Biotechnology: a tale of possibilities
As the science advances and humans help happenstance plot the future, both miracles and misdeeds will result, JMU experts say
Last year, when the governor of Virginia created a task force to make the commonwealth a center for the biotechnology industry, he hastened the dreams of the founder of a new JMU lab. This professor wants to see biotechnology training and manufacturing morph the Shenandoah Valley into a 21st-century Silicon Valley or Research Triangle Park with JMU as its nucleus.
That heady vision belongs to Bob McKown, who last fall received the 2002 Educator of the Year Award from the Virginia Biotechnology Association. McKown teaches biotechnology to integrated science and technology majors and opened JMU's Biomanufacturing Laboratory just over a year ago. Biotech leader Brandon J. Price, who co-chairs the advisory board for Gov. Mark Warner's Virginia Biotechnology Initiative and chairs the Virginia Biotechnology Association, calls JMU "second to none in the commonwealth and maybe in the whole country" in teaching skills for the new industry. Citing the popularity of the biotechnology subspecialty for ISAT majors, McKown says, "I think we'd be in a unique position to lead in education."
Biotechnology manufacturing means creating products from living organisms, which means JMU's future may be linked to tinkering with DNA -- genes -- the stuff of life. Such talk often evokes visions of a hunger-, disease- and crime-free utopia on one hand and cloned humans, mutant species and eugenic societies a la Brave New World on the other. While JMU's role might not mature for some years, these and other sensationalist visions point out the need to discuss what the possibilities really are.
JMU professors and alumni scientists confirm that biotechnology could, in fact, help feed the world's hungry with vastly increased yields from pest- and disease-resistant crops. Alternative fuels like hydrogen for fuel cells and new plant life made into ethanol could curb global warming and save scarce fossil fuel resources. In medicine, these experts see a future of designer drugs tailored to individual needs, prenatal tests to predict illnesses and cells that grow into replacement neurons or even major organs.
These same JMU experts, however, warn that technology based on genetic research could also lead to tougher pests, less biodiversity, deadlier bioterrorism and increased economic disparity, while threatening privacy and the sanctity of life.
Yet, as humanity finds itself wrestling with expanding definitions of evolution and identity and its increasing role in directing nature, JMU's scientists and professors make clear that the future of bio-technology will not be all good or all bad. "Probably some of each," says JMU philosophy professor Rick Lippke, who teaches medical ethics. "There is, after all, the profit motive, and that could lead people to use the knowledge for good or bad purposes."
As biology professor Chris Rose sees it, "Science is a human endeavor, and so there is always the potential for harm resulting from unpredicted results or byproducts of the science, or the science falling into the wrong hands, or the science simply getting out of control." His course, Biology in the Movies, helps students sort the horror fantasies from more credible cinematic forecasts.
Whatever the specifics of a biotech future, it is already beginning on campus. In a darkened room in McKown's biotech manufacturing laboratory, bacteria in a petri dish glow green. ISAT majors have spliced them with fluorescence genes from jellyfish; this year, their project is being turned into a basic curriculum exercise for fellow students. Those who select biotechnology -- one of the most popular ISAT specialties -- get to complete hands-on, real-world, mentored research. The 13 students who completed programs during the lab's first year of operation developed products for two pharmaceutical companies.
Last summer, JMU student Amy Goss received a Research Experience for Undergraduates award from the National Science Foundation for her work in McKown's lab. Students and professors there are collaborating with a University of Virginia lab directed by Gordon Laurie, who discovered a new human protein that might be used to treat dry eyes. McKown says they are working together "to clone, express and purify this protein so it can be tested in animal systems."
The biology department, meanwhile, is exploring the possibility of offering a biotech major with ISAT. It would be one of about 15 in the nation. "Biotechnology and specifically genetic engineering are important components of an undergraduate education in modern biology, says biology department head Murray Nabors. "The job market is good and will probably improve for students with expertise in these fields."
