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A Geneticist's and Breeder's Perspective on Cloning Texas Longhorn Cattle
©David M. Hillis, Professor, School of Biological Sciences, University of Texas, Austin, TX 78712
Recently, there has been considerable discussion about the potential problems and potential benefits of cloning Texas Longhorn cattle. I study the effects, patterns, and consequences of genetic variation, but I do not have any monetary or personal involvement in cloning. I am a Texas Longhorn breeder, but I have not used cloning in my own herd. I have neither opposed nor promoted cloning as part of my job or as a Texas Longhorn breeder. I have followed the developments regarding cloning in the Texas Longhorn breed from an academic and a personal interest, and I have heard many of the arguments for and against cloning and regarding the participation of clones in breed association activities. From a scientific standpoint, I think there is some truth to the arguments being made on both sides of the cloning issue, as well as some misunderstanding on both sides. My hope is that Texas Longhorn breeders will take into account the scientific facts about cloning in any deliberations about how and whether clones should or can be utilized in the breed. Here are some comments about various aspects of cloning that may prove helpful as the various breed associations addresses this important issue.
Health Aspects of Cloning
1. Many successful clones of cattle have been produced, and many individual adult cloned cattle appear to be in good health with no major health problems reported to date.
2. There is no evidence (or expectation) that food products from cloned animals are dangerous for human consumption. The genomes of all animals, cloned or otherwise, contain some new mutations that were not present in the previous generation. Although the nature of these mutations may differ somewhat in clones, and additional gene expressional differences occur as well, there is no evidence that any changes that result from cloning present any dangers to humans who may consume the milk or body parts of cloned animals.
3. To my knowledge, no differences or problems in the health of the offspring from cloned cattle (produced through normal sexual reproduction) have been reported, and the offspring of cloned cattle are not expected to differ genetically in any significant manner from offspring produced from non-cloned cattle.
1. There is good evidence that clones are generally not as healthy as the original animals from which they are cloned. This is an average, and individual animals can and do vary in their health status. Thus, all clones are not necessarily unhealthy. Nonetheless, the following problems have been documented:
a. In species for which appropriate data can be analyzed, clones have a reduced expected life span. This has been well documented in species with short generation times, such as mice. However, as the expected life spans of cattle are much greater than mice, and as the number of cloned cattle of sufficient age is not yet available, the extent of this expected reduced life span has not yet been sufficiently documented for cattle. Nonetheless, sudden deaths among previously healthy-looking clones have been documented in animals cloned from adult somatic cells, including cattle and sheep. There is evidence for some changes in genetic elements called telomeric sequences, which occur at the ends of chromosomes. The reduction of these sequences have been implicated in the normal aging of cells. However, the data from cloned cells have not been consistent, with some clones showing shorter telemetric sequences, and others showing longer telemetric sequences. It is possible that life span may simply be made more variable by cloning, with some clones actually living longer than normal, and others showing a reduced life span. There are not yet enough data from cattle to have a definitive answer to the question of the life span of cloned cattle, but most researchers expect cloned cattle will have a shorter life span than normal.
b. Cloned animals tend to have compromised immune systems and thus higher rates of infection. Again, this is better studied in cloned mice than in cloned cattle.
c. Some clones (including some cloned calves) are born abnormally large. These animals have abnormally enlarged organs, which usually lead to breathing and other problems. The reasons for this syndrome are not well understood. Companies that carry out commercial cloning do not pass these unhealthy clones onto the customer; instead, these clearly unhealthy animals are terminated.
d. There are gene expression problems in at least some cloned animals. In mice, researchers studied more than 10,000 liver and placental cells of cloned mice, and found that about 4% of the genes function abnormally in these cells of clones. These abnormal functions are not related to direct mutations, but instead to abnormal expression of otherwise normal genes. The cloning in this study was from stem cells, rather than adult somatic cells, and so it is not yet clear if similar problems occur from cloning of adult cattle.
