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Copyright Jessica Snyder Sachs, as first appeared in Popular Science

LIKE A COWBOY loosely holding the reins, Larry Weatherman steers up Deer Creek Road with his left hand on the wheel, his right arm ready at his side. His upper body rocks with the motion of the pickup as he navigates the dirt road's gauntlet of potholes and rocks. Since his retirement from the Missoula County Sheriff's Department in 2000, Weatherman has adopted the bushy white mustache and Stetson of a gentleman rancher. But on a snowy Saturday in March, he has driven 50 miles down from his 20 acres above Montana's Seeley Lake to take a visitor into the forlorn woods that served, three decades ago, as the dumping grounds for Montana's most notorious serial killer.

A gust of snow hits the windshield. Through the swirl, Weatherman spots a narrow break in the pine and fir trees lining the road. He pulls into a shallow ditch and opens his door. "He liked to take his girlfriends up here to party," he says.

Weatherman was a young officer in 1974 when he investigated the first in a series of gruesome murders that ended a way of life in Missoula, a place where people had left their doors unlocked and women felt comfortable walking home alone from the local bar. The first victim was a preacher's wife found gagged, bound, and shot in the basement of her home, her husband's handgun jammed between her legs. In addition to questioning the husband, Weatherman briefly suspected a high-school boy who neighbors had spotted in the victim's backyard that day. A grand jury found insufficient evidence to charge either suspect.

Over the next 12 years, the seemingly random murders continued. Three teenage girls and a married couple were killed, and the town suffered a spate of home intrusions thought to have been thwarted rapes. Then the improbable happened. In 1986 a would-be victim, already trussed and stabbed, managed to break free and kill 30-year-old Wayne Nance in a bloody struggle. Nance, a baby-faced furniture deliveryman and part-time bouncer, was the high-schooler Weatherman had suspected in 1974. Postmortem searches of Nance's bedroom and his father's house uncovered evidence of at least three additional murders and of other break-ins.

But hope for further information about the murders died with Nance. Weatherman was left with the unidentified remains of two young victims. One of them was "Debbie Deer Creek," a teenager whose skeleton he had chiseled out of a frozen grave alongside Deer Creek Road some 21 months before Nance's death. Several strands of dyed hair enabled Weatherman to connect her to a photo of a dark-haired drifter that bar patrons knew as "Robin" before she disappeared a few weeks after moving in with Nance. Weatherman sent out scores of bulletins to the FBI and regional law-enforcement agencies. But the girl's picture and street name failed to locate family.

It would take more than hair strands and a faded picture to identify Debbie Deer Creek. It would take technology--still two decades away--that could extract minute amounts of fractured DNA to reveal an indelible link to a victim's family. It would take one brother's unceasing search to find out what happened to his runaway sister. And perhaps most of all, it would take the U.S. Department of Justice's slow but horrifying realization that there may be far more serial killers on the loose in America than anyone had ever expected.

For two decades, a facial reconstruction made from Debbie Deer Creek's skull sat on top of Weatherman's bookcase facing that of another girl, "Christy Crystal Creek," discovered by a hunter two miles farther up the same mountain road above Nance's home. "I knew somebody once cared for them," he says.

The Silent Missing

Debbie and Christy are far from alone, and the same might be true of the likes of Wayne Nance. In a recent issue of the scientific journal Homicide Studies, criminologist Kenna Quinet wrote that conventional calculations seriously underestimate the number of serial murder victims. "The problem may be 10 times worse than we imagined," she says. Instead of 180 victims a year in the U.S., there may be as many as 1,800.

Quinet, a nationally renowned homicide expert at Indiana-Purdue University Indianapolis, bases her conclusions on simple arithmetic. According to the Department of Justice, up to 40,000 sets of unidentified human remains sit in police-evidence lockers and medical examiners' offices across the nation. If resolved cases are any guide, the majority are murder victims. Against this, Quinet factors the homicides suspected in a significant proportion--as much as 20 percent--of missing-person cases, more than 100,000 of which remain open at any time in this country.

Quinet bolsters her new estimates with evidence of the lengthy careers of the serial killers who are eventually caught and convicted. "Typically, these killers operate under the radar for years, even decades," she explains. Studies show that male serial killers average six to eleven victims over a nine-year period. Female serial killers (primarily health-care workers) average seven to nine victims over the same window.

And that's just those who get caught. "I would guess that at any given moment," she says, "there are at least two people in each state committing serial murder"--more than 100 serial killers on the loose. Washington State is currently tracking at least four: the so-called 22-Caliber Killer, the Index Killer, the Lewiston Valley Killer and the Snohomish County Dismemberment Killer.

Meanwhile, other serial killers are operating too randomly or infrequently to generate a pattern or are cunning enough to prey on those unlikely to be missed. Quinet calls these possible victims America's "missing missing," the tens of thousands whose disappearance is not taken seriously by law-enforcement agencies. They include those that law enforcement assumes to be "missing" by choice: runaways, transients, prostitutes, and anyone who has an outstanding bench warrant. (The irony, Quinet notes, is that the warrant can be for the missing person's failure to appear in court.)

John Morgan, deputy director for science and technology at the National Institute of Justice, the research arm of the Department of Justice, believes that part of the problem is the increasingly transient nature of American life. "We live in a more fragmented society," he says. "A lot of homicides that occur involve strangers." And for a greater number of the victims, living far from their hometowns and disconnected from a social network, their absence won't be noticed, or they will be dismissed as having simply moved on. As a result, Morgan says, it's now less likely "that a particular homicide will be resolved and the killer brought to justice."

The first step in solving these crimes--even before a detective can start to connect the clues--is connecting the bodies to the missing. "After all," Quinet says, "it's hard to conduct a murder investigation when you don't know who the victim is."

One in a Million

Derek Bachmann was 14 in 1984 when he helped his 15-year-old sister, Marci, pack her bags and run away from their Vancouver, Washington, home. "She told me my stepfather was touching her, making her touch him," he recalls. "I told her, 'You're right, you need to get the hell out of here.' " That was the last time he saw her. "The fact that I helped her pack has always haunted me," says Bachmann, now a Web marketer living outside St. Louis. "I mean, there were five different serial killers in the Northwest at the time." (In fact, there were at least eight.)

In 1991 Bachmann began to search for his sister, if only to confirm his fears. "I think I knew that if Marci was alive," he says, "she would have contacted me." He called and wrote to scores of homicide task forces and vice squads across the country, the latter in case Marci had fallen into streetwalking. "I tried everything," he says. "I tried psychics. I hired a private investigator, spent $10,000 on him. Got nothing."

By 2000, Web sites such as the Doe Network offered Bachmann a new resource. Maintained by amateur detectives and families of the missing, these cyber-bulletin boards feature case histories and, when possible, photos or artist re-creations of the unnamed dead, typically gleaned from news and police reports. Bach-mann began spending all-nighters at his computer. His obsession put a strain on a short-lived marriage, he admits with a slow shake of his head. "The atrocities I've seen looking for my sister."

Among them was a flower-adorned memorial page dedicated to a girl named Robin, with a photo of a dark-haired girl in glasses under the banner "Do you recognize this face?" Bachmann looked again. There was something familiar about the mouth and nose. "I showed it to my relatives," he recalls. "They said, 'No way. Marci never wore glasses.' " Besides, the hair color was wrong. Still, a few months later, he dialed the number provided for the Missoula County Sheriff's Department and left a message for Captain Greg Hintz. No return call.

When Marci left home in 1984, Seattle's Green River Killer was at the height of a spree that would eventually claim the lives of as many as 49 women, mainly prostitutes and teenage runaways. Bachmann wrote to King County detective Tom Jensen, head of the Green River Task Force, who promised to compare Marci's dental records with the impressions taken from the four unidentified victims in his custody. But no dental records were available, and Jensen added Marci's file to those jamming his filing cabinets.

In 2001, King County sheriff's deputies arrested 53-year-old truck painter Gary Ridgway for the Green River killings; two years later, he was sentenced to 48 consecutive life terms. The work of the Green River Task Force was finished. But Jensen still had more than 100 missing persons and suspected homicides in his files.

Jensen's captain assigned three detectives from the disbanded task force to review the cases and make a final effort to close them. And so, in the summer of 2005, detective Raphael Crenshaw called Derek Bachmann in Missouri: Was Marci still missing? Crenshaw told him about a new program that attempted to match family DNA against unidentified remains. Bachmann was eager to supply his, but Crenshaw also needed samples from his parents.

"I knew my dad would take a lot of convincing," Bachmann says. But he did convince his mother, who still lived in Washington. The next week, she rubbed a cotton swab against the inside of her cheek, sealed it in a plastic baggie, and sent it to the sheriff, who shipped it on to Texas.

Connecting DNA's Dots

When Nance and Ridgway were going about their grisly business, no method was available to connect the missing, like Marci Bachmann, to the dead. But there's now a lab, in Fort Worth, Texas, that can close the gap.

It's another March morning, and a steady rain has Fort Worth's Trinity River running high through the city's cultural district. On the other side of Camp Bowie Boulevard, employees and students are leaping over the ponds growing in the driveway of the University of North Texas Health Science Center. The third floor of this beige stucco high-rise is home to the university's Center for Human Identification, the only academic DNA lab in the country dedicated to identifying human remains.

Photo of Dixie Hybki and Rhonda Roby at the Center for Human Identification courtesy of the University of North Texas Health Science Center

In 1989, molecular biologist Arthur Eisenberg began using DNA to settle questions of identity in cases ranging from paternity to homicide. For the next decade, Eisenberg developed many of the procedures and standards used in DNA testing today. Around 2000, he began to focus on missing persons, and in 2001, he and his staff built a state DNA database. Since then, the center's capacity has grown to handle cases from across the country.

The victim specimens that arrive at the center range from well-preserved femurs (thigh bones) to broken slivers of bone that have been sitting inside police warehouses for decades. It's far easier to extract DNA from recent samples, and the center prioritizes easy identifications. Well-preserved or relatively fresh remains for which a family connection is already suspected take precedence over colder cases with no leads. The center has been able to solve one in every four of its cases.

Still, it's the difficult cases--the shots in the dark--that tantalize, says the center's project manager, Rhonda Roby. She speaks from experience, having spent her career developing methods for extracting DNA from severely degraded remains. In 1991 Roby began working in the Office of the Armed Forces Medical Examiner, where she helped develop methods for identifying the skeletal remains of American soldiers from Vietnam, Korea and World War II. In 2001 she flew to New York City to help set up protocols for the unimaginable task of identifying more than 20,000 pieces of human tissue retrieved from the ruins of the World Trade Center. She has also helped identify victims of Chile's Pinochet regime and, in a curious aside, the remains of Nicholas II and the Romanov family of tsarist Russia.

In 2004, shortly before Roby's arrival, the center achieved its first successful DNA extraction in an extremely cold case. The remains--a slender, yellowing femur--had arrived by FedEx. Forensic analyst Lisa Sansom cataloged the bone in the center's database as F2775.1EC and carried it into the lab's bone room, behind a door flagged "Forensic Low-Copy Area. AUTHORIZED PERSONNEL ONLY." The amount of genetic material retrieved from old bone tends to be so small as to be easily overwhelmed by the ambient DNA of a floating skin flake or a saliva droplet. Inside the Low-Copy Room, analysts don full gowns, face masks and surgical gloves. A positive-pressure system keeps "dirty" outside air from flowing in, and analysts have their genetic profile entered into the center's DNA database so that those will be excluded from target sequences.

The work differs from the kind of DNA fingerprinting used to identify biological evidence left at a crime. It is extremely difficult--sometimes impossible--to extract conventional nuclear DNA markers from an old bone. The center has become skilled in extracting and analyzing a hardier but less-known source of DNA: that of the mitochondria that reside in our cells.

Except for identical twins, each person's nuclear DNA is unique. But each of us has another set of DNA located outside the cell's nucleus and inside the mitochondria, the tiny organs that supply a cell with energy. We inherit mitochondrial DNA, known as mtDNA, directly from our mothers, and we share it with our siblings. It's not unique, but mtDNA is enough to narrow the search for a victim's family.

Sansom spent almost an hour scrubbing and sanding the femur's surface before attempting extraction. Few of the bones here contain marrow, which dissolves in the first two or three years after death. F2775.1EC had spent some 20 years in a box inside a police warehouse, so DNA would have to come from the scant cellular material inside the bone's white scaffolding.

She used a woodworker's dremel to cut a rectangular window in the thickened area of bone just below the femur's rounded head, where the thigh muscles once attached. Next she chilled, pulverized, and blended the sample inside a freezer mill loaded with sterilized ball bearings. Using an automated chemical process, she broke open the bone cells, released their genetic contents, and washed, concentrated, and purified the extract.

For genetic analysis, Sansom first had to increase the DNA to detectable amounts using a process called DNA amplification. Forensic software translated the results into a four-color graph of peaks and troughs. Drawing on her training and experience, she translated each graphic peak into one of the four nucleotide letters in the DNA alphabet. It took her about a week to process sample F2775.1EC.

When the amplification signals aren't clear, the chances for a reliable match plummet. In the worst case, the sequence data prove ambiguous, and workers must repeat the extraction and analysis. Sansom got her sequence on the first try. She uploaded it to the center's DNA database. No hits. Then she uploaded the data to the FBI's national missing-persons database. Again, no hits. Not yet.

Scaling the Backlog

In 2004 the center received a major investment to help realize Arthur Eisenberg's goal of establishing a National Center for the Identification of Human Remains. It was the first of several National Institute of Justice grants given over a five-year period totaling more than $7 million. The center's mission was to perform DNA testing on unidentified skeletal remains and "family reference" samples free of charge for any local or state law-enforcement agency that requested it. It's now a clearinghouse at the heart of an effort to address the thousands of missing persons and unidentified remains discovered each year--what the justice department calls "America's silent mass disaster."

"The World Trade Center attack devastated this country with its massive loss of life," Eisenberg says. "But if people only knew how many more unidentified murder victims there are . . . If you go back even 20 years, there are literally hundreds of thousands of families who have missing loved ones." Even with generous funding, progress will ultimately hinge on making identifications cheaper, faster and more definitive, he adds.

Laboratories such as the Center for Human Identification will be swamped now that more states mandate the collection of family-reference samples with missing-person reports. The center, Eisenberg says, must advance the technology used to identify human remains as it goes. By way of example, he cites a new program that can use broken bits of traditional nuclear DNA to identify weathered bones.

