2nd paper

Anthrax

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Biological warfare is the use of bacteria, viruses, or toxins to destroy things such as people or crops. The use of biological toxins extracted from plants and animals on arrow heads or poison darts to kill enemies and prey predates recorded history as we know it [1]. This technology is still being used by some African and South American cultures. In the developing world, there are many forms of biological (germ) warfare. Anthrax is one of the oldest recorded diseases used in biological warfare. It has infected animals such as cows, sheep, and other grazing herds. It has also affected humans who work with these animals and their by parts [2].

Cases of humans using biological warfare have been well recorded in history. During the middle ages, it was common to catapult dead bodies infected with smallpox or the bubonic plague over opposing city walls in battle [1]. In 1763, British troops gave Indians blankets used by people with smallpox. Japan contaminated food and released plague-infected ticks during their conflict with China during World War 2 [3]. In 1969 President Nixon terminated the U.S. biological weapons program. The program had two lethal biological agents, Bacillus anthrax and Francisella tularensis (tularemia), these were already standardized and weaponized [1]. Bacillus anthracis is the bacterium that causes anthrax [2]. In 2001, an anthrax letter in the United States infected twenty-two people and killed five [3].

Several differences set biological weapons apart from other weapons of mass destruction like nuclear and chemical weapons. Biological and chemical weapons share characteristics that are distinct from nuclear weapons [4]. The materials needed to create a weapon can be easily acquired because they either have other legitimate uses or occur in nature. An aspect that differs biological and chemical weapons is that once the agent is released it may not be immediately detectable [3]. There are systems that detect biological agents, but most have a delay between acquiring the agent and identifying it. The effects of an attack are not immediately detectable. People may become exposed to an agent soon after its release, but the infection requires time to cause illness. Thus, one of the first indicators of a biological weapon attack could be the outbreak of the disease [3].

Anthrax is commonly found in the ground or on a surface. Anthrax spores are relatively harmless, but once they come into contact with the right environment they begin to germinate. They need an environment that is rich in amino acids, nucleotides and glucose. These elements are also found in the blood and other tissues in humans and animals [2]. Anthrax can enter the body through the intestines through ingestion, the lungs through inhalation, or skin through cuts. An infected human will usually be quarantined. However, anthrax usually does not spread from an infected human to a non-infected human [5]. Repertory infection comes with cold or flu-like symptoms followed by severe respiratory collapse. This disease can rarely be treated, even if it is caught in early stages of infestation. Inhalation of anthrax is almost 100% fatal [5].

Intestinal infection is most often caused by eating anthrax-infected meat. It is characterized by serious intestinal difficulty, vomiting of blood, severe diarrhea, acute inflammation of the intestinal tract, and loss of appetite. Some lesions have been found in the intestines and in the mouth and throat. After the bacterium enters the bowel system, it spreads through the bloodstream throughout the body, making even more toxins on the way. Intestinal infections can be treated but usually result in fatality rates of 25% to 60%, depending upon how soon treatment begins.

Anthrax that shows up as a boil- like skin lesion that eventually forms an ulcer with a black center. The black center often shows up as a large, painless, ulcer, beginning as an irritating and itchy skin lesion or blister that shows up as a black dot at the site of infection. This type of infection is the least fatal form of anthrax infection if treated. But without treatment, approximately 20% of all types of the skin infection cases may progress to toxemia and death [5].

Viewed at the cellular level, an anthrax bacterium looks like a jointed rod. When it enters the body and finds the environment it needs, it moves to the lymph nodes. From there it begins to multiply and produce a toxin that attacks human cells resulting in swelling, a drop in blood pressure, and ultimately death [2].

The way it attacks the cells and exactly what it does, was in question for many years. In the mid 1980s, some interesting facts about the behavior of the anthrax bacterium when it finds a host were discovered. Researchers found that there are three proteins that are created by the anthrax bacteria. These proteins are harmless individually, but together can be deadly. These proteins are referred to as: Protective antigen (PA), Edema factor (EF), Lethal factor (LF) [2].

