Site hosted by Angelfire.com: Build your free website today!
Angelfire Free Home Pages Free E-mail Browse WhoWhere? People Finder
  1. Discuss all the steps used in genetic engineering to produce a bacteria cell which can make insulin.

Several biologically useful peptides were made and tested in clinical trials during the late 1970s and early 1980s. The first genetically engineered product to be approved for human use was human insulin made in bacteria. Insertion of the human insulin gene into bacteria was accomplished by the pioneer genetic engineering company Genentech. Testing, approval for medical use, and large-scale production of genetically engineered human insulin were carried out, and the first diabetic patient in the world was injected with human insulin made in bacteria in December 1980, making this the first genetically engineered product to enter medical practice. (Genetically engineered products are often identified by the prefix r, for "recombinant." Thus, genetically engineered insulin is sometimes written, r-insulin.)

In genetic engineering, plasmids are isolated, opened up for insertion of pieces of DNA from other sources, and then resealed; this hybrid DNA is called recombinant DNA. The new plasmid is placed into a receptor cell, "infecting" it as if it were a virus. The inserted genes then express themselves along with the normal genetic complement of the cell. A bacterium may be programmed in this way to produce a useful substance; human insulin, for example, is produced when human genes controlling insulin production are placed into a plasmid and then inserted into a bacterium.

Many genetic disorders and other human illnesses occur when the body fails to make critical proteins that are essential for proper functioning. For example, diabetes mellitus type I, also called insulin-dependent diabetes, is an illness that occurs when the body cannot make sufficient amounts of the protein insulin. Diabetes mellitus type I can be treated by regular injections of insulin or by an insulin pump. However, insulin is typically present in the body in very low amounts, making the large quantities needed for pharmaceuticals difficult and expensive to obtain. With the availability of genetic engineering techniques, this problem has been largely overcome. The genes encoding the protein insulin can now be inserted into bacteria, which then produce insulin. Because the host bacteria can be grown cheaply in bulk, large amounts of insulin can be easily obtained. Large amounts of insulin can be obtained through genetic engineering. The gene for insulin is cut out of its chromosome and inserted into a bacterial plasmid. The bacteria containing the plasmids produce insulin, which can be collected to treat disorders such as diabetes, as shown below

  1. Project the benefits both short and long term of completing the human genome project.
  2. There are a lot of benefits to the 15 year and $3,000,000,000 human genome project. One is that you give biologists something to do and create a field which many scientists can research or for research. Short term benefits could include anywhere from increasing the knowledge of genetics and biology to curing some diseases. Curing genetic disorders would be long term benefits of the Human Genome project since people wouldn’t be able to cure those diseases right away but in the long run. The Human Genome Project also would cure a lot of rare diseases. In other words, it would drastically improve people’s health.

    Treating gene-related diseases and conditions is a major hope of the Human Genome Project.

    The Human Genome Project is an ambitious plan to map and sequence all 100,000 or so genes found in human DNA. It is a task that has occupied hundreds of scientists in labs around the world since about 1986.

    The first human genes to be identified, back in the 1970s, were those connected with diseases such as cystic fibrosis. Part of the motivation to sequence the entire genome (that is, all the genes present in a complete set of chromosomes) was the desire to learn more about the genetic roots of disease and to discover more genes that might be used in gene therapy. In 1971, only 15 human genes had been localized to specific chromosomes, most on the easily identified sex chromosome. By the mid-1990s, researchers had mapped the location of about 2,000 genes - an impressive number, but still only 2% of the entire human genome.

    The ability to map genes was boosted by the development of recombinant DNA technology - in particular the use of restriction enzymes to cut DNA molecules into small fragments with known endpoints. The restriction enzyme cutting sites act as easily identified markers that let scientists compare different fragments for the presence or absence of particular genes. Bit by bit, they build up collections of fragments that overlap each other in known order until they have eventually spanned the entire length of a chromosome. Adjacent fragments form ordered chromosome libraries that help researchers locate particular genes.

