Saturday, November 12, 2011

Dancing into a Stem Cell Future

Tanay Gupta, a third year Biotechnology major at RIT, has decided to sever his ties with writing boring research papers for the time being. He is trying something relatively new; changing ideas and making science easy enough to be digested by a general audience. This piece was intended to be sent to the New York Times to get the general public to re-evaluate the prevalent opinion that stem cells are ethically wrong. In the piece, he shares the idea that stem cells are beneficial and prepares the world to dance to the stem cell beat.


Claudia Castillo doesn’t appear to be much more than the average 30 year-old. A Colombian by descent, she spends most of her time looking after her two children, 15 year-old Johan and 4 year-old Isabella. But there’s more than meets the eyes. In 2004, Claudia Castillo was practically bed-bound and was unable to take care of her children and carry out the simplest of tasks.

It was only after a good three months of her gasping for breath that she found herself at the doctor’s clinic. From one wrong diagnosis to the other, by the time her doctors figured out that she had tuberculosis, things had become complicated. The tube connecting her windpipe to one of her lungs had collapsed almost completely. From there on, conditions worsened and by 2008 Claudia was rendered nearly invalid. Castillo eventually arrived at the Hospital Clinic of Barcelona desperately hoping that the doctors could do something. She had two options: to have her left lung removed or become a guinea pig for an experimental procedure.

Four months later, her surgeon, Professor Paolo Macchiarini received a surprising phone call from Castillo at 5am. She wanted to let him know she had been dancing all night in a club in Ibiza. She had her left lung in place and was living a renewed life. Being the experimental guinea pig didn’t turn out bad after all. Claudia Castillo isn’t the average 30 year-old, she is the first person in the world to have an engineered windpipe rather than it being entirely donated.

Although most of us would think that the process behind this quite unimaginable result would be equally complex, it’s actually fairly simple. A section of the windpipe is taken from a dead donor and subsequently washed with chemicals that wash off all the cells from the dead person; this process leaves a sort of skeleton of the donor’s windpipe. It’s basically a section of the windpipe made of a fibrous protein called collagen minus the cells from the donor that coat it. As one would expect, the section from the dead donor is manipulated and shaped such that it exactly fits the damaged section in the recipient, in this case Claudia. Stem cells and normal cells lining the windpipe are taken from the recipient and used to encourage the stem cells to form the cells that surround the windpipe. The donor skeleton windpipe and the transformed stem cells are grown in a special rotating vessel and after the recipient’s cells have coated the windpipe in a process called seeding, it is ready to be transplanted. The idea here is that stem cells, which show the ability to divide indefinitely and reproduce to form different cell types, can create entire organs that will not be rejected by the immune system simply because the stem cells have been harvested from the recipient’s body itself. In effect, this abolishes the need to prescribe immunosuppressive medications (drugs which make the body more susceptible to infections of any sort) to keep the body from rejecting the transplant, and improve the overall efficiency of organ transplants.

Much like the improvement in organ transplantation, stem cells have great potential to revolutionize medical science as a whole. This is owed to their inherent ability to self-renew or multiply indefinitely, as well as their ability to divide to form different cell types. There are two broad classes of stem cells namely adult stem cells, which are found in various tissues of one’s own body, and embryonic stem cells, which are found in the early stages of an embryo’s development. The key difference between the two types is that while adult stem cells are multipotent and can generate only a few cell types, embryonic stem cells can generate all the cell types in the body, a property called pluripotency.

It naturally follows that embryonic stem cells (ES cells) are more useful to medicine since they can produce a much broader range of cell types. This sounds great, until you throw in ethics and morality. Embryonic stem cells are harvested at the blastocyst stage, which is the 5th day after fertilization, from the inner cell mass, the mass of cells that gives rise to the embryo. Therefore, an embryo has to be destroyed when embryonic stem cells are to be harvested. This very idea spurred a controversy that is still as persistent as it was in 1998 when a group of scientists first harvested stem cells. From the ethical and religious point of view, human life was being destroyed. But can we really call this “destruction”? Most opponents of embryonic stem cell research know very little about how, when and why these stem cells are harvested. They are more in favor of the pro-life idea and consider every human life sacred. To them human life begins when sperm and egg fuse and anything that violates “their definition” is murder. The real picture however, suggests that embryonic stem cell research isn’t all that immoral. I’m definitely not an advocate for the idea that embryos be destroyed, but can an embryo be seen as human life until it can survive outside the womb? The inner cell mass from where the stem cells are harvested is cluster of cells that have not differentiated into specific tissues, so they are equivalent to skin cells for all purposes. Is destroying skin cells murder? Definitely worth re-considering. Even if we sidestep the ethical argument and move to something more logical, embryonic stem cell research doesn’t hurt anyone. Fertilization of eggs and sperms outside the human body, in laboratories produces thousands of embryos. Of these thousands, many are marked for destruction. Instead of them being destroyed they could easily be used as a resource for embryonic stem cell research. Additionally, in countries where abortions are legal, destroyed embryos are discarded. There is no reason not to harvest embryonic stem cells from these embryos that are otherwise to be waste. It is disheartening that there is a wide misconception that these stem cells are anti-life when there is sufficient evidence to show that not only do they now evade the ethical violations, they are actually of tremendous use to medicine. It is important for us to remember that because stem cells differentiate into different types of cells, they can form tissues to treat diseases including Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. It’s not even as though all of this is mere speculation. Embryonic stem cell transplantation over seven days in mice with spinal cord injuries showed that the mice were able to walk around fairly well. Geron Corporation of Menlo Park, CA applied the same strategy to humans who had injured their spines one to two weeks before the embryonic stem cells were implanted. While an increase in their mobility is a possibility, the human trial was mainly designed to test whether the process is safe in humans. If the study shows favorable results, the same idea may help overcome even the greatest of disabilities.

