Science in Christian Perspective

Reproductive Biotechnology:

An Animal Scientist's Perspective

The "cultural mandate" implied in the first chapter of Genesis grants authority to humankind over the creation. Although authority was granted, how far does it extend and how far should we extend it? New technologies are being developed that manipulate the normal reproductive patterns of laboratory and domestic animals. These include changing the genetic composition of the genome, freezing embryos, in vitro fertilization, and even cloning of early stage embryos. The question of "how much manipulation should humankind be allowed to do on animals?" is then raised. This is a relevant question since most human medical advances are first developed in laboratory and domestic animals prior to their human application.

The Cultural Mandate

Biotechnology, the application of chemical, physical and engineering principles and techniques to biological systems, offers potential for significant benefits in medicine and agriculture. But does biotechnology sound as if it could be unbiblical, evil, or an enterprise with which we Christians should not associate? Should we abhor emerging technologies that deal, for example, with in vitro fertilization (test tube babies), or embryo transfer (the use of surrogate mothers), both of which are presently applied in human medicine? Is this a form of "creating a new life," tampering with something sacred, somehow playing God? Both secular and Christian scientists have already begun to deal with these issues.⁴

The new biotechnologies that are being applied in domestic farm animal production and in research on reproduction are nothing short of amazing. Artificial insemination with frozen semen, introduced in the 1950's, permits high quality bulls to be bred to cattle throughout the world. More recently, technologies related to the early embryo have emerged. Embryos may be split at early stages to produce identical twins.⁵ Production of two identicals can be very valuable to research scientists (a near-perfect control for experiments) as well as doubling the number of embryos for transfer from a genetically valuable mating. Another technique is that of freezing embryos for later transfer to surrogate mothers who may be located anywhere in the world.⁶ This ability is very valuable when an excess of embryos are produced for the available recipients. The sex of embryos can also be determined prior to transfer to a recipients.⁷ With some techniques the sex determination occurs after transfer or freezing, and the embryos of the undesired sex are then aborted or just never thawed. Newer technologies include altering the genome of animals by injecting the pronucleus of a one-celled egg with a gene⁸, or by using replication defective viruses to deliver the gene⁹; creating large numbers of identical individuals by nuclear transfer or cloning.¹⁰ The cloning procedure entails transferring nuclei from a pre-implantation stage embryo back to enucleated one-cell eggs. These eggs are then allowed to develop to the pre-implantation stage for transfer to a surrogate, recloning, or freezing for future cloning. In vitro fertilization, only recently well-developed in the cow and not in commercial practice, offers potential for the production of large numbers of eggs all fertilized with the same amount of semen usually required for a single cow, thus extending the possible genetic impact of a single bull many times.¹¹

These techniques can be used to both increase genetic gain, by extending the selection pressure, and provide a broader genetic base, by freezing large stocks of genetic material. All of these relatively new technologies are currently being researched and applied with success in livestock. Are these new technologies inherently evil?

If we understand Genesis 1 to actually mean that humankind has absolute authority over "every living thing," then we have the authority to develop and perform these techniques on domestic animals. But should we? These new techniques are all designed in some way or another to increase animal production. Do we need more production from our livestock species? With the current glut of agricultural products and depressed commodity prices one does wonder. More efficient agriculture may not be what the United States needs, but it is what the world needs. Self-proclaimed prophets have been predicting famine if agricultural production does not increase. Have we had famine? No, not in the U.S. Here we have seen the "Green Revolution." In 1800, 94% of the U.S. population was directly involved in agriculture. Dramatic increases in agricultural production have since occurred so that now less than 3% of the U.S. population is directly involved with agriculture, while the U.S. supplies about 30% of the world's agricultural exports.¹² What about other countries? An occurrence in some underdeveloped countries is low agricultural output. Politics or religious beliefs may contribute to this low level of output, but technology could help raise it. If plenty of food were both available and justly distributed, then time and resources could be spent developing other industries. This would in turn offer potential for improving living standards, such as constructing better housing, improving sanitation, transportation, and communication. Should new technologies be used to increase animal agricultural production?

