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What would happen in the world, if we had unlimited possibilities, unlimited research? A world where we could simply cure every disease, and every damaged organ.
Good morning ladies and Gentlemen. This future I have presented to you, seems like a dream doesn't it? Nothing could ever be that simple right? Well you're right nothing could ever be that simple, but it is possible. This ladies and gentlemen is the future of stem cell research. Some people say this ground breaking research is just a hype, that we are spending our government money on research that is going nowhere. Well I can tell you that this is not the case, the world of stem cells is just beginning and the future possibilities are endless. To understand where the future of this amazing research will lead us, we must first look at the past, to research and biology of where stem cells first began.
Firstly what is a cell? 'Cells are the structural and functional units of all living organisms' (National Centre for Biotechnology Information, 2004). They create everything from the tiniest hair on your head, to vitally more important brain and heart cells. All cells consist of; an outer cell membrane, and a cytoplasm; which is a jelly-like substance containing the fluid Cytosol. Cells are specialized to form many different and vital functions the organism need to survive. Cells are specialised through genetic information called DNA, and when this is achieved only the DNA related to the function will remain active. Thus deeming the cells for one particular function only.
However this is where stem cells defy this statement. A stem cell is an un-specialised cell, which remains in-active until needed. Stem cells have the amazing potential to develop into many different cells in the body. They have the ability to renew themselves through cell division, and serve as an internal repair system when certain cells are damaged or need replacing. This type of cell ladies and gentlemen is the cause of a vast and continual debate, which has lead the scientific world into the issue of ethics verse science.
Stem cell research began in the mid 1800's when it was discovered that some cells could generate into different cells. However the real research began in the early 1900's with the discovery the certain cells could produce blood cells. This latter developed into Ernest A. McCulloch and James E. Till, discovering there are two types of stem cells; embryonic stem cells, and adult stem cells. It was discovered that the embryonic stem cells developed into all the different cells in the body, whilst adult stem cells act as a repair and replenishing system for the body. Lastly the in 1978 it was discovered that stem cells were also present on umbilical cord blood. Since then much research has been developed from each of these different cells types, and many procedures have undertaken. However in relation to the research with embryonic stem cells, this has however provoked many people to debate the ethical issues associated with this controversial.
To understand both perspectives of this never ending debate, we must first understand the potential, and the biology that stem cells have placed in front of scientists. To grasp the enormity of stem cells, I want you to look to the person sitting next to, study them, look how big they are, look at all the different and complex features on their face alone. Well that person originated from a single cell, one tinny cell no bigger than a pin prick. This person came from a single fertilised egg that divided and grew into the person sitting next to you now. This ladies and gentlemen was all made possible by the miracle called stem cells.
When the egg is first fertilised it goes through a stage called cleavage. This means as the fertilised egg referred to as a zygote travels down the fallopian tube it starts rapid mitotic divisions which allow the un-specialised cells to divide into hundreds of smaller cells. This process usually takes about 5 days, and towards the end of the zygotes journey to the uterus this results in something called a blastocyst. Blastocyst's at this early stage are made of about 70-100 cells, and consists of two major parts; one the trophoblast which gives rise to placenta and other supporting tissues, and secondly and more importantly the inner cell mass. This inner cell mass is the stem cells that develop and differentiate into every single other cell in your entire body. These amazing cells within the blastocyst are what have thousands of scientists around the world today very excited for what the future could hold, in the way of treating disease and repairing what normally be considered irreparable damage to vital tissues and organs. This inner cell mass of the blastocyst is the basis for embryonic stem cell research.
However Embryonic stem cells are not the only cells that are providing potential for ground breaking research. There are three main types of stem cells; Embryonic stem cell, Adult stem cells, and umbilical cord blood stem cells.
'Adult stem cells are undifferentiated cells found among specialised (differentiated) cells in a tissue or organ after birth'(Commonwealth Scientific and Industrial Research Organisation,2011). Adult or somatic stem cells are found in such tissues as the brain, liver, bone marrow, skin, skeletal muscles, eyes, blood and blood vessels. Within these tissues they are thought to be held within a specific area called a 'stem cell niche'. Here they remain quiescent or in other words non-dividing, for extended periods of time until needed. Once they are activated they can replicate themselves in order to repair the damage needed. However, once removed from the body ability to divide is limited, and there is usually only a small amount of stem cells in each tissue. This has created a dilemma for scientist trying to grow large quantities of the Adult stem cells.