While the safety and success of embryonic stem cell transplantation can be considered slightly doubtful, adult stem cell therapy has already shown astonishing results. In fact, the stem cells used to treat Claudia Castillo were taken from her bone marrow, which makes them adult stem cells. We already know that adult stem cells naturally occur in the body, but that makes one wonder what role they are designed to play and how they do so. An adult stem cell is currently thought to be a unique cell found among normal cells in a tissue or organ that can renew itself and can divide to yield some or all of the major specialized cell types of the tissue or organ. The primary roles of adult stem cells in a living organism are the maintenance and repair of tissue in which they are found. Unlike their embryonic counter parts, which are defined by their origin (cells from the inner cell mass); the origin of adult stem cells in some mature tissues is still under investigation. Usually, the number of stem cells in tissue is very small and this makes it very difficult to isolate them efficiently. Researchers are still in the process of finding improved ways of harvesting adult stem cells and having them generate specialized cell types to treat injury and disease. It can easily be expected that improvements in the harvesting and transformation processes will not only improve the effectiveness of treating disease, but also add to the overall quality of life.

Stem cells, both embryonic and adult, have their own share of setbacks. While harvesting embryonic stem cells is unjustly seen as killing a life, adult stem cells are extremely challenging to find and grow outside the body. In this light, researchers began to question the idea of whether normal body cells could be changed in some way to yield stem cells. As unrealistic as that may sound, reality has a different story to tell. In 2006, Shinya Yamanaka and his team from Japan succeeded in converting mouse fibroblasts (cells that make structural proteins) to embryonic stem cells. Furthermore, Yamanaka and his team got together with another team to create the first embryonic stem cells from adult human cells using the same principle that was used in mice. This type of stem cells was found be pluripotent, meaning they could form all the cell types in the body and were thereby called induced pluripotent stem cells or iPS cells. The idea behind adult cells being reprogrammed to form iPS cells lies in forcing the adult cells, through genetic modification, to express genes that define embryonic stem cells. Although iPS cell research is a fairly new field and influential research is only in the rudimentary stages, these cells have already become a useful tool in drug development.

Current research on iPS cells is focused on creating a possible cure for sickle-cell anemia. Sickle-cell anemia is a genetic disorder that causes red blood cells to collapse into a sickle shape. These sickle-cells then clog blood vessels leading to pain, organ damage and even death. Scientists at Johns Hopkins have used a patient’s own cells to correct the genetic change in the hemoglobin gene that causes sickle-cell anemia. The researchers first isolated the patient’s bone marrow cells. After generating iPS cells, they put one normal copy of the hemoglobin gene in place of the defective one using genetic engineering techniques. Researchers are now working on fully maturing these engineered cells so that they produce normal levels of hemoglobin. Although, this technique is estimated to be years away from treating patients, it is both a promising and ethical approach to treating this severe disease.

Even after stem cells have shown promise in being able revolutionize most diseases and injuries; the notion that all stem cells are morally wrong continues to persist. Opponents of stem cells always to seem to have their own agenda to widely propagate the idea that stem cells are man’s attempt to become god and to become god is a violation of ethics. These claims and ideas are not only biased, but they also give the general public a set of ideas that are scientifically baseless for the most part. We can all agree that maybe destroying an embryo is morally wrong, but what about the ways we’ve found around embryonic stem cell harvesting? Adult stem cells and induced pluripotent stem cells don’t harm anyone. On the contrary, given a chance, they can completely change the way disease is seen. Diseases like cancer, Parkinson’s and Alzheimer’s or even deaths from serious injuries will become a distant memory if stem cell research makes progress. Although living in a world with barely any disease and low mortality rates is a utopian dream, stem cells can make it happen. Stem cells are standing proof of the fact that human being’s reach has well surpassed his imagination. The human journey with stem cells has long since begun and it will be exciting and worth the wait to be a part of the revolution it will bring.

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