    Mapping the location of genes on a chromosome is only the first step. The ultimate aim is to know the sequence of bases in each gene. This is an even lengthier task, since there are about 3 billion base pairs in a set of 23 human chromosomes.

    Many scientists found the launch of this huge research program stimulating - like the American drive to put a man on the moon during the 1960s. Reviewing the genome project in 1989, James Trefil, professor of physics at George Mason University, wrote: "It represents nothing less than the ultimate scientific response to the Socratic dictum 'Know Thyself.'" Other scientists were less enthusiastic, seeing much of the exercise as a colossal waste of time, money, and human resources.

    Critics of the genome project argued that the complete sequencing of each gene is simply unnecessary and tedious - "like mapping every tree in Borneo." For medical purposes, the simpler identification of genes responsible for disease is all that is needed.

    Furthermore, most of the genome is not, in fact, made up of genes that encode protein production. Long stretches of DNA have other functions, such as turning genes on and off, or helping cells duplicate genes during division. Other regions may simply be evolutionary baggage with no useful function, like the human appendix. Professional scientists showed their human side over the debate in passionate letters to learned journals and shouting matches at conferences.

    Another concern, shared by people at large, was that full knowledge of the human genome was a scary sort of power, evoking the story of Frankenstein. Are such worries inflated? Putting things in a different perspective, one writer stated in an issue of American Scientist in 1988: "[Genetic maps] will be like having a whole history of the world written in a language you can't read."

    The Continuing Story Of Gene Therapy

    The first actual use of gene therapy began in September 1990, with the treatment of a child suffering from a rare genetic immunodeficiency disease caused by the lack of the enzyme adenosine deaminase (ADA). ADA-deficient people have persistent infections and high risk of early cancer, and many die in their first months of life. The much publicized "bubble boy," David, had this disease. David lived for nine years in a plastic chamber to prevent contact with viruses, which his immune system could not combat.

    As with many other genetic disorders, the root of ADA deficiency lies in the body's inability to produce a key chemical because of a defective gene coding. The disease occurs only in children who inherit defective copies of the ADA gene from both parents. A child who inherits a defective copy from one parent and a normal copy from the other will not have the disease, but may pass on the defective copy of the gene to the next generation.

    Researchers had identified the normal ADA gene in human white blood cells during the early 1980s. They wanted to see what happened when they introduced copies of this normal gene into a lab culture of T-cells taken from ADA-deficient patients. T-cells were used because they are easy to obtain and grow in the lab, and they are easy to alter genetically.

    After ADA genes were transferred into the T-cells by genetically engineered viral vectors, the cells began to produce the ADA enzyme as predicted. The amount of enzyme produced was about 25% of normal, but more than enough to correct the conditions caused by ADA-deficiency. As well, the genetically altered cells had the same life-span as normal T-cells - longer than the life-span of uncorrected T-cells from ADA patients. The beauty of this technique is that the desired gene not only remains in the cell as long as it survives, but it is duplicated and passed on to all the cell's descendants whenever the cells divide.

    With the success of the lab experiment, researchers were ready to try out the technique on patients suffering from ADA-deficiency. The first to be treated was a 4-year-old girl, then, a year later, a 9-year-old. Early results were encouraging for both children. On a regimen of infusion with ADA gene-corrected cells every one or two months, both patients showed normal levels of active T-cells in their blood after a year, and both developed improved immune function.

    Because the altered T-cells won't last forever, it wasn't a permanent cure - that would require using bone marrow stem cells. It was a temporary therapy that depends on regular infusion of engineered T-cells. But, like the use of insulin by diabetics, it allowed these patients to lead relatively normal lives. Within a year of her initial treatment, the first little girl was able to attend school, swim, dance, and ice-skate with her family and friends, with no more risk of catching infections than they had.

