Johns Hopkins Magazine -- September 2000
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SEPTEMBER 2000
CONTENTS

S C I E N C E    &    T E C H N O L O G Y

Findings

Setting sights on a child-proof gun
New promise for appetite control
Bringing clarity to water problems
Quick... follow that storm!


Glorioso (l) and Rydingsward with their child-proof prototype of a Berretta.
Photo by Keith Weller
Setting sights on a child-proof gun

Two Hopkins undergraduates may have engineered an answer to a controversial question being debated by governors, congressional leaders, gun-owner lobbyists, protesting mothers, and the president of the United States: how to make guns safer.

Bryan Rydingsward and Rich Glorioso, both mechanical engineering majors who graduated in May, tackled the problem as their senior project. Their mission: child-proofing a handgun. The students spent about $4,500 in grant money. Their prototype uses a button device on the safety that can be easily manipulated by adults, yet appears too unwieldy for kids.

"We really had no idea what children are capable of, phyically and mentally, so we started with actual testing on children," Rydingsward, 22, says. The young researchers developed puzzles of a sort that did not resemble guns, and gave them to 35 children ages 4 to 12. They hoped to determine which design would prevent accidental shootings and yet be pragmatic for gun manufacturers and users.

The students looked at proposed child-proof designs, including trigger combination or key locks. They found, says Rydingsward, that gun owners are worried about the time and hassle of trying to remember a combination or find a key in the event of an emergency.

Instead, their concept focuses on the device meant to make guns accident proof--the safety. Many safeties are simple enough for children to navigate, researchers say. The students designed a metal plate that can be fastened atop the barrel of the gun, covering the safety lever and forcing it into the position that prevents firing. When two buttons are pressed, the cover slides open allowing access to the safety. Through a linkage with the handle, the device would also reset once the handle was released, say if a gun is set down on a table.

Rydingsward and Glorioso tested the child-proof replica with more than 50 adults and all were able to manipulate the device in less than two seconds. They admit that even that delay could draw complaints from some gun owners.

In designing the prototype, the students modified two replicas of a Berretta. The replica, which shoots blanks, functions like an actual 9 mm semiautomatic pistol, apparently a preferred gun style among homeowners. ("We didn't want to go through administration issues over having a real gun on campus," Glorioso says.) In tackling the design, they ruled out electrical or power sources or alterations of the inner workings of a gun. Again, gun owners are wary about such modifications.

The prototype device needs further research and fine tuning to be ready for possible manufacture.

Andrew Lincoln, a Hopkins injury epidemiologist who worked with the young engineers, was impressed by their sense of confidence in dealing with a controversial issue, including speaking with various media. "They showed a fearlessness or lack of intimidation that I found refreshing," Lincoln says. The two recent graduates, along with project colleague Curt Ewing, a lab administrator in the Department of Mechanical Engineering, already have filed for a U.S. patent for the design. -Joanne Cavanaugh Simpson



C-75 mice eschew food.
New promise for appetite control

It was somewhat ironic that the Hopkins scientists who attended a recent noontime seminar on a potential new diet drug munched on fat deli sandwiches and Pepperidge Farm cookies. After all, if they had been exposed to the drug that was the centerpiece of the seminar, they might have eschewed those foods and all others as well.

The new drug, C75, dramatically cuts food consumption, apparently by targeting a pathway in the brain that regulates appetite, professor of biological chemistry Daniel Lane told his colleagues. "It's a previously unrecognized mechanism for control of body weight," said Lane. However, C75 has not been tested in people.

Laboratory mice injected with C75 lost profound amounts of weight. Mice that received single injections of C75 ate 90 percent less than what their untreated littermates consumed. The researchers also administered C75 to a strain of genetically obese mice. These mice, too, lost tremendous amounts of weight.

Team members noted that C75-treated mice lost far more weight than even their fasting counterparts in the study. "Even more significant were metabolic differences," said pathologist Frank Kuhajda. "If you try to lose weight by starving, your metabolism slows down after a few days: It's a survival mechanism that sabotages many diets. We see this in fasting mice. Yet metabolic rate in the C-75 treated mice doesn't slow at all."

Lane told the cookie-munching crowd he believes that C75 holds great promise of working the same way in people as in mice. Hopkins has received a provisional patent on C75, and several drug companies are interested in conducting further tests of the drug's safety.

Lane and his colleagues, who reported their findings in the June 30 Science, said a serendipitous finding led to the current study. In the course of their longtime research on the abnormal fat metabolism in many cancer cells, Kuhajda and neuroscientist Gabriele Ronnett unexpectedly found that a fungi-produced chemical called cerulenin caused mice to stop eating--suggesting cerulenin might lead the way to new drugs for weight loss. But cerulenin is unstable and extremely reactive. So Hopkins chemist Craig Townsend developed a series of compounds that shared cerulenin's appetite-curbing ability but not its reactivity. The most effective was C75.