The Protective Antigen is the main part of the three part toxin we know as anthrax. After the PA activation on the surface of the cell, it forms a membrane inserter called the heptamer. The heptamer transfers the toxic enzymes. The Protective Agent can also translate other heterologous proteins[6]. The protective antigen is made up of anti-parallel beta sheets with four domains. The amino-terminal domain has two calcium ions and a proteases activation site. The heptamerization domain has a large loop in the membrane insertion. The third domain has an unknown function. The carboxy-terminal receptor-binding domain is also one of the four domains.

The lethal factor is a zinc dependent that creates a specific bond in signaling proteins, which also destroys the signaling ability [7]. Proteins of the mitogen-activated protein kinase family, gets cleaved by the lethal factor. The crystal structure of the lethal factor is very complex.

The edema factor is a calmodulin-dependant. It is the main factor in the skin infections of anthrax. The role of the edema factor has been uncovered by the crystal structure, coupled with calmodulin. When it enters the cell, it creates more AMP and complexes the calmodulin [7].

When these proteins are released, the protective antigen binds to the cell surface and forms a channel in the cell membrane that allows the edema factor and lethal factor to enter the cell. The edema factor, combined with the protective antigen, forms a toxin known as the edema toxin. The lethal factor, when combined with the protective antigen, forms a toxin known as the lethal toxin. It is the lethal toxin that does the most damage within the cell [2]. With what we know about anthrax, we can now cure 70% of all anthrax infections.

Blog from a while ago because i could not log onto the site

I thought the trip today to the community care center was both interesting and informative. It was a good combination of both biology and entrepreneurship, which are obviously two of the main topics of this class. It was cool to see a business run in a very unconventional way. Especially something as important as health care. I thought it was interesting that this actually worked very well. I am from Connecticut and I really don’t think this type of establishment could last in the north. There would be volunteers but it would be tough to get stuff donated and especially the charge ay the door. A lot of people would take advantage of the situation and it would be packed all the time. All in all I think it was a well designed field trip for the curriculum and you should continue to bring classes there.

Paper 2

Nick Oropall

FYS-Jed Macosko

3/5/08

Chris Chemokine

It seemed as if order was finally restored and the body was safe once again. Chris Chemokine and the rest of the body had learned a lesson they would not soon forget. To fully understand the story we’ll have to start at the beginning, before the invasion…

The body was always a good place to live, and was pretty well protected so all the cells and other residents were able to live care free and do their jobs. A large reason why this worked so smoothly was Chris Chemokine. His job was perhaps the most important of all, because he had a large control over many cells including the immune system. Chris was in charge of telling the cells where to go, growing new blood vessels, and inflammatory action in order to protect against bacteria, viruses and heal wounds. Chris was smart, he was good looking, and he was very good at his job. None of this seems as if it would be a problem, but it was. The problem was Chris knew this all too well. He was the cockiest resident in the body and believed he was better than everyone else. This didn’t stop the citizens of the body from applying for jobs with Chris. Although he may be conceited at times, he was still very good at his job and everyone felt they could learn a lot from him. Every day there would be a line of people outside his office waiting for interviews, and every day they would be turned away. When it came to getting jobs done Chris never asked for help and would never accept it if it was offered. He thought he was too good for help, and that it could only bring him down. Truth was that he really had never needed help, until one day, the day that leads us onto our adventure.

Chris’ day began as every other day of his life began. He woke up and got ready for his day while he admired himself in the mirror. Chris headed over to his office and sure enough there was a line of eager citizens waiting to interview for an intern position with the famous Chris Chemokine. He grumpily told them all to go away and that he didn’t need any help. A few minutes later as they all reluctantly walk away with their heads down, the mob clears and one teenage resident is left standing alone. “I said I don’t need any help”, Chris said as he waved the boy off.

