Designer People.

The Human Genetic Blueprint Has Been Drafted, Offering Both Perils and Opportunities for the Environment.

THE BIG QUESTION:

Are We Changing the Nature of Nature?

Princeton University microbiologist Lee M. Silver can see a day a few centuries from now when there are two species of humans--the standard-issue "Naturals," and the "Gene-enriched," an elite class whose parents consciously bought for them designer genes, and whose parents before them did the same, and so on for generations. Want Billy to have superior athletic ability? Plunk down the cash. Want Suzy to be exceptionally smart? Just pull out the Visa card at your local fertility clinic, where the elite likely will go to enhance their babies-to-be.

It will start innocently enough: Birth defects that are caused by a single gene, such as cystic fibrosis and Tay-Sachs disease, will be targeted first, and probably with little controversy. Then, as societal fears about messing with Mother Nature subside, Silver and other researchers predict that a genetic solution to preventing diabetes, heart disease and other big killers will be found and offered. So will genetic inoculations against HIV. Eventually, the mind will be targeted for improvement--preventing alcohol addiction and mental illness, and enhancing visual acuity or intelligence to try to produce the next Vincent Van Gogh or Albert Einstein. Even traits from other animals may be added, such as a dog's sense of smell or an eagle's eyesight.

What parents would see as a simple, if pricey, way to improve their kids would result, after many generations of gene selection, in a profound change by the year 2400--humans would be two distinct species, related as humans and chimps are today, and just as unable to interbreed. People now have 46 chromosomes; the gene-enriched would have 48 to accommodate added traits, Silver predicts in his aptly titled book, Remaking Eden.

We may already be on the path to change the very nature of nature. If you think it's a far-off prospect best left to future generations, think again. On June 26, 2000, with much fanfare, scientists with the taxpayer-supported Human Genome Project (working with the private Celera Genomics of Rockville, Maryland) announced that they had completed a working draft of a genetic blueprint for a human being. Many details still need to be filled in before scientists can build a human from scratch.

Sequencing the human genome requires identifying 3.2 billion chemical "letters" located on the 46 coiled strands of DNA, found in nearly every human cell. While researchers now know the order in which DNA is arranged on the chromosomes, they haven't identified all those chemical "letters," which contain the instructions for making the proteins that comprise the human body. About half of the genome sequence is in near-finished form or better; a quarter is finished. The 15-year project is to be completed in 2005 at a budgeted cost of $3 billion, though some of that tax money is spent on other genomic research.

While the implications for longevity, health insurance and discrimination of this milestone achievement have grabbed media attention, the ramifications for the environment--good and bad--haven't.

An Accelerating Timetable

How soon will all this happen? Silver believes that by around 2010 parents will be able to genetically ensure their babies won't grow up to be fat or alcoholic, and by 2050 arrange to insert an extra gene into single-cell embryos within 24 hours of conception to make babies resistant to AIDS. It is already possible to insert foreign DNA into mice, pigs and sheep. The obstacles to inserting them in humans are mainly technical ones. At this point in human knowledge, it could lead to mutations. Several techniques are under development to try to avoid that, however.

"For the near and midterm future, we're looking at science fiction. You'd have to be terminally reckless to do that type of human engineering on people [with what we know now]," argues law professor Henry T. Greely, co-director of the Program in Genomics, Ethics and Society at the Stanford University Center for Biomedical Ethics.

To change a baby's eye color or hair color within a fertilized human egg "would be a very expensive and dangerous proposition for such trivial purposes," says Dr. Marvin Frazier, who fields human genome questions as director of the Life Sciences Division of the U.S. Department of Energy's Office of Biological and Environmental Research. "It is also my opinion that this would be wrong," he added, "but that will not stop some people from wanting to try."

As for manipulating intelligence or athletic ability, Frazier says it will take scientists many decades to figure out how to do it. These particular traits don't rely on one gene, but on all genes. They also rely"to a significant degree" on nurture instead of nature. Even when scientists figure it out, "It is likely that to achieve the desired goals would require a lot of experimentation, which translates into many hundred or thousands of mistakes before you get it right." That means, Frazier says, "a lot of malformed babies and miscarriages."

