Johns Hopkins Magazine -- November 2000
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S C I E N C E    &    T E C H N O L O G Y


Vitamin D, without the toxicity
Mysteries unfold on Jovian moon
A laser that's out of this world
Of breakups and "babies"
New promise for producing infection fighters

Chemist Gary Posner (top) and graduate student Ken Crawford have designed compounds similar to vitamin D that protect against cancer-- without the toxic side effects.
Photo by Michael Purdy
Vitamin D, without the toxicity

Vitamin D would be a stellar tool for preventing cancer, if not for its toxic downside. In laboratory studies, the megadoses required to achieve protection have caused severe calcium loss, stunted growth, and even death.

But now Hopkins professor of chemistry Gary Posner reports that he has synthesized structurally modified versions of vitamin D, called deltanoids, that protect laboratory mice against skin cancer without triggering toxicity. The mice were treated topically with the deltanoids and exposed to a powerful carcinogen. Each of the four deltanoids tested diminished the number of skin tumors without causing significant calcium loss.

Posner and chemists Jae-Kyoo Lee and Qiang Wang spent the past several years tweaking the structure of vitamin D, building on research that drug manufacturers had reported, in search of a safer modified version, or analog. "Over the years, we've made probably 100 different analogs," Posner says.

"What we did was to take some of the best structural changes that large pharmaceutical companies have made public and incorporated those changes with a structural change that we discovered here 10 years ago in a different portion of the molecule."

Posner's team and professor of environmental health sciences Thomas Kensler selected the four deltanoids that showed the greatest ability to stop the growth of cancer cells, and used those in further animal studies. They reported their findings in the July/August Carcinogenesis.

The researchers plan to conduct further animal tests to see if the deltanoids protect against other forms of cancer. "It could be 10 years before the analog is available for clinical use," notes Posner. Ideally, physicians might one day be able to apply a topical gel to patients who are at high risk of developing skin cancer.

Vitamin D aids the absorption of calcium, and a deficiency of vitamin D can result in the soft bones disease known as rickets. The skin produces vitamin D using energy from the sun and vitamin D is added to milk, but those concentrations aren't enough to protect against cancer. --Melissa Hendricks

Mysteries unfold on Jovian moon

Sky gazers have wondered about the mysteries of Jupiter's moons ever since Galileo spied the satellites through his hand-crafted telescope and offered to name his discoveries for a grand duke he hoped would fund his scholarly lifestyle.

Now, images from NASA's Galileo spacecraft have led to the latest discovery--evidence of "folds" on Europa's cracked, icy surface that provide clues to the Jovian moon's geological history and dynamic behavior.

Louise Prockter, a fellow at Hopkins's Applied Physics Laboratory, and Robert Pappalardo of Brown University's Department of Geological Sciences, analyzed the high resolution images the Galileo spacecraft captured two years ago, during its series of 12 flybys of Europa--an icy sphere about the size of Earth's own moon.

What the researchers found were signs of surface folds they believe are formed when Europa's icy crust is squeezed by intense gravitational forces from Jupiter and the other Jovian moons. Based on Voyager images taken in 1979, scientists previously had learned that Europa's surface was pulling apart, with slushy, icy material moving up through the gaps (a process called "extension") to create Europa's signature cracked surface. But no one understood how the moon could keep its shape if it kept expanding.

"If you covered a balloon with wax and blew it up a little bit more, it would fracture in pieces," Prockter says. "But it was thought to be unlikely that Europa was still expanding. That usually happens very early on in a moon's or planet's history, and Europa is thought to be as old as anything else in the solar system."

The folds may indicate a flexing crust, which is both stretched by gravity-led tidal forces from Jupiter and its other moons, and squeezed by counterbalancing compression. In the August 11 Science, the researchers noted evidence of the flexing crust in mountain-like features in three areas of Europa's surface; the areas resembled patterns of fractures and ridges on Earth (such as the crests and valleys of the Appalachian Mountains or similar fold structures found on the ocean bottom).

The researchers believe that such tidal forces cause Europa's icy shell to rotate slightly faster above the moon's more tractable, warmer inner layers. Much like plate tectonics on Earth, the folds are created when material collides and pushes up. Prockter and Pappalardo first found the folds in Galileo's images of Europa's Astypalaea Linea fracture region. The relatively low crests, which are spaced 16 miles apart, would indicate a thin brittle lithosphere over a thicker region of "warmer," mobile glacier-like ice.

Just how warm the lower layers might be has been cause for scientific speculation: Does Europa harbor life? Voyager's images of Europa's surface showed what some scientists believe are red-colored seas. With a surface temperature believed to be -260 degrees F, the question is whether Europa's tidal tug-of-war with Jupiter and its other moons would create enough heat in those seas to sustain life. "Maybe Europa has a liquid ocean under there that makes it easy for the [icy shell] to move, but we don't know," Prockter says.

The researchers hypothesize that the folds "relax away" to be recycled back into the geological mix. Such a fold might take 100 million years to create, and another 100 million to relax.

