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article appeared in the July-August 2002 edition of Bovine Veterinarian magazine
Cloning cattle is already happening. How can this technology fit into our current
and future beef and dairy operations?
At first glance, these five good-looking Chianina calves are nothing special.
They’re cute, healthy, husky and playful like most 5-month old calves. In
other words, they are normal. So what’s so special about them? They are
genetically identical. All cloned from one popular Chianina bull from Oklahoma.
Cloning has made its way from science fiction to the farm, and it’s happening
at a more rapid rate than you may think. Since Dolly the sheep was cloned in 1996
(see cloning timeline sidebar), there have been hundreds of cattle and pigs that
have been cloned in the U.S. and abroad.
But before you wonder if that piece of steak or glass of milk came from a cloned
animal, you should know that currently the FDA has a voluntary ban in place against
the sale of milk, meat or eggs from cloned animals for use in the animal or human
food supply, pending public comment and scientific reports from the National Academy
of Sciences. This also includes other products from cloned animals, such as the
sale of semen.
From clone to calf
Cloned livestock aren’t just in labs and zoos anymore. You may have them
almost in your backyard and not know it. Don Coover, DVM, Galesburg, Kan., facilitated
the cloning of the five Chianina calves for a client of his from Oklahoma and
raised the calves since they were born last November until they were ready to
go back home at about 6 months of age.
Coover owns S.E.K. Genetics, a semen distribution company, and became interested
in cloning after hearing information about it at a meeting. He had an interested
client in Oklahoma with a very popular club calf bull whose semen was in such
high demand it was back-ordered. Coover contacted Cyagra, Inc., from Worcester,
Mass., and made plans for cloning the bull.
Coover took a biopsy notch from the bull’s ear and sent it to Cyagra
on medium they sent him. The company then produced cloned embryos that were shipped
and placed into recipient cows near Manhattan, Kan. Pregnancies were established
in seven cows, and those seven cows gave birth to nine calves -- including two
sets of twins.
Birthweights for the single calves were in the 105-110 lb. range, which Coover
says is not unusual for large club calves with a lot of bone and muscle, and the
twin calves were in the 75 lb. range. “One of the calves wasn’t viable
at birth,” says Coover, “and a couple of them never starting breathing,
which is not abnormal in newborn calves.” Six live calves were produced,
but at a later date one calf out of a twin pair was lost due to an accident, leaving
five identical calves.
Coover then took the calves and hand-raised them at his farm in southeast Kansas.
“They are as normal as any calves I’ve ever raised,” says Coover,
who has a herd of 150+ cows himself. “People who have come to look at these
calves have been a little disappointed because they are expecting something special.
Well, they are just calves. They are friendly, high quality and genetically spectacular,
but they are normal calves.”
Because the calves are so tame from being bottle-fed and exposed to a lot of
attention and visitors, Coover has been able study their personalities. “They
all have the same personality and are very friendly and curious. In a bunch of
calves, you might have one that will be really curious, but these are all fascinated
by everything, and their personalities and temperaments are so incredibly alike.
Their personalities, bones, makeup, hip structure and everything else is very
similar.” They all also have a peculiar tuft of hair right between their
ears that Coover’s other baby calves don’t have.
Objections to cloning
Many people object to cloning humans and animals for a variety of reasons, whether
it’s religious or scientific or just plain “spooky.” The term
“frankenfood” has been mentioned when talking about cloning food animals.
But cloning is not creating something new -- it’s creating a copy of something
that’s already there.
Naturally-occurring identical twins are clones in every sense of the word.
The difference between naturally occurring twins and clones is that clones are
“identical twins” of an older animal.
“I’ve had people say cloning is going to narrow the genetic pool,”
says Coover. “We do that already with artificial insemination and embryo
transfer. I see this as something that will take a lot of the guesswork out of
producing genetically superior animals and will take a lot or most of the variation
out of these animals. You can come up with animals you can very specifically select
for in terms of what you expect to see, how you expect to manage them and what
kind of environment they work well in.”
As far as not being “natural,” Coover says the producers who have
raised that objection often are also producers who use A.I. “I tell them
that A.I. is technology and freezing and storing semen for years then re-using
it is not exactly natural, but we’re so used to it now that it has become
the norm.”
And the objection that cloning livestock will lead to cloning humans? “There’s
a lot of emotional reaction to new biotechnologies,” Coover says. “That’s
sort of like saying we can’t eat animals because if we eat animals, pretty
soon we’ll be eating humans. I think that’s less than insightful and
that the technology that will be developed in this kind of industry application
will do an awful lot for many human applications.”
It’s been reported that cloned animals are not as thrifty and are technically
the same age as the animal they were cloned from, therefore they will exhibit
old-age problems while young. This has been fodder for debate for those opposed
to cloning, but science is disproving this theory. Infigen, Inc., completed a
four-year study in 2001 that followed cloned animals from birth to adulthood.
