• Realizing the Potential of Post-Genomic Medicine

The sequencing of the human genome prompted a titanic eruption of enthusiasm for the new future of medicine, based on the development of drugs targeted to the genes and protein products whose dysfunction can be implicated in human disease. Then the daunting work began of pursuing the connections among human disease, the genome's three billion base pairs and the hundred thousand proteins they generate in the course of operating and maintaining the human body: most of that trail still lies ahead. Since form follows function, a threshold issue is to determine the shapes of proteins, whose constituent chains of amino acids owe their sequence to their genetic encoding but their functionality to the three-dimensional structures they assume through a process of folding.

The best available experimental methods, NMR and x-ray crystallography, are exceedingly slow and labor-intensive for seeing protein shapes. Efforts to develop a new technique based on the growing power of computing technology and advances in modeling had been frustrated until a group of researchers, led by Carlos Simmerling, a member of the Department of Chemistry and the Center for Structural Biology, achieved the critical initial step toward this grail. The group succeeded for the first time in correctly predicting a protein's actual structure at the atomic level through computer simulation, based solely on the protein's gene sequence and the attraction and repulsion tendencies of its constituent amino acids. Even though the protein was relatively small, originally isolated as a fragment of a larger protein, the researchers had to build their own supercomputer with hundreds of PCs, and run a long and complicated computer program that they wrote to simulate the physics of the molecules, in order to achieve their successful results.

The results were confirmed by actual measurements on the protein, made through nuclear magnetic resonance spectroscopy, by a team at the University of Washington. News of the breakthrough, which points the way toward modeling much larger and more complex proteins, which can be composed of much longer amino acid chains, appeared around the world in languages ranging from Chinese and Korean to Russian, Danish and Basque. The group's report was published in the Journal of the American Chemical Society and may be found at-- http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/ja0273851

• Top Quark

In March of 1995, the DZero collaboration at Fermilab, led by Stony Brook scientist Dr. Paul Grannis, announced that they had discoverd the Top Quark, one of the six types of quarks theorized to exist. The Top Quark is the last type of quark to be observed, and this discovery is important evidence in support of the quark theory of the structure of matter—in which quarks make up all the protons, neutrons and electrons in the universe.

Scientists looked for top quark evidence using the Tevatron Accelerator, the world's highest energy particle collider. The collider brings atoms together at high speeds. The atoms break into their component parts, and scientists can observe data on the collisions to find out more about the structure of matter.

Another Fermilab collaboration, CDF, announced the discovery of the Top Quark simultaneously with DZero, further supporting the validity of the discovery.

• Lyme Disease

Lyme Disease, caused by the bacterium Borrelia Burgdorferi and passed by the deer tick, is most prevalent right here on Long Island . If found early the disease is highly treatable, but if left untreated it can lead to irreparable damage of the skin, heart, joints, and nervous system. Perhaps because of its unique location at the epicenter of the Lyme disease epidemic, Stony Brook has been a leader in Lyme disease research from the beginning.

Stony Brook researchers played key roles in discovering the cause of Lyme Disease. In fact, the first time that Borrelia Burgdorferi was isolated from a patient with Lyme Disease was at Stony Brook. Scientists quickly found an effective antibacterial regimen to combat the infection.

• Polio virus synthesis

The virus is one of the simplest organisms on earth; so much so that some scientists argue it is not a living being at all. The poliovirus, for example, is just a piece of DNA inside a protein shell. Simple, yes, but could it be manufactured in a lab? Recently, a team of scientists at Stony Brook University 's Department of Molecular Genetics and Microbiology did just that.

Like putting together a jigsaw puzzle, Drs. Eckard Wimmer, Anika Paul and Jeronimo Cello used commercially available DNA fragments and the already-published DNA sequence for polio to create a working replica of the “wild-type” virus.

With the current state of the world, many officials and scientists worldwide are considering the implications of the discovery as related to bio-terrorism. According to scientists on the project, polio, one of the most basic viral agents, was easy to make, but smallpox a much more dangerous and complex virus would be extremely difficult to manufacture. Still warns Wimmer, “The world had better be prepared.” The project was supported by the Defense Advanced Research Projects Agency of the U.S. Department of Defense.

• Nobel Prize Recognizes MRI's Start at Stony Brook

Some three decades after Nature published the results of Paul Lauterbur’s work at Stony Brook, his seminal contribution to the birth of MRI as the fundamental diagnostic tool we know today was recognized with the 2003 Nobel Prize in Physiology or Medicine. While others had speculated that the magnetic resonance signals of atoms could help distinguish cancerous tumors from benign human cells, Prof. Lauterbur figured out how to locate these tissues within the body and create a two-dimensional picture of them, laying the foundation for actual clinical use. By introducing gradients in the magnetic field, he could determine the origins of radio waves absorbed then emitted by the nuclei by analyzing their characteristics and thereby develop images of soft tissues and other structures that could not be visualized with other methods.

