Trial Version Science and Technology The Nature and Development of Science and Technology Case investigation – The important developments of science and technology Case 3: Biotechnology Activity and case-based learning & teaching resources Students’ version Table of Content (Students’ version) Outline Aims of study Scheme of work Background information 2 2 3 Teaching Resources Lesson 1, 2: What is biotechnology? Background Activity 1: Information collection and poster design Reference article Activity 2: “KARS” game <infectious diseases and biotechnology> Worksheet Additional background information 4 4 5 5-6 7 7 8 - 14 Lesson 3, 4: Development of modern biotechnology Background Activity 3: DNA extraction experiment Additional background information 15 15 16- 18 19- 23 Lesson 5, 6: What are the problems of biotechnology? 24 Background 24 Activity 4: Debate on the constraints and controversies on biotechnology 25-31 (Discussion questions and articles) Worksheet 32 Extended activities and readings 33-37 1 Students’ version Outline Aims of study The aim of these lessons is to introduce biotechnology - a rapidly developing knowledge and technology that affects human living in various aspects. Students should have a brief understanding on the development of biotechnology through the lessons. The course will motivate their interest to observe biotechnology through their daily lives, as well as to take part in some discussions about the development of biotechnology. Students have to find out the contributions of biotechnology from its history and constraints through ethical and safety issues. Through the group activities, students are encouraged to exchange ideas with each other, so as to have a better understanding on the strengths and constraints of technological development. Scheme of work Lessons Learning objective 1, 2 What is biotechnology? Teaching strategy 3, 4 The development of modern biotechnology 5, 6 What are the problems of biotechnology? Learning and teaching resources Brief explanation of the PowerPoint definition and examples of Fluorescent biotechnology pigments Brief explanation of the Worksheet milestone of biotechnology I Information collection of biotechnology topics “KARS” game Brief explanation of the milestone of biotechnology II DNA extraction experiment Debate on the constraints and the issues of biotechnology PowerPoint Experimental apparatus/ materials Worksheet PowerPoint Articles and debate topics Worksheet 2 Students’ version Background information Biotechnology is one of the most rapidly developing technologies in the world. The increasing popularity of modern biotechnology can be traced back to the 1970s when genetic researches have become mature that brought about a developmental breakthrough. In fact, biotechnology has had a close relationship with the human society long ago. From the examples of the Babylonian’s beer in 6000 B.C. and the Egyptian’s baked cakes in 4000 B.C., we can convince that humans have started to observe the new elements evolved from the changes of natural substances and from the life process of organisms during the ancient time. Although the ancient people cannot master the scientific principles yet, they can make use of their limited knowledge to fulfil the needs of their daily lives. Nowadays scientists have done biological researches widely and deeply, which decode lots of myths of lives. With the rapid development of electronics and engineering technology, the application of biotechnology is versatile and far-reaching. Even though the development of modern biotechnology has undergone just more than 20 years, its applications extend over different areas included the major problems of food, health, resources, energy and environment that humans are facing. Biotechnology is closely related to our lives and has a close relationship with our personal health. The antibiotics used for fighting against bacteria, vaccine inoculation and drugs produced from researches on molecular structures are all beneficial to our health. The rapid development of biotechnology continually not only brings novel technological breakthrough to humans, it also causes great impacts on ethics and in aspects of life and death. For example, the controversies on ‘animal cloning’ and ‘human cloning’ in the recent ten years as well as the discussions on researches of embryonic stem cells and gene therapy, all of which lead people from different sectors to have self-reflection on the problems of life, morality and ethics. 3 Students’ version Teaching Resources Lesson 1, 2: What is biotechnology? Background Although the relationship between biotechnology and us is very close, we may not be aware of what it is and how does it operate? How can we observe its footprint in our lives? What are its contributions and constraints? Biotechnology included two words, Bio (lives and organisms) and Technology (crafts and techniques). Simply speaking, the meaning of the whole term is ‘the techniques to use organisms to produce products’. However, the scope of this definition is very wide. For a more precise description, “biotechnology” is ‘the techniques applying biological process, biological cells or other metabolites to produce products and improve the quality of human living’. The application of biotechnology is very widespread and the related area is expending continually. Conventional biotechnology can be divided into three areas to be applied in agriculture, medicine and industry. Nowadays, the applications of biotechnology are even wider in chemical industry and environmental protection, resources and energy, marine resources exploitation and even in military development. Moreover, biotechnology has become the basic tool for investigating life science researches in academic researches. Modern biotechnology is flourishingly developing worldwide and are recognised as the most important industry in the 21st century. Activity 1: Information collection 〈Investigating biotechnology aspect〉 Activity guideline: Students are divided into 5 groups to collect information of each aspect and design a poster using the information as examples. The poster designed should be suitable for teaching and commercial purposes. The objective is to introduce new knowledge to readers and let them clearly understand the basic ideas of the chosen aspect. For examples, its developmental history, application, advantages, constraints and the ethical, legal and regulation problems, etc. Biotechnological areas Examples Medical Agricultural Environmental Military defences Scientific researches Student can start from some examples in their daily lives to design the poster. For example in the medical application of biotechnology, students might have taken antibiotics. Students can also try to collect information from different areas such as the basic function of antibiotics, the contribution of biotechnology and the invention of antibiotics, its applications and demands in the past and present and the problems induced by it such as 4 Students’ version drug abuse, etc. Reference article: http://www.nal.usda.gov/bic/bio21/execsum.html Biotechnology for the 21st Century: New Horizons Preface Through the use of advanced tools such as genetic engineering, biotechnology is expected to have a dramatic effect on the world economy over the next decade. Innovations emerging in the food and pharmaceutical sectors offer only a hint of the enormous potential of biotechnology to provide diverse new products, including disease-resistant plants, "natural" pesticides, environmental remediation technologies, biodegradable plastics, novel therapeutic agents, and chemicals and enzymes that will reduce the cost and improve the efficiency of industrial processes. To date, the Federal investment in biotechnology has been focused primarily on the health field. The results of this research are having a profound impact on medicine and health care, providing improved approaches to the diagnosis, treatment, and prevention of disease. While health-related research must remain a national priority, researchers are poised to build on the common foundation in basic science to bring the power of biotechnology to bear in other fields. Modest investments now in several rapidly developing areas of biotechnology research will lead to major economic and societal benefits, including foods that are more abundant and nutritious, a cleaner environment, and non- toxic biomanufacturing. This "second wave" of biotechnology research is the focus of this report, which is the result of a planning effort by the Biotechnology Research Subcommittee (BRS) of the Committee on Fundamental Science of the National Science and Technology Council (NSTC). The report outlines opportunities for Federal investment in research in four areas: (1) agricultural biotechnology; (2) environmental biotechnology, with a focus on bioremediation, (3) manufacturing/bioprocessing, including energy research; and (4) marine biotechnology and aquaculture. The plans were developed with input from the private sector. Following is a summary of the priorities identified in each area: Agriculture Agricultural biotechnology offers efficient and cost-effective means to produce a diverse array of novel, value-added products and tools. It has the potential to increase food production, reduce the dependency of agriculture on chemicals, and lower the cost of raw materials, all in an environmentally friendly manner. Environment The focus in environmental biotechnology is on bioremediation. This