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U.S. Department of Health and Human Services

Animal & Veterinary

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Developments in New Animal Technologies Show Rapid Advancement: CVM Keeping Pace

by Suzanne Sechen, Ph.D., Office of New Animal Drug Evaluation
FDA Veterinarian Newsletter 2007 Volume XXII, No I

In trying to increase the food production efficiency and health of animals, the livestock and pharmaceutical industries have been looking beyond traditional approaches, such as diet improvements, selective breeding programs, and drug development. Advanced forms of assisted reproductive technologies, new approaches to making and targeting drugs, and novel methods to alter the genetic makeup of animals are being used to unlock secrets into faster growing livestock, tastier and more healthful food products from animals, more environmentally friendly farming, and even the use of animals to produce human drugs and organs. These new technologies are yielding exciting developments into understanding the very being of life.

The Center for Veterinary Medicine in the Food and Drug Administration is keeping up-to-date on these developments to ensure the safety of food and other products as well as the health of animals developed through these technologies.

Cloning

Starting with artificial insemination and followed by embryo transfer, the livestock industry has been using assisted reproductive technologies for decades to acquire better genetics at a faster pace than that offered by traditional selective breeding methods. Cloning is an advanced form of assisted reproductive technology that has captured considerable public attention.

The ability to copy prized livestock and preserve the genetics of threatened species are some of the goals of animal cloning.

Cloning is essentially asexual reproduction, and it produces offspring that are genetically identical to the genetic donor. Early attempts at cloning in the 1970s involved techniques such as splitting an already formed embryo or blastomere nuclear transfer, which fused the nucleus of an embryo cell with an unfertilized egg that has had its own nucleus removed. However, characteristics of the animal clone resulting from these techniques were unpredictable because traits of the embryo could not be known until after the animal was born. The procedures also yielded a limited number of animal clones.

In the mid-1990s, cloning technology took a big step forward with the development of a technique called adult or somatic cell nuclear transfer (SCNT). The first successful SCNT cloning produced the famous Scottish sheep named Dolly. The new technique fuses the nucleus from a differentiated adult animal cell (such as a skin cell or kidney cell) with an unfertilized egg that has had its own nucleus removed. The new nucleus contains all the genetic material needed to create the clone. Biologists then stimulate the newly formed cell to reprogram the donor nucleus to behave as if it has just been fertilized, and initiate embryo development. The embryo is placed into a surrogate dam by a routine embryo transfer technique for gestation and birth. The SCNT approachallows copying of adult animals whose traits are well-known.

CVM carefully reviewed the critical issues of the safety of food products for human consumption from cattle, swine, goat, and sheep clones and their sexually reproduced offspring and the safety of the technology to the animals. The Center released on December 28, 2006, a Draft Animal Cloning Risk Assessment, Proposed Risk Management Plan, and a Draft Guidance for Industry, culminating years of a rigorous and transparent review process.

During this period, CVM continued to ask producers and breeders of clones to not introduce food products (such as milk or meat) from animal clones or their progeny into the human or animal food supply. The Draft Risk Assessment drew from published scientific literature, data from cloning companies, and preliminary evaluations. It concludes that, although there are risks to animals involved in the cloning process, cloning technology does not present any unique risks that have not already been observed in animals produced using other forms of assisted reproduction. However, the adverse outcomes may occur at a higher frequency with cloning than with other assisted reproductive technologies now in common use, such as in vitro fertilization or embryo transfer. The Assessment also concludes that food products derived from cattle, swine, and goat clones and any clone offspring are as safe to eat as food from their non-clone counterparts. Healthy adult clones are virtually indistinguishable from their conventional counterparts.

Biotechnology

Biotechnology might simply be defined as the use of biological processes to make or modify products. The term “biotechnology” often implies the use of recombinant DNA. A number of biotechnology processes and products involving or relating to animals are of potential regulatory interest to CVM.

Prior to the development of recombinant DNA technology, drug sponsors could manufacture large protein drugs (e.g., insulin, somatotropin, and prolactin) only by isolation and purification from animal endocrine organs or body fluids. High costs, purification difficulties, and low output made these products prohibitive for use in animal agriculture. The situation changed in the 1980s when recombinant DNA (rDNA) technology allowed drug sponsors to use bacterial fermentation systems of transformed microorganisms as factories to produce large quantities of protein drugs at relatively low cost. The technology involves isolation of a desired gene that codes for the protein of interest and inserting it into a bacterial host, usually Escherichia coli. The protein product is isolated and purified from the -bacteria.