As described by the National Academy of Sciences, “Lauterbur’s groundbreaking idea was to superimpose on the spatially uniform static magnetic field a second weaker magnetic field that varied with position in a controlled fashion .  .  .  .  Because the resonance frequency of nuclei in an external magnetic field is proportional to the strength of the field, different parts of the sample would have different resonance frequencies. Thus, a given resonance frequency could be associated with a given position.” He found through experimentation how to convert the differences in the varying resonance frequencies in an object — including a clam his daughter retrieved from Setauket Harbor near the campus — into an image. By 1974, he produced an image of the thoracic cavity of a living mouse.

• Fossil Bird

Around the world scientists are digging deep into the earth and finding more and more fossil evidence connecting modern day birds with dinosaurs. While excavating a quarry in Madagascar , a team of Stony Brook scientists lead by Dr. David Krause and Dr. Catherine Forster, found one of the most primitive bird specimens yet discovered. Rahona ostromi , is believed to have lived in the Late Cretaceous period (65 to 90 million years ago). This dating places Rahona around the same time as the oldest known bird fossil, Archeopteryx, and in fact, the two share many similarities. 

Rahona has skeletal characteristics of both birds and dinosaurs. For example, vestiges of feathers on wing bones are indicative of developing avian characteristics, while an important clue to dinosaur heritage is seen in the foot. Rahona has a large “sickle-like” middle front toe capable of bending far back and slashing prey or enemies. This ominous looking claw is a unique characteristic of certain dinosaurs like the Velociraptor.

The Stony Brook team has found many other fossils of importance in Madagascar , and the scientists have also set up the Ankizy Fund, to contribute the health and education of Malagasy children.

Image Courtesy: http://cas.bellarmine.edu/tietjen/images/theropod_ancestry_of_birds.htm

• ReoPro and Periostat

In the past decade, Stony Brook University has seen FDA approval for two drugs developed by its scientists. Both ReoPro, used with heart patients, and Periostat, used to treat periodontal disease, are widely used by the medical community.

Barry Coller, MD, developed ReoPro while studying platelet behavior at Stony Brook. During his research he isolated an antibody that inhibited platelets from sticking together in arteries—a major cause of heart attacks. The antibody, was found to be more effective than aspirin. Following FDA approval in 1994, ReoPro, as the antibody was named, became the most commonly used treatment for angioplasty patients, making the procedure safer for use during heart attacks and as a preventative measure.

Dr. Lorne Golub, Professor of Oral Biology and Pathology at the Stony Brook School of Dental Medicine, discovered that non-antibacterial tetracyclines can limit the production of tissue destroying enzymes, in turn limiting the breakdown of gum and bone tissue. He used this discovery to create Periostat, approved by the FDA for treatment of periodontal disease in 1998. New research shows that Periostat may be useful in treating heart disease, and possibly other illnesses.

Detail of a Hubble Photo of the Deep Field South

• Hubble Deep Field South

The first stars apparently started brightening the dark, infant universe just a few hundred million years after the big bang in an explosion of light unrivaled since the dawn of space and time, astronomers reported yesterday.

After a detailed analysis of the most sensitive images ever taken by the Hubble Space Telescope, a team of researchers concluded that the early universe was a much brighter place than had been assumed. "Previous measurements have missed a dominant fraction of the light from the most distant galaxies," Kenneth Lanzetta of the State University of New York at Stony Brook said at a NASA news conference. "Our results indicate the distant universe contained far more light, and hence far more stars, than was previously believed," he added. "In fact, we find as we look toward greater and greater distances, that is toward earlier and earlier times, the star formation activity of the universe increases to the earliest times we can see."

Star formation does not appear to have peaked at the limits of Hubble's ability to detect it. That peak, based on Lanzetta's research, must lie even farther back in time, closer to the big bang itself, perhaps within a few hundred million years. "We're pushing close to the earliest time we could have possibly seen stars, namely we're pushing probably close to that first burst of star formation that took place in early galaxies," Lanzetta said. Bruce Margon, an astronomer at the Space Telescope Science Institute in Baltimore, said the results are sure to be controversial because of the subtle nature of the analysis. But the payoff has definite rewards.

"There's a natural curiosity to think, 'Well, when did the very first ones appear after the big bang? Did the universe take a while to get its act together, or not?' " Margon said. "And the answer is, 'The universe got its act together and started making stars almost instantly.' " More powerful telescopes such as NASA's planned Next Generation Space Telescope, scheduled for launch around the end of the decade, will be needed to confirm Lanzetta's conclusions. But, in the meantime, Lanzetta's results provide a glimpse into an unimaginably early epoch when the universe was formed about 14 billion years ago. "He has teased out an incredibly subtle result . . . and it's probably about as good as Hubble is capable of doing," Margon said.

