Cloning paper

A few years ago if you were to ask someone about the possibilities of cloning they would most likely say it was impossible. This attitude towards cloning has been held into belief up until recently when scientists in Scotland cloned a sheep. And immediately after scientists in Oregon cloned a monkey (Fackelmann 276). The most major breakthroughs of the century in science has occurred and we are not ready for it. The scientific breakthrough of cloning has caused a great deal of controversy in the media and also in the government. The advantages of cloning are tremendous to the human race and cannot be ignored. I believe that cloning humans is what the human race needs to advance. Humans would be stronger, smarter, and more perfect. Scientists could remove bad genes from the parents and replace it with a good one. If one of the parents had a bad gene or hereditary disease this could be removed from the embryo and replaced with another "clean" gene. This process is called embryo screening it is used to determine if the child has received the defective gene. Several embryos could be cloned, then the DNA from one of the embryos would then be removed and standard genetic testing would be used to detect whether or not that embryo contained the genetic disease. If this cloned embryo containd a disease then one of the other embryos could be used for implantation in a parent, this guarantees that the child would be free of genetic disease (Marshall 1025). For those who disagree with cloning I am sure if there child could be saved from a genetic disease they would reconsider cloning. Imagine if one of your friends or family members was in need of a liver or kidney. Most likely you would donate your own liver or kidney to save there life. But then you are one organ short. Well this happens a lot and seems to work fine. But if they needed a new heart you might have trouble finding one. Not if you had a clone of yourself that could supply you with a new organ or maybe even a relatives organ that was naturally stronger (Cloning 1117). Someone could replace their old organs with new ones and extend their life span. Thousands of lives that could be saved if we had the technology and advanced science of cloning available. Even accepting an organ from a relative it may fail, it has to be compatible with our body system , if its your clone, then its a perfect match. Cancer is one of the largest killers and also one of the largest dilemmas scientists face today. Well, cancer research is possibly the most important reason for embryo cloning. Oncologists (People who study Cancer) believe that embryonic study will advance understanding of the rapid cell growth of cancer. Cancer cells develop at approximately the same great speed as embryonic cells do. By studying the embryonic cell growth, scientists may be able to determine how to stop it, and also stop cancer growth in turn (Watson 66). Whenever there is a draft for a war people protest hide and even leave the country why should people be sent to fight for something they don't believe in or even in my case a country they don't want to die for. We cannot dispense human lives as if they were candy. If we produced smart, strong and loyal clones, we could have the perfect soldier. There would no longer be humans in the military, there would be no worries about losing lives or family members. Clones made specifically with a sole mission to die for there country these perfect soldiers would make up a perfect army. Well, in the case of a lost relative, more specifically parents losing their child. Parents could clone a child who had died, as a homage of love. The saying "there is nothing that you can do to bring him/her back" would now be obsolete with the process of cloning. Of course parents could never have their child back exactly as he/she were but they could definitely start over again. Or parents could simply clone the traits of a famous person or favorable traits of someone else and put them in their child's embryo. Maybe even if they wanted twins or even sextuplets. Parents would be able to make more decisions on their child or children's traits. The benefits of cloning do not stop at humans it extends out to animals. A lot of controversy is brought about when animals are used for laboratory testing. We should clone animals specifically for laboratory tests, these animals would not be depleting any populations nor would they be taken away from their habitats destroying any food chains. Also farmers would benefit from cloning their select animals. This would also give the consumer better meat quality and lower the price of meat. Governments in countries where famine is present could master cloning techniques and provide for the starving populations in their country. One of the most beneficial effects of cloning animals is that species of animals whose populations are almost extinct could be replenished by cloning. Animals such as the Blue whale, the condor, and the Norfolk whale. These are only three examples of endangered species, there are practically hundreds of endangered species that could be saved with the process of cloning. We wouldn't be bothered by activists or any more "save the whales" foundations asking for you to donate money. If the amount of animals produced were controlled according to the food chains and habitats, these species could thrive once again. We could grow plants that would be immune to bugs or pesticides. Farmers would have crop that would survive the winter and frost. We could eliminate the loss of crops that forces the prices to go up in the supermarkets. Crops that require less water or can grow in certain types of soil. This would be could for California where water is scarce. This is only the begging of the benefits we can achieve from cloning. Creating a stronger and more advanced human race. Diseases would become weeded and cleaned out of humans' genetic makeup. Of course there is a chance of this getting in the hands of a madman or someone who would use it for ill purposes. But we can not let this amazing discovery stopped by people that can only see the bad side of cloning. They must also see the vast benefits of cloning, how it can save lives and entire species from extinction. I believe that cloning is a part of our evolution, our ancestors evolved by using their hands and minds, by creating language and civilizations, this advanced them. Cloning is what will advance our race more. Our bodies have stopped using and have disposed of unnecessary organs and body features which have proved to be useless. Diseases and deformities are useless and cloning can aid to the evolution of humans by cleansing our bodies of such ill and in some cases deadly burdens. There are too many adva ntages in cloning for us to ignore it.