involves the use of living organisms or their products to degrade wastes into less toxic or non-toxic products and to concentrate and immobilize toxic elements, such as heavy metals, to minimize industrial wastes and rehabilitate areas fouled by pollutants or otherwise damaged through ecosystem mismanagement. Manufacturing/Bioprocessing The demand for new and improved commercial products increasingly will be met through bioprocessing, a type of advanced manufacturing that employs chemical, physical, and biological processes employed by living organisms or their cellular components. Bioprocessing can provide products with unique and highly desirable characteristics and offers new production opportunities for a wide range of items. Marine Biotechnology and Aquaculture Oceanic organisms constitute a major portion of the Earth's biological resources, yet most 5 Students’ version of these organisms (primarily microorganisms) have yet to be identified. Recent advances in molecular biology, biosensor technology, aquaculture, and bioprocess engineering now promise fundamentally new approaches and opportunities for identifying, using, and managing biological resources from the seas. Biotechnology is poised to make major contributions to the economic growth of the United States and the world in the 21st century. Coordinated implementation of these priorities will enable the United States to retain its pre-eminence in this burgeoning field. A Report from the Biotechnology Research Subcommittee Committee on Fundamental Science National Science and Technology Council July 1995 Please answer the questions below: 1. Please list the biotechnological areas mentioned in the article: ____________________________________ ____________________________________ ____________________________________ 2. As mentioned in the article, techniques of medical biotechnology greatly improved the preventative, diagnosis and therapeutic methods of diseases, which give significant influence to human health. Can you observe any related examples in your daily lives? ____________________________________ ____________________________________ ____________________________________ 3. In the article, the great contribution of environmental biotechnology in processing pollutants has been mentioned. Can students think of another issues about environmental ecology? How can biotechnology assist in solving this problem? ____________________________________ ____________________________________ ____________________________________ 6 Students’ version Activity 2: “KARS” game 〈Infectious diseases and biotechnology〉 Infectious diseases have long been human killers. At the end of the 16th century, people invented microscopes, which enable us to observe cells, tissues and microorganisms, which cannot be observed by naked eyes. As scientists could observe the living phenomenon of bacteria, they could understand the causes of illnesses and it helps in diagnosing and curing diseases – it is an extremely important breakthrough in biology. Electronic microscopes were invented in 1930s, scientists were then able to observe viruses, which could not be seen before. We hope the simple game can inspire students thinking about the risk of infectious diseases and their relationship with biotechnology. Please group the infectious diseases below and choose the names of bacterial transmitted diseases, such as cholera, to fill in the appropriate boxes. Tuberculosis AIDS Measles Influenza Syphilis SARS Bacterial cases Hepatitis Meningitis Bird flu Cholera Chicken pox Tetanus Viral cases 7 Students’ version Additional background information: Summary of the history of the development of biotechnology BC 6000 Barbarians used yeast to brew beer 4000 Egyptians used yeast to bake bread AD 1590 H. Janssen and Z. Janssen invented compound microscope 1683 A.V. Leeuwenhoek observed bacteria 1796 E. Jenner discovered cowpox patients were immune to small pox and developed cowpox vaccines to prevent small pox infection. 1865 G. Mendel discovered basic materials of inheritance and established the foundations of genetic studies 1868 J. Miescher discovered DNA 1879 W. Fleming discovered chromosomes 1910 T. H. Morgan proved that chromosome exists in inherited genes. He was awarded the Nobel Prize (physiology or medicine) in 1933 1928 A. Fleming conducted researches on antibiotics (Penicillin) 1944 O. Avery and his colleagues proved that genetic materials exist in DNA but not in proteins. Scientists started to have intensive researches on DNA. 1953 J. Watson and F. Crick discovered the double-helix structure of DNA. In 1962 , Crick and Watson awarded the Nobel Prize (Physiology or Medicine)。 1957 F. Crick explained how different proteins are produced from DNA 1969 J. Beckwith and J. Shapiro, et al. isolated genes for the first time 1970 H.O. Smith and K.W. Wilcox discovered restriction enzymes which can selectively break the DNA strand (Restriction enzyme)。 1972 Paul Berg used restriction enzymes to break DNA into fragments, then used ligase to join two segments of DNA. DNA recombination succeeded. Paul Bergwon was awarded the Nobel Prize (Chemistry) in 1980 1973 S. Cohen and H. Boyer used the techniques of cutting and pasting DNA for DNA recombination to produce DNA recombinants. Recombinant DNA characterised the commence of biotechnology 1983 K. B. Mullis invented Polymerase Chain Reaction (PCR) to simultaneously copy and replicate large amount of DNA in a short time, which is an important method for biotechnology researches. Mullis won the Nobel Prize (Chemistry) in 1993. 1984 DNA Fingerprinting started to be applied in crime investigation 1990 HGP - Human Genome Project launched 1996 The first cloned sheep in the world, Dolly was born 1998 Human Embryonic stem cells (HESC) were successfully cultivated by J. Gearhart and J. Thomson 2003 HGP finished and released the 3 billion of base pairs sequence in human genome in the science magazine <Nature> 2005 The Genographic Project。 8 Students’ version Additional background information: Summary of biotechnological development – case investigation Polymerase Chain Reaction (PCR) (Extract) http://en.wikipedia.org/wiki/Polymerase_chain_reaction From Wikipedia What is PCR? Polymerase chain reaction (PCR) is a molecular biology technique, for enzymatically replicating DNA without using a living organism, such as E. coli or yeast. Like amplification using living organisms, the technique allows a small amount of the DNA molecule to be amplified exponentially. However, because it is an in vitro technique, it can be performed without restrictions on the form of DNA and it can be extensively modified to perform a wide array of genetic manipulations. The applications of PCR: PCR is commonly used in medical and biological research labs for a variety of tasks, such as the detection of hereditary diseases, the identification of genetic fingerprints, the diagnosis of infectious diseases, the cloning of genes, paternity testing, and DNA computing. PCR can be used for a broad variety of experiments and analyses. Some examples are discussed below. Genetic fingerprinting Genetic fingerprinting is a forensic technique used to identify a person by comparing his or her DNA with a given sample, such as blood from a crime scene can be genetically compared to blood from a suspect. The sample may contain only a tiny amount of DNA, obtained from a source such as blood, semen, saliva, hair, or other organic material. Paternity testing A paternity test is conducted to prove paternity, that is, whether a man is the biological father of another individual. This may be relevant in view of rights and duties of the father. Similarly, a maternity test can be carried out. This is less common, because at least during childbirth, except in the case of a pregnancy involving embryo transfer or egg donation, it is obvious who the mother is. This can be achieved by DNA analysis of the three individuals, although older methods have included ABO blood group typing, analysis of various other proteins and enzymes, or using HLA antigens. For the most part however, DNA has all but taken over all the other forms of testing. Detection of hereditary diseases The detection of hereditary diseases in a given genome is a long and difficult process, which can be shortened significantly by using PCR. Each gene in question can easily be amplified through PCR by using the appropriate primers and then sequenced to detect mutations. Cloning genes Cloning a gene, not to be confused with cloning a whole organism, describes the process of isolating a gene from one organism and then inserting it into another organism (now termed a genetically modified organism (GMO)). Mutagenesis Mutagenesis is a way of making changes to the sequence of nucleotides in the DNA. Analysis of ancient DNA Using PCR, it becomes possible to analyze DNA that is thousands of years old. PCR is an important technique in biotechnology and medicine, and its role would be more essential in the future. 