Science in Christian Perspective

The Biology Business
HARRYCOOK
Department of Biology 
The King's College 
Edmonton, Alberta Canada T5H 2MI

In 1979 the controversy surrounding recombinant DNA research was on the wane. 1980 saw a resurgence of the debate that still continues today. The earlier discussion centered on the desirability and safety of interfering with the genetic material of any organism; the new debate is concerned with moral questions that arise as recombinant DNA techniques become part of a new commercial technology. Commercial firms are scaling up the volumes of cultures of recombinant bacteria to reach the production stage and are applying for patents to cover bacterial strains and splicing techniques. Other new biological techniques are also being applied commercially to produce substances of value to medicine and research. In March, 1981, Time Magazine ran a cover story on "The Boom in Genetic Engineering".I

The Biological Basis¹

The DNA molecule, by virtue of the sequence of its subunits, specifies the proteins that a cell manufactures. The proteins produced.by a cell give each cell type its unique character. Thus, when a segment of DNA can be introduced into another cell and can be induced to govern pro tein synthesis as it did for the original owner, the new host  cell takes on some characteristics of the donor cell producing proteins that are characteristics for that donor. The significance of this may have been masked by the scientific jargon that has just been used. But imagine bacteria producing human insulin, or a mouse producing enzymes found only in the rat intestine!

 The synthesis of several biologically active substances has now been achieved with the new technology. The most significant of these are human insulin, human growth hormone, and foot and mouth disease antibodies. Other protein molecules, such as blood-clotting factors, hormones, and antibiotics will eventually be produced in the same way. Other possible products of "designer gene" technology are bacteria that can fix nitrogen in the roots of nonleguminous plants, bacteria that can digest cellulose in the human intestine, and bacteria that can be used to clean up oil spills. 

However, the possibility of dangers has also been suggested. E. coli is a normal inhabitant of the human digestive tract. A strain of E. coli, produced with recombinant DNA methodology by design or accident, which would produce dangerous toxins-not uncommon in other bacteria-or which had acquired dangerous new pathogenic habits, could conceivably do much harm to the human population. Furthermore, pathogenic bacteria might acquire a resistance to antibiotics which would make them more difficult to control. Such possible hazards have raised questions about this research in the minds of many people.

In 1973 several investigators had begun to have doubts about the safety of recombinant DNA research. These doubts surfaced at a conference and were subsequently described in a letter in the Sept. 21, 1973 issue of Science. Subsequently, Science (July 24, 1974) published a letter by eleven distinguished scientists, asking for a moratorium on recombinant DNA research until guidelines could be established to guarantee the safety of such research.²

The two letters in Science focused attention on the recombinant DNA debate. Newspaper articles, some informative, some with hair-raising scenarios for catastrophes, kept the issue in the public eye. The Asilomar Conference, held in February, 1975, in California, was convened specifically to formulate recommendations for procedures to guard the safety of recombinant DNA research. The National Institute of Health (NIH) immediately took these recommendations under study and arrived at guidelines. From the time of the second letter in July, 1974, until the NIH guidelines were announced on June 23, 1976 ³ no recombinant DNA research was carried out in the United States. Surprisingly, the dictum for science, "What can be done will be done," did not hold true during this period.

The NIH guidelines described two kinds of containment procedures to ensure safety of the research. The requirements for the first of these, physical containment, were described for four different risk levels. The second type of containment, biological containment, described for three different risk levels, depended on special strains of E. coli that cannot live outside the Laboratory. The guidelines banned certain experiments altogether, such as those with extremely pathogenic organisms and "shotgun experiments" in which the entire DNA complement of an organism is broken into fragments and systematically incorporated into E. coli. All federally supported work at universities and national laboratories in the U.S. was governed by the NIH guidelines. Industrial research by pharmaceutical and other companies was less tightly regulated because it is financed by private funds. Senator Edward M. Kennedy held hearings with the aim of formulating federal legislation governing recombinant DNA research, but because the furor over the topic waned, the legislation was not enacted.⁴

The public controversy extended to state and local governments. Several states enacted legislation governing DNA research. At the local level, the most publicized brouhaha occurred in Cambridge, Massachusetts, the location of both Harvard University and the Massachusetts Institute of Technology. The Cambridge Experimentation Review Board was appointed by City Council on August 6, 1976, to consider whether high risk level DNA research should be allowed to be conducted within the city. The review board, which consisted entirely of "lay" citizens, submitted a unanimous recommendation on February 7, 1977, to allow the research in question, with certain additional stipulations over and above the NIH guidelines.⁵ Many scientists at the two institutions were not accustomed to being held accountable to the public for their research in this manner.

