BIG PATIENTS, BIG SUCCESSOne way to understand the mechanisms of the virus is to have its genome sequenced. The Human Genome Sequencing Center (HGSC) at BCM is sequencing DNA from

Mending the MindMaggie, a former marathon runner, was diagnosed in2006 with multiple sclerosis (MS) - a disease whosesymptoms progress from relatively mild, such as the limbnumbness she experiences, to severe, such as paralysis orloss of vision. Could stem cell research lead to bettertreatments or even a cure for MS?

Hidden in Plain Sight Progesterone offers the hope of being the firstnew treatment for traumatic brain injury in 30years. It was there, under our noses, the wholetime.

Issue 3, Fall 2010

S AVESS AVES

178DVD INSIDE!

Full-length TV show“SurvivorTales:

Niemann-Pick Type C.”

BIG PATIENTS, BIG SUCCESS

For a team of scientists fighting to save elephants from adeadly virus, one calf's birth marks no small achievement.

6 Heart Transplant: A Life SavedCourtesy of Animal ResearchChuck Reynolds and his wife, Patricia,were both registered nurses and did notneed a textbook to understand the grimprognosis of congestive heart failure. Along string of visits to cardiologists hadbrought new prescriptions and newtreatments, but no reversal of the slidethat began with a massive heart attack in 1993.

15 Drop by DropKatelyn Denbow, just shy of her 13thbirthday, lives with Alström syndrome, arare genetic disorder. It results from adefect in just a single gene, but theimpact is profound. It affects vision,hearing, heart, liver, kidneys and othersystems. It also greatly shortens lifeexpectancy.

20 FETCH~LABTimmy is a 10-year-old springer spanielbasset mix, a service and therapy dog toowners Neil and Vonnie Young ofBerwick, Pennsylvania. He’s also thelatest recipient of a wireless hearing aid,installed by staff and students at theUniversity of Cincinnati’s FETCH~LAB.

RESEARCHS AVES

Issue 3, Fall 2010 FEATURES3 Giving Elephants a Fighting Chance

© Graciela Gutierrez

5 Preserving Vision with Robots© Susan Conova

6 Heart Transplant: A Life SavedCourtesy of Animal Research© David Tenenbaum

7 Clogged Arteries? Before You Need aPlumber, Call the Plaque Whisperer© Susan Conova

8 Hidden in Plain Sight© Sylvia Wrobel

14 On a Mission to Save Smiles© Lisa Spellman

15 Drop by Drop© Joyce Peterson

17 Mending the MindToward Stem Cell Therapies forNeurological Disease© Camille Mojica Rey, PhD

20 FETCH~LAB© Kathryn Cosse

22 Animal Health Timeline© Animal Health Institute

24 Essays

Editor-in-Chief: Paul McKellipsResearchSaves™ is a registered trademarkof the Foundation for Biomedical Research818 Connecticut Avenue, NWSuite 900Washington, DC 20006

All articles are reprinted in their entiretywith the expressed written consent ofthe authors and their associated institutions. Each article and photo isprotected under U.S. copyright law andremains the sole property of the authorsand their respective institutions.

© ResearchSaves.org. 2010 All Rights Reserved

Giving Elephants aFighting Chance

After a pregnancy lasting almost 23months, Shanti, a 19-year-old Asianelephant, delivered a healthy 348-poundmale calf. Healthy being the key wordthanks to advances made by BaylorCollege of Medicine (BCM) to significantlyreduce the threat of the potentially lethalelephant endotheliotropic herpesviruses, orwhat is commonly called elephant herpes.

3

ResearchSaves is a quarterly publication. Each issue contains a full-length DVD, poster oreducational program. The annual subscription price is $39 and includes shipping and handling.Complimentary issues are available to K-12 teachers, thanks in large measure to the generoussponsorships granted by individual biomedical researchers.

24 Nearly 400 students

from 59 schools wrote

essays that answered

the question, “Why

are Animals Used in

Biomedical Research?”

After a pregnancy lasting almost 23 months, Shanti, a 19-year-old Asian elephant, delivered a healthy 348-pound male calf.Healthy being the key word thanks to advances made by

Baylor College of Medicine (BCM) to significantly reduce the threat ofthe potentially lethal elephant endotheliotropic herpesviruses, or whatis commonly called elephant herpes.

The elephant, born at the Houston Zoo’s McNair Asian ElephantHabitat on May 4, was named Baylor by the zoo’s elephant careteam in honor of the two institutions' efforts to put a stop to thedeadly virus killing elephants across the globe.

“After months of preparation and tender loving care, the delivery wasactually quick and easy for Shanti,” said Daryl Hoffman, largemammal curator at the Houston Zoo. “The keepers helped Baylorget to his feet and he was standing on his own within 2 hours afterhis birth.”

The birth marks a success for both institutions, a healthy birth and achance to use a newly developed test on a newborn elephant.

The test, developed at BCM, specifically diagnoses the elephantherpes virus, when before a diagnosis was more complex. In manycases, an elephant was only diagnosed after it was too late to beginpotentially life saving treatments.

Development of the testLittle is known about elephant herpes. There are many strains, butthis one is particularly deadly. Because researchers cannot grow thevirus in culture, they cannot develop a vaccine or effective treatment.In fact, it is not known exactly how elephants becoming infected withthe virus.

Prior to the development of the current test, the diagnostic screeningprocess looked for all types of viral infections that an elephant mighthave.

“Our newly developed test looks specifically for the most commondeadly strain and its subtypes,” said Dr. Jeff Stanton, postdoctoralfellow in the department of molecular virology and microbiology atBCM. “While both tests are important, when it comes to thisparticular strain, a more sensitive screening process was needed.”

Since a virus has yet to be grown in a lab, researchers used archivalDNA samples from historical cases of elephant herpesvirus given to them by the National Elephant Herpesvirus Laboratory at theSmithsonian National Zoo in Washington, D.C. Using those samplesalong with samples from the Houston Zoo, researchers analyzed thevalidity of the new test.

Stanton, who worked as a veterinarian in St. Louis, Missouri, beforecoming to BCM, helped develop the new test while working in thelab of Dr. Paul Ling, an associate professor of molecular virology andmicrobiology at BCM. His lab focuses on the human herpes virus.

Time is of the essenceNot only is the new test more specific towards the deadly elephantherpes virus, it also produces a faster result – in as little as a day ifnecessary. Because the disease can kill within a week, the sooner adiagnosis is established, the sooner treatment can begin. In fatalcases, symptoms do not show up in elephants until it is too late.

“Right now we receive fluid samples from the zoo once a week fortesting. We want to catch the virus as soon as possible so treatmentcan begin immediately,” Stanton said.

The virus can potentially appear in a number of bodily fluids. Thecurrent test can be used on blood, urine, trunk washes and eventears. Being able to screen a number of sources will also help todetermine how an elephant becomes infected. ➤

Giving Elephants aFighting Chance

Fall 2010 ResearchSaves.org 3

Baylor Colleg

e of Med

icine

A new baby elephant is cause for celebration at the Houston Zoo, and also at Baylor College of Medicine.

© Graciela Gutierrez

4 ResearchSaves.org Fall 2010

So far during the screening program, noelephant at the Houston Zoo has testedpositive for the virus, but researchers arekeeping their eyes on 4-year-old Tucker,who is at the age when elephant herpes ismost likely to become active.

Diagnosis, then what?Now that the experts can diagnose theherpesvirus, they need better treatment. Theonly treatments available now are antiviralmedications effective for other herpes strains.

“Only about 15 percent of infectedelephants survive when treated, however, wearen’t sure if the antivirals actually made thedifference,” Stanton said. “We also aren’tcertain current treatments will be moreeffective if started sooner rather than later,by the time the elephants were diagnosed, itwas already too late.”

One way to understand the mechanisms ofthe virus is to have its genome sequenced.

The Human Genome Sequencing Center(HGSC) at BCM is sequencing DNA fromtissues of infected elephants to try and fishout the herpesvirus genome. The HGSC hasbeen successful in sequencing many typesof animal genomes. (See sidebar)

“In some sense, it will be like finding aneedle in a haystack, given the relativeamounts of viral and elephant DNApresent,” said Dr. Joseph Petrosino, assistantprofessor of virology and microbiology.“However, we know there is a lot of virus inthese infected tissues, and we know a lotabout the herpesvirus genome sequencealready, so we are hopeful that we will beable to fish out this particular virus genomefrom these samples.”

Stanton added “A complete sequence of thevirus genome could help in making avaccine. We would be able to identifyglycoproteins [proteins that containcarbohydrates and are essential in manycellular processes] that would give us moreinformation about how the virus works.”

Understanding the virusThe elephant endotheliotropic herpesvirusesaffect both Asian and African elephants butare more often fatal in the Asian type.

The elephant herpes virus was identified bythe National Zoo in 1995. Herpes virusesare usually species-specific but sharecommon features. Once inside a host,whether human or animal, the virus can gointo a latent phase after causing only mildsymptoms or no signs of the disease.

Many believe that only captive elephantsare susceptible to this virus. However, it isalso a problem for wild elephants, but thosestatistics have not been well documented.Stanton, along with researchers from theNational Zoo, have traveled to India tobegin testing wild elephants using the newlydeveloped test.

How it beganBCM and the Houston Zoo begancollaborating during a conversationbetween Dr. Alan Herron, director of theComparative Pathology Laboratory in theCenter for Comparative Medicine at BCM,and Dr. Joseph Flanagan, the HoustonZoo’s director of veterinary services. Herroncalled Flanagan to express sympathy after2-year-old elephant Mac died Nov. 9,2008. The talk quickly turned to howbeneficial it would be to be able to testappropriately and effectively for the disease.They also talked about how such workcould lead to development of a vaccine.

Herron, also a professor of pathology and a veterinarian, brought in two of BCM’sleading virologists and vaccine experts, Dr.Wendy Keitel, professor of molecularvirology and microbiology, and Dr. RobertAtmar, professor of medicine and molecularvirology and microbiology.

How will it end?“This virus is killing off elephants in zoosand in the wild,” Stanton said.

For those in zoos, it is affecting the breedingrate. Stanton says that without furtherresearch towards a vaccine and treatmentfor elephant herpes, the number of zooelephants will deplete.

In the wild, Asian elephants, which are mostaffected by the virus, are alreadyendangered. As their habitats are takenover, their herds get separated, reducingoptions for mating.

“The research being done now, as well asthe new testing method, will also be used tolook for ways to establish a screeningprogram for elephant herds in the wild,”Stanton said. “If researchers can develop avaccine, then we have the potential to savean entire species.”

Graciela Gutierrez, Senior CommunicationsSpecialist, Baylor College of Medicine.

To learn more about Baylor College ofMedicine’s ground-breaking research visitwww.bcm.edu.

Baylor College of Medicine’sHuman Genome

Sequencing Center

While collaboration with the Houston Zoois a first for Baylor College of Medicine,researching illnesses and understandinganimal genomes is nothing new for BCM.The Human Genome Sequencing Centerat BCM has successfully sequenced anumber of genomes since it wasestablished in 1996.

Most recently, the bovine genome wassequenced, providing a look at theevolutionary process of mammals includinghumans. This project took over 300scientists from 25 countries to complete.

Other genomes sequenced in cooperationwith the BCM sequencing center includethe mouse, fly, sea urchin and human.Currently the HGSC is working onsequencing the genome of the wasp andwallaby among many others.

The Center recently received additionalfunding from the National Institutes ofHealth to support the Human MicrobiomeProject, which seeks to understand how thetrillions of microscopic organisms that livein and on the human body affect humanhealth and lives.

Most notably, the DNA sequence of Nobellaureate Dr. James Watson, co-discovererof the DNA double helix and developer ofthe Human Genome Project, wasannotated and verified by researchers atBCM. Dr. Richard Gibbs, director of theBCM Human Genome Sequencing Center,was a part of the group that presentedWatson with his DNA sequence andannotation.

The BCM Human Genome SequencingCenter is currently one of three large-scalesequencing centers funded by the NationalInstitutes of Health.

PRESERVING VISION with RobotsOne of the first things Howard Fine does to prepare for a test run ofa new robot for eye surgery is to crack open an egg.

It’s not breakfast he is interested in; rather, Dr. Fine uses themembrane inside the shell of fertilized chicken eggs as an animalmodel for retina surgery. The tiny blood vessels in the membranesare nearly identical mechanically to those in the human retina andperfect for fine-tuning the robotic surgical techniques that Dr. Finehopes will soon be able to reverse what is a leading cause ofblindness in the United States.