9 Students’ version Human Genome Project (1990-2003) (Extract) http://en.wikipedia.org/wiki/HGP From Wikipedia The Human Genome Project (HGP) is a project to map and sequence the 3 billion nucleotides contained in the human genome and to identify all the genes present in it. Goals The goals of the original HGP were not only to determine all 3 billion base pairs in the human genome with a minimal error rate, but also to identify all the genes in this vast amount of data. This part of the project is still ongoing although a preliminary count indicates about 30,000 genes in the human genome, which is far fewer than predicted by most scientists. Another goal of the HGP was to develop faster, more efficient methods for DNA sequencing and sequence analysis and the transfer of these technologies to industry. The sequence of the human DNA is stored in databases available to anyone on the Internet. The U.S. National Center for Biotechnology Information (and sister organizations in Europe and Japan) house the gene sequence in a database known as Genbank, along with sequences of known and hypothetical genes and proteins. Other organizations such as the University of California, Santa Cruz, and ENSEMBL present additional data and annotation and powerful tools for visualizing and searching it. Computer programs have been developed to analyze the data, because the data themselves are difficult to interpret without them. The process of identifying the boundaries between genes and other features in raw DNA sequence is called genome annotation and is the domain of bioinformatics. While expert biologists make the best annotators, their work proceeds slowly, and computer programs are increasingly used to meet the high-throughput demands of genome sequencing projects. The best current technologies for annotation make use of statistical models that take advantage of parallels between DNA sequences and human language, using concepts from computer science such as formal grammars. Another, often overlooked, goal of the HGP is the study of its ethical, legal, and social implications. It is important to research these issues and find the most appropriate solutions before they become large dilemmas whose effect will manifest in the form of major political concerns. All humans have unique gene sequences, therefore the data published by the HGP does not represent the exact sequence of each and every individual's genome. It is the combined genome of a small number of anonymous donors. The HGP genome is a scaffold for future work in identifying differences between individuals. Most of the current effort in identifying differences between individuals involves single nucleotide polymorphisms and the HapMap. Benefits The work on interpretation of genome data is still in its initial stages. It is anticipated that detailed knowledge of the human genome will provide new avenues for advances in medicine and biotechnology. Clear practical results of the project emerged even before the work was finished. For example, a number of companies, such as Myriad Genetics started offering easy ways to administer genetic tests that can show predisposition to a variety of illnesses, including breast cancer, disorders of hemostasis, cystic fibrosis, liver diseases and many others. Also, the 10 Students’ version etiologies for cancers, Alzheimer's disease and other areas of clinical interest are considered likely to benefit from genome information and possibly may lead in the long term to significant advances in their management. There are also many tangible benefits for biological scientists. For example, a researcher investigating a certain form of cancer may have narrowed down his search to a particular gene. By visiting the human genome database on the worldwide web, this researcher can examine what other scientists have written about this gene, including (potentially) the three-dimensional structure of its product, its function(s), its evolutionary relationships to other human genes, or to genes in mice or yeast or fruit flies, possible detrimental mutations, interactions with other genes, body tissues in which this gene is activated, diseases associated with this gene or other datatypes. Further, deeper understanding of the disease processes at the level of molecular biology may determine new therapeutic procedures. Given the established importance of DNA in molecular biology and its central role in determining the fundamental operation of cellular processes, it is likely that expanded knowledge in this area will facilitate medical advances in numerous areas of clinical interest that may not have been possible without them. The analysis of similarities between DNA sequences from different organisms is also opening new avenues in the study of the theory of evolution. In many cases, evolutionary questions can now be framed in terms of molecular biology; indeed, many major evolutionary milestones (the emergence of the ribosome and organelles, the development of embryos with body plans, the vertebrate immune system) can be related to the molecular level. Many questions about the similarities and differences between humans and our closest relatives (the primates, and indeed the other mammals) are expected to be illuminated by the data from this project. The Human Genome Diversity Project, spinoff research aimed at mapping the DNA that varies between human ethnic groups, which was rumored to have been halted, actually did continue and to date has yielded new conclusions. In the future, HGDP could possibly expose new data in disease surveillance, human development and anthropology. HGDP could unlock secrets behind and create new strategies for managing the vulnerability of ethnic groups to certain diseases (see race in biomedicine). It could also show how human populations have adapted to these vulnerabilities. 11 Students’ version Additional background information: DNA project to trace human steps (The Genographic Project – 2005) (Extract) http://news.bbc.co.uk/1/hi/sci/4435009.stm By Paul Rincon BBC News science reporter A project spanning five continents is aiming to map the history of human migration via DNA. The Genographic Project will collect DNA samples from over 100,000 people worldwide to help piece together a picture of how the Earth was colonized. Samples gathered from indigenous people and the general public would be subjected to lab and computer analysis to extract the valuable genetic data. Team leader Dr Spencer Wells calls the plan "the Moon shot of anthropology". The $40m (£21m) privately funded initiative is collaboration between National Geographic, IBM and the Waitt Family Foundation charity. Participating in the five-year study are some of the world's top population geneticists, as well as leading experts in the fields of ancient DNA, linguistics and archaeology. Future resource "We see this as a resource for humanity going into the future. It could potentially become the largest genetic database ever created," Dr Wells told the BBC News website. Members of the public will be able to buy a kit that contains all the material needed to add their genetic information to the database. Already, evidence from genetics and archaeology places the origin of modern humans (Homo sapiens) in Africa roughly 200,000 years ago. It is thought, the first moderns to leave the continent set off around 60,000 years ago. By studying the Y (or male) chromosome and mitochondrial DNA (which is passed down exclusively on the maternal line), scientists have pieced together a broad-brush picture of which populations moved where in the world - and when. What is lacking, says Wells, is the fine detail, which could be filled in by this large-scale project. "We know which markers on the Y chromosome to focus on; we know our way around the mitochondrial genome fairly well. We just haven't had the large sample sizes to apply these technologies properly," Dr Wells explained. "There are still many questions we haven't answered. Was there any interbreeding with Neanderthals as modern humans moved into Europe? Did any of the migrations to the Americas come across the Pacific - or even the Atlantic?" Collection challenge But some researchers said experience on other projects suggested this one could run into trouble with indigenous groups - particularly those, such as Native Americans and Aboriginal Australians, with a history of exploitation. Project directors said they had already sought advice from indigenous leaders about their participation. 12 Students’ version IBM says it will use sophisticated analytical techniques to interpret the information in the biobank and find patterns in the genetic data. The IT giant will also provide the computing infrastructure for the project. Kits sold to the public contain cheek swabs used to scrape the inside of the mouth for a DNA sample. The swabs can then be mailed to a central laboratory for analysis. After four to six weeks, the results of the analysis will appear on the website behind an anonymous password contained in the kit. The exact budget available for the study will depend on how many test kits are sold to the public. The net proceeds will go back into the research and into a "legacy project" to support indigenous peoples. The Genographic Project's directors emphasize that the information in the database will be made accessible to scientists studying human migrations. "We see this as part of the commons of our species. We're not going to be patenting anything - the information will all be in the public domain," said Dr Wells. 