A Research Revolution in the Life Sciences
October / November 2004
Volume 2 Number 5
It seems just like yesterday that R&D meant faster computers, smarter industrial robots and more sensitive analytical equipment. However, a downsized space exploration program and the ending of the Cold War caused dramatic changes in our R&D focus and needs. Now, rather than hardware, spectrum analyzers and heat-resistant ceramics, researchers are now inventing new ways to improve healthcare, cure disease and protect the environment.
Already, the impact of the applied life sciences on our everyday lives is amazing and far reaching. Advancements range from improving the ancient fermentation methods used to make bread, wine and cheese to developing the technologies used to make genetically engineered insulin and hepatitis B vaccine and "smart" joint implants. These and other research and development innovations are already helping to solve a wide range of complex health, safety and environmental problems.
It is also important to remember that these efforts require the expertise and talents of broadly educated scientists, engineers and technologists. To meet the growing need for appropriately trained and educated employees, associate, baccalaureate and graduate degree-granting institutions are developing cross-disciplinary programs in biomedical engineering, bioinformatics, computational biology and biotechnology. This sort of commitment improves community quality of life by developing a competent and well-paid workforce and by generating long-term commercialization opportunities.
Biotechnology and Genomics
It took scientists nearly a century to learn enough about genetics, DNA and cell physiology to make the transition from purely exploratory research to developing commercially valuable products. In combination with the robotics and powerful computational algorithms developed at public and private research institutions such as the Los Alamos National Laboratory and the Institute for Genomic Research in Rockville, Md., scientists can rapidly make billions of DNA copies from single molecules and then dissect and interpret DNA-encoded information.
Called genomics, this technology has already produced nutritionally improved food crops, plants that require less water, fertilizer and pesticides, pharmaceuticals to treat infections and cancer and microbes able to convert toxic pollutants into environmentally safe substances.
The world's four largest biotechnology centers are San Francisco, Boston/Cambridge, Baltimore and San Diego. Recent figures from the California Healthcare Institute show that just in California, medically related biotechnology and medical device companies account for more than $13 billion in wages and more than $6.5 billion in private and federal research funding. In the United States, there are more than 1,300 biotechnology companies that employ more than 153,000 people in high-wage jobs.
Radioactive tracers
Genomics is just one of many applied life science innovations. The ability to use cyclotrons to make safe radioactive tracers to diagnose, treat or monitor conditions such as cancer, cardiovascular disease and thyroid abnormalities is a classic example of successful technology transfer and commercialization. The atom bomb and particle physics research, pioneered in the 1940s at the Oak Ridge National Laboratory, gave rise to the radioactive tracers clinicians now use to diagnose or treat one out of three hospitalized patients.
Medical Imaging
Medical imaging is another exciting applied life sciences field. Evolving from research in the basic sciences, clinicians now have a virtual palette of nondestructive medical imaging technologies. Medical imaging modalities such as X-rays, magnetic resonance (MR) and computerized tomography (CT) allow doctors to see the structural causes of health problems without having to do exploratory surgery. While these imaging modalities produce detailed and exquisitely beautiful images of internal body structures, certain MR and CT procedures require contrast media injections to highlight specific features such as brain vasculature or the intestines.
A new generation of contrast media that contain biological probes that ferret out and bind to tumors or compromised cardiovascular tissues will make medical imaging an even more powerful molecular imaging tool. One new MR technique, receptor-induced magnetic enhancement (RIME), uses biological molecules conjugated to contrast media substances to diagnose cardiovascular disease. Already undergoing Food and Drug Administration safety and efficacy trials, RIME may eventually replace a large percentage of the 4.5 million invasive angiograms performed each year in the United States.
Information Technology
Medical imaging procedures generate more than 400 million patient records per year. Today, hospitals and other imaging facilities use picture archiving and communication systems (PACS) to meet the challenge of interpreting, storing and retrieving this formidable number of data-intensive medical reports.
Because of high-resolution digital imaging systems, many facilities no longer use film as the archival media. In addition to being a space saver, digital imaging and PACS offer many advantages. Doctors can easily retrieve, view and compare medical images. Secure internet communication lines gives people in rural or medically underserved areas nearly instantaneous access to medical center expertise.
Pharmaceuticals
The development of new pharmaceuticals is another exciting and productive research area. Rational drug design, a method first developed in the late 1940s by Nobel Laureates George Hitchings and Gertrude Elion, at Glaxo Smith Klein (formerly Burroughs Welcome) in North Carolina's Research Triangle, uses biological clues rather than random testing of natural and synthetic substances, to guide the synthesis of new pharmaceuticals. Today, rational drug design protocols include using genomic, structural analysis and virtual molecular modeling tools to construct the pharmaceuticals used to treat conditions such as osteoporosis, anemia and the antimicrobial agents used to treat antibiotic resistant infections.
Some genically engineered products already on the market include Forteo® to treat osteoporosis and Epogen® and Ananesp® to prevent the severe anemia caused by life-saving kidney dialysis and cancer chemotherapy treatments.
Epidemiologists estimate that 45 percent of all postmenopausal women have decreased bone mass and are at increased risk for osteoporotic bone fractures. Therefore, drugs to prevent or control osteoporosis both improve the public's health and reduce medical and societal costs.
Because severe anemia is a common side effect associated with kidney dialysis and cancer treatment, red blood cell-boosting medications play an equally important role in improving patient quality-of-life.