Just as atherosclerosis clogs vessels in the heart, leading to heartattacks, atherosclerosis also obstructs the tiny vessels in the retina,which can lead to blindness. More than 2 million people are strickeneach year in the United States with obstructed retina vessels, andmore than a half million go blind from the disease. No treatmentexists to restore blood flow and prevent vision loss.

That’s where the Intra-Ocular Dexterity Robot comes in – designedby Nabil Simaan, PhD, assistant professor of mechanical engineeringand head of the Advanced Robotics & Mechanism Applications(ARMA) Lab at Columbia; Dr. Fine; two ARMA engineering graduatestudents, Wei Wei and Roger Goldman; and Stanley Chang, MD,chairman of ophthalmology. With two robots perched on a ring(which will eventually hover over a patient’s eye but now hangs overthe chick membrane), Dr. Fine uses joysticks to manipulate therobot’s dual snake-like arms to insert nearly invisible metal stentsinto blood vessels.

“While robots have revolutionized a number of surgical fields, theiruse has been lacking to date in ophthalmology, in part because ofthe small size and high precision required,” Dr. Fine says. This robotis one of the most precise medical robots ever built, capable ofmanipulating tools with 5-micron precision, an order of magnitudeimprovement over unassisted human hands.

With the fundamentals of the robot and the surgical procedure nowin place, Dr. Fine says it will probably take six months to a year oftinkering before the team can attempt the insertion of stents into theretinal blood vessels of lab animals. Once the stents appear safeover the long term, Dr. Fine plans to apply to the FDA to start aclinical trial in humans.

“I think we have the potential to help countless patients who havelost vision from retinovascular disease,” Dr. Fine says. “And if thistechnology is successful for ophthalmology, it might be useful inother areas of the body as well.”

Susan Conova, Editorial Director, Columbia University Medical Center


Columbia

University

© Susan Conova

❝While robots have revolutionized a number of

surgical fields, their use has been lacking to date

in ophthalmology, in part because of the small

size and high precision required,” Dr. Fine says.

Photo credit: Columbia University Medical Center

Uni

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isco

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Then, in 1983, cyclosporine, a drug derived from a soilfungus, began to be used to suppress the immune system,and lifesaving transplants of hearts, kidneys and otherorgans became almost routine. In 2008, 2,108 hearttransplants were performed in the United States. About 70percent of patients are alive five years after the operation.

Heart transplant is a last-ditch effort, available only topatients who are deathly ill, and many patients die on thewaiting list because a suitable organ does not becomeavailable.

Reynolds found the first year after surgery to be tougherthan expected, with repeat trips to the hospital asopportunistic infections took advantage of his suppressedimmune system. Gradually, his body responded to its newheart, and he was able to resume his life in the couleecountry of west-central Wisconsin.

Almost literally back from the dead, Reynolds returned tothe house he has lived in since 1976. Today, a few chickenspeck in the yard; a small garden will be planted in a sunnyspot; a beehive is being assembled. The house remainshumble, but it has been greatly expanded during the lastfew years.

Reynolds’s four sons are doing well. The twins, now 15,garden, run cross country, compete in forensics and dosome photography. Jay, 18, is graduating high school,exhibiting his paintings and developing as a birdwatcher.Teague, 35, works as a carpenter and firefighter, and playsas a cross-country skier and cyclist.

Patricia, who volunteers at the local school and continues towork as a registered nurse, is no longer worried aboutbecoming a widow.

And with his heart pumping plenty of blood, Reynolds, 62,has started volunteering at the library and returned tobicycling on the hilly roads around home.

Because he’s still taking some drugs to control his immunesystem, Reynolds is vulnerable to infection and thus unableto return to nursing, but he is working as a substituteteacher. He says he was attracted to the job because hecould decline work on days when he felt ill, but “It’s been along time since I had to say I was not available.”

David Tenenbaum, Public Information Officer, University ofWisconsin–Madison

HEART TRANSPLANT:A life saved courtesy of animal research© David Tenenbaum

Chuck Reynolds, a tall, laconic and bearded man with a dry sense of humor,remembers the winter and spring of 2001 as the time he spent waiting to die. Weak, short of breath, swollen with fluid, he was barely able to climb the stairs and essentially stuck in a recliner at his backwoods house near Lafarge,Wisconsin.

He wasn’t a lazy man. He was in the advanced stages of heart failure at age 54.

Reynolds and his wife, Patricia, were both registered nurses and did not need a textbook to understand the grim prognosis of congestive heart failure. A longstring of visits to cardiologists had brought new prescriptions and newtreatments, but no reversal of the slide that began with a massive heart attack in 1993.

By 1997, Reynolds had to quit nursing for less-stressful employment, workingpart-time at the post office and then delivering newspapers on Sundays.

“Basically, I was staying home with the kids,” he says. “It got so bad that I’d gogrocery shopping and have to stop for breath in the aisles.”

Patricia adjusted her nursing schedule to minimize the need for daycare for theirboys and bought a phone with a single button that would notify the emergencyroom 20 miles away.

“If you find daddy on the floor and he won’t talk to you, press this button andtell the people at the other end that he can’t get up,” she told Zack and Zeke,fraternal twins who were then 6 years old.

In April 2001, Reynolds visited the University of Wisconsin Hospital for anevaluation, and on June 1 the cardiologists told him that he was too unstable to leave the hospital. He needed a transplant.

“I was aghast. I thought, ‘You’re going to take my heart out of my chest?’” he says.

But Reynolds had already met heart-transplant patients who were doing wellyears after surgery, and his only other option – if you can call it an option – was to leave Patricia a widow and his sons fatherless.

For more than three months, Reynolds was trapped in the cardiology ward,tethered to monitors and catheters, as doctors struggled to keep his heartbeating long enough for a generous person to make a donation.

On Sept. 13, 2001, a young man from Wisconsin took his own life, and with his parents’ permission, his heart was quickly removed and flown to Madison, where Reynolds was waiting on an operating table.

The successful transplant leavened some of the depression of the dreadfulmonth of September 2001, but the surgery depended on tools and techniquesthat were honed first in animals and then in people over a full century.

In the early 1900s, scientists learned to suture the arteries and veins of animals.In 1912, the Nobel Prize was awarded to one of the researchers who achievedthis vital step in transplanting organs such as the heart, kidney or liver.

During the next six decades, animal researchers developed their transplanttechniques, with a focus on reducing organ damage by cooling the heart andspeeding the operation, and keeping the patients alive in the meantime withheart-lung machines. In the 1960s, doctors were confident enough to attemptheart transplantation in humans.

Some patients survived for a short while, but their hearts were inevitablydestroyed through an immune attack on the foreign tissue.

“I was aghast. I thought, ‘You’re goingto take my heart out of my chest?’”



Columbia

University

The danger of clogged arteries seems sosimple: Fat and cholesterol slowly build upinside a vessel, until one day, the growingplaque – like a clog of hair in a sink –completely jams the artery and shuts offblood flow. That’s how most lay peopleunderstand atherosclerosis. And it’scompletely wrong.

“If plaque just slowly accumulated inside ourarteries, it would not cause acute heartdisease,” says Columbia University MedicalCenter’s Ira Tabas, M.D., Ph.D. “Before thedeposits of fat and cholesterol could obstructan artery, the body would sense thereduction in oxygen supply and build newvessels to bypass the blockage.”

The real danger from the fatty deposits liesnot with their size, but with what liesunderneath the surface of the deposit. Likemagma underneath a volcano, rumblings inthe core can break open the plaques. Oncethe plaque ruptures, the body quickly tries tocover and repair the opening by forming ablood clot. “It is this sudden clotting thatrestricts blood flow and can cause a heartattack, stroke or sudden cardiac death,” Dr.Tabas says.

While a vast majority of atheroscleroticlesions are relatively harmless, the rest –some 2 percent of all plaques – eventuallylead to an acute blood clot and to heartattack, sudden death or stroke. Whatseparates the average blood vessel plaquefrom those that are at high risk for triggeringthe development of dangerous – even fatal –blood clots, is the “billion dollar question,”says Dr. Tabas, whose most recent findingson arterial plaque are presented in the coverstory of the May issue of Cell Metabolism.

Cholesterol-lowering drugs can reduce theamount of plaque stuck to our arteries, butit’s a tall order. Fatty streaks start appearingin our arteries by the time we’re in our teens,and atherosclerotic plaques continue todevelop from then onward.

The good news, Dr. Tabas says, is that“about 97 percent of plaques will neverbecome a problem. If we can make that100 percent, we would eliminate the number one cause of death in theindustrialized world.”

For that, doctors will need a plaquewhisperer. “The wave of the future inatherosclerosis treatment will be in preventing harmless lesions frombecoming dangerous ones, or soothingdangerous plaques so they don’t rupture,"says Dr. Tabas.

The best way to do that is unclear at the moment.Volatile plaques are complicated, and there arelikely many things that lead to instability andrupture.

But a graveyard of dead cells inside the plaqueundoubtedly contributes, Tabas says, in partbecause substances released by the dead cellstend to weaken the cap covering the lesion andthereby trigger clot formation.

A therapy that prevents the deaths of these cellsmay be able to reduce the number of vulnerableplaques and prevent heart attacks and strokes inthe 70 percent of people who aren’t protectedfrom cholesterol-lowering drugs.

Recently, using mouse models of atherosclerosis,Dr. Tabas pinpointed a major cause of the cells’death, opening the way to the possibledevelopment of cell-saving therapies. The killer –a slow but deadly increase in stress in one of thecell’s compartments – has also been seen invulnerable plaques found in people.

“Our results show that the stress inside the cell isreally killing the cells,” Dr. Tabas says, “and thatits presence in unstable human plaques is notjust a coincidence."

Though relieving this stress, or preventing celldeath, could soothe volatile plaques and be aneffective way to reduce heart attacks and strokes,it may take years before such a therapy isavailable. On the other hand, it may be possibleto bypass the problem of cell death by coaxingother cells in plaques to rapidly capture andclean up the dead cells before they do damage.

In the meantime, the best way to quiet volatileplaques is probably one that you’ve alreadyheard of. “Our understanding of atherosclerosismay be changing, but the old standbys, diet,exercise, and keeping your risk factors likecholesterol and blood pressure in check stillremain the best option,” Dr. Tabas says.

Susan Conova, Editorial Director, ColumbiaUniversity Medical Center

Ira Tabas

Clogged Arteries?Before You Need aPlumber, Call thePlaque Whisperer

© Susan Conova

P hoto credit: Columbia University Medical Center

❝The wave of the future in

atherosclerosistreatment will be inpreventing harmless

lesions from becomingdangerous ones, orsoothing dangerous

plaques so they don’t rupture.”


in plain sightEmor

y U

nive

rsity

Photography by Jack Kearse


© Sylvia Wrobel

he progesterone story began as a scientific puzzle, obstinately pursued by a stubborn Emory neuroscientist.

What cause d some female rats to survive brain injuries virtually unscathed while males with similar injuries died or had severe problems finding their way around once familiar mazes?

Many colleagues thought Don Stein was too obsessed with a potentially career-killing research dead-end. Two Emory doctors—Art Kellermann, then head of emergency medicine, and David Wright, an ER clinician and researcher—looked at Stein’s findings in rats and thought that maybe, just maybe, the scientist was on to something that could change the too often dismal outcomes of the traumatic brain injury (TBI) patients they saw in the emergency department.

Other Emory doctors and researchers stepped up to help them find out, in a clinical trial funded by theNIH, conducted from 2001 to 2005 at Grady Memorial Hospital, where TBI patients arrive withheartbreaking regularity.

Last winter, based on the promising results of that study, a second NIH clinical trial of the progesteronetreatment developed at Emory will begin at 17 trauma centers across the United States, including atGrady. Headed by Wright, the study will enroll 1,400 TBI patients. If progesterone works as well as it didin the smaller trial, clinicians will have the first new treatment in 30 years, and the first-ever safe andeffective treatment, for TBI. Progesterone could transform the way doctors treat head injury, not only inemergency rooms but also at the site of car wrecks or bombings and explosions in Iraq and Afghanistan,where TBI has become the signature wound.

The final answer could take five years, but hope of an effective treatment for TBI no longer sounds socrazy. Ask the NIH. Or, just ask Marc Baskett and his parents.