A deeper understanding of Europa will take some time--though not as long as an icy fold maneuver. The Galileo spacecraft will likely take no new high resolution images of Europa. But NASA has announced plans to launch a spacecraft named Europa Orbiter in the next few years. Says Prockter: "The purpose of the Europa Orbiter is really to answer all the questions the Galileo images opened up." --Joanne Cavanaugh Simpson

Working with NASA-Godard engineers, Hopkins's Jin Kang has set out to devise a fiber-optic laser system to measure changes in the Earth's atmosphere.
Photo by Jay Van Rennselaer
A laser that's out of this world

A fiber-optic laser system no bigger than a laptop computer could orbit Earth via satellite within the decade as the next high-tech tool to test the health of the atmosphere.

The project, to be led by researchers at the Whiting School of Engineering and NASA's Goddard Space Flight Center, would gather data for monitoring air pollution, the status of the ozone layer, and atmospheric changes that might be leading to global warming.

NASA recently awarded a three-year, $815,500 grant to the Hopkins-Goddard team. The new laser is one of a dozen proposals selected by NASA's Earth Science Technology Office, which is interested in developing better lasers for use in atmospheric sensing applications. Scientists hope to develop a prototype within three years.

The fiber-optic technology--simple, light, compact, and efficient--currently is used mostly in research and telecommunications, but is ideal for space travel. "Conventional lasers are inefficient and extremely bulky," says principal investigator Jin Kang, a Hopkins assistant professor of electrical and computer engineering. Among other limits, such lasers require carefully aligned mirrors, lenses, and other optical devices. In a fiber-optic laser, as the light goes around a loop of fibers, it becomes amplified, Kang says. "Fiber optic lasers are simple," he adds. "If you look at a thread of your clothes, it's not that much thicker."

Kang, who came to Hopkins in 1998, has specialized in photonics, working with fiber-optic lasers during his three years at the U.S. Naval Research Laboratory.

For the NASA project, Kang will design a high-powered ultraviolet laser light source. Goddard scientists will create the laser device and spacecraft. "All the power supplies, all the coolers, all of that has got to be shrunk down into one highly modular package rugged enough for the rigors of space flight," says Harry Shaw, associate branch head for Goddard's Component Technologies and Radiation Effects, in Greenbelt, Md.

The Hopkins-Goddard laser will likely become a critical device in advanced versions of NASA's LIDAR system, which works in a manner similar to radar but uses light instead of radio waves. Light beams aimed at the atmosphere hit gas molecules and bounce back, carrying a wavelength absorption "fingerprint" that indicates the type and density of the gas.

Under new technology applications, fiber-optic lasers could join other test instruments in smaller and cheaper satellites, allowing more widespread use in space. A satellite rigged with a UV fiber-optic laser also would better provide data gathered in the atmosphere's ultraviolet range, allowing more in-depth analysis of ozone levels and a more advanced glimpse into atmospheric chemistry. --JCS

The HST image shows the "mini- comets" that resulted when Comet LINEAR broke up.
Photo courtesy NASA/STSCI
Of breakups and "babies"

Hopkins astronomer Harold Weaver did not expect to see high drama when he began using the Hubble Space Telescope (HST) to observe Comet LINEAR, an erstwhile, unextraordinary comet. But Weaver got a surprise on July 5 when LINEAR dramatically increased in brightness as its core exploded. Over the next few days, the comet blew off a chunk of its crust and shot out an immense amount of dust, "like a giant geyser," says Weaver. The dust reflected sunlight, causing an intense brightening.

Later in the month, ground-based observers reported that the comet was missing in action. They assumed it had disintegrated. So in early August, Weaver went back for a second look with Hubble. He saw that LINEAR had broken up into dozens of smaller pieces and dust. "We saw all these mini comets, fragments, like comet babies," says Weaver. These smaller pieces appear now to have essentially vaporized.

Astronomers do not know what caused the explosion, says Weaver. Something may have forced LINEAR out of its normal orbit, sending the comet closer to the sun, heating an explosive section of the comet's core, he says. "But we don't really know why it broke up.

"It's the first time we've ever watched the breakup of a comet in such detail," he adds. The results support the popular theory that comet nuclei are really made up of a cluster of smaller icy bodies called "cometesimals." --MH

Leckta at work in the lab, sorting enantiomers. The process he developed could aid in the quest for finding new anti-bacterial drugs.
Photo by Michael Purdy
New promise for producing infection fighters

Driven by emerging diseases and growing bacterial resistance to existing antibiotics, scientists are eagerly pursuing new antibacterial drugs. Their quest could now be easier, thanks to a new process for synthesizing chemical compounds developed by a Hopkins team led by Thomas Lectka, associate professor of chemistry.

The process involves a class of drugs--including penicillin and other infection fighters--known as beta-lactams. Such compounds are "chiral," meaning they can appear in both a left-handed and right-handed form (with each form known as an enantiomer). Though identical in structure, the enantiomers can react differently to enzymes; one enantiomer may be beneficial and the other harmful, dramatically altering a drug's biochemical properties. To avoid the confounding effects posed by dual enantiomers, Lectka has focused on synthesis techniques that produce chiral compounds with just one form. As a catalyst, his team uses quinine--a natural substance that was once a premier malaria treatment and is itself enantiomerically pure--as a catalyst. A small amount of quinine can produce large batches of single enantiomer beta-lactams, and since quinine is not changed by the reaction, it can be used indefinitely, Lectka notes.

"Beta-lactams have been critical tools for fighting the spread of bacterial infections in the past, and they could be so again," says Lectka, noting that in addition to their use as antibiotics, "they have recently found use in treating patients with conditions ranging from arthritis to HIV." --Sue De Pasquale