Many of the molecular biologists who originally thought recombinant DNA research should be restricted, soon began to feel that the 1976 NIH guidelines were too strict. They thought that their research programs were unduly restricted, and they objected to the fact that DNA research was being carried out very fruitfully in countries with less restrictions. Furthermore, they were of the opinion that fears of the dangers of the DNA work were unfounded. NIH relaxed most of its guidelines in January of 1980 to facilitate recombinant DNA research in the United States.

Industrial firms had some concerns of their own. They felt that the 10 liter volume limit prescribed by the guidelines prevented scale-up research required to develop industrial processes. They were also afraid that disclosure of research procedures would endanger the need to keep commercially valuable information private. NIH has also relaxed the guidelines that affect industrial research in answer to some of these concerns.

In these controversies the scientific community in the United States has shown restraint and responsibility. The ban on recombinant DNA research was largely self imposed. R. Goodell has described how lobbying and uncritical press coverage has contributed to the lifting of constraints on investigation of recombinant DNA.⁶

In these controversies the scientific community in the United States has shown restraint and responsibility.

A New Source of Enzymes

Enzyme technology, while less dramatic than genetic engineering, also receives a considerable share of funds from companies interested in the biotechnology market. Separation of cell and the product can be made very easy by immobilizing these cells or their enzymes in a solid matrix or a small pore gel. As nutrients ("substrate") are passed by the cells, they are converted to the desired product by cell enzymes.⁸ Japan is leading in research and application of this technology. It seems to be a natural extension of that country's fermentation and antibiotics industries.

One gene that has received enormous interest and publicity is the one that contains the information for the synthesis of interferon, a substance that is produced by the body to fight viral infections.' Interferon is presently the subject of much medical research because it is thought to be an effective weapon against cancer. Initially, this substance had been painstakingly removed from white blood cells. Now it is available from other sources: from human cell cultures, in which fibroblast or lymphoblastoid cells are grown, not unlike bacteria. Recombinant bacteria, carrying the gene for interferon, have also been used to produce the substance. Several corporations and countries are interested in the production of interferon; a commercial plant for fibroblast interferon is being built in Israel by the Yeda Company of Japan and the Ares Company of Switzerland. The laboratory of Dr. Charles Weissman in Zurich, in research paid for by Biogen, a drug company, has produced a strain of recombinant bacteria that produces interferon. It is probable that this will lead to commercial production by Biogen before long. Interferon produced by recombinant technology may eventually be cheaper than that produced by cell culture techniques. The high cost of interferon presently available has made wide use impossible.

The story of interferon research in the United States reads like a spy novel. In the race for the production of a commercially suitable strain, the old habit of researchers of exchanging bacterial strains and other biological materials may have led to the acquisition of the interferon gene by the Genentech corporation. Nicholas Wade" gives one version of the story of how Genentech is thought to have obtained the interferon gene from UCLA researchers. Although Biogen seemed to have the lead in producing recombinant interferon, Genentech, in collaboration with Hoffman-LaRoche, announced in June, 1980, that they were able to produce two kinds of recombinant interferon, and that enough interferon would soon be available for clinical trials. Other pharmaceutical companies in the U.S. are thought to be in hot pursuit. It is ironic that despite all this

effort, the therapeutic effect of interferon on cancer remains unknown.

Another exciting development over the last two years is the production of pure antibodies by new tissue-culture techniques. Antibodies are substances produced by the body to neutralize harmful substances or organisms. While many cell types of the body can be grown in laboratory cultures, not unlike bacteria, the culture of antibody secreting cells had not been achieved successfully. However, British scientists were able to produce antibodies in tissue culture by fusing an antibody-secreting cell with a tumor cell. Cultures of this kind have been found capable of producing very pure antibodies. Such substances can be injected to fight a disease in the recipient. In the United States, several small companies, which will produce such ,'monoclonal antibodies", have been formed, and some commercial products that have been produced in this way are now on the market.¹¹

It is difficult to keep up-to-date on the commercial ventures that aim to capture a share of the biotechnology market. In recombinant DNA technology, four pharmaceutical firms, Cetus, Genentech, Genex, and Biogen, have captured most of the news, but many other small companies have made huge paper profits, and have made instant millionaires of many scientists who are connected with them.¹² Other companies, perhaps less spectacular, are pursuing other biotechnology projects in enzyme or monoclonal antibody production.

As the concerns of the biological community about safety recede into the background, developments related to the new biotechnology are giving rise to new controversies. Some of these are related to the task of universities and their faculties, to the desirability of patenting new strains of bacteria and their products, and to the role of national governments in fostering new biotechnology industries within their countries.

