The hard work of making cities smart and green

By 2050, 90 percent of Americans will live in cities that consume most of the nation's energy and generate most of its greenhouse gases. Whether sprawling cities devolve into ecological disasters or slowly transform into smart, sustainable economic growth engines will depend partly on the next generation of engineers and the technologies they invent.

To face the challenges posed by megalopolises, experts say Americans need to do more than just upgrade the current, rusting infrastructure. In a perfect world, future cities would boast advanced public transportation systems, renewable energy resources,"complete streets" and green roofs. Birmingham aspires to become such a place, with a new kind of UAB campus at its heart. Solar-powered electric vehicles would traverse its avenues passing facilities cooled in part by the breeze instead of fossil-fuel-burning air conditioning.

As a step toward this futuristic vision, Fouad H. Fouad, chair of the UAB Department of Civil, Construction and Environmental Engineering – and director of the UAB Sustainable Smart Cites Research Center – recently convened the second annual Sustainable Smart Cities Symposium. We thought the meeting made for a good occasion to ask him about related research frontiers. It's an exciting time, but there is still a long way to go, with progress slowed by economic hard times and the slow pace of technological development.  When will U.S.-made solar panels, for instance, be cheap enough to compete with fossil-fuel-generated electricity?

For any city re-imagining itself as sustainable, the effort must start with investment in smart, green infrastructure – power, transportation and buildings, according to Dr. Fouad.

Power
On the frontiers of alternative power generation, Alabama Power is currently testing solar panels at 50 locations across the state. Unfortunately, Alabama is not windy enough for massive wind power projects using current technologies, but engineers continue to experiment with the viability of rooftop units.

Research is underway in UAB Mechanical Engineering on the next generation of solar cells, some of the work done in combination with Alabama Power, said Dr. Fouad. UAB Energy Management’s dream is to carpet the roofs of UAB’s buildings with solar panels but presently, projects would take 30 years to generate enough savings to pay for themselves – in part due to the relatively low utility rates in Alabama.

Transportation

Smart, green transportation systems are a major ingredient in future-looking cities, with related efforts seeking to create new street plans that favor non-motorized traffic, take advantage of biofuels and launch electric vehicle fleets.

In terms of city planning research, Fouad said his team is doing many studies on congestion management.  Dynamic signaling systems may make it possible to better route traffic to lessen traffic jams.  Thanks to a grant from the U.S. Department of Transportation, UAB recently joined the National Center for Transportation Performance and Management to conduct multi-disciplinary research on sustainable transportation infrastructure, economic competitiveness and safety.

Other concepts under investigation by UAB civil engineers include the "complete street," where city streets are designed to accommodate foot and bike traffic as much as motorized traffic. A UAB demonstration project is planned for 10th Avenue in combination with The Regional Planning Commission of Greater Birmingham, said Dr. Fouad.

Under the heading of green fuels and vehicle fleets, the planning commission's partnering initiatives include Alabama Partners for Clean Air and the Alabama Clean Fuels Coalition. Recent related news includes the announcement by the City of Trussville that it's expanding its fleet of compressed natural gas vehicles and opening a CNG fueling station. Compressed natural gas is a fossil fuel substitute for gasoline that is more environmentally sound. CNG may also be mixed with biogas, produced from landfills or waste water, which doesn't increase the concentration of carbon in the atmosphere.

UAB Civil Engineering has a project underway in conjunction with the Jefferson County Transit Authority and the U.S. Federal Transit Administration to design and construct a prototype for a hydrogen fuel cell powered bus, which they hope could be the workhorse of new green public transportation fleets in Birmingham. The first vehicles should on the road later this summer, said Fouad. Such vehicles make electricity to power the car using hydrogen, and they give off nothing more than water vapor from the tailpipe. On the consumer front, Honda and Toyota are getting closer to producing hydrogen-powered cars that could be sold to consumers, but they will be costly to start.

Alabama Power is also experimenting with fleets powered by alternative energy sources, and to date has more than 100 electric vehicles and 50 charging installations. The UAB Department of Energy Management has purchased two electric cars that are charged entirely by solar panels, which offer them the chance to evaluate
a grid-free transportation technology with no carbon footprint.