It is difficult to find a biblical parallel to reproductive biotechnology. Two examples are found in Genesis 30:27-43, where Jacob bargains with Laban for all of Laban's imperfectly colored sheep and goats. Jacob uses techniques based upon superstition to change the ratio of offspring that are imperfectly colored. Later, to his credit, he acknowledges God's hand in controlling this ratio (Genesis 31:9). The second example is illustrated within the passage where Jacob selectively uses this technique when the strong animals are mating and not when the weak are mating (Genesis 30:41-42). This shows that Jacob mated the best males to the best females, and therefore imposed selection pressure on the matings that would result in imperfectly colored offspring. This selection pressure resulted in Jacob acquiring, although imperfectly colored, strong livestock.

It is interesting to note in the context of selective breeding (i.e., breeding the strong with the strong) that God's command for sacrifices would result in a negative selection pressure. The animals for sacrifice were required to be without defect (Genesis 12:5; Exodus 29:1; Leviticus 1:3; 3:1; 4:3; 5:15). Since the animals without defect were offered as sacrifices, a larger percentage of the animals that were allowed to mate would be imperfect, and thus the resulting offspring would more likely be imperfect. Thus, by God's cornmand the Jews likely maintained herds of livestock that had a broader genetic base than if only the strong were mated with the strong.

Should reproductive biotechnologies be used on domestic animals? Since God does not command against it, and it can increase the quality of life and help prevent famine and human suffering, the answer is then: "Yes, these technologies should be perfected and applied in animal agriculture!"

Now for the more difficult question of the application of some of these techniques in the human. Most advances in human medicine are first developed and perfected in laboratory and domestic animals. Some say that a number of these technologies ought not be applied in the human, and therefore should not be perfected in livestock. In some respects, human embryos would be easier to manipulate. Human embryos have relatively transparent cytoplasm, and they develop in vitro more readily than do livestock embryos.¹³ Should this research in animals be permitted? In other words, does the "cultural mandate" of Genesis 1 include reproductive biotechnology with human applications?

Often the answer too-quickly returns: "NO! Human life is sacred! You're playing God!" With current technologies this may be the best biblical answer. But as technologies improve and become more efficient the answer may change!

For example, suppose a couple has a genetic disorder such as hemophilia. Persons with this disease lack coagulation Factor VIII in their blood, and therefore

In 1722 Cotton Mather ... urged Bostonians to undergo immunizations for smallpox, but many resisted fo because it was somehow "playing God."

have problems with spontaneous or traumatic subcutaneous and intramuscular bleeding. This trait is genetically passed through generations and affects only males; although it is carried by females, they do not exhibit hemophilia. Suppose also that the DNA (Deoxyribonucleic Acid) sequence for Factor VIII were known and could be injected into embryos to correct this problem-not only for their children, but for their grandchildren and forever, never again to show up in their descendants. The potential is great. But to do this, with current technologies, over 50 fertilized human embryos would have to be surgically collected from the female, and the fertilized embryos surgically injected with the DNA or "gene" under a microscope. ¹⁴ This should yield a single embryo that will incorporate the DNA and correctly produce Factor VIII. This resulting child would have the DNA sequence in his or her cells, but the DNA sequence, or gene, would probably not be in the correct place on the chromosome, much less even the correct chromosome. You say "Great, but what about the other 49 embryos?" Some of the embryos would be destroyed by the injection procedure and those that survived, later transplanted and developed into adults, would not produce Factor VIII. With current biotechnical- techniques this alternative is neither biblical nor practical.