The tests scan some 40 lengths of highly fragmented DNA for single-nucleotide polymorphisms (or SNPs, pronounced "snips"), one-letter variations in the genetic code. The SNPs are then combined to create unique DNA fingerprints. If the center's tests are successful--and Eisenberg says they're making rapid progress--SNPs will allow forensic analysts to identify old bones more reliably than they can using mtDNA. "If SNPs pans out, it will be another revolution in how we deal with homicide," the National Institute of Justice's Morgan says. "There will no longer be a reason to have unidentified remains."

In addition to testing such systems, the Center for Human Identification is collaborating with other institutions in the effort to improve identification. It is working with the University of Tennessee, for example, to automate DNA analysis and speed up identifications for all the investigators and families tortured by a cold case. Right now, the center's tests produce a chart of several hundred peaks and valleys that a trained forensic analyst must read one nucleotide "letter" at a time. A second analyst then reads it again to verify its accuracy. Although complete automation of the process remains a distant dream, Tennessee scientists have designed a software program that can read "perfect" sequences, or unambiguous graphics. Soon it may be able to replace the second read and thus slash personnel costs and turnaround time.

But extracting and reading DNA from unidentified remains is only half the challenge. That DNA must get linked to the right missing person. What the country has sorely lacked, Morgan says, is a central repository for information such as photos, fingerprints, dental records, DNA sequences and other identifying information on both missing persons and unidentified victims. Make that database searchable, and it becomes a profitable tool for homicide detectives. Open it to the public, and it becomes a merciful resource for the thousands who currently spend their nights combing disturbing Web sites.

In 2005 the U.S. Attorney General's office formed a Missing Persons Task Force to develop the National Missing and Unidentified Persons System, or NamUs (identifyus.org). In 2007 the first part of the system--a searchable database of unidentified human remains--went live. Last year, the program opened up a national database of missing-person reports. And later this year, NamUs plans to connect the two, with a cross-searchable database that automatically matches the missing and the dead.

The Match

Before the NamUs database is complete, though, researchers at Fort Worth's Center for Human Identification have to rely on meticulous information-gathering and luck. The center has put together a DNA-collection kit for family members of the missing, which it sends out free of charge to the nation's police and sheriff's departments. Law-enforcement officers mail cheek swabs collected from the family back to the center, where workers analyze them in batches of up to 80 to yield both nuclear- and mitochondrial-DNA profiles of parents and siblings.

As each family member's DNA fingerprint comes off the line, it too goes through the databases to search for approximate matches among the dead. The process is spellbinding, claims forensic analyst Melody Josserand. Any of thousands of mysteries could be solved at that moment. "Even though I do searches 30 or 40 times a week, I've never walked away," she says. "I sit here with bated breath."

Josserand remembers the day in March 2006 when Unidentified Person F2775.1EC flashed across her screen. She had just uploaded family-reference sample F3352.1US, submitted by the King County Sheriff's office. Like the reels of a slot machine, twin columns of numbers rolled down her monitor. The rows for six out of six mitochondrial-DNA base pairs flashed green. A perfect match. But mtDNA alone, she knew, wasn't definitive. Fortunately, back in 2004, Sansom was able to pull seven markers for nuclear DNA from the victim's bone sample. Josserand compared the family-reference sample with that. All of them matched.

Josserand retrieved the folder for Unidentified Person F2775.1EC and checked it against the file for the family-reference sample. "The metadata all matched," she says of Debbie Deer Creek's physical descriptors: female; approximate age, 17; weight, 125; height, 5'7". Estimated date and place of death: 8/19/1984, Missoula, Montana.

From the missing-person report, Josserand read the name: Marcella Bachmann. Last contact: 5/1984, Vancouver, Washington. "All I could think was, 'I wonder how this poor girl got from here to there?' " she says. Still, certainty depended on more family samples, ideally from the biological father. So the call went out to Derek Bachmann through Detective Crenshaw in King County. Crenshaw didn't say anything about the bone from Missoula. "I gave him the spiel I give everyone, so as not to get hopes up," he says. " 'The lab wants more DNA samples to make sure that if there's a hit, they can narrow it down.' "

"I called up my dad," Bachmann says, "and flat-out told him, 'You have to do this. I have to know.' "

On March 22, 2006, the Center for Human Identification received two FedEx envelopes, one containing a cheek swab from Bachmann, the other from his father. The father's nuclear DNA matched all of Debbie Deer Creek's nuclear-DNA markers. To underscore the identification, Derek's mtDNA, like that of his mother, proved identical.

Following protocol, the Center for Human Identification relayed the news to the National Center for Missing and Exploited Children, which in turn called Missoula and Captain Hintz, who had submitted Debbie Deer Creek's femur after Larry Weatherman's retirement.

"I'll never forget his call," Bachmann says. "I was in a poker tournament and had to step outside." As Hintz spoke, Bachmann suddenly realized that he didn't want "closure" after all. "I instantly grasped the idea that he was finally calling back about the Web-site photo. I told him I'd been thinking about it, that the picture couldn't have been my sister," he recalls. "Well, he disabused me of that."

Photo of Derek and Marci in 1971 courtesy Derek Bachmann; Photo of Wayne Nance and "Robin" courtesy of Missoula County Sheriff's Office

The Final Identification

Almost exactly two years later, on this snowy March day in Missoula, Weatherman waits for Derek Bachmann to step out of the county truck they have borrowed for their second visit to the place where Weatherman unearthed Marci's frozen remains on Christmas Eve 1984.

Bachmann shivers inside his leather jacket. The snow quickly saturates his sneakers as he follows the retired lawman a quarter of a mile through the woods to a bluff above the Clark Fork River. A grove of spindly conifers still surrounds the mossy depression that once held Marci's body. "It was a lot harder the first time," Bachmann says of the visit. "Yeah," Weatherman acknowledges. "That was a hard one for you."

From beyond the bluff comes the rumbling sound of construction--or rather, deconstruction--echoing up from the Milltown Dam below. A strip of orange and yellow surveyor flags marks a path past Marci's gravesite to what will be a viewing platform directly above a river-restoration project. In addition to tearing out the old dam, the county plans to build a small park. Construction is due to begin in the spring. Bachmann has come back, in part, to ensure that nothing desecrates Marci's spot. Perhaps he can even persuade the county to raise a small memorial, he proposes. Weatherman nods in agreement.

"I suppose you're ready to put all this behind you," Bachmann offers as the men head back to the truck. "I don't suppose it ever will be," Weatherman says, "until we get Christy identified."

At press time, DNA from Christy's femur had been entered into the Center for Human Identification's database of cold-case remains, as well as the national DNA database. She's ready to be found.

This Germ Could Save your Life ... 
       Or at Least Keep Your Teeth Cavity Free

Copyright Jessica Snyder Sachs, first published in Popular Science Photo of Strep. mutans courtesy Jeffrey Hillman 

It's a drizzly morning on New York's Upper East Side, and Rockefeller University microbiologist David Thaler is sipping a double espresso amid the retro-hippie pillows and dangling paper stars of Java Girl, a favorite haunt of the neighborhood's brainiac Nobel laureates, aging poets and famous entertainers. Thaler somehow manages to embody all three-a long, graying ponytail curling down the middle of his back, wire-frame glasses askew over expansive brown eyes, and a schnozz to rival an Einstein, Ginsberg or Allen. Thaler is one of the leading cheerleaders for a new field of biotechnology aimed at engineering the bacteria inside us to deliver drugs, destroy tumors, actively fight infection, and even vaccinate against their disease-causing kin.

Our ancestors, Thaler explains, emerged from the Stone Age by genetically engineering plants and animals through selective breeding, transforming the wolves that preyed on their flocks into the domestic dogs that would guard them. "Except for wild-caught fish, virtually everything we eat today has been engineered," he says. "Meanwhile, we're walking through this ocean of bacteria and only looking at them as something that can make us sick, rather than something to cultivate." He believes that it's time to move humanity from being microbe exterminators to microbe farmers.

Thaler thinks we need what he calls a "second Neolithic revolution." Although his day job as a microbiologist at Rockefeller revolves around such abstract research as testing life's speed limit (current record for replication: eight minutes), he sees himself as an idea man, someone who might help advance an entirely different mind-set in medical microbiology: Instead of using antibiotics to kill harmful bacteria in our bodies and our environment, why not coax bacteria to do our bidding?

"The technology to harness these bacteria exists," Thaler says. Biotechnology firms already use bacteria like E. coli as tiny factories. Just slip the DNA instructions for, say, a new protein-based drug into E. coli and, in its endless quest to replicate itself, the bacterium will replicate the drug as well.

But it's one thing to employ genetically engineered bacteria to produce pharmaceuticals inside a sealed vat. It's quite another to deploy what some call "Frankenbugs" inside a patient. The same characteristics that make bacteria so amenable to genetic engineering-their malleability, their incredible replication speed, their genetic promiscuity-allow their newly acquired DNA to spread to other microbes, including potentially dangerous ones.

Such concerns have largely kept the first generation of engineered superbugs confined to biohazard-containment labs. But the few microbes that have made it into limited human trials-a cavity stopper, a tumor destroyer, a bowel soother-have been enticingly successful. And so the first standoff over body-ready bugs is taking place before the review boards of medical centers and government regulatory agencies, the people who will decide if the world is ready for engineered superbugs.

"I honestly think people are more comfortable with the idea of nano-robots scurrying through their bodies than they are of deploying bacteria," Thaler muses. "But when you think about it, you cultivate your lawn. You'd probably like to cultivate your internal landscape."

THE CAVITY KILLER

Jeffrey Hillman, an oral biologist for-merly of the University of Florida, is a poster child for the kind of biotherapeutic future that Thaler envisions. Hillman has spent a decade lobbying the FDA to let him test a transgenic tooth bug in volunteers. "Fortunately, we had no idea what was ahead," says Hillman of the gantlet of regulatory requirements he has had to tackle since 1996. That was the year Hillman founded Oragenics, a biotech firm dedicated to commercializing his patented cavity-preventing Streptococcus mutans, a genetically modified organism (GMO) that's the product of nearly 30 years of research.

Inside the mouth of most every person on the planet, colonies of S. mutans bacteria thrive on leftover sugars. The by-product of their digestion is the acid that eats away at tooth enamel and causes cavities. But there are many different strains of S. mutans, and some cause more trouble than others. In the summer of 1976, Hillman was trying to replace cavity-prone strains with those that secrete less enamel-eroding acid. Unfortunately, it seemed almost impossible to permanently eradicate a person's "native" S. mutans once his or her teeth became colonized in early childhood.

"We were trying all sorts of crazy things," Hillman recalls. "One time, we were painting volunteers' teeth with iodine. Then we tried fitting their teeth with trays filled with antibiotics." Yet no matter how thoroughly Hillman banished his volunteers' native S. mutans or how quickly he re-colonized their teeth with a benign strain, the switch-out never stuck. "Slowly but surely, a person's indigenous strain always came back," Hillman says.

In 1982 Hillman hit on the idea of first finding a strain aggressive enough to elbow out a person's native tooth tenants and then knocking out its genes for acid production. He conducted the microbial equivalent of cockfights, setting various strains of S. mutans against each other in crowded petri dishes. He knew he had found his ideal candidate when he saw that one "pinprick" colony had cleared a perfect circle in the lawn of other bacteria around it. When Hillman and two of his labmates introduced the strain into their own mouths, it quickly took over, banishing their native S. mutans in the process.

Next, Hillman deleted the microbe's gene for acid production, but the superbugs didn't survive the genetic tinkering. Most strains of S. mutans, including this one, use lactic acid to dispose of metabolic waste. Without acid excretion, the waste builds to toxic levels, killing the microbe.

Hillman solved the problem by making his bug produce alcohol instead of acid. To do so, he borrowed a gene for alcohol production from Zymomonas mobilis, which is used to make pulque, or Mexican beer. The resulting bug didn't produce enough alcohol to make its host at all tipsy. But in studies with lab rats, it replaced the animals' existing S. mutans and kept the rats mostly cavity-free on a high-sugar diet that would normally destroy their teeth.

The trouble was that Hillman now had a true transgenic-an organism that expressed the genes of two different species. The prospect of tests in humans meant that he had to go to the FDA for approval. The FDA eventually referred his case to the National Institutes of Health's Recombinant DNA Advisory Committee, created in 1974 in response to public concern over the safety of interspecies gene transfer. The committee, which includes ethicists and patients as well as scientists and physicians, reviews any application for a transgenic intended to be used outside a sealed laboratory.

In 2004, the committee gave Hillman the green light. Usually, this is enough for full FDA approval. But not this time. FDA regulators asked Hillman to cripple his bug to guarantee that it could be removed should it ever cause problems. "When we asked them what kind of problems, they had no idea," he recalls. "I guess we were setting a precedent."

The regulators saw a genetically modified bacteria that was robust enough to take over any person's mouth, and they were worried about its unchecked spread. Their decision reflected a common criticism of GMO biotherapeutics. "The main problem . . . is that [GMOs] are usually poorly contained," argues geneticist Joe Cummins. Recently retired from the University of Western Ontario, Cummins is a leading spokesman for the London-based Institute for Science in Society, an anti-GMO lobbying group. "They're bound to escape and to pollute the systems of people who don't require therapy."

So Hillman knocked out more genes, this time rendering his microbe unable to survive without an amino acid that test subjects would need to supply, twice daily, by rinsing with a specially formulated mouthwash. In addition, the agency required that Hillman test on patients wearing full dentures that could be dropped into bleach at the end of a week. The volunteers could not have children in their homes, and their spouses had to wear full dentures as well. And both the volunteers and their spouses had to be robustly healthy and under age 55. "We screened more than 1,000 potential volunteers," Hillman says, "and we found two."

The miniature, two-person trial proceeded without a hitch at the end of 2006, with no adverse side effects and complete elimination of the organism at the end of seven days. Last November, past the 10th anniversary of his original FDA application, Hillman received approval to use his crippled transgenic in a larger clinical trial. "Real people with real teeth!" he exults. For safety, the volunteers will spend the weeklong trial in a biocontainment ward.

Should his superbug prove as harmless as it appears, Hillman hopes the FDA will eventually allow him to skip the step where he renders it a nutritional cripple. Users could then dispense with the daily amino-acid mouthwash.

Might the bug then begin spreading from one person's mouth to the next? It's unlikely, Hillman says. When he and his labmates colonized their teeth with their GMO's ancestor, it did not spread to wives and girlfriends, even while remaining in their own mouths for decades.

Proponents like Thaler ask whether such an "uncontrolled release," if it were to occur, would be a bad thing. "What would it be like for us to have benign versions of Typhoid Mary walking around," he asks, "spreading their health-enhancing germs?" In some cases, though, uncontrolled release of genetically modified bacteria could lead to disaster, even if the intended effects were nothing but beneficial.

