HMB201 first semester notes.pdf

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Department
Human Biology
Course
HMB201H1
Professor
Paul Thompson
Semester
Winter

Description
The Biotechnology Century and Its Workforce Melina Kellermann 1.3 + 1.4  Genetically modified (GM) foods have become a controversial topic over the last few years, as have human embryos  Biotechnology is a multidisciplinary science with many powerful applications and great potential for future discoveries 1.1 What Is Biotechnology and What Does It Mean to You?  Biotechnology is broadly defined as the science of using living organisms, or the products of living organisms, for human benefit (or to benefit human surroundings) – that is, to make a product or solve a problem  Our early ancestors took advantage of microorganisms and used fermentation to make breads, cheeses, yogurts, and alcoholic beverages such as beer and wine  During fermentation, some strains of yeast decompose sugars to derive energy, and in the process produce ethanol (alcohol) as a waste product  For thousands of years, humans have used selective breeding as a biotechnology application to improve production of crops and livestock used for food purposes  In selective breeding, organisms with desirable features are purposely mated to produce offspring with the same desirable characteristics  Crossbreeding plants that produce the largest, sweetest, and most tender ears of corn is a good way for farmers to maximize their land to produce the most desirable crops  Zebra fish are important experimental model organisms – Casper will be important for drug testing and in vivo studies of stem cells and cancer. Casper has already proven to be valuable for studying how cancer cells spread: scientists injected fluorescent tumor cells into the fish’s abdominal cavity and were able to track the migration of those cells to specific locations in the body  Antibiotics are substances produced by microorganisms that will inhibit the growth of other microorganisms – used to treat bacterial infections in humans  Batch (large-scale) processes – in which scientists can grow bacteria and other cells in large amounts and harvest useful products in large batches – were developed to isolate commercially important molecules from microorganisms  As we have begun to unravel the secrets of DNA structure and function, new technologies have led to gene cloning, the ability to identify and reproduce a gene of interest, and genetic engineering, manipulating the DNA of an organism  Through genetic engineering, scientists are able to combine DNA from different sources. This process, called recombinant DNA technology, is used to produce many proteins of medial importance, including insulin, human growth hormone, and blood-clotting factors  Recombinant DNA technology has led to hundreds of applications, including the development of disease-resistant plants, food crops that produce greater yield, “golden rice” engineered to be more nutritious, and genetically engineered bacteria capable of degrading environmental pollutants  Gene cloning and recombinant DNA technology have had a tremendous impact on human health through the identification of thousands of genes involved in human genetic disease conditions  Ultimate project: the Human Genome project – international effort that begun in 1990, primary goal was to identify all genes – the genome – and their locations in each of the 24 human chromosomes Biotechnology: A Science of Many Disciplines  Biotechnology is an expansive, interdisciplinary field that relies on biology, chemistry, mathematics, computer science, and engineering in addiction to other disciplines such as philosophy and economics  Bioinformatics: the process of using computer science in sophisticated ways to study the sequence of a gene and analyze the structure of the protein produced by the gene  More than 65% of biotechnology companies in the US are involved in pharmaceutical production  Genentech, widely regarded as the world’s first biotech company, received approval for recombinant insulin as the first biotechnology product for human benefit (1982)  Over half of the new drugs in the development “pipeline” are designed to treat cancer  Many of the most widely used products of biotechnology are proteins created by gene cloning, these proteins are called recombinant proteins because they are produced by gene- cloning techniques. Majority of these proteins are produced from human genes inserted into bacteria to make the recombinant proteins used to treat human disease conditions  Scientists can identify a gene of interest and put it into bacteria or mammalian cells that are grown by a technique called cell culture – cells are grown in dishes or flasks within liquid culture media designed to provide the nutrients necessary for cell growth  Large culture containers, called fermenters or bioreactors, are used to mass produce cells containing the DNA of interest Ethics and Biotechnology  A wide range of ethical, legal, and social implications of biotechnology are a cause of great debate and discussion among scientist, the general public, clergy, politicians, lawyers, and many others around the world 1.2 Types of Biotechnology  There are many different types of biotechnology: Microbial Biotechnology  The use of yeast for