporarily knocks out the sump-pump proteins, then all those cancer chemotherapies that don’t work for a patient will work again.
“The ultimate goal of our research would be to find a compound that is safe and effective,” Wise said. Even with a supercomputer, however, the odds are steep.
“Out of a hundred good inhibitors that we might find, 99 of them might be extremely toxic and can’t be used. In the pharmaceutical industry there are many, many candidates that fall by the wayside for one reason or another,” he said. “They metabolize too quickly, or they’re too toxic, or they’re not soluble enough in the acceptable solvents for humans. There are many different reasons why a drug can fail. Finding a handful has been a great confirmation that we’re on the right track, but I would be totally amazed if one of the first we’ve tested was the one we’re looking for.”
Vogel is an associate professor and director of SMU’s Center for Drug Discovery, Design and Delivery. CD4 was launched by SMU’s Biological Sciences and Chemistry departments and has as its mission the search for new drug therapies and delivery methods that can be developed into clinical applications. — Margaret Allen
Researchers find that fruit flies overloading on carbs and protein not only gain weight but have shortened life spans — and develop insulin resistance, a hallmark of Type 2 human diabetes
With Type 2 human diabetes climbing at alarming rates in the United States, researchers are seeking treatments for the disease, which has been linked to obesity and poor diet.
Now biologists at Southern Methodist University, Dallas, report they have developed a new tool that will help researchers better understand this deadly disease.
By manipulating the diets of healthy adult fruit flies, the researchers developed flies that are insulin-resistant, a hallmark of Type 2 diabetes.
Until now, researchers largely have relied on rats, mice and other animals as model systems for exploring the metabolic and genetic changes that take place in diabetics.
A dye test in fruit flies uncovers whether fat cells are responding to insulin. On the left, insulin signaling is active. On the right, insulin signaling is inactive. (Credit: Bauer, SMU)
The fruit fly Drosophila melanogaster has been widely deployed in labs to investigate a wide range of human diseases, from Alzheimer’s to cancer. But the scientific literature hasn’t documented use of the adult fruit fly for studying the metabolic disruptions that are the hallmark of Type 2 diabetes. The fruit fly’s advantages include its low cost and a very short lifespan, both of which enable scientists to undertake rapid screenings in their search for new genetic and drug treatments.
The insulin-resistant fruit fly was developed in the lab of SMU biologist Johannes H. Bauer, principal investigator for the study. It was accomplished by feeding fruit flies a diet high in nutrients, said Bauer, an assistant professor in SMU’s Department of Biological Sciences. That process mimics one of the ways insulin resistance develops in humans — overeating to the point of obesity.
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The lab’s insulin-resistant fruit flies now can serve as a highly relevant and efficient model for studying Type 2 diabetes.
“We learned that by manipulating the nutrients of fruit flies, we can make them insulin resistant,” Bauer said. “With this insulin-resistant model we can now go in with pinpoint precision and study the molecular mechanisms of insulin resistance, as well as drug treatments for the condition, as well as how to treat obesity, how to block insulin resistance and how metabolic changes from a specific diet develop. The possibilities are endless.”
Two overfeeding diets, carb and protein, both result in insulin resistance Insulin, produced by the pancreas, is the hormone that tells our cells to absorb glucose, a necessary sugar molecule that provides our body, particularly the brain, with the energy to function, make repairs, move and grow.
In Type 2 diabetes, a person is insulin-resistant because his or her cells fail to respond to insulin’s signal to absorb glucose. The disregulation of glucose upsets the body’s delicate internal equilibrium, causing massive disruptions in normal cellular processes. These interruptions manifest in multiple disease symptoms, making Type 2 diabetes difficult to characterize, treat and cure.
To provide a good base model organism to study aspects of this complex disease, researchers in the Bauer lab wanted to determine whether flies develop diabetes-like metabolic changes when fed different diets. The researchers developed the insulin-resistant flies in two different ways: One group of fruit flies was overfed a carbohydrate-loaded diet; a second group of flies was overfed a protein-loaded diet. In both cases, the disruption had a profoundly detrimental effect on the flies’ health and physiology.
SMU biologist Siti Nur Sarah Morris, lead author on the study, said the results the researchers observed were both expected and unexpected. The researchers expected the flies to gain weight, which they did. Carb-loaded flies gained excessive weight and got fat, just like humans who overeat sweets, french fries, pasta and ice cream. Protein-loaded flies also gained weight, but upon extreme overfeeding they lost weight, just like humans who follow the popular Atkins Diet, a weight loss program in which participants eat only meat, seafood and eggs.
The researchers expected the carb-loaded fruit flies to develop insulin resistance, which they did.
In a surprising result, however, the fruit flies that overate protein also developed insulin resistance, but at a quicker and more severe rate.
“Carb-loaded flies gain weight. Protein-loaded flies gain and then lose weight. So the two diets have exactly opposite effects on metabolism,” Bauer said. “But too much of either one of them causes insulin resistance. That surprised us.”
Overfed flies had shortened lifespans, differences in fertility In other findings, carb-loaded flies experienced a profound decline in egg-laying, a measurement of fertility. In contrast, protein-loaded flies first experienced increased egg-laying, but the extreme diet led to decreased egg laying. Both diets led to shortened longevity, the scientists reported.
“The high-protein flies looked frail and unhealthy. They moved less, almost as if sedated,” Morris said. “The fatter flies on the high-carb diet had massively decreased fertility; they flew less but still tried to move.”
While both diets resulted in insulin resistance, differences were remarkable.
“The carb data imply a linear relationship between carb levels and health. The more carbs, the more weight, the more sugar storage and fat, the more insulin resistance and the less fertility,” Bauer said. “But with protein, this relationship becomes parabolic, meaning all readouts go up, then come down again. The decreased storage we liken to a catabolic state that is primarily destructive for the body’s optimum metabolic functioning, such as the ketosis typically seen in people eating Atkins-type diets.”
Besides Morris and Bauer, other authors on the study were SMU students Claire Coogan, Khalil Chamseddin and Santharam Kolli. Other co-authors, from Pennington Biomedical Research Center, Baton Rouge, La., are Jeffrey N. Keller, director, Institute of Dementia Research & Prevention, and Sun Ok Fernandez-Kim. The research was funded by the National Institute on Aging. — Margaret Allen
SMU is a nationally ranked private university in Dallas founded 100 years ago. Today, SMU enrolls nearly 11,000 students who benefit from the academic opportunities and international reach of seven degree-granting schools. For more information see www.smu.edu.
SMU has an uplink facility located on campus for live TV, radio, or online interviews. To speak with an SMU expert or book an SMU guest in the studio, call SMU News & Communications at 214-768-7650.
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