Evolution from a molecular Perspective

Introduction: Why globular evolution? Evolution has been a heavily debated issue since Charles Darwin first documented the theory in 1859. However, until just recently, adaptation at a molecular level has been overlooked except by the scientific world. Now with the help of modern technology, the protein sequences of nearly every known living thing have either been established or are in the process of establishment, and are widely accessible via the internet. With the knowledge of these sequences, one can actually look at several organisms genetic codes and point out the similarities. Entire genomes of creatures have been sequenced, and the human genome project is well underway and ahead of schedule. With this new knowledge comes worries, for humans, however. What if the information stored in our genes was available to the public? Would insurance companies and employers base their selections on these traits? Also, with the total knowledge of every sequence of every amino acid chain in a person's genome, couldn't a laboratory perceivably re construct an exact copy of, or clone, that person? These are all issues that will have to be dealt with in the near future, but for now we need only concern ourselves with the objective observation of these proteins in our attempt to explain our ever mysterious origin. As humans, we are the first creatures to question exactly where we came from and how we got here. Some cling to religious creationism as a means, while others embrace the evolutionary theory. As of now, and possibly forever, neither can be proven to be absolute truth with hard facts, and both have their opposing arguments. The point of this paper being composed is not to attempt to abolish the creationist view, a feat that at this point seems impossible, but merely to educate those seeking to unravel the mystery of our forthcoming by pointing out facts that exist in the modern world and that can be quite easily and independently researched. It is conceivable that the two ideas, creationism and evolutionism, can exist symbiotically due to t he fact that both views have very good points. Hemoglobin: Comparisons between species Of all the proteins in living things, hemoglobin is "the second most interesting substance in the world," as American biochemist L. J. Henderson once stated (Hemoglobin, 4). However bold this statement seems, it must be realized that hemoglobin is, at least in the scientific world, by far the most studied and most discussed substance in the human body, as well as in other living organisms. Hemoglobin is the carrier in blood that transports oxygen to our tissues and carbon dioxide out of our body, changing colors as it does so. Hence, hemoglobin has long been termed the pigment of our blood. Hemoglobin was one of the first proteins to be purified to the point where its molecular weight and amino acid composition could be accurately measured. This finding was very important in that it eventually lead to the understanding that a protein is a definite compound and not a colloidal mixture of polymers. Each molecule was built from exactly the same amino acid subunits connected in the same order along a chain, and had exactly the same weight. Most organisms have their own unique, individual chain of proteins to make up their hemoglobin, but all organisms share certain similarities, so striking that they are unable to be ignored. Let's take, for example, the first twenty-five amino acids in the alpha hemoglobin chains of 7 different animals: a human man, rhesus monkey, cow, platypus, chicken, carp (bony fish), and shark (cartilaginous fish) (See Table 1.1.) As is shown, the variations increase the further apart the organisms are on the proposed evolutionary scale. A human man differs from a rhesus monkey only twice in the first twenty-five amino acids of their alpha hemoglobin chains, whereas a man and a cow differ in three areas. This is the product of many thousands of years of natural fine tuning, if you will, through the slow but precise processes of natural selection and adaptation. The fact of natural selection shows us that while most genetic mutations usually prove fatal, a slim few are actually benef icial, and assist the mutant in living and procreating offspring. This assistance helps the mutant-gene's frequency grow in the gene pool and remain there since all progeny possessing this certain trait are going to have an advantage over the other organisms lacking this quality. This is the basis for evolution. The higher a certain species is on the evolutionary scale, the more advanced that organism is due to a slight change in the amino acid sequences of certain genes. An example would be that of the human man, the rhesus monkey, and the cow. There is a smaller difference in the amino acid sequences between a man and a monkey than between a man and a cow, and, respectively, a monkey is more advanced than a cow, genetically (monkeys and humans have far advanced apposable thumbs.) Also, where the amino acids have been conserved between all the studied organisms, such as in columns 27, 31, and 39, indicates that in order for the species to survive, that certain amino acid must be there. If it is changed in any way, the organism can not survive. There are thirty-four conserved positions in the first 141 amino acids in the seven studied organisms. After just these few demonstrations, how could anyone doubt the theory of evolution? This question leads me into a short interlude where I will discuss the arguments on both sides, and show just how endless this debate could be. Evolution -vs- Creation: Which Is Truth? When evolution is mentioned to many people, the first thing that enters their mind is the completely incorrect thought that man evolved from monkeys. Man did not, in fact, evolve from monkeys, this is a known and agreed upon fact. The only connection between modern day men and modern day chimpanzees, for example, is the fact that they must have shared a common ancestor. The "common ancestor" theory, as I have chosen to name it, states that all life living, or ever to have lived on this planet can be traced back to a single, common ancestor. At