Suppose, that in the future it would be possible, with new techniques, to construct a replication deficient virus to inject the DNA sequence, and the DNA sequence could be specifically directed to the right place on the right chromosome every time. Don't think that it cannot be done. God said ". . . nothing will be restrained from them [man], which they have imagined to do" (Genesis 11:6, KJV). The techniques using viruses to inject the DNA or RNA are already developed, and techniques are being developed to direct the exact site on a certain chromosome with which the DNA will be incorporated. This is being done in laboratories here at the University of Wisconsin-Madison and in laboratories on campuses across the nation. "¹⁵ This technique, if applied in the human, would require only one more step in the already-used in vitro fertilization programs, and could be very efficient, but most importantly it would not destroy any embryos as does the surgical injection procedure. A physician would then be able to treat the patient at the earliest possible moment, when he or she is still a single cell.

If the answer still returns, "You're playing God!" or "What if it is God's Will for you and your descendants to have hemophilia?", then the question to be asked of you is, "Are you not already playing God?" For example, in 1722 Cotton Matber, a leading minister in New England, urged Bostonians to undergo immunizations for smallpox, but many resisted because it was somehow "playing God."¹⁶ Have you ever received any vaccinations for smallpox, flu, mumps, tetanus, polio, measles, whooping cough, diphtheria, etc.? In 1752 one of our founding fathers, Benjamin Franklin, invented the lighting rod and proposed to save countless buildings from burning to the ground from lightning strikes. This was opposed by some because it was felt to interfere with Divine Providence. ¹⁷ But is this interfering with God's Will? Are we changing the directed path of lightning sent from heaven (job 37:3, KJV: "He [The Lord] directeth ... his lightning unto the ends of the earth")? Today does anyone even give a thought as to whether a building has a lightning rod on it or not before he or she enters?

The purpose of this article is not to persuade people that all biotechnology should be readily embraced and that genetic engineering offers only good, but to inform the reader of emerging technologies and to show an example of some good that can come of biotechnology and genetic engineering research. The above example of gene transfer via viral vector may be a futuristic ideal and does not address the questions raised with other applications of reproductive biotechnologies. These include: "What happens to frozen human embryos that are no longer desired?", "What happens to human embryos that are of the undesired sex?", and "Is making two or more identicals by splitting or cloning wrong?" To use some of these new technologies in human medicine for the sake of convenience is not consistent with the "cultural mandate."

Some of these new technologies, however, should not be automatically rejected. Many new technologies are not accepted at first because of the fear of the unknown. We simply do not understand bow they work, and therefore fear them. Or, because they could be used for evil purposes we do not accept them. Many feared the computer because they didn't understand

Many new technologies are notaccepted at first because of the fear of the unknown.

how it worked, and/or because it could be used by the Antichrist. Some still have reservations about using their bank card to make automatic withdrawals from savings or checking accounts to pay for groceries every week. This would be giving too much control to the banking industry, and could be used for evil as predicted in Revelation-where it speaks of the Antichrist's rule: "And that no man might buy or sell, save he that had the mark, or the name of the beast, or the number of his name" (Revelation 13:17, KJV). However, many of these technologies, such as the computer, have been used to help spread the gospel worldwide (for a review of objections to high technology see D.W. Aycock¹⁸). It should also be pointed out that these technologies, as all types of technology, will be used for evil. Man is inherently evil and without Christ will do evil. Already there is a published report in scientific literature of an attempt at cloning by nuclear transfer and a fictional book on the subject.¹⁹

Since humankind was given the "cultural mandate," we have the authority to use these technologies on animals, but we also have the responsibility of caring for them as implied in Genesis: "And the Lord God took the man, and put him into the garden of Eden to dress it and to keep it" (Genesis 2:15, KJV). The two key words of this passage are "dress" and "keep." Dress, also translated "cultivate," is derived from the Hebrew abad which means to serve or till, or to labor on behalf of.² This word is also used in Deuteronomy (28:39) in describing the care of vineyards. The second word, translated keep, is from the Hebrew shamar which means to watch, to preserve, to take care Therefore, humankind is a steward of the garden. A steward who must give account of and be responsible for his or her actions. As stated by F. Schaeffer: "We have dominion over nature, but it is not ours either. It belongs to God, and we are to exercise our dominion over these things not as though entitled to exploit them, but as things borrowed or held in trust. I am to use them realising that they are not mine intrinsically. Man's dominion is under God's dominion and God's domain. "²⁰

