Challenges
and Opportunities in the Real World*
Frank
F. Bartol, Carolyn E. Zorn, Donald
R. Mulvaney, Jacek
Wower
Department of Animal and Dairy Sciences
Auburn University, AL 36849-5415
INTRODUCTION
Historically, domestication of animals might be considered one of the earliest and most important biotechnologies. Recognition that: (i) animals, such as dogs, could be trained to assist with the hunt and reduce work required to ensure the next meal; (ii) animals could be herded or kept in flocks to ensure a steady, convenient source of food and fiber; and that (iii) large draft-type animals could be harnessed and used to increase the work done by one person, enabled nomadic societies to become more stable and changed human society forever. Now that we could stay in one place and be reasonably assured of a higher quality diet at less cost in terms of human capital, we had more time to think, more time to fantasize, and more time to envision a “brave new world” (Huxley, 1946).
Today, the word ‘biotechnology’ conjures visions of the DNA (deoxyribonucleic acid) double helix and cloned sheep. The road that brought us to this point is a long one. However, since the first accurate description of the structure of DNA in 1953, humankind has embarked on an intellectual and technical odyssey unprecedented in history. Already, efforts to understand DNA - the stuff that genes are made of - and how gene expression affects the behavior of cells, the structure of tissues, the development of organisms, and the fate of individuals, has revolutionized our understanding of the natural world in which we have evolved and our relationships with it. Continued efforts to unravel these mysteries promise to provide answers to questions that will enable us to prolong our lives, enjoy our futures, and even to solve problems that we have caused through our own impetuosity and desire to improve our position in the world.
History -- Milestones in the evolution of animal biotechnology are listed in Table 1 and are illustrated in the timeline. Clearly, animal biotechnology, as we know it today, did not simply appear on the scene with the discovery of DNA, but evolved over millennia in concert with the development of animal agriculture and the biological sciences. Advances in science and biotechnology now occur at a pace that challenges comprehension. The impact of such advances on our lives and futures continues to be both exciting and sobering. Implemented wisely, new biotechnologies hold incredible potential for the advancement of humankind
FEEDING THE WORLD IN THE 21st CENTURY
American citizens have rarely experienced food shortages. However, from a caloric view, about 20% of the global population is considered to be undernourished. According to the Food and Agricultural Organization (FAO), Asian countries produce 17 grams of animal protein per capita per day for 3.3 billion people. In the U.S., we consume about 65-70 grams, and other countries are increasing in consumption as well. Globally, it is speculated that agriculturalists will need to produce approximately 55 grams of animal protein per person/day by 2030. Certainly, economic crises, such as those occurring in the Asian sector today, will continue to affect patterns of affluence and global demand for agricultural products. For the sake of economic, environmental and political stability, it is essential that methods of food production from animal sources not only be refined, but that new approaches be developed that will allow us to meet global demands for animal products more efficiently, without endangering our futures. The biological law is “adapt or die”.
While it is easy to paint a dire picture of a hungry world, current global food supply has, in fact, out-stripped demand. In the short run, this may be fortunate. Decreased demand, over-supply, and phased out domestic commodity support programs have contributed to one of the most disheartening livestock markets in years. Producers able to withstand such extreme economic conditions will continue to be faced with real issues of air and water pollution regulations, animal health and well-being, rising production costs and food safety. Never the less, consumers, in ever increasing numbers, will continue to expect safe, economical products. Meanwhile, producers, whose ranks are diminishing, will be challenged to meet these demands under circumstances that will permit them to realize a fair profit. For this to happen production efficiency must be improved, but how? One approach to the solution, being pursued vigorously in this complex economic, regulatory and political landscape, is the development and application of biotechnologies that may enable the engineering of genetically modified organisms (GMO’s), or the generation of metabolically enhanced organisms, both plant and animal, with the goal of designing more robust, efficient, productive and profitable bioagricultural systems.
Genetic engineering of economically important large domestic animals is already technically, if not yet practically feasible. Use of such GMO's, engineered to grow and reproduce more efficiently, resist disease, accommodate extreme environments, produce higher quality nutrients, and even to produce molecules of value in human and veterinary medicine, could provide solutions to many of the challenges we now face. To be sure that we can exploit these technologies to their best ends, it will be essential to secure support for aggressive research and development efforts, and to recruit the best and brightest young minds into the bioagricultural sciences. Additionally, it will be essential to establish effective educational programs that will help the public understand and believe in the value of the work, as well as the potential and safety of technologies and products derived from it.
