The revolution in biotechnology; Genetic engineering: hopes for high profits mount; ethical and social questions persist
Biotechnology is as old as the art of making bread for your toast or vinegar for your salad dressing. It also is as new as the four to five dozen companies formed over the past half decade to exploit the wonders of genetic engineering.
The awesome ability to rewrite an organism's genetic instructions - to give it capacities nature never intended - promises to become the spearhead of the revolution sweeping through biotechnology today.
The revolution is being driven as much by rising oil costs as by new prospects for directly rewriting the genetic ''programs'' of microbes. Many basic industrial chemicals that have been made from natural gas and oil now can, or soon will be, made more economically by microbes using wood cellulose, organic wastes, or other so-called ''biomass.''
''The major economic impact of genetic engineering will be even greater in the chemical and energy industries than in the health-care field,'' says Edward Lanphier of International Resource Development Inc. (IRD). This is in spite of the fact the microbes have already taken over much of the pharmaceutical industry over the past four decades. Antibiotics worth $4 billion to $5 billion have been produced worldwide so far. IRD has projected a $3 billion annual market by 1990 specifically for drugs produced by genetically redesigned organisms.
However, the multibillion-dollar market for microbe-made medicinals pales beside IRD's projection of trillions of dollars of savings and goods produced through more extensive applications of biotechnology in the chemical and energy industries. By allowing energy-intensive chemical reactions to take place at relatively low temperatures and pressures, biotechnology can cut industrial energy use significantly. It can aid secondary and tertiary recovery of some 200 billion barrels of domestic oil worth over $6 trillion by, for example, supplying xanthum gum to help push oil out of wells. By helping farmers become less dependent on oil-derived chemicals for fertilizers and pesticides, biotechnology can substantially benefit agriculture, IRD believes.
Such an assessment is not mere hyperbole from promoters. Several recent reports from diverse sources also see biotechnology burgeoning. The congressional Office of Technology Assessment (OTA) in a detailed study released last April, concluded that ''the impact of this technology will cut across the entire spectrum of chemical groups. . . .'' It added, ''crude estimates of the expected economic impacts (including medicinals) are in the billions of dollars per year for dozens of chemicals within 20 years.''
Looking specifically at agriculture and related business, a study by the Policy Research Corporation and the Chicago Group foresees an annual market of $ 50 billion to $100 billion for products made by specially designed microbes by the end of the century.
Besides producing chemicals, biotechnologists also foresee new ways to control pollution. For example, Ananda M. Chakrabarty of the University of Illinois, who patented an oil-eating bacterium while working for the General Electric Company, now is developing bacteria that can eat toxic chemicals. ''In the future,'' he says, ''instead of banning chemicals . . . we'll be able to develop our own antidotes.''
Harking back to a technique believed used by the Romans, mining engineers anticipate using microbes more extensively to recover valuable metals from poor ores. Already, bacteria of the genus Thiobacillus are used commercially to win copper and uranium from low-grade ores. By breeding or genetically designing bacteria to be more resistant to heat and acids and more tolerant of metal poisoning, it may be possible to expand their role as miners.
Such is the vision of the biotechnical revolution. However, genetic engineering has raised questions of ethical and social responsibility since it first gained public notice in the early 1970s.
Put in its simplest terms, these techniques allow biologists both to read the genetic instructions that control the development and nature of a specific organism and, to some extent, alter those instructions. For example, the appropriate genes from one species of organism that produces a certain chemical (biologists would say the genes ''code'' for the chemical) can be given to a bacterium, typically Escherichia coli, which then can produce the chemical in appreciable quantity. In this way, bacteria have been enabled to make such natural human biochemicals as insulin or a growth hormone, using the actual human genetic instructions. The insulin gene, which is fairly short, was synthesized and then given to the bacterium. In the case of the growth hormone, the human gene itself was copied directly and inserted.
The developing ability to transfer genes between different biological species , genera, and even kingdoms - across the vast biological distance between human beings and bacteria - raised concern in the mid-1970s that biologists might be tempted to ''play God'' and repopulate Earth with their own creations. Formidable technical obstacles, including lack of much fundamental biological knowledge, bar such hubris. There is a world of difference between reprogramming E. coli to make certain biochemicals and redesigning the human race.
As this has been more widely realized, the concern about tinkering with earthly life has moved into the background, although it has not faded away. It remains as a backdrop to the biotechnical revolution. As the OTA noted last spring: ''Genetics - and other areas of the biological sciences - have in common a much closer relationship to certain ethical questions than do most advances in the physical sciences and engineering. The increasing control over the characteristics of organisms and the potential for altering inheritance in a directed fashion raise again questions about the relationship of humans to each other and to other living things.''
Concern about public safety has been more persistent. Again in the mid-1970s, biologists worried that they might create novel microbes that were dangerous life and that might escape from the lab. They urged strict volunteer guidelines to ensure nothing dangerous was let loose. In 1976, they were formulated as the National Institute of Health (NIH) guidelines, which became binding on federal agencies and grantees but remained voluntary for others. Some communities, such as Cambridge, Mass., asserted their own authority to control DNA work within their jurisdictions. Safety committees were also established at universities to supervise recombinant DNA research.