13 Students’ version Additional background information: Bacteria and viral cells under microscope: HIV virus (AIDS) Bacilli (Vibrio cholerae) Poliovirus (Poliomyelitis) Spirillum Source of figures: http://virology-online.com/presentations/index.htm 14 Students’ version Lesson 3,4: The development of modern biotechnology Background Biotechnology is not entirely an emerging technology. Traditional biotechnology can be traced back to the fermentation process used by ancient people to produce traditional food such as rice wine, vinegar, soya sauce and bread, etc. Meanwhile, modern biotechnology as an emerging discipline with the development of genetic engineering as the core, it is based on researchresults of modern biology from late 1970s to early 1980s. It allows people to modify the form and structure according to their default setting or to process raw biological materials for producing products and achieving some technical requirements. Although the hallmark of modern biotechnology is DNA recombination technology in the 1970s, this kind of technology is established from the results of conventional Biology and other disciplines, as well as the previous research outcomes on engineering technologies. The keys included the claim made by Oswald T. Avery, et al. in 1944 that DNA is the carrier of inheritance messages and the discovery of double helix DNA structure by James Watson and Francis Crick in 1953 that led to the later molecular biology researches. Since all living activities are the results of the functioning of enzymes and non-enzymatic proteins, the relationship between inheritance messages and proteins has become the key theme of investigating living activities. In 1961, Marshall Nirenberg explained how do the inheritance messages in DNA coding (A, T, G, C) transmit to proteins. In 1972, Paul Berg became the first expert of biological researches to accomplish the in vitro DNA recombination techniques successfully based on the results of the academic researches above. We can break up DNA strands, isolate and recombine the genes for inoculating into other organism and reconstructing cells now according to what we want. Use the simple organisms bacteria as an example, enormous amount of functional proteins used for drug and vaccine production are produced. These modified bacteria can even be injected into human body directly for gene therapy. In 1983, a scientist, Kary Mullis invented Polymerase Chain Reaction (PCR) to copy a DNA fragment to 10 billions to 100 billions times. This is a technique having great impact on biology and medicine as well as forensic science. 15 Students’ version Activity 3: DNA extraction experiment Guidelines: As time for the experiment is limited, teacher should ask the laboratory technicians to prepare suitable apparatus and tools before the experiment to ensure effective time-management. Materials Kiwi fruit 3 g sodium chloride (salt) 100 ml distilled water 10 ml detergent Egg white Chilled pure alcohol 60℃ hot water Iced water Apparatus Beaker Filter paper 100 ml measuring cylinder Large test-tube Blender Glass rod Thermometer Dropper Step 1: Preparation Pour 3 g of sodium chloride (salt) and 10 ml of detergent into beaker with 100 ml distilled water. Slice the Kiwi fruit into small pieces and immerse it into the detergent-salt liquid. Step 2: Soak in hot water Put the beaker with the liquid above in a water bath of 60℃ for 15 minutes and stir it gently (Figure 1). (Figure 1) (Figure 2) Step 3: Immersing in iced-water Put the beaker with the liquid in iced water bath for 5 minutes and stir it gently (Figure 2). Step 4: Blending Pick up the beaker and pour the liquid into the blender to blend for 5 seconds, and then filter the mixture (Figure 3). 16 Students’ version (Figure 3) Step 5: Filtration: Collection about 6 ml filtrate by test-tube and add 4 drops of egg white (Figure 4). (Figure 4) Step 6: Extraction Pour the chilled alcohol via the wall of the test-tube to the surface of filtrate slowly. (A milky layer will be formed between the upper layer of alcohol and the lower layer of detergent (Figure 5)) Use dropper to extract the milky substance in the layer and use universal indicator to test the pH value of the gene extract. Alcohol Kiwi DNA Detergent (Figure 5) Result The layer of milky substance is the extracted DNA. Since DNA is acidic, the test result is: the universal indicator changed from green to orange-yellow. Advanced activity (1) Use dye to stain DNA, then observe it under microscope (2) The gene extraction method of other biological tissues is similar to the proposed method 17 Students’ version above, students can try to extract gene from animal’s liver or that from microorganism. Safety rules Beware of safety when cutting or using blender. (Modified from the web site of “Promoting biotechnology education” by the Science Faculty of HKIED) http://www.ied.edu.hk/biotech/chi/exp/exp_onion2.htm Explanation of experiment: All the chemicals used in this experiment can help us to extract DNA from cells. Firstly, the cell walls have to be broken down. The cleaning detergent lead to burst of the outer part of cells and salts can assist in separating DNA and other molecules such as carbohydrates. Cooling can prevent the DNA remained in membranes and of cell nucleus to be digested by enzymes as the activity of enzymes digesting DNA are reduced in lower temperature. After removing unnecessary substances in the mixture by filtration, DNA material would become harder and precipitated after the liquid is cooled down. Please answer the questions below: 1. Do you understand the effect of different chemicals in the experiment? For examples, why do we add detergent into the Kiwi fruit? _____________________________________ _____________________________________ 2. Why does alcohol ‘float’ on the water in step 6? What is the use of alcohol in the experiment? ______________________________________ ______________________________________ 3. How important is the technique to extract DNA from organisms? ______________________________________ ______________________________________ 18 Students’ version Additional background information: Basic vocabularies of life science Cells Cells are the most basic unit of lives. All of the organisms are composed of and constructed by cells. Some cells exist in single and some cells exist in groups. Human cells can be divided into two parts: cell nuclei and cytoplasm. Cells can absorb water and food for keeping alive, they can also synthesize human tissues and organs. DNA DNA is the abbreviation deoxyribonucleic acid, which is the basic unit of organism inheritance. DNA can be linked into a long molecule and compose chromosome. DNA exists in the cell nucleus to control all cellular activities. DNA comprises of a sugar (deoxyribose), a phosphate and nitrogenous bases forming a double-helix structure. Its base pair sequence arrangement is an essential factor to determine biological characteristics. There are four kinds of nitrogenous bases and the DNA sequence is the characterised arrangement method to pair these bases. Genome Genome is the entire DNA combination of an organism. Gene Gene is the specified DNA sequence, which contains codes to direct the protein production of body and catalyse the biochemical reactions in the body. Protein Protein is the main cell structure, which carry out almost all the functions in the human body to maintain life. Protein is a polymer from combination of amino acids. 19 Students’ version Additional background information: DNA、RNA and proteins The basic principle of molecular biology is producing RNA from DNA, producing proteins from RNA, then producing different cells from different proteins and finally forming human body by enormous cells. As a result, the most basic life message is encoded in 3 billion DNA codes at the nucleus of the cell. You can completely understand what human being is once you have decoded the “human barcode” with that enormous figure. DNA molecules are often in double helix structures of 4 nucleobase A, T, G and C. When molecular biologists doing researches, they usually list the DNA sequence of one of the double strands. It is because you can predict the other strand by the DNA sequence of its pairing strand. When it is G at one side, the other side must be C and A must pair with T. As a result, molecular biology experts would only mention one strand when discussing about DNA even though it is actually a double helix. DNA and protein 20 Students’ version Additional background information: Modern bioengineering Biotechnology, which is also known as Bioengineering, indicates using modern biological science as the basis and combining different types of advanced engineering techniques and the scientific principles to design and modify organisms or process raw biological materials. It can produce different products according to human needs or achieve certain purposes in biochemical processes. The evolvement and development of bioengineering are related to many different disciplines, included molecular biotechnology, microbiology, genetics, cytology and biochemistry, etc. meanwhile it is also a system of technologies incorporating series of techniques including genetic engineering, cellular engineering, enzymatic engineering, protein engineering, fermentation engineering and biochemical engineering. Genetic engineering Genetic engineering is mainly the gene recombination technique. The development of genetic engineering is based on molecular biology. In 1953, Watson and Crick discovered the double helix structure of DNA. The success of gene recombination experiment in the 1970s leads to the evolvement of rapid development of genetic engineering. The basic techniques of genetic engineering is to apply different functional enzymes to cut and paste genes and for expression. We should first understand the structure, organisation, adjustment, control and function of genes, so as to recognize the growth and development, separation