Preface

 

Our project is based on this hypothesis:

 

How may genetic engineering help us to find solutions to medical diseases/disorders?

 

This paper is an interesting journey through the mysteries of the natures own miracel; genetic engineering. We chose this subject because we wanted to get to know more about the future of genetics. This is quite new area in medicine, therefore we had some difficulties finding information. We had to look through scientific literature, and search the net. Once again the web has helped us writing a paper. Reading this paper you will get an introduction to different aspects of genetic engineering. We decided to begin our paper with an explanation of genetic engineering because it is the basis for the rest of our project. You will also read about diseases/disorders caused by errors in the DNA, and how they may be treated. We chose to write include cloning because it is a new way of treating diseases/disorders. In the end we have som prospective aspects on the subject. We hope you will enjoy our paper.

 

Stian, Are, May, and Sadia

 

Genetic Engineering

 

This is a way of changing the inherited characteristics of an organism in a predetermined way by altering its genetic material (Microsoft Encarta’95). This is often done to create microorganisms, such as bacteria or viruses. This is done to synthesize increased yields of compounds, to form entirely new compounds, or to adapt to different environments (Microsoft Encarta’95). Genetic engineering also includes gene therapy. This technology is used in the treatment of people with cancer and AIDS (Acquired Imune Defciency Syndrome).

 

Genetic Engineering involves the manipulation of DNA (Deoxyribo Nucleic Acid). Important tools in this process are so called restriction enzymes. These are produced by various species of bacteria. Restriction enzymes can recognize a particular sequence of the chain of chemical units, called nucleotide bases, that make up the DNA molecule , and cut off the DNA at a wanted location. Fragments of DNA generated in this way can be joined by using other enzymes called ligases. Restriction enzymes and ligases therefor allows the specific cutting and reassembling of portion of DNA.

 

 

In this very complicated process of copying, errors might occur. This means that a «c» or a «t» could switch places, and create a new combination in the DNA structure. This is called a mutation.

 

This is what Darwin based his theory of evolution on - mutations makes slight differences in the inherited material, and can in the long run create different species.

 

One other thing that is also very important in the manipulation of DNA, are so called vectors. These are pieces of DNA that can produce copies of themselves independently of the DNA structure in the host cell where they are grown. Examples of vectors include plasmids, viruses, and artificial chromosomes.

 

This way one cell will always be able to produce as big quantities as wanted. The process of engineering a DNA fragment into a vector is called cloning. Multiple copies of an identical molecule is produced .

 

Another way, recently discovered, of producing many identical copies of a particular DNA fragment is polymerase chain reaction. This method is fast, and avoids the need for cloning DNA into a vector.

 

The benefits of genetic engineering are many. For example it can be used to make artificial insulin. Insulin is normally found only in higher animals, but by using genetic engineering it is now possible to «grow» insulin in bacterial cells. The bacterial cells can easily be produced in any wanted quantity, and makes the insulin much more available.

 

Genetests

 

Genetests can supply us with knowledge about diseases yet to come, and «errors». Both concerning us and our unborn children. The use of these tests creates several questions, both ethical and fundamental. And they confront us with fundamental questions: Do we want to know or not?

 

A genetest can be made at any time in the life of a human being, also during the fetus stage. The results of the tests are not dependent on the persons medical condition. Since the genes are inherited, one will also be able to tell if relatives will inherite the same disease. Genetests may also in some cases tell if a person is carrier of a gene that may strike his or hers children as a congenital and chronicle malfunction or disease.

 

Inheritable diseases

 

Inheritable diseases are caused by genetic errors. These diseases belongs to different categories.

 

Sex related diseases:

 

Sickness that affect boys and girls in different ways, because the gene which leads to the disease is on the X-chromosome, if one of the mothers X-chromosomes contains the defect gene. Her children will have a 50% chance to inherit this gene. Her daughters will usually just be carriers, while her sons will get the disease. The daughters other X-chromosome, which they inherit from the father will produce enough normal protein to increase the effect from the defect gene-copy, so they will be protected in the same way as their mother. An example of a sex related disease is hemophilia.

 

Not sex related recessive diseases:

 

Both of the parents have to be carriers, and each of them need to have a copy of the gene which is defected. The parents don’t have the disease because they have a “healthy” gene too. If both of the parents are carriers the chance for the children to be carriers is 50%, and to get the disease will be 25%. An example of a none sex related recessive disease is Cystic Fibroses.