Buildings and bridges
The UAB Department of Materials Science & Engineering has great research strength in the design of green composite materials for building, Dr. Fouad said. Often such materials are made from recycled materials and are lightweight, stronger and less expensive to use. His smart cities center will be participating in the Alabama Composites Conference starting on June 18 in Birmingham.

UAB Civil Engineering is also designing materials for use in the building of next-generation, critical infrastructures like the highways and bridges. Dr. Fouad is an expert, for instance, in autoclave-aerated concrete, which is filled with air bubbles such that it requires one-fifth of the weight of classical concrete to create a material that is much stronger. Composed of 80 percent air, it promises to deliver huge savings to the industry while creating an air-bubble barrier in building materials that insulates the building against energy loss. The barrier of air within the concrete acts as thermal installation, reducing heating/air conditioning costs.

UAB civil engineers are also looking at what's next for materials used to make bridges. Along with bridge materials research, projects underway are studying "bridge way in motion" sensors that send messages continually about the structural health of bridges to ensure timely maintenance, not to mention alerting authorities when trucks breaking weight limit laws cross bridges.

Also maturing are research efforts to develop green roof technology, where plants grown in soil beds on roofs conserve energy and improve air quality as plants turn carbon dioxide generated by cars into oxygen. Green roof test beds are currently in place atop the Hulsey Center, the Business and Engineering Complex, Campbell Hall and Hill University Center at UAB. They limit water runoff into the storm water drains, pumping it back through the irrigation system, which keeps polluted water from running into area creeks and the Black Warrior River. The presence of plants and surrounding soil controls water evaporation in a way that creates a cooling effect. Combined with the moist soil, this helps drop temperatures and has resulted in a 20 to 25 percent savings in power bills.

Both the vegetative and white reflective roofs are perhaps 80 degrees cooler in the mid-day summertime than standard black roofs, which can literally be used to fry eggs. The Alabama Department of Environmental Management is interested in promoting the adoption of vegetative roofs across the state.  

Impact on health
One of the most exciting projects underway is a partnership between Civil Engineering and the UAB School of Medicine's Division of Preventive Medicine. Called the "Go-ing Forward Project," it seeks to determine how the condition of the "built environment" in a city - the streets, lighting, housing, sidewalks, etc., - impacts the health of city dwellers. UAB researchers are going door to door surveying residents to determine how various aspects of the built environment are impacting their lives. The project's emphasis is looking at how transportation options, urban design, infrastructure decay, safety and security, and housing conditions affect obesity. More than one third of the American population is obese.

From the layout of streets to the options available for exercise, to the quality of air and water and to the condition and upkeep of residences, the built environment exerts silent but significant influence on the likelihood that people will be obese. Of all the engineering factors correlated with negative health outcomes, housing conditions are the most closely tied to health impacts. The presence of mold and its impact on asthma, poor indoor air quality in private homes and certain pollutants (e.g. estrogen-related compounds) in drinking water are all hypothesized to contribute to obesity risk.

Looking for partners
It was no accident that Richard Michos - global vice president, Smarter Cities, from IBM, was invited to speak at Fouad's recent UAB Smart Sustainable Cities symposium. UAB and the City of Birmingham hope to partner with IBM, perhaps through its Smarter Cities Challenge. This competitive IBM grant program is in the process of awarding $50 million worth of technology to 100 cities around the globe. These grants are designed to address the wide range of financial and infrastructure challenges facing cities today. Fouad met with Michos and Mayor Bell while Michos was in Birmingham, with their discussion covering the potential for IBM doing an assessment of the city's greatest sustainability needs, which is expected to yield a report and contribute to an action plan.

Speaking of partnerships, the City of Birmingham and UAB took a step toward smarter, healthier and more sustainable development with the Feb. 27, 2013, signing of a memorandum of understanding to partner on projects such as energy efficiency and city planning that accounts for a more “livable” city. Pilot projects expected out of the partnership include research into new recycling systems and lighting systems downtown that use less energy, perhaps in partnership with IBM.

UAB is also discussing the idea of creating a master's program in Sustainable Smart Cities, which would move forward with contribution from the deans and leadership of several schools across UAB.

For those interested in more information, other good sources include the UAB sustainabiltiy page and My Green Birmingham.

Image post 4: nanodiamonds may solve implant problem

While most posts from The Mix feature a science story, we have also begun sharing images coming out of UAB research. Here is an image of nanodiamonds currently being studied as a potential coating for artificial joints. UAB researchers are exploring whether such coatings can reduce wear on joints made of metal alloys. The work is important because more than 400,000 knee replacements and 300,000 hip replacements are performed each year in the United States.

