The Biotech Century

Harnessing the Gene and Remaking the World

The Biotech Century
Harnessing the Gene and Remaking the World

Never before in history has humanity been so unprepared for the new technological and economic opportunities, challenges, and risks that lie on the horizon. Our way of life is likely to be more fundamentally transformed in the next several decades than in the previous one thousand years. By the year 2025, we and our children may be living in a world utterly different from anything human beings have ever experienced in the past.

In little more than a generation, our definition of life and the meaning of existence is likely to be radically altered. Long-held assumptions about nature, including our own human nature, are likely to be rethought. Many age-old practices regarding sexuality, reproduction, birth, and parenthood could be partially abandoned. Ideas about equality and democracy are also likely to be redefined, as well as our vision of what is meant by terms such as "free will" and "progress." Our very sense of self and society will likely change, as it did when the early Renaissance spirit swept over medieval Europe more than seven hundred years ago.

There are many convergent forces coming together to create this powerful new social current. At the epicenter is a technology revolution unmatched in all of history in its power to remake ourselves, our institutions, and our world. Scientists are beginning to reorganize life at the genetic level. The new tools of biology are opening up opportunities for refashioning life on Earth while foreclosing options that have existed over the millennia of evolutionary history. Before our eyes lies an uncharted new landscape whose contours are being shaped in thousands of biotechnology laboratories in universities, government agencies, and corporations around the world. If the claims already being made for the new science are only partially realized, the consequences for society and future generations are likely to be enormous. Here are just a few examples of what could happen within the next twenty-five years.

A handful of global corporations, research institutions, and governments could hold patents on virtually all 100,000 genes that make up the blueprints of the human race, as well as the cells, organs, and tissues that comprise the human body. They may also own similar patents on tens of thousands of micro-organisms, plants, and animals, allowing them unprecedented power to dictate the terms by which we and future generations will live our lives.

Global agriculture could find itself in the midst of a great transition in world history, with an increasing volume of food and fiber being grown indoors in tissue culture in giant bacteria baths, at a fraction of the price of growing staples on the land. The shift to indoor agriculture could presage the eventual elimination of the agricultural era that stretched from the neolithic revolution some ten thousand years ago, to the green revolution of the latter half of the twentieth century. While indoor agriculture could mean cheaper prices and a more abundant supply of food, millions of farmers in both the developing and developed world could be uprooted from the land, sparking one of the great social upheavals in world history.

Tens of thousands of novel transgenic bacteria, viruses, plants and animals could be released into the Earth's ecosystems for commercial tasks ranging from "bio-remediation" to the production of alternative fuels. Some of those releases, however, could wreak havoc with the planet's biosphere, spreading destabilizing and even deadly genetic pollution across the world. Military uses of the new technology might have equally devastating effects on the Earth and its inhabitants. Genetically engineered biological warfare agents could pose as serious a threat to global security in the coming century as nuclear weapons do now.

Animal and human cloning could be commonplace, with "replication" partially replacing "reproduction" for the first time in history. Genetically customized and mass-produced animal clones could be used as chemical factories to secrete--in their blood and milk--large volumes of inexpensive chemicals and drugs for human use. We could also see the creation of a range of new chimeric animals on Earth, including human/animal hybrids. A chimp/hume, half chimpanzee and half human, for example, could become a reality. The human/animal hybrids could be widely used as experimental subjects in medical research and as organ "donors" for xenotransplantation. The artificial creation and propagation of cloned, chimeric, and transgenic animals could mean the end of the wild and the substitution of a bioindustrial world.

Some parents might choose to have their children conceived in test tubes and gestated in artificial wombs outside the human body to avoid the unpleasantries of pregnancy and to ensure a safe, transparent environment through which to monitor their unborn child's development. Genetic changes could be made in human fetuses in the womb to correct deadly diseases and disorders and to enhance mood, behavior, intelligence, and physical traits. Parents might be able to design some of the characteristics of their own children, fundamentally altering the very notion of parenthood. "Customized" babies could pave the way for the rise of a eugenic civilization in the twenty-first century.

Millions of people could obtain a detailed genetic readout of themselves, allowing them to gaze into their own biological futures. The genetic information would give people the power to predict and plan their lives in ways never before possible. That same "genetic information," however, could be used by schools, employers, insurance companies, and governments to determine educational tracks, employment prospects, insurance premiums, and security clearances, giving rise to a new and virulent form of discrimination based on one's genetic profile. Our notions of sociality and equity could be transformed. Meritocracy could give way to genetocracy, with individuals, ethnic groups, and races increasingly categorized and stereotyped by genotype, making way for the emergence of an informal biological caste system in countries around the world.

The Biotech Century could bring some or even most of these changes and many more into our daily lives, deeply affecting our individual and collective consciousness, the future of our civilization, and the biosphere itself. The benefits and perils of what some are calling "the ultimate technology frontier" are both exciting to behold and chilling to contemplate. Still, despite both the formidable potential and ominous nature of this extraordinary technology revolution, until now far more public attention has been focused on the other great technology revolution of the twenty-first century--computers and telecommunications. That's about to change. After more than forty years of running on parallel tracks, the information and life sciences are slowly beginning to fuse into a single technological and economic force. The computer is increasingly being used to decipher, manage, and organize the vast genetic information that is the raw resource of the emerging biotech economy. Scientists working in the new field of "bioinformatics" are beginning to download the genetic information of millions of years of evolution, creating a powerful new genre of "biological data banks." The rich genetic information in these biological data banks is being used by researchers to remake the natural world.