some point in time, between 3.5 and 4.1 billion years ago, a certain grouping of chemicals came together at just the right time and life began. From this single life-form, the slow process of natural selection began. First came the proteinoid microsphere, the first organisms on the planet to carry on all life functions. Eventually, then, came viruses, parasites, saprophytes, holotrophs, chemosynthesizers, and photosynthesizers, all mutants of the very first cell. Some have tried to use thermodynamics to disprove evolution, especially the second law. The second law of thermodynamics states that "all energy transfers or transformations make the universe more disordered." These speculatives claim that since man is more advanced than any other creature, we are more ordered. This is wrong. Man is more advanced due to the mutations in his genes. Compared to the very first life-form's genes, a human man's amino acid sequences are very dissimilar, or more disordered. Also, the first law of thermodynamics can be used for either argument. The first law of thermodynamics states that energy cannot be created or destroyed--in other words it has always been here. Using this law, the matter in the universe can either be thought of as always being here, or that the creator, with his infinite power, simply transformed the energy that he possessed into the matter of the universe. Both sides have an arguable point that agrees with the laws of thermodynamics. Another arguable point that is worthy of mention is the discrepancies in the fossil record. The Earth's crust, and all the fossils contained therein, can also be utilized as arguments for both sides. The "Pre-Cambrian Void" (Creation-Evolution: The Controversy, 362) shows very little sign of fossilization. Then, suddenly, massive amounts of fossilization can be found during the Cambrian times, pointing to some sort of catastrophe, like a flood. The Bible mentions a flood sent by God to destroy every living thing on Earth. The fact that a flood could have happened, in that sense, strengthens the creationists' views. The evolutionist theory can use these facts in two ways. One, when the selection pressure on a species is constant for a long time, a species could become so specialized that any slight change in their environment could lead to extinction, this is called a climax group. Around the time that the large amounts of fossilization was occurring, the Earth had cooled down enough to allow the immensely dense atmosph ere to condense, thus causing many years of rain. Would not this rain cause almost any climax group's entire population to become extinct? Also, before the rains came, the great majority of the organisms inhabiting the Earth were land creatures. Once the rains came, the Earth was covered in water, killing thousands of populations, and effectively burying them in the water. The water preserved their parts for fossilization. These have been just a few double sided arguments demonstrating that either side can turn any facts around to fit their own hypothesis. Leghemoglobin, Protein Relations Between Species, and the Evolution of the Globin Family Like animals, plants also carry a sort of hemoglobin, leghemoglobin. Leghemoglobin is a globin which is less evolved than that of hemoglobin or myoglobin. The whole globin family, itself, has undergone much evolution and mutation. At one time, animals had no globin at all. As life evolved, a single-chain oxygen-binding substance formed--we will call this the basic globin. Then life branched into two parts: animals carrying the basic globin, such as annelid worms, insects, and mollusks, and creatures (manly plants) carrying leghemoglobin, a mutation of the basic globin. The animal kingdom's globin eventually split into myoglobin (Mb) and hemoglobin (Hb). Since then, myoglobin has basically stayed the same in many organisms (See Table 1.3.) Hemoglobin, on the other hand, has undergone some major mutations. After the basic globin bifurcated into Mb and Hb, Hb split into alpha (a) and beta (b) chains. The a-chain eventually split into two parts, and has remained this way up to present times. The b-cha in split into many more parts. Everything that has been said up until now about the evolution of the globins from a common single-chained oxygen-binding ancestor has been summarized in Table 2. If one would compare sequences of globin between species, one would notice that the less amino acids that are different the more closely related two species are. If we used this theory on the vertebrates that were studied it would give us a "schematic family tree of globin containing vertebrates" (Hemoglobin, 78) (See Table 3). This same tree is obtained by comparing sequences of myoglobin, or the a or b chains of hemoglobin. This tree tells us that all organisms alive today are just as evolved as any other living organism. Different species evolve in different ways, that is the basis of evolution. Man is just as evolved as a chimpanzee, or a carp, or a rose bush. Different organisms simply evolved differently. Another excellent way of showing the relationships between organisms is the mean amino acid differenc es. The more amino acids that are different between two species, the further apart they are genetically. For instance, of the entire b-chain of human and rhesus monkey hemoglobin, there are, on the average, eight places where the amino acids are different. However, when comparing b-chains of man and platypus, there are thirty four average differences. A chart and a graph can help us better understand these points (See Table 4.) The amino acids that have changed are a result of mutated DNA that has proven beneficial to the carrier mutant. This process, as stated before, is the basis of evolution. Speaking solely of hemoglobin, the variances between species can be shown through greater or less affinity for oxygen. "H. F. Bunn has shown that mammalian hemoglobin can be divided broadly into two groups: the great majority have intrinsically high oxygen affinity, which is lowered in the red cell by DPG," (D-2,3-biphosphoglycerate) "while those of ruminants and cats (Cervidae, Bovidae, Felidae) and of one primate, the