Since Adam and Eve were created in the image of God, more restraint must be applied when considering the use of new technologies which will be directly used on humans. Although we know that any technology could be used for evil, we as Christians need to prayerfully evaluate technological advances and their possible positive uses: the spreading of the Gospel and the good of humankind. Remember: "And we know that all things work together for good to them that love God, to them who are called according to his purpose" (Romans 8:28, KJV)-even new biotechnology!

©1988

ACKNOWLEDGMENTS

1 would like to recognize the many stimulating discussions and helpful suggestions provided by R. L. Stiling and my wife J. L. Prather.

Randall S. Prather is a postdoctoral researcher with a dual appointment in the Departments of Zoology and Meat and Animal Science at the University Of Wisconsin-Madison. He received his B.S. in Aninwl Science and M.S. in Reproductive Physiology at Kansas State University, and his Ph.D. from the Endocrinology-Reproductive Physiology Training Program at the University of Wiscon. n-Madison. His current research revolves around how the nuclear envelope and nuclear matrix affect differentiation in preimplantation embryos of the domestic species.

NOTES

¹. The "cultural mandate," as some have called it, is clearly a very expressive figure of speech for: first, intense study of the earth (with all of its intricate processes and complex systems) and second, utilization of this knowledge for the benefit of the earth's inhabitants, both animal and human. Morris, H.M. (1976) in, The Genesis Record: A Scientific and Devotional Comnientary on the Book of Beginnings. Grand Rapids: Baker Book House, p. 77.

². Harris, R.L., C.L. Archer and Bruce K. Waltke (1980). Theological Wordbook of the Old Testament. Chicago: Moody Press. Brown, F., S.R. Driver and C.A. Briggs (1977). A Hebrew and English Lexicon of the Old Testament. Oxford: Clarendon Press.

³. Barker, K. (ed.) (1985). The New International Version Study Bible. Grand Rapids, MI: Zondervan, footnote to Genesis 1:5., p. 6.

⁴. McLaren, A. (1985). "Research on early human embryos from in latro fertilization (IVF): The Warnock recommendations." British Journal of Obstetrics & Gynaecology, 92:305-307. Walters, L. (1986). "The ethics of human gene therapy." Nature, 320:225-227. Jones, D.G. (1987). "Some implications of the new reproductive technologies. " Perspectives an Science and Christian Faith, 39:31-38.

⁵. Williams, T.J., R.P. Elsden and G.E. Seidel, Jr. (1983). "Bisecting bovine embryos: methods, applications, and success rates." Proceedings of the Annual Conference on Artificial Insemination & Embryo Transfer in Beef Cattle (Denmr). Columbia, MO: National Association of Animal Breeders, pp. 45-51.

⁶. Rall, W.F. (1986). Embryo cryopreservation: current application prospects for the future." Proceedings of the Annual Conference on Artificial Insemination & Embryo Transfer in Beef Cattle (Dentwr). Columbia, MO: National Association of Animal Breeders, pp. 48-52. Prather, R.S., M.F. Spire and R.R. Schalles (1987). "Evaluation of cryopreservation techniques for bovine embryos." Theriogenology, 28:195204.

⁷. Anderson, G.B. (1987). "Identification of embryonic sex by detection of H-Y antigen." Theriogenotogy, 27:81-97.