of organisms, the inheritance alternation of species and evolutionary pattern accurately. The above practises supply new materials, techniques and methods for the genetic engineering techniques. Cellular engineering Cellular engineering is closely related to genetic engineering and the major concern of cellular engineering is culturing of cells. Cellular culturing in a great scale can be divided into three levels, single cellular culturing, tissue culturing and organ culturing. Culturing techniques of plant cells and the protoplast may use in breeding, in accelerating the reproduction rate of plants and raising non-toxic seedling, seeds for long-term storage and on production of secondary metabolites. The culturing techniques used in animal cells culturing can make many cell products with application values like vaccine and growth gene. Drug and medicine monitoring can also be carried out using cell-culturing system. Some cultured cells can even be applied for therapy. In addition to cell culturing, the applications of cellular engineering also included cell fusion, cell conversion, chromosome operation and gene transfer, etc. Enzymatic engineering Enzyme is protein catalyst, which is also regarded as ‘promoters’ of organisms’ living activities. That is why it is the core of genetic engineering. Without the function of enzymes, no biotechnology techniques can be realised. Enzymatic engineering is making use of the catalytic activity of enzymes to convert some raw materials into useful substances. In its industrial and medical applications, its catalytic function has played an extremely important role. The laundry cleaner that we used in our daily lives is a good example of industrial application of enzymes. Protein engineering Protein is one of the most special substances among those in constructing an organism. It has a complex structure and various functions and it plays an important role in organisms, such as the conversion of nutrients, control of growth and differentiation, and oxygen transport actions, etc. 21 Students’ version Scientists discovered that the structure of protein is closely related to its function. The main purpose of protein engineering is to investigate the relationship between protein structure and function by generating ‘point mutation’ accompanying with recombinant DNA and synthetic DNA techniques. It allows researchers to have a deeper understanding of the phenomenon and evolution of lives. Fermentation engineering Fermentation was originated from the Latin word(fervere), which indicates the yeast reaction in fruit juice and budding cereals to produce carbon dioxide. Pasteur has examined the physiological meaning of alcohol fermentation and claimed it is the result of anaerobic respiration of the yeast, the yeast without oxygen supply. The biochemical definition of fermentation is “the metabolic process that microorganisms carry out in the absence of oxygen”. Nowadays, people use ‘fermentation’ to characterise the application of the life activity of microorganisms under aerobic or anaerobic conditioner to produce microbial fungi and its metabolites. 22 Students’ version Additional background information: Important equipment and facilities for modern biotechnology All the biotechnology areas must apply a large amount of modern precise equipments such as ultra speed centrifugal machine, electronic microscope, high efficiency liquid chromatography, DNA synthesizer and DNA sequence analyser, etc. All of these equipment is controlled by microcomputers and fully-automatic. The modern biotechnology nowadays relies on the integration of the modern microelectronic and computer technology techniques and biotechnology techniques. Important apparatus and equipments for modern biotechnology Name 1. Automatic DNA sequence analyzer 2. Biological reactor 3. Real Time PCR 4. Gel electrophoresis system 5. Ultra speed/ High speed centrifugal machine 6. Electronic microscope Function Automatically analyse nucleic acid and nucleotide sequence Continuously culturing of cells Rapid DNA replication Separation and analysis of protein and Nucleic acid Separating large molecular substances of organisms Observe microstructure of cells and tissues Result of electrophoresis gel Source:CashmereBiotech-Taiwan Human DNA under electronic microscope 23 Students’ version Lesson 5, 6 : What are the problems of biotechnology? Background Modern biotechnology development is thriving, which undoubtedly contributes to medical, food and environment protection areas in the human society. However, the fast development of biotechnology is similar to other technologies that undergo a lot of constraints. The application of biotechnology often leads to controversial debates on ethical, moral and legal viewpoints. Source:Scientific American Through the continually developing and modifying biotechnology techniques, scientists have already mastered the animal cloning techniques. The first cloned animal in the world, Dolly the Sheep, was born in Scotland in 1996. Lots of scientists followed the research and ‘cloned rhesus’, ‘cloned cow’, ‘cloned mouse’ and’ cloned dog’ started to appear successively. It should be noticed that ‘cloned human’ will appear in the days to come, and it would lead to worrying problems in ethical aspects. The success of embryonic stem cell research signified the new hopes to cure serious illnesses, however, the embryo cloning techniques also brings a difficult question to us, which is related to the nature of life. We may ask ‘Is the cloned embryo a human being? Should the embryonic stem cell be treated as life? When do we start to count for a life begins?’ Human Genome Project was completed in 2003. The purpose was to figure out the gene map including the whole set of human inheritance code. It brings together the computer hardwares and softwares to decode and analyse DNA code and gene function of human. The technique can even be developed into a DNA database, which is comparable, that of fingerprints. However, establishing DNA database would lead to sensitive problems such as privacy and ‘gene discrimination’. What kind of attitudes should we have for building up DNA databases in hospitals or schools in the nation? Recently, there is another biotechnological issue that attracts lots of interest, it is about the novel medical techniques ‘Gene therapy’. Conceptually, ‘gene therapy’ can give hopes to cure lots of serious genetic diseases. However, scientists still cannot master all of the theories in gene technology at the moment and have limited ideas on the related side effects induced by gene therapy, further investigations are needed to be carried out. Since gene therapy may lead to unpredictable danger to patients, legal and social problems including risk of medical treatment and the liability would be found. 24 Students’ version Activity 4: Group debating Students are divided into groups of 4 people and choose one of the two issues below to discuss. Each group should also choose to support or oppose the notion. Please refer to the related articles and prepare your debating scripts after collecting further information. Two issues included: 1. Cloning lives; 2. Embryonic stem cells research Issue 1. Cloning lives Please read the article below as debating information <Reference article 1> All the Reasons to Clone Human Beings (Extract) http://www.humancloning.org/allthe.php Simon Smith Medical breakthroughs - Human cloning technology is expected to result in several miraculous medical breakthroughs. We may be able to cure cancer if cloning leads to a better understanding of cell differentiation. Theories exist about how cloning may lead to a cure for heart attacks, a revolution in cosmetic surgery, organs for organ transplantation, and predictions abound about how cloning technology will save thousands of lives. Medical tragedies - Many people have suffered accidental medical tragedies during their lifetimes. Read about a girl who needs a kidney, a burn victim, a girl born with cosmetic deformities, a man who needs a liver, a woman who is infertile because of cancer, and a father who lost his only son. All these people favour cloning and want the science to proceed. To cure infertility - Infertile people are discriminated against. Men are made to feel like they are not "real men." Women are made to feel as if they are useless barren vessels. Worse, being infertile is often not considered a "real medical problem" and insurance companies and governments are not sympathetic. The current options for infertile couples are painful, expensive, and heart-breaking. Cloning has the potential to change the world for infertile couples almost overnight. A Child's right to be better than its parents - It's been suggested that parents have a duty to see that their children have better lives than they do. This may mean making our children live longer, helping them to be resistant to cancer, heart disease, any familial diseases, and all the other problems that can be cured using what we learn from human cloning technology. To take a step towards immortality - Human cloning essentially means taking a human being's DNA and reversing its age back to zero. Dr. Richard Seed, one of cloning's leading proponents, hopes that cloning will help us understand how to reverse DNA back to age 20 or whatever age we want to be. Cloning would be a step towards a fountain of youth. To make a future couple financially secure - With human cloning you could give a couple in the future both a child from your