Coming to say goodbyeThree weeks before high school graduation, everything went darkfor Baskett. He was riding in the car with his girlfriend. She hadtaken her eye off the road for an instant, then looked up to see atruck filling the windshield, crushing the passenger side of the car socompletely that emergency rescuers at first thought Baskett hadbeen thrown from the vehicle. Unconscious, unresponsive, he wasairlifted to Grady, the region’s only level-1 trauma center, some 70miles away.

There, a shifting phalanx of doctors began to treat the 19-year-old’smultiple injuries: damaged organs, cuts (650 stitches in his rightarm alone), a metal rod through his knee into his shattered rightfemur, another rod to hold together his crushed ankle. But noeffective treatment existed for his most devastating injury, that to hisbrain. Unable to open his eyes or respond to painful stimuli, Baskettscored 4 on the 15-point Glasgow Modified Coma Scale. He hadalmost no brain activity.

“Jeff and I believed we had come to Grady to say goodbye to ourboy,” says his mother, Johanna Baskett. “And not just us.” It seemedas if half of the small town of Commerce had closed up shop andfollowed the popular young athlete to Grady. When a young womanasked to talk to the family about a study Emory was conducting, adozen of Baskett’s coaches and teachers joined them. ➤

Progesterone offers the hope of being the first new

treatment for traumatic brain injury in 30 years.

It was there, under our noses, the whole time.

T

The journey of progesterone as a treatment for traumaticbrain injury began in Don Stein’s lab decades ago. Turns out,he was on to something.



The study coordinator explained that the researchers did not knowif progesterone could do for humans what it had done in lab rats.In fact, ProTECT (progesterone for traumatic brain injury–experimental clinical treatment) was a pilot study designed primarilyto evaluate whether progesterone could be safely and reliablyadministered intravenously. The 100 participating patients allwould receive state-of-the-art care; 80 would be randomly chosento also receive progesterone. The cluster of family and friendsagreed that the Basketts should sign. They had nothing to lose.

Within minutes, a vial was added to the drip of medicines alreadyflowing through Baskett’s veins. Because the study was double-blinded, neither his family nor the researchers knew whether thenumbered vial contained progesterone or saline, a standardresearch method to make sure researchers do not unconsciouslyscore patients in the experimental group as doing better. As theresearchers would find out when the data were analyzed, Baskettwas one of the lucky ones.

For three days, a steady infusion of natural, sterilized, human-grade progesterone bathed Baskett’s brain cells. Some cells hadbeen killed outright by the impact and by the swelling that beganeven while paramedics rushed him to Grady. These cells wouldnot revive (although other brain cells would take over some oftheir tasks). The progesterone treatment was intended tointervene in the devastating post-injury destruction of injured cellsor in further damaging healthy cells.

On impact, Baskett’s brain had slammed back and forth insidethe inflexible skull. Injured nerve cells began releasing freeradicals, toxic by-products that punched holes in the walls ofnearby still-functioning cells. Other brain cells called glia workedto mop up dead or dying cells, only to colla pse and diethemselves, releasing yet more toxins. Hemorrhages of tinyvessels freed blood cells into the brain, and immune cellsstruggled to repel these unfamiliar invaders, causinginflammation and then more swelling.

According to Stein’s animal studies, progesterone should slowthese processes down. And something appeared to be workingfor Baskett. After 2-1/2 weeks, he emerged from his coma,confused by the tubes, the blur of unfamiliar and familiar faces,but speaking, trying to smile. He had missed his high schoolgraduation; his teachers brought his diploma to him. After threeweeks, he was transferred to Children’s Healthcare of Atlanta forrehabilitation.

Given the usual outcomes, he could expect to be in the hospitalfor at least a year. But Baskett’s case was proving to be anythingbut usual. He left the hospital four weeks later, returning only toparticipate in a daytime rehabilitation program with a dozenother young people who had suffered vehicle crashes, falls, a horseback riding accident.

“I didn’t feel like I was going through what they were,” saysBaskett, “and I promised myself then I would do whatever I couldto make sure other head injury patients had access to the drugthat I knew I must have been given.”

A persistent pursuitDon Stein sometimes jokes that his becoming a scientist seemedunlikely. “If you grow up in an apartment complex in the Bronx,”he once told a reporter, “the last thing your parents want you todo is to work with rats.”

As a graduate student in the 1960s, Stein learned just how muchthose rats can contribute to science. His job was to surgicallyinjure the brains of anesthetized rats to see how the braindamage would affect their behavior. At the time, this approachwas critical to understanding the functioning of the nervoussystem in health and disease. What fascinated him, however, waswhy approximately a third of the female rats recovered, whileothers with the same injury remained seriously impaired.

Emergency medicine physician David Wright is leading the nationalresearch trial tor progesterone, which patients will receive within four hours of traumatic brain injury.

What cause d some female rats to survive brain injuries virtually unscathed while males withsimilar injuries died or had severe problems finding their way around once familiar mazes?

Photograph by Emory University


His professors, like all neuroscience leaders at the time, thought thefindings were merely natural variation in brain injury outcome. It wasthen taught that there was no possibility of repair or functionalrecovery in the damaged adult brain. Stay focused, they urged. Youhave a PhD to complete, a career to build.

Thus began a kind of double life for Stein that would continue forwell more than two decades. He spent his days doing the moretraditional “real work” – at the University of Oregon and MIT, wherehe completed doctoral and postdoctoral studies, at Clark Universityin Massachusetts, where he ran the brain research lab, and atRutgers, where he was dean of the graduate school and associateprovost for research. He spent his free time trying to solve themystery of those injured but still normally functioning female rats.

When Emory brought him on board in 1995, it was not so much forhis progesterone research but rather his administrative talents. Heretoo, for five years, he spent his days as dean of the graduate schooland vice provost and his evenings in a research lab in a doublewidetrailer previously discarded by the Veteran’s Administration, notuncommon during Emory’s then-building boom. With typical Steinhumor, he purchased a stash of plastic flamingos from a nearbyhardware store. The grounds crew would yank them up wheneverthey could, only to find a new pair gleaming in the morning sun.Stein finally decided he had been outsmarted when the crewreplaced the lawn with a rock garden of artfully placed boulders.

When it came to his work with rats, however, he did not quit.

Since the females typically did better, Stein thought that thedifference had to be hormonal. That helped explain anecdotal orsingle-case clinical reports that women were more likely than men torecover from similar brain injuries. Estrogen was the obviouscandidate, but he observed no correlation between estrogen levelsand recovery. He turned to progesterone.

“Progesterone was hidden in plain sight as a neuroprotective agent,”says Stein. A naturally occurring hormone produced in the brains ofboth sexes, progesterone’s protective properties become mostobvious during pregnancy when levels shoot up dramatically andstay elevated until the baby is born. Stein and others began torecognize that many processes involved in fetal development aresimilar to those that take place during tissue repair after injury.Perhaps, Stein theorized, the higher levels of progesterone in femalesat the time of their injury accounted for their better outcomes. Andsince progesterone levels fluctuate sharply during rats’ estrus andwomen’s menstrual cycles, perhaps the outcome depended on wherefemales were in their cycle when injured. ➤

“I promised myself then I would do whatever I could to make sure other headinjury patients had access to the drug that I knew I must have been given.”

– Marc Baskett

❝Progesterone was

hidden in plain sight as a

neuroprotective agent,”

says Stein.



By tricking the female rats’ bodies into thinking they werepregnant (a little like birth control pills do), Stein was able toproduce high levels of progesterone in the animals. It soonbecame evident that female rats injured when their progesteronelevels were high did much better after injury than either males orfemales with lower progesterone levels. The first thing he and hisstudents noticed was the high-progesterone females had virtuallyno brain swelling compared to those in other phases of theirestrus cycles. He was on the right track. But would it work formales? And if so, why?

In the years since Stein’s graduate school days, science hadadvanced considerably. Brain swelling was recognized as a majorcause of cell death after TBI. Many treatments, then and now,focused on preventing swelling to preserve still healthy braintissue. In 1991, Stein and his laboratory put progesterone to thetest. In earlier work, he had manipulated naturally occurringprogesterone. Now he gave progesterone by injection to bothmale and female rats within 24 hours after identical braininjuries. The progesterone-treated male and female animalsshowed no signs of brain swelling.

Research elsewhere also had found that injured brain cellsrelease free radicals and neurotoxins and that the immuneresponse to injury causes inflammation. Stein showed that, inrats, progesterone also intervenes at these points.

Heroic attempt or pig-headed waste?Although the scientific and medical world did not exactly beat apath to Stein’s trailer door, first the CDC and then the NIH beganto back his work. A few researchers in other labs repeated hisfindings, validating his results. But what really turned the corner,says Stein, was when he met Art Kellermann, a passionateadvocate for public health who introduced him to David Wright.For Stein, the maverick scientist, and Wright, the former flightphysician and rock band drummer, it was the beginning of whatthey call a beautiful friendship.

Wright wanted to believe that Stein had found something thatwould help brain-injured patients, but he also was a scientist. Hehad been part of the team that discovered the protein involved inMarfan’s syndrome (a disorder many believe afflicted Lincoln).With appointments in emergency medicine, injury control, thebiological and biomedical sciences and biomedical engineeringat Emory, he had strong and cautious research instincts. Workingin the trailer after his clinical shifts, he carefully repeated some ofStein’s rat studies and got the same promising results.

After that, Wright too became convinced that progesterone heldserious promise as a potential treatment for TBI. He and Steinworked with a statistician at Emory’s Rollins School of PublicHealth and with clinicians from neurosurgery, trauma surgery,and other Emory departments to design a clinical study to see ifprogesterone would work on injured humans without causingserious side effects. Progesterone had a long track record ofsafety for treatment of other diseases, but not at levels theresearchers believed would be most effective for treatment of TBIin humans. In 2001, the first of 100 patients enrolled in a three-year pilot study funded by NIH and headed by Kellermann andWright. All had suffered TBI within 11 hours before arriving atGrady, and all had an initial Glasgow Coma Scale score rangingbetween 4 (severe TBI like that of Baskett) and 12 (moderate TBI).

“The drug and all the

people who believed in

it gave us back our son,

with his mind,

personality, and sense

of humor intact.”– Johanna Baskett

Although the scientific andmedical world did not exactlybeat a path to Stein’s trailer door,first the CDC and then the NIHbegan to back his work.



At the end of the study, Wright and others on the team went toWashington, D.C., to find out the results from NIH analysts, theonly people aside from the team statistician who knew whichpatients had received progesterone, which placebo. Theresearchers’ nervousness was palpable. Were they closer to thetreatment for which they hoped?

Back in Atlanta, Stein was driving when his cell phone rang.When Kellermann told him to pull over before he heard theresults, Stein’s blood ran cold. What worked in rats did notalways work in humans. Would progesterone end up in thegraveyard of failed neuroprotective drugs? Had his researchcareer been a heroic attempt or a pig-headed waste of time?

Not only had progesterone caused no side effects, but fewer thanhalf the patients receiving progesterone (13%) had diedcompared with those on placebo (30%). Furthermore, functionaloutcomes and the level of disability were significantly improvedamong progesterone patients with moderate brain injury.

Soon after, a similar study in China also found progesterone tobe completely safe and patients receiving it to have superioroutcomes at three and six months after the injury.

Although not every progesterone patient in the Emory/Grady trialdid as well as Baskett, there were a number of other markedsuccesses, including a prominent businessperson who prefers thatpeople don’t know about the injury and a young man whocontinues to pursue a successful, prominent athletic career.

Saving time and brain cellsResults in hand, Wright, Stein, and the team began planning alarger clinical trial to more completely test progesterone’s clinicaleffectiveness. The process involved six Emory departments andthree schools (Emory’s schools of medicine and public healthand Morehouse School of Medicine). Wright then reached out topotential partner institutions in a plan the size and scope of asmall military campaign. Last fall, the NIH awarded the proposalmore than $27 million in funding.

During the next four years, 1,140 TBI patients will be enrolledacross 17 different institutions, each at a level-1 trauma center.Participating institutions will work under shared protocols andoperating and quality control standards developed at Emory. Theprogesterone, a natural substance, will be purchased from aleading pharmaceutical company and prepared, tested forquality control, and packaged in Emory laboratories, thendistributed to all participating centers.

As in the earlier study, patients must be 18 or older, with blunthead trauma (no penetrating injuries). In the new study, however,patients will begin treatment within four hours of injury. Given thesafety results of the first study, the FDA will allow the use ofexception from informed consent – a special research allowancefor cases where time to treatment is critical to the conduct of theresearch. Patients will be monitored daily for safety and clinicalmanagement. At six months, memory, cognition and behavior willbe measured, with outcomes stratified by severity of injury.