 

Not sex related dominant diseases:

 

Genetic defects which are inheritable from both parents, the children’s chance to get the disease is about 50%. An example of a not sex related dominant disease is Huntingtons syndrome.

 

 

A sick person and a healthy person having a child, have a 50 - 50% chance of getting a sick/healthy child

 

Diabetes

 

Diabetes Mellitus is a disease caused by defective carbohydrate, and characterized by abnormally large amounts of sugar in the blood and urine. Diabetes can damage the eyes, kidneys, heart and limbs. It could also endanger pregnancy.

 

The disease is classified into two types:

 

Type I: Insulin dependent diabetes mellitus (IDDM), this type is called "juvenile onset diabetes" because it occurs in children and young adults.

 

Type II; Non-insulin dependent diabetes mellitus (NIDDM), this type is called "adult onset diabetes", because it’s usually found in persons over the age of 40.

 

The human pancreas secretes a hormone called insulin. The insulin takes the sugar out of the blood, and stores it. When a person has diabetes, the problem is almost always a total or severe reduction of insulin.

 

Insulin was first obtained in 1921 from the pancreatic tissue of dogs. "In 1981 insulin made in bacteria by genetic engineering became the first human hormone obtained in this way to be used to treat human diseases." ("insulin", Microsoft Encarta) Today they use insulin from pigs. The human body accept this insulin because it’s almost the same as a human insulin.

 

Treating Diabetes with transplanted cells

 

Until about 15 years ago, the form of diabetes that usually strikes children and young adults was invariably lethal. Families and physicians watched helplessly as the victims died within weeks or months of diagnosis. By the early 1900s investigators knew that the problem lay with small clusters of pancreatic cells called the islets of Langerhans. These islets normally secreted a critical hormone, later named insulin, that enabled other cells to take up the sugar glucose from the blood for energy. It was also obvious that in the diabetic patients ( today said to have type I ) insulin production had ceased. Consequently, glucose from food accumulated in the blood while other tissues starved. People with the more prevalent, later onset form of diabetes ( type II, or non-insulin - dependent ) managed far better because they continued to make at least some insulin.

 

 

Prospect for type I diabetics improved dramatically in the early 1920s, when insulin extracted from animals proved lifesaving. For decades thereafter most people assumed daily injections of the hormone were tantamount to a cure. Unfortunately, they were mistaken. Over the years clinicians gradually came to realize that many patients eventually suffer from potentially devastating diabetes - related disorders. Microscopic blood vessels can slowly become damaged, often culminating in blindness or kidney failure, or both.

 

The key to ensuring long-term health, is to provide therapy that can maintain glucose values within normal limits at all times from the start of the disease. An ideal treatment would be implantation of islets, because functional islets would restore proper insulin production and, in theory, would have to be implanted only once; native islets survive for many years and carry within them the precursor cells needed to supply replacements for cells that die. Successful grafts would also avoid acute diabetes-related illnesses. These conditions include coma induced when glucose accumulates to extremely high levels in the blood, as well as insulin reactions (often marked by shakiness, confusion or blackouts), which arise when an injected dose of insulin lowers glucose levels too far. Islet transplantation is conceptually simple but has been difficult to implement. Finally, however, there is good reason to think this potentially curative therapy will be available to many patients within the next five years and will become routine for newly diagnosed patients within a few years thereafter.

 

Cancer

 

Genetic engineering will help us humans with several unsolved mysteries. What can it do for us when it comes to cancer? But first of all, what is cancer? Cancer is new growth of tissue because of abnormal cells which invade and destroy other, healthy tissue. It is cells which is not under the body’s control anymore because of malfunctions in the DNA or genes. Almost all cancers form tumors, which is many abnormal cells that clings together. The three major types of cancer are sarcomas, which appear from bone, nerves, bloodvessles, muscles and fat. The second one is called carcinomas. It is the most frequent form of human cancer. It arise from epithelial tissue, like skin and the lining of body cavities and organs. The third type is called leukemia and lymphomas. They involve blood-forming tissue. They invade for example the bone marrow.

 

You might also be wondering about what causes cancer. It is a difficult question, but basically one can say it is a genetic process. It is changes in the genes or DNA caused by heredity, viruses, ionizing radiation, chemicals and changes in the immune system. There is not one thing which causes cancer, but a series of things happening. That’s one of the reasons it is hard to protect oneself from it.