Collaborative research between scientists working at the University of Chicago, and the Argonne National Laboratories has revealed a new antimicrobial target. Stortase B is a bacterial enzyme responsible for harvesting iron, a nutrient bacteria need to grow, from human red blood cells.
Structural analysis of sortase B isolated from Staphylococcus aureus (a common cause of skin and blood infections) and Bacillus anthracis (anthrax) is helping scientists understand the relationship between enzyme shape and function.
Eventually pharmaceutical chemists will use this information to make antimicrobials that prevent or cure infections by interfering with iron-harvesting activity. This new antimicrobial class may also improve our ability to treat antibiotic resistant infections.
Biomedical Engineering
Novel ways to treat bone infections or osteomyelitis demonstrates how advances in biomedical engineering can solve difficult medical problems. Bone infections become chronic infections when thin layers of bacteria attach to tissues, support screws and hip and knee replacements. Called biofilms, microbes living within the biofilm matrix are less sensitive to antibiotics and disinfectants than free-living bacteria.
The risk of infection for total joint replacement surgeries ranges from 1 to 3 percent. With more than 400,000 knee and hip replacement performed each year in the United States, infections cause nearly 12,000 patients to endure longer or repeated hospital stays, long-term antibiotic treatments, additional surgeries and amputations. Devising ways to prevent microbial biofilm deposition is an active research area. Medical scientists are evaluating the effectiveness of giving patients protective antibiotics before and after surgery and of using of antibiotic-impregnated glues to attach artificial joints to bones.
Scientists are also developing "smart" hip and knee replacements that can recognize and respond to the first signs of a bacterial infection.
Allegheny-Singer Research Institute scientists in Pittsburgh are designing microelectronic mechanical systems, or MEMS, microbial detection systems. These scientists envision that MEMS devices on the joint implant surface will signal imbedded microchips to release antibiotics as soon as they detect bacterial waste products. While there are many engineering and logistics problems left to solve, using MEMS as a way to control biofilms is an intriguing technology with unlimited medical and industrial applications.
Clinical Laboratory
Point-of-care screening tests identify patients who need sophisticated testing procedures. For example, the urine dipstick test-strips found in nearly every primary care office, are a fast and inexpensive way to check all patients for indicators of urinary tract infections, diabetes and kidney disease. This simple procedure, based on abnormal or positive urine dipstick results, identifies those patients who need to undergo the costs and inconveniences of diagnostic laboratory tests.
Novel medical imaging procedures are providing new ways to detect infections without having to perform invasive or time-consuming microbial assessments.
Scientists at Palatin Technologies, located in Cranbury, N.J., are using target-specific monoclonal antibody molecules attached to technetium (a radioactive probe) to diagnose appendicitis, postoperative abscesses and diabetic osteomyelitis. Each year, nearly 500,000 people come to emergency rooms and physician offices with symptoms of appendicitis. Although physical examination and blood tests will indicate that nearly half of these patients require surgery, post-surgical inspection often reveals a healthy appendix.
Studies show that Palatin's product effectively binds to the blood neutrophils that accumulate at infection sites and reliably identifies people who are in the early stages of potentially serious infections. Therefore, doctors can now use medical imaging as a way to identify patients who truly require an appendectomy.
Because this is a very sensitive procedure, doctors can safely discharge those who have negative NeutroSpec® scans. In addition to reducing medical costs, this type of screening procedure helps people avoid unnecessary surgery.
Biological warfare
Our nation's experience with domestic terrorism has demonstrated the need for new molecular imaging tools to identify exposure to weaponized microorganisms such as anthrax spores. Researchers at Walter Reed Army Medical Center have tested NeutroSpec® as a way to image and identify inhalational anthrax infections. Advantages of this screening method include the ability to both evaluate asymptomatic patients who may have been exposed to anthrax and to identify early stage anthrax before it worsens and becomes difficult or impossible to treat.
Environmental
Genetically engineered crops are playing increasingly important roles in protecting the environment and improving health. From tobacco plants able to remove and degrade toxic polychlorinated biphenyls (PCBs) from contaminated soils to innovative ways to ensure the safety of our surface, ground and drinking water supplies, the applied life sciences are providing new ways to remediate and protect the environment.
The Clean Water Act is a complex collection of regulations and standards that local municipalities must follow to protect water from chemical and microbial pollutants. Protecting water from microbial contamination originating from wild and domestic animals and humans is a complex and expensive undertaking.
Environmental microbiologists use chemical, biochemical and bacterial source tracking methods to determine fecal pollution sources. Molecular methods include testing water for caffeine, an indicator of human waste, biochemical tests that differentiate strains of fecal bacteria and bacterial source tracking to identify community-specific antibiotic resistant bacteria.
Unfortunately, these techniques are expensive, labor intensive and require highly trained personnel. Since these studies play an important role in protecting the public's health and environment, developing more cost-effective methods is high priority research.
Limiting dependence on non-renewable fuel sources is another compelling need.
For many years, Germany, a world leader in biofuel development has used a mixture of rapeseed oil and methanol to fuel electricity and heat-generating power plants. By 2005, all European Union fuels will contain a mixture of non-renewable petroleum sources and biological fuels such as rapeseed oil.
Making this transition will be a challenge. In addition to fuel production and distribution considerations, fuel users need equipment that can handle sticky rapeseed oil resins.
Janet Yagoda Shagam, Ph.D., is a teacher and freelance writer based in Albuquerque.
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