DNA and the financial assets from your lifetime to start out financially secure instead of struggling as most couples do now. 25 Students’ version To be a better parent - Human cloning can improve the parent-child relationship. Raising a clone would be like having a child with an instruction manual. You would have a head start on the needs and talents of your child. We are not saying that a clone would be a carbon copy with no individuality. Our talents and desires are genetic, developmental, and environmental. We would have a head start on understanding the genetic component of a cloned child. Endangered species could be saved - Through the research leading up to human cloning we will perfect the technology to clone animals, and thus we could forever preserve endangered species, including human beings. Animals and plants could be cloned for medical purposes - Through the research leading up to human cloning, we should discover how to clone animals and plants to produce life-saving medications. Economics - Countries that fail to research human cloning will suffer economically. The industrial revolution and Internet revolutions enriched the United States of America. Biotechnology will lead the next economic revolution. Those countries that jump in first will reap the rewards. Those who fail to begin research right away will fall behind. As an example: Japan failed to jump on the Internet bandwagon and is now playing catch-up. Japan has banned human cloning and will probably suffer by falling behind during the biotech revolution. One day in the not too far distant future, Japan may realize its mistake. Because the sick will demand it - Those resisting human cloning research will probably find themselves shouted down by the sick and the maimed who desperately need such research. Human cloning technology promises to cure many or all incurable diseases and the moral weight of the dying and infirm will undoubtedly sway the politicians more than the arguments of the healthy, who often remain ignorant of the potential of human cloning, because they have never been motivated by suffering to look desperately for a cure. Living on through a later-born twin - Some childless people feel that by being cloned by their later-born twin would help them or their DNA to live on in the same sense that people who have children live on. <Reference article 2> HUMAN CLONING: PROBLEMS FACED TODAY (Extract) http://www.msu.edu/~daughe29/atl/finalpaper.html Since the first successful cloning of a mammal, a sheep named Dolly, was announced to the public in 1997 a worldwide debate has been occurring about whether cloning humans is ethical. Scientists have had the ability to clone organisms for decades now. The first cloning experiments are dated back to the 1970s when scientists used amphibians. It wasn’t until the public found out about Dolly that the debate on cloning started to heat up. With the ability to clone mammals, the possibility to clone humans now seems closer than ever. Congress, the scientific community, and the people around the world now are in a heated debate over the benefits and consequences of cloning, especially with all of the uncertainties that scientists still have today about cloning 26 Students’ version humans. The current lack of knowledge of mammalian cloning techniques presents too many risks to be used on humans. The first ethical debate about the cloning of humans is genetic diversity. Genetic diversity would be held to a screeching halt if humans were cloned instead of produced naturally. This could be disastrous for humans if a certain strain of disease was present in the DNA sequence of the clones. Then all of the clones would be susceptible to the same disease and it could in theory wipe out the clones that were created from the DNA sequence. Humans would not be able to adapt or evolve to certain situations. It would not be ethical to produce humans that would be plagued by a certain disease for life. Nor would it be beneficial to the human race. Another debate on cloning is focused on the therapeutic cloning procedures. This debate centers on the benefits of therapeutic cloning and the loss of having to destroy human embryos to obtain success. Therapeutic cloning is a procedure of cloning that provides many treatments for humans. Instead of cloning a whole human body, therapeutic cloning procedures only clone one specific part that needs “repair,” for example, making new organs for transplant. In order to produce new organs though, scientists use cells that are called stem cells. These stem cells are cells that have the ability to differentiate, or form, new types of cell tissue. Scientists are currently working on new ways to obtain these stem cells. As of now, scientists are getting these cells by taking them from human embryos. In order to this though, the embryos have to be destroyed. This has brought up a huge debate on whether the embryos are human and deserve basic human rights. If so, then this procedure would be murder. (Commentary on Human Cloning, Byrne, J.A.) Abortion rights in many countries have already stated that the choices of a grown adult override of those of the unborn embryo, while other pro-life advocates would argue otherwise. Some people as well as myself believe that a human embryo should have all the basic rights as a full grown human. Not granting the embryo a fair chance at life would be against the future human’s basic rights. Yet another ethical debate about cloning that has arisen is the abnormalities that take place during and after cloning procedures. Approximately one-third of the mammals that have been cloned have been born with or developed abnormalities. The most common abnormality that these clones are born oversized. If these procedures where to be applied to use in human cloning one-third of all humans that are cloned would suffer from these abnormalities. Many of the cloned animals also develop respiratory, circulatory, and many other developmental problems. The clones that do develop these abnormalities sometimes die because of the organ deficiencies that develop. Killian, a scientist who studies cloning, formed a hypothesis that predicts that the abnormalities in humans that would develop would be less than 30%. This number is significantly high. Since the scientists who study cloning already know that some abnormalities can and most definitely will take place should not risk human lives just to further their knowledge on cloning. The abnormalities that happen in natural human sexual reproduction is 3%. The deformities involved with the cloning procedure are much higher. The abnormalities that develop from natural sexual reproduction are not voluntarily planned. The most important argument against cloning humans is the present inefficiency of it. Many clones do not survive. Only a mere .1-5% of attempts at nuclear transfer from mammalian cells result in live births. Out of that little percentage of clones that are born, about 50% of newborns survive. All of the data means that 95-99.9% of all cloned mammals die. And of the ones that survive, there is no guarantee that no abnormalities will be present. There is a certain few failures when human sexual reproduction takes place also. These failures cannot be planned 27 Students’ version or predicted though. The failures of the cloning procedure have been proved. As of right now, scientists are not nearly close enough to successfully cloning mammals. Sure it has been done but not without a great deal of complications. Cloning humans now would be deliberately producing humans that may not be normal, and may not even survive. I believe that cloning humans should not be permitted because it is not ethical to produce humans just to study science a little closer. Too many human lives would be wasted in order to someday have the ability to clone humans successfully. Scientists should not be able to clone humans until further research is done to prove it is completely safe. Still too many uncertainties exist about human cloning, and it should not be permitted. Topic of debate: ‘Human cloning consists of some many problems violating human ethics, so it should be completely prohibited.’ Activity Guideline: Refer to the reference articles 1 and 2 and state the points supporting or opposing the notion about human cloning researches. Students should treat the authors’ personal ideas as references only. However, you should focus on the evidences stated by the authors in establishing their ideas. Hence, what are the information and evidences the authors have used to support their viewpoints? When students prepare the debating script, you should notice the reliability of the ideas and try to quote some reliable evidences such as the results of scientific researches to support yourselves. It can prevent you from just expressing personal subjective ideas in the debate. Issue 2. Embryonic stem cells research Please read the article below as debating information <Reference article 1> The Stem Cell Challenge What hurdles stand between the promise of human stem cell therapies and real treatments in the clinic? (Extract) http://www.sciam.com/print_version.cfm?articleID=000DFA43-04B1-10AA-84B183414B7F00 00 Robert Lanza and Nadia Rosenthal Stem cells raise the prospect of regenerating failing body parts and curing diseases that have so far defied drug-based treatment. Patients are buoyed by reports of the cells' near-miraculous properties, but many of the most publicized scientific studies have subsequently been refuted, and other data have been distorted in debates over the propriety of deriving some of these cells from human embryos. Provocative and conflicting claims have left the public (and most scientists) confused as to 28 Students’ version whether stem cell treatments are even medically feasible. If legal and funding restrictions in the U.S. and other countries were lifted immediately, could doctors start treating patients with stem cells the next day? Probably not. Many technical obstacles must be overcome and unanswered questions resolved before stem cells can safely fulfill their promise. For instance, just identifying a true stem cell can be tricky. For scientists to be able to share results and gauge the success of techniques for controlling stem cell behavior, we must first know that the cells we are studying actually possess the ability to serve as the source, or "stem," of a variety of cell types while themselves remaining in a generic state of potential. But for all the intensive scrutiny of stem cells, they cannot be distinguished by appearance. They are defined by their behavior. Most versatile are embryonic stem (ES) cells, first isolated in mice more than 20 years ago. ES cells come from the portion of a very early-stage embryo that would normally go on to form three distinctive germ layers within a later embryo and ultimately all the different tissues of the body. ES cells retain this potential ability to produce any cell type in the body, making them pluripotent. Most of the existing human ES cell lines in the world were derived from unused embryos created for couples seeking in vitro fertilization (IVF). Researchers working with these cells have found that they usually recover after freezing and thawing and can differentiate into assorted cell types in a culture dish. But it is becoming clear that not all human ES cell lines are the same. Seeking Stemness Some lines will differentiate into only certain cell types; others grow sluggishly in culture. To ensure that these cells are pluripotent before using them in research, two possible tests, already common in nonhuman ES cell studies, have been proposed by a group of American and Canadian biologists hoping to set standards for experimentation with human ES cells. One would involve injecting the ES cells into an animal's body tissue. If they form a teratoma--a distinctive tumor containing cell types from all three embryonic layers--their pluripotency is proved. Another way to test putative ES cells is to mark them, then inject them into a developing animal embryo. When the animal is born, if the marked cells turn up in all its tissues, the cell line is deemed pluripotent. But testing human embryonic stem cells in this manner would create a chimeric animal with human DNA throughout its body, a prospect many find ethically troubling. What is more, passing the latter test does not always guarantee that the cells will differentiate in the lab. The need to find more reliable markers that distinguish truly pluripotent ES cells is driving widespread attempts to catalogue the genes that are turned on or off at various times in cultured ES cells. Having such a gene expression profile would not only provide a way of identifying pluripotent ES cells, it would also offer tremendous insight into the properties that confer their "stemness." Unfortunately, to date, gene expression profiles of ES cells have yielded conflicting results, and the search for a clear ES cell signature continues. Of course, the goal of stem cell research is to replace or regenerate failing body parts, such as pancreatic insulin-producing cells in diabetics or dopamine-producing neurons in people with Parkinson's disease. But techniques for coaxing ES cells to differentiate into desired cell types are far from perfected. Putting cells to work It would be ideal if we could simply inject ES cells into the part of the body we wish to 29 Students’ version regenerate and let them take their cues from the surrounding environment. ES cells' pluripotency, however, makes this far too dangerous an approach for human therapy. The cells might form a teratoma or could differentiate into an undesirable tissue type, or both. In animal experiments, teratomas containing fully formed teeth have been reported. Rather than risk creating a tumor or a tooth in a patient's brain or heart with direct ES cell injections or struggling to produce specific functional tissues, many ES cell researchers are now striving for a middle ground. By coaxing ES cells into a more stable, yet still flexible, progenitor-cell stage before administering them, we can avoid uncontrolled differentiation while still taking advantage of environmental cues to generate the desired cell types. Even though these progenitor cells can take to their environment and initiate the generation of new tissue, they would still be subject to attack by the patient's own body. ES cells and their derivatives carry the same likelihood of immune rejection as a transplanted organ because, like all cells, they carry the surface proteins, or antigens, by which the immune system recognizes invaders. Hundreds of combinations of different types of antigens are possible, meaning that hundreds of thousands of ES cell lines might be needed to establish a bank of cells with immune matches for most potential patients. Creating that many lines could require millions of discarded embryos from IVF clinics. Topic of debate: ‘Embryonic stem cell therapy has completely neglected human ethics’ Activity Guideline: The reference article has raised the discussion on the imperfections of embryonic stem cell therapy, included technical incompleteness and some technical problems such as abnormal embryo. Lots of animals are used as subjects during biotechnology exploration. The vigorous controversy in embryonic stem cell therapy is owing to its relatedness to human embryo. What are your opinions on the issue about whether embryo should be regarded as a life? When students prepare the debate script, you should notice the reliability of the ideas and try to quote some reliable evidences such as the results of scientific researches to support yourselves. It can prevent you from just expressing personal subjective ideas in the debate. 30 Students’ version Activity 4: Group Debating Worksheet Please answer the question individually (not more than 100 words) after the debate: Imagine you are a patient waiting for kidney transplant and you are waiting for suitable organ donation for transplantation. Now a new research has been launched to use embryonic stem cells to cultivate kidney cells, are you willing to take part in it? If this research would use up more than millions of human embryos, what is your opinion? 31 Students’ version Extended Activity: Students can have further investigations and discussions on the topics below: Additional issue for debating: Gene therapy Topic of debate: Patients receiving ‘gene therapy’ has to take the risk that is still unknown and uncontrolled medically. From patient’s point of view and their vital interest, receiving ‘gene therapy’ does more harm than good. Reference articles: 1. <Cancer risk clouds gene cures> Author: Bob Holmes 2003.03.15 http://www.eurekalert.org/pub_releases/2003-03/ns-crc031203.php 2.〈論基因治療之科技風險與醫療傷害之救濟〉 撰文/牛惠之 助理教授 2003.01.15 國立清華大學科技法律研究所 http://www.bio.idv.tw/data/data2/2003011501.htm Issue for information collection:Ethical problems about DNA database Reference articles: 1. Original title: <The FBI’s national DNA database> Source: Nature Biotechnology 16 (1998), 987 Author: Russ Hoyle 2. <Genetic Discrimination in Health Insurance> http://www.genome.gov/page.cfm?pageID=10002328 3.〈冰島的浮士德契約?全國基因資料庫的建立與省思〉 撰文/何建志【生物科技與法律研究通訊】 – 第一期 – 1999 年 1 月 11 日 4. 〈美國參議院通過禁止基因歧視的法案〉 李裕勳整理,資料來源: http://www.nlm.nih.gov/medlineplus/news/fullstory23075.html http://www.medicalnewstoday.commedicalnews.php?newsid=20207 32 Students’ version Extended readings: Students can refer to the newspaper articles below to further discuss the ethical issues of science: Science turns monkeys into drones -- Humans are next, genetic experts say http://www.infowars.com/print/bravenewworld/monkey_drones.htm London Times October 17, 2004 The Times, London LONDON - Scientists have discovered a way of manipulating a gene that turns animals into drones that do not become bored with repetitive tasks. The experiments, conducted on monkeys, are the first to demonstrate that animal behaviour can be permanently changed, turning the subjects from aggressive to "compliant" creatures. The genes are identical in humans and although the discovery could help to treat depression and other types of mental illness, it will raise images of the Epsilon caste from Aldous Huxley's futuristic novel Brave New World. The experiments -- detailed in the journal Nature Neuroscience this month -- involved blocking the effect of a gene called D2 in a particular part of the brain. This cut off the link between the rhesus monkeys' motivation and reward. Instead of speeding up with the approach of a deadline or the prospect of a "treat," the monkeys in the experiment could be made to work just as enthusiastically for long periods. The scientists say the identical technique would apply to humans. "Most people are motivated to work hard and well only by the expectation of reward, whether it's a paycheque or a word of praise," said Barry Richmond, a government neurobiologist at the U.S. National Institute of Mental Health, who led the project. "We