The marriage of computers and genes forever asters our reality at the deepest levels of human experience. To begin to comprehend the enormity of the shift taking place in human civilization, it's important to step back and gain a better understanding of the historic nature of the many changes that are occurring around us as we turn the corner into a new century. Those changes represent a turning point for civilization. We are in the throes of one of the great transformations in world history. Before us lies the passing of one great economic era and the birth pains of another. As the past is always prelude to the future, our journey into the Biotech Century needs to begin with an account of the world we're leaving behind.

The End of the Industrial Era

The industrial saga is coming to an end. It was a singular moment in world history characterized by brawn and speed. We burrowed below the Earth where we found millions of years of stored sunlight in the form of coal, oil, and natural gas--a seemingly unlimited source of energy that could be used, with the aid of the steam engine, and later the electrodynamo, to speed the delivery of what we called material progress.

Our sense of place and space was fundamentally changed. Millions of human beings around the world were uprooted from their rural homes and ancestral lands and forced to make their way into sprawling new urban enclaves where they sought a new kind of work in dimly lit factories and bustling offices far removed from the changing seasons and the age-old customs and rituals of an agricultural existence.

Rails were laid across continents, followed in quick succession by telegraph and telephone wires and poles and miles of paved roads, changing our notions of time and distance. The Wright brothers took wings to flight and a few years later Henry Ford began supplying every American family with a standardized gasoline-powered automobile. Time zones and posted speeds heralded a new quickened pace of life, and in schools, businesses, and homes, the talk was of efficiency, the new mantra of a streamlined, hard-hitting, "future oriented" century.

Everywhere, cement foundations were laid and scaffolding went up, making way for a new vertical world of gleaming secular cathedrals made of iron, steel, aluminum, and glass. After centuries of working, living, and socializing side by side, we began a radical new experiment, living in relative isolation, one on top of another, always in search of that elusive prize which, for want of a better name, we loosely carted self-fulfillment.

It was an age of great abundance for some and growing destitution for others--giant department stores, and later, vast shopping malls were filled with exotica and trivia, staples, craft, and fine works of art. Fashion replaced necessities for millions of people.

Scientists and engineers became our new authorities on almost everything that mattered, their views and ideas sought out, revered, elevated, and enshrined. It was the century of physics and chemistry. We peered into the micro world of atoms and electrons and rewrote the book of nature with the discoveries of quantum mechanics and relativity theory. Scientists split the atom, harnessed a new form of energy more powerful than anything human beings had ever experienced, and created the atomic bomb. Physicists and engineers took man to the moon and back while chemists busied themselves with the creation of new kinds of more versatile synthetic materials. Plastics, a curiosity at the beginning of the century, became ubiquitous by the mid decades, seemingly as essential to our way of life as the very air we breathe. Petrochemical fertilizers and synthetic pesticides reshaped the agricultural landscape, coming just in time--claim many advocates--to help feed a growing human population that was doubling every two generations.

We built vast sewer systems underground, aerated and purified our water, improved our nutrition and increased our life expectancy by more than twenty years. Engineers invented the X-ray machine and later the MRI. Medical researchers gave us vaccinations, anesthetics, antibiotics, and other wonder drugs.

At long last, we are nearing the end of this unique period in world history--the industrial era spread across five centuries and six continents and fundamentally changed the way human beings lived, worked and viewed themselves and their world. It was, above all else, an age propelled by cheap and abundant extractive energy. Once regarded as nearly inexhaustible, the fuel reserves of the carboniferous era are steadily diminishing, making it more costly to extract and more expensive to consume. Watching the Persian Gulf War on television night after night as hundreds of oil derricks across the Kuwaiti desert poured fire into the sky, consuming millions of barrels of precious oil for weeks and then months at a time, was a powerful reminder of just how dependent the modern world has become on these precious fuels.

At the same time that our energy reserves are dwindling, the entropy bill for the Industrial Era is coming due, forcing us to look at the red ink on the modern ledger. Our affluence has been purchased at a steep price. The spent energy of hundreds of years of burning fossil fuels has begun to accumulate in the form of increasing greenhouse gases in the biosphere. Global warming is changing the very biochemistry of the planet, threatening temperature and climate changes of incalculable proportions in the coming century. Even a three-and-one-half degree Fahrenheit change in temperature brought on by global-warming gases--regarded by most scientists as a conservative forecast of what might be in store--would represent the most significant change in the Earth's climate in thousands of years. A climate change of this magnitude will likely lead to the melting of the polar ice caps, a worldwide rise in sea water level, the submerging of some island nations, the erosion of coastlines, and radical fluctuations in weather including more severe droughts, hurricanes, and tornadoes. Whole ecosystems are likely to fall victim to the radical climate shift. Agricultural regions are likely to shift far to the north, creating new opportunities for some and loss of livelihood for others.

The steady decline in fossil fuel reserves and the increasing global pollution brought on, at least in part, by the use of these same fuels is leading civilization to search for new, alternative approaches to harnessing the energy of nature in the coming century. The hard reality is that we are nearing the end of the age of fossil fuels and, with it, the end of the industrial age that has been molded from it. While the Industrial Age is not going to collapse in a fortnight or disappear in a generation or even a lifetime, its claim to the future has passed. That is not to say that the Industrial Age will not remain with us. It will, just as other great economic epochs still do. One can still travel the backwaters of the planet and stumble upon faltering pockets of neolithic and even paleolithic life.