The grinding force placed on joints causes the artificial versions to shed debris that can cause pain, limit mobility and hasten joint failure. Debris particles are absorbed by scavenging immune cells called macrophages, which then secrete chemicals that cause swelling and pain. This inflammation turns on bone-eating cells near implants, and bone-loss increases the likelihood implants will break loose and require a second surgery.

Diamond coatings may significantly reduce such shedding, and studies are underway to confirm that they are safe and effective. For more information on the work led by Yogesh Vohra, Ph.D.,  director of the UAB Center for Nanoscale Materials and Biointegration, read this 2012 article.

Jolie news highlights changing nature of mastectomy

Breast cancer cells

The world pays extra attention to diseases when celebrities have them, so it dominated the news this week when actress Angelina Jolie revealed that she recently had a double mastectomy. Tests had revealed she has the BRCA1 genetic variation known to drastically increase breast cancer risk. A sad detail in her case was her mother's death from the disease, which points to the interplay between genetic tests and family history when assessing risk.

The media did a good job of explaining that each case is different, and that women should make decisions with respect to breast cancer surgery in partnership with their doctors and genetic counselors. Included in the coverage was a fine piece by the Associated Press that described how women who make the same decision as Ms. Jolie now benefit from new approaches and technologies.

The nature of mastectomies has changed in recent years to save more of the breast, reduce scarring and pain and, in some cases, to enable breast reconstruction during the same surgery that removes the cancer. About 220,000 women are diagnosed with breast cancer each year in the United States, and 40,000 die.

We asked Helen Krontiras, M.D., co-director of UAB Breast Health Center and scientist at the UAB Comprehensive Cancer Center, for her take on the news and emerging trends in breast cancer surgery, which is her specialty.

Making it easier

Women who had double mastectomies in years past likely faced the removal of their entire breasts, including nipples and good deal of skin. They then faced a series of surgeries required to rebuild the breast with skin taken from the belly, construct a nipple and tattoo a ring around it.

Today, most women chose to have some degree of reconstruction done during the same surgery as their mastectomy, said Dr. Krontiras. For reconstruction requiring implant, surgeons must still, in many cases, put in expanders to stretch the skin for a time before a second surgery to put the implant in. Some patients go straight to implant at the time of mastectomy. According to the AP article,  about 25 to 30 percent of women nationally get immediate reconstruction.

Despite a growing focus on the cosmetic aspects of breast reconstruction, Dr. Krontiras emphasized that the first goal is obviously to remove all the cancer. Second to that, but still important, is the effort to preserve cosmetic outcome. In some patients, she starts with chemotherapy first to try to shrink the tumor to the point that patients become candidates for skin saving techniques. One factor making this possible is the increasing sophistication of chemotherapy against breast cancer based on the realization that breast cancer can be one of several cancers, with treatment now tailored for each patient's genetic make-up.

In addition, new approaches to mastectomy that save original nipples are gaining in popularity. Many studies now show that the rate of local breast cancer recurrence in patients that retain their nipple and areola are low and on par with older procedures that remove them, Dr. Krontiras said. Injections of body fat are used in some cases to fill in defects that may occur as a results of removing breast tissue.

Looking forward, women may one day benefit from an experimental out-patient technique called cryoablation. A liquid-nitrogen-cooled probe freezes bits of cancer to death, with the dead cancer tissue removed by normal bodily processes. The technique is currently being tested in clinical trials.

Talk it over

Jolie made the decision to have the double mastectomy because counseling revealed she had the BRCA1 gene, and because her mother had died of breast cancer. It has been reported that her health team told her she had an 87 percent chance of getting breast cancer.  Of course, such numbers are the opposite of universal, and vary greatly form patient to patient.

Dr. Krontiras recommends that women diagnosed with the BRCA 1 or 2 gene start with a discussion of options with their doctor and genetic counselor. Each patient’s risk for cancer will be managed by varying combinations of surveillance, chemoprevention and prophylactic surgery of breasts and/or the ovary.  There is no once-size-fits-all approach.

She added that she hopes the widespread attention generated by Jolie’s announcement does not lead to a whole-sale increase in requests for mastectomy. Genetic predisposition for breast cancer affects less than 10 percent of all women diagnosed with breast cancer.

