Human stem cell research is a controversial subject that illicits power reactions from all sides. The issues at stake are not only scientific. They are political, cultural and religious issues as well. Michael Bellomo sorts through the issues in a very objective fashion. He neither advocates nor opposes stem cell research.
The book is organized in three parts. Part one begins with an imaginary story of a young woman involved in an automobile accident. She was recovering well in the hospital when suddenly her condition deteriorated. A globule of marrow fat from her shattered femur had lodged in a blood vessel feeding her pancreas. Deprived of its cellular needs of oxygen, the pancreas died. The young woman’s doctor sent a sample of her cells to a laboratory where the nuclei from some of the young woman’s cells were transferred into the inner mass of a fertilized egg whose nucleus had been removed (stem cells). Thus, the undifferentiated cell mass was now genetically identical to the young female accident victim. The rate of division, chemical and physical environment of the cell were carefully regulated to prevent them from growing out of control, or differentiating into a specific cell type other than pancreas cells. The end result is that a pancreas is grown and sent back to the hospital for transplantation into the young accident victim. Since the organ was genetically identical to the woman’s own, there was no risk of rejection from the woman’s body. The new pancreas would not be attacked by her immune system as a foreign body. No dangerous immune suppressing drugs would need to be administered. Thus, the young woman’s life was spared. The story illustrates one possible outcome of stem cell research – as well as some of the sensitivity around the issue including the use of a fertilized egg.
The book goes on to give an overview of stem cell history and a rudimentary introduction to the related biology. One of the first scientists to make observations related to stem cells was the Dutch scientist Abraham Trembley in the 1700’s. Trembley discovered the regeneration and growth features of fresh water hydras. He observed that when cut in half, the hydra would regenerate into two identical hydras. He also observed that the process of regeneration followed the same pattern seen during the gestation of animal embryos. The most fascinating achievement of Trembley involves an amazing feat of surgical skill – he managed to turn one hydra inside out, like a sock, and then using a spike of boar’s bristle he jammed this inverted hydra down the “throat” of a second hydra. Instead of the inside out hydra being digested, the two organisms fused together forming a single, thicker hydra. This paved the path for scientific speculation that perhaps people would one day benefit from the ability to replace dead, dying or damaged skin and organs. The key to the hydra “mutation” is that the two layers of cells, inner endoderm and outer ectoderm, act as stem cells. The cells perform functions such as digestion, but they do not lose the ability to regrow into new tissue or new types of cells. This ability is at the heart of what drives modern stem cell research.
This ability to become different types of cells is called plasticity. The most common designation of plasticity is called pluripotency. Pluripotency regards stem cells that have the ability to become many different types of adult differentiated cells. Totipotency refers to the most precious ability to become any type of cell. Multipotentcy refers to stem cells that are limited in what type of cell they can become. An example of these would be hematopoietic cells, which are found in the blood. These types of cells can develop into many types of blood cells, but not nerve cells or kidney cells or any other type of cells. The least of stem cells in regard to plasticity are unipotent cells. Examples of these are the cells in the epithelium or outer most tissue layer of our skin just below the dead squamous epithelial cells. Current technology allows sheets of skin to be grown from these cells to form transplantable sheets of skin. Future progress holds a great deal of hope for generating cartilage to treat injuries of the knee and elbow.
Totipotent stem cells can only be found in one place – the inner cell mass of a blastocyst. The blastocyst is a hollow mass of cells that is created when the initial female egg is fertilized. The inner mass is called the embryoblast and these undifferentiated cells are the source of the highly controversial embryonic stem cells. As soon as these cells are removed and placed in culture, they begin to change and lose their plasticity. They retain a high degree of plasticity, but the disruption causes them to change into pluripotent rather than totipotent cells.
There are adult stem cells which should not be confused with embryonic stem cells. Typically, these are multipotent or unipotent cells and include cells (listed in order of decreasing plasticity) in the brain, bone marrow, digestive system, internal vessels, liver, pancreas, muscle, and skin cells. These adult cells are less plastic and thus less versatile and useful.
Much of the modern research on embryonic stem cells is the result of developments in invitro fertilization, or IVF in the 1980’s. People such as Dr. Ariff Bongso of the National University Hospital of Singapore developed ways to grow embryos, improve their sustainability, and increase the odds they would survive the transplantation procedure. This resulted in the creation of lines of cells that could be grown into tissues at a later date for treating disease. The cells Bongso worked with grew up until the day 5 blastocyst stage at which point the inner mass of stem cells was removed. It was only a short time after this the cells would differentiate and lose plasticity. Additional research and developments were made by people such as Dr. James Thomson at the University of Wisconsin that allowed the cells to retain their plasticity in the lab. Thomson obtained his cells from the extra human embryos left over from IVF clinics. The IVF process involves the creation of several fertilized eggs, only one of which can be implanted in the patient’s womb. The surplus embryos are either kept frozen or discarded. Thomson was concerned that the research would generate controversy. He mandated that he would only use cells up to about day 5 of the blastocyst phase. He also wished to avoid coming close to the 14th day of embryonic development since this is when the first nerve cells start to differentiate and form the barest silhouette of a nervous network. He intentionally avoided this 14 day mark to avoid any argument that his work could cause an embryo the sensation of pain.
A substantial portion of the mid section of the book discusses the political processes and religious opposition to stem cell research. President George W. Bush announced his administration’s policy in 2001 would be to allow federal funds for research and experimentation on embryonic tissue to only the existing, roughly 60, cell lines – those already cultured and stored in laboratories. In California, they responded by passing a bill in September 2002 allowing therapeutic cloning, which Governor Gray Davis signed into law. Following this bill was the California Stem Cell Research and Cures Initiative, or Proposition 71, which made stem cell research a state constitutional right, allocated 3 Billion dollars over ten years, and made embryonic stem cell research a priority. In May 2005, the Republican-controlled House passed a bill allowing federal funds to be used for embryonic stem cell research. Republican senator Dr. Bill Frist broke from the pack to support the legislation, saying:
“Because they have a property called pluripotence — the ability to become almost any other type of body cell — embryonic stem cells could eventually help treat spinal cord injuries, mitigate diabetes, repair damaged organs, relieve pain and preserve lives. Even though cures may take years to develop, I believe that we cannot ignore the promise these cells hold. But I also believe that whatever research the federal government funds should follow clear ethical guidelines and use only embryos that would otherwise be destroyed.”
President Bush vetoed the Bill. The ban on federal funding was lifted by President Barack Obama in March, 2009.
Though Proposition 71 succeeded and established a board called the California Institute for Regenerative Medicine (CIRM), it is unclear if the grants will ever be issued. A lawsuit challenging California’s open meeting laws, and other suits from the People’s Advocate, National Tax Limitation Foundation, and California Family Bioethics Council attack the way CIRM is structured. The suits are tying any progress in knots.
The deadlock on embryonic cell research has led to developments in the use of adult stem cells as well as the use of “cord blood”. An entire industry has grown to salvage and store the blood remaining in the umbilical cord after birth. This blood is one of the richest sources of stem cells and is removed from the umbilical cord and the placenta right after the cord is cut.
The future holds great promise of treatment for cancer and a host of other diseases, regeneration of tissues and organs, grafting of spinal cords. There are many ethical and political hurdles that must be overcome in addition to the medical and scientific ones. Bellomo proposes that once feasible therapies are available for widespread disorders such as sickle-cell anemia, the demand for cures will exceed the opposition. The question then becomes where will these therapies emerge? He predicts such advances and demand within the next ten years.
Stumble it!