This approach to producing drugs required new approaches by the FDA to review the manufacturing capabilities of the drug sponsor. However, the drugs themselves are reviewed for safety and effectiveness similar to other new animal drugs developed using more conventional methods. A recombinant bovine somatotropin (rbST) product approved by FDA in 1993 to increase milk production in dairy cows is produced with this technology.

Genetic engineering using rDNA has progressed beyond the modification of bacteria and plants, and has advanced to the point where it is now possible to use the same technology to introduce desired changes into animals. Various techniques are used to produce genetically engineered animals, such as using components of viruses to introduce the rDNA into cells, microinjection of the gene(s) of interest into early embryos, taking advantage of the cell’s normal physiology to insert gene(s) of interest into specific regions of the genome, or by genetically modifying somatic cells, followed by their use in SCNT.

It is important to note that genetically engineered animals produced by SCNT are not the subject of the agency’s Draft Risk Assessment on Animal Cloning released last December. Animal clones do not have any additional DNA added to them, and they are intended to help propagate naturally occurring, desirable traits throughout the herd.

Objectives of genetic engineering in animals are broad. Added genes might enhance disease resistance, increase size, improve food production efficiency, produce lean meat that remains tender, or animal food products with a fat content considered more healthful for humans. Beyond agricultural interests, scientists are evaluating “biopharm” uses of animals. For example, much like the use of transformed E. coli to produce protein drugs, biopharmaceutical substances might be produced inexpensively in the milk or eggs of animals. Scientists are also examining the use of genetically engineered animals to produce tissues (including blood) or organs that will not be rejected by the human body to help meet the growing needs for organ and tissue replacement.

Another potential application of genetic engineering is gene therapy, which introduces genetic material into the body to replace faulty (mutated) or missing genetic material responsible for diseases or other abnormal conditions. The most common approach to gene therapy is to insert a normal gene to replace the abnormal gene in affected (target) cells using a carrier molecule. Modified viruses are typically used as the carrier, although fatty particles called liposomes are also being tested for this purpose. Other gene therapy techniques are also being evaluated, such as inactivating (“knocking out”) mutated genes that are not properly functioning, or reverse mutations to repair an abnormal gene. Many technical challenges must be overcome before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.

Biotechnology also affects the feeds given to animals. Bioengineered feeds, such as corn, soybeans, and cotton by-products have been developed by inserting genes that, for example, improve insect resistance and plant tolerance to herbicide application to improve the control of weeds.

Genomics, proteomics, and pharmacogenomics

Also of interest to the FDA and pharmaceutical industry are the related fields of genomics, proteomics, and pharmacogenomics. Although not subject to regulatory approval by FDA in the same way as drugs and genetically engineered animals, these fields serve as tools to study gene expression and drug responsiveness. The information gained from these fields may ultimately play an important role in preventing, diagnosing and treating a variety of diseases.

The focus of these fields is how information encoded in an -individual’s genes is converted into the actual functioning of cells and, ultimately, the body. Genes are made up of DNA, which is “transcribed” into RNA. The cell then “translates” the RNA to synthesize proteins. These proteins and their products are fundamentally responsible for all cellular behavior.

  • Genomics is the study of genes and their interactions and function in the whole living organism.
  • Proteomics defines the proteins encoded by a specific gene. It identifies when and where proteins are produced in a cell so as to establish their -physiological roles in an organism. Proteomics also examines how protein synthesis in cells is changed in response to different environments, such as a drug treatment or a disease state.
  • Pharmacogenomics studies how the genetic makeup of an organism affects its response to drugs in terms of both safety and effectiveness. Examination of drug responsiveness in specific populations or disease states and how the drug response is altered by genetic variation might allow more specific targets for drug treatments, more precise dose levels, and improved safety.

Nanotechnology

One of the newest areas of interest in pharmaceuticals is nanotechnology. The premise behind this technology is that tiny structures with unique properties and functions due to their size are able to penetrate tissues with little impediment. In terms of pharmaceutical uses, interest lies in designing the particles to target and even repair specific diseased cells. The manufacturing of these products and their safety and effectiveness would be regulated by FDA. Like many of these new technologies, FDA’s review of new drugs based on nanomaterials may require new approaches to assessing safety and effectiveness.

Working group

With the rapid development of new technologies involving animals, CVM developed an internal working group, involving scientists representing different areas of expertise. This group, the Animal Biotechnology Working Group (ABWG), keeps abreast of the latest developments in new technologies and keeps the Center and its management apprised of those developments. (See related article, “Working Group Keeps CVM Abreast of New Animal Technologies.”)