BIOTECHNOLOGY: THE NEW FRONTIER
The first recombinant DNA experiments, carried out in 1973, involved Escherichia coli (E. coli), a common and usually harmless bacterium found in human gut. Significant advances in molecular biology and related disciplines over the past 25 years provided necessary information and new tools once envisioned only in the realm of science fiction. Examples include: growing human cells and tissues outside of the body (cell/tissue culture); targeting genetic modifications of plants and animals; designing drugs that can be targeted to specific organisms or malignant cells; and engineering microorganisms to destroy polluting chemicals. Development of new molecular tools has already had tremendous impact on many overlapping human activities including agriculture, medicine and commerce, and is opening up opportunities for refashioning our way of life in the next century.
Genomics -- The Human Genome Initiative provides a solid foundation for the biotechnological revolution. Initiated by a handful of scientists working in different areas of molecular biology, this project is now embraced by thousands of physicians, agriculturalists and entrepreneurs. Begun in 1990, the goal of the human genome project is to determine the sequence of the 3 billion bases that make up the human genome (genetic blueprint). This information will be stored in computer databases accessible to scientists worldwide. Molecular biologists are also analyzing the genome of several other target organisms including E. coli, fruit fly, mouse, pig and cow.
Sequencing and cataloging hundreds of thousands of genes is an enormous task, requiring an investment of billions of dollars from public and private sectors. In addition, this initiative involves collaborations between thousands of molecular biologists, who isolate and sequence DNA, engineers, who build powerful sequencing robots, and computer scientists, who develop novel technologies for storage and analysis of DNA sequences. Information generated by the Human Genome and related initiatives is quickly disseminated through public electronic databases and used by all researchers who have access to the internet.
To date, only about half or less of the human and pig genomes have been sequenced. Even so, data generated through these efforts have had tremendous impact on biomedical and agricultural research and practice, providing unprecedented understanding of genetic and cellular mechanisms regulating reproduction, growth and disease. Whether enabling identification of molecular markers of production traits in domestic animals, facilitating the identification of heritable diseases, or providing unique insight into mechanisms regulating critical life processes or disease states, discoveries spinning out of the Human Genome Initiative are occurring at a truly staggering pace.
Transgenics -- Progress in genomic research stimulates development of novel technologies that not only allow precise characterization of small (e.g. bacteria) and large (e.g. plants and animals) organisms, but also provide information necessary for customizing their genetic blueprints. Until recently, selective breeding was the only way to improve domestic animals genetically for traits such as milk yield, rate of weight gain, meat quality, and wool characteristics. During the 1980s, advances in genetic engineering and embryo manipulation technologies made the first genetic customization of domestic animals possible, through procedures involving the introduction of specific foreign genes into fertilized eggs (see Table 1). Adoption of new molecular techniques by agricultural scientists led to the development of transgenic (containing foreign genes) animals and crops. Over the last 10 years transgenesis has become an increasingly powerful technique for the expression of pharmaceutically valuable proteins in the mammary glands of large animals. This led to the development of “pharming”, a new agricultural industry born from the idea that milk from transgenic farm animals can be a source of novel drugs of medical and commercial value. Examples of proteins made by transgenic approaches include: (i) protein C, a blood clotting agent, made by a cow genetically modified by GenPharm researchers; and (ii) the cystic fibrosis transmembrane receptor protein expressed in goats and produced by Genzyme Transgenics as a therapy for cystic fibrosis. Transgenesis has also been applied to modify commercially important plants. Agricultural scientists have introduced many foreign genes into crops to improve pest and drought resistance, as well as other traits. Recent developments in plant transgenics make it possible to design plants that can actually produce synthetic polymers used in plastics or as lubricants. Such technology could provide alternatives to petrochemicals. Similarly, plants can be engineered to express animal proteins, such as insulin, used in the treatment of diabetes. Clearly, transgenics has the potential to redefine agriculture and our concept of renewable resources.
Animal Cloning -- “Pharming” technology moved a step closer to commercial reality when DNA from the mammary gland of an adult sheep was substituted for that in an otherwise normal egg in order to produce a sheep named ‘Dolly’, the first mammal to be cloned from an adult. Such experiments were quickly replicated in other laboratories, which soon announced successful cloning of mice, pigs, cows and primates. The ability to make identical copies of mammals represents an important milestone not only in animal research but also in agricultural and medical biotechnology. The prospects for animal cloning are endless. Animal cloning will provide researchers with genetically identical animals. Consequently, fewer animals will be needed for experimentation and research efficiency will be dramatically improved. One of the most immediate advantages of animal cloning will be in the area of commercial production of pharmaceutically important proteins in transgenic goats, pigs and cows. Genetic manipulation and cloning, when combined, will allow scientists to produce genetically customized domestic animals with the efficiency and predictability required by industrial quality controls. Engineered animal clones may also be used to provide organs for human transplantation.