The industrial epoch marks the final stage of the age of fire. After thousands of years of putting fire to ore, the age of pyrotechnology is slowly burning out. Fire conditioned humankind's entire existence. In the Protagoras, Plato recounts how human beings came to possess fire and the pyrotechnological arts. According to the myth, as the gods began the process of fashioning living creatures out of earth and fire, Epimetheus and Prometheus were called upon to provide them with their proper qualities. By the time they came to human beings, Prometheus noticed that Epimetheus had already distributed all the qualities at their disposal to the rest of the plants and animals. Not wanting to leave human beings totally bereft, Prometheus stole the mechanical arts and fire from the gods and gave them to men and women. With these acquisitions, humanity acquired knowledge that originally belonged only to the gods.

Fire, said Lewis Mumford, provided human beings with light, power, and heat--three basic necessities for survival. Commenting on the role of fire in human development, Mumford concludes that its use "counts as man's unique technological achievement: unparalleled in any other species." With fire, human beings could melt down the inanimate world of nature and reshape it into a world of pure utility. As the late historian Theodore Wertime of the Smithsonian Institution observed:

There is almost nothing that is not brought to a finished state by means of fire. Fire takes this or that sand, and melts it, according to the locality, into glass, silver, cinnabar, lead of one kind or another, pigments or drugs. It is fire that smelts ore into copper, fire that produces iron and also tempers it, fire that purifies gold, fire that burns stone which causes the blocks in buildings to cohere [cement].

The age of pyrotechnology began in earnest around 3000 B.C. in the Mediterranean and Near East when people shifted from the exclusive use of muscle power to shape inanimate nature to the use of fire. Pounding, squeezing, breaking, mashing, and grinding began to give way to fusing, melting, soldering, forging, and burning. By refiring the cold remains of what was once a fireball itself, human beings began the process of recycling the crust of the planet into a new home for themselves.

Now that humanity has fashioned this second home, it finds itself in short supply of the fossil fuels necessary to keep the economic furnaces afire while increasingly vulnerable to the effects of accumulating global-warming gases that threaten to radically change the Earth's climate. The industrial way of life has also become increasingly inhospitable to the rest of the Earth's creatures, who are largely unable to adjust to this alien manmade environment. Overpopulation, logging, grazing, and land development are resulting in massive deforestation and spreading desertification. The process is leading to the extinction of many of the remaining species of life, threatening a wholesale diminution of the Earth's biological diversity upon which we rely for sources of food, fiber, and pharmaceuticals. To put the magnitude of the problem in perspective, it is estimated that during the dinosaur age, species became extinct at a rate of about one per thousand years. By the early stages of the Industrial Age, species were dying out on the average of one per decade. Today, we are losing three species to extinction every hour.

Humankind, then, faces three crises simultaneously--a dwindling of the Earth's nonrenewable energy reserves, a dangerous buildup of global-warming gases, and a steady decline in biological diversity. It is at this critical juncture that a revolutionary approach to organizing the planet is being advanced, an approach so far-reaching in scope that it will fundamentally alter humanity's relationship to the globe.

A New Operational Matrix

Great economic changes in history occur when a number of technological and social forces come together to create a new "operating matrix." There are seven strands that make up the operational matrix of the Biotech Century. Together, they create a framework for a new economic era.

First, the ability to isolate, identify, and recombine genes is making the gene pool available, for the first time, as the primary raw resource for future economic activity. Recombinant DNA techniques and other biotechnologies allow scientists and biotech companies to locate, manipulate, and exploit genetic resources for specific economic ends.

Second, the awarding of patents on genes, cell lines, genetically engineered tissue, organs, and organisms, as well as the processes used to alter them, is giving the marketplace the commercial incentive to exploit the new resources.

Third, the globalization of commerce and trade make possible the wholesale reseeding of the Earth's biosphere with a laboratory-conceived second Genesis, an artificially produced bioindustrial nature designed to replace nature's own evolutionary scheme. A global life-science industry is already beginning to wield unprecedented power over the vast biological resources of the planet. Life-science fields ranging from agriculture to medicine are being consolidated under the umbrella of giant "life" companies in the emerging biotech marketplace.

Fourth, the mapping of the approximately 100,000 genes that comprise the human genome, new breakthroughs in genetic screening, including DNA chips, somatic gene therapy, and the imminent prospect of genetic engineering of human eggs, sperm, and embryonic cells, is paving the way for the wholesale alteration of the human species and the birth of a commercially driven eugenics civilization.

Fifth, a spate of new scientific studies on the genetic basis of human behavior and the new sociobiology that favors nature over nurture are providing a cultural context for the widespread acceptance of the new biotechnologies.

Sixth, the computer is providing the communication and organizational medium to manage the genetic information that makes up the biotech economy. All over the world, researchers are using computers to decipher, download, catalogue, and organize genetic information, creating a new store of genetic capital for use in the bioindustrial age. Computational technologies and genetic technologies are fusing together into a powerful new technological reality.

Seventh, a new cosmological narrative about evolution is beginning to challenge the neo-Darwinian citadel with a view of nature that is compatible with the operating assumptions of the new technologies and the new global economy. The new ideas about nature provide the legitimizing framework for the Biotech Century by suggesting that the new way we are reorganizing our economy and society are amplifications of nature's own principles and practices and, therefore, justifiable.

The Biotech Century brings with it a new resource base, a new set of transforming technologies, new forms of commercial protection to spur commerce, a global trading market to reseed the Earth with an artificial second Genesis, an emerging eugenics science, a new supporting sociology, a new communication tool to organize and manage economic activity at the genetic level, and a new cosmological narrative to accompany the journey. Together, genes, biotechnologies, life patents, the global life-science industry, human-gene screening and surgery, the new cultural currents, computers, and the revised theories of evolution are beginning to remake our world. All seven strands of the new operational matrix for the Biotech Century will be explored in the chapters that follow.