2. Repeated, serial cloning of the same clonal family will result in the accumulation of deleterious mutations through time, as well as increase the risk for gene expression problems. Each clonal generation will be expected to have more of these genetic errors than the previous generation. Each time an animal is cloned (and indeed, every time any cell is replicated), a few errors are introduced into the replicated genome. The effects are generally considered to be small each generation, but they result in some of the problems noted above. However, it is clear that repeated, serial cloning is not advisable. The clones will not improve from generation to generation. If cloning were perfect, the best that could be expected is that the 2nd generation clones would be as good (from a genetic standpoint) as the original animal, or the 1st generation clone. However, since mutations (including nucleotide substitutions, and deletions of regions such as the telomeres) do occur each time a clone is made, a 1st generation clone is expected to be genetically more fit than a 2nd (or subsequent) generation clone.
Cloning and the human food supply
The US Food and Drug Administration has stated that food from cloned animals is safe for human consumption. However, because of public concern, and because additional studies are still being conducted, the restrictions on selling products from cloned animals for human consumption have not been lifted. This is unlikely to present an issue for some time for cattle, as cloned animals are too expensive to be used for anything except breeding purposes, but it is true that cloned animals can not contribute to the commercial food supply at this time.
How can clones be utilized to improve the Texas Longhorn breed?
1. One obvious beneficial use of cloning concerns the case of an exceptional steer that the owner regrets having castrated. The resulting cloned bull could then contribute to the genetic diversity of the Texas Longhorn herd, which would otherwise not be possible. In such a case, cloning the steer has some clear benefits. The same principle holds for cloning a freemartin (a sterile female fraternal twin of a bull calf). The clone of a freemartin would not be sterile, since the clone would not share placental circulation with a bull calf, as did the original freemartin.
2. Cloning can be used to replace a particularly valuable animal that has died pre-maturely, as in an accident, or has been injured so that it can no longer reproduce. Cloning could also be used to replace a valuable animal that has to be put down because of the threat of an infectious disease outbreak in a herd.
3. Exceptional cows can be cloned so that the clones can produce more offspring than the original cow could produce on her own.
4. In some cases of bacterial diseases that prevent an animal
from being used in a breeding program, a disease-free clone may be produced.
5. Many traits, such as horn length, are affected by both genetic and environmental effects. Thus, it is true that if one were to clone a cow with exceptionally long horns, the clones may well develop longer (or otherwise different) horns from the original, especially if they are kept in a superior nutritional environment. Environmental factors that may affect trait development include nutrition provided in the uterus of the birth dam, the birth dam’s milking ability, supplemental food and minerals provided to the calf, the range conditions where the calf is raised, the temperatures at which the calf is raised, etc. However, it should be noted that none of these changes affect the genetic potential of the clone. Thus, from a genetic standpoint, any two clones from a single individual are expected to have the same genetic potential for any given trait. In other words, the shortest-horned clone from a group of clones has the same genetic potential to produce long-horned offspring as does the longest-horned clone from the same animal. This is another reason that serial cloning (for instance, re-cloning the longest-horned clone from a group of clones) is not advisable. The environmental effects cannot be passed on from generation to generation, and some additional degradation of the genome will occur through accumulation of deleterious mutations.
Can cloning potentially hurt the Texas
1. Inbreeding of cattle is a potential danger for any breed. Inbreeding occurs when the number of genetically distinct animals in a herd is reduced, so that the effective population size is small. Traditionally, the greatest sources of inbreeding in cattle have been (1) intensive linebreeding to establish a morphologically uniform breed type (not much of a problem in Texas Longhorns, but a considerable source of genetic uniformity in other breeds); and (2) the repeated use of a relatively small number of popular herd sires. Inbreeding has been much less of a problem in Texas Longhorns than in most other breeds, in part because Texas Longhorn breeders actually select for diversity in some traits (such as color). This has had the benefit that Texas Longhorns have maintained a far greater level of genetic diversity than have most other breeds of cattle. This genetic diversity translates into the greater disease resistance, adaptability, and general health that characterizes Texas Longhorns.
Cloning of cows has the same potential to decrease genetic diversity as does repeated use of the same bull. If both of these factors are used simultaneously, genetic diversity would be reduced dramatically. However, inbreeding is usually viewed as a personal choice made by an individual breeder, and not something that should be regulated by the breed association.