Before the discovery of stem cells, umbilical cords where traditionally discarded after birth. However it was found that the blood in the umbilical cord is rich in stem cells. Umbilical cord stem cells have proven useful in many ways, and have the ability to treat the same diseases as that of Adult stem cells. The great thing about umbilical stem cells is they are less prone to rejection; this due to these cells not developing features, or immune cells which are recognised by the recipient's immune system.
Types of stem cells
Lastly there are two types of embryonic cells that are being researched. Embryonic stem cells, which are usually derived from un-wanted embryos, and Embryonic germ cells which are taken from a part of a foetus that will ultimately produce gametes, or in other words egg or sperm cells. The problem with embryonic germ cells, is that they are derived from Primordial Germ Cells which are found further along the growth process than embryonic stem cells. Therefore in Australia due to the ethical issues only mouse embryonic germ cells are being studied.
These 3 main types of stem cells have sparked major interest and excitement in the world of science. Grasping the full power of these stem cells would ensure the cure to many diseases which currently have no cure. Once a stem cell has become specialised due to a trigger needed for re-pair it has the ability to produce the same cell which is now relevant to that organ or tissue. This insures the quick recovery for many damages that can be made to the fragile human body. If scientists can grow and manipulate these cells to transform into any cell they like, this can lead to curing almost any problem or destruction to the human body.
These stem cells are classified by their potency. This means their potential to form into other types of cells. The Highest rating of potency is called a Totipotent cell. These cell has the ability to form every cell in the entire human body, however they are only found in 8 cell zygotes. The second highest potency rating is pluripotent cells. Pluripotent cells have the ability to form any tissue or cell from the three germ layers of the body, this means they can become any cell other than the extra-embryonic membrane or the placenta. This type of cell would be classified as the embryonic stem cells which are cultured for human research. However, it is also found that we can now induce pluripotency on somatic stem cells as well. Multipotent is the final potency level of cells relevant to this specific stem cell research. Multipotent stems are what would be considered adult or somatic stem cells. They have the ability to differentiate into certain cells within a family type. Such as a blood or Hematopoietic stem cell can transform into any type of blood cell, this would include red blood cells, white blood cells, and platelets. Other family types include, skeletal muscles, cardiac muscles, brain cells, and liver cells.
Obtaining the stem cells
All of these different types of stem cells are obtained in similar ways. Embryonic stem cells are harvested from the inner cells mass of a blastocyst, whilst adult stem cells are either removed from the umbilical cord or other tissues. Once embryonic stem cells are derived they are placed in a culture dish. Here they may grow for many months in the controlled culture which allows the cells to divide but not differentiate in a pre-implantation form. If cells survive they will multiply enough to cover the dish, this is called an embryonic stem cell line. Once these lines are large enough they are removed and split into several more fresh cultures. This process can be repeated many times, and result in many embryonic stem cells from the original culture. By continually examining these subculturing stem cells, this ensures that the cells are pluripotent, and are capable of long term growth and self renewal.
Controlling the differentiation of the embryonic stem cells
After this process is complete the stem cells lines can be frozen and transported. Now the difficult part begins; trying to control the differentiation of the embryonic stem cells. Scientists are able to study the differentiation via microscopes to see how the pluripotent cells from the three germ layers. The germ layers consist of the ectoderm layer which produces the nervous system and the skin, the mesoderm layer which produces the blood, heart and muscle tissue, and lastly the endoderm which makes the pancreas, liver, gut and lungs. As you can see within these three germ layers there are very different tissues such as the ectoderm layer which produces the nervous system and the skin. So in order for scientist to control this process of differentiation they must understand how these stem cells are turned into specific cells. This is done through the cells turning on and off genes in order to express certain characteristics which are specific to their function. Such as a red blood cell forming a biconcave lens shape, and expressing haemoglobin and oxygen. To discover this, the nucleic acid would be extracted from the cell, and using the RnA which represents the genes that have been expressed, a probe would be made. The probe would then be labelled with a florescent marker. This would then be applied to a DNA chip, which is a small microscope slide that has a copy of all the genes in a human genome. This chip will discover the exact genes that are on or off. Thus determining what kind of a cell it will become, as each differentiated cell has a different pattern on the DNA chip. By understanding which type of cells are developing scientists are able to control which cells the embryonic stem cells will turn into. This is achieved by changing the chemical composition of the cultures, modifying the cells by inserting certain genes, or altering the surface of the culture dish. However this is a difficult process which is not always reliably.
