BIOTECHNOLOGY
At Georgia Tech, bioengineering and bioscience are leading the way into an amazing future for medicine.
by Amy Stone
IN YEARS PAST, biologists researched living organisms while engineers, often working in distant buildings, focused on building machines. Now, developments in technology and a better understanding of biology have enabled engineers to apply the principles of their science to biological problems.
photo by Billy Howard
Ph.D. student Stewart McNaull investigates endothelial
cell adhesion related to sickle cell anemia. Such adhesion
leads to blockage of microvessels in
sickle cell patients. The work is being done in Dr. Timothy Wick's
laboratory at Georgia Tech.
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This union has created the hybrid field of bioengineering, which is elevating the expectations of many people. They hope the field will generate products and innovations that improve human health and boost the nation's economy. Indeed, bioengineering already has produced innovations such as artificial skin, pacemakers and new pharmaceuticals. It also is boosting the bankrolls of researchers, institutions and companies who develop, license and market the innovations.
Faculty at the Georgia Institute of Technology are leaders in applying engineering principles to some of the largest biological questions of our time. To enhance and encourage research in this area, Georgia Tech is physically bringing together all of the bioengineering and biosciences research on campus under one umbrella — the Parker H. Petit Institute for Bioengineering and Bioscience.
The Petit Institute comprises three centers: the Bioengineering Center, the Biosciences Center and the Biomedical Interactive Technology Center. Faculty also have forged interinstitutional partnerships with Emory University (the Emory-GT Center) and the Medical College of Georgia (the MCG-GT Center). Current external research funding is about $10 million.
"The role of the institute is to foster biomedical research by bringing together engineering, information technology and the sciences," says Dr. Robert Nerem, director of the Petit Institute. "Georgia Tech has long been a strong engineering school. But, in the future, to be a premier technical institute will require a strong commitment to biosciences and the engineering and technology that flow from it."
The institute, endowed by a $5 million gift from Healthdyne founder Parker H. "Pete" Petit, will be housed in a new building, which broke ground in March. The facility is designed with multi-disciplinary research in mind, Nerem says. By assigning space based on projects, rather than on departments, the institute hopes to break down barriers to collaborations.
"When I decided to make the endowment, I had already seen 10 years of exciting progress at Georgia Tech in this area," Petit says, referring to his endowment of a chair in engineering and medicine a decade before his gift to the Petit Institute. "In the years ahead, we will see breakthroughs come out of this program that will enhance the quality of life for many."
Following are examples of Petit Institute projects that exemplify the excitement and promise of bioengineering.
Researchers are applying engineering principles to human physiology,
enabling them to create artificial substances to aid or replace damaged
or defective body parts.
Creating artificial tissues
In addition to directing the Petit Institute, Nerem maintains an active
research agenda. Half of his laboratory is devoted to understanding the
effects of blood flow
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Dr. Athanassios Sambanis, an associate professor in the School of Chemical Engineering, works in the same field, but with a different emphasis. Sambanis' research focuses on an artificial tissue, which once implanted can control the body's level of blood glucose. Functioning as an artificial pancreas, this tissue would negate the need for insulin injections among diabetics. Sambanis has encapsulated cells that produce insulin in response to glucose in a membrane that allows passage of nutrients into cells and insulin out of cells.
The pores of this membrane are small
enough to exclude antibodies and lymphocytes, thus preventing an immune
system rejection of the artificial tissue. Sambanis also is developing
a "smart" membrane, which would allow blood vessels to grow in its outer
part, thus providing the cells within with increased amounts of oxygen and other nutrients. He is conducting
experiments with such a membrane implanted in rodents.
Understanding blood flow
Blood vessel damage occurs in specific places in the human body. This
damage eventually causes plaque build-up, which can rupture and cause
heart attacks and strokes. Dr. David Ku, a professor of mechanical
engineering at Georgia Tech and a professor of surgery at Emory
University, wondered why this damage always starts in the same places.
By studying the mechanics of blood flow in those places, he found that
oscillatory shear stress is occurring. Simply, in those areas prone to
developing problems, blood may flow back and forth, instead of just one
way. The back-and-forth motion can lead to focal disease.
Because one area of blockage occurs in the heart, Ku is applying his findings to create a biomaterial for a replacement artery. The material is a hydrogel, mainly composed of water. It allows new cells to grow into it, effectively making it part of the body. This substance is a platform technology, meaning it can be applied to different biological problems. For example, drug delivery — where multiple drugs could be placed in an implant and diffused in the correct amount over a predetermined time — is an additional use of this material.
Ku also is working in the tissue culture area of keeping entire arteries alive outside of the body. "Growing individual cells in culture may not tell you how they will behave when they work together in tissues," he says. So Ku simulates many disorders, including high blood pressure, in these arteries to see what happens when interventions, such as balloon angioplasty, are applied.