Isolating and Recombining Genes

The new operational matrix began to take shape in the 1950s, when biologists discovered ways of locating and identifying chromosomes and genes. In the mid 1950s, cytologists--biologists who study the workings of cells--began experimenting with ways of separating chromosomes from the rest of a cell's makeup and organizing them so they could be analyzed under a microscope. The process is called karyotyping. In their book Genome, Jerry Bishop and Michael Waldholz point out the significance of the new cytogenetic tools: "For the first time, geneticists could correlate abnormalities in human chromosomes with genetic disease." The result was the birth of "a new science of medical genetics, embracing the study of human genetic disease at both the patient and chromosome levels."

In 1968, Dr. Torbjorn O. Caspersson and Dr. Lore Zech, both cytochemists at the Karolinska Institute in Sweden, invented a process for identifying chromosomes, opening the door to the mapping of genes. The researchers realized that genes have different ratios of each of the four base nucleotides G, A, T, and C. They then found a chemical, acridine quinacrine mustard, that has an affinity for the G base, and stained the chromosome with it. When placed under ultraviolet light, the chromosome "glowed in a pattern of bright and dim spots reflecting high and low concentrations of base G." Using the new banding pattern technique, Caspersson was able to identify individual human chromosomes. Other stains were subsequently developed and by the mid-1970s, researchers were studying alterations in banding patterns of chromosomes and connecting them to specific genetic traits and genetic disorders.

The first international workshop on gene mapping was convened in January of 1973 at Yale University in New Haven, Connecticut. Researchers reported on fifty newly mapped genes. At that time, only 150 genes had been mapped to specific chromosomes. By 1986, however, more than 1,500 genes had been mapped to specific chromosomes. A year later, in 1987, Collaborative Research Inc., a small biotech start-up company in Bedford, Massachusetts, and researchers at MIT's Whitehead Institute, announced the compilation of "the first human genetic map."

That same year, the United States Department of Energy (DOE) proposed an ambitious government-funded project to determine the sequence of all three billion G, A, T, and C base pairs that make up the human genome. Shortly thereafter, the National Institutes of Health (NIH) expressed its own interest in mapping the human genome and set up an Office of Human Genome Research to oversee the effort. In the fall of 1988, the government agencies agreed to join forces in the multibillion-dollar Human Genome Project, with NIH concentrating on gene mapping and the DOE on gene sequencing. Other governments established their own human genome projects, followed closely on the heels by private commercial ventures. Genome projects have also been established for plants, microorganisms, and animal species.

Currently, hundreds of millions of dollars are being spent on research all over the world to locate, tag, and identify the genes and the functions they serve in creatures throughout the biological kingdom. Vast amounts of genetic data on plants, animals, and human beings are being collected and stored in genetic databanks to be used as the primary raw resource for the coming Biotech Century.

The new methods for isolating, identifying, and storing genes are being accompanied by a host of new techniques to manipulate and transform genes. The most formidable of the new tools is recombinant DNA. In 1973, biologists Stanley Cohen of Stanford University and Herbert Boyer of the University of California performed a feat in the world of living matter that some biotech analysts believe rivals the importance of harnessing fire. The two researchers reported taking two unrelated organisms that could not mate in nature, isolating a piece of DNA from each, and then recombining the two pieces of genetic material. A product of nearly thirty years of investigation, climaxed by a series of rapid discoveries in the late 1960s and 1970s, recombinant DNA is a kind of biological sewing machine that can be used to stitch together the genetic fabric of unrelated organisms.

Cohen divides recombinant DNA surgery into several stages. To begin with, a chemical scalpel, called a restriction enzyme, is used to split apart the DNA molecules from one source--a human, for example. Once the DNA has been cut into pieces, a small segment of genetic material--a gene, perhaps, or a few genes in length--is separated out. Next, the restriction enzyme is used to slice out a segment from the body of a plasmid, a short length of DNA found in bacteria. Both the piece of human DNA and the body of the plasmid develop "sticky ends" as a result of the slicing process. The ends of both segments of DNA are then hooked together, forming a genetic whole composed of material from the two original sources. Finally, the modified plasmid is used as a vector, or vehicle, to move the DNA into a host cell, usually a bacterium. Absorbing the plasmid, the bacterium proceeds to duplicate it endlessly, producing identical copies of the new chimera. This is called cloned DNA.

The recombinant DNA process is the most dramatic technological tool to date in the growing biotechnological arsenal. The new techniques for identifying and manipulating genes are the first strand in the new operational matrix of the Biotech Century. After thousands of years of fusing, melting, soldering, forging, and burning inanimate matter to create useful things, we are now splicing, recombining, inserting, and stitching living material into economic utilities. Lord Ritchie-Calder, the British science writer, cast the biological revolution in the proper historical perspective when he observed that "just as we have manipulated plastics and metals, we are now manufacturing living materials." We are moving from the age of pyrotechnology to the age of biotechnology. The speed of the discoveries is truly phenomenal. It is estimated that biological knowledge is currently doubling every five years, and in the field of genetics, the quantity of information is doubling every twenty-four months. The commercial possibilities, say the scientists, are limited only by the span of the human imagination and the whims and caprices of the marketplace.