    Blood cells can be genetically altered and reintroduced to the body by a simple injection into a blood vessel. But what if you want to alter genes in the cells of an organ, such as the liver? One approach is to remove a piece of the liver, divide it into individual cells, insert the appropriate genes into each cell, and transplant the engineered cells back into the patient.

    A second approach, according to gene-transfer pioneer William French Anderson and others, is to develop smart vectors - ones that can find their own way to diseased tissue inside the body. Rather than inserting genes into cells in petri dishes, we would inject the new generation of vectors directly into patients to carry genes to their targets like guided missiles. This could be achieved by attaching molecules to the vector that recognize specific proteins found on the surface of cells in the target organ.

    Gene Therapy to Obstruct Disease

    The type of gene therapy I've described adds normal genes to a patient to produce something the patient lacks due to genetic defects. Another type of gene therapy works in a different way, by obstructing genes that cause disease.

    In this strategy, called antisense therapy, scientists add a gene that mirrors the target gene - say, one that causes arthritis. The engineered gene produces RNA that complements the RNA of the troublesome gene, binding onto it and blocking its action. So, for example, if the disease-causing gene produces an unwanted protein, antisense therapy will prevent the protein from being formed. If the gene suppresses the formation of a wanted protein, the therapy will allow for normal protein production.

    The first stage of gene therapy - identifying genes associated with disease - is fairly well established, thanks to the Human Genome Project. News reports frequently announce the discovery of genes responsible for this or that condition, from Alzheimer's disease to baldness. Research efforts now concentrate on the second and third stages of the process: delivering genes safely to their targets in the body and controlling gene expression in the altered cells. These steps are crucial to gene therapy's success and are likely to take the next 10 to 20 years to develop.

    Much of modern medical treatment depends on the use of chemicals, and a large part of the medical biotech industry involves producing large quantities of pure drugs tailored for specific tasks. Some are extracted from natural sources, some are manufactured synthetic compounds, but more and more are produced by engineering cells with recombinant DNA.

    The Interferon Story

    The first big success story in the commercial production of drugs by genetic engineering was interferon, a naturally occurring compound connected with the immune system. Discovered in 1957, interferon is produced by cells in the human body in response to viral attack. It promotes production of a protein that stimulates the immune system, interfering with the spread of infection.

    Although the usefulness of interferon was recognized at once, it could not be marketed for widespread medical use. The chemical is produced by the body in such tiny amounts that it would take the blood from 90,000 donors to provide only one gram of interferon, and even then the product would be only about 1% pure. In 1978, a single dose of impure interferon cost about $50,000 to obtain.

    All that changed dramatically with the birth of genetic engineering. In 1980, Swiss researchers introduced a gene for human interferon into bacteria, the first time such a procedure had been done with human genes. Cloning millions of bacterial cells from the original engineered one, they were then able to produce a cheap and abundant supply of the previously rare protein. By the mid-1980s, supplies had shot up, and pure interferon was being produced for about $1 per dose.

    It was an example of the kind of achievement that makes supporters of medical biotechnology so enthusiastic. Interferon is now used not only to combat viral infection in transplant patients, but also to fight other viral diseases (including the common cold), and as an anticancer drug.

    Genes and Vaccines

    A big advantage of using genetic engineering to produce drugs is that it's possible to mass-produce chemicals that might otherwise be difficult and costly to extract, or simply unavailable by conventional means. Another important advantage is that drugs produced in this way are pure and, if made using human genes, fully compatible with use in people.

    For example, before engineered bacteria were cloned to manufacture human insulin, the main source of this hormone (used to treat diabetes) was the pancreas of cattle or pigs. Although similar to human insulin, animal insulin is not identical and causes allergic reactions in some patients. The human protein produced by bacteria with recombinant DNA, however, has no such effect.

    To take another example, vaccines against disease are traditionally prepared from killed or "disarmed" pathogens (disease-causing microbes). They are effective in the vast majority of people, but a small percentage of the population have allergic reactions to vaccines. There is also a very small risk of vaccine organisms reactivating to their former pathogenic state. Genetically engineered vaccines are safer because they contain no living organisms - only the proteins that stimulate the body to develop immunity.