Another promising project of Ku's could allow physicians to predict a patient's risk of atherosclerotic plaque ruptures. Scientists know arterial blockage can occur years before patients feel symptoms. Ku examined this phenomenon from a mechanical engineering point of view. He found that blood flow increases to the constricted part of the artery, causing decreased pressure in the diseased artery near the plaque. Because the pressure is lower inside, the compression can cause plaques to break. In turn, this causes platelets to stick to the exposed collagen underneath, building up an occlusion. Using this information, Ku has developed a model to predict which patients have a high likelihood of arterial blockage.
Engineering can define the body mathematically. Thus, engineers can
quantify the body's blood flow and electrical currents, and then use
probabilities to predict certain biologic aspects of those systems.
Closed circuits
If you reduce the movements and senses of the body to their bare
essences, you are left with circuits. Hands clap, and the resulting
sound waves are funneled into your ear and translated into electrical
impulses the brain understands.
photo by Stanley Leary
Georgia Tech graduate students examine a rat used in testing new
selenium-based antihypertensives.
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If the sound signals danger, your brain instructs various muscle groups to move. Dr. Stephen DeWeerth, an associate professor in the School of Electrical and Computer Engineering, uses integrated circuit technology to create models of neurobiological systems. The models help researchers understand how and why these systems work, and may eventually lead to replacement of defective links in them.
"We're taking what physiologists have learned and are building mathematical, software and hardware models of systems," he says. "We are trying to find the structure underlying complex systems."
The applications of this research are broad. They include the existing
example of cochlear implants, which provide the missing bridge to
translate sound waves into electrical impulses the brain understands. In
the future, this type of research will yield artificial limbs that
respond to electrical signals from the body. Also, engineers may be able
to create implantable electrical stimulators. These devices could
connect electrodes in the brain to the spinal cord, allowing people with
spinal cord injuries to regain movement. DeWeerth's group is primarily
interested in motor systems — specifically, how muscles are controlled
and reflexes occur, and what patterns of muscle movement and feedback
develop in activities such as walking.
Defibrillating hearts
When a heart goes into fibrillation, the cells of either the atrium (one
of the upper chambers) or ventricle (lower chamber) fire out of sync,
creating a rapid, irregular heartbeat that does not properly pump blood.
Dr. William Ditto, an associate professor of physics and electrical and
computer engineering, uses sensory dyes that plot electrical activity in
the body to capture on film the wave pattern of these misfiring cells.
He has shown that electrical waves start circling the damaged cells,
creating spiral waves.
"Think of a rock near the shore in the ocean and how waves break around it," Ditto explains. "The defective cells are like that rock, in that they cause the normal pattern of electrical waves to be disrupted."
This spiral pattern falls into the category of chaos behavior — that which lies between purely random behavior and periodic behavior. Some call it controlled irregularity. By characterizing the chaotic system of fibrillation, Ditto hopes to find keys that will help the heart defibrillate itself. For now, doctors rely on large machines that deliver a hefty electrical wallop to defibrillate the heart. Ditto's work may make possible smaller machines, which require less energy to get the heart restarted on a normal rhythm.
In a related project, Ditto is exploring the feasibility of an
implantable pacemaker in the brain to decrease seizures. The pacemaker
would create an electromagnetic field, which could be adjusted to
suppress seizures.
Viewing vessels
Meanwhile, Ku is addressing an important imaging problem. Imaging
arteries with magnetic resonance imaging (MRI) is safer and cheaper than
imaging arteries with radioactive dye X-rays, the standard method of
examining blocked vessels. But the turbulence inside of an artery near
an occlusion causes a signal loss when imaging with MRI. This loss of
image at the crucial point creates a dilemma because physicians base
their recommendations for bypass surgery on quantifying the degree of
blockage in an artery. To counter the MRI signal loss, Ku has created a
knowledge-based software that allows computers to learn signal loss
pattern recognition and equate it with a specific amount of disease. It
has proven 98 percent accurate, can be adapted to current MRI machines
and should enable physicians to make more accurate diagnoses, Ku says.
Dr. Ajit Yoganathan, the associate director of the Petit Institute, is using MRI technology to understand blood flow patterns in children who are born with heart defects. In an example of research physicians are taking directly to the operating room, Yoganathan consults with pediatric surgeons to create better surgical correction techniques.
As genetic knowledge grows, so too does the need to manage this knowledge. For example, the amount of information contained in a strand of DNA is staggering. To be useful, it must be translated into genes, which ultimately control inheritable traits, and proteins. Such quantitative analysis research develops tools to manage and decipher biological information.
