Beefing up muscle without steroids or hormones; rejuvenating damaged skin and heart tissue; ratcheting up memory function.


A decade ago, these medical treatments might have seemed like pure science fiction. But thanks to ever-faster breakthroughs in biotechnology, therapies that promise to enhance human abilities are nearing the marketplace. To be sure, each of these treatments remains in the research stage. And such advances face business hurdles, including a dismal investment climate for biotech firms. Yet another obstacle is the set of ethical questions raised by proposed human-enhancing medical procedures, including debate over embryonic stem cells and cloning and whether the therapies will widen the rift between haves and have-nots.


In the near-term, however, cutting-edge scientists continue pressing forward with their research. And should treatments like these eventually win regulatory approval, they stand a good chance of winning an ally in corporate America, suggests Sean Nicholson, professor of health care systems at Wharton. After all, memory-honing and muscle-toning procedures could make for sharper, stronger employees. “It should be an easy sell to the employer if these things can be shown to improve productivity,” Nicholson says.


Since ancient times, people have longed to boost their powers, be they physical, mental or sexual. Modern medicine and technology have brought those dreams closer to reality. In July, the National Science Foundation and Department of Commerce released a report concluding that the convergence of nanotechnology (that is, molecular-scale engineering), biotechnology, information technology and cognitive science holds the potential of “a tremendous improvement in human abilities, societal outcomes and quality of life.” In the next 20 years, the report’s authors say, technology could provide us with benefits such as direct brain-to-machine interfaces that transform work, wearable sensors that allow us to monitor our health and environment, and upgraded flesh and bone. “The human body will be more durable, healthy, energetic, easier to repair, and resistant to many kinds of stress, biological threat, and (the) aging process,” the report states.


Recent pharmacological advances have been achieved with therapeutic uses in mind, but they also can serve as enhancement tools. Take recombinant human growth hormone, which matches the amino acid sequence of naturally occurring human growth hormone and was cloned by biotech pioneer Genentech in 1979. Genentech has won approvals to use the synthetic hormone to treat children and adults with growth hormone deficiency. But athletes are suspected of using the stuff to boost their performance. The International Olympic Committee, in fact, has launched an effort to develop ways to detect biosynthetic growth hormone in athletes. Viagra also raises the therapy vs. enhancement issue. Regularly providing sexual potency to 80-year-olds may fix a malady, but it also endows them with unprecedented abilities.


Medical therapies now in development aim to offer even more miracles. With the aging Baby Boomer market holding out a huge carrot, memory improvement is a target of several biotech firms. Axonyx, for example, has the rights to a compound called Gilatide that’s based on the saliva of the gila monster (a venomous lizard found in parts of the U.S. and Mexico). Other firms racing after what Forbes called “Viagra for the Mind” include Memory Pharmaceuticals and Helicon Therapeutics.


Mighty Mouse Lives On

Therapies to tweak genes into building more muscle is another avenue of research. H. Lee Sweeney, chair of the physiology department at the University of Pennsylvania’s Penn’s Health Care System, has been a leading figure in this effort. Through the use of a virus, Sweeney altered the leg muscle genes of mice to increase the amount of a substance called insulin-like growth factor I. IGF-1 is thought to activate so-called satellite muscle cells, which create new cells that repair muscle tissue. Sure enough, as the mice aged, the genetically enhanced leg muscles were “as big and strong as they were in a young mouse,” Sweeney said.


The experiment also demonstrated the gene therapy’s potential to beef up people in their prime: In young adult mice, Sweeney’s treatment increased muscle strength by 15% over untreated muscle.


More recently, Sweeney created a hybrid mouse out of one strain with muscular dystrophy symptoms and another strain with high levels of IGF-1. The results were promising, with increases in muscle mass and muscle force along with a reduction in muscle cell death. Sweeney is not the only mighty mouse man. Last year Johns Hopkins researchers built on earlier studies to show that muscular mice would result from blocking the gene for a growth regulator named myostatin.