    Vaccines are the second-largest category of over 200 drugs now being produced by American pharmaceutical companies using biotechnology. Other products include hormones, interferon’s, blood-clotting factors, antisense molecules, and enzymes. Most of these drugs are still undergoing clinical testing and are designed to combat cancer, AIDS, asthma, diabetes, heart disease, Lyme disease, multiple sclerosis, rheumatoid arthritis, and viral infections.

    But the bottom line is that mapping and even sequencing genes is only a beginning. That knowledge alone won't tell us the gene's functions. Of the 2,000 or so genes whose locations are mapped today, we know the functions of only a few hundred. And knowing the functions won't tell us how those functions are actually carried out - how genes are expressed and what the biochemical steps are between the coding for a protein and the symptoms of a disease.

    Although advancing knowledge is rapidly closing in on these areas, we needn't worry just yet about having all the secrets of life.

  3. Discuss the current uses of genetic engineering. (at least six)
  4. Curing Genetic Disorders

    In 1990 the first attempts were made to use genetic engineering to combat genetic disorders. Many genetic disorders arise when an individual lacks a normally functioning copy of a particular gene. One obvious way to cure such disorders is to give the person a working copy of the gene. Until recently this approach was not practical for three reasons. First, the defective gene was difficult to identify and isolate. Second, it was hard to transfer a healthy copy of such a gene into the cells of body tissues that use it. Finally, it was necessary to find a way to keep the altered cells or their offspring alive in the body for a long time. With genetic engineering, it is now possible to overcome these difficulties.

    One of the first gene therapy attempts involved two young girls, who suffered from an immune system disorder caused by a defective gene. Doctors extracted bone marrow cells from the girls and replaced the defective gene, which failed to produce an important immune-system enzyme, with a normal gene. These cells were returned to the girls’ bones and began to produce the missing enzyme. Because this kind of bone marrow actively divides, researchers hope that offspring of the genetically engineered cells will continue to secrete the enzyme into their blood for a long time.

    Genetic engineering is also providing a new and powerful weapon in the battle against cancer. All humans have white blood cells that secrete a protein called tumor necrosis factor (TNF). TNF attacks and kills cancer cells. Unfortunately this does not happen often. Genetic engineers recently developed a method of adding the TNF gene to a kind of white blood cell that is very effective at locating cancer cells but not very effective at harming them. Once armed with this TNF gene, however, these white blood cells will secrete TNF and kill cancer cells. Genetic engineering has enabled these cells to become like cruise missiles with a deadly payload zeroing in on cancer cells.

    Transporting Genes Into Plants

    The key to the great progress in genetic engineering of plants I recent years was the discovery of a suitable vector to transport a gene from one plant to another. For years, genetic engineering in plants was not possible because, unlike bacteria, plants have few viruses or plasmids that can perform this critical role. Said simply, genetic engineering lacked a suitable vector to carry the gene into plant cells.

    The breakthrough came in the form of an unusual bacterial plasmid responsible for crown gall, a disease characterized by large bulbous tumors. This plasmid is called the Ti plasmid ("Ti" stands for tumor-inducing). The Ti plasmid easily infects broadleaf crop plants such as tomatoes, tobacco, and soybeans. When it has infected a plant cell, it proceeds to insert itself into the plant cell’s chromosome. To make a genetic engineering vehicle, scientists removed the tumor causing genes from the Ti plasmid. The vacant space in the now-harmless plasmid was then filled with DNA introduced by the scientists. This DNA could then be carried into the chromosome of a target plant.

    Making Genetically Engineered Vaccines

    A vaccine is a solution containing a harmless version of a pathogen (disease causing microorganism) or its toxins. When a vaccine is injected, the recipient’s immune system will recognize the pathogen’s surface proteins. The immune system will then respond by making defensive proteins called antibodies, which will later combat the pathogen. Antibodies will stop the growth of the pathogen before the disease it causes can develop.