 

There are many ways to treat cancer, but no treatment is 100% reliable. There is not a drug one can take and get healthy. To treat cancer it has to be discovered at an early stage. Doctors have to regularly examine persons who are in the high risk group( smokers, other in family with cancer, people who sunbathe a lot). The most used treatments are:

 

Πsurgery

 

 radiation therapy

 

Ž chemotherapy

 

If one goes through a surgery the whole tumor is removed. That way the surgeon hopes to get rid of all the abnormal cells. The use of radiation therapy is effective. The body is exposed to ionizing radiation which one hope will kill the abnormal cells. The last few years one has found out that expotion to radiation only weakens the cell so the p53 gene will activate the cells suicide mechanism. Another discovery is that radiation therapy may also in fact be fatal for the patient because if the p53 gene isn’t healthy it won’t kill the abnormal cells, and the tumor will grow. The last treatment is chemotherapy. With the use of drugs one kill the cells by interfering with DNA functions.

 

The gene which kills cancer - p53

 

In 1979 two scientists named David Lane and Arnold Levine discovered a new gene, p53. At the time it didn’t create any speculations because it seemed to cause, not kill cancer. Some years later, in 1989, Lane and Vogelstein did an extraordinary discovery. p53 kills tumors. They found out that if p53 is healthy it keeps the cell it is in normal, but if it is absent, damaged or tied up by other molecules, it may create cancer. “p53 acts as the cell’s director of damage control. A healthy cell usually keeps a small number of p53 proteins around, continuously degrading them and replenishing the supply. But if something - ionizing radiation, a chemical carcinogen, chemotherapy drugs - damages a cell’s DNA in a way that threatens to set in on the pat of cancer, the cell switches into high alert. If everything is working right, something signals the p53 to stop degrading, and tells it that it’s time to be active”. (Newsweek, January 13th 1997, page 38)

 

The p53 cell switch off a damaged cell, so it can restore itself. When it is restored p53 turn the gene on again. This way it prevents tumors. p53 can also kill a cell by activating its suicide mechanism. The p53 gene is good for humans when it’s healthy, but when it’s damaged it may be a factor in creating cancer. The gene may be damaged when it mutates or is affected by chemicals. If so happens the p53 gene will stimulate cell division rather than suppress it. It also turns on a new set of genes which makes cells immune to cancer drugs.

 

If someone inherit a mutant p53 gene, and not any healthy p53 genes, they are most likely to die fast of cancer. Most p53 mutations are not inherited though. They arise from copying errors and affect by chemicals, for example cigarette smoke. One mutant gene is enough to create a deadly tumor.

 

Vaccines

 

With the discovery of the p53 gene one found out how the body itself treat cancer. In the last few years scientists have experimented with different approaches to find a cure to cancer. One hope to be able to provoke p53 genes to attack abnormal cells. Scientists have succeeded in isolating isolate white bloodcells that will kill cancer, and they have found proteins that will train the immune system to attack tumors. In this way they might be able to develop a vaccine. Today there are a dozen in development. The naturally produced white blood cells (T-cells) attack proteins it doesn’t recognize. Scientists inject proteins from cancer cells into patients, and that will activate the immune system. In this way they might be able to develop a vaccine. Today there are a dozen in development.

 

Cancer vaccines are different from the ones used to prevent diseases. Cancer vaccines are supposed to treat diseases which already exists. Still there is a long way to go before there will be a cancer vaccine on the market.

 

Genetherapy

 

Genetherapy is a new discovery, and there isn’t much information about it. First experiments on human beings started in the late 1980 `s.

 

When one use genetherapy one supply a functional gene to cells lacking that function. In that way one hopes to correct genetic disorders (Genetic disorder is loss of a gene in the DNA. You can only get it by heritage, for example Huntigtons syndrome and Cystic Fibrosis) or acquired diseases (cancer). Insertion of a gene can be used to correct an inherited genetic defect, to counter or correct the effects of a gene mutation, or to program a cell for an entirely new function or property. There are two ways of genetherapy:

 

Πalteration of germ cells (sperm or eggs)

 

 somatic cell transplant

 

Alteration of germ cells will result in permanent genetic change for the whole organism and the following generations. This way of genetherapy is not an option because of ethical reasons.

 

One repair/replace defect genes with healthy ones. It’s done in three ways:

• if the genetic inheritable disease is in the man’s sperm the procedure can be done before the egg is fertilized.
• the same procedure can be used on women’s eggs.
• if it shall be done on a fertilized egg, it has to be carried out within a few hours after the conception.

