PIGS BIOTECHNOLOGY TRANSGENICS

HOGS FOR YOU AND ME: BIOTECHNOLOGY DELIVERS THE GOODS

Bob Petters
Department of Animal Science
North Carolina State University
Raleigh, NC 27695-7621

Introduction

When was the last time that you heard about biotechnology and pigs? Do you remember what was promised and whether it was produced? Few of us keep track of promises and proposed improvements to the point that we could answer these questions. The promised leaner, faster-growing pig produced by genetic engineering is still under development. While the pig of the future may yield better meat and larger profits, hogs are now being produced for reasons other than pork chops and barbeque. Some day hogs may save lives and prevent blindness among other uses. The genetic engineering of pigs is being closely watched by doctors as these hogs are produced and studied.

Genetic Engineering

Genes control what a pig looks like and how fast it grows. Pigs are different because they have different genes. Here, genetic engineering means that we try to add an extra gene to the pig. While the purpose may differ, the basic idea is that the extra gene will have some effect on the pig such as faster growth or leaner growth. But beyond production traits (growth, leanness), there are many other possibilities even life-saving possibilities for you and me.

Genetic engineering is not really complicated, but it is somewhat difficult to accomplish. First, we must isolate a gene from the thousands of other genes in the pig. The gene we isolate is usually well-known and important to us. In order to transfer this gene to pigs, the gene must be copied many times over or cloned so that we will have millions of copies of that gene. Cloning of individual genes is the basic technique behind genetic engineering.

Once we have the gene, the time approaches to attempt to transfer the gene to the pigs. Presently, the actual transfer of the gene to the pigs is difficult and time-consuming to accomplish. First, one-cell embryos are obtained surgically during the late stages of estrus. Each pig is anesthetized, a midventral incision is made, the reproductive tract exposed and flushed to obtain the embryos. Each surgical recovery of embryos requires 3-5 people for 2 hours and on average yields 12 embryos (20-22 with superovulation). The embryos are now passed to two other people, the embryologist and the embryo microinjectionist. In a small room near the surgery, these two people prepare for the second part of the procedure, microinjection of each embryo with a solution containing hundreds of copies of the gene.

The embryos are quickly cared for very carefully. They are kept warmed under conditions very similar to what they were used to in the sow. In order to accomplish the tricky task of microinjection, the embryos must first be centrifuged. Spinning the embryos at high speed does not damage them but allows the microinjectionist to see important structures within the embryo. And now, the embryos are lined up under a powerful microscope and handled with fine micromanipulators. The embryos, the size of a speck of dust, are each microinjected with an almost infinitesimal volume of our gene solution. Only half of the embryos survive this injection procedure; the others die a quick death in the petri dish or will die later. All of the embryos are now transferred back to a sow for gestation to term. In order to transfer a gene to pigs--to produce transgenic pigs, hundreds to thousands of embryos must be microinjected and transferred to recipient sows.

When the recipient sows farrow, a tissue sample is taken from each piglet. DNA is extracted from this sample and tested for the presence of the gene we were trying to transfer. If all phases of the protocol have been working well, we can expect to find a few piglets that are transgenic. These pigs are raised to sexually maturity and mated to determine whether the transgene (the gene transferred) is passed on thru the germline. The offspring from the transgenic founder pigs are then carefully studied to determine how the transgene affects them.

We have to understand that insertion of a gene into an animal does not always lead to the results that we might predict. A good analogy might be a classic 8 cylinder motor in a 1966 Chevy Chevelle. What will happen to that motor if we decide to insert a second cam shaft somewhere in that engine without removing the original one? In the case of the pig, we don’t even know how the pig works. How can we hope to make changes in something we don’t understand? Genetic engineering can help us learn more about pigs, just like we know more about car engines, so that in the future, we can use these techniques to improve the product and improve the profitability of pig production.

Where are we now?

Pigs designed to grow faster and leaner have been produced with genetic engineering (1). Unfortunately, these pigs were also affected in negative ways by the expression of the transgene. Obviously, we did not understand how pigs work and what the consequence of the transgene would be. In this case, it was like the extra camshaft and the pigs did not do well. At this time, the emphasis is on controlling the expression of the transgene so that postitive effects are possible on growth rate and leanness but negative effects on fertility and soundness are minimized. It is clear that when we know more, we probably will be able to produce pigs by design that will be better for consumers and for producers. These pigs will be the barbeque of the future.

Pigs of a different sort are being produced now for medical purposes (2). Pigs happen to be very much like people in many ways. This fact can be used to advantage in medical research and therapy.

A cooperative project between North Carolina State University, Duke University and the National Institutes of Health has resulted in the production of transgenic pigs (3) that will help prevent a type of inherited blindness called retinitis pigmentosa (RP). In this project, a lowly farm animal has become elevated to be the object of medical research. These animals are very useful in trying to understand the cellular and molecular mechanisms of RP. Most importantly, clinical therapies are currently being tested using the transgenic pigs. At this time, RP has no treatment--patients that have the disease are blind by 40. The transgenic pigs bring hope to a previously hopeless situation.

We have all heard about the use of heart valves from pigs being used to treat people. What about whole organs such as the heart or liver? To this point, such attempts of transplantation between species have always failed because of complete and quick rejection of the organ. However, pigs are being genetically engineered so that the risk of quick rejection of the organ will be greatly reduced. In the future, will people walk around with pig hearts rather than human hearts? Can the pig of the future really save lives? Organ donor pigs would be the ultimate in Healthy Hogs; they would soon become man’s best hope for medical miracles.

Suggested Reading

Jin, DI, RM Petters and KS Im. 1994. Transgenic livestock. Review. Asian-Australasian J. Anim. Sci. 7:1-17.

Petters, RM. 1994. Transgenic livestock as genetic models of human disease. Reprod. Fertil. Dev. 6:643-645.

Petters, RM, CA Alexander, KD Wells, EB Collins, JR Sommer, MR Blanton, G Rojas, Y Hao, WL Flowers, E Banin, AV Cideciyan, SG Jacobson and F Wong. 1997. Genetically engineered large animal model for studying cone photoreceptor survival and degeneration in retinitis pigmentosa. Nature Biotechnology 15(10):965.