Efficiency and speed lie at the heart of the new genetic engineering revolution. Nature's production and recycling schedules are deemed inadequate to ensure an improved standard of living for a burgeoning human population. To compensate for nature's slower pace, new ways must be found to engineer the genetic blueprints of microbes, plants, and animals in order to accelerate their transformation into useful economic products. Engineer the genetic blueprint of a tree so that it will grow to maturity quicker. Manipulate the genetic instructions of domestic breeds to produce faster-growing "super animals." Redesign the genetic information of cereal plants to increase their yield. According to a study by the United States government's now-defunct Office of Technology Assessment, bioengineering "can play a major role in improving the speed, efficiency, and productivity of. . . biological systems." Our ultimate goal is to rival the growth curve of the Industrial Age by producing living material at a pace far exceeding nature's own time frame and then converting that living material into an economic cornucopia.

Some students of history might argue that human beings have been interested in increasing the quality and speed of production of biological resources since we first embarked on our agricultural way of life in the early neolithic era. That being the case, it might well be asked if genetic engineering is not simply a change in degree, rather than in kind, in the way we go about conceptualizing and organizing our relationship with the biological world. While the motivation behind genetic engineering is age-old, the technology itself represents something qualitatively new. To understand why this is the case, we must appreciate the distinction between traditional tinkering with biological organisms and genetic engineering.

We have been domesticating, breeding, and hybridizing animals and plants for more than ten millennia. But in the long history of such practices we have been restrained in what we could accomplish because of the natural constraints imposed by species borders. Although nature has, on occasion, allowed us to cross species boundaries, the incursions have always been very narrowly proscribed. Animal hybrids (mules, for example) are usually sterile, and plant hybrids do not breed true. As famed horticulturist Luther Burbank and a long line of his predecessors have understood, there are built-in limits as to how much can be manipulated when working at the organism or species level.

Genetic engineering bypasses species restraints altogether. With this new technology, manipulation occurs not at the species level but at the genetic level. The working unit is no longer the organism, but rather the gene. The implications are enormous and far-reaching.

To begin with, the entire notion of a species as a separate recognizable entity with a unique nature becomes an anachronism once we begin recombining genetic traits across natural mating boundaries. Three examples illustrate the dramatic change that genetic engineering makes in our relationship to nature.

In 1983, Ralph Brinster of the University of Pennsylvania Veterinary School inserted human growth hormone genes into mouse embryos. The mice expressed the human genes and grew twice as fast and nearly twice as big as any other mice. These "super mice," as they were dubbed by the press, then passed the human growth hormone gene onto their offspring. A strain of mice now exists that continues to express human growth genes, generation after generation. The human genes have been permanently incorporated into the genetic makeup of these animals.

Early in 1984, a comparable feat was accomplished in England. Scientists fused together embryo cells from a goat and from a sheep, and placed the fused embryo into a surrogate animal who gave birth to a sheep-goat chimera, the first such example of the "blending" of two completely unrelated animal species in human history.

In 1986, scientists took the gene whose product emits light in a firefly and inserted it into the genetic code of a tobacco plant. The tobacco leaves glow.

These results could never have been achieved even with the most sophisticated conventional breeding techniques. In the biotech labs, however, the recombinant possibilities are near limitless. The new genetic technologies allow us to combine genetic material across natural boundaries, reducing all of life to manipulatable chemical materials. This radical new form of biological manipulation changes both our concept of nature and our relationship to it. We begin to view life from the perspective of a chemist. The organism and the species no longer commands our attention or respect. Our interest now focuses increasingly on the thousands of chemical strands of genetic information that comprise the blueprints for living things.

With the newfound ability to identify, store, and manipulate the very chemical blueprints of living organisms, we assume a new role in the natural scheme of things. For the first time in history we become the engineers of life itself. We begin to reprogram the genetic codes of living things to suit our own cultural and economic needs and desires. We take on the task of creating a second Genesis, this time a synthetic one geared to the requisites of efficiency and productivity.

Remaking the World

Today, hundreds of new bioengineering firms are setting the pace for the biotechnical revolution. With names like Amgen, Organogenesis, Genzyme, Calgene, Mycogen, and Myriad, these pioneers are blazing a trail for what some industry experts regard as the second great technological revolution in world history. Dozens of the world's leading transnational corporations are also pouring funds into biotechnical research. They include Du Pont, Novartis, Upjohn, Monsanto, Eli Lilly, Rohm and Haas, and Dow Chemical.

In nearly every life science field, development guidelines are being laid out, long-range retooling of equipment is being hurried along, new personnel are being hired, all in a mad rush to introduce the new genetic commerce into the economy, readying civilization to taste the first fruits of the biotechnological age.

There are already 1,300 biotech companies in the United States alone, with a total of nearly $13 billion in annual revenue, and more than 100,000 employees. All of this development has occurred in only the first decade of a technological and economic revolution that will likely span several centuries. The Nobel Prize-winning chemist Robert F. Curl, of Rice University, spoke for many of his colleagues in science when he proclaimed that the twentieth century was "the century of physics and chemistry. But it is clear that the next century will be the century of biology." The new biotechnologies are already reshaping virtually every field.

In the mining industry, researchers are developing new microorganisms that can replace the miner and his machine in the extraction of ores. As early as the 1980s, tests were being conducted with organisms that consume metals like cobalt, iron, nickel, and manganese. One company reported that it had successfully blown a certain bacterium "into low-grade copper ores where [it] produced an enzyme that eats away salts in the ore, leaving behind an almost pure form of copper." For low-grade ores that are difficult to extract with conventional mining techniques, microorganisms will provide a more economical approach to extraction and processing. For example, scientists are now using microbial agents to degrade the minerals in which gold is trapped prior to chemical extraction, to increase the recovery rate of the gold. In the future, the mining industry is expected to turn increasingly to bioleaching with microorganisms as a more economical way to utilize low-grade ores and mineral spoils that might ordinarily be discarded. Research is even going on to design microorganisms that can consume methane gas in the mines, eliminating one of the major sources of mine explosions.