The boy refused to leave without saying a word. Chris threatened to call security, but still nothing. “I like your persistence, but I don’t need help from anyone, therefore I don’t need to help anyone”, Said Chris, trying to break the young mans spirit.The man in the doorway slowly walked away with his head down while Chris carried on with his day as usual

It’s amazing how he could just carry on his day without even thinking about that young man waiting for an interview. However, he managed to do it and the beginning of the day went as usual. There were a few minor scrapes that he had to lead the immune system cells to in order to induce the inflammatory response, and even a scare of some bacteria. But besides that the day ran smoothly and Chris felt on top of the world, as always. Even though he didn’t know that Chris’ day and even life were going to change, and he was going to learn a lesson he would never forget.

The body was a small town, people knew each other, and they knew each others business. When somebody did not belong, everyone knew it. That day there was a new person in the body, he introduced himself to everyone as Clyde Cancer. He seemed a little interesting and not too different looking yet there was something about him. Something made the citizens a little uneasy about Clyde. However, there was one person who was not at all bothered by or worried about Clyde. Of course, it was Chris Chemokine. Some of the people that were worried called Chris and asked if there was anything they should do or if there was anything he could do to help. Chris would simply shrug the people off because he thought they were overreacting and he didn’t think it was a problem. He had even met Clyde and thought he was a little interesting, but Chris was too blinded by himself to realize that something was about to go terribly wrong in the body.

Over the next few days weird things started to happen, and no one knew what the cause was. The population of the body was growing rapidly because cells were reproducing much faster than normal, and many of the cells were even much different looking than they normally do. Everyone was concerned and looked to Chris for help. After all it was his job to regulate many of the cells activities. The interesting thing was that during this period Clyde had gone in and talked to Chris many times about having him regulate these cells. However, Chris was convinced that Clyde was a normal cell.

The whole body went into panic mode and people were going crazy, no one knew what to do. These cells were growing a dividing so quickly that the population was going haywire. The townspeople begged Chris to watch Clyde, because this problem had occurred since the day he arrived in the body. Chris continued to refuse, he could never be wrong. He was convinced that Clyde was normal and that everyone was overreacting. In the meantime Chris was doing everything he could to keep this growth and division under control, but there was nothing he could do.

One day Chris suddenly realized that his worst nightmare was coming true. He woke up from his sleep one night to find Clyde Cancer using his abilities in order to divide cells more quickly. Everyone was right Clyde was behind the rapid cell division. Chris couldn’t believe he missed something like this. “But why was Clyde doing this?” Chris wondered.

Then it hit him. The cell divisions, the mutations and changed cells, it was all part of Clyde’s plan to take over the body. Clyde was causing the body to uncontrollably divide mutated cells and he had been using Chris the entire time without him knowing! Chris jumped up and confronted Clyde about the situation. “So what? If you figured me out” said Clyde. “I have been using you this entire time to aid in my evil plan and now there is nothing you can do to stop me. I even created a base of operations ‘The Tumor”. Chris was not quite sure what to do but he figured he could do what he always did, try to go out and save to body on his own, after all he was Chris Chemokine.

He started his normal routine to fix the body. He told the immune system cells where to go and what to do. He thought he was getting some progress done, but Clyde was right. He had already built an army, and his base was too powerful. Whenever he tried to help or fix something it only got worse, Clyde was using Chris to divide the cells and make more mutations. Nothing Chris could do would help, no matter how hard he tried Clyde’s army could withstand it.

Chris panicked, for the first time in his life he actually did not know what to do. What if Clyde was right, what if there really was nothing he could do and his evil plan was going to be a success? The whole body would die, and Chris would be the man responsible for it all. He should have listened to some people; he should have listened to everyone. For once in his life, Chris knew he needed help.

Then out of nowhere, as if it was a miracle, someone showed up. It was a young man who Chris recognized. It was the young man who stayed in the doorway in the morning. Chris asked what his name was, he responded “Alex Allostery.” Clyde didn’t seem too amused, He reiterated that he was using Chris in order to make new cells and no matter what he did the army would keep expanding and there was nothing that he nor this puny little man could do to stop him.