Biotech training is crucial, McKown says, because "Very soon, lifesaving products won't reach the market because of lack of manufacturing capacities." As demands increase, he hopes Harrisonburg-area businesses like Merck and Coors will expand their capacities to plunge into the industry, fed by JMU-trained work forces.
Bringing a new biopharmaceutical to market requires an investment in research, development and startup of around $400 million. And, adds JMU economics professor Bill Wood, the basic research preceding application is even more expensive and financially risky. Typically, it requires government funds, funneled through universities, "the ideal place for research," Wood says.
In addition to bringing biopharmaceuticals to market, such research holds even more prospects for life-sustaining products. Wonder foods, for instance -- pest-, disease- and drought-resistant crops -- could feed millions. Cindy Klevickis, who teaches genetics at ISAT, points out that about 50 percent of our groceries already contain unlabeled, gene-altered ingredients that make farming returns more predictable and food-manufacturing profits higher. Whether fears about long-term effects of ingesting such products prove justified, she feels "people have a right to know."
When it comes to these genetically altered foods, Wood notes, "The risks are unknowable. There are things we don't know until we do it on a large scale. But the productivity gains are real. That's why you can't just shut the door."
Altering genes did not begin with human expertise, of course, notes biology professor Jon Monroe, the 2001 recipient of the American Society of Plant Biologists' Excellence in Teaching Award. "Plants evolve chemically because they can't run away, so they produce all kinds of nasty things. The herbs and spices you cook with probably evolved as defenses."
Working with undergraduates, Monroe finished sequencing a gene, Aglu-1 on the Arabidopsis thaliani genome, in 1996. This mustard-like weed remains the only fully sequenced plant. Now Monroe seeks the function of the enzyme produced by his gene: alphaglucosidase. This biologist calls his work basic science -- discovery, not applications. Yet there is a possibility that alphaglucosidase may retard fungus. If so, Monroe's findings could apply to future crop engineering.
"The potential benefits are far greater than the downside," he says, but concedes that toxic chemicals could produce hardier pests and over-reliance on a single miracle hybrid could lead to the devastation of an entire crop by one equally powerful patho-gen. "If everybody's planting the same thing, a pathogen could come in that would wipe it all out."
Debate over the wisdom of substituting human judgment for the randomness of nature should not presuppose human intervention is something new. "People have been improving plants and animals for thousands of years, since the dawn of agriculture, by selecting the best plants and animals to use as a source of germ plasm for the next generation," biology's Nabors says. "People have also been moving apparently useful plants and animals from their natural habitats to locations around the world. Both of these activities have caused environmental problems. Genetic engineering seeks to improve plants and animals, but in a more technological fashion than traditional methods. It's simply a logical next step to plant and animal improvement."
What happens, however, if plants genetically altered by humans naturalize and displace native plant life -- or if a glowing squirrel escapes to crossbreed with native squirrels, making the entire population more visible to predators?
Risks may be minimized by making such altered organisms sterile, notes Betty Mansfield ('75, '86M), team leader of the Human Genome Management Information System in Oak Ridge, Tenn. The downside, say critics of crop manipulation, is that sterile, genetically manipulated seeds leave farmers dependent on suppliers. A benefit from sterile products, however, could come from a different use -- as "biomass," says Mansfield. Trees such as poplars, tweaked to grow thicker and faster than natural specimens, may be pulped to make ethanol. Such energy biomass may reduce fossil fuel and petroleum dependence and, thereby, global warming. The Department of Energy's Genomes-To-Life project, which builds on the Human Genome Project 2000's sequencing, funds biomass research, says Mansfield, who worked in cancer research before taking on her current role at Oak Ridge.
HGMIS is the educational outreach arm of the federally funded Human Genome Project. Contrary to misperceptions, Mansfield says its work by no means ceased once the HGP draft was published and made big news. In fact, it opened up a host of research questions. Mansfield, who claims six family members as JMU graduates, is founder and managing editor of Human Genome News and maintains Web sites on genetics directed both to scientists and the lay public. They can be found at www.ornl.gov/hgmis and www.DOEGenomesToLife.org.