Lanzetta's team analyzed three so-called Hubble Deep Field images, the equivalent of ultra-long time exposure photographs of visually empty patches of the northern and southern skies. The target areas, about the size of a grain of rice held at arm's length, were chosen to provide clear views out of Earth's Milky Way galaxy and into the depths of space. The images were shot in 1995 and 1998. Amazed astronomers later counted about 5,000 galaxies in the resulting images, a set of photographs that ranks as one of the most scientifically significant accomplishments in the space telescope's 11-year orbital history.

All but about 150 of the galaxies were too faint for the follow-on spectroscopic measurements needed to pin down precisely how far away -- and thus how old -- each star swarm might be. Even so, astronomers were able to use other techniques to determine that the dimmer, more reddish galaxies dated back to roughly a billion years or so after the big bang. Lanzetta's team developed a subtle new technique for analyzing the deep-field galaxies, carefully characterizing the color variations that provided clues to their actual distances. The color characterizations matched up with the galaxies that could be spectroscopically studied. After observations of nearby galaxies, Lanzetta's team also developed a correction factor to account for the way light from a more distant galaxy appears dimmer than the light from one that is close by.

The correction factor, in effect, added back the light "missing" from more distant galaxies. Finally, the researchers included a measure of the gas density of the early universe based on the spectroscopic analysis of remote quasars. In the nearby, "local," universe, high gas density implies high rates of star birth. Putting it all together, the researchers were able to turn the two-dimensional Hubble Deep Field images into a three-dimensional look back toward the big bang. "What we have realized is that even the deepest, most sensitive images of the universe ever obtained by the Hubble Space Telescope . . . are not sensitive enough to detect most of the light of the very most distant galaxies recorded," Lanzetta said. "That light is just too faint, and it's been missed by all previous measurements." In other words, he said, the raw Hubble images reveal the tip of the iceberg "and the bulk of the iceberg is missing." "What we've done is develop a technique to account for this missing light, and we have found that the distant early universe contains far more light, and hence far more stars, than was previously believed," Lanzetta said.

• Virtual Colonoscopy: Ready for Prime Time

In a major step forward for the technology of "virtual colonoscopy," in April, 2004, the U.S. Food and Drug Adminstration announced approval of the use of a 3-D computer visualization technology developed at Stony Brook as a patient screening tool for detecting colon cancer, including polyps, masses and other lesions. The technology, licensed to start-up Viatronix, Inc. [www.viatronix.net], a tenant company in the Long Island High Technology Incubator on the University campus, is the first of the virtual systems to obtain FDA approval. The decision presumably reflected the results of a groundbreaking virtual colonoscopy study published in the December, 2003, New England Journal of Medicine [content.nejm.org/cgi/content/abstract/349/23/2191] and American Journal of Roentgenology, which reported that the new three-dimensional virtual colonoscopy detected about 93% of polyps larger than 8 millimeters, while some 90% of polyps were detected by screening with the more invasive conventional colonoscopy procedure.

The study, conducted by radiologists from the University of Wisconsin, Bethesda Naval Hospital and Walter Reed, and the National Cancer Institute, reported the largest prospective evaluation to date of virtual colonoscopy as a colorectal screening test, involving over a thousand asymptomatic adults who were at average risk. A less favorable report, subsequently published in the Journal of the American Medical Association [jama.ama-assn.org/cgi/content/abstract/291/14/1713] actually covered an older study, completed more than two years ago, using a 2-D virtual scanning technology. The contrasting reports were assessed in a Wall Street Journal article, "Tale of Two Studies: Cutting Through Confusion on Virtual Colonoscopies," April 27, 2004.

The 3-D process is based on images constructed from a CT scan, which requires about 10 minutes and no sedation, in contrast to the hour or more required -- with sedation strongly advised -- for the conventional procedure.

The most important impact of the new diagnostic technology may be to encourage patient compliance. Although the procedure is recommended for everyone over age 50, and colon cancer -- the second largest cause of cancer-related death -- has a 90% cure rate if identified early, only about 40% of Americans at risk for the disease seek out screening because they say the procedure is unpleasant. An editorial in the same issue of the NEJM concluded, "If the results of this well-designed study are reproducible on a wider scale, and if the important questions regarding the appropriate size threshold and the surveillance of smaller polyps can be resolved, then screening virtual colonoscopy is ready for prime time."

A simulated fly-through showing full forward-backward, 360 degree point of view can be seen here--
http://www.viatronix.net/V3D-Colon_Demo.asp