“Not so fast!” Alex exclaimed. He began to explain to Chris how he could block Clyde from using Chris to divide more cells. In order for Clyde to divide he needed to enter a specific place on Chris like a key into a keyhole. Once this “lock” was unlocked, he could use Chris as he pleased. Alex could enter Chris at a different point and this would change the shape of the keyhole Clyde and his troops needed to enter. Therefore, the key no longer fit the keyhole. It was brilliant. Once they could get Clyde to stop dividing they could take care of the rest of his troop on their own, as Chris normally did.

Alex’s plan worked to perfection and once Clyde could no longer divide, Chris was able to destroy the rest of his army using the immune system. The day was saved, and it was not only thanks to Chris, this time a lot of the thanks was due to someone else, Alex Allostery. The town of the body was so pleased with both of them that they threw them a celebratory parade of red blood cells. The most important part was that Chris had learned his lesson, and would never work without a partner again. His new partner was Alex Allostery.

Sources

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX3-47FFRNR-6&_user=793338&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000029698&_version=1&_urlVersion=0&_userid=793338&md5=f3499f79dd412feff9a72df931f91143

http://molpharm.aspetjournals.org/cgi/content/full/73/3/855

http://en.wikipedia.org/wiki/Allosteric

http://www.blackwell-synergy.com/doi/abs/10.1111/j.1747-0285.2006.00330.x

http://en.wikipedia.org/wiki/Chemokine

Paper 1

Nick Oropall

FYS

12/10/08

Chemokines: Cancer’s Nemesis?

Solution structure of interleukin-8, a chemokine of the CXC subfamily

Cells, the so called building blocks of life, are comprised by something smaller, something more complex. Molecular machines control many activities in the cell in surprisingly robotic or even humanistic ways. From molecular tweezers, which can hold guests between its arms, to molecular sensors which interact with abnormalities in order to make it recognizable, there are all types of molecular machines for all types of jobs. Simply put, be it the most feasible or complex jobs within a cell are done by one or a grouping of molecular machines. Though scientists have created methods to halt and even cure types of cancers, the power of bionanomachines has yet to be completely harnessed in the fight against cancer. The key to unlocking this enigma may lie in a type of protein called a Chemokine.

Chemokines come from a grouping of proteins secreted by cells, otherwise known as cytokines. Chemokines are classified as proteins that have characteristics such as small size and a three dimensional shape due to the presence of four cysteine residues. Chemokine can be categorized into four groups but overall they fit into two basic groups: pro-inflammatory and homeostatic. They can be found in many types of living organisms such as all vertebrate and some viruses and bacteria, yet none have been found in any invertebrate. The pro-inflammatory can promote cells of the immune system to a site of infection during an immune response. The homeostatic are responsible for controlling the movement of cells during tissue maintenance or development. The chemokines biological effects are shown when they interact with chemokine receptors found on the surface of their target cells.

Proteins are not just classified into the chemokine family because of their ability to attract cells. They are put into the category based on their structure. One defining characteristic is that chemokines are all very small. Chemokines have 20-50% in common with each other. This means that their amino acids are very similar and put in a similar order. Every chemokine also contains the amino acids necessary to form its three dimensional (tertiary) structure. Generally these amino acids are four cysteines. These cysteines work in pairs to form the “greek key” shape that is a major characteristic in chemokines. Each cystein is put in a specific place. The first and second are located near the N-terminal end. These two are the only two that are close together. The third is found near the center of the molecule. Finally, the fourth is found near the C-Terminal end. The first two cysteines have a loop of approximately ten amino acids that follow them called the N-loop. The chemokine then gets even more complex and the N-loop is followed by more loops called the 30s, 40s, and 50s loops. These loops are made of a single-turn helix, called a 310-helix, three β-strands and a C-terminal α-helix. The third and fourth cysteins are found in the 30s and 50s loops.

If the protein was not shaped the way it was it would not be able to bind with its receptors and carry out its jobs. In order for a chemokine to bond to a receptor it has to mold to fit the shape. This molding would not be possible without the flexible N terminus. This conformation completed by the N terminus allows the chemokine to fit the shape of the receptor and carry out activation. There are many different variations of chemokines but because of their largely identical shapes and amino acid patterns they all function in almost the same way.