A Pivotal Moment

To University of Washington professor Phil Bereano, among others, now is the time for all of us to talk with friends and colleagues to hash out the ethical and societal implications of this Brave New World. Do we really want to commodify people? Could it be a Pandora's box? Unfortunately, the box may already be open: Many nations have banned genetic engineering on humans, but the United States has not.

"If scientists don't play God, who will?" said supporter James Watson, former head of the Human Genome Project, speaking before the British Parliamentary and Scientific Committee in June.

"The key question is not whether human [genetic] manipulation will occur, but how and when it will," says a confident Gregory Stock, director of UCLA's Program on Science, Technology and Society in a report entitled, "The Prospects for Human Germline Engineering."

Meanwhile, a long-anticipated September report by the American Association for the Advancement of Science (AAAS) surprised some observers by failing to call for a ban on making inheritable genetic changes in humans--that is, genetic changes that would be carried on by progeny. Indeed, while the report says that such research "cannot presently be carried out safely and responsibly on human beings," it also leaves wiggle room. "Human trials of inheritable genetic changes should not be initiated until reliable techniques for gene correction or replacement are developed that meet agreed-upon standards for safety and efficacy," says report co-author Mark Frankel, director of AAAS' Scientific Freedom, Responsibility and Law Program.

Noting the public outcry after the cloning of Dolly the sheep--which raised the possibility of cloned human beings--the report stresses the importance of public discussion about genetic research before major technical innovations occur. So instead of a ban, the report suggests "rigorous analysis and public dialogue."

But there's no shortage of opposition to human engineering. The San Francisco-based Exploratory Initiative on the New Human Genetic Technologies seeks, among other things, to alert a largely unwitting public to what is going on. "It really is a nightmare vision," says Rich Hayes, who coordinates the campaign from his Public Media Center office. "Once we start genetically re-engineering human beings, where would we stop? We should have the maturity and wisdom to ban the modification of the genes we pass to our children."

Designer Genes

The futuristic notion of choosing a child's genes from a catalog can certainly capture the imagination. Just as parents today enroll their children in the best possible schools and pay for orthodontics, the parents of the future--perhaps in a few decades--would be able to choose from an ever-increasing suite of traits: hair color, eye color, bigger muscles and so on.

Maybe they'd like to add a few inches to a child's height. Or improve a kid's chances at longevity by tweaking inherited DNA. Or ensure a resistance to viruses. Neighborhood clinics could, by appointment, insert a block of genes into a newly fertilized egg. As one cell broke into two, then four, and so on, each cell would contain the new traits. And the child would pass on those traits to all subsequent generations. Who could blame parents for going for this?

But to Stuart Newman, professor of cell biology and anatomy at New York Medical College in Valhalla, New York, the effect on human biology could be analogous to transforming wild areas into artificial areas, or wild food into artificial food.

We "might be changing people into products--genetically engineered products," says Newman, who also is chairman of the Human Genetics Committee for the Council for Responsible Genetics in Cambridge, Massachusetts. "That's something that's opened up by the Humane Genome Project."

"We believe that certain activities in the area of genetics and cloning should be prohibited because they violate basic environmental and ethical principles," Friends of the Earth President Brent Blackwelder and Physicians for Social Responsibility Executive Director Robert Musil said in a 1999 joint statement. "The idea of redesigning human beings and animals to suit the primarily commercial goals of a limited number of individuals is fundamentally at odds with the principle of respect for nature."

Proponents and critics alike envision a future in which those who can't afford gene enrichment will be relegated to second-class citizenship. "As far as I'm concerned, this thrill we have about the future will end up being one big elitist ripple," says Beth Burrows, director of the Edmonds Institute, a suburban Seattle nonprofit institute that works on issues related to environment, technology, ethics and law.

The Green Dimension

And what about the environment? Burrows says several important questions arise about genetic tampering: What are we creating? How will it affect the natural world? What will be the effect on evolution for each species involved? How will it change feeding patterns, or food for other animals? Without understanding interactions, she says, "We may do some extremely stupid things. If people are concerned that there was such a severe backlash against genetically modified foods, I think they haven't seen anything compared to the backlash when we are able to alter the human genome in significant ways--even insignificant ways," says Burrows.