"It looks like the drug is acting directly on neurons in the brain"--pathways in those neurons responsible for monitoring the body's fuel supply, explained biochemist Thomas Loftus.

According to this hypothesis, the brain keeps constant tabs on the amount of fuel that is being converted into fatty acids. If the fuel supply (i.e., food) is plentiful, then the brain responds with messages that say, in effect, "cease eating." If fuel is scarce, then the brain signals, "eat!"

C75 apparently fools this system. By inhibiting an enzyme known as fatty acid synthase, C75 prompts the brain to send its stop-eating messages--even if the mouse is ravenous.

Exactly how the message is conveyed is not clear, but further studies in fasting animals suggest a role for yet another molecule--an appetite-stimulating molecule found in the hypothalamus called neuropeptide Y.

Normally, fasting animals have extremely high levels of neuropeptide Y. This substance is presumed to serve a protective function, prompting animals to have the desire to eat. But mice treated with C75, the researchers found, had extremely low levels of neuropeptide Y. "The drug is sending a signal to the brain that the animal has been fed," concluded Loftus.

"This makes fatty acid synthase an attractive target for controlling body weight."

As the seminar wound down, scientists in the audience had a few questions. Did C75 show any toxic effects? None, said Kuhajda. What about the rebound effect? When mice stopped receiving C75, they did regain the weight they had lost, Lane replied.

If C75 makes it to clinical use, it would find an enormous market: Half of all American adults are overweight. -Melissa Hendricks



Charles O'Melia
Bringing clarity to water problems

As a child growing up in New York, Charles O'Melia was fascinated with the Brooklyn Bridge and other manmade spans he saw from the subway on his way to school. Then, one day he took a closer look at what flowed beneath them.

Today O'Melia is a world-renowned expert on water quality and filtration in both treatment plants and natural waterways. An oft-honored engineer and author of more than 100 technical publications, the Hopkins professor of environmental engineering just won one of the most prestigious prizes in his field, the Athalie Richardson Irvine Clarke Prize sponsored by the National Water Research Institute. The prize includes a gold medallion and $50,000 award.

O'Melia, who joined Hopkins in 1980, is keeping the medallion and donating the money to educational institutions, including the one that helped get him here--Manhattan College, where he earned his BS in 1955. It was there his interest switched from bridges to the emerging field of environmental engineering, as stories about toxins in his favorite swimming and sightseeing haunts--the Hudson River, East River, and Atlantic Ocean--captured his imagination. Among other projects, O'Melia has led research efforts on the desalination of water supplies, a process that could prove critical in areas with water scarcity problems, such as the Middle East.

One recent project marked a coming home. Because of his experience in potable water treatment, he chaired an advisory committee that reviewed the management of New York City's water supply: about 1.5 billion gallons of water is supplied daily to 9 million people. New York doesn't filter its drinking supply, though it is treated with chlorine. And the city is trying to avoid a multibillion dollar investment in filtering technology by focusing on reducing pollutants into its water supply in watersheds west of the Hudson River that O'Melia knows so well.

This time, he can do much more than gaze and wonder. "Some of the things they are committed to doing aren't enough," O'Melia says, noting the committee's finding that the city must do more to control disease-causing microorganisms such as cryptosporidium. -JCS



Quick... follow that storm!

Thanks to the efforts of two scientists at Hopkins's Applied Physics Lab, it's now easier than ever to follow a storm--not on TV but via the Internet. And with the National Weather Service predicting a stormy fall for the Atlantic region, many people will be logging on rather than tuning in.

"We started doing this for fun, and also for educational purposes," says Steve Babin, an APL meteorologist, describing the web site that he and Ray Sterner developed at fermi.jhuapl.edu/avhrr.

But for some people around the Eastern seaboard this information is more than educational. When Hurricane Floyd hit in September 1999, the site received over 13,000 visitors per day. "We spent a lot of time [at the website] waiting out the storm," said Jim Raymond of Florida Hospital in Orlando. "Based on the information from the site, we were able to determine when to let [hospital staff] go home."

Unlike the images that you see on the nightly news, the APL Atlantic hurricane web pages offer near-real time satellite images (within two to three hours) and the key components of storm information, at any time of the day or night. While there are other websites that offer storm tracking information, the APL site boasts several unique features: high-resolution images of the storms' cloud formations, which give more detail than the satellite images shown on TV and on other websites; sea-surface temperature maps, which can provide clues about the potential of a storm as it heads toward warmer or cooler waters; and storm track maps, created to show a storm's path.

In 1999, the site was recognized with an educational excellence award from StudyWeb. That's not to say that APL is the only one providing this kind of information. In fact, Sterner and Babin note that their site is for educational purposes only; official storm information can be found at NOAA's National Hurricane Center website ( www.nhc.noaa.gov).

Whatever their purpose, it seems that Babin and Sterner started what has become the newest trend in weather information distribution. Other universities are beginning to offer similar online information, and if the trend continues, the demand for real-time, online storm imaging and data will only increase. -Diana Whitman


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