As both a scientist and a communicator of science, Mansfield is well aware of the possibilities and limitations of biotechnology. She and Klevickis look forward to custom-made "designer drugs," which Mansfield hopes will reduce trial-and-error medical tests. Klevickis foresees tests "to diagnose exactly which part of the neuron is defective. We can design drugs based on the molecular structure of the protein itself." If a disorder results from a neurotransmitter being slightly too short, therapy might lengthen it.
Most new knowledge entails trade-offs, other JMU alumni point out. Predicting disease can present hard choices. At Alfigen Inc./The Genetics Institute, in Pasadena, Calif., genetics counselor Megan McCoy ('97) assists couples expecting children and concerned about family histories. They select tests that screen for muscular dystrophy and mental retardation. What can parents do when embryos test positive? "The bottom line is, it's never my decision," says McCoy. She links clients with support networks.
At Fairfax's Preimplantation Genetics Diagnosis Laboratory, by prior agreement parents are never told if they have the Huntington's trait, but only Huntington's-free embryos are implanted, says Gary Harton ('87), Genetics and IVF Institute director.
People fear that all this intimate genetic knowledge, once gained, might find its way into the wrong hands. Neither McCoy nor Harton have encountered insurers, employers or police demanding records -- yet. McCoy, however, has heard of patients avoiding genetic tests or paying cash for them, because they fear discrimination by insurance companies or employers based on the results. Mansfield, citing ways medical records are shared now without patients' consent, thinks science is making privacy legislation urgent. Discrimination, she notes, could affect anyone.
Rose poses a question central to practitioners and consumers of biotechnology: "Just how much correlation will be found between genes and such traits as alcoholism, athletic ability or intelligence?"
In the National Institute of Mental Health Laboratory of Genetics, Jason Inman ('99), an ISAT graduate and Johns Hopkins University doctoral candidate, uses microarrays to probe "what genes are turned on or off in a given tissue." He thinks research will improve treatment of mental illness, not eradicate it. "The complexity of the mind is incredible," he says, and "many causes of mental illness [like trauma] are external," not genetic.
Mansfield asks, in fact, "If we knew the genes associated with certain forms of depression and could wipe them out of the population, should we do that?" Noting the recessive gene for sickle cell anemia helps bearers resist malaria, she says, "When you enhance one trait, you might mess something up. There's something to be said for random happenstance."
Even now, Rose notes, humanity is circumventing natural selection: "The rate at which the environment is selecting us is very, very low." How much lower should it go? And how much should we expect from gene improvement alone? Klevickis notes, even identical twins do not show 100 percent correlation for such genetically linked disorders as diabetes, autism or schizophrenia.
Actually, says Rose, "The problem is that at the genetic level we are all different." McKown notes that spots on the cloned cat, "CC," differ from those of her genetic mother, "Rainbow." It's more complicated than just having the gene and making it."
Rose, reflecting on a gene therapy trial subject's death at Johns Hopkins, warns that until scientists know more about the
1 in 1,000 genomic base pairs that differ between individuals, "It is impossible to predict how their protein products might interact with the products of new genes."
Should such engineered interactions succeed, Mansfield says, "Theoretically, you could replace any part of the body." Liver replacement might be completed with a mere needle-stick. Mansfield does not expect such science to make humans immortal, however, nor even provide us wings or exoskeletons.
But it does present humans with some tough issues. Public debates often confuse therapeutic cloning (reproducing cells to replace damaged tissue) with reproductive cloning (making new animals, such as "Dolly" the sheep and perhaps one day, new people. (At press time, scientists remained skeptical of Clonaid's unsupported claim to have produced the first human clone). The federal government has restricted re-search with embryonic stem cells, which could grow into any kind of tissue. Yet early embryos are routinely set aside in IVF labs such as Harton's, where discarded blastomeres -- embryonic pre-stem cells -- are used to test new diagnostic procedures. Though such research has critics, Harton says, "We're helping people."