UCLA's Gregory Stock agrees the impact of human genetic modification is profound, but he likes it. "This technology will force us to re-examine even the very notion of what it means to be human," he wrote in a recent report. "For as we become subject to the same process of conscious design that has so dramatically altered the world around us, we will be unable to avoid looking at what distinguishes us from other life, at how our genetics shapes us, at how much we are willing to intervene in life's flow from parent to child."

Ignacio Chapela of University of California at Berkeley is troubled by still other implications the Human Genome Project may bring for the natural world--including plants engineered specifically to produce human proteins, and pigs produced to have antigens that are more human-like in a quest to help humans. To Chapela, a professor in the Department of Environmental Science, Policy and Management, the concept, say, of using chimpanzees as surrogate mothers for human embryos is "abhorrent--degrading for chimpanzees, and for humans, as well. I think what we're talking about is a very deep understanding of what it means to be part of an intricate web of life, and why we have boundaries between species." To Chapela, proponents see the world as a sphere smeared with mix-and-match DNA. "Evolutionarily, it makes sense to have boundaries," he says, "and we're just willy-nilly breaking them down."

A Brave New World

None of these developments will occur in a vacuum; great advancements in robotics are also expected, portending a trend toward the melding of man and machine in a quest for greater human longevity--to age 110, 130 and beyond. UCLA's Stock dubs this new human/machine "Metaman," a "global superorganism." If it seems like mere musings stolen from a science-fiction film, consider this bit of reality: In March, Berkeley researchers announced that they had invented the first "bionic chip"--part living tissue, part machine. Eventually, such chips and circuitry could help in the development of body implants for treating genetic diseases such as diabetes.

"It's a key discovery because it's the first step to building complex circuitry that incorporates the living cell," mechanical engineering professor Boris Rubinsky, who created the device with a graduate student, said afterward. "The first electronic diode made it possible to have the computer. Who knows what the first biological diode will make possible?"

UCLA's Stock isn't concerned about the effects of human genetic engineering on nature. "Even if half the world's species were lost, enormous diversity would still remain," he argues in his 1993 book, Metaman: The Merging of Humans and Machines into a Global Superorganism. "We best serve ourselves, as well as future generations, by focusing on the short-term consequences of our actions rather than our vague notions about the needs of the distant future ... If medical science develops an easy cure for cancer, [nuclear] wastes may not be viewed as a significant health hazard after all. If robots can be employed to safely concentrate and reprocess the radioactive materials, they might even be valuable."

Not so fast, says another architect of the modern world, Bill Joy, the father of Java software and co-founder of Sun Microsystems. Joy posits with some feeling of guilt that "our most powerful 21st-century technologies ... are threatening to make humans an endangered species." In a celebrated article in Wired magazine last year, Joy blamed the possible extinction of humans on a few key causes, including genetic engineering and robotics. Artificial intelligence should match that of humans within 20 or 30 years.

To combat the perceived inevitability of this Brave New World, Marcy Darnovsky, a Sonoma State University instructor who works with the Exploratory Initiative on the New Human Genetic Technologies, calls for three things: First, a global ban on inheritable genetic engineering on humans; second, a global ban on human reproductive cloning; and third, an effective and accountable regulation of other human genetic technologies.

Burrows says we need to be pondering such weighty questions as: Do we really want to merge with machines? "There are tremendous--awful--choices to be made," she says. "It's very risky to have these discussions because they're about common values. The subject is difficult, painful and easily avoided. But we have to stop focusing on the science and think of ourselves as part of an ecosystem."

Chapela is also worried about the lack of civic discourse. But the advocates are talking, particularly among themselves. At a Berkeley conference, one of them, Extropy Institute President Max More, stood before the crowd and read an open letter to Mother Nature:

   Sorry to disturb you, but we
   humans--your offspring--come
   to you with some things to say ...
   You have raised us from simple
   self-replicating chemicals to
   trillion-celled mammals ...
   What you have made us is glorious,
   yet deeply flawed ... We will no
   longer tolerate the tyranny of aging
   and death. Through genetic
   alterations, cellular manipulations,
   synthetic organs, and any necessary
   means, we will endow ourselves
   with enduring vitality and remove
   our expiration date."