 

Somatic cell transplant is synonymous with organ transplant. Doctors take some blood from the spinal marrow, bring the blood to a laboratory and add healthy, correct genes. Then the blood is injected into the artery. One hope that the bloodcells with the healthy genes will start to divide themselves, and convey the body with loads of fresh DNA. Then the body will heal. The defect DNA will still be in the body, but the immune system will be restored by the healthy DNA. So far scientists can only treat diseases which is caused by an error in one gene. They cannot correct several genes at the same time.

 

In time genetherapy may provide effective treatment of many diseases and disorders, including cystic fibrosis, muscular dystrophy, and juvenile diabetes. Scientists also tries to find a way to treat disorders which not are inherited. An example is AIDS. Scientists are doing research on how to make cells genetically resistant to the infection which AIDS causes.

 

Cloning

 

A clone is an organism, or group of organisms, which is derived from another organism by an asexual (non-sexual) reproductive process. The word clone has been used about cells as well as organisms, which means that a group of cells stemming from a single cell is also called a clone. Usually the members of a clone are identical in their inherited characteristics, which means they have identical genes, except of course for any differences caused by mutation. Identical twins, for example, are members of a clone, they originate from the division of a single fertilized egg, while non-identical twins are not members of a clone because they originate from two separate fertilized eggs. A number of simple organisms, such as bacteria, many algae and some yeasts, and even some higher organisms, for example flatworms and plants such as the dandelion, reproduce by cloning. So cloning isn’t something that humans created, but in recent years advances of genetic engineering has brought us beyond the natural limit and in to a new era.

 

Scientists can now isolate an individual gene (or group of genes) from one organism and grow it in another organism belonging to a different species. The species chosen is usually one that can rapidly reproduce asexually, such as yeasts and bacteria. Because they multiply so fast, these methods makes it possible to produce many copies of a particular gene. The copies can then be isolated and used for the purposes of study, for example, to investigate the chemical nature and structure of the gene, or for the purposes of medicine, for example to make large quantities of a useful gene-product, such as insulin. This technique is called cloning, because it uses clones of organisms or cells. It has a great medical potential and is the subject of active research. Identical-twin animals may be produced by cloning too. An embryo in the early stage of development is removed from the uterus and split, then each separate part is placed in a surrogate uterus. Mammals such as mice and sheep have been produced in this way since 1986.

 

Another development has been the discovery that a whole nucleus can be taken from a cell and injected into a fertilized egg, whose own nucleus has been removed. The division of the egg brings about the division of the nucleus, and the descendant nuclei can, in their turn, be injected into eggs. This cloning technique is in theory capable of producing large numbers of genetically identical individuals. Such experiments have been successfully carried out with frogs and mice, but the cloning of higher mammals beyond an early embryonic stage has been considered not possible. Until recently. On January the 23^rd this year, 1997, the whole world was presented to Dolly, a sheep produced by cloning. And she was produced through a totally new and revolutionary method. The nucleus was removed from a mature egg, and the «emptied» egg was then «melted» together with a normal cell through an accurately calculated electric shock. The result was one living egg cell with the genes from the normal cell, which acted like a fertilized egg. The egg was then placed in a uterus and after the certain amount of time, Dolly was born, identical to the one the normal cell belonged to, and with no father. Technically, there is no reason why this technique shouldn’t be used to clone humans. But it is a tough ethical issue. A lot of people are afraid that someone will misuse this knowledge to their own benefit. But on the other hand, cloning may help us find solutions to inherited diseases. (See appendix for more information on human cloning)

 

Ethics and future prospects

 

We all have our dreams of an utopia. A society without problems, disease, pollution. What you know are going to read is yet just another dream. It’s just philosophical thought on how genetic engineering might be used in the future.

 

When it comes to genetic engineering, you can’t avoid the ethical dilemmas. Genetic engineering is a very vulnerable issue because it may affect every living thing on this planet. A lot of people are afraid of what it may lead to in the future, while some just think of the possibilities to find solutions to every disease known to man kind.

 

Genetic engineering may be the solution to many diseases/disorders, such as cancer, aids, inherited disease and to diseases/disorders caused by genetic «errors». There isn’t any solutions for those today. But do we know that the information we get will be used in the right way? We’ve already seen that knowledge may lead to things that are highly thought-provoking. We can now find out if people suffer from, for example Downs syndrome before they are born.

 

Imagine that you are in year 2200. You are blind. But hey, don’t worry. Scientists have made a biological computer which they operate into your brain. It gives you your sight back. Just by mixing some genes together scientists make anything. Cancer and AIDS are defeated. A cure was found years ago.