ATTACKING CROHN'S

On day three of the study at the Academic Medical Centre in Amsterdam, the 43-year-old Dutch farmer felt so good that he was packing his bags to leave the hospital. The nurses caught him just as he was headed out the door of the center's new biocontainment ward for gene therapy. Its rooms are kept under negative pressure so that even if a window breaks, bacteria-laden air will flow in, not out. The man had been spending his days confined to little more than a glorified hospital room, with doctors and nurses coming and going in head-to-toe surgical garb. The bug that was healing his body had to remain isolated, by government order. "We had to explain to him that he was not free to leave, no matter how wonderful he felt," recalls study leader Maikel Peppelenbosch.

Over the previous eight months, Peppelenbosch had managed to win government approval for a clinical trial that deployed a genetically modified cheese-making bacterium, Lactococcus lactis-Thy12, to relieve Crohn's disease [launch the gallery

here, to see how it works]. This excruciating bowel disorder is caused by the immune system mistakenly attacking the intestines' normal complement of digestive microbes. The result is a vicious cycle of painful inflammation and gaping ulcers that can progress to life-threatening perforations of the colon.

Dutch approval of the trial-and the willingness of patients to cycle through 11 days of biological isolation-was a testament to both the seriousness of the disease and the lack of reliable cures, Peppelenbosch says. "These were patients for whom taking out the bowels was their last remaining option." Funding for the study came from the U.S., by way of a private research grant from billionaires Eli and Edythe Broad, whose son suffers from Crohn's.

The way to treat the disease is to turn off the immune system's attack on the intestines' native bacteria. Researchers have long known that lab animals whose bodies fail to produce the immune-calming molecule interleukin-10 develop severe inflammatory bowel disorders similar to Crohn's. But efforts to administer IL-10 are fraught with problems. Stomach acid destroys the protein, so it can't be taken by mouth. And introducing it into the bloodstream risks paralyzing a patient's immune system.

Any solution must deliver the immune-calming molecule exactly where it's needed-inside the intestinal tract-but nowhere else. That's where Lothar Steidler's creation comes in. In 1999 Steidler was pursuing postdoctoral studies into Crohn's-disease treatments at Ghent University in Belgium. In an impressive molecular sleight of hand, Steidler took the gene for IL-10 and slipped it into L. lactis.

But he didn't stick it just anywhere in the cheese bug's genome. Steidler understood how important it was to prevent his bug from escaping into, say, the sewer system, where any number of nasty, disease-causing bacteria might pick up the IL-10 gene. The result could be pandemic disaster: a pathogen out in the wild with the ability to cripple the body's disease-fighting response.

"I knew I had to build in some sort of suicidal mechanism," he explains. He also had to prevent gene swapping between his "good bug" and a potential bad guy. So Steidler made sure that the incoming IL-10 gene always replaces another gene needed to produce the nutrient thymidine. That way, his new bugs can't make thymidine, and so they die of nutrient starvation within a few days. That fleeting life span is enough to complete their mission but not long enough to survive in the waste that flushes down the toilet.

Even better, if the inserted gene jumps into another organism, it replaces that microbe's thymidine gene. So any bug that receives the gene likewise becomes a doomed nutritional cripple. "Fortunately, Lothar designed this bacterium very well," says Peppelenbosch, who collaborated with Steidler to usher the transgenic through regulatory approval in the Netherlands. Their proposal received no objections from either regulators or the public-an unexpected feat in rabidly anti-GMO Europe, he notes.

The team faced no lack of volunteers for the trial. The doctors at the Academic Medical Centre saw scores of patients with severe Crohn's that failed to respond to standard anti-inflammatory drugs. The researchers ushered 10 patients into their containment ward, one by one, for their seven-day treatment and 11-day isolation.

Eight of the 10 Crohn's patients experienced relief from pain and diarrhea, five dramatically so. One withdrew early for unrelated reasons, and none experienced any worsening of symptoms or problematic side effects. Most important for the prospect of larger studies, Steidler demonstrated that his transgenic microbe completely disappeared from the volunteers' stool within a day of swallowing their last capsules of live bacteria.

As expected, the patients' symptoms reappeared a few weeks after they returned home, and several came back to plead for continued treatment. "We couldn't, of course," Peppelenbosch says, because the trial was over. Steidler and Peppelenbosch are seeking Dutch approval for a larger, placebo-controlled trial, this time without the onerous restrictions of isolating patients on a biohazard ward. 

Built-in suicide mechanisms such as Steidler's may prove key to the widespread use of GMO biotherapeutics. "Now that the biocontainment issues are being fully recognized and achieved, I think it's all going to move very quickly," predicts North Carolina State University micro-biologist Todd Klaenhammer.

THE TUMOR BUGS

In January 2002, doctors at the Mary Crowley Medical Research Center in Dallas began injecting a genetically modified breed of salmonella into three cancer patients with large, inoperable tumors that had failed to respond to radiation or chemotherapy. For reasons still poorly understood, salmonella proliferates inside malignancies, perhaps because cancerous tumors tend to remain beyond the reach of the immune system. This salmonella was special, though. A Yale University team led by microbiologist David Bermudes inserted an E. coli gene into the bacteria. The gene produced an enzyme that activates a highly noxious, tissue-destroying drug. "The beauty is that neither the enzyme nor the drug that it activates does anything toxic except in places where they end up together," Bermudes explains. In other words, the system is engineered to be harmless outside a tumor but deadly inside it.

The 2002 pilot trial proved a success, in that the bioengineered salmonella delivered its enzyme payload, produced a modest shrinkage in tumor size, and did no harm to the three patients, but the trial was too small to make any claims of a cure. To move into larger, meaningful trials would require following in Hillman's footsteps through a battery of federal regulatory review boards. That costs money. Even if the researchers received approval to go ahead, they would need to come up with the many millions of dollars needed to usher any potential cancer treatment through large-scale patient trials.

That investment would most likely come from Vion Pharmaceuticals, the Connecticut biotech firm that currently holds Bermudes's patent on the tumor-busting salmonella. Vion has no plans to tackle the regulatory process in the near future, however, says Ivan King, Vion's vice president for research and development. "As a small company, we cannot move many things forward at any one time," he says. What's needed, he believes, is interest from a larger pharmaceutical company with much deeper pockets-just the kind of company that has yet to show interest in highly experimental bioengineered bacteria.

THE NATURAL WAY

Meanwhile, some researchers are focusing on unmodified microbes that could benefit the body. These "probiotics" are sold in grocery and health-food stores, yet few of the numerous available products have been rigorously tested. One of the exceptions is Lactobacillus GG, or "Culturelle," isolated in the 1980s by Sherwood Gorbach and Barry Goldin of Tufts University. Over the past two decades, Gorbach, Goldin and others have published 250 scientific papers on this strain's disease-fighting effects. Studies suggest that the bug has an immune-calming effect that may ease some food allergies. But its one clear and proven benefit is to reduce a person's risk of picking up one of the many nasty intestinal bugs that cause food poisoning, traveler's diarrhea and antibiotic-induced gastroenteritis, which results when antibiotics kill off a person's normal intestinal bacteria and a disease-causing invader moves in.

In Europe, where probiotics have long been popular, they have also been used to prevent chronic respiratory and ear infections. In the early 1990s, Swedish ear-nose-and-throat specialist Kristian Roos developed a throat spray containing a medley of throat bacteria that dramatically reduced the recurrence of chronic strep infections. A few years later, Roos developed a similar concoction that protected toddlers and preschoolers who were predisposed to ear infections.

Roos's probiotics demonstrated their worth in small clinical trials. But they also illustrate the challenge of developing a natural probiotic into a medical therapeutic. A small clinical trial may be enough to put a health claim on a nutritional supplement sold over the counter. But Roos wants to see such cures in the hands of doctors, who would judiciously prescribe them to patients. To do that, he must prove that his probiotics work in the same kind of large, multimillion-dollar trials that have stymied Bermudes's cancer-fighting GMO.

For that kind of money, Roos admits, investors are right to expect an ironclad patent to protect their investment. But that's difficult to do with bacteria that occur naturally on and in the human body. "Even though we can patent our particular mixture of organisms, it would be easy for someone else to come along and put together something slightly different from the hundreds of protective strains found in people's throats," he explains. Without the assurance of some meaningful patent protection on his product, he has been unable to attract financial investors, and his treatments languish in a storage freezer.

THE GOOD-MOOD BUG

Microbiologist John Stanford of University College London and his wife, Cynthia, discovered Mycobacterium vaccae while searching for a tuberculosis vaccine booster in Uganda in the early 1970s. Experts had long proposed that the widely variable efficacy of the TB vaccine stemmed from bacteria in a region's soil that provided a natural booster effect. The Stanfords, crisscrossing the African nation in search of this bacterium, isolated M. vaccae, a benign genetic cousin of Mycobacterium tuberculosis, from the muddy shores of Lake Kyoga, an area where the TB vaccine proved unusually effective against both tuberculosis and leprosy. The Stanfords hoped that injections of M. vaccae would help prevent or cure TB, but at best their vaccine proved only mildly beneficial. More curious were anecdotal reports of unexpected benefits-regressions of allergies, asthma and even cancer.

In 1992 John Stanford and his colleague Graham Rook went on to form a publicly traded company, SR Pharma, to test these immune-boosting benefits in clinical trials with late-stage lung-cancer patients. But in 2001, under a spotlight of media attention, the trial failed to appreciably increase patients' survival time. SR Pharma's stock crashed, and following a dispute over the company's future focus, the company removed Rook and Stanford from its board of directors.

Yet the trial did produce one bona fide benefit: a significant increase in "quality of life" among patients who got M. vaccae injections versus those who received a placebo. That dovetails with the work of University of Colorado neuroscientist Christopher Lowry, who last May published a study where he used M. vaccae in psychotropic experiments with rats. Lowry discovered that the bug increased brain levels of the mood-enhancing hormone serotonin and decreased depressive behavior. Even more promising, Lowry showed that M. vaccae appeared to be more discriminating than antidepressant drugs in the kinds of brain neurons it activates. It switches on the serotonin neurons associated with enhancing mood, without stimulating those that increase hyperalertness-that is, anxiety and sleeplessness. "Prozac without the side effects," he calls it. In addition, recent studies have shown that M. vaccae may be effective against TB-the Stanfords' original studies didn't supply enough doses-and may increase the survival times of some late-stage cancer patients.

It's just this sort of surprising potential that inspires researchers. "We're always saying things like, 'I feel lousy today. I must have caught a bug,' " Thaler says. "We never say, 'I feel great. I must have picked up an endorphin-producing one.' What would it mean to cultivate yourself to be contagiously healthy?"

 Jessica Snyder Sachs is a contributing editor at Popular Science. Her most recent book is Good Germs, Bad Germs: Health and Survival in a Bacterial World.

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photo courtesy US Fish & Wildlife Service

Richard Stroud is the nation's chief medical examiner for wildlife, and he's getting a state-of-the-art lab. Poachers beware.

copyright Jessica Snyder Sachs, as first appeared in Popular Science

When it comes to fatal gunshot wounds, forensic pathologist Richard Stroud likes to examine things from the inside out. The bruising and tissue trauma, the size difference between entrance and exit wounds--everything becomes more obvious from the underside of the skin. Consequently, Stroud has developed a habit of skinning out the victims that pass across his autopsy table.

"Of course, I don't have to worry about families wanting the body back for burial," Stroud says.

On this day, the luckless fatality is a Mexican wolf that had been part of a reintroduction program in the Southwestern brushlands of Arizona and New Mexico. Unlike some of the bedraggled specimens Stroud has seen of late, this wolf appears to have been making a success of it, judging from the healthy feel of its coat and skin. Then it met up with someone unimpressed with the wolf's protected status under the U.S. Endangered Species Act.

A preliminary examination of the wolf revealed what appeared to be a bullet entrance wound--no bigger than a baby's pinky--on the animal's rear-left flank and a ragged exit wound--around the size of a man's thumb--behind the right shoulder. But a head-to-haunches X-ray failed to reveal the typical snowstorm of shiny flecks that result when a hunting bullet begins disintegrating on impact, leaving a mushroom of bullet fragments inside the animal's body. With no bullet or bullet fragments to retrieve for a ballistics report, Stroud decides to assess internally, hoping for clues that might guide field investigators as to what kind of bullet and bullet casing to look for--and where--in the area where the carcass was found.

Stroud is on his way out of his office to begin the necropsy when he gets a call from the Fish & Wildlife special agent who FedExed the victim--neatly folded and frozen in a 4-foot-by-1-foot cooler--the previous Friday. "Don't worry, I'm on my way to do your dog," Stroud reassures, with the implied promise that he'll have something useful to report in a few hours.

In essence, Stroud is the nation's chief medical examiner for wildlife. His autopsy suite: a converted garage attached to the U.S. Fish & Wildlife Service's forensic laboratory in Ashland, Oregon--the world's only crime lab dedicated to animals. In addition to helping investigate the poaching of threatened and endangered wildlife, the lab has earned an international reputation for its ability to analyze and identify just about anything that could have come from or been made out of a wild animal.

In preparation for today's wolf necropsy, Stroud pulls a blue lab coat over his usual plaid flannel shirt and Levis and yanks on a pair of surgical gloves. Stroud's sunspotted hands, like his freckled face and thinning sand-and-salt hair, reflect a half century spent as much as possible outdoors. An avid hunter and fisherman since boyhood, Stroud says his years of field dressing deer and elk have proven highly useful throughout a career that began as a wildlife biologist studying the stomach contents of Arctic marine mammals in the late 1960s. Clearly, Stroud hails from the old school of wildlife management--one that views animals as natural resources to be managed rather than lovable friends needing protection for their own sake. "It's no longer cool to collect data the way we used to," says Stroud of the politically incorrect days when he was killing fur seals for science, right alongside hunters doing so for profit.

In the early 1970s, Stroud graduated from veterinary school with a specialty in pathology, and later adapted what he had learned working on pets and livestock to wildlife at the San Diego Zoo. Twenty-five years ago, he began working for U.S. Fish & Wildlife, with a primary focus on the diseases that afflict migrating waterfowl.

In 1989, Ken Goddard, the founding director of the wildlife agency's newly opened $4.5 million forensic lab, proudly invited Stroud to tour his facilities. A former police-crime-lab director, Goddard had designed the lab to include the latest equipment and resources in all areas of criminalistics, from toxicology and DNA to ballistics and trace-fiber evidence.

Says Stroud of the visit, "I told him, 'This is all very nice, but where do you examine the dead animals?'"