Klevickis attributes controversy to misunderstanding: "Maybe people would be more receptive to the idea of cloning if they knew that what researchers want to do isn't cloning babies, but taking a single cell and culturing it into a neuron, pancreatic cell or other cell type in a way that would help with Parkinson's disease or diabetes."
Yet fears persist. Lippke recalls that when in vitro fertilization appeared in 1978, "Many people were hysterical about it, the way they are now about human cloning." In both cases, critics have charged that "we are 'playing God' or interfering with nature. But we've done that for a long time. As I point out to students, almost all medical treatment interferes with nature. The body is trying to kill us. We try to stop it. Presumably that's not a bad thing."
JMU chemistry professor Barbara Reisner has incorporated such issues in a biotechnology unit this semester for her chemistry-majors' course, Ethics in Communication and Science. Once students read up on stem-cell research and cloning, Reisner may have them "take an issue out of a hat and argue why this is a good thing or a bad thing."
Rose's film course explores issues via Hollywood. "The most reasonable scenario of how things could go wrong is presented in Gattaca," he says. The 1997 production depicts a genetically engineered aristocracy, the "Valids," exploiting a naturally born underclass, the "In-Valids." "Society may use genetic screening and genetic engineering for frivolous [cosmetic] or immoral [eugenic] purposes," Rose explains, while shrugging off themes about mutant races and "cloned Hitlers."
By preference, most ethicists and scientists say "better health care, yes; 'designer babies' [with talents and appearance produced on spec], no." Wood suspects the latter will someday emerge: "My instinct as an economist teaches me that when something becomes possible, and people will pay a lot, it will happen." Harton says not to look for such infants any time soon, though: "It's not like a gene determines how tall you're going to be, or your hair color. It's a series of genes, and no one knows yet how they work."
Whatever biotechnology produces, fortunes are an expected byproduct. In medicine, which now supplies more than 90 percent of biotech revenues, McKown notes the worth of a drug developed in a living organism far exceeds that of gold or diamonds. "It's infinitely renewable. You've got a monopoly."
And what of the millions who cannot afford it? Mansfield says, "In the end, genetics could make the practice of medicine cheaper." Wood explains, "Early in its life, a new technology worsens inequality. Later, it reduces inequality" as supplies increase.
Health care inequalities did not begin with biotechnology, of course. Ditto for bioterrorism. Rose notes wayward scientists, trained in biological weaponry during the Cold War, could find ways to make trouble using DNA -- just as they can wreak havoc with old-fashioned viruses.
None of JMU's experts seem certain of a biotech paradise, nor are they ready to slam the door on a Pandora's box.
"There is an old saying that 'with power comes responsibility,'" recalls Inman, "but who and what determines the responsibility, and how to deal with those that shirk the responsibility, is a difficult matter." Economist Wood mentions an obvious, though elusive, answer: "What is needed is an ethical population." Chemist Reisner admits to misgivings about cloning, but says, "I have an optimistic view of humankind. I think they'll do the right thing." Mansfield agrees: "There are at least 1,000 unsung Mother Teresas for each Hitler that humankind produces."
Students, meanwhile, prepare for a brave new, uncertain future. Those in McKown's ISAT lab isolate their own DNA to check whether they have a "junk DNA" insert, ALU. Rose's lab students assist research into how genes control amphibian development. They use thyroid hormone to speed transformations in salamanders and frogs, while studying tadpoles implanted with extra jaw cartilage.
Klevickis' Computer Applications in Biotechnology students illustrate three-dimensional protein structures with molecular graphics. Numbers on a screen segue into a revolving, rainbow structure linked to a double helix. Her Human Genetics students probe such puzzles as "What makes a male a male?" and "Mitochondrial DNA -- the Neanderthal mystery."
Like other JMU professors, Klevickis says she emphasizes research methods: "It's changing so fast you don't want to learn just facts."
Learn more about Betty Mansfield and the Human Genome Project. Go to www.jmu.edu/montpelier/monty/GenesAndFamilyLinks.shtml for more information.
Story by Chris Edwards, Photos by Wayne Gehman, Design by Leah Bailey ('00), Illustration by Scott Trobaugh ('98)