The most important and main function of chemokine is to control migration of cells. The homeostatic chemokines are secreted without any need to stimulate its source cell. These chemokines “round up” the cells of the immune system and bring them where they need to be in order to aid in immune response. Lymphocides and lymph nodes are an example of the cells of the immune system the homestatic chemokines control. The lymphocites and lymph nodes screen for pathogens residing in tissue. A second job of chemokine is to control the growth of new blood vessels, otherwise known as angiogenesis. Along with the growth of new blood vessels chemokine is also in control of cellular maturation. Like the foreman of a job chemokine guides cell tissues which in tern provide the specific signals necessary for cellular maturation. Inflammatory chemokines which provide possibly the most relevant job are key to the immune system and immune response. Inflammatory chemokines are released from a plethora of cells in order to combat bacterial infection, viruses, and anything in general harming the body. Specific inflammatory chemokines trigger cells to begin the immune response as well as promote wound healing.

In many types of cancers there is an extensive chemokine network. It is very likely that these networks influence the growth and behavior of angiogenesis, the leukocytes, tumor cell growth, and migration. The presence of leukocytes in both tumor and stromal cells can be attributed to chemokines. Although there is an abundance of chemokine in epithelial tumors, there has been no discovery of chemokine receptors on the infiltrating leucocytes. However, in certain forms of ovarian cancer there have been an abundance of chemokine receptors found on leukocytes.

In certain types of tumors, chemokine doing its job may be directly contributing to the problem. As the foreman of the job chemokine controls the movement of cells and calls cells to “worksites.” It’s possible that certain cells the chemokine attracts not only do not help, but may even contribute to the immunosuppressive environment. Another example of how chemokine doing its job may be promoting the opposite affect than originally intended is with its abilty to promote cell growth. Excessive chemokine receptors have been found in melanoma cells which may mean that chemokine is actually contributing to the tumor’s growth and survival. Chemokine receptors such as CCR7 have been found on many different cancerous cells, which lead scientists to believe that chemokine could be a definite aid to tumors.

Although there is certainly a recipe for disaster with the combination of chemokine and cancer, there is also a bright light for success. This could prove to be a difficult task, yet, in order to fight cancerous cells and tumors, chemokine’s control over cells would need to be harnessed. If the chemokine did not attract the leukocytes to inhibit the cancerous cells it could prevent angiogenesis, survival and spread of tumor cells. Another method to halt the development of cancerous cells would be to decrease the amount of chemokine or chemokine receptors. In order for chemokine to fully function it needs its receptor and it would have nothing to affect if there were no leucocytes. The three need to be present in order to have an affect so the depletion of one would be sufficient to inhibit growth of cancerous cells. Coincidentally, another approach that has been tested that would not involve directly affecting the work the chemokine does, is by overflowing the cancerous cell with chemokine. Over expression of certain chemokine types can suppress tumor growth, by attraction dendritic cells which activate tumor specific cytotoxic T lymphocytes.

The full extent of chemokines and their work on cancer has not been completely explored, yet, further research is certainly warranted, and will yield positive results. With work the power of molecular machines in general can be used to achieve and aid in many things. Chemokine in particular has serious potential involving the immune system, and experiments already suggest that it can aid in not only the fight against cancer but also against HIV.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WWY-4C9HJ21-5&_user=793338&_coverDate=06%2F30%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000029698&_version=1&_urlVersion=0&_userid=793338&md5=a9b33661e2e30c402694238ebbd12f5b

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T1B-42P62MN-N&_user=793338&_coverDate=02%2F17%2F2001&_fmt=full&_orig=search&_cdi=4886&view=c&_acct=C000029698&_version=1&_urlVersion=0&_userid=793338&md5=72550f23c961c543e06015651696766e&ref=full

http://en.wikipedia.org/wiki/Chemokine

http://en.wikipedia.org/wiki/Cancer

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WX3-47FFRNR-6&_user=793338&_coverDate=02%2F28%2F2003&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000029698&_version=1&_urlVersion=0&_userid=793338&md5=cd3be7f6cf40d17c828a96353f55d662