The safety of progesterone makes for numerous possibilities, saythe researchers. Stroke, for example. Stein’s recent animal studiessuggest that progesterone is highly effective in reducing the sizeof blood clots and, unlike tPA, has no risk of causing bleeding inthe brain. Wright and Michael Frankel, director of Emory’s StrokeCenter, are readying for a stroke trial.

Children with TBI were excluded from the first progesteronestudies because researchers were uncertain how the hormonewould affect development. Clinicians in the Emory Children’sCenter, Emory Center for Injury Control, and Children’sHealthcare of Atlanta have brought their expertise to studies nowbeing designed.

Stein, Wright and the other researchers also would like to exploremoving progesterone beyond the emergency department setting,saving time and consequently saving brain cells. They are workingwith Emory chemists to create a highly stable, heat-resistantprogesterone product. If an injection device loaded withprogesterone became part of emergency response med-pacs bothat home and in the military, a person believed to have suffered ahead injury could be given an injection of progesterone at thescene, without waiting for arrival at a hospital.

The progesterone story—the science, teamwork, perseverance,and ability to think outside the box—shows what can happenwhen science is at its best.

The Basketts take a more direct view. “This drug and all thepeople who believed in it gave us back our son, with his mind,personality, and sense of humor intact.”

Sylvia Wrobel, Communications Officer, Emory University.

The progesterone story—

the science, teamwork,

perseverance, and ability

to think outside the box—

shows what can happen

when science is at its best.


On a Mission toSave Smiles © Lisa Spellman

Until the flood of 1988, few had paid attention to cleftlip and palate in the rural hillsides of Bangladesh.

That changed when Ali Nawshad, D.D.S., Ph.D., arrivedto help with relief efforts.The young dental student wasstruck by the number of children he saw with thedeformity. Suddenly, his plans to practice dentistryseemed insignificant.

“I realized then that I wanted to study craniofacialdeformities,” said Dr. Nawshad, associate professor andresearcher in University of Nebraska Medical Center(UNMC) College of Dentistry.

Twenty years after that fateful flood, he received a $1.8million grant from the National Institutes of Health tocontinue his work to eliminate cleft palate in fetuses.Cleft lip and palate occurs when the palatal shelves inthe roof of the mouth fail to grow and fuse.

“Although it is not life-threatening, it does disrupt feeding,digestion, speech, hearing and respiration,” he said.

It also can lead to emotional, psychological, social andlearning problems and is an economic burdenamounting to $1 billion in health care costs annually inthe United States, according to the January 2006Morbidity and Mortality Weekly Report from the Centersfor Disease Control and Prevention.

Dr. Nawshad has spent the past decade studying – firstat Harvard Medical School with renowned embryologistElizabeth Hay and now at UNMC – how to fix cleftpalate in children before they are born.

Although the protein TGFß had been implicated inpalate development, Dr. Nawshad has identified thepathways that TGFß uses during palate development.

“If you knock out this gene in mice, they are always bornwith cleft lip and palate and no other deformity,” Dr.Nawshad said.

He also learned there are lesser, but just as important,genes essential for normal palate development.

“Our goal is to reintroduce those genes into the pups ofpregnant mice to determine if the deformity can becorrected in the womb,” Dr. Nawshad said.

While the rates of cleft lip and palate are still high inBangladesh, he said, the highest incidence is amongAmerican Indians, as well as the indigenous people ofSouth America. The lowest incidence rates are inAfrican-Americans.

“As we better understand the basic science of cleftpalate, we can improve the lives of children around theworld,” Dr. Nawshad said.

Lisa Spellman, Publications/Media Specialist, University ofNebraska Medical Center.

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Photo credit: Peggy Cain, UNMC College of Dentistry


The Jack

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A FEW MONTHS SHY OF HER 13TH BIRTHDAY,Katelyn Denbow is not quite child and not yet woman. She’s stylishly dressed in teen standard garb of leggings, denim skirt and glittery T-shirt, but on a tourof her room she goes straight to her immaculately organized collection ofAmerican Girl® dolls.

Picking up a brown-skinned doll, Katelyn says, “Addie’s one of my favorites,because I’m very interested in black history and the Civil War.” With theconfidence of a history professor, Katelyn describes Addie’s life growing up ona plantation and her escape via the Underground Railroad.

“I’m very excited because when we go to Georgia in June, we’re going to visita real plantation,” she adds with a big smile.

The main reason for the Denbow family trip to Georgia is to attend thetriennial International Family Conference, Medical Research Clinic andScientific Symposium organized by Alström Syndrome International (ASI), anonprofit organization. Katelyn lives with Alström syndrome, a rare geneticdisorder. It results from a defect in just a single gene, but the impact isprofound. It affects vision, hearing, heart, liver, kidneys and other systems. It also greatly shortens life expectancy.

Katelyn’s love of reading, her astonishing recall of historical facts and her shelffull of public speaking trophies make her one of the top students in her class.She’s growing up in a unique environment: Campobello Island, a tiny,picturesque community on the Canadian side of a land bridge near Lubec,Maine. Her father is in the fishing industry and her mother, Gina, teaches inKatelyn’s school—in fact, she teaches both Katelyn and her brother Cody.

Mother and daughter sit close together on Katelyn’s bed, alternating betweenaffectionate hugs and teasing banter. “At school I try to ignore her,” Katelynsays. “Typical,” her mom responds. Away from school, the two often readtogether, mother reading aloud to daughter when the Braille books run out(“she reads them faster than they can send them”). But sometimes a girl justhas to hang out with her friends and watch TV (current obsession: “iCarly”).

Alström syndrome is a recessive disorder, meaning that a child must inherit thegene variant for the disease from both parents. It’s rare even by rare-diseasestandards, with fewer than 700 patients identified worldwide and only 266cases reported in the medical literature. Yet the Alström community – thefamilies affected by the disorder and the researchers who study it – is vast,spanning 47 countries. And the hub of this community is only about 100 milesfrom Campobello Island, at The Jackson Laboratory in Bar Harbor, Maine.

In 1996, Jackson Laboratory Professor Jürgen Naggert and his collaboratorand wife, Professor Patsy Nishina, published a paper on their discovery of agenetic mutation that causes a cluster of symptoms similar to those found inAlström syndrome in a mouse model known as tubby, including obesity,blindness and hearing deficits. At that time, Jan Marshall, a research assistantto Naggert, conducted the laborious genealogical study that traced Alströmsyndrome back through 13 generations to an ancestral couple, whoemigrated to what is now Nova Scotia in the 1600s. Since then, mutations in the gene have been identified in hundreds more unrelated families.

Today Jan Marshall also serves on the board of ASI; her husband, Robin, isthe executive director and runs the organization out of their home in thewoods of Mount Desert, Maine, a few miles from The Jackson Laboratory. Aspart of ASI’s outreach efforts to Alström patients and their families, Marshallhas known the Denbows since Katelyn was a little girl of 4.

“One of the blessings of working with a really raredisorder,” Marshall says, “is that you get to know thesekids personally. They’re all my kids! Of course all peopleare different—some are shy, some are anything butshy—but the Alström kids I know are all so bright andloving, with a great sense of humor.”

She adds that many of the Alström patients check in withher to ask how the research is going. “Every once in awhile I’ll get an email from a kid asking, ‘How’s themouse?’ We have a running joke that there’s just onemouse, and his name is Carl-Henry,” after Carl-HenryAlström, the Swedish doctor who first identified thesyndrome.

“One young man used to call me and, when I picked upthe phone, would say, ‘Why are you answering thephone? Why aren’t you working?’” The smile fades fromMarshall’s bright blue eyes. “That boy has since died.The hardest part of my job is when we lose a patient. We know them all, we’ve hugged them, we’ve been apart of their lives. And then you lose them. We lose themtoo young.” ➤

Drop by Drop© Joyce PetersonPhotos: The Jackson Laboratory, www.jax.org

Above: KatelynDenbow holds herdamlaya pendant,which symbolizesprogress being madeto cure Alströmsyndrome.

Right: Katelyn with hermother, Gina Denbow.


At The Jackson Laboratory, in a small instrument room with awindow view of Frenchman Bay, Gayle Collin studies a computerscreen attached to a microscope. Like Marshall, Collin has beeninvolved in studying Alström syndrome for most of her professionallife. It was she who, in 1996, successfully pinpointed the generesponsible for Alström syndrome, ALMS1, to a location onchromosome 2.

Pointing at a pink and purple histology image on the screen, Collinsays, “This is a retina in a 3-month-old mouse with a mutation in theALMS1 gene, and it’s already showing significant degeneration inthe photoreceptor layer. Normally we don’t see this kind of damageuntil 9 to 12 months of age. This is because we have placed thedisrupted gene on a different genetic background, and thatbackground is clearly making the condition worse.”

The genetic “background” is made up of all the different genes that mice (and humans) have that aren’t directly related to thedisease being researched. Different mouse strains have differentbackgrounds, and, as with Alström syndrome, they have a significanteffect on many diseases. Understanding just how the “background”genes of a mouse interact with the ALMS1 gene to make Alströmsyndrome symptoms more or less severe, Collin says, could provideinsight into possible paths for treatments.

In Alström patients, modifying effects of other genes could explainwhy some experience earlier onset or worse symptoms, or whyothers survive longer with fewer medical problems. “There are somany ways that this gene can go wrong,” Collin says, “and so manyways the background can make it worse or compensate for it.”

As Collin removes her white lab coat, a clear, teardrop-shaped glasspendant swings from her neck on a black cord. “This is a damlaya,”Collin says. “We wear them to remember that small steps lead tobig results.”

Marshall explains, “One of ASI’s board members, Nevin Bengur,once mentioned a Turkish proverb when we were having a toughday. “Damlaya damlaya göl olur” means ‘Drop by drop a lake isformed,’ and this has become a slogan for us. We found these glassdrops to symbolize our community, and started wearing themeverywhere.”

What’s surprising is how often people recognize the symbol of thisvery rare syndrome.

“So many people at The Jackson Laboratory and around the worldare working together to help patients with Alström syndrome,”Marshall says, “and the patients themselves are wonderfulambassadors, fundraisers and awareness-raisers.

“Dollar by dollar, drop by drop, we can all make a difference.”

Joyce Peterson, Public Information Officer, The Jackson Laboratory.

Alström Syndrome International board members Jan Marshall, Robin Marshall, Nevin Bengurand Phyllis Aschenbrenner plan the upcoming ASI conference in Georgia.

❝One of the blessings of working with a really raredisorder,” Marshall says, “is that you get to knowthese kids personally. They’re all my kids!”

Left: Gayle Collin.Like Marshall, Collin has beeninvolved in studying Alströmsyndrome for most of her professional life.

Right: Jan Marshall. In 1996, Marshall conductedthe laborious genealogicalstudy that traced Alströmsyndrome back through 13generations to an ancestralcouple, who emigrated towhat is now Nova Scotia inthe 1600s.


California

Institute for Reg

enerative M

edicine

© Camille Mojica Rey, PhD

Maggie, a former marathon runner, was diagnosed in 2006 with multiple sclerosis—adisease whose symptoms progress from relatively mild, such as the limb numbness sheexperiences, to severe, such as paralysis or loss of vision.

Maggie asked that her last name and hometown not be used due to potentialemployer discrimination. Some employers, she says, do not want to hire someone theythink will become increasingly disabled.

There is no cure for MS, but medication has slowed the progression of Maggie’sdisease. She is still able to run 20 miles per week and, last year, she helped her teamraise $20,000 for MS research by participating in a fundraising walk-a-thon.

Maggie says she is excited about the possibility that stem cell research might lead tobetter treatments for MS or even a cure. Millions of Americans whose lives aretouched by neurological disease, like MS, Alzheimer’s disease, Parkinson’s disease orspinal cord injury, share her hope. These disorders are among the most hotly pursuedby stem cell researchers around the world and in California. Of California Institute forRegenerative Medicine-funded research projects that target a particular disease area,31 percent focus on neurological disorders. ➤

❝My hope is that there is a cure by the time mychildren might have symptoms,” says Maggie, a 35-year-old poet and teacher living in Texas.

Mending the MindToward stem cell therapies for neurological disease


Supporting the survivorsOne early concern about stem cell–based therapies forneurological disease was one of functionality. Even if embryonicstem cells can mature into an appropriate nerve type, how can theyever replicate the complex connections of nerves that carrymemories of your children’s names or your spouse’s face?