2. There is a potential of introducing new deleterious mutations into the breed through cloning. However, new deleterious mutations can also be introduced through sexual reproduction. In general, the risk of this problem with cloning is not expected to be substantially greater than from other forms of reproduction. However, since cloned animals are relatively expensive, there may be a smaller likelihood that owners would be willing to cull cloned animals if they exhibited a genetic defect.
3. As noted earlier, if serial cloning is conducted, there is a much greater danger of accumulated mutations. There are no added benefits of 2nd generational cloning, and there are increased risks to the breed that are associated with this practice.
Entry of clones into shows and contests
Cattle shows and contests are generally considered showcases for breeders and owners, who have worked to produce new genetic combinations of cattle through their breeding programs. There are elements of skill and chance in producing the best show cow or bull, or in producing the longest-horned Texas Longhorn. Breeders study the best genetic lines, and experiment by crossing cows with bulls that they think will produce unique or superior genetic combinations.
Cloned animals, in contrast, produce a known and non-unique genetic combination. Clones are replicates of animals—typically animals that are already known to be among the best in the breed. From a genetic standpoint, allowing entry of clones into a show or contest is exactly like allowing the same animal to be entered twice in the same show (perhaps once by the breeder and once by the owner). Should the same animal be allowed to claim more than one spot in a show? Should the same animal be allowed to compete year after year in the same age class?
Allowing clones to compete in a show or contest removes the elements of breeding skill and genetic chance. From a genetic point of view, it does not seem reasonable to let clones (of known genetic potential) compete against animals of original, new genetic combinations (or unknown genetic potential). However, allowing the non-clonal offspring of clones to compete in shows is reasonable, since these offspring have the same level of genetic variability (and the same chances for quality, both good and bad) as any of the offspring of the original animal.
Likewise, there may be reasons to compete clones against one another. Although the genetic potential of the animal is known, the environmental conditions may differ. So, a person may wish to demonstrate the effects of a superior diet, for instance. For this reason, it would not be unreasonable to have a separate category for clonal animals in competitions.
1. There are legitimate reasons to clone Texas Longhorns that can result in potential benefits to the breed. There are also potential dangers in cloning. Thus, the decision to clone or not clone requires an individual choice, based on the scientific factors as well as personal views. The same could be said about many other choices made by individual Texas Longhorn breeders. I do not think there is a scientific reason to prohibit clones from breed registration. Instead, this is a matter of personal preference, and thus a matter for association membership to decide, both collectively as well as on an individual basis.
2. If clones are to be allowed in shows or contests, such as the Horn Showcase, I recommend that separate categories be created for clones. The elements of skill are limited in the case of clones to nutritional and other environmental conditions of the calves, whereas competitors who do not use cloning are competing primarily in producing new genetic combinations of cattle. The two objectives are clearly distinct, and it does not make sense to combine and confuse the competitions.
3. Offspring of cloned cattle, produced through normal sexual reproduction, should be allowed to compete in the standard category of shows and contests (that is, compete against other non-clonal animals). Using a cloned cow to produce new genetic combinations is similar to using the semen (through artificial insemination) from a popular bull. In both cases, methods are being used to increase the breeding opportunities of the respective animal.
4. Serial cloning of animals (more than one generation of cloning, or the cloning of clones) should be discouraged, and the association should consider whether registration of such animals is in the best interest of the breed. Each subsequent generation of clones will accumulate additional genetic mutations. The probability that these mutations will be deleterious far outweighs the chance that they will be beneficial, so a genetic degradation of the successive clones is expected.
5. Ownership of cell lines and genetic material should be treated exactly like ownership of the animal itself. When a person sells an animal, he or she is free to sell partial ownership of the animal, as long as the conditions are made clear at the time of sale. The same principle should hold true for cloned animals, cell lines, and genetic material that can potentially be cloned. Any retention of such material should be treated like partial ownership of the animal, since the clones are not individually distinct. Otherwise, ownership of any genetic material or cell lines should be transferred along with the animal from which they are taken.
I hope these comments will prove helpful to Texas Longhorn breeders as they consider the pros and cons of cloning. Please feel free to send questions or comments to DoubleHelix@att.net.
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