The study found that nuclear transfer-based cloning produced cows and pigs
with normal health and genetic characteristics. The study included 120 live calves
and more than 50 piglets derived from unique non-embryonic derived (somatic) cell
lines.
Advanced Cell Technology (ACT) in Worcester, Mass. (parent company of Cyagra),
also reported that in a study of 30 cattle cloned from proliferating skin cells,
80% of the clones were vigorous and remained alive and healthy one to four years
later -- by comparison, survival to adulthood normally ranges from 84% to 87%.
Results of general health screens, physical examination and immune function were
normal for all clones, including laboratory analysis on blood and urine, biochemistry
and behavioral responses. This information was published in the November 30, 2001,
issue of Science.
Earlier in April 2000, ACT reported that cells from cloned animals actually
have longer DNA tips, or telomeres, than the original cells and show other signs
of youthfulness, which should dispel concerns that clones will die earlier than
normal.
It appears that the products derived from cloned animals are identical to non-cloned
animals as well. Infigen presented a detailed analysis of milk harvested from
cloned Holstein cows. A preliminary biochemical fat and protein analysis found
that the milk is identical to milk taken from non-cloned cows found in the general
population and is safe for human consumption, according to the company.
How can your clients benefit?
Right now cloning is expensive -- it took about $50,000 to produce the five Chianina
calves, but, as technology does, it gets less expensive over time. Coover says
even at $50,000 for the group, or $10,000 per calf, they can still make money
performing like their sire. “A bull like this can produce 1,000 units of
semen in a couple of weeks, and producers will pay $50 per unit,” says Coover.
“That’s $50,000 in a couple of weeks from one animal.”
Cloning is not for any old bovine, however. “In genetically superior
and high demand bulls, the cost of cloning is not an insignificant factor, but
it can approach that, especially when the costs go down,” says Coover. “Obviously
you can’t do this for a stocker animal that is worth $500 at the sale barn.
But for truly genetically elite animals in high demand by the industry, it’s
a viable economic option.”
Coover likens the impact cloning may have on the female side of the industry
to what AI did for the male side of the cattle industry. For example, being able
to clone a genetically superior dairy cow to produce daughters just like her could
do two things: produce more consistent dairy animals and reduce the number of
lesser-valued bull calves.
Cloning cattle may also open more export doors by sending cloned embryos or
disease-free animals cloned from other animals that would not be able to be exported
otherwise.
Not everyone is excited about the potential for cloning animals, however, including
some breed associations. Coover says several breed and dairy associations have
said they will register cloned animals, but other breed associations say at this
point they will not. “Some believe this technology is less advantageous
to the small producer, and only big operations will benefit,” he explains.
“We heard the same argument with A.I. and embryo transfer years ago.”
Coover believes the opposite is true. “This gives the little guy the
opportunity to extend and more widely utilize the better genetics that are produced,
which gives him the advantage of quality over the advantage of numbers that the
larger producers have. I think it’ll become an issue of quality over quantity.”
Why clone cattle?
Here are some potential benefits to cloning cattle:
You transmit 100% of the genetics, eliminating costly trial and error breeding.
You can increase and assure the supply of semen and embryos.
You preserve desired genetic traits from old, diseased or dead animals.
You can re-create cows and bulls without the original’s reproductive
deficiencies.
You can eliminate some diseases.
You can eliminate titers caused by vaccinations.
You can create a bull from a high performing steer.
You can have a uniform herd that enables production and management to be improved.
You can supply proven bulls for
natural breeding.
Excerpted from Cyagra, a subsidiary of Advanced Cell Technology, Inc.
Xenotransplantation and cloning
Xenotransplantation is the transfer of cells, tissues or organs from one species
to another. The fundamental problem with transferring organs between species is
rejection by the recipient’s immune system.
Cloning of livestock, especially pigs which have many similar organs to humans,
may be able to help in this endeavor when cloned animals have “knocked-out”
cells. PPL Therapeutics, Inc., cloned five pigs in December of 2001 that are missing
alpha 1,3 galactosyl transferase (GT) gene. This gene is responsible for making
an enzyme that adds a sugar to the surface of pig cells, which is recognized by
the human immune system as foreign and which therefore triggers and immune response
leading to hyperacute rejection by the human patient of the transplanted organ
or cell within minutes. The ability to delete or “knock-out” this
gene, therefore, provides a vital step in producing pigs with organs and cells
useful in humans.
PPL says the “GT knock-out” pig will serve as the platform for
adding up to three more genes and include a T cell tolerance regime to address
all stages of rejection. PPL’s program has aimed to overcome the causes
of rejection and allow the development of a stock of transgenic animals containing
genetic modifications that can be used as organ donors for humans.
For more information on xenotransplantation, visit PPL’s website at www.ppl-therapeutics.com.
What is a clone?
Clones occur naturally when identical twins or other genetically identical multiple
births occur. Other life forms including bacteria, protozoa, yeast, hydras, flatworms,
other simple animals and plants can be cloned through asexual reproduction or
the process of regeneration.
