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Ultimate Genetics

When Scotland's Roslin Institute cloned Dolly the sheep last year, the world reacted with awe. Last January, Ultimate Genetics of Franklin, TX, stunned the cattle industry when it announced the birth of the world's first transgenic cloned calves (created from the combination of cloning and genetic engineering).Seven Holstein bull calves were produced using fetal cell cloning and genetic manipulation

When Scotland's Roslin Institute cloned Dolly the sheep last year, the world reacted with awe. Last January, Ultimate Genetics of Franklin, TX, stunned the cattle industry when it announced the birth of the world's first transgenic cloned calves (created from the combination of cloning and genetic engineering).

Seven Holstein bull calves were produced using fetal cell cloning and genetic manipulation technology developed by University of Massachusetts scientists Jim Robl and Steve Stice. The pair founded Advanced Cell Technology (ACT) of Worcester, MA.

But that was only the start. In January, the staff at Ultimate Genetics, led by its president and co-founder Charles R. Looney, joined with Cyagra, an agricultural subsidiary of ACT, to form Ultimate BioSystems. Under the arrangement, Ultimate BioSystems will contribute the technology and Ultimate Genetics will provide the cattle and reproductive management resources necessary to make cloned livestock economically feasible. Charles Long, who served with the USDA Germplasm and Gamete Physiology Laboratory at Beltsville, MD, is the firm's chief scientific officer.

The new venture will explore cloning and transgenic technology for animal agriculture, mainly beef cattle but also dairy, pigs and small ruminants. All procedures will take place in a new laboratory at the 10,000-acre Camp Cooley Ranch in Franklin, TX.

"We are looking at several different genotypes in Angus, Brangus and Charolais cattle here at the ranch," says Looney. "We're also doing special projects with genetic modifications at Texas A&M University with scientists Jorge Piedrahita and Mark Westhusin."

BEEF sat down with Looney and discussed the implications of this innovative new procedure.

1.How do the two cloning procedures differ? Previous cloning technology utilized early embryos as the nucleus donor. We used that system when I worked with Granada Land and Cattle Company, which successfully cloned embryos in the mid- '80s. But we couldn't keep them growing. We could only get a maximum of 100 cells from an embryo. This limited the number of attempts one could make with each genotype. More importantly, we couldn't apply the genetic engineering technology to the embryonic cells.

The new ACT technique of cloning was developed using fetal somatic (body) cells taken from 1-3 months of gestation. These cells, called fibroblasts, grow in the incubator for weeks giving us millions of cells that can be used as the nucleus and have millions more frozen for future use. Moreover, the fetal fibroblasts are genetically modified more easily.

The basic cloning procedure utilizes an egg (oocyte) from slaughter cows. We don't need the genetic material in that egg, only the cellular hardware, so the nucleus is removed. The new nucleus from the fetus is then selected and transferred next to the egg, which now contains the full complement of DNA, plus an additional genetic marker.

Technicians then apply an electrical charge that fuses the nucleus with the egg. In five to six hours, the cellular hardware of the egg reprograms the nucleus back to day one and you have a cloned embryo. Ultimate BioSystems has licensed the ACT technology with patents pending.

2. What is your immediate goal?

Ultimate Genetics and ACT are taking a two-tiered approach. ACT is mainly working on new developments, improving the basic understanding of the cloning technology and bringing new projects to the table.

Our focus is to apply the cloning technology to produce better quality livestock for our customers. It isn't as commercially feasible as we would like. We'd like to get pregnancy rates up in the 50% range and embryo production up to 25-40%. But mainly, we must be sure cloned calves will have normal births.

Our first target is to improve carcass traits for bulls produced in the southern U.S. - a real niche market of 400,000 head a year. Then to use the technology to produce 30-40 identical range bulls so a rancher can put them out and get more uniformity in the herd and offspring. We are in the beef business and our focus is on marbling, tenderness, increased muscle, growth rate and disease resistance.

John Hopkins University has done research in mice to modify a gene that increases muscling. When altered in the donor cells, this gene leads to increased muscling, almost like double muscling.

We're also looking at marbling, but haven't isolated the genes yet using gene mapping where you actually identify genes and follow them from one generation to the next. You do that with genetic markers. As an example, you could modify these genes in Zebu cows and improve the beef quality of their product in the first generation without diluting the high value of their genetics.

