1. How can we make drugs in the future?

2. GMO – Genetically Modified Organisms  Genetically modified organism (GMO), an organism whose genome has been engineered in the laboratory in order to favour the expression of desired physiological traits or the production of desired biological products.

3. Biopharmaceuticals  In medicine, genetic engineering (GE) is used to make biopharmaceutical drugs. Various organisms are engineered for use at factories to produce the drug product.  Bacteria are the preferred option, as they are the easiest to culture and scale-up for production, but depending on the complexity of the drug’s molecular structure, other organisms such as yeasts, mammalian cells, etc., can also be used to express the drug product.  The first GE drug approved for use was insulin. By the year 2000, there were over 100 GE drugs on the market. Currently, people’s lives are changed every day by drugs like Remicade, Epo, Avastin, and Neulasta.RemicadeEpoAvastinNeulasta

4. Biopharmaceutical drugs in use today  Remicade (infliximab) – used to treat auto immune diseases  Epo (Erythropoietin) – usually produced in the kidney but can be genetically synthesised to promote red blood cell production  Insulin – genetically synthesised hormone normally produced in the pancreas that helps to convert glucose into glycogen  Avastin (Bevacizumab) – an angiogenesis inhibitor, a drug that slows the growth of new blood vessels  Neulasta – a genetically synthesised injection that reduces the chance of infection due to a low white blood cell count and is used in people with non-myeloid cancer who receive chemotherapy (which can cause fever and low blood cell count)

5. How drugs can be produced  Genetically Modified Microorganisms 1. The genes for the protein (drug) is isolated using restriction enzymes 2. The gene is copied using PCR 3. Copies are inserted into a vector, plasmids from a bacterial cell can be used 4. The plasmids are transferred into a bacterial cell 5. The modified micro-organisms are grown in large containers usually fermenters so that they divide and produce many copies of the useful protein from the inserted gene 6. The protein can be purified and used as a drug

6. Example of how drugs can be manufactured by micro- organisms

7. How drugs can be produced  Genetically modified animals 1. The gene for the protein (drug) is injected into the nucleus of a fertilised animal egg cell 2. The egg cell is then implanted into an adult animal – this then grows into a whole animal that contains a copy of the gene in every cell in the animal 3. The protein produced from the gene is usually purified from the milk of the animal

8. Example  Antithrombin III, which prevents blood clotting during surgery, is secreted in the milk of transgenic goats.  To create these transgenic goats, scientists used a needle thinner than a human hair to inject the DNA sequence for antithrombin III into goat eggs. Then they transplanted the fertilized transgenic eggs into female goats.

9. How drugs can be produced  Genetically Modified Plants 1. The gene for the protein (drug) is inserted into a bacterium 2. The bacterium then infects the plant cell 3. The bacterium inserts the gene into the plant cell DNA 4. The plant is now genetically modified 5. The plant cell is grown into an adult plant – the whole plant contains a copy of the gene in every cell 6. The protein produced from the gene can be purified from the plant tissue or the protein (drug) can be delivered by eating the plant

10. Benefits of Producing Drugs Using GMOs  Some disorders can now be treated with human proteins from genetically engineered organisms rather than animal proteins.  Producing proteins such as insulin using GMOs is much faster than using animal proteins.  Producing drugs using plants and animals is very cheap once the genetic modification has been made  Vaccines produced in plant tissues do not need to be refrigerated.

11. Risks of Producing Drugs Using GMOs  Some people think it’s unethical to genetically modify animals purely for human benefit.  Many people are concerned about the long term impacts of using GMOs.  If GMO crops used for drug production interbreed with crops used for food people may end up consuming drugs in their food which they do not need which could have harmful consequences on an individual’s health due to the risks associated with drug overdoses.

12. Example – Producing insulin using Genetically modified bacteria  Benefits of GMO Insulin: Bacteria and yeasts reproduce more rapidly and with fewer resources than complex mammals, they can be grown at a lower cost than sources of pork or beef insulin. Their faster rate also negates the wait associated with the maturation of animal sources, and the space needed to support these specialized bacteria colonies is significantly smaller than that needed to raise livestock. The International Diabetes Federation considers the supply of insulin produced from bacteria to be unlimited, since it does not depend on the quantity and availability of bovine or porcine pancreases. The insulin produced this way is also identical to insulin produced naturally by the human pancreas.

13. Example – Producing insulin using Genetically modified bacteria  The Risks of GMO Insulin The Society for Diabetic Rights states that a significant number of diabetics have experienced bad reactions to GMO insulin, and that some of these have resulted in death. Although GMO insulin poses a risk to some consumers of insulin, its comparatively greater availability and lower cost of production have prompted insulin manufacturers such as Eli Lilly to limit or disband production of pork or beef insulin. Diabetics who are unable to use GMO insulin find animal insulin more difficult to acquire. The Mayo Clinic website notes that a lack of insulin, which could result from this scarcity, exposes diabetics to additional problems, which include blindness, nerve damage and kidney damage.