    Traditionally, vaccines have been prepared either by killing a specific pathogenic microbe or by making it unable to grow. This ensures that the vaccine will not cause the disease. The problem with this approach is that any failure in the process to kill or weaken a pathogen will result in the transmission of the disease to the very patients seeking protection. While the majority of vaccines are safe, a fraction of a percentage of vaccines cause the treated individuals to contract the disease. This small, but real, danger is one of the reasons why rabies vaccines are administered only when a person has actually been bitten by an animal suspected of carrying rabies.

    Today there is a new and much safer method of making vaccines. Using genetic engineering techniques, the genes that encode the pathogen’s surface proteins can be inserted into the DNA of harmless bacteria (or viruses). The modified, but still quite harmless, bacteria become and effective and safe vaccine. These harmless bacteria can be used to stimulate the body to make the antibodies that will attach the pathogen. As a result, the body is protected against infection.

    Among the vaccines now being manufactured in this way are ones directed against the herpes II virus (which produces small blisters on the genitals) and hepatitis B virus (which causes a sometimes fatal inflammation of the liver). A major effort is underway to produce a vaccine that will protect people against malaria, a disease caused by a protozoan for which there is currently no effective protection.

    Making Genetically Engineered Drugs

    Many genetic disorders and other human illnesses occur when the body fails to make critical proteins that are essential for proper functioning. For example, diabetes mellitus type I, also called insulin-dependent diabetes, is an illness that occurs when the body cannot make sufficient amounts of the protein insulin. Diabetes mellitus type I can be treated by regular injections of insulin or by an insulin pump. However, insulin is typically present in the body in very low amounts, making the large quantities needed for pharmaceuticals difficult and expensive to obtain. With the availability of genetic engineering techniques, this problem has been largely overcome. The genes encoding the protein insulin can now be inserted into bacteria, which then produce insulin. Because the host bacteria can be grown cheaply in bulk, large amounts of insulin can be easily obtained. Large amounts of insulin can be obtained through genetic engineering. The gene for insulin is cut out of its chromosome and inserted into a bacterial plasmid. The bacteria containing the plasmids produce insulin, which can be collected to treat disorders such as diabetes,.

    In 1982, the U.S. Food and Drug Administration approved the use of the first commercial product of genetic engineering – human insulin. Today, hundreds of pharmaceutical companies around the world are busy producing other medically important proteins using genetic engineering techniques. These products include anticoagulants (proteins involved in dissolving blood clots), which are effective in treating heart attack patients, and factor VIII, a protein that promotes blood clotting. A deficiency in factor VIII leads to hemophilia, an inherited disorder characterized by prolonged bleeding. For a long time, hemophiliacs received blood factors that had been isolated from donated blood. Unfortunately, some of the donated blood was infected with viruses such as HIV and hepatitis B, which were then unknowingly transmitted to those people who received blood transfusions. Today, the use of genetically engineered factor VIII eliminated the risks associated with blood products obtained from other individuals. Other genetically engineered pharmaceutical products are Colony-stimulating factor, Erythropoetin, Growth Factors, Human growth hormone, Interferon’s, Interleukins, etc.

    Improving Livestock Production

    A very interesting advance in agriculture has been the introduction of growth hormone into the diet of dairy cows, which greatly improves milk production. Instead of extracting this hormone at great expense from the brains of dead cows, the relevant gene has been introduced into bacteria. The bacteria then produce the hormone so cheaply that it is practical to add it as a supplement to the cows’ diet.

    Extra copies of the gene encoding the same growth hormone have been introduced directly into the chromosome of both cattle and hogs to increase their weight. Through still underway, these attempts promise to create new breeds of very large and fast-growing cattle and hogs. The human version of this same growth hormone is now being tested as a potential treatment for dwarfism, a disorder in which the pituitary gland fails to make adequate amounts of growth hormone.

