OECD Workshop on the Development of a Unique Identifier for Bacteria

Genetic testing

Genetic testing involves the direct examination of the DNA molecule itself. A scientist scans a patient’s DNA sample for mutated sequences.

There are two major types of gene tests. In the first type, a researcher may design short pieces of DNA (“probes”) whose sequences are complementary to the mutated sequences. These probes will seek their complement among the base pairs of an individual’s genome. If the mutated sequence is present in the patient’s genome, the probe will bind to it and flag the mutation. In the second type, a researcher may conduct the gene test by comparing the sequence of DNA bases in a patient’s gene to a normal version of the gene.

Genetic testing can be used to:

• Diagnose a disease.
• Confirm a diagnosis.
• Provide prognostic information about the course of a disease.
• Confirm the existence of a disease in individuals.

With varying degrees of accuracy, predict the risk of future disease in healthy individuals or their progeny.

Genetic testing is now used for:

• determining sex
• carrier screening, or the identification of unaffected individuals who carry one copy of a gene for a disease that requires two copies for the disease to manifest
• prenatal diagnostic screening
• newborn screening
• presymptomatic testing for predicting adult-onset disorders
• presymptomatic testing for estimating the risk of developing adult-onset cancers
• confirmational diagnosis of symptomatic individuals
• forensic/identity testing

Some genetic tests are already available, although most of them are used in developed countries. The tests currently available can detect mutations associated with rare genetic disorders like cystic fibrosis, sickle cell anemia, and Huntington’s disease. Recently, tests have been developed to detect mutation for a handful of more complex conditions such as breast, ovarian, and colon cancers. However, gene tests may not detect every mutation associated with a particular condition because many are as yet undiscovered, and the ones they do detect may present different risks to different people and populations.^[11]

Pharmaceutical products

Traditional pharmaceutical drugs are small molecules that treat the symptoms of a disease or illness - one molecule directed at a single target. Biopharmaceuticals are large biological molecules known as proteins and these target the underlying mechanisms and pathways of a malady; it is a relatively young industry. They can deal with targets in humans that are not accessible with traditional medicines. A patient typically is dosed with a small molecule via a tablet while a large molecule is typically injected.

Small molecules are manufactured by chemistry but large molecules are created by living cells: for example, - bacteria cells, yeast cell,animal cells.

Modern biotechnology is often associated with the use of genetically altered microorganisms such as E. coli or yeast for the production of substances like insulin or antibiotics. It can also refer to transgenic animals or transgenic plants, such as Bt corn. Genetically altered mammalian cells, such as Chinese Hamster Ovary (CHO) cells, are also widely used to manufacture pharmaceuticals. Another promising new biotechnology application is the development of plant-made pharmaceuticals.

Biotechnology is also commonly associated with landmark breakthroughs in new medical therapies to treat diabetes, hepatitis B, hepatitis C, cancers, arthritis, haemophilia, bone fractures, multiple sclerosis, cardiovascular as well as molecular diagnostic devices than can be used to define the patient population. Herceptin, is the first drug approved for use with a matching diagnostic test and is used to treat breast cancer in women whose cancer cells express the protein HER2.

Modern biotechnology can be used to manufacture existing drugs more easily and cheaply. The first genetically engineered products were medicines designed to combat human diseases. To cite one example, in 1978 Genentech joined a gene for insulin and a plasmid vector and put the resulting gene into a bacterium called Escherichia coli. Insulin, widely used for the treatment of diabetes, was previously extracted from sheep and pigs. It was very expensive and often elicited unwanted allergic responses. The resulting genetically engineered bacterium enabled the production of vast quantities of human insulin at low cost.^[8]

Since then modern biotechnology has made it possible to produce more easily and cheaply the human growth hormone, clotting factors for hemophiliacs, fertility drugs, erythropoietin and other drugs.^[9] Most drugs today are based on about 500 molecular targets. Genomic knowledge of the genes involved in diseases, disease pathways, and drug-response sites are expected to lead to the discovery of thousands more new targets.^[10]