Fifteen years later, Goddard admits, "I hadn't really thought of it." Understandably so. Even the most sophisticated police crime laboratories leave autopsies to the nearest medical examiner. Unfortunately, at the time, there was no such thing as a forensic veterinary pathologist. "All I could do was tell the special agents to dig the bullets out of their victims as best they could and send them in to us for ballistic analysis," says Goddard.

That all changed a few months later, when Stroud finagled a departmental transfer and career change that included medical examiner training at the U.S. Armed Forces Institute of Pathology, in Washington, D.C.

For the most part, the merger of crime lab and medical examiner's office has proven amicable, says Goddard, aside from Stroud's impatience with the perennial requests that he use more air freshener in the course of his work. "As a police investigator, I've worked my share of floaters," says Goddard of his own tolerance for even the rankest of human corpses (floaters being the partially submerged corpses often found in an advanced state of decomposition). Apparently, wildlife carcasses can be far worse. "We're convinced the man has no sense of smell," Goddard says of Stroud's indifference.

On the other hand, many of Stroud's cases involve what he calls "dinner-quality meat," owing to his practice of having field agents freeze their carcasses before shipping. Today, the wolf on Stroud's table is just such a fresh-frozen kill, thawed over the weekend for a Monday autopsy. On the whole, it proves odorless until dissection of the stomach exposes pieces of animal even deader than it is. Stroud retrieves and tags several pieces of fur and bone for DNA analysis--to identify what may have been the victim's last meal.

More pertinent to this investigation, Stroud reaches past the wolf's internal organs to feel whether its spine has sustained damage. It has not, which suggests that the wolf would have continued to run for some distance after being shot. That's bad news for the field investigator, who'll find it harder to locate bullet casings and other evidence than if the wolf had dropped on impact.

But then Stroud makes a contrary finding. Using a long wooden dowel to probe the entrance wound, Stroud traces the bullet's path through the belly and up through the chest. "It hit the postcava," he says, referring to the large blood vessel that leads from liver to heart. Consequently, the wolf would not have gotten far before dying of massive blood loss. Stroud will tell the special agent to figure that the wolf was shot within a 100-yard radius of the spot where he found the carcass.

Stroud finishes skinning the wolf with a kitchen fillet knife, then lays
the intact pelt, fur side down, on a tarp spread across the concrete floor of the necropsy suite. He again threads the long wooden dowel through the entrance wound on the rear, left flank and pushes it across to the ragged exit wound behind the right shoulder.

Stroud's assistant, Shelley O'Connell, steps up to take a photograph that Stroud says will help him show a jury that the wolf was clearly running away when shot. This may prove crucial in refuting any claim that the animal was shot in self-defense.

The size of the exit wound, in turn, speaks of someone firing the bullet from a high-powered weapon such as a rifle, but not using a typical hunting bullet, which would have left a larger, more ragged hole. Military ammo, Stroud speculates. But only a ballistics report on an actual bullet fragment or casing can confirm his suspicions.

For now, the dismembered wolf goes back in the deep freeze--folded, compressed, and bagged in bundles sealed with evidence tape and tagged to show chain of custody. Any criminal case will likely go nowhere unless some combination of luck and skill leads the field investigator to the crucial evidence.

Eventually, the wolf's pelt may end up in a classroom or nature museum; its skull in a research collection, after being rendered down to clean bone by the colony of flesh-eating beetles that the lab's forensic morphologist keeps in a large box.

Stroud averages 500 to 600 such necropsies a year. Last year alone, they included a record 24 wolves and around 150 eagles, as well as scores of other animals protected under the provisions of the U.S. Endangered Species Act or by other laws. Still other cases involve "illegal takes," as when hunters use firearms during archery-hunting deer season (often faking a legal kill by sticking an arrow in the bullet hole), use nets to harvest fish in streams open only to hook-and-line sports fishing, or shoot animals from aircraft (a violation that Stroud has documented by the angle of gunshot wounds).

In each case Stroud must go beyond merely determining cause of death--the traditional role of the veterinary pathologist. "To your typical veterinarian, a gunshot wound is a gunshot wound. End of story," he says. By contrast, a forensic autopsy is built around re-creating the death in a way that's useful to a criminal investigation. In poisonings, for example, Stroud must not only retrieve tissue samples for toxicological analysis, but also determine whether the resulting wildlife deaths were deliberate.

In the recent mass poisoning of a bald eagle colony in Wisconsin, Stroud found that the birds had gorged on muskrats--and pellets of highly toxic pesticide carbofuran. Could the muskrats have eaten the pellets in some farmer's field before their dying convulsions made them easy prey? A superficial necropsy would have suggested so. But Stroud noted a suspicious absence of fur in the eagles' gullets, then went on to document knife marks on several undigested chunks of muskrat. His conclusion: The muskrats had been skinned.

This detail ultimately led investigators to a muskrat trapper who reported selling meat to the owner of the land where the dead eagles were found. Skinning would have involved gutting the muskrats, so any carbofuran pellets found with the meat had to have been added intentionally before it was set out for the eagles' dining pleasure.

"Apparently the eagles' roost tree was on property that the land owner wanted to develop," says Stroud. "But under the Endangered Species Act,
the habitat of a threatened species is also protected."

A somewhat similar case involved a Minnesota man suspected of a string of wolf poisonings in the mid-1990s. From the necropsy of the latest victim, Stroud sent samples of brain, liver and kidney for toxicological analysis, and chunks of deer meat from the wolf's stomach for DNA analysis. The toxicology report confirmed Stroud's suspicion that the wolf had died of massive cyanide poisoning (evident on necropsy by bright red tissues). DNA analysis matched the chunks of deer inside the wolf to venison found in the suspect's freezer.

Both the above cases resulted in convictions, says Stroud, who has taken the witness stand around 25 times in the past 15 years, a modest number given the hundreds of necropsies he has performed. Nonetheless, the Fish & Wildlife Service is impressed enough to have pledged $12 million for a new forensic pathology suite at the Ashland facility, slated to be built within the next three years.

"It'll look just like a state-of-the-art medical examiner's office," says Goddard. And that's exactly what it will be.

Additional reporting by Dawn Stover.

Jessica Snyder Sachs, a contributing editor to Popular Science, is the author of Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG) and Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus/Basic Books).

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Does the cold nose know?
Canine "nose witnesses" may be more convincing than reliable.

Copyright Jessica Snyder Sachs, as first appeared in Popular Science

Nothing brings a little light into a dismal courtroom like the goofy grin and thumping tail of a hound. And as witnesses go, nothing beats a canine for sincerity and trustworthiness.

"The jury eats it up," says police K-9 handler Pat McAlhany, a veteran of the Miami-Dade County Sheriff's Office. "From a prosecutor's standpoint, there's nothing better than my actually bringing my dog into the courtroom for a demonstration."

Indeed, the practice of using dogs as "nose witnesses" to finger, as it were, the accused is rapidly growing. A rape case that passed through the Los Angeles court system last year illustrates the procedure. A young woman came into the police department and described a brutal attack. Two men had dragged her from a bus stop in an industrial part of the city into an alleyway, where they sexually assaulted her. Traumatized, she initially did not report the attack. But two days later she found a necklace she thought one of the rapists had ripped from her neck. It lay outside the school where she worked. Did one or both of the attackers live in her neighborhood and know her daily habits? She also spotted a man at a local market who reminded her of one of the attackers. Now terrified, she went to the police.

The delay meant a rape kit could not provide DNA evidence. Not a problem. Enter Reilly, a confident, experienced expert witness with boundless enthusiasm for his job. Under the leash of volunteer scent-evidence K-9 handler Joseph D'Allura, this chocolate Lab's scent-detection skills had put killers behind bars. For the rape case, D'Allura created a "scent lineup," using a scent transfer unit that worked like a Dustbuster, sucking the perpetrator's odor off the snatched jewelry and onto a sterile gauze pad placed over the vacuum's air intake. He then vacuumed a piece of clothing taken from the neighborhood resident who had aroused the rape victim's suspicions in the local market.

D'Allura prepared the scent lineup by placing the suspect's pad alongside three decoys infused with scent from other individuals. Finally, he presented Reilly with the necklace scent pad and directed him to find its match. Passing over pad number one, the dog gave the second sample a wag and a bark--an "alert" in dog-handling lingo. The police had a positive ID.

Or did they? Juries may love a dog show, but some experts remain skeptical. "In all honesty, we don't know what a dog is picking up on when it alerts," says Lawrence Myers, an Auburn University sensory and behavioral biologist called as an expert witness for the defense in the rape case. Over the past 21 years Myers has trained more than 50, and studied hundreds, of scent-detecting dogs under laboratory and field conditions, mostly for federal agencies wanting to perfect the use of dogs for finding explosives, drugs, trapped disaster victims and hidden graves.

Myers considers the canine nose the ultimate odor-detection system in use today. But in many ways, he says, "we're still dealing with a black box." Scientists have yet to fully understand the process of canine odor identification. Neither have they defined the limits of a dog's sense of smell, nor isolated any universal "scent factor" that dogs use to distinguish one person from another.

The widely held view is that dogs pick up on variations in the chemical makeup of the skin flakes and perspiration residue we all continually shed. But no one knows which aspects of this microscopic brew grab a dog's attention as it plays a forensic game of mix and match. Might racial or gender differences skew results? Or, for that matter, some yummy-smelling food the person ate the previous day?

When it comes to something as complex as human scent, Myers believes that different dogs likely tune in to different things. And no dog is perfectly consistent. Myers's research has shown that something as mundane as dental tartar can have a ruinous effect on a dog's powers of discrimination. "Clean the teeth and you get an almost immediate recovery of smell," he says. Scent dogs also have off days, suffer allergies, get colds. "Trouble is," he says, "you can't cross-examine a dog and ask, 'Are you sure?' "

So Myers has deep misgivings about the growing number of calls he's getting to testify in rape and murder cases that hinge largely on a doggie's positive ID. "It's like the floodgates have opened," he says.

Dog scent lineups aren't new, how-ever. Estimates suggest they've played a role in more than 1,000 criminal cases in the United States, going as far back as 1923. Today, most states and the District of Columbia admit dog scent evidence as valid identification of the accused, "provided a proper foundation is laid."

Despite this long history, a scientific basis for that proper foundation has never been established. Many prosecutors try to skirt that fact by arguing that scent lineups are no more than a logical continuation of the practice of employing dogs to track fugitives or sniff out drugs--uses that have long passed legal muster. Some judges buy that argument, some don't.

The courts rely on handlers to demonstrate a dog's reliability by
submitting training records. But it's widely known in handler circles that many are loathe to record a dog's mistakes, lest the errors later be used to discredit the dog's identifications.

Research reveals that even experienced and well-trained dogs sometimes misidentify individuals. In studies conducted in Europe (where scent lineups have become tightly regulated and standardized), dogs' identification scores varied from a high of 58 percent to a low of 22 percent. Researchers have conducted such studies both on-lead (with a handler holding the dog's leash) and off, in an effort to tease out or exclude a handler's influence.

That some handlers inadvertently prompt their dogs is a major criticism of scent lineups. And the critics include some of the nation's most experienced search-dog handlers. "We have a saying in dog training circles," explains police K-9 instructor Roger Titus, vice president of the National Police Bloodhound Association. "Your body language goes down the leash." A well-trained dog becomes hyperaware of its handler's every move, Titus explains. "You lean forward, it moves. You slow down, it does too. You walk down a lineup of six baseball caps, and all you have to do is think you're at the right one, and the dog picks up on it." Some call it the Clever Hans effect, after the 19th-century equine genius whose mathematical prowess turned out to be nothing more than the horse responding to the unconscious nod of his trainer's head.

Dog-evidence enthusiasts have reason to be cautious, Titus warns. Much of the precedent-setting case law, including murder convictions, behind the acceptance of scent lineups came from the now discredited work of a single handler, who was later shown on videotape to be cuing his dog.

The expanding use of scent lineups has become a hot-button issue in the police-dog handler community. The National Police Bloodhound Association and the Law Enforcement Bloodhound Association have both developed guidelines for proper lineup procedures, while their memberships remain deeply divided over the legitimacy of the practice.

"The fact that a dog might send somebody to the electric chair places a tremendous responsibility on the handler," admits McAlhany. "That said, my confidence in my dog and myself is very high. I would feel comfortable going to court and testifying that, yes, she can use a scent article and make a positive ID."

Confidence in dog and handler aside, the scent-collecting process itself is not above controversy. "Scent is a fragile creature to begin with," argues Titus. "In my opinion, the use of scent machines takes the whole idea further down the line of pipe dreams."

The scent transfer unit's inventor, Bill Tolhurst of the Niagara County (New York) Sheriff's Department, dismisses that argument. Tolhurst says he's successfully run dog scent lineups using evidence pads stored for more than 11 years in frozen, heat-sealed plastic bags. Tolhurst, a three-time past president of the National Police Bloodhound Association, says he's pulled human scent off shell casings from drive-by shootings. Among his proudest accomplishments, he says, is a conviction in a kidnapping and attempted murder case in which his bloodhound matched the defendant to scent vacuumed off the seat of a car last driven by the offender.

To date, Tolhurst has sold more than 80 of his scent-collecting machines to law enforcement agencies--including 35 to California police and sheriff's departments and 7 to the FBI.

Lawyers will be arguing about the merits of dog-witness identifications and procedures for years. In the rape case described earlier, the judge ruled Reilly's scent identification inadmissible, citing, among other things, D'Allura's lineup procedure. D'Allura stopped the lineup as soon as Reilly alerted on the second pad, rather than allowing him to proceed down the line. In addition, D'Allura couldn't recall when or from whom he'd made the lineup's three decoy pads. Were they from individuals of the same race as the suspect? D'Allura couldn't say.

Of course, having evidence dismissed is part of the legal process; win some, lose some. D'Allura points to several cases in which Reilly's testi-mony played a decisive role. In a major coup for scent lineup proponents, a California appeals court recently upheld Reilly's identification of a teenager convicted of a double homicide, as well as the young man's sentence of two consecutive life terms.

Does the cold nose know? Criminal juries may be happy to say yes. But the scientific jury remains out.

Jessica Snyder Sachs, a contributing editor to Popular Science, is the author of Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG) and Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus/Basic Books).

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Welcome to the Dollhouses of Death

Barbie's dead. Did Ken do it? How miniature death-scene dioramas are used to teach modern CSI techniques.

Copyright Jessica Snyder Sachs, as first published in Popular Science magazine

After the class work in fingerprinting, ballistics and firearm identification, the laboratory exercises in blood spatters, tool marks, shoe prints and drag marks, the death-investigation lectures and the autopsy, the demonstrations in detecting and collecting trace evidence . . . after all that, when Tom Mauriello's students have worked their way through every aspect of crime scene investigation in his renowned criminalistics course, it's time to play with his dollhouses.