Energy companies are beginning to experiment with renewable resources as a substitute for coal, oil, and natural gas. Scientists hope to improve on existing crops, like sugar cane, which is already producing fuel for automobiles. Ethanol, derived from sugar and grain crops, is expected to provide more than 25 percent of U.S. motor vehicle fuel by the mid years of the coming century. Researchers are working on even more sophisticated approaches to biofuels, in the hope of replacing fossil fuels altogether. Scientists recently developed a strain of E. coli bacteria that can consume agricultural residues, yard trimmings, municipal solid waste and paper sludge, converting it to ethanol.

Scientists in the chemical industry are talking about replacing petroleum, which for years has been the primary raw material for the production of plastics, with renewable resources produced by microorganisms and plants. A British firm, ICI, has developed strains of bacteria capable of producing plastics with a range of properties, including variant degrees of elasticity. The plastic is one hundred percent biodegradable and can be used in much the same way as petrochemical-based plastic resins. In 1993, Dr. Chris Sommerville, the director of plant biology at the Carnegie Institution of Washington, inserted a plastic-making gene into a mustard plant. The gene transforms the plant into a plastics factory. Monsanto hopes to have the plastic-producing plant on the market by the year 2003.

Researchers are experimenting with even more exotic ways of creating new fibers and packaging materials. The United States Army is inserting genes into bacteria that are similar to the genes used by orb-weaving spiders to make silk. The spiders' silk is among the strongest fibers known to exist. Scientists hope to grow the silk-gene-producing bacteria in industrial vats and harvest it for use in products ranging from aircraft parts to bulletproof vests.

Biotechnology is also being looked to as a key tool in environmental cleanup. Bioremediation is the use of living organisms--primarily microorganisms--to remove or render harmless dangerous pollutants and hazardous waste. A new generation of genetically engineered organisms is being developed to convert toxic materials into benign substances. Researchers are using genetically engineered fungi, bacteria, and algae as "biosorption" systems to capture polluting metals and radionuclides including mercury, copper, cadmium, uranium, and cobalt. One biotech company, The Institute for Genomic Research, has successfully sequenced a microbe that can absorb large amounts of radioactivity. Company scientists hope to use the genes that code for the "uranium-gobbling pathway" to fashion new biological means of cleaning up radioactive dump sites. With more than 200 million tons of hazardous materials being generated annually in the U.S. alone, and the costs of cleaning up toxic waste sites now estimated to be in excess of $1.7 trillion, industry analysts see bioremediation as one of the growth industries in the Biotech Century.

Forestry companies have also turned to the new science in hopes of finding genes that can be inserted into trees to make them faster growing, resistant to disease, and better able to withstand heat, cold, and drought. Scientists at Calgene recently isolated a gene for the enzyme that controls the formation of cellulose in plants. They hope to enhance the enzyme to create trees with more cellulose in their cell walls, making a more efficient tree for harvesting in the pulp and paper-making industry.

In agriculture, bioengineering is being looked to as a partial substitute for petrochemical farming. Scientists are busy at work engineering new food crops that can take in nitrogen directly from the air, rather than having to rely on the more costly petrochemical-based fertilizers currently in use. There are also experiments under way to transfer desirable genetic characteristics from one species to another in order to improve the nutritional value of plants and increase their yield and performance. Scientists are experimenting with genes that confer resistance to herbicides, help ward off viruses and pests, and can adapt a plant to salty or dry terrains, all in an effort to upgrade and speed the flow of agricultural products to market.

The first commercially grown gene-spliced food crops were planted in 1996. More than three-quarters of Alabama's cotton crop was genetically engineered to kill insects. In 1997, farmers planted genetically engineered soy on more than 8 million acres and genetically engineered corn on more than 3.5 million acres in the United States. The chemical and agribusiness companies hope to see a majority of farmlands converted over to gene-spliced crops within the next five years.

Meanwhile, the first genetically engineered insect, a predator mite, was released in Florida in 1996. Researchers at the University of Florida hope it will eat other mites that damage strawberries and other crops. Scientists at the University of California at Riverside are inserting a lethal gene into the pink bollworm, a caterpillar that causes millions of dollars of damage to the nation's cotton fields each year. The killer gene becomes activated in the offspring, killing young caterpillars before they can damage the cotton, mate, and reproduce. Researchers Thomas Miller and John Peloquin hope to raise millions of the genetically engineered bollworms to adulthood and then release them into the environment to mate with wild bollworm moths. The offspring will contain the lethal gene and die en masse in this new form of pest management.

Several biotech companies are working in the new field of tissue culture research, with the goal of moving more agricultural production indoors in the coming century. In the late 1980s, a U.S.-based biotechnology firm, Escagenetics of San Carlos, California--now defunct--announced it had successfully produced vanilla from plant-cell cultures in the laboratory. Vanilla is the most popular flavor in America. One-third of all ice cream sold in America is vanilla. Vanilla is expensive to produce, however. The plant has to be hand-pollinated and requires special attention in the harvesting and curing processes. Now, the new gene-splicing technologies allow researchers to produce commercial volumes of vanilla in laboratory vats--by isolating the gene that encodes the metabolic pathway that yields vanilla flavor and growing it in a bacteria bath--eliminating the bean, the plant, the soil, the cultivation, the harvest, and the farmer.

Researchers have also successfully grown orange and lemon vesicles from tissue culture, and some industry analysts believe that the day is not far off when orange juice will be "grown" in vats, eliminating the need for planting orange groves. Scientists at the U.S. Department of Agriculture (USDA) have "tricked" loose cotton cells into growing by immersing them in a vat of nutrients. Because the cotton is grown under sterile conditions, free of microbial contamination, researchers say it could be used to make sterile gauze.

