Genetically Modified Animals and Drug Production An EMPACTS Project for Biology 1544

1. Genetically Modified Animals and Drug Production An EMPACTS Project for Biology 1544 Northwest Arkansas Community College Melissa Mathison Meredith Reynolds Magdalena Carranza Chantel Litton Amy Saferite

2. Purpose of EMPACTS Projects • The purpose of this EMPACTS project is for Biology 1544 students at Northwest Arkansas Community College to better understand the material given throughout the semester. • This presentation varies in our research concerning genetically modified animals producing pharmaceutical drugs. It contains information on the generalities of the genetically modified animals producing these drugs, the benefits and disadvantages of animals being used, and information on FDA regulations. • (These specifically include farm animals/mammals that produce eggs and milk such as cows, chickens, and goats. Several varying articles in our research were used in gathering the information instead of seeing it firsthand, due to the fact there was no farm or company that genetically modifies animals in the Northwest Arkansas area. However, all research is valid.)

3. An Introduction: Generalities over Genetic Engineering of Animals to Create Pharmaceutical Drugs There are many pharmaceutical drugs used today to treat illnesses that have come from genetically modified animals, or transgenic animals. This is slowly becoming a common way to create drugs that we otherwise could not create due to lack of a certain modification we could find elsewhere to create the drug or costly expenses. Expensive meaning it could cost the government millions of dollars because of the lack of effectiveness without animal modification and would also be expensive for patients. “Many therapeutic proteins for the treatment of human disease require animal cell specific modifications to be effective, and at the present time they are almost all produced in mammalian cell-based bioreactors” (Eeneenam, pg.2).

4. An Introduction: Generalities over Genetic Engineering of Animals to Create Pharmaceutical Drugs • The process of genetically modifying an animal usually starts with combining certain fragments of DNA together in a laboratory, known as recombinant DNA. Then it is put into the animal which can pass on the recombinant DNA to the offspring. These animals contain an additional protein from the constructed DNA needed to create the drug. • Genetic modification is best in mammals; According to Dr. Eeneenam of the University of California, genetically engineered mammals/animals may provide an important source of these protein drugs, because the production of recombinant proteins in the milk, blood, or eggs of transgenic animals present a much less-expensive approach to producing therapeutic proteins in animal cells. Many drugs are produced from milk, blood, or eggs from animals; mainly cows, chickens, pigs, and goats.

5. IMPORTANT TERMS TO REMEMBER

6. Methods We Used We did online research on certain animals, mainly farm animals such as cows, chickens, and goats, and finding information on the drugs produced from them and the processes of genetically modifying them. We also added the generalities of engineered animals to better explain the topic given, with the added information on the ethical and moral views of genetically modifying animals for drug reasons and the FDA regulations. However, there was one concern during this project because of the fact there is no near-by area that works on the processing of genetically modified animals producing pharmaceutical drugs. We also attempted to reach certain companies and institutes, such as HermitechInc. and Roslin Institute in the UK by email, but they were unavailable. This research paper was part of a project to better understand the material being learned in class throughout the semester. This included cell reproduction, mitosis, meiosis, genetics, etc. which is somewhat put into the EMPACTS projects.

7. The Basic Process of Genetic Engineering Many animals are being used to produce pharmaceutical drugs, mainly milk and egg producing animals such as chicken, goats, and cows. The common way to genetically modify animals is a certain process performed in the laboratory The gene of interest is isolated on a strand of DNA DNA is cut at specific points by restriction enzymes. The enzymes recognize certain sequences of bases on the DNA strand and cut where those sequences appear. The cut DNA joins with a vector, which may be a virus or part of a bacterial cell called a plasmid. The vector carries the gene of interest into the organism that will produce the protein. Transformation occurs when the gene carried by the vector is incorporated into the DNA of another organism where it initiates the action desired (Unfortunately, the letters are too small to read in step 4. but with further research, it states that drugs can be produced also in E-coli bacteria or plants. However, with animals, it is much more efficient.

8. The Basic Process of Genetic Engineering (continued) Plasmid removed from E-coli cell The Plasmid is opened by a special enzyme DNA coding for human drug is inserted in the opened Plasmid. Recombination – Plasmid closed by another special enzyme Introduction of Recombined Plasmid into E-coli host cell. Host cell divides into new cells identical to the original. The implanted DNA induces the cell to produce the drug.

9. Examples of Drugs Made from Genetic Engineering of Animals • ATryn • Insulin • Lactoferrin (Breast Milk Supplement • Anti-Cancer Drugs • Erythopoietin

10. ATryn

11. ATryn • Goats are one of the first animals to be used in the genetic engineering process. • Biotech Therapeutics currently owns a farm in Charlton, Massachusetts. • 30 goats are currently being used to make the anti- blood clotting protein, Antithrombin, on this farm. • Antithrombin is produced from the mammary glands of transgenic goats, and harvested from their milk. • In 2009, GTC- Biotherapeutics Ovation Pharamceuticals Inc. announced that the Food and Drug Administration (FDA) had approved ATryn (Antithrombin Recombiant) for the prevention of blood clotting in Antithrombin deficient patients. • Choosing to genetically engineer goats to produce the drug is an efficient method and useful because Antithrombin is hard to come by or is simply not available. • After furthur clinical trials, this is expected to be available in the pharamacy by 2012.