However, women who do carry such a gene can have an up to 85 percent lifetime risk for breast cancer. Therefore, asking questions about family history are important, and patients need to learn about risk on both their mother’s and father’s sides of the family.

While the BRCA genes are important predictors of breast cancer risk, they are likely to be the first of many as yet undiscovered genetic and familial factors that contribute to risk, Dr. Krontiras said. Even those with negative BRCA tests should be watched closely if family members have developed breast cancer.
     
Women and family members interested in genetic counseling with respect to breast cancer can visit the UAB Cancer Genetics Clinic site. There is a website offered by The National Society of Genetic Counselors that has information about family history, as well as another by the National Cancer Institute on preventive mastectomies.  More commentary is available in this UAB news story and in this article and video from Medpage Today.

Image post 3: dangerous clumps of fungus

While most posts from The Mix feature a science story, we have also begun sharing images coming out of UAB research. Below is a brief description of what we are looking at and how related work may help to diagnose and treat fungal infections.

Here is a scanning electron microscope image of the fungus called Aspergillus. It's in the process of germinating, or emerging from round spores (at the center) to begin growing. The fungus has sprouted long, branching filaments called hyphae.

Most people breathe in Aspergillus spores daily without incident, but those with lung diseases or weakened immune systems can contract Aspergillosis, symptoms of which range from allergic reactions to severe lung infections. The fungus is a major player in some forms of allergic asthma, as clumps of hard-to-remove hyphae build up in the lungs.

According to the CDC, fungal infections pose an increasing threat to public health because of the growing number of people with weakened immune systems, including AIDS, cancer and transplant patients. In addition, treatment-resistant fungal infections have emerged as a growing problem in hospitals, and global warming may be contributing to an increase in infections, as fungi thrive in warm, moist conditions. Please see the CDC fungal page for more.

Current treatments are largely incapable of reducing morbidity and mortality in Aspergillosis, said John Kearney, Ph.D., professor in the Department of Microbiology within the UAB School of Medicine. He and his team are developing a new kind of vaccine that could provide protection against invasive Aspergillosis. Bacteria elicit a stronger human immune response than fungi but contain some of the same proteins (e.g. chitin). Based on these common building blocks, it may be possible to develop a vaccine where bacterial protein vaccine ingredients are used to activate immune cells that also target a fungus and remove it from the body.

This image was made by Dr. Jeffrey Sides from the Kearney laboratory at UAB using an instrument made available by the UAB School of Engineering.

Image post 2: Worm gonads and Lou Gehrig's disease

While most posts from The Mix feature a science story, we have also begun regularly sharing images coming out of UAB research. Below is a brief description of what we are looking at and how related work may help diagnose and treat Lou Gehrig's disease.  As we get more of these, we will add them to a slide show on the blog page and share them via Facebook, Tumblr and Pinterest.

This image is a dissection of a species of worm called  Caenorhabditis elegans (C. elegans), among the most famous of worms because it has made possible several discoveries in molecular biology. It did so by serving as a simple model of cellular processes conserved by evolution and still at work in humans.

The picture shows the worm's intestine running across the middele (in blue), which is working to provide fatty building blocks (e.g. omega-3 polyunsaturated fatty acid) to the worm's egg-producing cells (oocytes) in green. The egg-producing cells then convert the fatty acids into chemical cues called prostaglandins that help sperm find the sites (purple areas) where they can fertilize the eggs. C. elegans sperm in turn release a protein called major sperm protein (MSP), which tells the egg to prepare for fertilization.

Interestingly, the studies related to this image are providing key insights into how prostaglandins and MSP are made and function in humans.While MSP, for instance, was first found in worms and in connection with reproduction, it appears to have been put to work by human evolution in signaling roles in many cell types.

For instance, Michael Miller, Ph.D., associate professor in the UAB Department of Cell, Developmental and Integrative Biology, and creator of the attached image, last year published key work showing that MSP may be involved in the development of amyotrophic lateral sclerosis, or Lou Gehrig's disease. This unexpected connection may provide new approaches to diagnosing and treating the disease.

Note: if you have an amazing UAB research image you would like to share, please email me at gdw@uab.edu.