You won't find anything at FAO Schwarz like Mauriello's tiny, gory crime-scene reconstructions. They look at first glance like some sort of grotesque joke-violence-drenched outsider art, maybe, or Addams Family playroom props. Blood is spattered on a little wall. A tiny telephone receiver dangles off a hook. A red car idles in the closed garage, wisps of fiberglass exhaust curling out from the tailpipe. And, of course, there are bodies-on the garage floor, face up on the kitchen linoleum, slumped on a bloodstained carpet, tucked into bed with a Bible, a gun and a bullet between the eyes.

Mauriello teaches at the University of Maryland, College Park. Each of his six crime scene dioramas contains clues to preliminarily determine cause of death-accident, suicide or homicide-and each comes with a sort of dollhouse docent, a real live student supplied with reports and findings that are divulged when students ask the right questions.

In an era of computer-assisted 3-D blood-spatter pattern analysis and crash-scene reconstruction software, Mauriello's dollhouse approach seems nostalgic. But he argues there is no substitute for hands-on experience-even if the hands are on a tiny rubber deathbed figure, a German doll chosen by Mauriello because he could bend it into a rigor mortis pose and touch up its skin color with paint for telltale lividity. The dent in another doll's head matches the shape of a nearby lamp, indicating blunt trauma.

"I teach my students to peel the crime scene," he says. "I want them to physically pull back the bedsheets, turn over the victim, examine the body, pull out the instrumentation in the laboratory and use it, even if it's on a miniaturized scale."

This is not something they can do at a real crime scene, he reminds them. "Access to a real crime scene is impossible. It's closed off. You'd violate the integrity." (Mauriello used to take over an entire university house and convert it temporarily into a life-size crime scene replica. It was a huge job, taking days to prepare. Dioramas are portable and reusable, thus much more convenient.)

There is precedent for Mauriello's dollhouses. He modeled his miniatures after a set of 19 death scenes crafted in the 1940s and '50s by the eccentric millionairess who founded Harvard's department of legal medicine, the nation's first university program in forensic pathology. International Harvester heiress Frances Glessner Lee created her famous "nutshell studies" for another of her pet projects-a yearly homicide investigation seminar that 40 to 50 of the nation's leading investigators jockeyed to attend.

Between each colloquium, Lee, an honorary captain in the New Hampshire state police force, retreated to her mansion in the White Mountains to construct exact one-inch-to-one-foot-scale recreations of real death investigations, all to challenge (and often stump) "her boys."

Lee spent as much as $3,000 on each diorama-you could probably buy a full-size house for that amount of money back then-and equipped them with working doors, windows and lights. Magazines, calendars and prescription labels were finely printed. Bullets and shotgun shells were exquisitely miniaturized. Lee lovingly knitted the clothing for each victim, using two stickpins and sewing thread.

Jerry Dziecichowicz, administrator of the state of Maryland's office of the chief medical examiner, which continues to host Lee's Harvard Associates in Police Science seminars some 40 years after her death, says several of Lee's most difficult dollhouses have since been retired. Too hard to crack, he says. "When you have a room full of guys with guns, you don't like to keep telling them they're wrong."

In contrast to Lee's finicky ship-in-a-bottle approach, Mauriello is not above using a gauze finger bandage for a hold-up man's ski mask or the metal end of a mechanical pencil for a spent bullet casing. What his crime scene dioramas lack in obsessive perfection, however, they make up for in modern CSI context. Mauriello dabs his crime scenes with an invisible compound that fluoresces just as saliva or semen would when students scan with black lights. A student sharp enough to spot the stain of urine in the toilet of a hotel-room death scene can send it for DNA analysis, just as a professional crime scene investigator would.

Mauriello says it doesn't take long to spot which students will have difficulty with a real death-scene investigation: They're always the ones who are reluctant to touch. "In order to get the answers, they have to examine everything-look inside bedclothes, turn over dead bodies, pick up the newspaper on the floor to see the date."

If you don't play with the dolls, you won't solve the crime.

|Contributing Jessica Snyder Sachs is the author of CORPSE: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus)and Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG).

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It's arson, bomb, and booby trap week at one of the nation's toughest forensics academies.

Copyright Jessica Snyder Sachs, as first published in Popular Science

All photos courtesy NFA.

A morning mist clings to the foothills as 15 crime scene investigators from across the country approach a shrapnel-pierced Pontiac Bonneville outside Knoxville, Tennessee. Minutes before, a fiery blast engulfed the car's passenger area, exploding the side windows and sending the crazed-glass windshield arcing, slo-mo, 50 feet through the air.

Scene commander Tom Sparks, a beefy lieutenant with the Hartselle, Alabama, police department, designates a sketch artist and photographer to record the vehicle exactly as found and assigns five more CSIs the task of dismantling it for evidence regarding the cause of the blast. Another seven line up with Sparks along one side of the scene perimeter. "Step," he bellows. They move one stride forward before bending to mark potential clues. "Step!" Within minutes, the sodden ground blossoms with orange evidence flags.

Back at the Bonneville, Joy Smith, a tall, blonde evidence specialist from Modesto, California, peers into the red-clay hole where the passenger seat and floorboard had been. She searches for anything remotely bomb-like in the surrounding jumble of shredded wiring, metal and plastic. "Now I see the wisdom of spending time at Radio Shack," she says. "It all looks like car parts to me."

Thirty minutes into the investigation, crucial clues emerge. From inside the passenger door a team member pulls a chunk of galvanized steel with threads on one side and the raised imprint "1 1/4" on the other. "Looks like we've got a 1 1/4-inch pipe," he says. Others pull matching bits of steel shrapnel from the perforated headliner. A cobalt-blue sheen marks the shorn edges of several pieces-the signature of a high-power explosive.

From the shredded driver's seat, Ohio crime technician Matt Dulaney digs out a curl of flattened metal and holds it to his nose. "Gunpowder," he says. "Doesn't a windup clock have a round spring?" The perimeter searchers, for their part, have found shreds of duct tape that, all agree, could have held a pipe bomb and detonator together. The CSIs confront a grizzled former Marine turned explosive ordnance expert. "Very good," he says, nodding. "I put a pound of C4 in the pipe, used a clock timer, and shoved it all under the passenger-side seat."

Time to move on: Knoxville bomb-squad commander Van J. Bubel has other surprises in store this morning. He directs the group's attention to a shoe bomb laced to the elegantly turned foot of a fashion mannequin standing across the field.

"She's just like that guy on the airplane," says Bubel, a detonator cord in hand, "only smarter."

Kerrrrack-BOOM!

So goes a typical day in Week 7-arson, bombs and booby traps-at the National Forensic Academy, a joint project of the National Institute of Justice, the University of Tennessee, Oak Ridge National Labs and a host of state and local law enforcement agencies. The 10-week course includes units on postmortem fingerprinting, blood spatter, skeletal scatter, grave detection, cybercrime and weapons of mass destruction, and wraps with students resolving a gauntlet of mock crime scenes under the demanding eye of an FBI evidence recovery team.

Now in its second year, the National Forensic Academy aims to establish high national investigative standards for a field that sorely lacks them. The truth is, unlike the highly specialized lab scientists on TV's CSI, most U.S. crime scene investigators come from the rank and file of local police departments and sheriffs' offices. Their training varies as widely as the budgets of their municipalities. The result: Countless cases get dropped when lack of expertise results in missed clues and spoiled evidence; other cases get shredded in court a la O.J. Simpson, when defense attorneys attack less-than-perfect crime-scene procedures.

Not that the academy's cadets are greenhorns. Virtually all the men and women in this, the school's fifth session, have already attended a half-dozen or more courses in evidence collection and served years on the CSI beat. Modesto evidence specialist Smith, to name one, arrived with more than 450 hours of training and eight years of field experience under her belt. "But you can't compare sitting in a classroom listening to someone lecture out of a book to coming here and getting hands-on training from the best people in every field," she says.

Indeed, the academy has already earned an international reputation for the sharp realism of its training exercises and the unprecedented caliber of its faculty. One has only to consider the macabre list of school supplies: Each class works with a half-dozen human cadavers, two sets of skeletal remains and several pints of fresh blood. Academy coordinators Jarrett Hallcox and Nathan Lefebvre also scrounge up two cars and a couple of condemned houses for each class to blood-spatter, burn, and bomb.

The academy's hallmark style of extreme authenticity stems in large part from the University of Tennessee's world-renowned forensic anthropology department. Its outdoor anthropological research station-widely known as the Body Farm-is the only place where exercises in grave detection and body recovery involve actual (donated) human remains.

The value of working with "the real stuff" can't be overstated, says Hallcox. "Some of these investigators come from areas where body exhumations are once-in-a-lifetime events. But after our training, they'll be able to meet the challenge with genuine experience." There are limits, Hallcox admits.

"We didn't use a real body for the shoe bomb," he explains apologetically during bomb week, "because Nathan and I would have gotten stuck with the cleanup." Students also spend three days at the state medical examiner's office in Nashville, where they learn to fingerprint cadavers (a chunk of Silly Putty helps roll prints off decomposing fingers) along with trickier techniques such as lifting prints off thighs and buttocks. The latter can prove crucial to cracking homicides that include rape or physical struggle. But no students in the class had ever mastered the skill before Week 4, when Art Bohanan-inventor of the portable "superglue" fuming technology featured on CSI-taught them to warm the body part to around 70?F, fume it with cyanoacrylate (heated superglue), dust it with magnetic powder, and lift the clearly visible print with contact paper.

The academy's world-class faculty also includes renowned forensic anthropologist and Body Farm founder William Bass, who in Week 5 taught the class how to extract fingerprints from the sloughed off "glove" of skin sometimes found next to a decomposed cadaver. (Soak the tissue overnight in a bucket of water, and slip your own hand inside the stocking-like glove.) Paulette Sutton, the widely published protegee of Herbert MacDonnell (the father of bloodstain-pattern analysis in North America), runs blood-spatter week; and forensic biochemist and time-of-death expert Arpad Vass of Oak Ridge National Labs does triple duty with bloodborne pathogens (Week 1), human decomposition (Week 5) and weapons of mass destruction (Week 9).

Day two of burn and bomb week finds the National Forensic Academy's forensic anthropologist Joanne Devlin striding away from a kerosene-doused Chevy Citation she just torched. A burned-bone expert, Devlin teaches fire-fatality and arson investigation, with special emphasis on the recognition and recovery of charred skeletal remains. Her expertise lies in the interpretation of the burn-altered signs of bullet wounds and other trauma. She has also become the academy's designated arsonist, having spent the previous weekend burning down a four-room farmhouse for a Wednesday field practicum.

Today Devlin and her co-instructors intend to teach these CSIs to make preliminary, on-the-scene determinations concerning the possibility of arson-whether for profit (insurance scam), for revenge or to cover up murder. Such quick determinations often prove crucial, because getting results from a crime lab can take weeks to months, and clues missed at the start may be washed away or demolished in the interim.

Already, the class has watched Devlin, veteran fire investigator Mike Dalton and special agent Dennis Kennamer of the Bureau of Alcohol, Tobacco, Firearms and Explosives burn two furnished "burn cells" (mock rooms with one wall left open for viewing) to illustrate the aftermath of accelerant-fueled arson and the results of a lighted wastepaper basket strategically placed in the corner of a room.

The most obvious clues of criminal intent include gasoline trails or "splash and dash" burn marks on carpeting, furniture and walls. Window glass provides other clues: Long shards directly inside the windowsill point to a prior break-in, while small chunks of crazed glass suggest a heat-related shattering.

Where did the fire start? Look up: "Lightbulbs have the obliging tendency to bubble and extend toward intense heat, as if to say, 'Look here, dummy,'" explains Dalton.

Earlier the same morning, the class looked without a flinch at Devlin's PowerPoint presentation from hell. The close-up photographs featured one fire fatality after another, each graphically illustrating the telltale signs that distinguish victims who perish during a fire from those already dead when the fire began-the latter being a red flag for possible homicide.

A mask of soot around the nose and mouth, for instance, paints the picture of a fire victim still gasping for breath when engulfed. A face-down position suggests an attempt to crawl to safety or huddle from overhead smoke. A face-up victim raises more questions. On the other hand, Devlin warns her students against mistaking the drawn-up "pugilistic pose" of a severely burned corpse as a sign of struggle or self-defense. In fact, the pose results from the contraction of cooked muscle.

After a break to let the torched Chevy cool, Devlin herds students to the smoldering vehicle and cajoles them to reach into the char to gauge the fragility of the cremated remains. The student investigators have more difficulty with Devlin's mock human victims-three animal carcasses were burned in this car-than with the half-dozen cadavers they handled in previous weeks at the state morgue and Body Farm. They hang back. So Devlin pushes open the trunk and picks up a molar from the blackened remains of a raccoon. "What if this is the tooth you need to make a positive ID?" she asks, pinching it to dust between her thumb and forefinger. "Oops."

As students begin handling the charred bones, Devlin points out that though the hands, feet and facial characteristics have burned away, the underside is intact: There is not so much as a singed hair where the body rested against the trunk floor.

Devlin also wants her CSIs to experience the difficulty of distinguishing charred bones from other fire debris. Among her class exhibits she includes a dark version of "Where's Waldo?"-a trough of charred skeletal remains mixed with look-alike fire debris such as burned and crumbled ceiling tiles.

The previous weeks of fieldwork have already sharpened the students' powers of observation in ways they had not imagined possible. During a Week 5 daylong exercise in "surface scatter," the class divides into two teams, each assigned to recover a separate set of 30 skeletal fragments in different sections of the Body Farm. Instructors planted the weathered bones in the wooded enclave's thick underbrush, just as wild animals might scatter the remains of a homicide victim. "The bones looked just like sticks and chunks of wood," says Baton Rouge crime tech Pammy Anderson. Nonetheless, Anderson's team found all but one of its scatter set while the other team found every bone plus an ulna (forearm) left by the previous class. It's a matter of utmost pride: The score of the two teams combined surpassed that of any previous session.

By Thursday night, the academy's fifth class is ready for some mindless entertainment, having doffed class uniforms (black boots, combat pants, and polo shirts emblazoned with a skull, gun and fingerprint) for jeans and sweats. By 9 p.m., most of the crew has settled, beer and pizza in hand, in front of the TV at one of the corporate apartments that serve as the school's upscale dorms. It's time for America's favorite prime-time drama, a show that some in the room love and some hate but all agree features a lot of "in your dreams" stuff: CSI. The show has also heightened the public's expectations of what CSIs can do and how fast they can do it.