Current methods of stem cell therapy
Current methods of stem cell therapy include serious diseases such as, cancers, blood diseases, skin grafts and brain or spinal cord injury. They are also used for treating less serious things such as hair loss, or aging skin. Leukaemia, a cancer of the white blood cells is treated with stem cells when other methods such as Chemotherapy and radiation alone are not enough to cure the patient. The stem cells are obtained from a donors bone marrow, and introduced into the patient's blood stem, thus replacing the deformed cells with healthy ones. This procedure however is extremely invasive and painful for the donor, and without finding an exact matching donor this procedure would be rejected by the patient's immune system. Another way of treating Leukaemia, or other blood disorders is through the peripheral blood stem cells. This is a much less painful and invasive treatment option for donors. However, unfortunately there are only a small amount of the stem cells present within the blood stream, therefore in order to collect enough to perform a successful treatment is a tedious challenge. Another proven method is healing burns with skin grafts. As skin is rich in stem cells, when transporting skin grafts from healthy parts of the skin, to severely damaged or burnt parts, the stem cells work to repair the damage. The problem with therapy is only the patient's own skin will work, as donors skin will be rejected by the immune system. This has posed a dilemma for patients who don't have enough healthy skin to treat all there wounds.
Potential uses of stem cells
The ultimate goal with stem cells, and particularly embryonic stem cells is to be able to create any organ, or cure any disease. This could be anything from replacing someone's heart, by growing a new one from embryonic stem cells in a culture dish, to treating diseases such as type one diabetes. 'Diabetes develops when the body's immune system sees its own cells as foreign and attacks and destroys them' (U.S. Department of Health and Human Services, 2009). Due to this the islet cells that produce insulin in the pancreas are destroyed, allowing for the build up of glucose in the blood. The idea with embryonic stem cells is that they could be engineered to avoid the immune reaction, and grow and produce islet cells which produce the insulin needed to cure diabetes. 'Recent studies in mice show that embryonic stem cells can be coaxed into differentiating into insulin-producing beta cells, and new reports indicate that this strategy may be possible using human embryonic cells as well' (U.S. Department of Health and Human Services, 2009). There is also hope with adult stem cells for the cure of diabetes. However, it is very difficult to coax adult cadavers into islet cells. This is due to when the cells are cultured it is very difficult to grow a stem cell line which both produces both insulin and also proliferates. It is also shown that these cells do not produce enough insulin to reverse and cure diabetes. Therefore the research will continue to find ways in which we can prevent these flaws in order to cure many diseases.
It is obvious that stem cells have the potential to cure many unfathomable diseases, and grow and replace damaged organs. However there are many things are holding this ground breaking research back. Firstly there is the cost of not only the research but also the tremendous cost for stem cell treatments. 'Total funding of $100 million has been awarded to the ASCC by the Australian Government and is administered by the Australian Research Council and the Department of Innovation, Industry, Science and Research' (Australian Stem Cell Centre, 2011). On top if this a further $11 million has also been provided from the Victorian state government. For treatments such as a cure for spinal repair, it would then be an estimated cost of around four billion dollars to cure all of the patients which suffer from this disease and damage. Another example would be curing diabetes, it is expected to cost around $100 000 to $200 000 to actually collect the amount of stem cells needed to cure each patient.
Due to the sufficient funding needed for stem cell research, there has been much talk on the need to specialise research. There is also many other flaws with this miraculous research. In order to discover where we should be putting are money and time into we must first look at the different types of stem cell research and the pros and cons of each.