Bird flu: to fear and not to fear

I find it frightening when new strains of bird flu emerge somewhere in the world. Perhaps it's the combination of having two boys, knowing enough science to realize that a global pandemic is possible and having seen too many disaster movies like Contagion, Children of Men and Outbreak.

The Wall Street Journal reports that, as of last Saturday night, there were 120 confirmed cases of the latest strain of bird flu, H7N9, which has caused 23 deaths so far in mainland China. Last week, the virus spread for the first time outside of the Chinese mainland, with one case diagnosed in Taiwan. The virus is probably just a few small changes away from becoming a global threat, and yet the chances of that happening are very small. It makes for an odd mix of comfort and dread.

The Mix asked Ming Luo, Ph.D., professor in the Department of Microbiology within the UAB School of Medicine, to answer some common questions about bird flu, and about why its jump from birds into humans makes it dangerous. He also updated us on his work seeking to design new drugs against flu viruses. Bottom line: a vaccine for the new bird flu would take 6-10 months to get ready, and new classes of antiviral treatments are years away. Researchers will probably one day come up with a vaccine that protects us against all flu viruses, but until then I get jumpy as each strain emerges.

Q. Why are bird flu viruses so deadly when they jump into humans?

A. When humans are infected by a virus from another species, the human immune system has had no chance to develop any immunity against it, said Dr. Luo. Our immune cells do not recognize the new invader,and so cannot quickly ramp up a massive counterattack against them. The new flu virus is also dangerous because it appears to make copies of itself very quickly once inside human cells, and to cause more severe lung damage than does a typical flu virus.

Q. What are the chances that the new virus becomes a global pandemic?

A. This new H7N9 flu virus is closer to a human flu virus than all previously known avian flu viruses, which makes it easier for the virus to jump from birds to humans, Dr. Luo said. Should a few more mutations, small random genetic changes, occur in the virus, it could result in a virus that is passed from person to person worldwide. The last such pandemic happened in 1918. That said, the spread of current H7N9 virus has largely ceased, or has at least greatly slowed down. In its current form, it is very unlikely to become transmissible from human to human, Dr. Luo said.

Q. Why are poultry versions of influenza viruses spreading now as opposed to 20 years ago?

A. Researchers see more cases of human infections by avian flu viruses because of increased density of the human population, more global travel and more consumption of live poultry in large cities in places like China.

Q. How would you rate the current government/health care surveillance systems designed to catch and isolate new cases of new flu viruses to prevent their spread?

A. The global surveillance system worked very efficiently in this latest case. Within weeks of the first infection, the new H7N9 virus was identified, and the information was shared globally so that any new case could be identified around the world. Authorities in places like Hong Kong are shutting down and sterilizing live poultry markets, and health authorities are watching for and isolating cases.

Q. What kind of birds are spreading the virus to humans?

It looks like chickens as opposed to migrating birds, which are often the vectors that spread viruses through poultry populations.

Q. What advances have been made in the field that promise to deliver new treatments in time to prevent an influenza pandemic?

A. To develop a H7N9 vaccine will take 6-10 months, said Dr. Luo. There is always a long delay in developing a flu vaccine against a new strain. Preliminary efforts are underway to develop a universal flu vaccine, but it may take years.

A. Antiviral drugs will, in the future, represent another effective alternative to prevent and treat flu infection. Preliminary tests showed that this H7N9 virus is sensitive to currently available drugs in the class called neuraminidase inhibitors, including Tamiflu, Relenza and Peramivir, the latter of which was developed in a partnership between UAB and the company BioCryst. Many governments participate in antiviral drug stockpiling programs in case of pandemic infection.

Note: BioCryst and UAB have had a close relationship since BioCryst was founded. Former BioCryst CEO, Dr. Charles E. Bugg, was also a past director of the UAB Center for Macromolecular Crystallography. Former BioCryst CEO, Dr. J. Claude Bennett, was previously UAB President. Several of BioCryst's early drug development programs originated at UAB. Currently, BioCryst has research agreements in place with UAB focused on influenza neuraminidase and complement inhibitors.

Q. What is neuraminidase, and why do current antiviral drugs seek to inhibit it?


A. Neuraminidase is a viral enzyme located on the surface of flu virus particle. Neuraminidase inhibitors are drugs that bind to neuraminidase tightly and shut it down, which stops the ability of flu viruses to spread from cell to cell.