making beer and wine – one of the oldest applications of biotechnology  By manipulating organisms such as bacteria and yeast, microbial biotechnology has created better enzymes and organisms for making many foods, simplifying manufacturing and production processes, and making decontamination processes for the removal of industrial waste products more efficient  Microbes used to make vaccines and to clone and produce batch amounts of important proteins used in human medicine Agricultural Biotechnology  In “ago biotech,” we examine a range of topics from genetically engineered, pest-resistant plants that do not need to be sprayed with pesticides, to food with higher proteins or vitamin content and drugs developed and grown as plant products  Already a big business that is rapidly expanding  Provides solutions for today’s farmers in the form of plants that are more environmentally friendly while yielding more per acre, resisting disease and insect pests, and reducing farmers’ production costs  The use of plants as sources of pharmaceutical products is an application of agricultural biotechnology commonly called molecular pharming – ie. Tobacco plants Animal Biotechnology  Animals can be used as “bioreactors” to produce important products  For example goats, cattle, sheep, and chickens are being used as sources of medically valuable proteins such as antibodies – protective proteins that recognize and help body cells to destroy foreign material  To achieve large-scale production, scientists can create female transgenic animals that express therapeutic proteins in their milk. Transgenic animals contain genes from another source  Animals are important in basic research as model organisms – gene “knockout” experiments, in which one or more genes are disrupted, can be helpful for learning about the function of a gene  Dolly – first mammal created by a cell nucleus transfer process Forensic Biotechnology  DNA fingerprinting – a collection of methods for detecting an organism’s unique DNA pattern – is a primary tool used in forensic biotechnology  First used in 1987 to convict a rapist in England  Also used to track diseases Bioremediation  The use of biotechnology to process and degrade a variety of natural and human-made substances, particularly those that contribute to environmental pollution  Bioremediation used to clean up many environmental hazards that have been caused by industrial progress Aquatic Biotechnology  One of the oldest applications of aquatic biotechnology is aquaculture, raising finfish or shellfish in controlled conditions for use as food sources  Through the use of genetic engineering, disease-resistant strains of oysters and vaccines against viruses that infect salmon and other finfish have been produced  Transgenic salmon have been created that overproduce growth hormone, leading to extraordinary growth rates over short growing periods  Bioprospecting efforts are ongoing around the world to identify aquatic organisms with novel properties that may be exploited for commercial purposes Medical Biotechnology  From preventative medicine to the diagnosis of health and illness to the treatment of human disease conditions, medical biotechnology has results in an amazing array of applications designed to improve human health  Gene therapy approaches, in which genetic disease conditions can be treated by inserting normal genes into a patient or replacing disease genes with normal genes, are being pioneered  Stem cell technologies are some of the newest, most promising aspects of medical biotechnology Biotechnology Regulations  Most biotechnology products must be carefully examined before they are available for use  FDA sets standards for biotechnology products, often US department of agriculture and the environmental protection agency involved too  One of the most heavily regulated industries  Two important aspects include: quality assurance (QA) and quality control (QC) 1.3 Biological Challenges of the Twenty-First Century  2001: rough draft of the human genome project  Human genome project was completed in 2003, consisted of far fewer than the estimated 100,000 genes  A better understanding of human disease will require that we understand the structures and functions of the proteins that genes encode, the proteome, the collection of proteins responsible for human cells  One area expected t be a great aid in the diagnosis of genetic disease conditions will comprise applications involving single nucleotide polymorphisms (SNPs) – they are single nucleotide changes or mutations in DNA sequences that vary from individual to individuals  SNPs are the cause of some genetic diseases, such as sickle cell anemia  On average, each person is found to carry approximately 250 to 300 loss-of-function variants in studied genes and 50 to 100 variants in genes causing inherited disorders  The significance of this can be seen in the drugs that have been developed for human breast cancer. The two well-known breast cancer genes, BRCA1 and BRCA2, have about 1,700 variants worldwide  Before these genes were know, all breast cancers were treated with the same drugs  Testing one’s DNA for different SNPs is one way to identify the disease genes that a person may be carrying  One way to do this is to isolate DNA from a small amount of the patient’s blood and