2nd Paper

HPV, a new epidemic

Cancer is a very frightening disease. It seemingly targets people at random, striking them down with ease. The survivors are hailed above many others for the ordeal they have gone through. Many cancers may be caused by a single mistake in the coding in the DNA of one cell. Cervical cancer, on the other hand, is caused by a virus, HPV. HPV, Human papillomavirus, is a category of viruses that contains more than 100 similar viruses. Some forms of HPV cause warts or papillomas that are generally benign or non cancerous. The issue with HPV comes from the more than 40 types that are genital HPV. They are passed through the same methods as STIs. Some of these HPV strands merely cause warts whereas others can cause cervical or other rarer types of genital cancer. Cervical cancer is developing into one of the biggest health threats to women today.

In the United States around 11,070 women will be infected with cervical cancer and 4000 women will die from cervical cancer in 2008 alone according to the American Cancer Society. This presents HPV as a clear threat in the US, but also it threatens countries beyond its borders. Around the world cervical cancer is the third most common form amongst women. Around 500,000 women will develop it each year with about half (274,000) dying as a result of the cancer.[1] In the United States the number of cases that continue to death is reduced in comparison to many nations because of the large number of options for treatment in the US that are no available in other nations.

The problem with HPV is not that there is no treatment. There are methods of identification, treatment, and prevention, but they are only available in some places in the world. These methods target the most virulent and dangerous forms of HPV. HPV-16 and HPV-18 are the two major cervical cancer causers and may account for as much as 70% of cervical cancer cases globally. [1] Despite the imminent threat posed by this virulent strand there is hope. A vaccine has been developed that effectively prevents HPV 16 and 18 from changing the cells to cause cervical cancer. To understand how this takes place, a closer look at how HPV infects cells is necessary.

TP53 Website

When HPV infects a cell two E6 and E7 proteins act as oncoproteins.[2] Oncoprotein is simply a term to establish the E6 and E7 proteins as cancer causing factors. These proteins coded in HPV 16 and 18 play a role in the development of cervical cancer upon contraction of the HPV virus. E6 works by negating the effects of the p53 tumor suppressor protein.[3] P53, protein 53, functions in cell regulation causing it to be a cancer suppressant. When a cells DNA is damaged by any means p53 causes repairs to take place or tells the cell to destroy itself. When p53 is damaged or inactivated the potential for cancer development is much higher. E6 binds to p53 and causes it to be inactive removing part of the cells tumor suppression.[4]

E7 proteins also affect the infected cell. They bond to Rb tumor suppressors preventing them from functioning. Rb plays a key role in regulation of cell proliferation, survival and differentiation, and regulates cellular division. [5] The combined affect of both E6 and E7 proteins drastically reduces the host cell’s ability to prevent its transformation to a cancerous cell, which may potentially for a carcinogenic tumor.

Not only do E6 and E7 play a vital role in the disabling of human cell’s cancer defenses, they also play a vital role in the life of the HPV virus. Later in the viruses infection process they play instrumental roles in the stability of different portions of the virus. It has bee shown that a mutated E7 protein in HPV16 affects the viruses ability to amplify its DNA in later infection processes.[2] Also it has been discovered that E6 and E7 cause polyploidy in human keratinocytes.[6] This process directly contributes towards the progression of cancer.

When the tumor suppressors are turned off in HPV target cells they can cause cancer. It is how these proteins can be stopped from disabling the cells regulation devices that holds the key to prevention. There are many supposed methods of treating HPV and preventing it, but the most exciting is the HPV vaccine. Two vaccines on the market in the US and other countries, produced by Gardasil and Cervarix, are being used to target the sexually transmitted strands of HPV.

VLPs assembled from L1 protein of HPV-16~~CDC, HPV and HPV Vaccine

The vaccine is made up of virus-like particles(VLPs) that are assembled from HPV.[7] HPV16 and 18 are the two strands that it mainly targets.[7] The goal, as with most vaccines, is to create an immune response to a non lethal threat in order to develop the body’s natural defenses before an actual assault. With antibodies present HPV strands will find it difficult to infect the cells and thus will not be able to cause cervical cancer.[8] Although one problem is that the antibodies generated by VLPs are extremely type specific and will only affect particular strands of the HPV virus. It’s not too much of an issue because HPV-16 and HPV-18 account for around 70% of cervical cancer cases and therefore if only those were prevented it would put a large dent in cervical cancer cases world wide.