lemur, have an intrinsically low oxygen affinity that is little, or not at all, lowered by DPG ("Species Adaptation in a Protein Molecule", 16). DPG is one of the ligands that "reduces the oxygen affinity of hemoglobin in a physiologically advantageous manner by combining preferentially with the T structure." ("Species Adaptation in a Protein Molecule", 3) For instance, the mole (Talpa europaea) lives in its burrows under conditions lacking a rich oxygen supply. This creatures hemoglobin has adapted to having a high oxygen affinity, a high concentration per unit volume of blood, and a lo w body temperature. This high affinity is due to the mole's hemoglobin's low affinity for DPG. So as you can see, DPG asks as a type of buffer. The more DPG the creature's hemoglobin can hold, the less space it has for oxygen. Since the environment has low amounts of oxygen, the blood needs to hold as much oxygen as possible, so the mole has adapted. Which Came First? One final point that should be mentioned is the question of which change came first. Did a mutation occur that adapted a species to a new environment take place before the species occupied that environment, or did the genetic change occur after the environment changed in order to assist the creature with living in its new surroundings? "W. Bodmer suggested that once a large change in chemical affinities produced by one mutation had enabled a species to occupy a new environment, its effect might have been refined by later adaptive mutations, each contributing minor shifts, over a long period of time." ("Species Adaptation in a Protein Molecule", 22.) For example, did a llama's hemoglobin adapt to a higher grazing altitude by increasing the oxygen affinity, or did the oxygen affinity increase and the llama then realize that it could graze higher than some other animals. This could show the "punctuated equilibria" (Biology, 296) in the evolution of a species. What Does It All Mean? After seeing all of these demonstrations of adaptation at a molecular level, you may ask what it adds to the betterment of the world. The truth is, merely knowledge. It is doubtful that the evolution-creation controversy will ever be settled, but without interest, research, and work by people in all corners of the debate, be it theological, or scientific, the answer will never be discovered. It is quite possible that neither hypothesis is correct--perhaps the truth lies in a combination of the two, or something completely different. I believe that the truth, at least a partial truth, can be found somewhere at the molecular level. If the genes, and amino acid sequences are examined, I believe that the actual evolutionary time table can be reconstructed. The human species, however, must be the last "stem" on this branch of the evolutionary tree, due to our personal views of mutations. We all see mutations as negative, when some may actually be positive. If a child is born with twelve fingers instead of ten, two are surgically removed, and the child becomes less attractive to the opposite sex, and may not get his mutated genes back into the gene pool. This process has almost always worked in the opposite way in every species up until now--the mutant with the beneficial, but different, genotype and (perhaps) phenotype has had an advantage that makes him more attractive to the opposite sex, and his genes are passed on to his offspring. One of the only mutations that could, and has, gone unnoticed is the expansion of the control of the mind. Over the hundreds of years of human existence, especially in the past few decades, the knowledge of the modern man has expanded dramatically, and now, with the ease of the internet, anyone can learn about anything imaginable. People are tired of mind-numbing thoughtless hours spent in front of the television, and are now expanding their minds in their free time. I can only hope that this paper has inspired some thought about the subject, and has brought us a small step closer to the conclusion of the debate.

Salt Pollution

As awareness for pollution increases, other forms of pollution are defined. Almost everyone knows about toxic waste and carbon dioxide pollution, but not many people have heard of salt pollution. Salt pollution has been on the increase since the evolution of the automobile. With more pressure on government agencies to keep the highway clear and safe, an increase in the use of salt has developed. It is important to understand why salt is used and how it work as well as the environmental effects to understand the salt pollution problem. Salt is a necessary and accepted part of the winter environment. It provides safety and mobility for motorists, commercial vehicles and emergency vehicles. Salt is used as the principal deicer because it is the most available and cost-effective deicer. Rock salt is preferred because it is cheap and effective. It costs 20 dollars a ton where as an alternative like calcium magnesium cost around 700 dollars a ton. Some 10 million tons of deicing salt is used each year in the U.S. and about 3 million in Canada. Salt is used to keep snow and ice from bonding to the pavement and to allow snowplows to remove. When salt is applied to ice and snow it creates a brine that has a lower freezing temperature than the surrounding ice or snow. Salt is the ideal deicing material because it is: •the least expensive deicer •easy to spread •easy to store and handle •readily available •non-toxic •harmless to skin and clothing Salt pollution is broken into two main groups. Water, which includes the effects on ground water, surface water and aquatic life and land. Most of the salt applied to the roadways eventually ends up in the ground water. It is estimated that 30% to 50% of the salt used travels into the ground water. Salt effect two areas of ground water, chloride concentration and sodium concentration. Chlorides may be present in the form of sodium chloride crystals or as a ion in a solution. Normal concentrations in the water are average around 10 mg/litre. Concentrations found in ground water near major highways have been recorded as high as 250 mg/litre which is around the threshold of taste. The main factor with ground