then apply it to a DNA microarray, also called a gene chip  Microarrays contain thousands of DNA sequences. Using sophisticated computer analysis, scientists can compare patterns of DNA binding between a patients DNA and the DNA on the microarray to reveal a patients SNP patter  Discovery of SNPs partially responsible for the emergence of pharmacogenomics, or customized medicine. It involves tailor-designing drug therapy and treatment strategies based on the genetic profile of a patient – that is, using his or her genetic information to determine the most effective and specific treatment approach  SNP and microarray information could be used to figure out a person’s risk of developing a particular type of cancer  Metabolomics, a biochemical snapshot of the small molecules – such as glucose, cholesterol, ATP, and signaling molecules that result from a cellular change – produced during cellular metabolism  This snapshot directly reflects physiologic status and can be used to monitor drug effects on disease states  Between 2,000 and 10,000 human metabolites  Nanotechnology, or applications that incorporates small devices – development of small particles that can be used to deliver drugs to cells: nanoparticles containing chemotherapy agents can be specifically directed to target cancel cells by a coat of tumor-specific proteins bound to the target cells  Gene therapy technologies involve replacing or augmenting defective genes with normal copies of them  Obstacles currently prevent gene therapy from being widely used in humans: • How can normal genes be delivered to virtually all cells in the body? • What are the long term effects of introducing extra genes into humans? • What must be done to be sure that the normal protein is properly made after the extra genes are delivered into the body?  Another new technology with the potential for modifying a genetic defect by silencing a genes is being aggressively pursued using small interfering RNA (siRNA)  Most stem cells are obtained from embryos (embryonic stems cells, ESCs)  There are also stem cells derived from adult tissue (adult-derived stem cells, ASCs)  There are also induced pluripotent stem cells (iPSCs)  Regenerative medicine is the phrase used to describe the approach of using stem cells to replace damaged tissues of failing organs 1.4 The Biotechnology Workforce  Biotechnology companies are looking for people who are comfortable analyzing complex data and sharing their expertise with others in team oriented, problem-solving working environments The Business of Biotechnology  1976: small company, Genentech Inch, near San Francisco, California, was founded – generally recognized as the first biotechnology company  Countries without a traditional history in research and development (R&D) worldwide are turning to biotechnology for high-tech innovations. For example, biotechnology is a rapidly developing industry in India and China What Is a Biotechnology Company?  Large pharmaceutical companies are commonly referred to as “big pharma” – i.e. Johnson&Johnson  Pharmaceutical companies are involves in drug development by chemically synthesizing or purifying compounds used to make the drugs – products such as aspirin, antacids, and cold medicines  Pharmaceutical companies typically do not use living organisms to grow or produce a product (such as a recombinant protein), as is the focus of biotechnology companies  Biotechnology companies vary in size  Historically, many biotechnology companies begin as a startup company formed by a small team of scientists who believe that they might have a promising product to make. The team must then seek investors to fund their company so that they can rent or buy lab facilities, buy equipment and supplies, and continue the research and development necessary to make their product  Biotechnology startup companies rely on financial investments in the company, such as venture capital (VC) funds provided at an early stage to startup companies with a potential for success – venture capital funds make money by owning equity in startup companies  Angel investors – affluent individuals who provides VC capital for a startup in exchange for company ownership – are key to providing startup biotechnology companies with the funds needed to carry out the research and testing necessary to make their product  Initial public offering (IPO): available for the public to purchase shares of company stock Jobs in Biotechnology  Research and development: • Development of a new biotech product is a long and expensive process • Individuals in R&D are directly involved in the process of developing ideas and running experiments to determine if a promising idea can be developed into a product • Without new discoveries, companies cannot make new products • Most positions require a bachelor’s or associate’s degree in chemistry, biology, or biochemistry • Laboratory technicians: cleaning and maintaining equipment used by scientists and keeping labs stocked with supplies • Research assistants or research associates: carry out experiments under supervision of established and experiences scientists • Principal or senior scientist: usually have a PhD and considerable practical experience in research and management skills for directing other scientists • Bioinformatics: needed to analyze, organize, and