For starters, several rush to point out, CSI's college-educated, city-roaming cast of characters would, in real life, belong to the ranks of don't-get-your-hands-dirty "lab rats" who work within the confines of state and regional crime laboratories. Some of these labs do, in fact, field mobile units to assist local police with the occasional scene investigation, "but most of the time, we're on our own," says Tim Horne, an investigator with the Orange County, North Carolina, sheriff's office. "We collect it, and 90 percent of the time, we process it ourselves." And in a typical, medium-size law-enforcement agency such as Horne's, in-house processing means whatever the local investigators can pull off in the ad hoc evidence room.

As for the technology employed on CSI, this audience agrees that, for the most part, it's real, even if pricey, exaggerated and needlessly flashy. Hooting begins as they watch an audiovisual expert in the fictional Las Vegas crime lab zoom in for a close-up of a mole on the neck of an out-of-focus figure in a confiscated snuff film. As every investigator learns when dealing with security camera videos, you can't focus an already out-of-focus picture. (Digital sharpening can produce an image that looks more focused but at the cost of detail and accuracy.) Nor, investigators point out, can you get blood to fluoresce in broad daylight, something the fictional Warrick accomplishes after the next commercial break.

But the biggest beef this class has with Hollywood's glitzed-up version of their work is the speed with which the prime-time CSIs get their results. "They scan in a fingerprint and presto, up comes the name of a convicted felon," scoffs Houston crime technician Christopher Duncan. "I wish!" In reality, fingerprint matching takes days to weeks using AFIS, or Automated Fingerprint Identification Systems, the computer database that searches for matches against the prints of persons arrested in a given state or region. Even then, the computer database spits out not one but an array of close matches, leaving it to the investigator to make the painstaking side-by-side print comparisons.

As for getting a match for a DNA sample lifted from a crime scene, try months to over a year, depending on the backlog of cases being run through such state and national databases as CODIS, or Combined DNA Index System. "All you can do is submit your evidence and take a number," says Horne. "Our case may be important, but so are those of every other agency in the state."

All agree that the show has wildly distorted crime victims' expectations as to what investigators can or will do. "One lady demanded to know why I wasn't swabbing her windowsill for DNA," relates Mississippi detective Craig Burdett. "Even if I could get a sample, we're not going to run a $500 DNA test over a $50 stolen TV."

Whether they come from rural sheriffs' offices or big-city police departments, every one of these crime scene investigators knows the frustration of begging for funds to pay for outsourced tests such as DNA fingerprinting, as well as the basic chemicals and equipment needed for evidence processing. "Just because we know how to do it doesn't mean we'll get the materials," explains Horne. "So while we appreciate all the cutting-edge stuff we've been learning, the best is when they give us the Wal-Mart version."

Which explains why the class's hands-down favorite technique is an on-the-scene print-lifting method learned in Week 3. It employs superglue and cigarette ashes in a jerry-rigged print-fuming chamber made from a Styrofoam cup. They also enthuse over recipes for fingerprint-lifting gels and strips cooked up using dollar-store items like glue sticks, glass cleaner and a dozen-odd types of duct, masking and adhesive tapes. "Our department's a lot more likely to let us buy a $3 stick of Elmer's blue glue than a $25 bag of chemicals," Horne says.

Eager to apply their new tricks, the students mull the convictions that might have been: "For years, I've been trying to get prints off the cheap sandwich bags our druggies stuff with marijuana and crack," says crime technician Steve Smith of Montgomery, Alabama. (Apparently, higher-grade Ziploc bags give up their secrets more easily.) But now Smith knows a correspondingly cheap trick that will bring out prints on the flimsiest of plastic. Using an ordinary aquarium as a fuming chamber, he will heat a few drops of superglue to create a cloud of whitish fumes that adhere to the print's amino acids. He'll then gently stretch his evidence across an embroidery hoop and spray the print (faint white from the superglue) with a fluorescing dye so that it pops up bright orange for a photograph clear enough to run through the AFIS database. Others brood over the killers they might have put behind bars had they known then what they know now. Tim Carnahan of Burlington, Kentucky, describes a case in which a young woman was bludgeoned to death in her garage after a wild chase that started at the front door and wound throughout the house. "We had a good idea who did it," says Carnahan. "But we didn't know how to read the blood spatter to determine the weapon, or even the number of attackers. Next time will be different," he vows. (A suspect has since emerged and Carnahan plans to revisit the blood-spatter evidence.)

Already, alumni of the academy's inaugural year, 2001, have begun to make their mark. Back in Cocke County, Tennessee, detective Derrick Woods prepares for grand jury testimony with full confidence that he has a murder conviction all but in the bag. "I told the guy flat out that it couldn't have happened that way," he says of a shooting to which he responded a week after graduating from the academy in the summer of 2002. When Woods arrived on the scene-a disheveled mobile home-he found a corpse crumpled in front of a couch and a suspect. "The individual told me he'd pointed the gun at the victim just to scare him," Woods recalls. "He claimed that the victim jumped up and grabbed the gun," which went off accidentally during the ensuing struggle.

The shot was at close proximity all right, says Woods. "But there was no blood above the couch. It was on the side wall, and when I looked closely I saw that both the direction and depth of the spatter pointed down." Woods says his academy training told him that the victim had to have been shot at an angle from above. "When I confronted the individual with what I saw, he admitted I was correct."

For session four graduate Bobby Moore, a Lynchburg, Virginia, investigator, the puzzle pieces began falling together even before he left Knoxville. Moore describes a shooting that occurred 6 months before he left for the academy. Police found the victim, a middle-aged woman, shot in the head and sitting upright on the floor in a room barely heated by a wood-burning stove. Crime-lab tests on the gloves she wore came back positive for gunpowder residue, suggesting she'd been handling a gun, though no gun was found at the scene. Even more confusing, bleeding from her massive head wound had produced a strange pattern of staining: strips of blood-soaked clothing alternating with completely blood-free fabric.

"It was one of those cases that just didn't add up," Moore says. "When I came to the academy, I left behind a lot of uncertainty as to what happened and exactly where this woman had been when she was killed." By the time Moore got back, he says, "I could see the whole scene play out in front of me." Moore applied his new understanding of gunshot residue and bloodstain pattern analysis to reconstruct how the victim, shot from the front at close range, had tumbled forward onto the wood-chip-littered floor, then raised her gloved hands to her face, smearing them with gunshot residue from her skin. Blood pouring from the wound soaked through her clothes, except where folds of fabric had crumpled together when she fell. Consistent with this scenario were the splinters and wood chips Moore had noticed in the victim's hair-a sign that at some point she had been on the unswept floor. "What I found really interesting," says Moore, "is that someone had then lifted her up off the floor to look at her." And in so doing, had unfolded the pleats of clothing that had remained clean. "Only someone who cared about the victim would have done that."

On his return from the academy, Moore went to the prosecutors who were considering pressing charges against the dead woman's boyfriend. "I could explain a lot of things to them," he says, "and we were able to line up all our evidence in a row." Faced with the overwhelming case against him, the boyfriend pleaded guilty to second-degree murder.

Such stories validate the academy's mission of raising the caliber of crime scene investigation in this country through effective training. Already, 66 graduates have returned to their communities not only to use what they have learned but to disseminate it to colleagues. Still, with classes kept small to maximize hands-on training, there's little hope of teaching even a single representative from each of the nation's approximately 18,000 local law enforcement agencies.

"We see ourselves as a model," says Hallcox, "and a possible avenue for setting national training standards in many aspects of crime scene investigation." The Department of Justice appears to agree, if its award of an additional $1 million in hard-won federal funding is any indicator. The money will subsidize police departments and sheriffs' offices that can't afford the $6,500 tuition, and provide seed money for the first research grants awarded by the academy's umbrella group, the National Forensic Science Institute at the University of Tennessee.

Not that real-life crime investigation will ever resemble the seductive wizardry that has turned blood-spatter analysis into prime-time entertainment. "In real life, it's down-on-your-hands-and-knees dirty business," says Anderson. "Ninety percent of the time, what we do is tedious," she adds. "But that other 10 percent makes it all worthwhile."

Contributing editor Jessica Snyder Sachs is the author of Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG) and Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus).

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Forensic scientists in Switzerland are pioneering a whole new way to do autopsies. No scalpel required.

 

Copyright Jessica Snyder Sachs, as first published in POPULAR SCIENCE magazine

 

A light shines under the closed door of a radiology suite, down a darkened hallway deep inside the University Medical Center in Bern, Switzerland. Outside the building, under the glow of a fluorescent street lamp, an empty hearse waits in the loading dock. Tonight the local undertaker is earning some extra money making a special delivery. Entering the radiology room through a back door, he gently deposits a body-double-wrapped inside a blue bag-on the sliding bed of a full-body scanner. The bag, through which x-rays can easily pass, will remain closed while the body is scanned, both to respect the privacy of the dead and so as not to disturb any nonforensic personnel in the room.

Without the bag, the university's Institute of Diagnostic Radiology would not have approved the use of its aseptically clean research facilities for postmortem studies, says forensic pathologist Michael Thali. The Swiss emphasis on orderliness and precision extends to the task of death investigation.

 

This cultural passion-some would say obsession-for precision becomes clear to any visitor arriving by train here in Switzerland's 800-year-old, meticulously preserved capital. Rows of clocks line the train station corridor, all perfectly synchronized down to the sweep of their prominent second hands. In this spirit, Thali and his colleagues at Bern's Institute of Forensic Medicine are perfecting the ultimate no-mess autopsy: precise, objective and nondestructive, with death's every data point captured permanently on compact discs that the scientists store in the vault of a nearby Swiss bank (where else?).

 

Thali calls the technique "virtopsy," or virtual autopsy. Specifically, his research team has adapted the twin medical- imaging technologies of computed tomography (CT) and magnetic resonance imaging (MRI) to create three-dimensional, high-resolution computer images of a crime victim's internal organs. Thali pours these digitized blood and guts into a hollow-man replica of the victim. The result is a head-to-toe cybercorpse that a pathologist can view-wounds and all-from any depth and angle, including inside out.

 

Besides being a bloodless approach to an otherwise messy job, the digitally preserved bodies of the Virtopsy Project have the added benefit of permanency. "Murder victims have the unfortunate habit of decomposing," Thali notes. Of course, police and pathologists have long documented such disappearing evidence with photographs and detailed medical reports. Photos, however, are limited by their two-dimensionality and the inherent distortion of camera angles. And medical reports, according to Thali, remain unacceptably subjective.

 

It's a criticism supported by the cacophony of the courtroom, where prosecutors and defense lawyers often present dueling pathologists, each reinterpreting autopsy reports to favor one side or the other. Complicating a jury's difficulty in following such arguments are the typically gore-drenched autopsy photos that prompt many to turn away in horror. "We [in Switzerland] are not so used to shows like CSI," Thali points out. "It can be a real problem."

 

In the future that Thali envisions, any pathologist taking the witness stand can bloodlessly redissect the victim in full view of the jury by calling forth the original data stored on the discs. "Graphic, yes. Gory, no," he says.

 

Over the past three years, Thali has performed more than 100 virtual autopsies, each followed by a traditional autopsy to confirm his findings. Although his experimental technique has proved highly accurate, he expects to complete at least 100 more cases before the first virtopsy debuts in a court of law.

 

"Virtopsy is still like a little baby," Thali says. "It is not yet ready to stand alone." First he must show that it is at least as accurate as traditional autopsy. So far, he says, virtopsy has been particularly good for detecting the internal bleeding, bullet paths and hidden fractures that can be maddeningly difficult to

isolate amid the mass of blood and gore that results when a pathologist is forced to essentially eviscerate the body.

 

Best of all, perhaps, is the way CT and MRI scans highlight emboli-air bubbles that obstruct blood vessels and that have most likely entered the body through a wound of some sort. Such effervescent evidence can vanish as soon as a pathologist slices open a vein or organ to look for it, Thali explains. "So difficult is this problem that some have proposed performing underwater autopsies in swimming pools to detect escaping air bubbles," he says.

The scans also make it much easier to detect aspirated, or inhaled, water and blood in the lungs. These forensic "vital signs" tell a pathologist that a victim was alive when he entered the water or sustained an injury, which can be crucial for determining whether an apparent drowning or car crash was staged to cover up a murder. Pockets of air, blood or water show up clearly on CT and MRI scans as spots-black, bright white or gray-against the background of body tissues.

 

On the negative side, virtopsy remains woefully inadequate for diagnosing poisoning, as well as common natural causes of death such as infection or heart failure. "Obviously," Thali admits, "it's very important to be able to rule out such natural causes in a case of suspected murder."

The forensic question before Thali tonight is whether or not the elderly woman inside the body bag was dead before she ended up under the chassis of a Volvo sports sedan the previous afternoon. The Volvo's driver insists that he checked his rearview mirror before backing into the parking stall where the body was found. Given the woman's age-70ish-the possibility of a prior heart attack or stroke seems plausible.

 

Thali's research team began their examination of the body earlier in the day, as it lay face-up on the stone examining table in the forensic institute's second-floor autopsy bay. Visualization specialist Ursula Buck and pathology resident Emin Aghayev prepared the body by affixing buttonlike reference markers across its surface and photographing it with a digital camera from nine angles. Using an overhead light and transparency, they then projected a numbered grid of black points across the body before initiating a computer-guided 3-D scan using cameras mounted on an overhead beam. Turning the body over, Buck and Aghayev repeated the procedure before placing the corpse in a bag and sending it, by private hearse, to the university's Institute of Neuroradiology, several blocks away, for its MRI scan.

 

Magnetic resonance imaging has become fairly routine in medical diagnostics since its introduction in 1980. Using radio waves beamed through a powerful magnetic field, MRI produces 3-D internal images of unsurpassed detail. But the process remains far from automated, requiring operators to learn elaborate protocols to extract images from different types of body tissue. Complicating matters for the virtopsy project, MRI technologist Karin Zwygart has had to create special protocols to compensate for the lower body temperatures of Thali's refrigerated research subjects. The cooler temperatures would otherwise wreak havoc on results, because the MRI machine operates by translating the signature vibrations emanating from the nuclei of different kinds of atoms. At cooler temperatures, these nuclear vibrations slow down.