THE BUSINESS OF BIOTECHNOLOGY
Many small start-up companies have appeared in recent years, built completely around a few selected products from molecular biotechnology. As with any industry, these biotech companies create jobs and multiplier economics for their state and region. In some cases, these small companies can develop proof of a concept more easily than established corporate giants. Regardless of size, the single most important aspect of corporate business landscape which favors investment in discovery and development of selected biologies or technologies relates to the ability to patent and/or license rights. Patent laws, which start the patent clock from the point of filing disclosure as opposed to the time of patent issuance, have made competition more fierce. In fact, it may be financially more logical to purchase or form alliances with companies possessing intellectual property rights than to develop a technology or product directly. Nevertheless, a high percentage or exclusive market share of a breakthrough technology with patent protection could be worth billions. The magnitude of the financial gain must be substantial and worth the risk, as it may take a company a decade to bring a product or application to the market with discovery and development costs exceeding a quarter of a million dollars before a single dollar is invested in marketing!
Development of a biotechnology-driven product with application to agriculture occurs in phases and usually takes several years before it enters the marketplace. Efficacious technologies may be shelved for many reasons. The decision making process for product development, while relevant to the future of biotechnology, is quite complex and beyond the scope of this presentation. An established company typically has multiple, focused divisions. Within each of the divisions there are opportunities for people with a variety of skills. A list of corporate divisions and therefore areas of expertise needed could include: Research and Development (which may or may not include Discovery), Quality and Production Control, Sales, Marketing, Regulatory Affairs, Legal Affairs, and Management. People with virtually all levels of education are needed. The broad area of biotechnology represents one of the fastest growing areas in the workforce. By 2000, over 1500 US biotechnology companies will be producing over $50 billion in revenue and employing over 500,000 people.
Through employment, agribusiness will continue to touch the lives of 60-70% of the US population and biotechnology is permeating all of agribusiness at ramp speed. From an animal science perspective, young people with knowledge of animal agriculture, who possess skill sets and understanding of cell and molecular biology, as well as mathematical requirements and computer skills needed for bioinformatics, should have a bright employment future. As with nearly all disciplines, corporations rate highly the need for graduates to have effective communication, leadership and problem solving skills to complement the technical skills. For the livestock producers in the next millennium, there will be ever increasing pressure to be familiar with scientific and technological advancements just to survive.
UNIVERSITY-INDUSTRY ALLIANCES
If the cost of knowledge is high, the cost of innovation is higher, both in terms of cash and human capital. Provided with a base of operation that may include an office, a laboratory and some rudimentary equipment, university faculty are expected to identify and obtain much if not all of the support for their research from sources outside of their institutions. University scientists conducting research involving animals must compete for support from federal agencies such as the National Science Foundation (NSF), the National Institutes of Health (NIH), and the United States Department of Agriculture (USDA). Even with very recent projections of increased funding in some of these arenas, competition for support is fierce, and many excellent ideas remain little more than that due to lack of funds. However, the demonstrated profit potential inherent in novel applications of basic knowledge has established the university-industry alliance as an increasingly important venue for research funding.
Industry sponsorship of research at universities is growing as opportunities for technology development and transfer to the private sector increase, and other funding resources change or disappear. Funding pressures in both university and industry sectors have faculty members learning about patent procedures and intellectual property, and industry sponsors evaluating the relative merits of sponsoring research and development (R&D) programs at institutions of higher learning as a means of reducing their costs in terms of both facilities and personnel.
Under the best of circumstances, university-industry alliances can benefit all parties. Faculty members obtain funds for research. Universities recover costs that can be used to improve facilities, upgrade equipment and enhance the academic environment for students and faculty alike. Royalties from patents or inventions generated through collaborative R&D programs may be shared. Industry sponsors and the pubic profit from the realization of ideas and generation of products and(or) processes that enhance corporate and general economic growth. Increasingly, ‘biotech incubators’, supported through university-industry collaborations, are spawning start-up biotech companies that can enhance the economic viability of the university community, the region and, in time, even the nation.
Conclusions
Though tenets of animal husbandry and breeding will remain important, an armamentarium of new ideas and technologies, born from understanding of fundamental processes such as gene expression, growth, development, reproduction and metabolism, will be essential if we are to progress at an adequate pace. In this regard, the future is bright. Opportunities abound for students of bioagricultural sciences to explore, imagine and, ultimately, invent solutions to the many problems we face. It is very clear that the language of agricultural biotechnologies in the new millennium, as is already the case, will be grounded in cell and molecular biology, biochemistry, physiology and computer-based bioinformatics.
Lines between biomedical and agricultural sciences have never been more blurred. Discoveries with biotechnological applications in one arena inevitably have complementary applications in the other. Increasingly, it may not only be pointless, but malignantly myopic, from scientific, economic, and administrative standpoints, to make gross distinctions between fundamental efforts in these areas. University-industry alliances will play increasingly important roles in facilitation of discovery, as well as in stabilizing academic environments and ensuring a source of bright young scientists and agriculturalists. Though challenges will always loom, opportunities in animal biotechnology have never been greater.
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Web Sites:
Genomics:
A Global Resource