Arnold Kriegstein, M.D., Ph.D., director of the Eli and Edythe BroadCenter of Regeneration Medicine at the University of California,San Francisco, says if stem cell-derived transplants were to be putinto the brains of elderly patients with neurodegenerative diseaseslike Parkinson’s and Alzheimer’s, they would have to migrate to theright place, form connections and function seamlessly. “That is adifficult thing to do in a young brain, much less an aged brain,” he says.

Because of the intricacy of neural connections, Theo Palmer, Ph.D.associate professor of neurosurgery at Stanford University, expectstransplanted stem cells will first be used to support remaining cellsrather than replace function. “This will improve or extend the qualityof life,” Palmer says, even if they don’t cure the disease entirely. Hehas been studying stem cell-based approaches to treatingParkinson’s disease.

A CIRM-funded team led by researchers at the Salk Institute forBiological Studies in La Jolla and the University of California, SanDiego proposes replacing the support cells surrounding the neuronsdamaged in amyotrophic lateral sclerosis (also called Lou Gehrig’sdisease). Rather than replacing the function of the damaged cells,which would require forming new connections, this approach wouldprotect remaining neurons from damage.

Likewise, a stroke team led by Stanford University researchers isanticipating that inserted stem cells would protect cells that survivedthe stroke rather than replacing those that were lost. Another CIRM-funded project has early evidence in mice that an approach usingembryonic stem cells could protect nerve cells in people with MS.

These attempts to maintain existing neurons have proven successfulin several animal models of disease. In mice, researchers haverestored the abnormal gait of Parkinson’s disease, improved thememory loss of Alzheimer’s and eliminated the jerky bodymovements of Huntington’s disease. The challenge is translatingthose successes to therapies that effectively help people with thediseases.

First to the clinicThe idea of maintaining surviving cells underlies the first embryonicstem cell-based clinical trial to receive approval from the U.S. Foodand Drug Administration (currently on hold pending additionalsafety reviews). This trial, sponsored by Geron, would test atreatment for spinal cord injury based on findings by a team ofresearchers from the University of California, Irvine led by HansKeirstead, Ph.D.

In 2005, Keirstead and his colleagues showed that they could makeparalyzed rats walk again by injecting early-stage oligodendrocytecells that had been derived from embryonic stem cells into thespinal cord within seven days after injury. Oligodendrocytes aren’tthe cells that carry the electric signal up and down the spine,relaying "that hurts" or "move here" signals to and from the brain.Instead, they wrap the cells that do carry those signals in aprotective blanket. In spinal cord injury, these injected cells appearto preserve message-carrying nerves that would ordinarily witherafter the injury.

The fact that the approach protects existing cells rather thanforming new connections is one reason for it’s speedy path to theFDA. Another is the fact that the site of injury is relatively accessiblecompared to the injury that results from diseases of the brain.Scientists working to cure Huntington’s or Parkinson’s disease, forexample, also have to devise ways of delivering the cells to the rightspot.

Bringing this spinal cord trial to the FDA in just four years was nosmall feat, says Keirstead, who is associate professor of anatomyand neurobiology at the UC Irvine Sue and Bill Gross Stem CellResearch Center.

“The trial was approved only after rigorous safety testing andconsultation of countless experts in the field,” said Keirstead, who isalso affiliated with the Reeve-Irvine Research Center for spinal cordinjuries, in a statement at the time of the FDA approval.


Keirstead has a warning for his fellow stem cell researchers. “Basicscientists need to understand the pre-clinical path before they needit so that they don’t invent something that can’t make it to humans,”he says. (See Manufacturing Cures, sidebar.)

Disease in a dishIn some cases stem cells may directly treat a neurological disease.In others, they may prove most useful for understanding the diseaseand finding new drugs. “Both approaches are being used andproviding some pretty exciting leads,” says Palmer.

Fred Gage, Ph.D. at the Salk Institute for Biological Studiesdeveloped a model of ALS in a lab dish and hopes to use thatmodel to test drugs to treat the disease. Without stem cells therewas no way to model the disease and study it directly in the lab.

Using this model, Gage and his colleagues gained new insight intothe complicated relationship between motor neurons andastrocytes, support cells critical for the survival and well-being ofthose neurons. A study published in 2008 by Gage and hiscolleagues confirmed that in ALS dysfunctional human astrocyteskill off healthy motor neurons.

Gage said this model could be used to verify drugs and targetsbefore they reach human trials. “A variety of drugs that haddemonstrated significant efficacy in mouse models didn’t keep theirpromise in both preclinical and clinical trials,” says Gage, aprofessor in the Laboratory for Genetics.

At the University of California, San Diego, Lawrence Goldstein,Ph.D., professor of cellular and molecular medicine and director ofthe UC San Diego Stem Cell Program, has been using a similarapproach to study the origins of Alzheimer’s disease. He says theprevailing theory that the disease is caused by amyloid plaques hasnot been strongly supported. “Furthermore, there are no drugs thatalter the course of the disease,” he says.

Goldstein, who is also a Howard Hughes Medical InstituteInvestigator, wants to know if any existing drugs can alter theprogression of the disease in his laboratory model. “We can use stemcell lines to test all known drugs for off-label use. It’s a long shot, butit is one worth taking,” Goldstein says. “If we can find a drug thatworks, that would be preferable to transplanting cells into the brain.”

A team at the Parkinson’s Institute in Sunnyvale, CA, has a similargoal, using stem cells to screen drugs that improve the functionalityof cells showing signs of Parkinson’s disease in a dish.

The pace of progressFor all its challenges, UCSF’s Arnold Kriegstein predicts that stemcell transplants will one day be used to cure disease.

“I don’t expect any homeruns from the early trials. The homerunswill come later. We all need to be prepared for that. These trials areabout the limits of the current technology,” Kriegstein says.

Though the pace of research may mean that some cures are yearsaway, Maggie hopes her children will not endure the symptoms ofMS – or hide the fact that they have it – the way she has had to do.“I am hoping for a cure for MS for the next generation.”

Camille Mojica Rey, PhD, Copywriter, California Institute for RegenerativeMedicine.

MANUFACTURING CURESHans Keirstead says his work leading up to the first embryonicstem cell-based clinical trial has given him the benefit ofhindsight. He says many researchers, as well as the generalpublic, need to understand the enormous effort and technicalchallenges to making a treatment ready for prime time.

Keirstead calls the following the four pillars of clinical trialpreparation.

MANUFACTURING LARGE QUANTITIES OF HIGH-GRADECELLS. In order to comply with FDA regulations, any cells that will be used in humans must be manufactured in what iscalled a Good Manufacturing Practices (GMP) facility. Thesefacilities cost tens of millions of dollars to construct and makingthe cells costs several million dollars more.

“Ours was the first treatment in which these high-purity cells weredeveloped. That’s the primary reason it’s first,” Keirstead says.

PRE-CLINICAL EFFICACY. By the time clinical trials are beingplanned for, scientists have conducted studies that show that thetreatment works in animal models. They then have to use thenewly generated clinical-grade cells to repeat those initialexperiments to confirm that the new cells work in the same way.

PRE-CLINICAL SAFETY. The next step is to pay millions of dollarsfor a third party to repeat the animal experiments showing thatthe treatment is safe. “Researchers from Geron and the testingfacility completed all of the analyses to show that the treatment issafe,” recalls Keirstead.

CLINICAL PREPARATION. Finally comes a step that isunderestimated by most basic researchers. In order to prepare for a clinical trial, Keirstead says, “You have to conduct about 15 different focus groups comprised of 15 to 30 experts todiscuss different aspects of the clinical trial.” One panel ofexperts, for example, might be responsible for deciding thecriteria for including patients. Another might decide on the details of post-operative care.

“This involves a lot of debate and you have to come to aconsensus. After about a year you condense that into a clinicalsynopsis, and that’s your plan,” Keirstead says.


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FETCH~LAB © Kathryn Cosse

It’s taken some time, training and lotsof treats, but Timmy is getting used

to his new hearing aid.

Timmy is a 10-year-old springer spaniel-basset mix, a service and therapy dog toowners Neil and Vonnie Young of Berwick,Pennsylvania. He’s also the latest recipientof a wireless hearing aid, installed by staffand students at the University ofCincinnati’s (UC) Facility for Education andTesting of Canine Hearing and Laboratoryfor Animal Bioacoustics, or FETCH~LAB.

Created in 2007, FETCH~LAB is home to research on animal hearing andvocalization and a canine audiology clinic.Its 24-member staff includes clinicians andresearchers from UC and CincinnatiChildren’s Hospital Medical Center, alldedicated to studying the interaction ofhumans and animal vocalization throughresearch and education.

The lab is the creation of Peter Scheifele,PhD, UC assistant professor of bioacoustics,neuroscience and communications sciencesand disorders. Scheifele established thelab’s canine audiology clinic both to helpdogs and their owners and to expand theunderstanding of canine hearing andhearing loss.

FETCH~LAB’s faculty includes audiologists,veterinarians, geneticists and imagingspecialists, all who came together to workwith Timmy and his owners in the fall of2009.

The Youngs brought Timmy to FETCH~LABafter Neil noticed Timmy wasn’t respondingto commands. That was of extra concern forNeil, as Timmy is more than an averagehouse pet.

Not only does Timmy work as a service dogfor Neil, who has narcolepsy, but as part ofthe Youngs’ Funny Farm, he works as acertified therapy dog at local hospitals,schools and nursing homes. After 9/11,Timmy worked at Ground Zero, offeringcomfort to emergency and rescue workersat the scene.

With fundraising help from the Berwickcommunity and consultations withFETCH~LAB staff, Timmy and the Youngsreturned to UC in December 2009 to getthe aid installed. The Bluetooth-baseddevice can transmit communication from awireless microphone held by Neil or amplifyambient noise from the environment.

Timmy is the fourth dog FETCH~LAB staffhas fit with hearing aids and the secondone to be fit with wireless aids.

Almost weekly, Scheifele and his doctoralstudents at FETCH~LAB see dogs prone toage or noise-induced hearing loss,including Dalmatians and Australianshepherds. Using modified versions of testscommonly used for humans, likeelectrophysiology, EEG and sonography,they view images from the inner ear andbrain to provide thorough hearing lossassessments.

The work provides research opportunitiesfor the students, who use the non-invasivetechniques to gather baseline data aboutthe dogs they see. That data, says Scheifele,can be used to determine what degree ofhearing loss is normal in aging dogs andestablish best practices for treating caninehearing loss.

But FETCH~LAB’s research extends beyondUC’s campus. In Cincinnati, its faculty andstudents partner with the Cincinnati Zoo &Botanical Garden to study the relationshipbetween vocalization and mating patterns

of endangered rhinos and noise impacts on pregnant polar bears in their den.

A retired member of the U.S Navy, Scheifelehas also used his expertise in animal andmarine mammal bioacoustics to partnerwith aquariums to study noise impact tomarine animals and with computerengineers to study methods of hearingtesting.

“Students are learning to improveequipment, upgrade hearing aids and evencreate ear-to-ear communication devicesusing ultra wide band signals,” saysScheifele.

Though they work with dogs and dolphins,the students also learn new things abouthuman neuroanatomy and the physiologyof hearing and vocal systems.

“Ultimately, this research will hopefully leadto better testing and diagnostics for hearingand vocal disorders and a betterunderstanding of the brain’s role inprocessing sound and creating andunderstanding speech,” says Scheifele.

Right now, he says the work is enhancingthe welfare of its subjects, allowingresearchers to understand how noise, stressand distress affect animals from an acousticperspective.

For Timmy, his work is getting used to hisnew hearing aid and using it with hisowners. Young says Timmy is doing well,wearing the aid for several hours at a timeand getting back to work with their othertherapy animals. As Timmy resumes hisactivities, the Youngs communicateregularly with FETCH~LAB to update themon his hearing and progress.

“The stages of ‘awareness’ that we areseeing dogs like Timmy go through inaccepting and using hearing aids issomewhat similar to what happens in ayoung deaf child and that child’s family,”says Scheifele. “It’s another area ofexploration that FETCH~LAB is engaged inwith all of our collaborators.”

Kathryn Cosse, Public Information Officer,University of Cincinnati Academic HealthCenter

❝Right now, there’s really no data about canine hearing loss,yet many dogs and families are dealing with this issue,” hesays. “Hearing screening is also paramount for assistance,military and police dogs.”