water pollution is the risk to human health. The raised level in sodium in water can cause high blood pressure and hypertension. With people who already suffer from these problem it is necessary to keep their salt intake relatively low, they should not drink water above 20 mg/liter. Although this is recommended, a study of private well water in Toronto showed that half the wells exceeded this limit, twenty percent exceeded 100 mg/litre and six percent exceeded 250 mg/litre. This increase in sodium and chlorine can also cause problem with water balance in the human body. As well as surface water, ground water is also affected by road salting. Although the effects are not as great as ground water, they still pose problems to the environment. The problems are based on the salt ions. The salt ions interact with heavy metal that fall to the bottom of the body of water. An example of this is when sodium and chlorine ions compete for mercury to bond with. This cause the release of mercury into the water system. The risk of mercury poisoning is far greater than that of sodium or chlorine. This increase of sodium and chlorine as well as mercury and other heavy metal also cause changes in the pH of water. The increase of salt around bodies of water also effect aquatic life in the area. Two main areas that are effected are osmotic regulation in fish and the death of micro-biotic life in ponds and lakes. Most fish life can only tolerate a narrow range of salt content in the water. The increase of salt in the water produced by road de-icing cause freshwater fish to swell up with water. The increased salt cause a lower concentration of water in the fishes cells. To compensate, the fishes body takes in water to restore equilibrium. This can kill fish if the salt concentration becomes to high. Just as important as fish, microorganisms are also effected in a detrimental way. Microrganisms are tiny organism that sustain aquatic life in all bodies of water. They are more susceptible to the effect of salt pollution than fish. These microorganism are at the bottom of the food chain, when they die, it doesn't take long for the rest of the food chain to follow. Large increase in salt concentration can cause 75% - 100% death for these microorganisms, The effect of salt is almost immediate. Most of the organism are only one cell big and blow up in contact with increased amounts of salt. Water insects are also effected by the increase in salt in the environment. The number of insects lowers because the inability for water insects to reproduces in the presence of high salt concentrations. With the decreasing numbers in microorganisms, insects and fish, it is easy to see the effect it would have on the rest of the food chain even though other animal may be more salt tolerable. Salt pollution also is a major factor to land. It can also be broken up into the effects on soil, vegetation and animals. The effect of salt on soil may seem relatively less important than the other topics mentioned so far, but it leads up to more important things. The effect salt has on soil is that it alters the soil structure. Sodium chloride actually deteriorates the structure of the soil. This cause a decrease in soil fertility. In most cases calcium in the soil is replaced by sodium in a anion exchange. The make the soil less usable by vegetation. This also occurs with magnesium. This depletion of calcium and magnesium also causes the soil to increase in alkalinity with pH of nearly 10. Normal pH for the soils tested were between 5.4 and 6.6. High concentrations of sodium in the soil also makes the soil less permeable. In some case soil may be encrusted in a layer of salt. As a result, moisture content in the soil may be drastically decreased. High concentrations of salt may also cause clay to have a decreased concentration of water. This makes the clay harder and vegetation is less likely to grow. Although salt already effects the soil vegetation grows in, it also can directly effect vegetation itself. Vegetation can be dehydrate to the point of death when in contact with high levels of salt. This occurs because the osmotic stress put on the plant make it react like it was in a drought. A decrease in roots production and burns to leaf tips cause the plant to go into shock. Salt injury will also occur when plants come into contact with increased levels of salt. Salt injury is when foliage damage is present by leaf burn, die-back, defoliation and brooming. It can also cause fruit trees to have reduced quantity and quality of fruit. This occurs with only a small amount of salt comes in contact with the plant. It only take 0.5% of the plants tissue dry weight to become salt before the plant reach toxic levels. Increased chlorine levels can also cause salt injury to a plant in the same way. Salt injury also effect trees as well as small plant life. Growth of plants in also effected by the presence of sodium and chlorine. Animal are also greatly effected by roadway de-icing. Although animals tolerance to salt intake is quite high using salt for de-icing road presents unusual dangers. Moose and deer become susceptible to salt pollution because of their attraction to salt. Deer and moose are know to drink the salty water around roads. It becomes an addiction to them and reduces the level of fear when in contact with cars and people. They have also been found licking the gravel and the side of the road and even the road itself in search for salt. Small animals are effected more by the toxicity of high levels of salt. Increased levels of salt in small wildlife caused kidney hemorrhaging, depression, excitement, tremors, incoordination, coma and death. Rabbits seem to be the most susceptible because their inability to stop consuming salt. Household pets are also effected. once outside, salt collects on their feet. Pets consume a lot salt when cleaning their feet. This causes cats and dogs to get inflamed stomachs. As one can see, the effect of roadway de-icing on the environment are tremendous. The use of salt causes a great burden to both land and water. One must weigh the pro's and con's of de-icing when learn about the effects of salt on the environment.