Advanced Cell Technology explains the nuclear transfer process:
ENUCLEATION: Chromosomes of each egg are drawn into a needle. A pipette holds
the egg still.
AFTER ENUCLEATION: Chromosomes are removed, all that remains inside the zona
pellucida is cytoplasm.
·TRANSFER: A skin cell, or fibroblast, from the animal is transferred
underneath the zona pellucida, where it remains separate from the egg cytoplasm.
FUSION: Each unit is exposed to an electric shock that fuses the skin cell
with the egg cytoplasm. The skin cell’s nucleus, with its genes, enters
the egg cytoplasm. Within a few hours the embryo begins to divide.
EMBRYO: Seven days later the cloned embryo is ready for transfer into a recipient
cow.
Reprinted with permission from Advanced Cell Technology
Graphics: (these are used with permission from Advanced Cell Technology)
FDA’s position on cloning
The following is excerpted from the FDA Center for Veterinary Medicine’s
“Update on Livestock Cloning”, July 13, 2001:
“The CVM is considering the safety of animals and their progeny that
are produced as a result of somatic cell nuclear transfer (also known as somatic
cell clones or NT clones). ‘Dolly the Sheep’ is the most famous animal
produced in this manner, but the technology also has been applied to rodents,
cattle, swine and other species.
“In evaluating animal cloning, CVM’s first priority is to examine
the safety of food products (e.g., meat, milk, eggs) from animals developed through
somatic cell cloning but are otherwise unmodified.
“CVM has been interested in cloned animals for some time. Last fall,
when it became evident that commercial ventures were developing somatic cell clones
for use in breeding food-producing animals, CVM contracted with the National Academy
of Sciences (NAS) to conduct an independent, scientific peer review of available
safety data on cloned animals and the food derived from them. This review, including
the safety of cloning to the animals and environment as well as any food derived
from the animals, will help CVM decide how these animals should be regulated,
including whether there may be circumstances in which CVM ordinarily would not
need to exert its authority. NAS has indicated that this review should be completed
by mid to end of summer, 2002.
“Until the Center has scientific information on safety, the Center for
Veterinary Medicine has been asking the companies not to introduce these cloned
animals, their progeny, or their food products (such as milk or eggs) into the
human or animal food supply.”
CVM and the Pew Initiative on Food and Biotechnology are planning to hold a
public symposium on animal cloning Sept. 26. The goal is to provide a forum for
the perspectives of various groups, including the cloning companies, the animal
producers, the groups marketing food products (such as milk) derived from clones
and their progeny, retailers in the position of selling these products and consumers
who might buy these food products.
For more, visit the website of the FDA’s Center for Veterinary Medicine
www.fda.gov/cvm/ or the Pew Initiative home page at pewagbiotech.org/events/0924/form.
Cloning timeline
As early as the 1950’s scientists were cloning amphibians such as frogs
and salamanders (2002 World Book, Inc.). Some interesting livestock cloning milestones
include:
1996: Dolly the sheep, the first clone of an adult mammal, by Scottish company
PPL Therapeutics, Inc.
1997: ABS Global, Inc., produced a calf using a cloning procedure more efficient
than that used for Dolly.
1997: Scientists combined cloning procedure with genetic engineering techniques
to produce two lambs with a human gene for a particular blood protein in their
cells. These transgenic animals carried the human gene that caused their bodies
to produce factor IX, a human blood-clotting protein useful for treating hemophilia.
1998: Cyagra and Advanced Cell Technology, Inc., create the first transgenic
calves (three) through a method similar to that used to create the two transgenic
lambs.
2000: Scientists at PPL Therapeutics create the world’s first pig clones
(five) using genetic material take from a body cell of an adult female pig.
2000: Future clone of two-time All-American and three-time All-Canadian Holstein
cow Lauduc Broker Mandy EX-95 was purchased for $82,000 at the World Classic during
the 2000 World Dairy Expo.
2001: “Mandy II,” clone of Lauduc Broker Mandy EX-95 was born at
Infigen Inc.
2001: “Cookies” and “Cream,” 2-year old, cloned Holstein
cows, gave birth at the Infigen, Inc. farms to one healthy heifer calf and one
healthy bull calf.
2001: Advanced Cell Technology, produced the first clone of an
endangered species, a type of wild ox called a gauer, but it died just two days
later from a common bacterial infection.
2001: Five cloned Chianina bull calves were produced by Cyagra.
2001: PPL Therapeutics produced “knock-out” piglets with a gene
knocked out that can help transplanted pig organs and cells to not be rejected
by human patients.
2001-2002: Infigen and Genmark clone two widely known boars. Clones were produced
from non-fetal (adult) cells.
2002: Scientists at the University of Georgia and ProLinia, Inc., produced
a calf from genetic material extracted from the kidneys of a cow two days after
it was slaughtered.
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