Early Innovations 1980

Congress passes the Virus-Serum-Toxin Act in 1913 to protect farmers from “snake oil” sales, ushering in the modern era of government-approved animal medicines. Hog cholera serum is

health products. Hog cholera, like many other

eradicated from the United States.

bacterial diseases in animals. Many early products helped farmers produce better animals and helped to meet growing demand for meat products due to a growing and more prosperous American population.

1980 medicines that kill internal

parasites in livestock and pets are developed. Better control

of parasites such as roundworms and tapeworms improve the lives of pets. The availability of medicines that

control a wide range of livestock parasites contribute

to animal welfare.

1989 New preventative heartworm medicines allow dogs to be treated monthly, replacing the need for daily use of medicines to control this deadly disease in pets.

1990 Major developments are made in the control of external

dogs and cats. These medical advances help reduce human exposure to ticks that spread

Lyme disease.

1990 A new generation of safer medicine is developed for pain management for dogs and horses

quality of life in older animals.*

1985 A preventative Foot and Mouth disease vaccine for animals is developed in conjunction with the United States Department of Agriculture. The U.S. government is provided with large supplies of the vaccine in case of a potential outbreak.

1990

Congress passes the Virus-Serum

ANIMAL HEA


Ani

mal H

ealth

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itute

2000 Antidepressants to treat obsessive-compulsive disorder and separation anxiety in dogs are developed to help improve pet behavior and strengthen the bond between people and their pets.

2000 2009

2008vaccines is created to reduce the amount of E. coli 0157:H7 in cattle that will ultimately decrease human exposure to this deadly foodborne pathogen.

2006 Animal health scientists create a West

Nile virus vaccine for horses in response to

the outbreak in the U.S. This innovation has

improved the health and welfare of horses by

protecting them from the spread of the virus.

2007 cancer treatment drug are

time that the U.S. government has approved a therapeutic vaccine for cancer in animals or humans. Research and development for animal medicines could result in improved cancer treatment for all.

A LTH TIMELINE

2005 Animal health companies work with USDA to develop an

potential threat of a human and

government is provided with large supplies of the vaccine in case of a potential outbreak.

2009 The U.S. Department of Agriculture and the animal health industry are cooperatively working toward an animal vaccine for H1N1 that will give veterinarians a tool to help control the disease in pigsif needed.



Students Honored for Winning Essays onBiomedical ResearchEach year the Pennsylvania Society for Biomedical Research (PSBR) holds astudent essay contest that asks students "Why are Animals Used inBiomedical Research?" This year, 391 students from 59 schools wrote essays that answered that question. Winners were selected after three rounds ofjudging by Pennsylvania Society for Biomedical Research (PSBR) members and friends, whose decisions were based onidentifying students who demonstrated a superior understanding of the topic and artfully conveyed their ideas in writing. Theessay contests marry the science of animal research with the art of writing, requiring students to apply their skills in both subjectswithin a single project. One of the strategic goals of PSBR is to educate students about the role of animals in biomedicalresearch, and the essay contests are a major component in that undertaking.

The winners were honored at the PSBR annual dinner on May 25 at the Villanova Conference Center in Radnor, PA, receivingcash awards of between $100 to $500. Each winner also received a letter of congratulations from Gov. Ed Rendell, which wasdelivered by Jessie Smith, special deputy secretary for dog law enforcement, Pennsylvania Department of Agriculture. TheGovernor wrote that he is “always excited to hear of talented students who demonstrate a real passion for learning and themotivation to use their knowledge and skills outside of the classroom… Your knowledge and skill in the craft of writing will openworlds of opportunity as you pursue your academic career in your special interest.”

About PSBR: The Pennsylvania Society for Biomedical Research was established to promote a better public understanding of the value ofanimal-based biomedical research. Its membership comes from universities, medical schools, pharmaceutical firms and professionalsocieties in Pennsylvania, Delaware and New Jersey. PSBR focuses on educating students about the vital role played by the responsible useof animals in improving the quality of human and animal health; advocating for public policies that support responsible animal-basedresearch; and informing the public and key stakeholders about animal research issues. PSBR strongly supports the continued role ofanimals in research when no reliable alternative exists. Visit www.psbr.org.

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In 1921, at the age of 39, Franklin Delano Roosevelt wasdiagnosed with polio, a disease that causes paralysis. Rooseveltspent the remainder of his life in a wheelchair, able to walk onlywhen using steel braces. Though his abilities were limited, hisbravado was admirable; he carried out his presidential duties withdignity and efficiency. Now, thanks to the polio vaccine developedin 1955 by Dr. Jonas Salk, polio has never again become anepidemic, and cases are rare. This life-changing vaccine could notand would not have been developed without the use of animals. Itis the view of many that using animals in biomedical research isboth unjust and cruel, but in truth, the animals used are treatedvery well, hundreds of medical advances have been made, andanimals, too, benefit from the research.

First, the use of animals in biomedical research is justified by thefact that the animals are treated with excellent care and attention.Organizations such as the IACUC (Institutional Animal Care andUse Committee) and the USDA (United Sates Department ofAgriculture) demand that certain standards be met in any facilitythat uses animals for such research. One demand is that aveterinarian is always present during the procedures so that personswith experience will be handling and caring for the animals. Theseveterinarians have taken an oath that commits them to the humanetreatment of animals. The Animal Welfare Act states thatveterinarians must administer pain relief for any procedure thatwould conceivably cause pain in a person. The animals’environments must also meet certain standards. The IACUC hasvery specific requirements that those housing the animals mustmeet, including providing toys, exercise, medical care, and ahealthy social environment for all animals. There is no doubt thatanimals used in research are cared for and treated with greathumanity.

Next, the many diseases and conditions that have been overcomegrant justification for the use of animals in research. Treatments foreverything from severe burns, to asthma, to cancer have beendeveloped with the help of animals. Vaccinations for diseases likepolio, hepatitis, mumps, and measles would not have been possiblewithout animal use. Incredible advancements have been made insuch areas as treating diabetes and bacterial infections, preventingand treating birth defects, and managing epilepsy and cysticfibrosis. By using animals in testing for biomedical research, doctorsand scientists can treat and even prevent many of the illnesses thatwere at one time incurable. Humans fighting illnesses would be in amuch worse place today if it were not for the use of animals inresearch.

Finally, animals themselves reap benefits from biomedical research.Animals have medical conditions just like humans do, and many ofthem could not be treated if methods were not first developed forhumans in research. Cancer treatments, hip replacements, andcardiac valves, to name a few, would not exist for dogs or otheranimals unless first created for humans. Procedures such as thesehelp to prolong the healthy lives of domestic and farm animals.Research involving animals also helps veterinarians to care moreeffectively for pets. In addition, scientists learn things frombiomedical research that allow them to better understand and assistendangered species in the wild. Humans are not just using animalsfor their own benefit; they’re offering better health for the animalsin return.

The use of animals in biomedical research is justified in that theanimals are treated with excellent care, hundreds of life-changingmedical advancements have emerged, and animals and humansboth enjoy the benefits of the research. Those who fight for animalrights do so because they want animals to be treated humanely.What many don’t realize is how well the animals really are caredfor. The world owes many of the new discoveries in medicine toanimals and their veterinarians. Nothing could be done for thosebrave people of the past who, like Roosevelt, fought crippling andeven deadly diseases. But with the help of animals and biomedicalresearch, many of those devastating illnesses have been defeated.Because of this, the world’s dream of a healthy, happy future canfinally come true.

KIMBERLY BASTON will be a sophomore inhigh school in the fall of 2010. She spendsher time playing the piano and doingthings with her family. Kimberly especiallyenjoys reading and writing, and tookpleasure in participating in the PSBR essaycontest. She has been a Girl Scout for 10years; she has earned her Silver Awardand is working towards the Gold Award.She is very involved in her school, beingpart of the gifted program, the chorus, andtheater club. After high school, Kimberlyplans to attend college; she aspires tohave a career in English.

Why Are Animals Used inBiomedical Research?

Kimmi BastonNorwin High SchoolNorth Huntingdon

Bibliography

Columbia University. (2005). Medical Research with Animals. RetrievedFebruary 8, 2010 from http://cumacolumbia.edu/research/animal,

Howard Hughes Medical Institute. (2009). FDR and Polio: Public Life,Private Pain. Retrieved February 16, 2010 fromhttp://www.hhmi.org/biointeractive/disease/polio/polio2.html

Nolan, R. S. (2010). Primate veterinarians promote animal welfare,biomedical research. American Veterinary Medical Association. RetrievedFebruary 8, 2010 fromhttp://www.avma.org/onlnews/javma/aug09/090815a.asp

University of Pittsburgh. (2008). Institutional Care and Use of AnimalsCommittee Policies. Retrieved February 8, 2010 fromhttp://wvvw.iacuc.pittedu/policies.htm

University of Pittsburgh. (n.d.). Remembering Polio. Retrieved February 16,2010 from http://www.polio.pitt.edu/

FINALIST


When biomedical research is mentioned, the first thing manypeople think of is how it is wrong to use animal testing. But whatexactly is it? Biomedical research is the area of science that studiesthe processes of life, the prevention and treatment of disease, andthe genetic and environmental factors related to disease andhealth. It looks for disease prevention and treatment that caneliminate illness and death in people and animals. Biomedicalresearch requires careful experimentation, development, andevaluation by many scientists, biologists, and chemists. There aremore positives of animal use in biomedical research than negatives.Yet many people do not like the idea, so they make an effort to endbiomedical research with animals because they misunderstand howscience really works and the gains we have achieved.

Animals are used in biomedical research because their organs andbody systems are similar to those of humans and other animals.Humans and animals have similar anatomies and physiologies.Animals are susceptible to the same diseases that affect humans.Both humans and animals share some of the same diseasesincluding many cancers, diabetes, allergies, birth defects, asthmas,influenzas, and heart diseases. Secondly, it would not be right toexpose humans to health risks in order to observe the course of adisease. Another reason for using animals is because of their shortlife-cycles. This makes it easy for a scientist to study them throughtheir life-spans, or even across many generations. Also, theenvironment around animals can easily be controlled. Examples arefood, lighting, and temperature. It is easier to change an animal’senvironment than a human’s environment. Without animals, almostevery major medical advance made for both humans and animalsduring the last century would not have been possible.

Animals are a very important part of the research process. Usingthem in biomedical research helps scientists understand how ourbodies work, solve medical problems, cure and treat diseases, testnew drugs for safety, and develop new techniques and treatments.Before giving a new drug to a human, it must first receive legalapproval. It is critical for scientists to do research on laboratoryanimals because it provides information that helps to predict theeffects of a new drug or procedure on a human. Biomedicalresearch saves lives. When researchers study animals, they discoverinformation that can’t be learned from studying other sources.Thanks to the use of animals in biomedical research, nearly onemillion children age 5 and under survive after being accidentallyexposed to potentially poisonous substances and 12 millionAmericans age 6 and older have medication to control high bloodpressure. Also, cats and dogs are benefited. Thousands receivevaccinations each year which spare them from diseases such asrabies and parvo, just to name a few.

There are federal laws that make sure animals being used inbiomedical research are not being harmed and are being welltaken care of. A wide variety of different animals are used inbiomedical research. In the United States only about 22 percent ofthe work being done in biomedicine involves animals. About 90percent of these animals are mice, rats, and other rodents whileless than 10 percent of the animals used are dogs, cats, orprimates. It’s important to remember that more than 99 percent ofthe animals used by humans are for food, while only less than onepercent is used for research.

Why are animals used in biomedical research? Biomedical researchnot only benefits humans, but our pets and wildlife as well.Researchers are always finding new cures and treatments that couldnot be possible without laboratory animals. While use of animals inbiomedical research is popular today, it may die out one day due toadvances in technology. The research community came up withwhat is called "The Three Rs." This stands for reduce, refine, andreplace. Researchers are trying to reduce the number of animalsused in biomedicine, refine their techniques, and replace animalswhenever possible. But until that happens, animals will continue tobe used to save lives.

ALANNA DESAVINO is a risingjunior at Valley View HighSchool, where she is co-captainof the varsity basketballcheerleading squad. Alanna isalso a member of the Healthand Physical Education Club,National Honor Society, and thetennis team.

Bibliography

The Use of Animals in Biomedical Research.http://www.manhattan-institute.org/. MI, 2009. Web. 7 Feb. 2010.

The Use of Animals in Biomedical Research: Improving Human and AnimalHealth. http://www.aalas.org/. AALAS. Web. 7 Feb. 2010.

