Engineers are fighting disease and building healthier people, but tough questions have yet to be answered.

By Joannie M. Schrof

While millions of people are eating carrots and tofu, sweating their way through workouts, and downing herbal concoctions in hopes of living longer, healthy human cells are just lounging around in petri dishes in Menlo Park, California, enjoying immortality, thanks to the biologists who decoded the aging mechanisms in the cells' DNA. Up the coast at the University of California, San Francisco, geneticist Roger Pederson leaves a collection of "stem" cells-the human cells that have not yet decided which of the 210 types of body tissue they will become-to themselves in a dish for two weeks, and returns to discover them all beating in unison as heart tissue.

The early days of an era that seems like science fiction are here. Biologists are beginning to understand what it takes to reverse or even stop human aging, to build fresh organs, and to alter the genes and proteins that make each one of us who we are. The medical possibilities are endless, the ethical dilemmas tougher than ever. Not only is medicine on a path to double the human life span, it may even revolutionize our notions of what constitutes the good life.

But none of this will ever come to fruition without the brainpower of a key group of professionals-engineers. Whether the goal is to make a drug stick to a tiny molecule within a blood vessel without getting washed away by the current, to grow structurally perfect organs and body parts, or to make a model of the body that will allow researchers to experiment on "virtual" human guinea pigs rather than real ones, bioengineers are crucial to today's most exciting medical advances.

In fact, National Institutes of Health Director Harold Varmus has declared that there no longer is such a thing as biology without engineering, and set up the Bioengineering Consortium at NIH to help usher in the new era of biomedicine. More than 40 universities now have both undergraduate and graduate bioengineering degree programs; at most schools it has become the fastest-growing enrollment category and, at some, bioengineering has already become the most popular engineering specialty.

It's no wonder students are flocking to the field-biomedical engineers are in the mind-blowing business of literally building better humans. Tissue engineering is perhaps the most developed of the fledgling biomedical specialties; two types of cultured human tissue have already been approved by the Food and Drug Administration and are now in use. One is skin, grown by Advanced Tissue Sciences in huge sheets in a San Diego lab, cultured from, of all things, foreskin. The other is Genzyme's bioengineered cartilage, created by taking cells from a person's body, setting them inside a scaffolding made of a polymer that will dissolve over time, and manipulating the cartilage cells so that they will multiply and fill out the scaffolding in a shape and size tailored to fit the individual. The process is already used to replace knee and hip joints.

This same approach is being used to create full-fledged organs, such as a liver or a lung. By creating a scaffold shaped like a liver and "seeding" it with liver cells, researchers hope to encourage the growth of those cells in just the right way to create a functioning organ. In this way, physicians avoid transplant rejection by starting with cells taken from a patient's own liver. Already, researchers in Wisconsin have created an early version: a "bioartificial" liver, which is a set of liver cells housed inside a shell that is inserted into the body and acts like a liver, purifying the blood.

One of the best ways to find out how a new bit of tissue or organ-or for that matter a drug, surgery, or any other therapy-will affect the human body is to create a computerized model of the body that is sophisticated enough to respond to input. The first step in this modeling is combining information obtained from a variety of imaging methods-including computer tomography, magnetic resonance imaging (MRI), and optical imaging-to produce a single, very elaborate composite image. For example, at some medical centers, physicians preparing for hip replacement surgery can now image the patient's actual hip, then feed that data into a rapid prototyping machine that will create a 3-D model of the patient's hip for the doctor to hold and study to better prepare for surgery.

At Johns Hopkins University, bioengineer Raymond Winslow takes things a step further by actually treating a virtual heart. First, he prompts the computerized heart, created from reams of data that biologists have garnered for decades about how the heart functions, to have a virtual heart attack. Then, he can treat the heart with any number of virtual drugs to see how it responds. He also uses the model to better understand things like how congestive heart failure can lead to arrhythmia. Data from the model also helped prove that a new blood pressure medication was unlikely to cause arrhythmia, a dangerous side effect that has kept many other drugs off the market.