Adult stem cells have been used to successfully treat things such as cancers, blood disorders, and skin grafts. Other breakthroughs have presented advancements in treating Parkinson's disease, juvenile diabetes and spinal cord injuries. However the most impressive one is a report of a man being cured of HIV aids. While being treated for leukaemia he sought someone that has a genetic mutation resistant to HIV. This mutation seemed not only to cure the leukaemia but the HIV as well, showing major potential in regards to stem cells. This major issue with Adult stem cells is there is only a very small frequency of stem cells in the tissues they are harvested from. They are also Multipotent which means there differentiation potential is restricted, and they do not proliferate very well. This is due to once they have been removed from the body they can no longer have the same ability to divide. Another issue with adult stem cells is that they are prone to rejection. Such as with skin grafts can only come from the same person who needs them, otherwise they will be rejected. Also with bone marrow transplants donors must exact matches, and even these can sometimes be prone to rejection. However the great thing about Adult stem cells is there are no ethical issues involved with the process, as they are derived from consenting adult donors.
Another variation of adult stem cells are umbilical cord stem cells. As they are harvest from the discarded umbilical cord, they also present no ethical issues. The umbilical cord is rich in stem cells, however once they are used up there are no more. They have advantages over regular adult stem cells as they are less prone to rejection due to they have not yet developed features that are recognised by the patient's immune system. They also have the possibility to be more versatile then adult stem cells, but currently they are only used to treat patients the same way bone marrow or peripheral blood stem cells do.
Adult stem cells where originally thought of to be only Multipotent, and unable to have the ability to be as useful as embryonic stem cells. However, in 2007 the first human Induced Pluripotent stem cells were reported. Induced Pluripotent stem cells or iPS cells is the act of reprogramming a somatic or adult stem cell back to its pluripotent state. This is achieved by integrating of up to four different DNA-transcription factors into the adult stem cell, thus reprogramming the cell to make it pluripotent. This has created a great hype in the medical industry, as it has made it possible to have diverse pluripotent cells without the ethical issues of using an embryo. 'In addition, tissues derived from iPSCs will be a nearly identical match to the cell donor and thus probably avoid rejection by the immune system' (U.S. Department of Health and Human Services, 2009).But before we get to excited about this research, there are still many flaws in the type of stem cells, and before they can be used in stem cell therapies there is a lot of work which must be done. The first problem with IPS cells is that in studies results have show not only a few cells were forming abnormalities but the entire population of cells were prone to forming cancers. The cell death rates otherwise called apoptosis are also much higher than the death rates for embryonic stem cells. They also don't proliferate as well as embryonic stem cells, in fact anywhere between 1,000 to 5,000 fold less. Therefore it would be very hard to grow sufficient lines of iPS cells. This would result in having to produce ten lines for just one patient, and with the already limited supply in human's tissues, we have to consider is iPS cells really a realistic option? iPS cells are currently been used in experimenting with different drugs and viruses. However the results of these tests are now coming into question. This has to do with the apoptosis or cell death that is occurring. It is now being considered that the drugs that are being tested may not be affecting this, but in fact the way in which the cells where created has more relevance. As you can see ladies and gentlemen whilst the idea of not destroying and embryo is very appealing, everyone seems to be looking past the flaws and jumping straight to the conclusion that because these cells are more ethical they will be effective.