 

If you’re pregnant and you really want a blond, medium sized, smart, funny boy you just go to the hospital and tell them. There you’ll get a list of all the characteristics you want to give your child. Well, it costs, but when you really want a bright boy who cares? Or if you want a pretty girl just let them know.

 

And the food. Let’s say you don’t like carrots. Then you just buy carrots which tastes like chocolate or strawberries or whatever you like. You’ll get all the vitamins, but it tastes whatever you want it to taste! Isn’t that great? Say you have beef, carrots, potatoes and brown sauce for dinner. It’s healthy, but you don’t like potatoes or brown sauce. Well, buy it with apple taste. Cool. Your children will love dinner! Not to mention how easy it will be to “keep the food”. By mixing lettuce with some of the genes from pine it will stay crispy and green forever. Isn’t this the society we all dream of? Or is it?

 

Will it be cool to eat beef, potatoes, carrots and brown sauce when it all tastes like chocolate? What’s the point of getting pregnant if you may decide on how your child shall be. There will be no excitement raising your child. If we exterminate all diseases, won’t there come another which is worse in time? Think about it. Genetic engineering may do so much, but do we want all of it? Shouldn’t there be a limit?

 

Everything has two sides. All of the above is crazy stuff genetic engineering may lead to, but what may it do for us when it comes to medical issues? One example is that it may exterminate genetic differences like the Downs syndrome. Normally a person has 23 pairs of chromosomes, a person with Downs syndrome has one pair to much. The syndrome may be exterminated by removing the two extraneous chromosomes during labor. If the baby turns out to have the syndrome, the mother automatically have the right to have an abortion, even after the twelfth week.

 

Genetic engineering can also give us solutions on how to repair mutations in the DNA. By repairing these mutations doctors will be able to cure gene based illnesses. We have already mentioned the Downs syndrome, but it also includes all forms of cancer which is inheritable.

 

Genetic engineering has good and bad sides. We will have to compare both sides and decide on which side we like the most. But it all ends up in ethical questions like “do we want a society without diseases and people with handicaps”, and “ do we have the right to decide who gets to live and who doesn’t”?

 

Genetic engineering leave us with a lot of possibilities, but few answers. Where do we draw the line? How will we know when to stop? Will we in the future see a society with no illnesses, a perfect world, or will we have a society where only the ones with perfect genes can benefit from social security, insurance, loans and so on. Will they become someone important? Maybe there will be fought wars to get access to the newest information. Maybe we will have world wide viruses that kills most of us because there is no genetic variation, a result of cloning. Maybe none of this will happen. Nobody knows, all you can do is guess.

 

Today we have the opportunity to clone. But what are the consequences? This is the most debated issue. Many people say that they are against all genetic engineering, because we don’t know were it might lead. When the train was invented people said the same. Some of us will always be afraid of the new and unexplored, while others blindly look at the possibilities.

 

Conclusion

 

Genetic engineering is a puzzle - one never knows where the next piece shall be placed. There are many ways to treat diseases/disorders with the help of genetics.

 

This project has given us many answers to our hypothesis. We have learned how genetherapy may treat non-functional genes, and we have seen how genetic engineering can help us treat diseases of today. We think of genetic engineering as a thing of tomorrow. We learn more as every day goes by.

 

Even though it can do “wonders” there are some dangers lurking behind the tree. An example is the potential dangers of cloning. Genetic engineering may also in the end make humans resistant to antibiotics. There are many ethical dilemmaes which still needs to be debated. There are no answers, just questions! This is why it is important that everybody get involved. All of us have to decide on whether or not they support the progress.

 

Our last words will be what President Clinton so elegantly put it:

 

Don’t play God!

 

Sources

 

Internet

• The Cancer Letter
• Time - the cloning breakthrough
• “La oss tukle med naturen” by Elin Brodin
• University of Oregon

 

Brochure

• “Gentesting - nye muligheter, nye dilemmaer” by Bioteknologinemda

 

Magazines

• Newsweek Jan. 13th 1997, Jan. 27th 1997
• American Scientist

 

Books

• Vitenskapens verden #19
• “Inn i genalderen” by Kristin Aalen Hunsager/Audgun Oltedal, Samlaget 1988
• “Mer enn gener - utredning om bioteknologi og menneskeverd” by Kirkerådet 1989
• “Genet og genteknologi - er det noget for os?” by Kaskalot Pædagogisk Særnummer 1992

 

Encyclopedias

• Microsoft Encarta’95 (Cd-rom)
• “Store Norske leksikon” by Ascheoug og Gyldendal
• Americana