 

On the plus side, the resulting images are of such clarity that they draw amazed inquiries from radiologists whenever Thali displays them at international conferences. "Not only do they not fidget," he says of the corpses, "there is no beating heart, no circulating blood, no digestive motions to blur our images."The body's final appointment of the night brings it to the University of Bern's Institute of Diagnostic Radiology. Here it passes through the doughnut-shaped hole of a CT scanner, which constructs 3-D images of the body from a series of x-ray slices. In the radiology suite's darkened computer room, Peter Vock, director of the imaging institute, shares a computer with neuroradiologist Luca Remonda. As intent as schoolboys with a new videogame, the two men take turns clicking and dragging screen controls to manipulate the image on the monitor. Vock defines and deletes the CT scanner's bed to leave the woman's body suspended in midscreen. Slowly he melts away silvery layers of skin, muscle and connective tissue to reveal a bare white skeleton. He rotates the image, head over heels, pausing to note multiple rib fractures, a broken sternum, a shattered collarbone and crushed vertebrae. Then, layer by layer, he reassembles the body. When he reaches the level of fascia-midway between bare bones and full muscle-he stops again, intrigued by the abnormally high position of the woman's stomach and the telltale indentation, like an overly tightened belt, around the organ's midsection.

 

"We call this a collar sign," Vock explains. "We think that perhaps the woman's stomach was pushed up through a break in her diaphragm," the large muscle that separates the lungs from the abdominal organs. To get a better look, Vock finishes reconstructing the torso and then slices down through its midsection, five millimeters at a click, until he discovers a dark gap in the white muscle of the diaphragm.

 

Vock turns the controls over to Remonda, and Thali asks the radiologist to look for signs of inhaled blood in the woman's lungs. Earlier, during the MRI scan, Thali noted light areas in the woman's muscle tissues. If this represented active bleeding, it would suggest that she was alive when the car crushed her body against the pavement. But postmortem injuries can produce some internal blood seepage. More telling would be a clear indication of aspirated blood-a confirmation that the woman was still breathing when she sustained the injuries.

 

Remonda is on his second or third slice through the lungs when the first white splotches appear. As he continues to click down through the tissues, each bright spot melts away, only to be replaced by others. Clearly, aspirated blood.

 

Remonda and Vock turn to Thali for his pronouncement as to probable cause of death. "Thorax instability secondary to crushing injuries," he concludes: suffocation following rib fractures so massive that the victim was unable to take a breath.

 

The next morning Richard Dirnhofer, Thali's boss and the director of the Institute of Forensic Medicine, will perform a conventional autopsy for confirmation. "It will be a bloody mess, to be sure," Thali says with a grimace. "Nobody likes to show that to a jury."At the same time that Dirnhofer is making his first cut, visualization specialist Buck will be hauling her surface-scanning equipment to the police garage where the suspect's Volvo remains impounded. There she will create a 3-D computer image of the car's surface, the same way she photographed the corpse. Buck and Thali will then bring the body and automobile together in cyberspace, matching wounds to car surfaces until they can determine the woman's position as she sustained each of her injuries. Thali is particularly interested in how well the car's rear bumper and trunk lid will match up against the gouges seen in the surface scan of the woman's knees and the deep bleeding the MRI picked up in the muscles over her hips. "This is not some animation program using artificially created models," Thali insists. "You are looking at real data from the original car, the original person, the original wounds and bones." Depending on how the data match up, the driver could face manslaughter charges.

This dynamic matching of wound to weapon is an offshoot of a larger collaboration between Thali's forensic pathology team in Bern and the Scientific Forensic Service of the Zurich police. In 1995 Bern's Dirnhofer called Zurich's chief of forensics, Walter Brschweiler, with a challenge. He wanted a better way to match wounds and suspected weapons than the usual method of laying a photo of one over a photo of the other.

"That is when I thought of Marcel," Brschweiler says. Zurich traffic detective Marcel Braun had been adapting the new technology of photogrammetry for use in accident investigation. Photogrammetry software-originally developed for topographical mapmaking-turns a calibrated series of photographs into a 3-D model. In essence, Braun was using it to rewind multi-vehicle traffic accidents, extrapolating back from the dents and twisted metal of the final pileup to see who hit whom, all the way back to first impact. In collaboration with Thali, Braun adapted the technique to re-create violent deaths from the resulting damage seen on and within the corpses.

 

One of the most interesting cases on which the Bern and Zurich forensic scientists have collaborated came to trial in July 2003. It was a triple homicide, with three prostitutes found beaten to death in an apartment outside Zurich. Police had

a suspect who admitted to having sex with the women but insisted that they were all alive when he left the apartment.

 

 

The murder investigation focused on a deep bite mark gouged into the shoulder of one victim. The man denied biting anyone, and DNA swabs of the wound yielded a mixture of genetic fingerprints that would not stand up in court. The possibility remained that the women had killed each other. Indeed, judging from the size of the bite mark, police originally proposed that the bite on the woman's shoulder came from one of the other two victims. And when the Zurich police obtained dental casts from the other women's mouths, one did fit fairly well with their photographs of the wound.

 

Meanwhile Thali's team had completed their virtopsy of the three women, with Braun performing the 3-D surface scans. They could now go beyond matching dental casts against two-dimensional photos, to re-create how the teeth penetrated the dead woman's skin.

 

On a recent morning in his Zurich office, Brschweiler replays the results on his laptop computer-calling up the digitized, silvery-gray replica of the male suspect's teeth and bringing it in contact with the full-color virtopsy scan of the victim's bruised and bloodied shoulder. As the front teeth begin to enter the skin, Brschweiler switches to an underside view. "You see, there is not yet a reaction from the victim," he

narrates, "only the motion of the biter." But as the premolars break through, the teeth begin to drag laterally, widening the wound. "Now see, the woman reacts to the bite. She begins to pull away."

 

Re-running the simulation again, even slower, Brschweiler underscores the perfect match between teeth and bite marks. He then calls up the digitized dental cast of the dead woman whom police originally linked to the bite. "It matches on the left, but the angle is not the same," he says. "And look here, the small gap between the front teeth is not a perfect match." Importantly, Brschweiler says, the judge and jury were able to follow the re-creations and the science behind them during the suspect's murder trial, which resulted in a conviction.

 

In their shared pursuit of more-accurate murder re-creations, the Zurich Police Department and the Virtopsy Project have enlisted the additional help of the Swiss army, which has invested a considerable peace dividend in science. Switzerland has the distinction of ranking simultaneously among the world's most peaceful and most militarized nations, having avoided war for more than 150 years while enlisting virtually every male citizen in its military reserves.

 

"We have the time, people and peace to spend time in research," says Swiss Department of Defense mathematician Beat Kneubuehl, an internationally recognized expert on wound ballistics-the physical dynamics of how bullets, their fragments and their associated air jets pass through the human body. Kneubuehl's interest in gunshot wounds dates back to 1978, when the Swiss army asked him to design a line of ammunition and demonstrate that it met international conventions against unnecessary suffering.

To prove that his bullets would pass through a leg or arm without causing the kind of massive bone and blood-vessel damage that results in amputation, Kneubuehl decided to use simulated body parts instead of cadavers or animal carcasses, partly for ethical reasons. "We Swiss frown on that sort of thing," he says. But the major offense to Kneubuehl's Swiss sensibilities was the imprecision of such targets. "Every cadaver, every human or animal bone is a little bit different from the next one," he explains. "When I want to isolate one variable-the design of my bullet-I must expunge all other variables from my experiments."

 

Kneubuehl's line of faux body parts fracture, splatter, and shred like the real stuff-just more consistently so. His simulated bone consists of two layers of polyurethane sandwiching an inner layer of gelatin and coated with a thin veneer of rubber. His skulls are melon-shaped spheres with a corked hole for adding gelatinous brain and fake blood. They have been useful for re-

creating fatal beatings and shootings.

On one of Kneubuehl's recent test days, Thali joins him at the Swiss army's wooded training grounds outside the Alpine village of Thun. The sound of machine-gun fire alternates with that of birdsong as the two men enter the smallest of the site's three underground ballistic-test tunnels. Built in the early 1990s to minimize noise disturbance to Thun residents, the 100-, 200- and 500-meter tunnels are the largest underground firing ranges in the world.

 

Kneubuehl's goals for the day are to study the fleeting expansion of brain tissue caused by the air jet that accompanies a bullet and to measure the velocity of the skull fragments that enter the "victim's" brain. First he uses high-speed stop-action video to capture the expansion of his skull-brain models as each takes a bullet or shotgun load to the head. He then blasts the same ammo through sheets of synthetic bone strapped to big blocks of glycerin soap. Having thoroughly measured the glycerin's consistency, Kneubuehl can mathematically determine the energy of the imploding bone fragments by measuring how far they pass into this test material.

 

The glycerin soap has the added advantage of preserving the cavity created by the expanding jet of air that accompanies a bullet's passage through soft tissue. Actual brain tissue, in contrast, would immediately collapse on itself. "We know that the dynamic

cavity during the shot is considerably larger than the wound seen on autopsy," Kneubuehl explains.

 

Thali's mission for the day is simpler: He slips a wig onto one of Kneubuehl's head models for an "execution style" shooting. Thali wants to determine whether it's better to collect gunshot residue from the hair with adhesive tape or to shave the head and go for the scalp.

 

To the uninitiated, the test shot appears to result in the ultimate "oops" moment, with the brain ending up on the floor as the shattered skull flies against a far wall. "Actually, we see this sometimes in our cases," Thali says. "In Europe, we call it kroenlien, or evisceration of the brain." He retrieves the gunpowder-speckled wig and skull for later analysis and deposits the blob of synthetic brain in a garbage barrel.

 

As academically interesting, and even entertaining, as these experiments can be, the question remains: How might the Swiss approach to forensics translate in the down-and-dirty world of American murder investigation? Having spent a year working in the U.S., Thali appreciates that few if any American pathologists have the luxury of pursuing experimental methods and exhaustive research studies. "The medical examiner in a city like Baltimore probably sees as many murders in a weekend as I see in a month," he says.

 

 

Try closer to a year. The 10 full-time pathologists at Bern's Institute of Forensic Medicine oversee a region of southwestern Switzerland with a population of 1.5 million and perform about 500 autopsies a year, 10 to 20 of which turn out to be homicides. The Maryland Medical Examiner's Office, based in Baltimore, employs a similarly sized staff of 14 full-time pathologists. But the similarity ends there. Overseeing a state with a population of five million, the Baltimore staff performs an average of 4,100 autopsies a year, including 500 to 600 homicides.

 

Moreover, Switzerland's six institutes of forensic medicine all come under the auspices of the country's well-funded university system. The offices of American medical examiners, on the other hand, derive their funding from budget-strapped city, county and state governments.

 

The equipment required for a virtual autopsy includes an MRI machine costing upward of $1 million, a CT scanner priced at about $500,000, and 3-D surface-scanning equipment worth more than $100,000. "A lot of medical examiners consider themselves lucky if they have an x-ray machine," says William Rodriguez, deputy chief medical examiner for special investigations at the Armed Forces Institute of Pathology in Washington, D.C. "For the short term, this type of extremely expensive technology will be considered a big luxury."Meanwhile, the need to be prepared to deal with mass casualties has the U.S. Department of Defense extremely interested in setting up virtual-autopsy facilities-despite their high cost-at its massive morgue at Dover Air Force Base in Delaware, Rodriguez says. "As the technology becomes more efficient, this becomes a way to scan many more bodies in a shorter amount of time with fewer pathologists," he explains.

 

Already Department of Defense medical examiners use a conveyor-belt scanner, similar to those used to screen baggage in airports, to look into soldiers' bodies for bullets, shrapnel and unexploded ordnance. "As the body goes through the machine, we also see skeletal structures and get a pretty good idea of what we have in terms of large injuries," Rodriguez says. "Something more along the lines of what Dr. Thali is doing would allow us to take this down to levels of minute detail."

 

"Perhaps we in Switzerland have this role to play," says Thali of the opportunity to explore and perfect techniques that might someday transform postmortem exams for the rest of the world. He predicts that virtual autopsy will eventually speed and improve the procedure by guiding the pathologist's scalpel and preserving a record of what the internal tissues looked like before dissection. Still, the word "autopsy" comes from the Greek for "seeing with one's own eyes," and no one believes that virtopsy will ever replace the pathologist's scalpel completely. "What we see with our own eyes," Thali says, "will remain the gold standard in autopsy."

Science Writer Jessica Snyder Sachs is the author of Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus Books) and, more recently, Good Germs, Bad Germs: Health and Survival in a Bacterial World (FSG).

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Police sketches from eyewitness accounts are notoriously unreliable. Will "DNA sketches" prove any better?

Copyright Jessica Snyder Sachs, as first published in Popular Science

Nothing in American police work is more controversial than racial profiling. Minorities are targeted for small offenses in the hope of uncovering bigger crimes, and the practice has generated successful lawsuits by the ACLU and pledges from state governments and law enforcement agencies to clean up their discriminatory acts.

Add to this charged atmosphere the prospect of a DNA-race angle. By now most Americans know that when criminals leave traces of themselves--blood, semen, hair, a scrape of skin under a victim's fingernails--at crime scenes, they leave a unique genetic fingerprint that can establish their presence at the scene with great certainty. Less known but more controversial is that DNA traces also leave clues about ancestry and appearance, clues that, as genetic science matures, might be used to generate a sort of police sketch.

Racial differences constitute small notes within the great opus of the human genetic code, but the very fact that genetic markers linked to ethnic origin are, in a sense, cosmetic--that is, they affect outward appearance--makes them potentially useful in the hunt for criminals. Is a suspect of fair Celtic stock or of darker African origin? His or her DNA may tell. Such information could prove far more useful to street-pounding cops than notoriously unreliable eyewitness reports. But unless the science proves reliable, there is risk here: The use of DNA markers could confer authority on police searches--isn't genetic information more reliable than even fingerprints?--that, in the area of racial markers and appearance, it may not deserve.

Until recently, genetic markers have not been used in manhunts, but that changed earlier this year when a private gene lab concluded that an unknown serial killer was a medium-to-dark-skinned black, not the white man that police had been focused on. The lab, it turned out, was correct, and although its conclusion did not directly lead to the arrest of the suspect, it advanced the case for supporters of the DNA sketch idea.

In 1997, when members of the national DNA Advisory Board officially selected the gene markers for DNA evidence matching, they could have included a few markers associated with ancestral geographic origins (European, East Asian, sub-Saharan African)--which are a good indication of race and ethnicity. "We deliberately chose not to do so," says Ranajit Chakraborty, director of the University of Cincinnati's Center for Genome Information. Chakraborty says the board skirted the racial-marker issue in part because of the political minefield it represented. Thus today's standard American DNA fingerprint, with its battery of 15 gene markers (two were recently added to the standard 13), is a sort of bar code identifier that is fine for matching two DNA samples but offers no hints about the human package from which a crime-scene DNA sample is derived.