Other proponents are more sober, and include Nobel laureate scientists. "This is no `marginal' movement or way of thinking," Chapela says. "The group advocating human re-engineering includes extremely powerful, influential and wealthy people. So don't expect them to roll over easily or soon." CONTACT: Council for Responsible Genetics, [phone], www.gene-watch.org; The Exploratory Initiative on the New Human Genetic Technologies, [phone], e-mail: [e-mail]; Human Genome Project, [phone], www.ornl.gov/hgmis; The Loka Institute, [phone], www. loka.org; Stanford University Center for Biomedical Ethics, [phone], www. stanford.edu/dept/scbe.

The Good News: Toxic Testing, Chemical Reactions and Longevity

The Human Genome Project may offer some good news for the environment, too. Some examples:

* Faster Determination Of What Is Toxic--And For Whom. Everybody wonders what causes cancer. Researchers could place, say, cadmium directly onto a few strands of DNA, and immediately, right before their eyes, watch how the DNA responds, says Andrew Savitz, partner, Environmental Advisory Services Practice, at Price-Waterhouse-Coopers in New York. In this way, researchers could predict how people with certain genetic makeups would react to particular chemicals, agrees Dr. Samuel Wilson, deputy director of the National Institutes for Environmental Health Services in Maryland. Researchers may even watch mutations as they happen, Savitz says. That beats the current system--conducting controlled studies for years to prove which chemicals are toxic, or waiting to see a two-headed fish swim downstream. "It will eliminate some of the guesswork," Savitz predicts. "To me, that's an immediate benefit" of the human genome research.

* Testing Water For Many Strains Of Bacteria Simultaneously. "It could help improve the quality of life for all of us--easily determining if there's bacteria in the water," says Anne Bowdidge, spokesperson for Affymetrix, a company in Santa Clara, California, that takes raw data from the Human Genome Project and packages it for scientists. The biological diagnostic company bioMerieux Vitek aims to use DNA probes as the basis of diagnostic kits for rapidly identifying bacteria.

* Want To Live To 110, Or 130? Longevity may increase, at least for the richest people, thanks to advancements that trace to the Genome Project. That's good news for one segment of the natural world--humans. The possible downside: Since the world's wealthiest people consume resources at a greater rate--one rich person equals 20 Bangladeshis, roughly speaking--that's hard on natural resources.

* Population In Poor Nations Could Stabilize (Or Not). It all depends on whether the advances coming from research on the human genome--and the genomes of infectious agents and food crops--trickle down to help poor countries. "If genomics improve child survival and food production in poor countries, population growth rates are likely to slow and prosperity is likely to increase. If poor countries are deprived of the opportunity to benefit from genomics, inequity and instability will increase," says Rockefeller University population expert Joel E. Cohen, author of How Many People Can the Earth Support?

* Advances in Microbe Research. Methodologies and technologies used during the course of the Human Genome Project will go on to be applied to other tasks--such as increasing scientists' limited understanding of "microbes that can modify wastes in the environment, hopefully in ways that make them less-threatening to all of us." So says Daniel Drell, a biologist at the U.S. Department of Energy Office of Biological and Environmental Research.

-- S.D.

Many Rivers to Cross

What Are Genetically Engineered Drugs Doing to Our Water Supply?

Venturing from New Orleans' Tulane University to the nearby Mississippi River and Lake Pontchartrain every week, Glen Boyd's students didn't know what they might find as they dipped containers into the water and took them back for tests. What turned up? Medicine.

There was cholesterol medication. There was the hormone estrone, a form of the estrogen prescribed to help menopausal women. And there was a strong pain reliever called naproxin. Low levels of these medications have also shown up in surface waters in other parts of the world.

While no one claims this mildly rewed-up water hurts humans--it is further diluted before it reaches home faucets--some scientists are concerned about negative effects on the environment. And with a flood of new drugs as findings from the Human Genome Project are released, researchers wonder: How many more medications will end up in rivers and lakes?

After all, drug companies now target about 500 known biochemical receptors in the human body. That number is soon expected to jump as much as 20-fold--to 10,000 targets, says Environmental Protection Agency scientist Christian Daughton.

"The enormous array of pharmaceuticals will continue to diversify and grow as the human genome is mapped," says Daughton, whose research on the topic appeared in the peer-reviewed journal Environmental Health Perspectives. He says the large number of drugs being introduced "is adding exponentially to the already large array of chemical classes, each with distinct modes of biochemical action, many of which are poorly understood."