    Developing Crops That Need No Fertilizer

    Nitrogen is an element that all plants must have in order to make proteins and DNA. The most abundant source of nitrogen in the environment is atmospheric nitrogen, N2. However, plants cannot obtain nitrogen from the air. All of the nitrogen that plants needed must be obtained from the soil. How does this nitrogen get in soil? Bacteria living within the roots of soybeans, peanuts, and clover "fix" nitrogen by converting N2 gas from the atmosphere into nitrates, nitrites, and ammonia, which are forms of nitrogen that plants can use.

    Because crops rapidly consume nitrogen, farmers replenish the soil by adding high-nitrogen fertilizers. Farming would be much cheaper and far more productive if major crops such as wheat, rice, and corn could be grown without such massive application of fertilizer—or without any fertilizer at all. The task of genetically engineering major crops to carry out nitrogen fixation has become the focus of many researchers. The problem has not been an inability to discover and isolate the necessary genes or to get them into crop plants. The problem is that when bacteria are introduced into plants, the do not seem to function properly in their new host. Researchers all over the world are working to find a way around this difficulty.

  5. What is the difference between selective breeding and genetic engineering. Be specific, and use examples.

There is a significant difference between selective breeding and genetic engineering. In selective breeding, you carefully pick out the most perfect examples and bread those to get better crops, agriculture, livestock, etc. In genetic engineering you can get those crops right away or get whatever you need to be perfect. To explain this with an example, if you wanted an intelligent football player, you would get a very intelligent woman and a good football player with the right body and you would bread those two. Then out of their children, you would pick the better ones and again breed those with an intelligent person or a football player. You would continue doing this for about 6 generations until you would have that football player. With genetic engineering you could just insert the right genes into the DNA for intelligence and for a football player like posture and have this type of person within 1 generation without all the hassle of selective breeding. Genetic engineering is definitely a more powerful tool than selective breeding but with this so-called powerful tool comes a lot of ethical issues and problems. Selective breeding on the other hand is easy to do and doesn’t involve all the money for research and all the technology and isn’t nearly as complicated as genetic engineering is.

5. What are some future uses of genetic engineering. Anticipate at least six uses or misuses. Explain!

Computers, telecommunications and robots may make doctors and hospitals more efficient and safer. Biology will take medicine to places that are not even dreamed of--yet. In the past two decades scientific discoveries have turned biology from being a discipline dedicated to the passive study of life into one that can alter it at will. Biologists today believe that by tinkering with people's genes, the units of heredity, they will eventually be able to eliminate most of the diseases that now plague the world. Tomorrow, such extraordinary ambitions may seem modest, as scientists start to work on improving a person's genetic lot in life.

It all started in the early 1970s, when scientists first learnt how to clone and engineer genes. In cloning, a single gene is isolated from millions of others. Before this, scientists were confronted with the genetic equivalent of noise. Now they were free to study the structure and function of gene entities in isolation. By the end of the decade, Genentech, in San Francisco, had launched the first-ever genetically-engineered drug, human insulin. What Genentech had done was to take the cloned gene coding for human insulin and transfer it to bacteria. Genentech had synthesized a new life-form, a bug capable of making a protein foreign to itself. For centuries selective breeding has produced novel crops or cattle, but always with unpredictable results. With genetic engineering, scientists can be surer of outcomes: that a particular bacterium will produce insulin, say.

[Thumbnail Image]

Scientists now have a rag-bag of new tricks to help them probe nature. Mike McCune of SyStemix in Palo Alto, California, an experienced geneticist, points to four other bits of cleverness crucial to the progress of biotechnology, as the new field of biology became known. On the McCune list are the cloning of pure antibodies, polymerase chain reaction, differential hybridization and multi-parameter flow cytometry. Without going into the details of what this jargon means, all four aim broadly at the same goal: to provide a better understanding of what makes nature tick. This knowledge is now being put to good effect, with the discovery of powerful new medicines.