The late Martin H. Rogoff and Stephen L. Rawlins, both former biologists and research administrators with the USDA, envision a hybrid form of agriculture production in both the fields and the factory. Fields would be planted only with perennial biomass crops. The crops would be harvested and converted to sugar solution by the use of enzymes. The solution would then be piped to urban factories and used as a nutrient source to produce large quantities of pulp from tissue cultures. The pulp would then be reconstituted and fabricated into different shapes and textures to mimic the traditional forms associated with "soil-grown" crops. Rawlins says that the new factories would be highly automated and require few workers.

The many changes taking place in agriculture are being accompanied by revolutionary changes in the field of animal husbandry. Researchers are developing genetically engineered "super animals" with enhanced characteristics for food production. They are also creating novel transgenic animals to serve as "chemical factories" to produce drugs and medicines and as organ "donors" for human transplants. At the University of Adelaide in Australia, scientists have developed a novel breed of genetically engineered pigs that are 30 percent more efficient and brought to market seven weeks earlier than normal pigs. The Australian Commonwealth Scientific and Industrial Organization has produced genetically engineered sheep that grow 30 percent faster than normal ones and are currently transplanting genes into sheep to make their wool grow faster.

At the University of Wisconsin, scientists genetically altered brooding turkey hens to increase their productivity. Brooding hens lay one-quarter to one-third fewer eggs than nonbrooding hens. As brooding hens make up nearly 20 percent of an average flock, researchers were anxious to curtail the "brooding instinct" because "broodiness disrupts production and costs producers a lot of money." By blocking the gene that produces the prolactin hormone, biologists were able to limit the natural brooding instinct in hens. The new breed of genetically engineered hens no longer exhibits the mothering instinct. They do, however, produce more eggs.

Much of the cutting edge research in animal husbandry is occurring in the new field of "pharming." Researchers are transforming herds and flocks into bio-factories to produce pharmaceutical products, medicines, and nutrients. In April of 1996, Genzyme Transgenics announced the birth of Grace, a transgenic goat carrying a gene that produces BR-96, a monoclonal antibody being developed and tested by Bristol-Myers Squibb to deliver conjugated anti-cancer drugs. By the time Grace is one year old, she is expected to produce more than a kilogram of the experimental anti-cancer drug. Genzyme is also preparing to test a transgenic goat who produces anti-thrombin, an anti-clotting drug. Companies like Genzyme hope to produce drugs at half the cost by using transgenic pharm animals as chemical factories in the coming years. The company's CEO makes the point that Genzyme's new $10 million facility, which makes drugs for Gaucher disease, could be replaced in the near future with a herd of just twelve goats. Grace, by the way, is worth $1 million, making her the most valuable goat in history.

Not to be outdone, researchers at PPL Therapeutics, in Blacksburg, Virginia, announced the birth of a transgenic calf named Rosie in February of 1997. The cow's milk contains alpha-lactalbumin, a human protein that provides essential amino acids, making it nutritious for premature infants who cannot nurse. In Boulder, Colorado, Somatogen has created transgenic pigs who produce human hemoglobin.

The new pharming technology moved a step closer to commercial reality on February 22, 1997, when Ian Wilmut, a fifty-two-year-old Scottish embryologist, announced the cloning of the first mammal in history--a sheep named Dolly. Wilmut replaced the DNA in a normal sheep egg with the DNA from the mammary gland of an adult sheep. He tricked the egg into growing and inserted it into the womb of another sheep. The birth of Dolly is a milestone event of the emerging Biotechnological Age. It is now possible to mass-produce identical copies of a mammal, each indistinguishable from the original.

Shortly after the announcement of Dolly's birth, Wilmut and a research team led by Dr. Keith Campbell of PPL Therapeutics reported the birth of a second cloned sheep named Polly who contains a customized human gene in her biological code. Researchers added a human gene to fetal sheep cells growing in a laboratory dish and then cloned a sheep from the enhanced cells. The experiment caught even normally staid scientists by surprise. "After Dolly, everyone would have expected this, but they were saying it would happen in five to ten years," said Dr. Lee Silver, a molecular geneticist at Princeton University.

Together, genetic manipulation and cloning will allow scientists to both customize and mass-produce animals, using the kind of quantifiable standards of measurement, predictability, and efficiency, that have heretofore been used to transform inanimate matter and energy into material goods. Agribusiness, pharmaceutical, and chemical companies plan to mass-produce customized and cloned animals for use as chemical factories, to secrete a range of drugs and medicines. The meat industry is also interested in cloning. Being able to reproduce animals with exacting standards of lean-to-fat ratios and other features provides a form of strict quality control that has eluded the industry in the past.

Animal clones will also be used to harvest organs for human transplantation. Being able to mass-produce exact replicas of animals will assure the kind of bioindustrial quality control that will be necessary to make xenotransplants a major commercial business in the Biotech Century. Biotech companies like Nextran and Alexion are inserting human genes into the germ lines of animal embryos to make their organs more compatible with the human genome and less likely to be rejected. Nextran is already in Phase I clinical trials to test the efficacy of using transgenic pig livers outside the body to help treat patients with acute liver failure, while they wait for a suitable human donor. In the procedure, doctors pump blood from a vein in the patient's leg through the pig liver, which is kept in a container at the patient's bedside. The blood is then pumped back into the patient's body through the jugular vein. Nextran's CEO, Marvin Miller, estimates the commercial value of his transgenic pig livers to be as high as $18,000 apiece. With more than 100,000 Americans dying each year because a human organ was not available in time, the commercial market for xenotransplants is likely to be hefty. Salomon Brothers, the Wall Street investment company, estimates that more than 450,000 people, worldwide, will take advantage of xenotransplants by the year 2010. The market value of the new organ industry is likely to exceed $6 billion by then.