CURRENT STATUS OF MALARIA VACCINOLOGY

In order to assess the current status of malaria vaccinology one must first take an overview of the whole of the whole disease. One must understand the disease and its enormity on a global basis. Malaria is a protozoan disease of which over 150 million cases are reported per annum. In tropical Africa alone more than 1 million children under the age of fourteen die each year from Malaria. From these figures it is easy to see that eradication of this disease is of the utmost importance. The disease is caused by one of four species of Plasmodium These four are P. falciparium, P .malariae, P .vivax and P .ovale. Malaria does not only effect humans, but can also infect a variety of hosts ranging from reptiles to monkeys. It is therefore necessary to look at all the aspects in order to assess the possibility of a vaccine. The disease has a long and complex life cycle which creates problems for immunologists. The vector for Malaria is the Anophels Mosquito in which the life cycle of Malaria both begins and ends. The parasitic protozoan enters the bloodstream via the bite of an infected female mosquito. During her feeding she transmits a small amount of anticoagulant and haploid sporozoites along with saliva. The sporozoites head directly for the hepatic cells of the liver where they multiply by asexual fission to produce merozoites. These merozoites can now travel one of two paths. They can go to infect more hepatic liver cells or they can attach to and penetrate erytherocytes. When inside the erythrocytes the plasmodium enlarges into uninucleated cells called trophozites The nucleus of this newly formed cell then divides asexually to produce a schizont, which has 6-24 nuclei. Now the multinucleated schizont then divides to produce mononucleated merozoites . Eventually the erythrocytes reaches lysis and as result the merozoites enter the bloodstream and infect more erythrocytes. This cycle repeats itself every 48-72 hours (depending on the species of plasmodium involved in the original infection) The sudden release of merozoites toxins and erythrocytes debris is what causes the fever and chills associated with Malaria. Of course the disease must be able to transmit itself for survival. This is done at the erythrocytic stage of the life cycle. Occasionally merozoites differentiate into macrogametocytes and microgametocytes. This process does not cause lysis and there fore the erythrocyte remains stable and when the infected host is bitten by a mosquito the gametocytes can enter its digestive system where they mature in to sporozoites, thus the life cycle of the plasmodium is begun again waiting to infect its next host. At present people infected with Malaria are treated with drugs such as Chloroquine, Amodiaquine or Mefloquine. These drugs are effective at eradicating the exoethrocytic stages but resistance to them is becoming increasing common. Therefore a vaccine looks like the only viable option. The wiping out of the vector i.e. Anophels mosquito would also prove as an effective way of stopping disease transmission but the mosquito are also becoming resistant to insecticides and so again we must look to a vaccine as a solution Having read certain attempts at creating a malaria vaccine several points become clear. The first is that is the theory of Malaria vaccinology a viable concept? I found the answer to this in an article published in Nature from July 1994 by Christopher Dye and Geoffrey Targett. They used the MMR (Measles Mumps and Rubella) vaccine as an example to which they could compare a possible Malaria vaccine Their article said that "simple epidemiological theory states that the critical fraction (p) of all people to be immunised with a combined vaccine (MMR) to ensure eradication of all three pathogens is determined by the infection that spreads most quickly through the population; that is by the age of one with the largest basic case reproduction number Ro. In case the of MMR this is measles with Ro of around 15 which implies that p> 1-1/Ro " 0.93 Gupta et al points out that if a population of malaria parasite consists of a collection of pathogens or strains that have the same properties as common childhood viru ses, the vaccine coverage would be determined by the strain with the largest Ro rather than the Ro of the whole parasite population. While estimates of the latter have been as high as 100, the former could be much lower. The above shows us that if a vaccine can be made against the strain with the highest Ro it could provide immunity to all malaria plasmodium " Another problem faced by immunologists is the difficulty in identifying the exact antigens which are targeted by a protective immune response. Isolating the specific antigen is impeded by the fact that several cellular and humoral mechanisms probably play a role in natural immunity to malaria - but as is shown later there may be an answer to the dilemma. While researching current candidate vaccines I came across some which seemed more viable than others and I will briefly look at a few of these in this essay. The first is one which is a study carried out in the Gambia from 1992 to 1995.(taken from the Lancet of April 1995).The subjects were 63 healthy adults and 56 malaria identified children from an out patient clinic Their test was based on the fact that experimental models of malaria have shown that Cytotoxic T Lymphocytes which kill parasite infected hepatocytes can provide complete protective immunity from certain species of plasmodium in mice. From the tests they carried out in the Gambia they have provided, what they see to be indirect evidence that cytotoxic T lymphocytes play a role against P falciparium in humans Using a human leucocyte antigen based approach termed reversed immunogenetics they previously identified peptide epitopes for CTL in liver stage antigen-1 and the circumsporozoite protein of P falciparium which is most lethal of the falciparium to infect humans. Having these identified they then went on to identify CTL epitopes for HLA class 1 antigens that are found in most individuals from Caucasian and African populations. Most of these epidopes are in conserved regions of P. falciparium. They also found CTL peptide epitopes in a further two antigens trombospodin related anonymous protein and sporozoite threonine and asparagine rich protein. This indicated that a subunit vaccine designed to induce a protective CTL response may need to include parts of several parasite antigens. In the tests they carried out they found, CTL levels in both children with malaria and in semi-immune adults from an endemic area were low suggesting that boosting these low levels by immunisation may provide substantial or even complete protection against infection and disease. Although