I am very concerned about the growing influence of industry on academic science ... The direction of research influenced by industry rnay not be the direction that is in the public interest. Corporate requirements for scientific research may be at odds with pressing societal needs. There are many examples one could cite, especially in environmental research, nutrition and biomedical science. (S. Krimsky in an interview, Nature, January 10, 1980, p. 130-131)

Many have suggested that the biotechnology business can compromise the academic integrity of universities. Universities and their faculty members are rushing to become involved in biotechnology projects. Such involvement can take several forms: by faculty members serving as consultants to biotechnology firms, by faculty members in universities forming their own commercial enterprises, and through the funding of private or department research by corporations. While some faculty members are happy to cash in on their new-found and unexpected commercial worth, others have serious questions about the commercialization of the university. The magnitude of the gene boom should not be underestimated: a Harvard faculty member estimated that one half of his colleagues are involved in companies in one form or another. This has led to tensions within some universities, and to envy by scientists in more traditional disciplines.¹³

Commercial enterprise by a university is not a new phenomenon. The University of Toronto operated Connaught Laboratories at arm's length for many years, for example. Patents on the products of scientific research that benefit academic institutions have been common also. Departments such as engineering and medicine would not be able to attract faculty members if consulting activity or private practice would not be allowed. Nevertheless, the questions being posed in the current debate seem to have a new urgency.

In the Supreme Court decision there seems to be a particular insensitivity to the uniqueness of living creatures.

What is the task of a university? I have difficulty accepting the usual statements about objectivity and academic freedom. Rather, I would stress the importance of a university's commitment to respond with research and teaching to human and societal needs. It seems to me that it is the university's ability (or willingness) to respond to such needs that is compromised by the commercial involvements. Where do the institution's commitments fie, to the development of new commercial bio-medical products or to the society that make its existence possible? When the economic dominates the academic, some research options that should be pursued, will be ignored. "Just as war related academic research compromised a generation of scientists, we must anticipate a similar demise in academic integrity when corporate funds have an undue influence over academic research," states S. Krimsky in the interview cited above.

Faculties of applied sciences such as medicine and agriculture are in a particularly touchy position. Faculty members in agriculture, for example, often are hired with research on problems in the industry of agriculture, or developmental research at an experimental station, as part of their job description. J. L. Fox has described how the ability to respond to the needs of agriculture can be endangered when a member of an agricultural faculty becomes involved in entrepreneurial activities.¹⁴

Scientific communication, an important component of the academic enterprise, is endangered by the new entrepreneurial spirit in several ways. Disclosure of methods and results by way of conferences or research publications, the usual means of sharing scientific information, is hardly advisable when these methods and results are part of a production process in a commercial enterprise. I I Furthermore, not giving in to the lure of the game may be even less fruitful. The discoverer of monoclonal antibodies, C. Milstein from Great Britain, did not apply for a patent on his new production process, preferring to give away cell cultures and procedures, only to find that the Wistar Institute in the U.S., and two it its employees had applied for, and had been granted, a patent for the new technique.¹⁶

Graduate students and "post-docs" have charged that faculty advisors tend to neglect their duties when commerce enters the lab. Faculty advisors have less time to discuss research projects, or research conferences are designed to glean information for the advisor's company. Others experienced that advisors were more interested in recruiting a young PhD graduate for their private firm than helping him or her obtain an academic position.¹⁷

Dr. Derek C. Bok, president of Harvard University, announced in November, 1980, that the university had decided not to become a partner in a firm that would exploit findings of the laboratory of one of its faculty members, Professor Mark Ptashne. Harvard's decision was reached after a great deal of discussion and internal controversy. Dr. Bok suggested in a subsequent article that the decision not to participate in the new company leaves many questions unanswered, questi6ns to which the Harvard community will have to address itself." At other universities commercial involvement has been initiated without much protest.

One group of countries that will not be participating in the establishment of biotechnology industries are those of the Third World.

There is precedent for granting patents on life forms. In many western countries, including the United States, seeds and nursery stock can be patented. Patenting of seeds has been possible for many years, but is becoming embroiled in a controversy of its own because it is felt that such patenting is eroding the genetic base of the world's food supply, and is making some needed seeds unavailable to Third World farmers.²⁰ Seeds and plants are covered by patent legislation passed by U.S. Congress in 1930 and 1970. Fungi and bacteria were specifically excluded by the 1970 law. The Supreme Court decision now grants bacteria the same status as plant varieties.