The cost and time savings of such models have the potential to be enormous. According to the Pharmaceutical Research and Manufacturers of America, it now takes an average of 15 years and $500 million to develop a new drug. But using computerized technology like Winslow's, scientists can test 10,000 treatments a day. Structural Bioinformatics, a start-up company in San Diego, claims it has the technology to screen 50 million compounds within a single day, and to identify those that are most promising.

Most computer models study only one organ at a time, but since organs in the body interact, more complex models are needed. Perhaps the ultimate modeling goal is the Physiome project, the term bioengineers are giving to the second phase of the Human Genome Project. Now that science is almost done mapping each and every one of our genes, it is time for engineers to step in and put the pieces back together again to see how they work. This is a task that no human mind, and most computers, could ever accomplish alone.

Understanding what all the genes do in one single cell is a mammoth undertaking, let alone understanding what all the body's systems do in tandem. But already, scientists are cooperating to link heart, lung, and blood vessel simulations to see how changing one changes the others. A Nevada firm is creating a model of the gastrointestinal system, and a San Francisco-based firm, Entelos, is creating a model of the immune system. Eventually, says the University of Washington's James Bassingthwaighte, who is spearheading the Physiome project, bioengineers will put Humpty Dumpty back together again, and know how each protein, each gene, each interaction affects the entire human system.

Along with knowledge about the body itself, bioengineering is yielding new ideas for treating the body in as painless a way as possible. For example, scientists at Georgia Tech may make it possible to do away with syringes. They are designing a tiny silicon chip with dozens of microneedles that  quickly and painlessly deliver drugs through the skin. And when it comes to internal treatments like chemotherapy, researchers hope to get rid of the terrible side effects by finding ways to target only the needed areas, and not allow the chemicals to flow freely throughout the body.

At the Massachusetts Institute of Technology, Robert Langer is developing polymers that would allow drugs to be ingested and absorbed into the system, but then released slowly, over years as the material disintegrates, to allow one-time only treatment for chronic conditions or to act as a lifelong vaccine. "The days of children crying in the doctor's office may soon be over for good," notes Joel Shein, CEO of Siga Pharmaceuticals, which is developing vaccines against strep throat and other childhood maladies.

As scientists learn about how each and every cell regulates itself, they are learning to mold and shape human beings in ways never thought possible. While scientists in California learn to keep body cells from dying, others are learning to shape the course of a human from before birth. The Genetics and IVF Institute in Fairfax, Virginia, for example, has created a device that can sort Y and X chromosomal human sperm-allowing a couple to choose whether they conceive a girl or a boy. Other scientists want to manipulate the genes of a fetus while it's still in the womb, in order to get rid of genetic diseases. Some scientists are opposed to tinkering with the reproductive cells because such changes affect not just the individual but future generations.

With each new biomedical advance come new ethical tangles. For example, the ability to create new tissue reshapes the organ transplant problem. Today there are 57,000 people waiting for transplants, and 4,000 of them die each year. Who will own the new technology? And will only the wealthiest patients get treated? Once we can watch the human brain in action, will children who are not learning fast enough be given drugs to enhance their cognitive abilities? With our emerging ability to manipulate the genetics of any living thing, how will we limit those who wish to create "designer babies"? As our knowledge of how genes foster things like shyness or shortness, will our definition of genetic disease expand?

These are the kinds of questions that Maxwell Mehlman, director of the Law-Medicine Center at Case Western Reserve University in Ohio, ponders for a living. "The bottom line is that you can't avoid the Brave New World," Mehlman says, referring to the 1932 Aldous Huxley novel that presaged some of these same biotech ethics questions. "It's horribly frightening to think of things like eugenics, but most scientists are in the business of saving lives, and that's what I think most of this technology will do," he adds.

Most scientists say that the toughest decisions-about designing humans, enhancing cognitive function, or screening people for violent tendencies-are still 20 years off. In other words, today's bioengineering students will be the ones charged with making the calls

Joannie M. Schrof is a senior editor at U.S. News & World Report

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