these test were not a huge success they do show that a CTL inducing vaccine may be the road to take in looking for an effective malaria vaccine. There is now accumulating evidence that CTL may be protective against malaria and that levels of these cells are low in naturally infected people. This evidence suggests that malaria may be an attractive target for a new generation of CTL inducing vaccines. The next candidate vaccine that caught my attention was one which I read about in Vaccine vol 12 1994. This was a study of the safety, immunogenicity and limited efficacy of a recombinant Plasmodium falciparium circumsporozoite vaccine. The study was carried out in the early nineties using healthy male Thai rangers between the ages of 18 and 45. The vaccine named R32 Tox-A was produced by the Walter Reed Army Institute of Research, Smithkline Pharmaceuticals and the Swiss Serum and Vaccine Institute all working together. R32 Tox-A consisted of the recombinantly produced protein R32LR, amino acid sequence [(NANP)15 (NVDP)]2 LR, chemically conjugated to Toxin A (detoxified) if Pseudomanas aeruginosa. Each 0.4 ml dose of R32 Tox-A contained 320mg of the R32 LR-Toxin-A conjugate (molar ratio 6.6:1), absorbed to aluminium hydroxide (0.4 % w/v), with merthiolate (0.01 %) as a preservative. The Thai test was based on specific humoral immune responses to sporozoites are stimulated by natural infection and are directly predominantly against the central repeat region of the major surface molecule, the circumsporozoite (CS) protein. Monoclonal CS antibodies given prior to sporozoite challenge have achieved passive protection in animals. Immunisation with irradiated sporozoites has produced protection associated with the development of high levels of polyclonal CS antibodies which have been shown to inhibit sporozoite invasion of human hepatoma cells. Despite such encouraging animal and in vitro data, evidence linking protective immunity in humans to levels of CS antibody elicited by natural infection have been inconclusive possibly this is because of the short serum half-life of the antibodies. This study involved the volunteering of 199 Thai soldiers. X percentage of these were vaccinated using R32 Tox -A prepared in the way previously mentioned and as mentioned before this was done to evaluate its safety, immunogenicity and efficacy. This was done in a double blind manner all of the 199 volunteers either received R32Tox-A or a control vaccine (tetanus/diptheria toxiods (10 and 1 Lf units respectively) at 0, 8 and 16 weeks. Immunisation was performed in a malaria non-transmission area, after completion of which volunteers were deployed to an endemic border area and monitored closely to allow early detection and treatment of infection. The vaccine was found to be safe and elicit an antibody response in all vaccinees. Peak CS antibody (IgG) concentrated in malaria-experienced vaccinees exceeded those in malaria-naïve vaccinees (mean 40.6 versus 16.1 mg ml-1; p = 0.005) as well as those induced by previous CS protein derived vaccines and observed in association with natural infections. A log rank com parison of time to falciparium malaria revealed no differences between vaccinated and non-vaccinated subjects. Secondary analyses revealed that CS antibody levels were lower in vaccinee malaria cases than in non-cases, 3 and 5 months after the third dose of vaccine. Because antibody levels had fallen substantially before peak malaria transmission occurred, the question of whether or not high levels of CS antibody are protective still remains to be seen. So at the end we are once again left without conclusive evidence, but are now even closer to creating the sought after malaria vaccine. Finally we reach the last and by far the most promising, prevalent and controversial candidate vaccine. This I found continually mentioned throughout several scientific magazines. "Science" (Jan 95) and "Vaccine" (95) were two which had no bias reviews and so the following information is taken from these. The vaccine to which I am referring to is the SPf66 vaccine. This vaccine has caused much controversy and raised certain dilemmas. It was invented by a Colombian physician and chemist called Manual Elkin Patarroyo and it is the first of its kind. His vaccine could prove to be one the few effective weapons against malaria, but has run into a lot of criticism and has split the malaria research community. Some see it as an effective vaccine that has proven itself in various tests whereas others view as of marginal significance and say more study needs to be done before a decision can be reached on its widespread use. Recent trials have shown some promise. One trial carried by Patarroyo and his group in Columbia during 1990 and 1991 showed that the vaccine cut malaria episodes by over 39 % and first episodes by 34%. Another trail which was completed in 1994 on Tanzanian children showed that it cut the incidence of first episodes by 31%. It is these results that have caused the rift within research areas. Over the past 20 years, vaccine researchers have concentrated mainly on the early stages of the parasite after it enters the body in an attempt to block infection at the outset (as mentioned earlier). Patarroyo however, took a more complex approach. He spent his time designing a vaccine against the more complex blood stage of the parasite - stopping the disease not the infection. His decision to try and create synthetic peptides raised much interest. At the time peptides were thought capable of stimulating only one part of the immune system; the antibody producing B cells whereas the prevailing wisdom required T cells as well in order to achieve protective immunity. Sceptics also pounced on the elaborate and painstaking process of elimination Patarroyo used to find the right peptides. He took 22 "immunologically interesting" proteins from the malaria parrasite, which he identified using antibodies from people immune to malaria, and injected these antigens into monkeys and eventually found four that provided some immunity to malaria. He then sequenced these four antigens and reconstructed dozens of short fragments of them. Again using monkeys (more than a thousand) he tested these peptides individually and in combination until he hit on what he considered to be the jackpot vaccine. But the WHO a 31% rate to be in the grey area and so there is still no decision on its use. In conclusion it is obvious that malaria is proving a difficult disease to establish an effective and cheap vaccine for in that some tests and inconclusive and others while they seem to work do not reach a high enough standard. But having said that I hope that a viable vaccine will present itself in the near future (with a little help from the scientific world of course).