What is Biomedical Research?. http://www.njabr.org/. NJABR, 1995-2005. Web. 7 Feb.

Why are Animals Used inBiomedical Research

Alanna DeSavinoValley View High SchoolArchbald, PAGRAND ESSAYIST


Using animals in biomedical research is a controversial topic. Weas a culture are very close to animals; we rely on them for food,keep them as pets and share our lives with animals. This closerelationship serves only to cloud the issue. At the heart of thedebate is the simple question. What are the real benefits ofanimal testing? I began researching this topic with a negativeview on animal testing; I had many emotional preconceptions butlittle fact to base them on. At the end of my research I was insupport of animal’s being used in biomedical research. Thispaper is an outline of the facts and arguments that persuaded meto change my mind.

I began my research by finding out the facts about animal use inbiomedical research. According to the American Association forLaboratory Animal Science, rodents make up 90 percent of theanimals used in biomedical research. Rats, mice and hamstersare used often because they are small in size, easy to maintainand handle and have bodies that function similarly to humans. It is also beneficial to scientists that they reproduce quickly,because they provide them with more test subjects. Other animalscommonly used in biomedical research include cattle, swine,rabbits, dogs, frogs, birds, fish, reptiles, and nonhuman primates.To ensure the animals used in research were handled humanelythe Animal Welfare Act was passed. This act requires thatminimum standards of care and treatment be provided foranimals used in research. The researchers also must consult withthe institutions’ veterinarian and their Institutional Animal Careand Use Committee (IACUC) which every research facility has tomaintain. The IACUC’s job is to ensure that all non-animalalternatives have been considered, and that pain management isgiven unless it interferes with the study. Animal research is notundertaken lightly, and these facts are what began convincing meto be pro-animal research.

Now that the facts of animal research have been presented, Iwould like to talk about the positive things that have come out ofanimal testing for both humans and animals. According to theAmerican Association for Laboratory Animal Science, manymedical procedures we have today are the result of animalresearch. A few examples include heart by-pass and organtransplantation as well as vaccines such as polio, measles,smallpox, rabies and the tetanus vaccine. Because of animalresearch thousands of pets are vaccinated and thousands ofpeople are able to receive life saving organ transplants each year.As you can see, animal research has saved countless lives andgreatly expanded our medical capabilities. After I discovered howmuch care and consideration is given to the animals used inresearch and how much good has come out of this research, I nolonger maintained a negative outlook on it.

Despite the positive things that have come out of animal researchthere are still some problems. The Medical ResearchModernization Committee wrote a paper on contemporaryanimal research. It stated that cancer research is usuallyconducted on mice, yet mice are actually considered poor modelsof the majority of human cancers. Animal models have alsoproved unhelpful in AIDS research since the early 1980’s. Whilemice, rabbits and monkeys under the right conditions can beinfected with HIV, none of them actually developed the humanAIDS virus. When presented with this information I was stunnedthat research today on some of the most debilitating diseases ofour time was proving ineffective. However, I continue to maintainmy pro-animal research status because while animal researchmay sometimes not produce the desired results, the benefits itoffers are overwhelming.

At the end of my research I realized that animal research isnecessary in today’s world. I only had to look at what it has donefor my generation as well as future generations to realize that ithad many astounding benefits. Today almost no children inAmerica are afflicted with polio because of animal research. Also,if I were to need a new lung, the technology that would make thispossible came as a result from animal research. Along the courseof my research I realized that animals are used in researchbecause of the overwhelming benefits and ultimately became asupporter of animal research. As in anything in life, animalresearch isn’t perfect. However, deeming it wrong is too simple ofa response; instead we should work together to fix its faults and tomake it beneficial to all.

A Discovery of the Benefitsof Animal Research

Emma Jean Kulik DicksonNorwin High SchoolNorth Huntingdon, PA

Besides science, EMMA JEAN KULIKDICKSON has many other interestsincluding playing field hockey for NorwinHigh School’s team, painting, reading andplaying soccer. Additionally, Emma is amember of her local Girl Scouts andvolunteers at a local hospital.

Bibliography

Animal Welfare Information Center. December 22, 2009. United StatesDepartment of Agriculture. February, 21 2010<http://awic.nal.usda.gov/nal_display/index.php?info_center–3&tax_level=3&tax_subject=182& topic_id=1118&leve13_id=6735>.

A Critical Look at Animal Experimentation. Medical ResearchModernization Committee. February, 21 2010 <http://www.mrmcmed.org/critconc.html>.

IACUC.org. American Association for Laboratory Animal Science.February, 21 2010 <http://www.iacuc.org/aboutus.htm>.

The Use of Animals in Biomedical Research. American Association forLaboratory Animal Science. February, 21 2010<http://www.aalas.org/pdf/improve_human_animal_health.pdf>.

FINALIST


Bioscience research is exploring life’s processes and diseases andhas high importance in the world. It affects everybody, and nomatter who we are, what we do or where we live, bioscienceresearch affects our lives daily. Scientists have been exploring life’sprocesses for a very long time. Their research gives us theinformation to make choices that allow us to take care of ourhealth. Scientists have learned a lot about why we get sick and howwe can get well. They have created vaccines to keep us fromgetting diseases and antibiotics to fight disease-causing bacteria.

Research is the process of seeking information. By simply askingquestions, anyone can become a researcher. In actuality, bioscienceresearch can be a very slow and intense process. When scientistsconduct research, they use the scientific method and follow thesesteps: l. They observe and ask questions. 2. They form and testhypotheses. 3. They analyze the data and draw a conclusion.However, scientists have more in-depth research methods. Thesemethods include: simulations, in vitro (Latin for “in glass”) tests,animal models, human clinical trials, and epidemiological studies.Scientists generally use simulations to imitate and comprehendliving systems, generate new ideas, and work out problems in theearly stages of research. In vitro tests often use cells or tissues froma human, animal or plant that is “cultured,” or grown in lab dishesthat contain all of the nutrients they need. In vitro tests are easilycontrolled, so the results are easy to reproduce. The next step inbioscience research is using animal models. Animal models allowscientists to study something in a whole, complex living system thatreacts similarly to that of humans. Research in animals is useful infinding out many things including finding out how people mayrecover from a surgical procedure, or how they might respond to adrug, chemical or something in the environment. Animal modelsgive scientists a way to study how a substance will act before testing it on humans. The fifth and final stage of research isepidemiological studies. These studies sort out the causes,allotment, and control of diseases in groups of people. Scientistswill gather information on whom, how, and where a human mightget a disease. They also look for connections to the disease andresearch for possible causes of the specific disease.

The three types of bioscience research are basic, applied, andclinical. Basic bioscience research gives scientists a betterunderstanding of life processes and how diseases work. It is notdirected to cure any specific disease in humans or animals. But wewouldn’t have the information needed to develop cures without it.Basic research has brought us blood transfusions, organtransplantation and gene therapy. Applied bioscience research isdirected toward something specific like developing a new drug,treatment or prevention. Finally, clinical bioscience research is usedafter the other stages of research have taken place. It is the testingthat takes place in humans to measure the effectiveness and safetyof a treatment.

Research does not always have a clear direction or application. It isgaining knowledge for knowledge’s sake and that way, we alreadyhave the information when we need it. Though researchers havenot found cures for diseases such as AIDS, they have unraveledmany of its mysteries thanks to valuable clues from the studies ofgenetics, microbiology, virology and animal models. Researchersstudying the environment and the things in it give us information tohelp us protect ourselves and our world.

ERIN LUCATORTO is 14 years old and livesin Yardley, PA with her parents andyounger sister. She is a recent 8th gradegraduate of St. Ignatius of Antioch School.Erin will be attending Notre Dame HighSchool in Lawrenceville, NJ in the fall.Erin is looking forward to high school andthe new experiences it will bring. Erin hasalways enjoyed playing a variety of sports,reading, and going to the beach.

What’s the Point ofBioscience Research?

Erin LucatortoSaint Ignatius of Antioch SchoolYardley, PA(7 & 8 Grade First Place)

FIRST PLACE


Humanity’s policy towards the treatment of animals has always beena precarious one. In particular, the issue of animal research hasgrown increasingly contentious between the scientists involved andthe activists who argue that such treatment of animals is unjust.However, despite their commendable intentions, the latter ignore thetruth of the matter: that animal research does the world good byminimizing animal pain while saving millions of humans and animalsthrough past and continued research. Thus, continuing animalresearch is not only justified, but also the moral course of action forall scientists.

This research provides an invaluable contribution to the worldthrough the innumerable medical advances that have saved bothhuman and animal lives alike. Animal research allows for datagathering that cannot be accomplished through tests on humans forethical reasons; consequently, it has given researchers the neededinformation to produce many important medical innovations of thelast century. Blood transfusions, open-heart surgery, anesthetics,chemotherapy, immunizations against polio, mumps, and measles —these are just a sample of the hundreds of breakthroughs that animalresearch has resulted in (“Benefits” FBR 8). Indeed, estimatesindicate that this research has helped increase U.S. life expectancyby nearly 25 years, preventing millions of deaths that wouldotherwise have resulted from diabetes, leukemia, polio, and otherdiseases now treatable thanks to animal research (“Using” SavingLives Coalition 3).These innovations are not limited to humandiseases, though: as noted by Dr. Franklin Leow, “Most ... veterinarymedicine ... [has] come either directly from animal research orhuman medical practice that was originally based on animalresearch.” Protective vaccines for rabies and tetanus, treatment ofnumerous parasites, and animal surgery have all resulted fromanimal research, and all save thousands of animal lives every year.

Despite these realities, many activists still object to continuing animalresearch under the impression that other methods of research exist;this assumption, however, is false. While new methods of researchare being developed, such as cell culture testing and computermodeling, these methods are useful adjuncts to animal research.They are far too simple to replace animal tests, unable to accountfor the complex interactions between organ systems, tissues, and theorganism as a whole. For instance, toxicology, (the study of poisons)is an exemplar of this idea: Washington Post writer Erin Marcusconcludes that “it is impossible to figure out the concentration ofmost substances to which different organs in the body are exposed... what happens in an animal is not just what happens in ananimal.” Animals are currently being used to investigate treatmentsfor Alzheimer’s disease, cancer, cystic fibrosis, and spinal cord injury(“Essential” PSBR I ); only through animal testing can thesetreatments develop further.

The gross mistreatment of animals in research is a myth: it ismarkedly minimized through numerous regulations. The scientificcommunity was the first to create organizations designed to enforcethe proper treatment of animals (“Humane” NABR 1);): the AmericanAssociation for Laboratory Animal Science, the Society forNeuroscience, the American Heart Association, and the NationalInstitute of Health are examples of organizations that ensure thepreservation of animal welfare. Regulations exist outside the scientificcommunity as well, codified through the Federal Animal Welfare Actwhich registers and authorizes facilities to conduct humane animalresearch, and the Public Health Service Act (“Humane” NABR 4).Lastly, the morality of the individual scientists themselves reinforcesthe external regulations; the mistreatment of animals is diametricallyopposed to the Hippocratic oath of upholding and enhancing thewell-being of the world’s inhabitants. And if all this wasn’t incentiveenough to deter animal cruelty, the minimization of distress is alwayspreferable since an unhealthy or stressed animal can cause skeweddata in laboratory tests. Such persuasive evidence contributes to thefact that most research (94%) is not painful to animals involved(“Figures” PSBR I ).

In the end, humane animal research allows for myriad innovationsand breakthroughs in medical research, saving human and animallives without sacrificing the well-being of animals in the process. A utilitarian understanding of ethics – the greatest good for thegreatest number of sentient beings – underscores the idea thatanimal research is both morally viable and necessary, for it savesmillions at the expense of none. Whether testing the body’s responseto a certain drug or the effectiveness of surgical techniques, toconduct animal research in the biomedical field is to do good in thescientific community, for all of humanity, and for the world at large.

Works Cited

Benefits of Biomedical Research. Foundation for Biomedical Research.

Figures on Painful Experiments. Foundation for Biomedical Research.1992.

Loew, Franklin. Animals as Beneficiaries of Biomedical Research OriginallyIntended for Humans.

Marcus, Erin. New Research Methods Seen Unlikely to Eliminate AnimalTesting. Washington Post, August 28 1990.

"The Essential Need for Animals in Medical Research. Pennsylvania Societyfor Biomedical Research.

The Humane Care and Treatment of Laboratory Animals. NationalAssociation for Biomedical Research Issue Update. 1993.

The Importance of Animals in the Science of Toxicology. Society ofToxicology.