Q. I understand you are working to develop antiviral therapies that block the ability of influenza to fuse with and enter a human cell on the way to turning human cells into virus factories?  What progress are you making in that design effort, and what’s next?

A. Neuraminidase inhibitors target a viral protein called neuraminidase, but this protein regularly changes shape in quickly evolving viruses. These shape changes could eventually enable flu viruses with mutated proteins to become resistant to all current neuraminidase inhibitor drugs. Thus, the field is striving to develop drugs that target different viral proteins as a backup.  Dr. Luo's lab is working on fusion inhibitors that target a viral protein called hemagglutinin, and by blocking it, take away the ability of a virus to enter into human cells. In the lab, our fusion inhibitors block cell infection by many strains of influenza virus, including those already resistant to neuraminidase inhibitors. We are testing this class of novel inhibitors in animal studies.

Q. How would the viral fusion inhibitors you are working with complement neuraminidase inhibitors?

A. Our studies already showed that influenza viruses that are resistant to neuraminidase inhibitors are sensitive to our fusion inhibitors. The two classes of inhibitors target two unrelated viral proteins so changes in one may not affect the other. When two drugs target a disease process via independent mechanisms, they can in some cases be combined in potent antiviral drug cocktails.

Note: the H7N9 name of the newly emerged bird flu strain refers to the versions of hemagglutinin (H) and neuraminidase (N) found to be specific to the virus, and more precisely, to the fragments of those proteins that trigger our immune systems to respond to them.

Q. How long before human testing can start with your clinical candidate drugs?

A. We are testing these fusion inhibitors in animal models now. If it works in an animal model, it will still take years before human testing can begin for the new drugs. We need to begin studies of new drugs long before new threats of pandemic flu appear.

For the most recent updates on bird flu, see the Disease Outbreak News bulletins from the World Health Organization.

Goal: keep your transplanted organ permanently

Unless you have an identical twin, needing an organ transplant comes with a serious problem even beyond the fact that you need a transplant. Assuming the surgery goes well, the minute the new organ is grafted into your body, your immune system will recognize it as foreign, akin to invading bacteria, and seek to destroy it.

Taking the kidney for an example, there was a time 25 years ago when half of kidney transplant recipients lost their transplant due to immune rejection. The field of transplant immunology has in recent years become very good at preventing this during the first year after transplant using drugs that turn down the immune response, but long-term rejection remains commonplace.

The immune systems of many organ recipients eventually destroy transplanted kidneys over ten to 15 years. Worse yet, patients live through those years with a suppressed immune system; making them vulnerable to viral infections, some of which cause cancer.

Research efforts to solve these thorny, remaining problems in transplant immunology continue, but the field is under duress thanks to cuts in federal research funding, says UAB's Rosyln Mannon, M.D., director of research at the UAB Comprehensive Transplant Institute and a kidney transplant specialist. She was among the organizers of a recent transplant immunology symposium held by the institute.

Dr. Mannon sat down with The Mix to talk about research frontiers in transplantation, including efforts to design drugs that precisely turn down the activity of immune cells involved in transplant rejection, while ignoring those that fight infection.


Show notes for the podcast:

1:05  As we develop in the womb, special proteins are built on the surfaces of all our cells that serve as tags that say "self," and thus keep our immune cells from attacking them.  A transplanted organ obviously has different cell-surface, protein labels.

1:31  When surgeons put in a transplanted organ, the proteins labels on the organ surfaces are picked up and carried by immune cells to nearby lymph nodes, where they trigger the building of an army of cells designed specifically to attack the new organ. Several sets of immune cells are swept up into the effort to destroy the transplanted organ (also called a graft), including T cells and antibodies, two workhorse cells of the adaptive immune system.

1:47 Thus, the response to a transplanted organ that immunologists must deal with when preventing transplant rejection includes a mix of proteins, including antibodies that glom onto and remove foreign cells,    and cells that swarm to the transplant site and release destructive chemicals (e.g. cytokines).

3:15 The field of transplant immunology has been "incredibly successful" at preventing acute transplant rejection in the first year after the transplant using a subtle, powerful mix of drugs that damp down the immune system to protect transplanted organs.

3:39  The average person who receives a kidney this year from a diseased patient can expect the graft to last ten years. If the organ came from a living donor, the transplant may continue to function for 15 years, and especially if the organ came from a well matched family member. Despite these advances, all patients see their transplants fail eventually. About half of them "fail" because the patient dies, some from heart disease. Others organs fail because the medicines taken to suppress immune systems leave patients vulnerable to infection.