EBOLA

Imagine going on vacation to a foreign country and when youcome home you are horribly sick. Your head hurts, you have a highfever, and you start vomiting. Chances are that you may havecontracted the Ebola virus. Ebola was first discovered in the village of Yambuku(1) nearthe Ebola River in Zaire. Since its discovery, there have beenfour outbreaks of this disease. There are three known strains, ofvariations of ebola. There is no known cure for this disease(2).Ebola has become one of the most mysterious and feared viruses onthe face of this earth. Ebola's first documented appearance was in Zaire in 1976. Noone knows where ebola comes from or what the original host is.However, scientists know that man is not ebola's natural host(3).The host was first suspected of being carried by monkeys in theAfrican rain forests(4), but in one case the monkeys at a holdingfacility broke out and had to be killed. In the pursuit of a cure and an origin, there have beenseveral teams of scientists whose top priority is to find theviruses origin(5). The teams have trekked through the rainforests of Africa to collecting different species of animals,bugs, and plant life. Bugs are also collected from the hospitalsand from the surrounding huts of the villages. So far 36,000specimens have been collected. Once they have been gathered, thespecimens are put into liquid nitrogen and flown back to theUnited States, where they are studied at the Centers for DiseaseControl in Atlanta Georgia and the Army Medical Research Instituteof Infectious Diseases at Fort Detrick Md.,(6). Researchers havediscovered the source of human infection for all level fourorganisms except ebola(7). This means that all organisns thatcause deadly viruses have been contained and studied, and have hadantibodies created to ward of the illnesses that are caused. Although Ebola is a mystery to humans, the virus isrelatively hard to catch and it kills quickly, lessening thechance victims will infect others. It is transmitted by contactwith bodily fluids like blood, vomit and semen or contaminatedsyringes and is not known to be passed along through casualcontact(8). When the first outbreak of ebola occurred, it was in 1976 inZaire and in Sudan at the same time. There were 318 casesreported in Zaire and 240 of those cases proved to be fatal. InSudan, there were 284 cases and 134 of those cases proved to befatal. In 1979, there was another small epidemic in the sameregion of Sudan. In 1989 there was a breakout in Reston Virginia,at a monkey holding facility, that killed over 400 monkeys thathad been shipped from the Phillines. This strand however, is onlylethal to monkeys and id not a threat to humans(9). In 1995, therewas an outbreak in Kikwit Zaire that claimed 233 lives. At least7 people survived that outbreak becauses of a new breakthroughthat is a possible solution to the loss of lives that are sufferedin a outbreak. Blood from one surviving patient can be transfusedto a person of the same blood type to possibly save the personslife. Such was the case in 1995(10). Scientists were able tofind who the first person to contract the virus was in 1995. Theman's name was Gaspard Menga. Menga infected his family, and hisfamily infected others(11). Menga is known as the index patient.The reason it is so important to have the index patient is thatthis way they can trace the patients movements and try to find theorigin of the virus. Scientists are now arguing that if therewasn't so much interference with the rain forests that therewouldn't be new diseases emerging all the time(12) The most recent outbreak happened in January of 1996 in asmall village in inland Zaire. Two children were playing when thecame upon a dead chimpanzee and they took it back to the villagewhere the villagers celebrated for the finding of such a wonderfulthing. The reason this was so celebrated was because meat is rarein that village. Anyone who helped clean or cook the animalbecame ill with the deadly ebola virus. The final death count was16 people. Villagers have been warned not to eat any animals thatthey find already dead and to be careful not to eat any sickanimals that they may encounter. Scientists now believe that monkeys are not the original hostbecause they seem to just as susceptible to the disease as humans.Scientists are hoping that they will make some substantialdiscoveries with this outbreak.(13) Scientists do know that ebola is a strand of sevenproteins(14) that belongs to a family of viruses calledfilovirusus. The virus consists of a shell of proteinssurrounding genetic material. The virus attaches itself to a hostcell, and changes the chemicals makeup to fit its own so that itcan reproduce(15). Ebola is a hemorrhagic virus that has a short incubationperiod of about two days to two weeks(16). It causes high fever,chills, internal and external bleeding, vomiting, the eyes turnred and the skin becomes blotchy and bruises appear. The surfaceveins and arteries erode. Organs liquify and blood flows fromevery opening in the body including the eyes and ears(17). Thisis followed by a painful death that usually occurs within threeweeks(18). There are three known strains of The virus. Ebola Zaire,ebola Sudan, and ebola Reston. Ebola Zaire is the most lethal ofthe three followed by ebola Sudan and then ebola Reston. EbolaReston is the least worried about because it has not proved to behostile to humans. The question of whether or not this virus could becomeairborne has struck fear in many. Scientists say that it isunlikely that it will become airborne, because it is killed byultraviolet rays within seconds. The only way that it couldsurvive is if it mutated to become resistant to ultraviolet rays. At this point, a person is more likely to contract HIV thanit is to contract the ebola virus, although it takes ten years toaffect a person the way ebola does in ten days. Even though ebola is a very mysterious and feared disease, itis in the process of becoming more understood. It can destroy anentire city in a matter of weeks, and could wipe out an entirenation if it ever became airborne, but it is a very difficultdisease to contract so the united states is probably safe from anynear future epidemics. On the other hand many third worldcountries could have serious problems if there is an outbreak dueto unsanitaryliving and medical conditions. The hospitals and medicalpersonnel reuse needles that have been infected and they don't uselatex or any other kind of gloves which can be a cause of widespread sickness. Everyone hopes that diseases like ebola will notget out of control before a cure can be found. Such hopes seemunreasonable due to the facilities available in some areas of theworld. lable in some areas of theworld.