Dr. Mark Borodovsky, a professor of biology and mathematics, develops statistical pattern recognition for DNA and protein sequence analysis. He has developed a
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The Human Genome Project is striving to completely decipher the genome of the human species, as well as the genomes of certain organisms, including bacterial pathogens. For instance, understanding the genomes of Haemophilus influenzae (bacteria that cause lung disease) or Heliobacter pylori (bacteria that cause peptic ulcers) could help scientists design new drugs. Researchers used Borodovsky's GeneMark software to decipher the genome of these organisms.
Now, GeneMark is the most popular software tool for finding genes in bacterial species, including archeabacteria. Also, Borodovsky and his colleagues have created a new program, GeneMark.hmm, to find genes in DNA of higher organisms, including humans.
Since 1993, researchers from around the world have sent DNA sequences to Georgia Tech via the Internet to obtain important information on gene locations. Now they can plug sequences into the Web server to see immediate results of their analyses. Borodovsky's lab also has supplied the gene-finding programs to academia and industry.
Technology is allowing researchers to create innovative ways to remotely
manage patients' health and to economically teach medical students new
techniques.
Long-distance medicine
The concept of the "electronic house call" is a new twist on the
long-forgotten practice of physicians visiting patients in their homes.
Researchers at Georgia Tech and the Medical College of Georgia (MCG)
have placed two-way audio/visual systems in patients' homes and
connected them to monitoring stations in remote locations. This
connection has enabled physicians to monitor their patients' health,
while allowing patients to stay in their homes. Physicians have tested
this example of what is known as telemedicine technology in private
homes and a nursing home. Now, Georgia Tech and MCG have entered into a
licensing agreement with a private firm, CyberCare Inc., to bring the
technology to market.
"A client/server database structure has been developed to capture and store vital signs measurements performed by the patient," says Michael Burrow, a senior research engineer at Georgia Tech. "This allows the care provider to access the patient's data from any location and to input additional data. Eventually, the system will be compatible with hospital database systems, which will create another avenue to input and access patient data."
Burrow sees "electronic house calls" as including not only patients in private homes, but also in institutions, such as prisons, where it is costly to transport patients to medical facilities.
Through the telemedicine technology of the Georgia Statewide Academic and Medical System (GSAMS), physicians can consult with specialists in different locations. The largest such distance learning and medical network in the country, GSAMS is operating 32 out of 54 planned telemedicine sites.
A related telemedicine project lets healthcare workers measure vital
signs from a distance. The concept of remotely measuring heart rate and
respiration was originally developed for the military to assess the
status of wounded soldiers. Now, scientists are adapting this technology
in homes and hospitals: A microwave device mounted in a patient's room
will provide physicians with medical information on the patient.
Virtual Surgery
Allowing surgeons to practice procedures on a simulator can give them
valuable feedback. Researchers at Georgia Tech, including Dr. Norberto
Ezquerra, John Peifer and Michael Sinclair, are creating simulations for
endoscopic procedures and eye surgery. Surgeons operate using virtual
tools with force feedback on computer-generated anatomical models.
Scientists base rational drug design, discovery and development on an in-depth understanding of chemistry, and the biochemistry and physiology of the human body. The process can yield compounds that are both effective and selective, which can result in fewer side effects.
Dr. Sheldon May, associate director of the Petit Institute and Regents' professor in the School of Chemistry and Biochemistry, recently announced a new class of antihypertensive drugs that may do more than control hypertension. May's drugs are selenium-based compounds, which, in addition to their antihypertensive qualities, possess the benefits of an antioxidant. In fact, strong, recent evidence indicates that selenium, in low levels, may protect humans against cancer.
"There are lots of antihypertensive drugs out there," May says. "This compound may not be significantly better in controlling hypertension, but it demonstrates the feasibility of harnessing the unique chemistry and biochemistry of selenium for a therapeutic purpose."
The development of this class of drugs exemplifies the collaborative nature of the Petit Institute: May's colleagues in engineering disciplines performed much of the background work, such as blood flow analyses and Doppler imaging.
Another example of rational drug design hinged on a discovery by May into how the body works. The body's process called amidation occurs to activate certain peptides. Amidation requires two enzymes to proceed; May's research group identified one of them. In inflammatory diseases, such as arthritis and colitis, amidation occurs too frequently. May has developed inhibitors of these amidating enzymes, which exhibit anti-inflammatory activity.
As the above examples show, the products and innovations originating in laboratories at Georgia Tech are rich with potential for improving the quality of life for many.
"The future of bioengineering represents a new initiative for Georgia Tech in the 21st century," Nerem says. "It is one that will further enhance Georgia Tech's reputation, will provide significant benefits to the public and also add to the region's economy."
For more information, you may contact Dr. Robert Nerem, Petit
Institute for Bioengineering and Bioscience, Georgia Institute of
Technology, Atlanta, GA 30332-0363. (Telephone: 404/894-2768)
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