Companies will milk cloned cows for drugs, organs.

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Companies will milk cloned cows for drugs, organs

By Judy Stringer staff writer JStringer@...

The birth announcement of Charlie and - cloned calves conceived in a

UMass-Amherst laboratory and born on a Texas cattle ranch - last week in Boston

not only created a windfall of news reports and sexy headlines, but also marked

an important first, created at the hands of local researchers.

It denoted the first time transgenic calves, those containing genes from

another species, have been engineered through the combination of transgenics

technology and somatic cell cloning. The breakthrough has many applications in

the pharmaceutical and agricultural industries.

" In our minds it's not the cloning itself that is the feat, but the

combination of transgenics and cloning, " said Stice, chief scientific

officer at Worcester-based Advanced Cell Technology (ACT), presenting the

cloning accomplishment to more than 500 international reproductive biologists at

last week's meeting of the International Embryo Transfer Society in Boston.

ACT collaborated with UMass-Amherst Animal Scientist Robl in producing

the cloned bovine duo.

The process the team used begins with somatic cells collected from a cattle

slaughter house. The term somatic cell refers to any cell of the body other than

reproductive cells. Robl and Stice used fibroblast cells, which are associated

with the production of connective tissue.

The researchers then insert into millions of somatic cells, a transgene - a

gene from another species - that they want to be integrated into the calf's

genetic information and a marker gene. The trial transgene used by Robl and

Stice was a gene that programs for resistance to a certain antibiotic.

Only about one in a million of the somatic cells will seize the desired

genetic alteration, said Stice. Those that do are harvested in a petri dish and

then used in a process called nuclear transfer technology, which involves

transferring the complete genetic material from the genetically engineered cell

into an unfertilized egg cell whose own nucleus has been removed.

The resulting embryos are implanted in surrogate cows. Embryos prepared by

the ACT/UMass team were sent via FederalExpress to a company in Texas that

implanted them and saw to the mothers' care under contract. Charlie and

were delivered by Texas A&M veterinarians. Genetic test have proven they carry

the same genetic instructions, including the transgene and the marker.

Robl said that in the future, the cell could be modified with various

transgenes, a technology that has multiple commercial applications.

In addition to making ACTÊan attractive partner to corporate collaborators,

the validity of cloning animals that have been enriched with transgenes is also

good news for Genzyme Transgenics, the Framingham-based company " betting the

farm " on its ability to produce conventional human protein drugs in the milk of

transgenic cows and goats.

" This is a new technology that is going to speed up the entire process of

breeding a transgenic herd, and that's very integral to what Genzyme Transgenics

is doing, " said Elise Wang, an analyst in New York with PaineWebber. Wang

believes that news of the birth of transgenic clones is a big step not only for

privately-held ACT but for Genzyme Transgenics. " Investors are going to be

excited by this. "

In a pact worth $10 million, last October Genzyme Transgenics agreed to fund

a collaboration with ACT to produce cloned transgenic cows that have been

altered so that a human protein, human serum albumin, is secreted in their milk.

Once purified from the dairy milk, this milk-derived protein could compete

directly with conventional albumin extracted from human blood.

Approximately 440 metric tons of albumin are used annually worldwide with

sales of about $1.5 billion. Wang said there are concerns about the safety of

blood-sourced albumin, which could feasibly transmit diseases. Many consider

deriving the protein from cow milk safer.

Cows are also considered a more efficient source. An individual cow will

produce approximately 8,000 liters of milk per year, which could provide an

estimated 80 kilograms of albumin annually, according to Genzyme Transgenics.

The company has a pact with Fresenius, a German health care company, worth up to

$17 million in milestone payments and abundant royalties payments once a albumin

derived from transgenic cows gains product approval.

Company spokeswomen Pat Diamond would not comment on whether news of the

cloned calves triggers milestones payments from Genzyme Transgenics to ACT or

from Fresenius to Genzyme, but did say an announcement regarding at least one of

these partnerships will be made next week.

Genzyme Transgenics has already produced the first milk-derived human

therapeutic to reach clinical trials - antithrombin III, an anti-coagulant it

derives from goat milk - and the company has expressed some 20 other proteins of

medical interest in the milk of transgenic mice and goats. However, replacing

its conventional " shot gun " approach to genetically manipulating animals with

the more efficient cloning technique is attractive in several ways, said

Diamond.

" It makes the process much more effective and controlled, " she said.

In conventional transgenic animal production, the gene of interest is

injected in vitro directly into the host egg at the fertilized, one-cell embryo

stage, using a technology called micro-injection. The altered egg or embryo is

then transferred to a female who will carry the offspring to full term. Only

about 5 percent to 10 percent of the animals born from micro-injection will be

transgenics, because when, where and to what extent the injected DNA will be

picked up by the host cell's genome is largely left to chance.

Moreover, several of the transgenic animals will be male, and thus will not

produce milk. These obstacles mean it takes several generations to develop a

sizable herd of transgenic animals using the conventional process. In contrast,

ACT's cloning technology allows researchers to select only cells that have

integrated the desired genes into their genetic material and that come from a

female cell line for implantation into the surrogate.

Besides milking drugs from animals, technology to clone transgenic cattle

would also be useful to the $140 billion beef industry, said Robl. For instance,

cloning cattle would allow the design of an all male herd that have genes making

them resistant to diseases, such as Mad Cow, and the animals would be of similar

dimensions so that they could be easily slaughtered by machinery.

Stice said that ACT, which has been collaborating with UMass for three

years, is also close to cloning the first transgenic pig. The company is

currently looking for a corporate collaborator to jointly develop genetically

altered pigs for harvesting human organs that could be used in life-saving

transplant operations. He said that cloning a founder pig with the genetic

information to manufacture human organs or tissue would be more efficient and

effective that current breeding techniques for the production of transgenic

offsprings, where there is some uncertainty that the genetic alterations are

passed on.

" The opportunities here are really endless, " Stice said, adding that several

clinical trials are already underway by biotech companies to test the viability

of using pig cells to treat various diseases, including diabetes and liver

disease.

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