Except for some concern that the NIH guidelines were not generally binding on industry, there was wide agreement that reasonable public safeguards had been established. Dangerous experiments with such things as pathogenic organisms were either banned or very strictly controlled. Much other research had to be done under tight laboratory conditions.It became apparent that biologists had been overly cautious. Most, if not all, of their bacterial rejiggering was no more exotic than what occurs naturally. Even E. coli with the ability to make human growth hormone is believed to pose no threat, for it would not be likely to survive outside of the carefully controlled environment of laboratory glassware or industrial vats. This has led biologists to seek a relaxation of the guidelines which many of them now consider needlessly restrictive and even alarmist. Most other countries with biotechnical research have already come to this conclusion. In Britain, for example, only the most potentially dangerous experiments need prior approval. Now the NIH Recombinant DNA Advisory Committee (RAC) urges relaxation in the US. On Sept. 9, by a vote of 16 to 3 with one abstention, the RAC gave preliminary approval to a proposal originally put forward by David Baltimore of the Massachusetts Institute of Technology and Allan Cambell of Stanford University. Guidelines now mandatory would become voluntary. Conditions for working with redesigned organisms would be relaxed. Only two dangerous types of experiments would continue to be banned - those using genes able to synthesize extremely toxic poisons and those which would transfer drug resistance if this were deemed detrimental to public health.It remains to be seen whether or not the RAC recommendation will be sustained. Debate within the committee was intense, even though most members reportedly acknowledged that past fears had been exaggerated. Also, local communities with recombinant DNA facilities would likely be uneasy with any weakening in the rules. Boston, for example, now has an ordinance to compel compliance with current standards and Cambridge has toughened its 1977 law to control privately funded DNA work more closely.Molecular biologists hope that local communities will recognize that the supposed dangers of their work are much less than had been thought and will not reimpose restrictions that NIH now is prone to relax. Nevertheless, many of those working in this new biological field do recognize the importance of public participation in resolving this issue. ''We need to provide an established, available, open forum for consideration of these issues over the next five years,'' says Mr. Baltimore, ''so the public can understand . . . their concerns have not been forgotten.'' Meanwhile, back on campus, new ethical issues have arisen as the lure of big money reaches into academic laboratories. This is not just a matter of university professors being enticed into industry. A number of them are staying on campus but dividing their time and loyalty with outside companies, some of which they have helped establish. Another factor is the inflow of industrial money to set up special arrangements for priority access to discoveries in exchange for research funds. In July, for example, the Du Pont chemical company announced a five-year, $6 million deal with Harvard Medical School to support research in molecular genetics, with Du Pont receiving an exclusive license on any practical discoveries. This followed within a month the announcement of a similar 10-year, $50 million arrangement between Harvard and the German chemical company Hoechst AG. The immediate payoff in application of recombinant DNA research is expected to be in medically related areas such as drug manufacture.As though such deals for exclusive licensing weren't enough of a threat to free publication of academic research, the scientists themselves are beginning to conceal their findings in hopes of gaining patents. ''The lure of the dollar makes people clam up,'' says Doris Merritt of NIH, the main sponsor of DNA research in the US.''We are already beginning to see serious threats against the usual modes of scientific communication,'' warns Stanford University president Donald Kennedy. He explains: ''Proprietary restraints on the free exchange of data have already begun to crop up at biomedical research meetings and are presenting challenges to the policies of scientific societies and journals accustomed to open publication. Even more damage has been done to the informal routes of communication that characterize most vigorous fields of basic biological research.''Noting that the problems brought by big money in the commercialization of biomedical research are harbingers of what will happen in other areas of the new biology, Kennedy has called for a conference to lay down some ethical guidelines, just as biologists once met to establish safety guidelines. At this writing, he has had no takers. Indeed, the thinking in regard to ethical standards for universities in this matter is in disarray.Meanwhile, there is the question of the public's interest in the fruits of research that has been funded largely by tax money. At a hearing on this issue before subcommittees of the House Science and Technology Committee, Rep. Albert Gore Jr. (D) of Tennessee expressed a widely held concern when he said, ''My gut feeling is that the taxpayers are not being given sufficient consideration.'' He said he felt ''uncomfortable with the arrangement with Hoechst'' which he thought would allow foreigners to tap knowledge paid for by US citizens.For their part, both universities and the companies involved point out there will be a rich return from taxes paid on any profits. For example, J. Leslie Glick, president of Genex Corporation says, ''We project the financial return to the public (as cost savings and corporate taxes) in the year 2000 on worldwide bulk sales of products whose manufacture will have been affected by recombinant DNA technology to be $4.7 billion.''The ethical issues are far from being resolved. They hang as a small but dark cloud on the otherwise bright horizon of biotechnology. Also on that horizon is the question of how far scientists should go in tinkering with organic life. Biologists and the rest of society will have to face up to that one someday.