Pharmacogenomics

Main article: Pharmacogenomics

Pharmacogenomics is the study of how the genetic inheritance of an individual affects his/her body’s response to drugs. It is a coined word derived from the words “pharmacology” and “genomics”. It is therefore the study of the relationship between pharmaceuticals and genetics. The vision of pharmacogenomics is to be able to design and produce drugs that are adapted to each person’s genetic makeup.^[6]

Pharmacogenomics results in the following benefits:^[7]

1. Development of tailor-made medicines. Using pharmacogenomics, pharmaceutical companies can create drugs based on the proteins, enzymes and RNA molecules that are associated with specific genes and diseases. These tailor-made drugs promise not only to maximize therapeutic effects but also to decrease damage to nearby healthy cells.

2. More accurate methods of determining appropriate drug dosages. Knowing a patient’s genetics will enable doctors to determine how well his/ her body can process and metabolize a medicine. This will maximize the value of the medicine and decrease the likelihood of overdose.

3.Improvements in the drug discovery and approval process. The discovery of potential therapies will be made easier using genome targets. Genes have been associated with numerous diseases and disorders. With modern biotechnology, these genes can be used as targets for the development of effective new therapies, which could significantly shorten the drug discovery process.

4. Better vaccines. Safer vaccines can be designed and produced by organisms transformed by means of genetic engineering. These vaccines will elicit the immune response without the attendant risks of infection. They will be inexpensive, stable, easy to store, and capable of being engineered to carry several strains of pathogen at once.

History

Main article: History of Biotechnology

Early cultures understood the importance of using natural processes to breakdown waste products into inert forms. From very early nomadic tribes to pre-urban civilizations it was common knowledge that given enough time organic waste products would be absorbed and eventually integrated into the soil. It was not until the advent of modern microbiology and chemistry that this process was fully understood and attributed to bacteria.

The most practical use of biotechnology, which is still present today, is the cultivation of plants to produce food suitable to humans. Agriculture has been theorized to have become the dominant way of producing food since the Neolithic Revolution. The processes and methods of agriculture have been refined by other mechanical and biological sciences since its inception. Through early biotechnology farmers were able to select the best suited and highest-yield crops to produce enough food to support a growing population. Other uses of biotechnology were required as crops and fields became increasingly large and difficult to maintain. Specific organisms and organism byproducts were used to fertilize, restore nitrogen, and control pests. Throughout the use of agriculture farmers have inadvertently altered the genetics of their crops through introducing them to new environments, breeding them with other plants, and by using artificial selection. In modern times some plants have been genetically modified to produce specific nutritional values or to be economical.

The process of Ethanol fermentation was one of the first forms of biotechnology. Cultures such as those in Mesopotamia, Egypt, and Iran developed the process of brewing which consisted of combining malted grains with specific yeasts to produce alcoholic beverages. In this process the carbohydrates in the grains were broken down into alcohols such as ethanol. Later other cultures produced the process of Lactic acid fermentation which allowed the fermentation and preservation of other forms of food. Fermentation was also used in this time period to produce leavened bread. Although the process of fermentation was not fully understood until Louis Pasteur’s work in 1857, it is still the first use of biotechnology to convert a food source into another form.

Combinations of plants and other organisms were used as medications in many early civilizations. Since as early as 200 BC people began to use disabled or minute amounts of infectious agents to immunize themselves against infections. These and similar processes have been refined in modern medicine and have lead to many developments such as antibiotics, vaccines, and other methods of fighting sickness.

In the early twentieth century scientists gained a greater understanding of biochemical and genetic mechanisms and began to explore ways of manufacturing specific products using microbiological techniques. In 1917, Chaim Weizmann first used a pure culture in an industrial process, that of manufacturing corn starch using Clostridium acetobutylicum to produce acetone, which the United Kingdom desperately needed to manufacture explosives during World War I.^[3]

The field of modern biotechnology is thought to have largely began on June 16, 1980, when the United States Supreme Court ruled that a genetically-modified microorganism could be patented in the case of Diamond v. Chakrabarty.^[4] Indian-born Ananda Chakrabarty, working for General Electric, had developed a bacterium (derived from the Pseudomonas genus) capable of breaking down crude oil, which he proposed to use in treating oil spills.