4:20 Physicians typically take a biopsy of a failing kidney to see why it has failed after working well for so long. In some cases, the slides will reveal that the immune system finally overcame immunosuppressive drugs to recognize the transplant as foreign and attack it. Interestingly, sometimes it will be one part of the immune system that finally tracks down the organ (e.g. antibodies), and sometimes another (T cells).  In still other cases, the biopsy may reveal that a longtime, undetected viral infection has destroyed the organ, or maybe it was fibrosis, the wear-and-tear scarring that comes with age.

5:15 The failure of organ transplants many years after implantation for these varied reasons is the central, remaining problem facing transplant immunologists and their patients.

5:43 The drugs used to suppress the immune system on the way to protecting a transplanted organ have evolved. In the old days, transplant recipients received steroids like prednisone (an anti-allergy drug) and drugs called anti-metabolites. In the mid-1980s, a set of drugs called calceneurin inhibitors arrived, including cyclosporin and then later Prograf. Most patients in those days got large doses of drugs like these, some of which themselves scar the kidneys. Other risks of such therapy included knocking the immune system thoroughly enough to encourage viral infections like the Epstein-Barr virus, cytomegalovirus and related cancers viruses.  The latter make random genetic changes in the cells they infect, some of which accidentally cause the abnormal growth seen in cancer. Presentations at the recent symposium talked about ways of fine-tuning immunosuppressive treatments to minimize damage related to their use.

7:47 Newer FDA-approved treatments appear to have fewer side effects, but still have the same problem as older drugs: they knock down the immune system broadly instead just the cells attacking the new organ. All physicians can do is gradually reduce the dose of immune suppressing medications over time under the assumption that the immune system has come to see the transplant as self, but doing so may result in the late-stage rejections currently observed five and ten years down the line.

8:53 Frontiers in the field include research efforts to design therapies that influence only the subsets of immune cells most associated with transplant rejection. Certain kinds of immune cells "remember" they have encountered a foreign protein, for instance.  Therapies may destroy most of those cells, but those that remain eventually become capable of re-launching the attack on the transplant.  On the other hand, one subset of T cells, called Tregs, are known to damp down the immune response in a careful way. What if engineers were able to deploy a person's own Tregs to damp down response to specific proteins on the surfaces of transplanted tissue?

10:11  Research efforts looking suppressing specific immune mechanisms, while the future of the field, are still in the early phases. Dr. Mannon hopes they suppress more surgically than the global suppression seen with older drugs.

10:45  The recent UAB transplant immunology symposium was timely, said Dr. Mannon, because UAB has been working to establish a collaborative consortium of transplant centers in the Southeast. UAB is one of the largest clinical transplant centers in the country, as is its partner in this symposium, the Emory Transplant Institute. Vanderbilt and the Medical College of South Carolina also have a strong interests in this area. The symposium was the first forum to identify and discuss the central, remaining problems in transplant immunology, and to launch joint efforts to solve them.

11:15 Among the research frontiers discussed was how best to arm patients with the ability to fight off infections without jeopardizing their transplants. One way may be to harness the bacteria that live in the human gut. What role do the bacteria that permanently colonize the body have in the immune system and transplant rejection? Can the interaction between our gut bugs and antibiotics for instance be manipulated to improve long-term outcomes of transplant patients by damping down system-wide inflammation?

14:24  Dr. Mannon is the newly elected president of the American Society of Transplantation, the second president in a row to come from UAB after Dr. Robert Gaston, M.D.  UAB has for years been recognized across the Southeast for the large volume of clinical transplant procedures done here, but having the presidency sends a message to the nation about the strength of the basic and translational research underway.

15:45 The society has been very active on Capitol Hill in terms of lobbying for the support of related research, and that stance will continue during Dr. Mannon's term. As for the group's legislative agenda, they have been trying for 12 years to get a bill passed that would provide coverage for immunosuppressive therapy for the life of those with kidney transplants. Currently, Medicare pays for such medications for three years after the transplant, after which medications the become prohibitively expensive for those without private insurance. Another bill would ensure that those who donate a kidney to another person cannot have their coverage dropped by an insurer after they give the gift of life.