Biotechnology has made big promises before, without delivering on its early hype. But as Glaxo's Sir Richard Sykes points out: Just the past year has seen a paradigm shift in modern biology, because it is revealing so much information about the basic mechanisms of disease for which drugs can be developed. In the past, pharmaceutical firms relied on serendipity to find new drugs. In future that is not the way to go if the idea is to produce medicines of value. The rest of the drug industry feels the same way. According to Steve Burrill, a biotechnology buff, in the year to June 1993 drug firms formed around 100 strategic alliances with small biotech firms to tap into their know-how--twice as many as in the previous year. Research successes have fuelled a huge expansion of the biotechnology industry. In 1993 Mr. Burrill counted 1,300 biotech firms in America, 200 in Britain, and 400 elsewhere in Europe. Mr. Burrill reckons that by 2010 biotechnology firms' sales will have grown ten-fold compared with 1993, to some $100 billion. Because of the long lead-times involved, products began to trickle out of biotech R&D laboratories only about five years ago. Two drugs already have sales in excess of $1 billion a year, because they are so good at what they do: Amgen's EPO, which prevents anemia during kidney dialysis, and its Neupogen, which decreases the incidence of infection in cancer patients undergoing chemotherapy. But these two seem dull compared with what the next generation of biotech products will bring. Views differ about where biotechnology's biggest contribution will be made. But for a 2010-plus outlook the overwhelming vote goes to human genetic engineering.

The Gene Genie

On September 14th 1990, after years of foot-dragging, America became the first country to allow new genes to be introduced into people. On that day French Anderson, Michael Blaese and Ken Culver, all at the National Institutes of Health (NIH), used a gene drug to treat a four-year-old girl with severe combined immunodeficiency (SCID), a rare and dreadful disease, whose sufferers once had to live inside a sanitized plastic bubble. Those with SCID lack a gene that controls the production of an enzyme known as adenosine deaminase (ADA), which plays an important role in the body's immune defenses. Dr Anderson put copies of the ADA gene into the girl's white blood cells. In early 1991 a nine-year-old girl with ADA deficiency was also treated under the gene therapy programmer. In May 1993 the two young girls appeared at a press conference looking happy and healthy. The striking results achieved in these two cases have spurred on the use of "gene drugs".

ADA deficiency is one of 4,000 known disorders that result from a single genetic flaw. Most are as rare as SCID; a few, such as cystic fibrosis, are quite common. "But the grand strategy of gene therapy", says an NIH booklet, "also envisages a much broader use of the new techniques to include assaults on heart disease, diabetes and other major health problems that are influenced by the functioning genes." The development of such diseases depends on how a person reacts to environmental factors, such as pollution or smoking. However, the body's susceptibility to them is imprinted in a mix of bad genes inherited from parents. Gene therapy tries to correct these genetic faults to abolish or at least reduce the spread of disease. Dr Anderson, now at the University of Southern California School of Medicine in Los Angeles, says that "it can be used to treat disease, but its primary value will be in prevention." Genetic screening at birth can tell what diseases a person is susceptible to--so genetic protection can be given to prevent the diseases appearing in later life.

In 1993 a lot of progress towards this goal was made. The Centre d'Etude du Polymorphisme Humain (CEPH), in Paris, published the first genetic map of a human genome, the totality of human DNA. Before then, only 2% of the genome had been mapped. What the French did was to establish landmarks (marker genes) among the 100,000 genes that stretch along the human genome. This helps to track down genes that cause most inheritable diseases; patients suffering from such diseases often also inherit distinctive marker genes that are absent in healthy people. With the new map researchers can quickly isolate genes closely associated with the markers to determine which ones cause a disease. The map will also help to obtain a more detailed account of the human genome itself. Thanks to the global efforts of the Human Genome Project, it is hoped that by 2010 the structure and function of almost all human genes will be understood.