12. Video on ATryn

13. Lactoferrin & Insulin

14. Lactoferrin & Insulin Most common from genetically modified cows are lactoeferrin, breast milk produced from cows in the form of a supplement, and insulin. Normal human milk from a mother given to the baby is nutritional, but from genetically modified cows , there is more of a “nutritional boost”. So it is much healthier for the baby. Lysozome, which fights bacteria and improves infants immune system in their few days of life, can be found in genetically modified cows, which has properties of breast milk. Researchers believe human milk from cows could be a better alternative than baby formula. Insulin can also be made from genetically engineering cows. Insulin is more strong and beneficial this way. Insulin is used to treat diabetes.

15. This figure better explains genetically engineering of Insulin

16. Lactoferrin & Insulin . After completing the new specially designed DNA, the scientists will plan a certain action desired, such as signally telling the protein where to go to make the insulin, lysosome, lactoferrin, etc. Recently, there have been various places working on this production in cows. “Whether developing treatments for antibiotic-resistant infections or producing new drugs to help defend against bio-terrorism, Hematech, Inc. is utilizing the latest advances in technology to help fight diseases. The company, headquartered in Sioux Falls, South Dakota, is currently developing cattle that can efficiently produce human antibodies. The genetically altered cattle, known as TC Bovine™, will be used for the production of large quantities of polyclonal antibodies. These antibodies are expected to help in the treatments of viral or bacterial infections, autoimmune disorders and other medical conditions occurring in humans.”( Hermatech Inc.) These medical conditions include organ transplant rejection, cancer, autoimmune diseases, such as rheumatoid arthritis. Cows from Hermitech Inc. farm

17. Anti-Cancer Drugs

18. Anti-Cancer Drugs Chickens are also being used in the process of producing pharmaceutical drugs. A specific area found was the Roslin Institute in UK. They have started genetically modifying chickens to produce cancer drugs, which contain lifesaving, immune system proteins in their eggs for cancer patients. Not all of the eggs that are laid contain the protein needed for the drug. Only about four percent of these eggs actually contain this protein but a single egg laid contains enough protein to treat a handful of cancer patients for one year. This is a very cheap and efficient method of making pharmaceutical drugs. Normally this process would take a very long time. Using chickens to produce this drug makes it faster than any other method of drug manufacturing Chickens at Roslin Institute in UK

19. Anti-Cancer Drugs . This particular method does not transmit the bird flu virus. Chickens are also being GM to treat lung, cervical, and breast cancer. Chickens naturally produce proteins. Genetically modifying makes the protein value increase. As said in the table, “to ensure the desired protein was only produced in the egg they linked the therapeutic protein gene with the chicken Ovalbumin Gene which is only found in the egg white part of an egg.” The drug is currently in clinical trials. There is some concern as to whether the drug is pure, but there is high hopes that these drugs will be regulated soon and sold in pharmacies.

20. Erythropoietin

21. Erythropoietin (Epoetin Alfa or EPO) • Many mammals are being genetically engineered to produce Erythropoietin, like sheep or cows. EPO is used to treat anemia or given to patients after chemotherapy. “EPO is a glycoprotein (protein-sugar conjugate) that serves as the primary regulator of red blood cells (erythrocytes) in mammals” (Ritter). Recombinant DNA isolates the human gene erythropoietin and is put into the mammal to target a more modified and better version of erythropoietin. EPO is a natural substance produced from the kidneys in our bodies but transporting the gene to a mammalian animal, such as a sheep, causes a large quantity and quality of the drug. Recombinant DNA of EPO

22. Erythropoietin (Epoetin Alfa or EPO) • “Erythropoietin [epoetinalfa (Epogen, Procrit)] is used in many installation-fitting clinic. The most common use is in people with anemia associated with abnormal function (dysfunction) kidney. When the kidneys are not functioning properly, they produce less than normal amounts of erythropoietin, which can lead to the production of red blood cells are low, or anemia. Therefore, by replacing erythropoietin with an injection of erythropoietin from a genetically engineered animal, anemia associated with kidney disease may be treated” (World of Health). • Many athletes, such as cyclists and runners, use EPO because the increasing number of red blood cells can increase oxygen capacity and produce improved physical activity. Creating Erythropoietin through genetic engineering, it is much more efficient than what humans can produce alone.

23. Concerns on Genetically Modifying Animals A lot of people, mainly animal-rights activists, are concerned about genetically modifying animals to create therapeutic pharmaceutical drugs.