found we could remove that link and create a situation where repetitive, hard work would continue without any reward." The experiments involved getting rhesus monkeys to operate levers in response to colour changes on screens in front of them. Normally they work hardest and fastest with the fewest mistakes if they think a reward for the "work" is imminent. However, Mr. Richmond's team found that they could make the monkeys work their hardest and fastest all the time, without any complaint or sign of slacking, just by manipulating D2 so that they forgot about the expectation of reward. The original purpose of the research was to find ways of treating mental illness, but the technicalities of permanently altering human behaviour by gene manipulation are currently too complex, he said. However, he and other scientists acknowledge that methods of manipulating human physical and psychological traits are just around the corner, and the technology will emerge first as a lucrative 33 Students’ version add-on available from in vitro fertilization clinics. "There's no doubt we will be able to influence behaviour," said Julian Savulescu, a professor of ethics at Oxford University. "Genetically manipulating people to become slaves is not in their interests, but there are other changes that might be. We have to make choices about what makes a good life for an individual." In a presentation at a Royal Society meeting titled Designing Babies: What the Future Holds, Yuri Verlinsky, a scientist from the University of Chicago who is at the forefront of embryo manipulation, said: "As infertility customers are investing so much time, money and effort into having a baby, shouldn't they have a healthy one and what is to stop them picking a baby for its physical and psychological traits?" Gregory Stock, author of Redesigning Humans and an ethics specialist from the University of California, agrees. "I don't think these kind of interventions are exactly round the corner, they are a few years away, but I don't think they are going to be stopped by legislation," he said. Sperm And Eggs Grown From Stem Cells http://www.rense.com/general66/spermandeggs.htm Maxine Frith Social Affairs Correspondent The Independent - UK 20/6/2005 The shortage of donated eggs and sperm for fertility treatment could be solved after British scientists found they can both be grown from laboratory stem cells. But some specialists warned the discovery raised serious ethical questions, saying it could mean that a single man could provide both the sperm and egg for fertility treatment, making him genetically father and mother of his child. They also claimed the technique came close to human cloning, although scientists who conducted the study denied that. Researchers from the Centre for Stem Cell Biology at the University of Sheffield studied six human embryonic stem cell (HESCs) lines taken from very early embryos that had been donated by couples undergoing IVF treatment. HESCs are the building blocks of human development and turn into any type of cell, such as organs or tissue. But scientists have not been clear about when HESCs begin to differentiate into primordial germ cells (PGCs), which are the ancestral cells that eventually form sperm and eggs. The Sheffield researchers allowed the human stem cells to develop into collections of cells called embryoid bodies, and then tested them to see which genes were active in them. 34 Students’ version Within two weeks of development, a very small proportion of cells in the embryoid bodies had begun to "express" some of the genes found in PGCs. Some also began to express proteins that are only found in maturing sperm, suggesting that human stem cells can develop into PGCs, and eventually eggs and sperm. Dr Behrouz Aflatoonian, who led the research, said: "Ultimately, it might be possible to produce sperm and eggs for use in assisted conception treatments. This is a long way off, and we would have to prove that it was safe because, for example, the culture process may cause genetic changes. "For some men and women, this would be the only route for producing sperm and eggs. It would not be reproductive cloning as fertilisation would involve only one set of gametes produced in this way, and a unique embryo would form." One in seven couples in Britain experiences fertility problems, and about 7,000 a year are treated using donated eggs or sperm. Some couples are able to use their own eggs or sperm, but others with particular problems are reliant on donated samples. Only 250 men and 1,100 women donate their sperm or eggs each year, meaning there is a drastic shortage. There are also concerns that fewer people may be prepared to become donors after the rules governing anonymity changed, making it possible for children born as a result of fertility treatment to obtain details about their biological parents. ©2005 Independent News & Media (UK) Ltd. 35 Students’ version Human Skin Cells Turned Into Stem Cells http://www.isscr.org/public/conversion.htm Jason West, Shannon McKinney-Freeman, Ph.D., Susan Garfinkel, Ph.D., and Suzanne Kadereit, Ph.D. In the August 2005, issue of the journal Science, Kevin Eggan and colleagues at Harvard University fused human skin cells and human embryonic stem cells. The resulting hybrid cells retained properties of the embryonic stem cells, suggesting that specialized adult cells can convert into a less specialized state. Prior to this study, the ability to coax a more specialized adult cell (or the DNA of an adult cell) into a less specialized state had been demonstrated via the process of somatic cell nuclear transfer. In that process, an adult cell is fused with an egg, whose own genetic material is removed, so the egg contains the genetic material from the adult cell. The egg is then coaxed to develop like a fertilized egg, and at the blastocyst stage of development (about 4-5 days and 100-200 cells), embryonic stem cells can be isolated that are a genetic match to the adult cell donor. This procedure has generated much controversy due to its use of unfertilized human eggs (which must be donated) and the creation, and subsequent destruction, of human embryos to enable the isolation of embryonic stem cells. The current study directly fused adult skin cells with existing human embryonic stem cells, so no human eggs were involved. Although the fused cells still contained the genetic material, or DNA, from both of the two cells used (adult skin cells and embryonic stem cells), they behaved very much like embryonic stem cells. The fused cells could generate many different cell types of the body, including brain cells, hair cells, skeletal muscle and intestine and also expressed many genes that are characteristic of embryonic stem cells. It remains to be determined if the fused cells, which contain twice the amount of DNA as a normal cell, will form functional cells that will be useful for treatments. Even embryonic stem cells derived in the classical way (from human eggs at the blastocyst stage) have yet to be used successfully to treat human disease. Thus, many challenges still remain in simply characterizing these exciting new cells and understanding the extent to which they mirror embryonic stem cells. Clinical uses are undoubtedly years down the line, if at all. However, despite these limitations, this research offers an exciting hope that someday any adult cell could be converted into an embryonic stem cell. Normally, a cell is guided through development from a less specialized state to more specialized state by a specific program. Although cells share common DNA, specific factors within cells influence the DNA, allowing one cell type to be distinguished from another. For example, a nerve cell and a heart cell within a person have the same DNA, but other factors program the nerve cell to be a nerve cell and the heart cell to be a heart cell. Thus, changing these factors will change, or reprogram, one cell into behaving like a different cell. This research showed that factors present within the embryonic stem cells, instead of human eggs, caused adult cells to reprogram. Future studies aimed at identifying what factors are responsible will likely grow out of this research. In addition, the reprogramming of adult cells by embryonic stem cells, in lieu of human eggs, has overcome the hurdle of getting enough raw materials to study the factors causing reprogramming, since human eggs are a scarce commodity and embryonic stem cells are available in vast numbers. Nonetheless, the current procedure still required the use of embryonic stem cells that were created from human embryos, and therefore 36 Students’ version still raises controversy among some groups opposed to research using embryonic stem cells. In the future, knowledge of factors necessary for reprogramming could potentially allow for the creation of “embryonic” stem cells arising directly from an adult cell without the use of any preexisting embryonic stem cells or human eggs. It must be noted, however, that years of research on other model systems such as the frog and mice have failed to identify such factors that allow for successful reprogramming of an adult cell without the use of eggs or embryonic cells. Thus, this procedure currently only allows for the generation of fused cells with twice the genetic content of normal human cells and does not offer an alternative to using human embryonic stem cells. Even so, it offers an exciting new tool to study reprogramming for stem cell researchers. 37