Using Animals in Research is Necessary. Saving Lives Coalition.March 1993.

The Benefits of Animal Research

Rohan SamarthState College Area High SchoolState College, PA

ROHAN SAMARTH is a high school juniorinterested in both the sciences and theliberal arts, especially literature. He ispresident of the debate team, a memberof the Science Olympiad team, a schooljazz band guitarist, and a second degreeblack belt in Tang Soo Do. An aspiringbiologist with a love for animals, Rohanbelieves that when alternatives are notviable, animal research, done underregulated and humane conditions,provides the data for important medicaladvances.

GRAND ESSAYIST


Dear Mama and Papa,

Don’t worry, I am comfortable and treated well at the OrlandoBiomedical Research Center. I know that you two are against thisbiomedical research that I contribute to, but the value of thisresearch is important to finding new medicinal cures. Also, thesescientists and veterinarians are not deserving of the criticism thatanimal rights groups give them for performing biomedicalprocedures. Animal biomedical research is a practical system, andit benefits both humans and animals.

Biomedical research centers are very cautious about the animals’conditions, and they would never intentionally harm me or mymouse friends. You see, when I am tested on, I will be injected withanesthetic drugs to assuage my pain. If you are wondering whetherthis is legal, there are federal laws that standardize my pain,including “the Animal Welfare Act and the Public Health ServiceAct” (“Frequently”). In addition to the federal laws, the IACUC wasestablished — a committee that protects my animal welfare. Thecommittee can end the research test if it causes unnecessary harm.Although they supply me with anesthetics, most of the procedures atthis research center do not involve pain. In fact, my stress affects theresearch results, and the scientists do not want inaccuracy in thetests. Therefore, they will not injure me because they do not wantinaccurate results from the test. After I have served as an aide toscience, I will be euthanized. It is for a good cause because theresearch center needs my body tissue for “pathological evaluationand for use in in vitro tests” (“Frequently”). I am proud of myselfbecause I feel that I am a hero for helping in this specialbiomedical research center.

The use of animals in biomedical research is valuable because itbenefits both humans and animals. This research supports humansand animals, and “animals are necessary to medical research whenit is impractical or unethical to use humans” (“Questions”). Theanimals utilized have biologically similar organs to humans, andthey help the researchers learn about different health troubles. Also,the animals and I help guarantee the accuracy of experimentalmedical treatments. We mice, consequently, specialize in theprocedures that involve cures for cancer and aging treatments.Mama, I know you were thinking of receiving Botox, but I think weare close to finding a new anti-aging product! Major medicalmilestones have been reached because of animal biomedicalresearch. The most important accomplishment is that the “lifeexpectancy in the United States has improved dramatically” sincethe research has been held (“Use”). The biomedical research that Iparticipate in is crucial to the discovery of many cures for theadvantage of humans and animals.

Many of the animal biomedical researchers are criticized for theirwork. They do not deserve this criticism because they are kind andcaring towards animals. They maintain the temperature and lightingin the laboratory for me. Not only do they make me feel content,they also discover various vaccines and cures. Most people have nounderstanding of what goes on inside the laboratory, and theymake assumptions that the scientists are horrible and mean. Animalactivists are especially averse to what I partake in, and they make“grossly exaggerated or false claims” about these biomedicalresearchers (“Use”). People who disagree with this research wantthe scientists to use prior knowledge and not experiment withanimals. Do these protestors really know what happens behindthese laboratory doors? It is heinous for these animal rights groupsto criticize scientists for claims that are not realistic.

My companions and I are happy and treated well in the OrlandoBiomedical Research Center. The scientists use anesthetics to relieveour pain, if we have any. This research that I am participating in isextremely important to the future of medicine. Vaccines have beencreated through these tests. There is one component that is mostimportant for these tests: I feel gratified to help find cures fordiseases. Animals are experimented in biomedical researchbecause their bodies are biologically similar to humans. Under nocircumstances do these researchers deserve to be criticized for theirwork by the protestors. Please, Mama and Papa, it is my words, notthose of animal rights groups, that you should believe. The use ofanimals in biomedical research is a huge contribution to themedicinal world, as they continue to aid towards new discoveries.

Love your son,

Bernard C. Mouse

Works CitedFact vs. Myth. Foundation for Biomedical Research. 2006.Frequently Asked Questions About Animal Research. Foundation forBiomedical Research.Proud Achievements of Animal Research. Foundation for BiomedicalResearch. 2006.Questions People Ask About Animals in Research. The AmericanPhysiological Society. 2001.Use of Animals in Biomedical Research: Understanding the Issues.American Association for Laboratory Animal Science.

MACKENZIE MARA SMITH lives in BuckCounty, Pennsylvania and is a junior atCouncil Rock High School North. Shedecided to write for the contest to voiceher opinion on animal research, and shealso wanted to practice her creativewriting. Her favorite topic to learn aboutin school is U.S History. She also loves tolearn Spanish, and is entering her fourthyear in the language. Mackenzie enjoysspending time with her friends, playingsoftball, dancing, and running. She is ahuge Philadelphia Phillies fan, and lovesto attend the games at Citizens Bank Park.

No Worries

Mackenzie SmithCouncil Rock High School NorthNewtown, PA(Creative Category Winner)

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“Gene therapy helps blind boy see1, “Gene increases effectiveness ofdrugs used to fight cancer allow reduction in dosage2, “New MRItechnique could mean fewer breast biopsies in high-risk women3.”These news headlines from 2009 and 2010 underscore the profoundimpact of biomedical engineering in the medical world. At its essence,biomedical engineering is a hybridization of the problem solving skillsof engineering and the intricacies of medical and biological sciences.This field has helped to advance healthcare diagnoses and treatmentsof complex diseases. It has thus served mankind quite well. The field’ssub-disciplines overlap with other engineering and medical fields,including clinical engineering, pharmaceutical engineering andgenetic engineering.

Clinical engineers are professionals who advance patient care byapplying engineering skills to healthcare technology. They advisemedical device producers regarding potential design improvementsbased on their interpretation of clinical feedback4. Some clinicalengineers supervise the progression of high-tech and redirect hospitalprocurement patterns accordingly. This not only improves patient care,but also reduces the unnecessary money, time, and effort that aretypically spent. Pharmaceutical engineers concentrate on the idea,design, creation, and operation of research provisions andmanufacturing factories. Technical knowledge, leadership,professionalism, and adaptability to the field’s continual changes areimportant traits to have when one aims to be a successfulpharmaceutical engineer5. Unlike these two subspecialties, geneticengineering focuses primarily on manufacturing DNA. Geneticengineers work on understanding the genetic coding of biologicprocesses, figuring out the role of genetics in pathologic diseases,discovering ways to alter the structure of genetic material like DNA inliving organisms, animals and even human beings6. They arespecialists in the field of genetics and conduct research in a broadrange of biological sciences.

Most careers in this field need a bachelor’s degree as an entry-levelrequirement. Biomedical engineers usually incorporate formal trainingin mechanical engineering along with biomedical coaching to workoptimistically in this specific career scope. Unlike many otherengineering fields, most biomedical engineers hold a master’s degreeeven at an entry level.

Johns Hopkins Department of Biomedical Engineering is regarded asthe top program of its kind in the world. The program is committed tosolving important clinical problems. With the connection ofquestioning and discovery, the school combines biology, medicine,and draws upon the substantial strong points of Johns HopkinsSchools of Engineering and Medicine7. Our very own University ofPennsylvania has a marvelous BME program. The program is one ofthe oldest and most successful bioengineering divisions in the UnitedStates. I had a chance to participate in “Penn Gems,” an engineeringcamp for girls held at the University of Pennsylvania. There, I spent mytime learning about the field, and focused on Genetic Engineering.My lab instructor, Dr. Andrew Tsourkas, gave me phenomenalinformation on genetic engineering. I had the opportunity to not onlyask a countless number of questions, but to also experiment and workwith the genetic material. Along with that wonderful experience, I wasable to have an interesting conversation with the researcher behind

the cure of congenital blindness – Dr. Jean Bennett. We discussed hercareer and about its advantages and disadvantages. One of hercomments was as follows: “The disadvantage of having this job has tobe the paperwork. Writing grants can be tiring. A striking advantageof working in the field has to be continuing to learn new things everyminute of everyday. I am and always will be a perpetual student8.

With the 14, 000 biomedical engineers working in the nation, themajority are employed in medical equipment manufacturing. Thedemand for sophisticated, improved medical tools is increasing. As amatter of fact it is estimated that there will be a 21 percent rise ofemployers in the industry including clinical, pharmaceutical, andgenetic engineering. The Bureau of Labor Statistics also estimated thatabout 3,000 new careers would be created in the field of biomedicalengineering in 20169.

In general, one immediately thinks of doctors when asked about aprofession that has the most impact on the world. It is simply becausepeople rely on them when their life is on stake. Doctors give swine fluvaccinations; they check our heart rate; they diagnose the cause offever and treat it. The underlying question is, “Whom does a doctordepend on to provide all these challenging and complex tasks?”Without a simple syringe that is manufactured by biomedicalengineers, doctors cannot give that vaccine shot. Without thestethoscope, they can’t determine the heart rate. Without thebiomedical engineers, doctors would not have the tools required tounderstand biology, diagnose the pathology and treat their patients. Itis beyond any doubt clear to me that biomedical engineering is theprofession that directly and indirectly serves to keep mankind healthy,able and happy. I wonder if the impact of biomedical engineering ontoday’s population would perpetuate through future generationsthrough their genes!

Works Cited1. “Gene Therapy Helps Blind Boy See - The Early Show - CBS News.” Breaking NewsHeadlines: Business, Entertainment & World News - CBS News. CBS, 26 Oct. 2010.Web. 12 Feb. 2010. <http://www.cbsnews.com/stories/2009/10/26/earlyshow/health/main5421926.shtml>2. “Gene increases effectiveness of drugs used to fight cancer and allows reduction indosage.” Science Daily: News & Articles in Science, Health, and Environment &Technology. 31 Dec. 2009. Web. 27 Feb. 2010. <http://www.sciencedaily.com/releases/2009/11/091124103611.htm>.3. “New MRI Technique Could Mean Fewer Breast Biopsies In High-risk Women.” ScienceDaily: News & Articles in Science, Health, Environment & Technology. 8 July 2009. Web.15 Feb. 2010. <http://www.sciencedaily.com/releases/2009/06/090629132156.htm>.4. “Clinical Engineers.” American College of Clinical Engineering (ACCE). 2009. Web.18 Jan. 2010. http://www.accenet.org/default.asp?page=about&section=definition#do>5. “Clinical Engineers.” American College of Clinical Engineering (ACCE). 2009. Web.18 Jan. 2010.http://www.accenet.org/default.asp?page=about&section=definition#do>6. “Genetic Engineering - how do they do that?” Eureka ! Science - the easy way to learnbiology, get homework help and the latest science news. Mar. 2008. Web. 18 Jan. 2010.7. Whiting School of Engineering.” Johns Hopkins University Whiting School ofEngineering. 25 Feb. 2010. Web. 14 Feb. 2010. <http://engineering.jhu.edu/bme/>.8. “Interview on Biomedical Engineers with Jean Bennett.” Personal interview. 5 Jan. 20109. “Biomedical Engineers: Training, Salary, & Career Information.” CollegeGrad.com.2008. Web. 18 Jan. 2010. <http://www.collegegrad.com/careers/proft09.shtml>.

SITARA SOUNDARARAJAN has just completedeighth grade at Welsh Valley Middle School andwill be entering high school in September. In thesummer of 2009, Sitara earned 3 first placenational awards for her events in the TechnologyStudents Association. She has also won first placein the Biomedical Essay challenge in the 2010TSA State Conference that is being published inthis edition of ResearchSaves Magazine.

Sitara participates in many after school activitiesincluding World Affairs and is an editor-in-chiefof her school newspaper. She attends a localIndian classic dance academy and hasperformed Bharathanatyam dance and Carnaticmusic at various venues across the country. Shealso plays piano and attends tennis lessonsregularly on weekdays. Sitara intends to pursuea career in the engineering or medicine field.

How Biomedical EngineeringImpacts Medicine

Sitara SoundararajanWelsh Valley Middle SchoolNarberth, PA

MIDDLE SCHOOL

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BIG PATIENTS, BIG SUCCESSOne way to understand the mechanisms of the virus is to have its genome sequenced. The Human Genome Sequencing Center (HGSC) at BCM is sequencing DNA from