Stem-cell research also takes aim at rejuvenating old or damaged tissue. Stem cells are cells that can develop into many different sorts of tissue. Scientists believe these cells could revolutionize the treatments of a wide range of ailments including heart disease, diabetes, burns, rheumatoid arthritis and Alzheimer’s. For heart disease, the idea is to prod stem cells into becoming healthy heart cells and transplant these into a failing heart.


Biotech companies working on stem-cell treatments include StemCells, Osiris Therapeutics and Geron. Currently, Geron is conducting animal experiments with neural and bone marrow cells derived from stem cells. By the end of the year, the firm expects to launch animal tests of heart muscle and insulin-producing pancreatic cells derived from stem cells. “If everything goes well, we have probably three years of work ahead of us before we go into human trials,” says David Greenwood, Geron’s chief financial officer and senior vice president of corporate development.


Geron also is at the forefront of cloning, which could be a more potent technique than stem cell research alone in repairing or replacing human tissue. Also known as nuclear transfer, cloning involves putting the nucleus of an adult animal cell into an unfertilized egg cell. Cloning can create a whole new creature – as in the case of Dolly the sheep. But another strategy is to generate stem cells and use the stem cells to create healthy new tissue. That tissue could be implanted in the nucleus-donor, and it likely would be acceptable to the patient’s immune system.


Geron is working with researchers at Scotland’s Roslin Institute – famous for cloning Dolly – to develop a nuclear transfer technique using regular cells rather than harvested egg cells. The company believes cloned tissue using only adult cells from a would-be transplant recipient would not trigger any immune system rejection.


Resetting Our Genetic Clock

Another branch of Geron’s work hints at the prospect of enhancing our very lifespan. Geron researchers and their partners have found that parts of our chromosomes called telomeres serve as a genetic “clock” for cellular aging. Telomeres shorten with each division of the cell and at a certain length turn off the division process, which seems to lead to destructive effects. On the other hand, an enzyme called telomerase “is capable of restoring telomere length, or resetting the ’clock,’ thereby increasing the lifespan of cells,” as Geron literature puts it.


The firm has focused its telemerase technology on goals such as improved wound-healing and cancer treatments. Geron, Greenwood points out, has never suggested its products will allow people to live forever. “That’s science fiction,” he says.


But some see science quickly turning the fiction into factual possibilities. The recent NSF report, for example, envisions that later in this century death may become “ambiguous” as “people upload aspects of their personalities to the Solar System Wide Web.”


Titled Converging Technologies for Improving Human Performance, the 405-page study doesn’t simply describe what’s possible in ability-enhancing technologies. It makes the case that a greater focus on such research could be vital in preventing a societal “catastrophe.” The answer to human brutality and new forms of lethal weapons is a kind of tech-triggered social harmony, the authors suggest. “Technological convergence could become the framework for human convergence … The twenty-first century could end in world peace, universal prosperity, and evolution to a higher level of compassion and accomplishment.”


That vision is largely shared by Max More, a futurist for consulting firm ManyWorlds and president of the Extropy Institute. The Extropy Institute promotes the advance of human life through technology. In the years ahead, More expects to see a massive market for memory-enhancing drugs and treatments giving us greater control over our emotions. Eventually, he says, we’ll have the option of uploading our consciousness into synthetic bodies to visit a far-off place. “Avis, instead of renting cars, [would] rent bodies,” More says.


However, there are plenty of potential potholes before Avis adds bodies to its fleet. Most immediately, biotech firms are struggling amid the economic downturn and investor malaise. In June, for example, Geron laid off 43 people, or 30% of its employees in Menlo Park and Edinburgh, Scotland. Like other biotech firms, Geron is not profitable. These companies may require years of financing before their products win regulatory approvals and turn red ink into black.


Funding, however, is hard to come by these days. Venture capital investments in healthcare during the first quarter of 2002 fell 30% quarter-over-quarter to $1.1 billion, according to a joint survey by Ernst & Young and VentureOne. Nor are the public capital markets attractive for biotechs. Like shares of other public life-science firms, Geron’s stock has plummeted. Geron shares are trading at less than $5 from a high of roughly $70 in early 2000.