Even without the map, in 1993 the genetic causes of several diseases were found. A gene that leads to Huntington's disease, a form of dementia, was found after years of searching. Scientists are close to tracking down genes that cause breast cancer. Tests to screen several diseases were also invented in 1993. Oncor, a tiny biotechnology outfit in Gaithersburg, Maryland, launched a genetic testing service for breast cancer that uses computers to interview patients about family cancer history. It also screens for gene markers associated with breast cancer. As soon as genes that cause breast cancer are found, these too will be screened for to predict a person's chances of contracting the disease. Those with bad test results could opt to take the radical step of having their breasts removed. In time, however, they may get gene drugs that prevent the disease from occurring altogether.

Some 250 patients are now being treated with 12 different gene drugs in 74 approved trials around the world: the majority are for cancer, the rest for single-fault genetic diseases, which include hemophilia. The results of several trials are trickling in. Patients with abnormally high levels of cholesterol have, after receiving gene drugs, seen their cholesterol levels fall. Three out of eight patients with terminal brain cancers have experienced a reduction in the size of their tumors. Nobody has reacted adversely to any of the drugs, except for one cystic-fibrosis patient who had breathing difficulties for a few hours. That may have been because the drug was administered through the trachea.

Such technical problems of delivery, which is currently laborious and painful, are slowly being sorted out. There is still some worry about the safety of the delivery system, because viruses, even though inactive, are involved. The virus is a vehicle that carries gene drugs to cells in patients' bodies. Apart from the treatment of cystic fibrosis, the therapy has been administered by extracting bone-marrow cells from the patient, treating them with a virally- packaged form of the gene drug in the laboratory, and then returning them to the body. In 1993 Vical, a biotechnology firm in San Diego, found that by combining fat with DNA, it could bypass this procedure and inject genes direct into the bloodstream, much like any conventional drug. Dr Anderson is also working on injectable gene drugs. Researchers are trying to refine delivery systems so that they are longer-lasting and require only a single shot in a lifetime. It is still early days to be sure of the results, but most of the signs emerging from the research are encouraging.

So encouraging, indeed, that Daniel Cohen of CEPH reckons that by 2010 gene doctors will have found a way of dealing with most diseases caused by single gene defects. Over the next 50 years most common serious diseases will also succumb to gene therapy. And 50 years, he adds, is almost no time at all in the history of medicine (penicillin is now 50 years old). These are inspiring goals.

More controversially, gene doctors also want to shape human destiny. So far they have confined themselves to delivering genes to the somatic cells that make up most of the body. Germ cells in the testes and ovaries are not affected; the new genes are not passed on to the next generation, which remains as vulnerable as its parents to disease. But germ-line gene therapy would correct a genetic defect in the reproductive cells of a patient; offspring would also be corrected and disease could be eradicated.

Human genetic engineering could also enhance or improve "good" traits--for instance an extra copy of the human-growth-hormone gene could be added to increase height. On December 31st 1993 a scientific journal, Nature Genetics, published an article by CEPH that examined two genes in a group of 338 French people over 100 years old. They found that the centenarians had different levels of genes compared with younger people. A person carrying the right gene variants had twice the chance of reaching old age. This was the first time that genes had been linked to longevity. It follows that gene therapy might extend life-expectancy. And though scientists still do not understand enough about the genetic processes that make humans intelligent or beautiful, it might eventually be possible to tailor people to taste.

Some scientists believe that nature will act as a brake on genetic tinkering, because the human genome might be able to accommodate only a limited number of extra genes. It would also be hard to deal with multi-gene traits. As with the genie in Aladdin's lamp, people may be offered a fixed number of wishes: a cure for cancer, a height-inducer or whatever. Once their wishes are used up their genetic make-up will be unalterable--at least by their own hand. Yet no matter how they are dressed up, such uses of gene therapy will have moved medicine from the business of curing or caring into the more ethically dubious areas of life-enhancement and eugenics: two issues to which this survey will return later.