⁸. Hammer, R.E., V.G. Pursel, C.E. Re road, Jr., R.J. Wall, D.J. Bolt, K.M. Egbert, R.D. Palmiter and R.L. Brinsxter (1985). "Production of transgenic rabbits, sheep and pigs by microinjection. " Nature, 315:6

⁹. Rubenstein, J.L.R., J.F. Nicolas and F. Jacob (1986). "Introduction of genes into pre-implantation mouse embryos by use of a defective recombinant retrovirus." Proceedings of the National Academy of (USA), 83:

¹⁰. Seidel, G.E. Jr. (1983). "Production of genetically identical sets of mammals: Cloning?" Journal of Experimental Zoology, 228:347-W4. Willadsen, S.M. (1986). "Nuclear transplantation in sheep embryos." Nature, 320:63-65. Prather, R.S., F.L. Barnes, M.M. Sims, J.M. Rohl and N.L. First (1987). "Nuclear transplantation in the bovine embryo: assessment of donor nuclei and recipient oocyte. " Biology of Reproduction, 37:85-866. Prather, R.S. (1988). "Nuclear transplantation: nuclear equivalence, species specificity?" in, The Molecular Biology of Fertilization, Schatten and Schatten (eds.). Orlando: Academic Press, 1988 (in press). Marx, J.L. (1988). "Cloning sheep and cattle embryos." Science, 239:463- 464.

¹¹. Sirard, M.A. and R.D. Lambert (1986). "Birth of calves after in vitro fertilization using laparoscopy and rabbit oviduct incubation of zygotes." Veterinary Record, 119:167-169.

¹². Campbell, J.R. and J.F. Lasley (1985) in, The Science of Animals that Serve Humanity (3rd edition). New York: McGraw-Hill, pp. 33-36.

¹³. Tesarik, J., V. Kopecny, M. Plachot and J. Mandelbaum (1986). "Activation of nuclear and extranucleolar RNA synthesis and changes in the ribosomal content of human embryos developing in vitro." Journal of Reproduction and Fertility, 78:463-470. Kane, M.T. (1987). "Culture media and culture of early embryos." Theriogenology, 27:49-57.

¹⁴. Anderson, W.F. (1984). "Prospects for human gene therapy." Science, 226:401-409.

¹⁵. Smithies, O., R.G. Gregg, S.S. Boggs, M.A. Koralewski and R.S. Kucherlapati (1985). "Insertion of DNA sequences into the human chromosomal B-globin locus by homologous recombination." Nature, 317:230-234. Wake, CT., F. Vemaleone and J.H. Wilson (1986). "Topological requirements for homologous recombination among DNA molecules transfected into mammalian cells." Molecular and Cellular Biology, 5:2080.2089.

¹⁶. Miller, P. (1953) in, The New England Mind From Colony to Province. Boston: Beacon Press, pp. 345-wi. it should be pointed out that Mather's immunization procedures were unproven at this time in history. Therefore, two major questions were raised with Mather's proposed immunizations: 1. Did the procedure really work? and, 2. Did immunization interfere with divine providence?

¹⁷. Franklin, B. (1753). Poor Richards Almanac. Philadelphia. Bruce, W.C. (1917). Benjamin Franklin Self-Revealed. New York: G.P. Putnam's Sons, P. 358.

¹⁸. Aycock, D.W. (1986). "Christian objections to high technology: analyzing the resistances." Journal of the American Scientific Affiliation, 38:88-95.

¹⁹. Shettles, L.B. (1979). "Diploid nuclear replacement in mature human ovawith cleavage." American Journal of Obstetrics & Gynaecology, 133:222-225. it should be noted that the accuracy of this paper should be questioned after analysis of two of the figures and legends. The cell used as a recipient contained a nucleus, and according to the description should have been in metaphase 11 of meiosis. Secondly, the supposed morula, if truly a morula, is certainly abnormal and may be a result of fragmentation, not division. Rorvik, D.M. (1978). In His Image. Philadelphia: Lippincott Company.

20. Schaeffer, F.A. (1970) in, Pollution and the Death of Man. London: Hodder and Stoughton, p. 51.