This process by which HPV works and how the vaccine developed will allow prevention provided continued treatments as its viable protection period is only 4.5 years. [8] The vaccine is a major contribution towards a reduction in the cases of cervical cancer and HPV infections in the US. The problem is the ability to fight HPV in third world countries, who account for more than 80% of the cervical cancer deaths in the world[1]

There are many sources to the inability to properly treat these countries. Money and government distrust are just a couple. Money is one of the larger factors. If the vaccine would be able to make it to a third world country the price of the treatments to provide the immunity would need to be drastically marked down compared to US standards. A price close to $1 or $2 would be more viable for regions that have very low per capita, making the vaccine affordable.[1] Another big issue is the competition amongst importance of vaccinations in the developing nations. There is conflict amongst whether the prevention and treatment of the wide spread of STIs, such as HIV, is more important than the treatment and prevention of HPV.

The vaccine should be given to girls before they reach an age of active sexual activity. Once HPV has been contracted the vaccine cannot fight it, but merely prevent the infection of other strands of HPV. In the United States girls around age 12, before sexual activity, should be vaccinated in order to prevent the infection.[1] In an attempt to develop better methods of distributions over cultural barriers, Merck and GlaxoSmithKline recently received a 27.8 million dollar grant from the Bill and Melinda Gates Foundation to research methods of better distribution of HPV vaccine throughout developing nations. [9]

HPV is a problem, but it has a solution. Like many diseases before it a manmade vaccine is able to provide immunity to the most dangerous strands, HPV16 and HPV18. By the activation of an immune response to dead HPV cells the body develops immunity. The oncoproteins E6 and E7 will not have a chance to block the effectiveness of P53 and rb tumor suppressors. This will lessen the threat of cervical cancer to the female population on not only the US, but the whole world. If programs and projects can be developed to spread the vaccine to the farthest corners of the globe HPV may be put in the past as another disease that man has nearly eradicated from the earth, though this disease will also be removed from developing nations also.

1. Agosti, J.M. and S.J. Goldie, Introducing HPV vaccine in developing countries--key challenges and issues. N Engl J Med, 2007. 356(19): p. 1908-10.

2. Oh, S.T., M.S. Longworth, and L.A. Laimins, Roles of the E6 and E7 proteins in the life cycle of low-risk human papillomavirus type 11. J Virol, 2004. 78(5): p. 2620-6.

3. Huibregtse, J.M. and S.L. Beaudenon, Mechanism of HPV E6 proteins in cellular transformation. Semin Cancer Biol, 1996. 7(6): p. 317-26.

4. Zamzami, N. and G. Kroemer, p53 in apoptosis control: an introduction. Biochem Biophys Res Commun, 2005. 331(3): p. 685-7.

5. Wenzel, P.L., et al., Rb is critical in a mammalian tissue stem cell population. Genes Dev, 2007. 21(1): p. 85-97.

6. Patel, D., et al., Human papillomavirus type 16 E6 and E7 cause polyploidy in human keratinocytes and up-regulation of G2-M-phase proteins. Cancer Res, 2004. 64(4): p. 1299-306.

7. Lowy, D.R. and J.T. Schiller, Prophylactic human papillomavirus vaccines. J Clin Invest, 2006. 116(5): p. 1167-73.

8. Harper, D.M., et al., Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine against human papillomavirus types 16 and 18: follow-up from a randomised control trial. Lancet, 2006. 367(9518): p. 1247-55.

9. Studying HPV Vaccine Rollout Barriers In Developing Countries Is In Merck's, GSK's Self-Interest, Editorial Says. 2006 3/7/2008 [cited; Available from: http://www.medicalnewstoday.com/articles/46492.php.