Researchers say drugs reach rivers and streams the old-fashioned way: With each flush of the toilet, body wastes containing traces of pharmaceuticals leave for septic tanks, which too often leak. Or they flow through wastewater treatment facilities that don't scrub pharmaceuticals from water. From there, the water that once sat in toilets and bathtubs eventually rejoins rivers and lakes, especially when storms rush in, overwhelming storm and sanitary sewers.

What does this mean for the environment? Many chemicals are designed to profoundly affect humans' physiology. Therefore, Daughton says, it wouldn't be surprising if they affected fish, birds, frogs and insects, as well. Yet, unlike pesticides, these drugs --as well as shampoos, sunscreens and other personal care products rushing down the drain--aren't examined for their effect on the environment before they're placed on the market. "This is surprising," Daughton says, "especially since certain pharmaceuticals are designed to modulate endocrine and immune systems." Hence, they "have obvious potential as endocrine disruptors in the environment."

Some products, meanwhile, have "very high acute aquatic toxicity," Daughton reports. It's impossible to predict how many of the pharmaceuticals would affect nature. After all, scientists don't even understand the process by which some drugs affect humans. After Canada's federal environmental agency, Environment Canada, found high levels of estrogen and birth control compounds in the effluent of sewage treatment plants in 1998, a Trent University researcher replicated these conditions in a laboratory, reports Rachel's Environment & Health Weekly. Some fish developed characteristics of both sexes.

Lots of water sources are apparently affected. Field studies conducted at wastewater treatment plants in California, Arizona and Texas found in their recycled sewer water a substance called organic iodine--a chemical used in medicinal X-ray examinations, says Joerg E. Drewes, associate director of Arizona State University's National Center for Sustainable Water Supply. These seem to be slow to break down in the environment; they were still found at high concentrations in groundwater six to 12 months later.

Drewes has found plenty of chemicals in treated wastewater--an antibiotic, a chemical used in perfume production, the muscle relaxant drug carisoprodol, and its metabolite meprobamate, among others. Meanwhile, in metropolitan Kansas City, more than 40 percent of stream samples analyzed by U.S. Geological Survey scientist Donald Wilkison had detectable concentrations of common over-the-counter drugs--notably ibuprofen and acetaminophen--as well as prescription medicines for high-blood pressure (diltiazem) and antibiotics (trimethiprim-sulfamethoxazole). Even more stream samples--60 percent--had detectable levels of an anti-bacterial agent found in newfangled soaps (triclosan). "Deleterious environmental impacts are likely, either as agents of endocrine disruption, or through direct harm to bacterial and aquatic health," Wilkison reports.

While this rash of new drugs portends bad news for the environment, there could just as easily be good news, some scientists say.

The genomics revolution may make it possible for doctors to more finely target drugs to particular types of people. How many times have you tried a variety of medications to knock out a cold before finally landing on one that works? "It seems to me that we are entering a phase where we will understand more about individual's drug metabolism," says Dr. Paul R. Billings, co-founder of GeneSage, an Internet-based health company that provides genetic information, services and products. "That might reduce overall drug use. It will also allow us to subtype humans and ask if environmental influences affect all the same or differ."

"I think it's a pretty far stretch to draw a conclusion one way or another," says Taylor Crouch, CEO of Variagenics, a leading Boston-area company that applies genetic-variance information to the drug development process. "You could argue that if we get patients on more appropriate medications, they'll metabolize them better, more efficiently and, therefore, we would see less drug waste. But that's not necessarily provable." Yet, he adds, "to the extent that we can get less trial-and-error medications into patients," he does predict "a slight decrease in the overall excreted medications."

So, what does the future hold? It depends. if manufacturers are aware that some personal-care products "survive and potentially accumulate in the environment, they might design more biodegradable agents," says Drewes, adding, "We have to change something, that's for sure." CONTACT: National Center for Sustainable Water Supply, [phone], www.eas.asu.edu/~civil/ncsws/front. html; U.S. Environmental Protection Agency, www.epa.gov/esd/chemistry/arma/index.htm.

-- S.D.

SALLY DENEEN is a Seattle-based freelancer who writes frequently for E.