Embryonic stem cells are still the cells that have shown the most promise, but also the biggest debate. Some say embryonic stem cell research is cheapening the value of human life, that we should never disregard and embryo for the name of science. However people forget that there are laws governing this process. The legislation states that, act 2002 allows for the research of IVF embryos including for the derivation of human embryonic stem cells and prevents not only cloning for reproductive purposes but also somatic cell nuclear transfer (Australian Stem Cell Centre, 2010). This basically means that any research with embryonic stem cells, is only done with IVF embryos, where the donors are fully aware and consent, and the embryos would otherwise be just discarded. As said by Paul Berg, Cahill Professor of Biochemistry, 'Surely, obtaining cells from legally obtained abortions or from early stage embryos that are destined to be discarded in the course of IVF procedures and making them available for potential life-saving purposes would be viewed as ethically permissible if not a moral imperative.' A survey of 7579 people from Australia nationwide, showed a majority of people don't believe an embryo is a human being at the moment of conception, but rather a it is slow process of developing into one. As you can see they majority favoured the probably not category with 28%. It is also shown within this survey that the majority of people that subside more towards the defiantly yes category are religious in particular Catholics. Therefore is this really a battle of moral ethics, or rather religion? No matter the potential however, there are still certain issues with embryonic stem cells. Scientists have had trouble with embryonic stem cells spontaneously creating tumours. Also it has sometimes been hard to maintain embryonic stem cell lines, due to some of cells mutating. 'The main problem with embryonic stem cell research is the problem is tissue incompatibility' (Rich Deem, 2009). Although this is true, it is now shown that embryonic stem cells have underlying immune privilege. This means embryonic stem cells have the full potential to persuade the immune system to accept these tissues. Embryonic stem cells also proliferate easily, this means they can be cultured and re-cultured, producing thousands of stem cells without the need for using more than one embryo. Until recently embryonic stem cells where only being tested on mice. Through many years of testing researches have comprised some amazing results, one of these was of a rat that had severe spinal damage. After being injected with oligodendrocytes from an embryonic stem cell line, the rat was cured of its disability with only a slight limp. Many thought that embryonic stem cells where a thing for the distant future, used only for testing in mice, and until recently where not considered safe for human trials. This theory has now been obliterated with the first human trial using embryonic stem cells commencing in the United States, in October 2010. This trial is being used on a person who has suffered from a paralysing spinal cord injury. It was conducted much in the same way as the rat, injecting the cultured embryonic stem cells containing Oligodendrocytes, in hopes they will release compounds that will repair the damaged nerves and regenerate the spinal cord. This trial has sparked a major new interest in the potential embryonic stem cells, and gives the many researches that have been tirelessly working, a much deserved moral boost. As said by Professor Chris Mason, 'We can only do so much to animals, now's the time to see if they really work in man.' Initial results have shown no negative signs of rejection, but the full extent of results will be withheld until the end of the one year trial. About 6 weeks post this procedure United Sates president Barack Obama lifted the ban on funding for embryonic stem cell research, igniting the way many trails to come.
Stem cell research has given potential to many researchers and scientists around the world to make possible a world in which disease and damage can be cured. There has always, and will always be a heated debate over the topic of the ethical issue of embryonic stem cells. However, is a 5 day old IVF embryo which was going to be discarded, more important than finding the cure which could help hundreds of thousands of people? Now the true potential is now finally starting to be realised, with the first human trials, this has opened the door for many other trials to come. Imagine a world where disease is no more. Now with the potential these embryonic stem cells have shown, this dream now seems to be becoming more of a reality. The age of stem cells is now upon us, and it is our choice whether with chose to take this knowledge and use it for the better of mankind.
Stem cell problems
http://www.godandscience.org/doctrine/stem_cell_research.html - Rich Deem (2009)
http://www.npr.org/templates/story/story.php?storyId=5204335 - Terry Gross (2006)
http://www.abc.net.au/news/stories/2010/12/16/3095333.htm - ABC news (2010)
http://www.abc.net.au/science/articles/2010/10/12/3035781.htm - Kim Landers (2010)
http://www.aish.com/ci/sam/48969936.html - Daniel Eisenberg, M.D. (2001)
http://www.allaboutpopularissues.org/history-of-stem-cell-research-faq.htm - All About Popular Issues.org (2011)
http://www.aph.gov.au/library/pubs/CIB/2002-03/03cib05.pdf - Commonwealth of Australia 2002
Spenceley, M. Weller, B. Mason, M. Fullerton, K. Tsilemanis, C. Evans, B. Ladiges, P. McKenzie, J. Batterham, P. (2004) 'Biology- A contextual approach', Heinemann QLD.
http://www.biotechnologyonline.gov.au/human/sctypes.html - Commonwealth Scientific and Industrial Research Organisation (2011).