Jeremy Rifkin has discussed the implications of the Court decision.²¹ He is firmly opposed to the patenting of new bacterial strains because recombination effected in the laboratory transgresses natural boundaries, is dangerous, and only benefits large corporations. He calls upon church leaders and other concerned Christians to work towards stopping recombinant DNA work. Since the time of the article, research and development of biotechnology products has gone ahead with very little public reaction. Goodell, in a perceptive article, has explored why it is that the press now supports DNA work so enthusiastically and optimistically.²²

The Christian community should continue to raise meaningful questions about the new biotechnology. Is the safety issue less of a concern now, two years later? Will the new technology help those people who need it most, namely the sick and the hungry? Is there concern for developing medical products for third world diseases?

in the Supreme Court decision there seems to be a particular insensitivity to the uniqueness of living creatures.

The bottom line of the Supreme Court's decision is that it does not matter whether something is living or not: Its patentability depends on whether it is a product of nature or man-made ... The Supreme Court's thinking therefore follows the reasoning of a lower court, ... which concluded after its review of the case: "In short, we think the fact that micro-organisms, as distinguished from chemical compounds, are alive, is a distinction without legal significance."²³

One need not be opposed to the new DNA technology to object to this view of nature. It is important that Christians resist such exploiting language, and the view of nature that it conveys.

Not only is there pressure on a government to invest in the development of biotechnology within its borders, there is also pressure to relax whatever research guidelines there may be. There is a considerable loss of employment and prestige when a large corporation decides to move its laboratories to another country, where more favourable financial and regulatory conditions apply. There is also a tendency for research scientists to move out of a country if the research they wish to pursue is not possible there.²⁴

One group of countries that will not be participating in the establishment of biotechnology industries are those of the Third World. This is ironic because these countries desperately need the help that biotechnology can provide in fighting parasitic and other diseases, and in fighting hunger by providing such products as single-cell proteins for diet supplements. It is a necessary part of development aid that developed countries see to it that the countries of the third world share in the benefits of the new technology.

REFERENCE

¹Parts of this section of this paper have appeared in: H. Cook, "The Recombinant DNA Debate", Pro Rege (published by the faculty of Dordt College, Sioux Center, Iowa), 7 (1979), 2-7.
²For a discussion of these and subsequent events see: William Bennett and Joel Gurin, "Science that Frightens Scientists, The Great Debate over DNA", Atlantic, Feb. (1977), 43-62.
³Federal Register, 7 July (1976), 41-131.
⁴Barbara J. Culliton, "Recombinant DNA Bills Derailed:, Congress Still Trying to Pass a Law", Science, 20 Jan. (1979), 274-277.
⁵'The Cambridge Experimentation Review Board", Bulletin of the Atomic Scientists, May (1977), 23-27.
⁶Rae Goodell, "The Gene Craze", Columbia Journalism Review, Nov.-Dec (1980), 41-45.
⁷Nicholas Wade, "Recombinant DNA: Warming Up for Big Payoff" Science, 9 Nov. (1979), 663-665; Ronald Wetzel, "Applications of Recombinant DNA Technology", American Scientist, 68 (1980) 664-675.
⁸See several articles under the heading "The Biology Business" in Nature, 10 Jan. (1980).
⁹See articles by N. Wade in Science, 16 May (1980), 688-692, and 26 Sept. (1980), 1492-1494.
¹⁰N. Wade, 26 Sept. (1980).
¹¹IN. Wade, "Hybridomas: A Potent New Biotechnology", Science, 16 May (1980), 692-693; Cesar Milstein, "Monoclonal Antibodies", Scientific American, Oct. (1980), 66-74.
¹²IN. Wade, 16 May (1980), 688-692.
¹³Jeffrey L. Fox, "Can Academia Adapt to Biotechnology's Lure?", Chem ical and Engineering News, 12 Oct. (1981), 39-44.
¹⁴Ibid, pp, 40-42.
¹⁵N. Wade, 26 Sept. (1980).
¹⁶N, Wade, "Inventor of Hybridoma Technoloey Failed to File for Patent", Science, 16 Mav (1990), 693.
¹⁷J. L. Fox, 40-42.
¹⁸D. Bok,---Presidential Address", Harvard Magazine. May-June (1961) See also Nature, 27 Nov. (1980), 311, and 4 Dec. (1980), 423-424.
¹⁹N. Wade, "Court Says Lab-Made Life Can be Patented". Science, 27 June (1980), 1445.
²⁰P. R. Mooney, Seeds of the Earth, Inter Pares, Ottawa, 1980.
²¹J. Rifkin, "Playing God", Sojourners, August (1980), 9-10.
²²R. Goodell, pp. 41-45,
²³N. Wade, 27 June (1980).
²⁴The Jan. 10 (1980) issue of Nature (pp. 122-131) "reviews the state of the art of biotechnology around the world". See also several articles in Nature, Jan. 24, (1980), 319-325.