share DNA and protein sequence information  Operations, bio-manufacturing, and production: • Oversees specific details of product development, such as the equipment and laboratory processes involved in producing a product • Often includes scale-up processes, in which cultured cells making up a product must be grown on a large scale • Biomanufacturing and production units maintain and monitor the large-scale and large-volume equipment used during production, and they ensure that the company is following proper procedures and maintaining appropriate records of the product  Quality assurance and quality control: • Federal agencies require that manufacturing follow exact methods approved by regulatory officials • Quality assurance: guarantee the final quality of all products • Quality control efforts are designed to ensure that products meet stringent regulations mandated by federal agencies • QA and QC workers are also responsible for monitoring equipment, facilities, and personnel, maintaining correct documentation, testing product samples, and addressing customers inquiries and complaints, along with other responsibilities  Clinical research and regulatory affairs: • Regulated by a number of different agencies  Marketing, sales, finance, and legal divisions: • Sales representatives: work with medical doctors, hospitals, and medical institutions to promote a company’s product • Marketing specialists: devise advertising companies and promotional materials to target customer needs for the products a company sells • Finance divisions: typically run by vice presidents or chief financial officers who oversee company finances and are also often involved in raising funs from partners or venture capitalists seeking investments in technology companies • Legal specialists: work on legal issues associated with product development and marketing, such as copyrights, naming rights, and obtaining patents Salaries in Biotechnology  Biotechnology industry has only been around for about 25 years Lecture 1: Biotechnology: An Overview Slides 25-31 + Slides 39-42  Second came: Molecular Manipulations – it started in the 1980s. First regulatory approval and marketing of GM plants modification: 1995  In the 19 century, systemic public health interventions began o Pasteurization (after Louis Pasteur) o Vaccinations (e.g. William Jenner and smallpox) o Sewage treatment and organic waste composting – both fermentation processes using macro-organisms th  In the 20 century, a major medical biotechnology o Discovery, by Alesander Fleming, in 1929 that the fungus Penicillium notatum produced a substance that could destroy of inactivate a wide range of bacteria  Biotechnology defined broadly: the commercial use of naturally occurring or human- designed organisms (which include viruses) or parts thereof, to produce a product or to affect a change in some other organism or material – all intended to benefit of humans  Biotechnology is very old  However, since the 70s biotechnology has been used more restively: biotechnology is the application of molecular genetic knowledge to the engineering (manipulation) of the DNA of a class of organisms in order to produce a humanly useful product  European Federation of Biotechnology (EFB) define biotechnology as: the integration of the natural sciences and organisms, cells, parts thereof, and molecular analogues for products and services  We will use the broader definition  Science and technology: corn fields o Since the 1930s, biologically based technology (double cross, single cross,) were used which increased the corn yields in comparison to open pollinations. In 1995 molecular-based technology was used, increased it even more  Challenges ahead: 1. Scientific • We have learned a great deal in the last half century BUT • We need to know a lot more about gene structure and function • We need to know a lot more about developmental processes and gene-environment interaction o Less important when working with micro-organisms o Very important in plant and animal modification and some medical biotechnology 2. Commercialization • Scaling up 3. Social, Political, Ethical • Scientific knowledge and techniques are increasing rapidly • Public acceptance and public policy is lagging badly o Public concern with altering life is paramount 4. Economic • this is a crucially important part of biotechnology: applications of biotechnology are commercial activities • E.g., cheap old and gas prices, until the last decade, made many potential biotechnological applications untenable • This highlights an important general principle • For any particular specific biotechnology: Input + production + delivery costs < product income < any non-biotech methods of product production  Biotechnology is multi-disciplinary o There is no discipline, “biotechnology” o It is a large number of disciplines working together on a specific technology o The term “multidisciplinary describes a quantitative extension of approaches to problems which commonly occur within a given area. It involves the marshaling of concepts and methodologies from a number of separate disciplines and applying them to a specific problem in another area o In contrast, interdisciplinary applications occur when the blending of ideas which
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