Marine biotechnology is also expected to reap large profits in the coming decade. Scientists at Johns Hopkins University have already successfully transplanted an "anti-freeze" gene from flounder fish into the genetic code of bass and trout so that the fish will be able to survive in colder waters and provide new commercial opportunities for fishermen in northern climates. The Hopkins research team also inserted a mammalian growth hormone gene into fertilized fish eggs, producing faster-growing and heavier fish. Other researchers are experimenting with the creation of sterile salmon who will not have the suicidal urge to spawn, but rather remain in the open sea to be commercially harvested. During the long journey back upstream to their birthing place, salmon stop eating and lose body weight. Scientists hope to break the reproduction cycle, by shocking salmon eggs to produce a doubling of the chromosomes, which results in the production of sterile fish. Michigan State University scientists say that by breaking the spawning cycle of chinook salmon, they can produce salmon whose body weight will exceed seventy pounds, compared to less than eighteen pounds for a fish returning to spawn.

Most marine biotech research is geared to engineer customized fish that can be mass-produced through cloning techniques and be reared in fish farms. With one out of every five fish sent to market today coming from a fish farm, scientists hope the so-called "blue revolution" in marine biotechnology will rival the "green revolution" in agriculture. "By the year 2020," says Malcolm Beveridge, an ecologist at the University of Stirling's Institute of Aquaculture in Scotland, "[aquaculture] will be bigger than fisheries."

Millions of people are already using genetically engineered drugs and medicines to treat heart disease, cancer, AIDS, and strokes. In 1995 researchers tested more than 284 new gene-spliced medicines, an increase of 20 percent over the previous year. Many conventional drugs have been replaced altogether with the new gene-spliced substitutes. Genetically engineered human insulin has virtually eliminated the use of naturally derived insulin from cows and pigs for more than 3.4 million Americans suffering from diabetes. Erythropoietin, produced by Amgen, is used by nearly 200,000 people who are on kidney dialysis each year. The gene-spliced product stimulates the growth of red blood cells, reducing the need for risky blood transfusions. Genentech's tissue plasminogen activator (tPA) dissolves blood clots. Avonex and Betaseron, the beta-interferons, are used as therapies for multiple sclerosis. Pulmozyme (DNase) is used to treat lung congestion in cystic fibrosis patients.

These new genetically engineered drugs are only the beginning of the vast possibilities that lie ahead, say researchers in the field. Scientists in a number of genetic engineering laboratories are working on new ways of altering the genetic characteristics of insects who are the carriers of deadly human diseases, rendering them harmless as infective agents. Researchers at the National Institute of Allergy and Infectious Diseases are genetically engineering mosquitoes to make them unable to spread serious diseases. In one set of experiments, scientists have genetically engineered mosquitos with altered salivary glands making the insect unable to inject malarial parasites when it bites its victims. At Yale University, a medical research team is introducing "disease-prevention" genes into bacteria that live in the intestine of an insect called the "kissing bug." The bug, which is native to South America, spreads a parasite that causes the deadly Chagas disease. The genetically altered bacteria produce an antibiotic that kills the disease-causing parasite in the insect's digestive tract.

Scientists claim that some of their current research with animal models may offer new hope for cures for diseases that have long been untreatable. In May of 1997, Drs. Se-Jin Lee, Ann M. Lawler, and Alexandra McPherron of Johns Hopkins University reported on their discovery of a gene that regulates growth in the muscle cells of mice. The researchers, who are affiliated with a Baltimore biotech company called MetaMorphix, found that the isolated gene produces a protein, myostatin, that regulates and controls muscle growth. When the regulatory gene is deleted, the mice grow more muscle. The researchers deleted the muscle-regulating gene in mouse embryo cells. The first of the new breed of mice, dubbed "Mighty Mouse," developed bulging muscles, huge shoulders, and broad hips. MetaMorphix hopes the research will lead to promising new treatments for muscle-related diseases like muscular dystrophy, and for diseases resulting in the wasting away of muscle like AIDS and cancer.

Even more astounding, a Japanese research team reported in May of 1997 that they had successfully transplanted an entire human chromosome into the genetic code of mice, a feat thought unattainable by most scientists in the field. The Japanese team, led by Kazuma Tomizuka of the Kirin Brewery Technology Laboratory in Yokohama, fused human skin cells containing the chromosomes into mouse embryo cells. Some of the mouse embryo cells took up human chromosomes 14 and 22, which contain the genes that make human antibodies. The researchers took those embryonic cells and implanted them into female mice. The offspring carried the human chromosomes and produced antibodies made of human components when a foreign protein was introduced into their bodies.

Although scientists had inserted DNA into animals for years, they were only able to transplant a small bit at a time. The human chromosome inserted into mice in Japan contained nearly a thousand genes, or fifty times the amount previously transferred. Howard Petrie, director of the monoclonal antibody core facility at Memorial Sloan-Kettering Cancer Center, called the experiments "stunning." Petrie said the Japanese breakthrough meant that animals in the future might be engineered and mass-produced through clonal propagation and be used to make virtually unlimited amounts of therapeutic products such as human antibodies. In elevated doses, the antibodies could shrink tumors and kill viruses and bacteria.

(C) 1998 Jeremy Rifkin All Rights Reserved

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