http://jme.bmj.com/content/32/11/665.full - H.W Denker (2006)
http://www.brighthub.com/science/medical/articles/27331.aspx - Robyn Broyles (2009)
http://www.brighthub.com/science/medical/articles/27338.aspx - Robyn Broyles (2010)
http://www.brown.edu/Courses/BI0032/embgerm/egc3.html - Rebecca Burke & Jackie Parente (2002)
http://www.buzzle.com/articles/history-of-stem-cell-research.html - Gaynor Borade (2011)
http://clearlyexplained.com/nature/life/cells/stemcells.html - Richard Conan-Davies (2009)
http://www.clinicaldiscovery.com/readArticle.aspx?articleId=35 - Sumanth Kambhammettu, Pharmaceuticals & Biotechnology, Healthcare (EMEA), Frost & Sullivan (2006)
http://www.csa.com/discoveryguides/stemcell/overview.php - Preeti Gokal Kochar (2004)
http://www.dummies.com/how-to/content/explore-current-stem-cell-treatments.html - Lawrence S.B. Goldstein and Meg Schneider (2011)
http://www.funsci.com/fun3_en/blood/blood.htm - Daniela Tagliasacchi, Giorgio Carboni (1997)
http://hbswk.hbs.edu/item/6601.html - William Sahlman (2011)
http://www.heritage.org/research/reports/2005/05/federal-stem-cell-research-what-taxpayers-should-know - Robert Moffit , Kelly Hollowell , Phil Coelho and The Honorable Dave Weldon (2005)
http://www.icr.org/article/ten-problems-with-embryonic-stem-cell-research/ - Kelly Hollowell
J. Angelbeck, M.Chinery, J. Clark, N. Curtis, G. Edmonds, A. Fisher, W. Gould, I. Graham, W. Hemsley, J. Muirden, J. Paton, B. Ward, W. Wasels, P.way. (1998). 'Science Encyclopaedia,' Kingfisher London.
http://learn.genetics.utah.edu/content/tech/stemcells/sctoday/ - Kevin Taylor
University Information Technology (2011)
http://www.mayoclinic.com/health/stem-cells/CA00081 - Roger W. Harms, M.D. Kenneth G. Berge, M.D. Philip T. Hagen, M.D. Scott C. Litin, M.D. Sheldon G. Sheps, M.D. Brooks S. Edwards, M.D.(2010)
http://www.medicalnewstoday.com/info/stem_cell/ - Peter Crosta (2011)
http://www.nature.com/nature/journal/v451/n7180/full/451858a.html - George Daley (2008)
http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html - National Centre for Biotechnology Information (2004).
http://www.pacificfertilitycenter.com/welcome/lab_embryo_blastocyst.php - Pacific Fertility Centre (2011)
http://www.pbs.org/newshour/science/stem-cells/cellbasics.html - Karyn Schwartz (2004)
http://www.pharmaceutical-technology.com/features/feature84985/ - Frances Penwill-Cook (2010)
http://www.scientificamerican.com/article.cfm?id=cell-induced-pluripotent - Charles Q. Choi (2010) Â
http://www.sciencedaily.com/releases/2008/04/080411082935.htm - Dr Nathan Robertson (2008)
http://www.stemcellcentre.edu.au/About_ASCC.aspx - Australian Stem Cell Centre (2011)
http://www.stemcellcentre.edu.au/For_the_Public/About_Stem_Cells.aspx - Australian Stem Cell Centre (2010)
http://www.stemcellcentre.edu.au/For_the_Public/Legislation.aspx - Australian Stem Cell Centre (2010)
http://www.stemcellcentre.edu.au/For_the_Public/Patient.aspx - Australian Stem Cell Centre (2010)
http://www.stemcellgateway.net/ArticlePage.aspx?DOI=10.1007/s12015-010-9123-8 - Minal Patel. Shuying Yang (2010)
http://stemcells.nih.gov/info/basics/basics1.asp - U.S. Department of Health and Human Services (2009)
http://stemcells.nih.gov/info/basics/basics3.asp -U.S. Department of Health and Human Services, (2006)
http://stemcells.nih.gov/info/basics/basics4.asp - U.S. Department of Health and Human Services (2010)
http://stemcells.nih.gov/info/basics/basics6.asp - U.S. Department of Health and Human Services (2009)
http://stemcells.nih.gov/info/basics/basics10.asp - U.S. Department of Health and Human Services (2009)
http://stemcells.nih.gov/info/scireport/chapter7.asp - U.S. Department of Health and Human Services (2009)
http://stemcells.nih.gov/StemCells/Templates/StemCellContentPage.aspx?NRMODE=Published&NRNODEGUID=%7bA604DCCE-2E5F-4395-8954-FCE1C05BECED%7d&NRORIGINALURL=%2finfo%2ffaqs%2easp&NRCACHEHINT=NoModifyGuest#wherefrom - U.S. Department of Health and Human Services (2010)
http://www.web-books.com/MoBio/Free/Ch8F1.htm - J. Clin. Invest (2000)
http://www.wiziq.com/tutorial/32875-Human-Stem-cells-application-Part-2 - Douglas A. Melton