The stock market generally has fallen this year, and the biotech industry has its own scandal in ImClone Systems to make matters worse. Shares of ImClone fell sharply late last year after the FDA said it would not review the firm’s bid for marketing approval of anti-cancer drug Erbitux. Since then, ImClone’s former CEO has been charged with insider trading and the company is under investigation by the SEC. ImClone’s troubles have made even more waves thanks to the firm’s connection with domesticity diva Martha Stewart. Reports have said federal officials are investigating whether Stewart sold ImClone stock based on insider information, and have raised the possibility she misled authorities.


Forging Alliances

Wharton’s Nicholson, though, isn’t too worried about biotech firms surviving the business trough. “This is not new,” he says. “There have been many periods of boom and bust since the 1970s.” Nicholson says one sound strategy for smaller biotech firms is to forge alliances with the bigger, older pharmaceutical companies. And those partnerships are becoming more common. In a paper he co-wrote and published earlier this year, Nicholson found the average yearly number of biotechnology alliances signed by each of the top 20 pharmaceutical firms increased from 1.4 in 1988-1990 to 5.7 in 1997-1998.


Even if biotech firms with ability-enhancing treatments emerge from the current downturn, their therapies still face ethical challenges. The U.S. House of Representatives already has banned human cloning. And Senators Sam Brownback and Mary Landrieu have introduced parallel legislation in the Senate. “We should not create life just to destroy it,” Brownback says. Competing legislation effectively would ban the birth of a human clone but preserve “therapeutic cloning,” or nuclear transfer research.


The Senate debate follows on the heels of stem cell research controversy. Some observers have objected to stem cells taken from embryos or aborted fetal tissue. Even though embryonic stem cells come from in-vitro fertilization clinics that would otherwise destroy excess embryos, critics warn the process desecrates life. They suggest using stem cells taken from adults, umbilical cords or placentas, though these cells haven’t appeared to be as flexible in creating different organs or tissue. Last year, President Bush tried to find a middle ground, allowing federal funds to go to research on existing lines of embryonic stem cells only.


Aside from the sanctity of life issue is a question about the socio-economic impact biotech advances may have. It’s possible that strength, memory and life-span-enhancing treatments could primarily benefit the wealthy, and thereby widen the gap between the haves and have-nots. Alan Hillman, professor of medicine and health care systems at Wharton, suggests biotherapies on the horizon threaten to exacerbate a U.S. health care system that already offers better care to the well-heeled.


When it comes to public financing for research into ability-enhancing therapies, Hillman is skeptical. “We’re not answering the need for pre-natal care, primary care, preventive care,” he says. “That should be step one.”


More, on the other hand, says some subsidized research into human-enhancing treatments may be appropriate. He argues that the distinction between therapeutic treatments and elective, enhancing therapies will fade as we find ways to optimize our abilities. “If you set your standard for health as what you are when you’re at your best, then you’re (deficient) when you’re not at your best,” he says.


Businesses may end up agreeing. If cognition-boosting drugs meant fewer clerical errors and strength-enhancing gene therapies led to better warehouse workers, the treatments may lift companies’ bottom lines. That could prompt employers to foot the bill for ability-augmenting drugs and procedures.


If these advances overcome business hurdles and ethical quandaries to make it to the mainstream, our society is bound to look different. But in what ways? A recent essay in Wired magazine suggested the coming wave of wonder drugs will bring out the worst in us. Writing about topics including muscle-building gene therapy and a potential pill that might simultaneously suppress the appetite, create a tan and increase the libido, Wil McCarthy described our destiny as “the drug-fueled extreming and professionalization of shallowness itself.”


Max More is more optimistic. Sure, bulging biceps may be common as the therapies take root, he suggests. But the treatments should encourage people to be creative as well. “There’ll be new options for exotic personalities, exotic physiques,” he says. “People growing gills. Feathers instead of hair.” In the end, More says, we’ll have greater power “to choose (what) we want to be.”