24. What are they concerned about?? • the confusion between cloning and genetically engineering • the morals and ethics concerning the welfare of the animals • transference of diseases by taking the drug

25. Concern: Confusion between Cloning and Genetically Engineering The idea of clones appears in the concerns in these animals because it is such a widespread controversy. Many people feel that cloning is harmful for the animals. However, unlike clones which are “supposed to be genetically identical to animals that already exist, genetically engineered animals have DNA from other organisms, often other species, inserted into their genome” (Northwestern University). Since the DNA is already made, it is safe.

26. Concern: The Morals and Ethics Concerning the Welfare of the Animals • The goal to use animals for human needs has been a long-term goal for many scientists. Not only does it “have vast potential for patients, but also that it can be carried out without harm to the animals” (Washington Post). • Martin Stephens, the vice president for animal research issues at the Humane Society, acknowledges that the technique of this drug production does not harm the goats but still feels troubled by the development. He says that it “represents a dark cloud on the horizon in that we would rather not see more uses of animals drummed up” (Washington Post). • Peers feel like genetically engineering animals to produce drugs could hurt the animals, but this is usually monitored very closely to keep this from happening to patients so fortunately, this is a safe process • Some also have negative feelings over the animals welfare because of the fear these animals may end up just being used for breeding so the recombinant DNA is passed on to the offspring. Transgenic animal research is still subject to existing regulations governing animal research.

27. Concern: Transference of Diseases There is also an added concern with cows & chickens, because the fear of transference of diseases through drugs, such as mad cow disease and bird flu. However, there are so many clinical trials the animals and the drugs go through that this is not common at all. So therefore, it is safe to use. Plus, scientists genetically engineer these animals to keep them from producing these diseases and becoming immune, so this should not be a concern.

28. CONCLUSION Genetically modifying animals to produce pharmaceutical drugs will slowly become a common and efficient way to treat diseases. Not only because it is safe, based on the regulations of the FDA, it also is beneficial for the economy because of the inexpensive processing. It also can provide drugs/treatment for a lot more patients, because animals can produce a larger amount than humans using genetic engineering. Concerning the future, it can lead to progress in medical science and maybe eventually a cure for cancer. The FDA has regulated many of the drugs produced, basing on the fact if the drug is safe and effective. They also keep in mind the ethical concerns of the community. It is pertinent that the community keeps in mind the idea of using animals for the better good because it can help the overall health of the common people at an affordable cost and efficient timing.

29.  That’s all Folks!

30. OUR SOURCES Jones, By Hilary. "Chicken Eggs Make Human Drugs | COSMOS Magazine." COSMOS Magazine | The Science of Everything. Web. 07 Nov. 2011. <http://www.cosmosmagazine.com/news/966/chicken-eggs-make-human-drugs>. Lavine, G. (2009). FDA approves first biological product derived from transgenic animal. American Journal Of Health-System Pharmacy, 66(6), 518. doi:10.2146/news090023. EBSCO. "Scientists Develop Genetically Modified Cow That Produces 'human' Breast Milk | Mail Online." Home | Mail Online. Web. 07 Nov. 2011. http://www.dailymail.co.uk/sciencetech/article-1372836/Scientists-develop-genetically-modified-cow-produces-human-breast-milk.html Pollack, Andrew. "F.D.A. Approves Drug From Gene-Altered Goats - NYTimes.com." NY Times Advertisement. 06 Feb. 2009. Web. 07 Nov. 2011. <http://www.nytimes.com/2009/02/07/business/07goatdrug.html>. "Genetically Modified Cows Produce Milk Akin To Human Milk | Popular Science." Popular Science | New Technology, Science News, The Future Now. Web. 07 Nov. 2011. <http://www.popsci.com/science/article/2011-04/genetically-modified-cows-produce-milk-human-qualities>. "FDA OKs Drug from Genetically Altered Animals - Health - Health Care - Msnbc.com." Msnbc.com - Breaking News, Science and Tech News, World News, US News, Local News- Msnbc.com. Web. 07 Nov. 2011. <http://www.msnbc.msn.com/id/29054736/ns/health-health_care/t/fda- oks-drug-genetically-altered-animals/>. Eeneenam, Alison. "Genetically Engineered Animals: An Overview." Http://agribiotech.info/details/AlisonGE%20Animalssent%20to%20web%2002.pdf. Department of Animal Science University of California, Davis, 22 June 2008. Web. 7 Nov. 2011. "Bio-10--Pharmaceutical Production from Transgenic Animals." Office of Biotechnology: Iowa State University. Web. 07 Nov. 2011. <http://www.biotech.iastate.edu/biotech_info_series/bio10.html>. Ritter, Steve. "Erythropoietin." Acs.org. Chemical & Engineering News. Web. 10 Nov. 2011. http://pubs.acs.org/cen/coverstory/83/8325/8325erythropoietin.html "Genetic Modification." Making the Modern World. Web. 22 Nov. 2011. (no author) <http://www.makingthemodernworld.org.uk/learning_modules/biology>