Not that DNA hasn't already been quietly used for ethnic identification. Following the 9/11 terrorist attacks, Chakraborty acceded to the request of a family whose son had been a passenger on United Flight 93 (the thwarted terrorist mission brought down in Pennsylvania). "We had a specimen that consisted of at least two individuals' remains, one of which was their son's," he explains. "The family was reluctant to bury it with his other body parts if it contained any remains that might belong to a hijacker." Chakraborty determined, with 95 percent certainty, that the unidentified tissue did not belong to anyone of Middle Eastern ancestry.

"We may not be able to tell German from French," says Chakraborty, "but we can place individuals in major continental groups." In turn, within each of these groups, certain types of hair texture, eye and skin color, and other facial features predominate. Such information could prove useful in an investigation, admits Chakraborty. "But (it) should not be interpreted that you can say with 100 percent accuracy that a person will have, say, brown eyes."

Because geneticists have largely kept mum about ethnic markers, it proved something of a shock when DNAPrint Genomics concluded last March that a Louisiana serial killer's "biogeographical ancestry" was 85 percent sub-Saharan African and 15 percent Native American. At the time, the police were on an altogether different track: They had been seeking a white man who had been seen lurking in the neighborhood of one of the crime scenes.

"Basically, the phone line went
silent," says Tony Frudakis, research director at DNAPrint, describing the conference call in which he revealed the lab's results to police investigators. They were dubious, Frudakis says, and asked to see DNAPrint's analyses of 20 other DNA samples of known individuals they'd sent along with the killer's sample to test the lab's reliability. "We got them all right," Frudakis says.

The investigators were convinced enough to expand their search to include African-Americans, then had a break in the case due to an unrelated incident. Derrick Todd Lee, called in for questioning about two unrelated killings, voluntarily gave a DNA sample, which police say matched DNA from the serial murders. Arrested on May 27 and now awaiting trial, Lee is African-American.

A basic ancestry profile may be just the beginning for the DNA-based police sketch, boosters say. "To be honest, most of us are mongrels," says Frudakis. "We reside somewhere along a continuum rather than as members of physically distinct groups." He says DNAPrint is developing genomic tests to detect more specific physical traits, and it hopes to have the first such test--Retinome, for eye color--ready for market by the end of 2003. "After that, give us another year for hair color," he says. The latter is a particularly bold boast, since not much is known about hair color markers beyond one associated with red hair.
DNAPrint is not the first to claim progress toward a gene-based police sketch. In the late 1990s, Britain's Forensic Science Service trumpeted the development of something called a DNA photofit. Emboldened by the identification of the gene marker for the "Celtic look" (fair skin and red hair), it poured money into an ambitious project at University College London. Scientists scanned the faces of hundreds of volunteers in an attempt to correlate digitized facial geometry with genetic markers.

The approach made intuitive sense, and it would have closely paralleled the anthropometric tricks used by police sketch artists, who build their drawings around a witness's best recollections of certain landmark geometries, such
as nose height and width, eye shape and the distance across the broadest part of the face.

The Forensic Science Service had faith that the University College team could deliver in a couple of years, says team member Alf Linney, a medical imaging expert at University College London. But the connection between genes and facial appearance proved too complex for the London scientists, and the project was suspended in 2000.

"We may never be able to fully reconstruct a suspect's face from genes alone," says Mark Benecke, one of Germany's most respected forensic biologists. "Genes coordinate the whole thing, but events during development and illnesses or malnutrition during childhood greatly influence facial symmetry."

As every high school biology student learns, genotype plus environment equals phenotype--the physical expression of our genes. All of which Frudakis concedes. Still, he argues that the sophistication of new "high-throughput" computer analysis of genetic information greatly expands the layers of genetic clues that can go into a DNA-based best guess about a person's physical appearance.

"We're using neural networks and sophisticated pattern detection methodology to systematically determine genetic sequences over the whole genome for thousands of people," Frudakis says. "So when we're searching for genes associated with hair color, in essence we're doing a grid search. It's a treasure hunt in which we systematically determine, OK, the treasure isn't here, let's search the next grid." This contrasts, he says, with gene searches of just a few years ago, which were much more hit-and-miss.

Critics fear that the DNA sketch concept opens the door to biased, unscientific racial profiling based on unproven gene markers for behavior, including criminal behavior. "The temptation will be to run DNA data through computers to conclude, for example, that you can identify markers for, say, sexual offenders," warns sociologist Troy Duster, author of Backdoor to Eugenics and a consultant to the National Human Genome Research Institute. Imagine such a data crunch based on the DNA of convicted criminals, given the preponderance of black and Hispanic men in American prisons. "It would be like going to the NFL and concluding that the DNA marker for sickle-cell anemia (associated with African ancestry) makes you a good football player."

Despite such objections, forensic biologists like Benecke predict that the accuracy of DNA-based descriptions will edge past that of eyewitness accounts within 15 years, barring legal roadblocks. Germany currently outlaws the disclosure of DNA-gleaned information, except in medical situations with a patient's consent. "Technically, we're not even supposed to notice if there's a Y (male) chromosome," says Benecke. "But how can it be an invasion of privacy if we're only looking at things that can be seen from the outside?"

Unencumbered by such privacy laws, U.S. forensic labs already have nearly everything they need to develop their own "genetic witnesses." Given the time and money, they will continue with the genomic sifting and sorting. Frudakis makes this bold prediction: "A few years from now, we're going to have figured out so many traits that a criminal might as well leave his driver's license at the scene of the crime."

Jessica Snyder Sachs, a regular contributor to Popular Science, is the author of Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG) and Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus/Basic Books).

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Post-9/11 laws protect Americans from the mishandling of potential bioterror agents. They could also slow down some vital medical research.

Copyright Jessica Snyder Sachs, as first published in Popular Science, March 2003

It's impossible to miss the note of fear in the voices of prominent American bio-scientists when talking about the laws rushed onto the books in the wake of 9/11. Specifically, the laws in question introduce new criminal penalties for improper handling of potential bioweapon materials, and the first prosecutions have made it clear that the feds mean business.

 
Section 175 of the USA Patriot Act, which sailed through Congress during the height of the postal anthrax terror, applies to anyone working with, storing, or transporting some 60 "select agents." The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 piled on more fines and more jail time.

Of course, anything to do with bioweapons can strike fear in the average American, who might reasonably expect that the government would ratchet up penalties for careless handling of controlled materials in the age of al Qaeda. Problem is, the select agents list covers a broad array of microbes and toxins of longstanding interest to medical researchers looking for vaccines, cures or antitoxins.

The list includes the Ebola, yellow fever and Marburg viruses; anthrax and brucellosis-causing bacteria; food-borne aflatoxins and botulinum toxin, as well as ricin, the castor-bean-derived toxin whose manufacture in a north London flat led to several arrests in January; and a lot more. All are causes of human and animal disease, and research work requires that the toxic materials themselves be widely held.

Samples can be found in more than a thousand science and medical labs across the country. Hence, there are a lot of scientists who feel newly exposed to a risk of inadvertently making a now-criminal error. One side effect of tougher laws could be a reduction in the amount of materials available for necessary research -- and thus a reduction in the amount of research -- nationwide.

"In scientific research," says Ronald Atlas, president of the American Society for Microbiology, which represents more than 42,000 members, "we're used to regulations that stipulate you have 30 days to correct a situation, not years in jail."

Of course, the legislation was not intended to prevent research, and specifically exempts "prophylactic, protective, bona fide research or other peaceful purposes." So it might be easy to dismiss fears of the legislation as overblown--until you consider the ordeal of the first researcher to fall afoul of the Patriot Act.

In November 2001, FBI agents visiting a University of Connecticut pathology lab found two vials marked "anthrax" in the freezer of graduate student Tom Foral. The anthrax-laced tissue samples came from the necropsy of a cow that had died of natural anthrax years earlier. Foral had saved them, along with an assortment of other pathology specimens, after a professor asked him to clear out a malfunctioning storage freezer. Foral says he had taken "clear out" to mean "save what you can use and destroy the rest." His professor told the FBI that he assumed Foral had destroyed everything. Foral's frozen, unprocessed specimens posed no direct health threat, though someone could have cultured anthrax from the contaminated tissue and blood.

Foral's supervisors tried to explain to criminal investigators that when the student added the specimens to his reference collection he was doing nothing out of the ordinary in this line of research. "That's the training graduate students get," says Kirklyn Kerr, dean of the University of Connecticut agricultural college, where Foral continues to study the West Nile virus. "My own faculty advisor used to tell me, â€Never discard anything unless you have a duplicate.'"

Last July, federal prosecutors formally charged Foral with "unjustified possession of a select agent" under the rules of the Patriot Act, a crime punishable by up to 10 years in prison and a $250,000 fine. "He wasn't authorized to save it," says U.S. Attorney spokesperson Delcie Thibault, explaining the decision to prosecute. "He had never done any research with anthrax, and he had no plans to do so."

Citing Foral's cooperation throughout the investigation, the prosecutors offered a deal involving visits to a probation officer, community service and the insertion of a letter in Foral's ROTC file detailing his "illegal activities" -- no small matter for a student who had long planned a career as a military doctor. Foral felt trapped: "I had no choice but to accept [the deal]. Lawyers are too expensive, and I'm in the midst of applying to medical schools."

Was this the intent of the law?

"Certainly it puts a chill over anyone trying to do research," says Harvard microbiologist John Collier, a leading anthrax researcher who has since destroyed his sole strain of the bacteria.

Naive students are not the only researchers to run afoul of new federal interest in the handling of toxic materials. In January, prominent infectious-disease researcher Thomas Butler, of Texas Tech University Health Sciences Center, ended up in handcuffs after he was alleged to have falsely reported several vials of plague bacteria as missing. According to the journal Science and other publications, Butler admitted he made the false report to cover up the fact that he had forgotten to properly document destroying the bacteria, as required by the new rules. Released on bond, he was made to give up his passport, agree to stay entirely away from biological research materials, and wear an electronic monitor, pending trial. Butler was asking for trouble, clearly, but a colleague at his university described the incident as "a minor problem that's been handled with a wartime mentality."

Not surprisingly, some liability-conscious universities have begun advising their scientists to immediately destroy stocks of any biological agents not currently in use. Among the instances most disturbing to researchers was Iowa State's wholesale destruction of its entire anthrax collection -- the original "Ames strain" linked to the fatal postal contaminations.

Although other institutions have isolates of the strain, no two collections remain exactly alike in a world of rapidly evolving microbes. Indeed, the profligate gene variation of bacteria and viruses explains why researchers, from graduate students to tenured professors, continually save specimens from different sources and from one year to the next. By studying the subtle genetic changes between isolates, researchers come to understand a microbe's vulnerabilities, as well as variations in the toxicity and antibiotic resistance of different strains. The forensic tracking of bioweapons to their sources likewise depends on being able to compare the genetic "fingerprints" of the broadest possible array of isolates.

So although the scientific community as a whole has rallied around the demand for greater national security, many scientists argue that the overzealous application of new laws may hamper the fights against both bioterrorist threats and natural disease.

"I'm very worried that the nation is going to shoot itself in the foot by imposing too strict regulations," says Collier, now part of a National Academy of Sciences committee examining ways to minimize the misuse of biotechnology while making regulations more conducive to vigorous, open research.

Speaking before a House committee on scientific discourse and terrorism, Atlas recently argued that advances in lifesaving treatments depend on researchers having access to reference cultures. "We must remember that natural infectious diseases are a greater threat than bioterrorism," he warned.

The White House Office of Science and Technology Policy (OSTP), alarmed about the destruction of irreplaceable specimens, recently urged microbiologists not to destroy dormant stocks but to send them to the federal government's Chemical Demilitarization Facility, in Edgewood, Maryland.

Edgewood is no specimen bank, however: Once researchers surrender their biological agents to the government they can't get them back. At some point, says Rachel Levinson, assistant director for life sciences for OSTP, the government might open up the Edgewood cache for federally funded studies. "Or they could be kept there as reference material for forensic purposes."

Other sticky issues include restrictions prohibiting certain individuals from access to select agents under any circumstances. For example, it may seem logical that the acts exclude access to military misfits and anyone from a country known to support terrorism. But some fine scientists have fled countries such as Iran and Cuba, says Atlas. Consequently, the American Society for Microbiology has lobbied Congress to amend the laws to allow the U.S. Attorney General to exempt individuals "when in the national interest." Even more troubling to some, the prohibition of anyone who's been dishonorably discharged from the Army includes, for example, people discharged for sexual preference.

"A top issue at any university is diversity, and that includes sexual preferences," protests Kerr. "We can't and don't want to discriminate. Yet this law forces you to do so."

It likewise prohibits access to anyone who has ever been committed to a mental institution. Taken literally, that includes anyone who's checked into a hospital ward or in-patient psychiatric clinic for depression or even an eating disorder such as bulimia. Trickier yet may be the exclusion of "any unlawful user of a controlled substance."

"Without downplaying the importance of being careful and handling agents appropriately, we're still talking about research going on within a university environment," frets Kerr. "As an administrator, I don't want to put technical staff, graduate students, and postdocs at risk of being charged under this law for pursuing research."

As dean of the University of Louisville's graduate school, Atlas echoes Kerr's fears: "If you're working with a select agent, the Patriot Act says you have to exclude restricted persons or they go to jail and you go to jail, as does anyone who has given them access, right down to the janitor who unlocked the laboratory door."

All this may slow some important research -- though Barbara Johnson, president of the American Biological Safety Association, scoffs at such concerns and predicts the opposite result. "The concept of potential prison time or large monetary fines is not new to science and research," she says, citing the consequences of breaching Occupational Safety and Health Administration (OSHA) rules on workplace safety in the laboratory. Johnson contends that even if the new regulations result initially in a small drop in research on select agents, that will change dramatically when the federal funding spigots open up. "When the bioterrorism dollars start flowing, those institutes that are compliant with this new law are going to be able to expand their programs tremendously, and those that don't have programs will want to start them."

Maybe, but the road to a golden age of bioterrorism research may be lined with a few victims of the new legislation. Ask graduate student Foral, who describes his ordeal with the FBI and U.S. Attorney's office as Kafkaesque.

"Wouldn't it have been a reasonable solution to have just told me to get rid of them?" he asks of the two pathology specimens found in his freezer. "To this day, I really can't understand why that wasn't done."

Jessica Snyder Sachs, a contributing editor to Popular Science, is the author of Good Germs, Bad Germs: Health and Survival in a Bacterial World (Hill&Wang/FSG) and Corpse: Nature, Forensics, and the Struggle to Pinpoint Time of Death (Perseus/Basic Books).

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