Human medicine can also benefit from this new technology. Biopharmaceutical companies are currently looking at the cloning and genetic modification techniques for creating cattle that produce life saving medical products in their blood, milk or produce organs for tissue transplants that will resist injection.

For us, the human pharmaceutical market is only a conduit to increase the efficiency of the technology and to pave the way for commercialization of the livestock cloning market. Here at Ultimate Genetics, we realize that we must become more efficient in order to compete with the vertically integrated pork and poultry industries.

3. How far away is achieving this goal? We'd like to have it tomorrow. Although only a few cases have been reported, cloning from adult animals of proven genetic merit would give us opportunities to make these animals consistent and predictable in carcass and beef quality. But as for cloning adult animals, we may be a year away if we're lucky, three years away is more likely.

We still don't understand the cellular reprogramming that occurs with adult cloning. We still have significant research and development before full commercialization is possible. We will probably get the first cattle from the best genetics at Camp Cooley Ranch within the next year, then we can put those offspring on performance test for the next two years.

We'd rather use our own animals, because we have to test genetics first and answer questions about the technology and how to use it. Then we'd have internal control over our own genetics, and particularly cattle where we can evaluate birthweight and calving ease.

It's a slow process. We take DNA samples from all animals to make sure everything is right. We'll check carcass quality and production traits using ultrasound and progeny testing of bulls. Cloned bulls will be bred to cows with the calves taken to the feedlot to get second generation data. We have to show our customers, seedstock producers, packers and consumers that this is something coming along of value to them.

4.Can you produce these clones competitively? At the start, no. In the future, yes. If we keep costs down, the clones will be marketable. We already have certain purebred breeds that want us to do this kind of work for them. Then as word gets out that we are working on consistency of product, we will get interest from those who sell branded products.

5. What part do you and Camp Cooley play in selecting the bloodlines to clone? Mark Cowan and staff at Camp Cooley Ranch test and select the bloodlines for us to clone. In fact, a year ago we collected a sample from each line we felt was important. Not all are bull lines, because there are some females lines with traits we want to expand.

We do the mechanics of getting the cells and producing the clones and Camp Cooley does the performance testing. In the future, we can identify traits that are unacceptable in a line, then modify the genetics and make it better.

6.If you produce 40 identical bulls with the qualities you want, won't you run into some roadblocks from other seedstock producers who think you're going to run them out of business?

It's competition, I guess. Anybody can do cloning if they want to. We do have proprietary genetic lines to work on. Some we own ourselves, and some will come from other breeders.

There are others working on the concept. But we feel we're lucky to be involved at the ranch in an established genetic program. We also have a big recipient cow herd and an established program in which to implement the technology.

To create a factory, you have to have the raw materials. In this case, that's oocytes and cell lines. Then we have the equipment to produce the cloned embryos, the embryo transfer expertise to transplant them into recipient cows and the established program for evaluation after calves are born. That is part of our business.

We have a lot of different collaborators. Among others, feedlots and alliances are involved because it takes everybody's ideas to make it work all the way down the chain, although it will probably have a different sound by the time it gets to the end.

It has to be a package decision. If we produce identical replacement females, then breed them back to an initial bull line, we can go back to those bull lines, modify them and continually improve on them because at some time each individual genetic line could develop into an industry.

This is the beginning of making maternal and paternal lines of cattle, similar to the pork and chicken industry. However, if the seedstock industry doesn't bring in new genetics to improve their lines, they'll never get any better.

At Ultimate Genetics we have independent thoughts, the right players and a good chance to win. People in our organization are real cattle people at the grassroots. If it doesn't work for us, it probably won't work for the industry.

7.What effect will this technology have on the export market? We're sending a lot of embryos to northern Brazil and Argentina as well as other countries. It's a real niche opportunity for us.

To do that, the cattle have to be adapted to the diseases and insects they have there. If, for instance, we could make them tick-resistant by transgenics, the cattle will go down there and produce a better beef product. Of course, there is a flip side. They may compete directly with our beef industry.

8. What's your reaction to concerns about cloning humans? We're not involved in human cloning and don't want to be. But the technique can be used to help humankind to cure diseases like cancer, diabetes, and Parkinson's disease and reduce organ transplant rejections. We support that type of research, but to create another person is something that shouldn't be considered.