IQP-43-DSA-7640 IQP-43-DSA-5620 IQP-43-DSA-4570 IQP-43-DSA-2286 STEM CELLS AND SOCIETY An Interactive Qualifying Project Report Submitted to the Faculty of WORCESTER POLYTECHNIC INSTITUTE In partial fulfillment of the requirements for the Degree of Bachelor of Science By: ____________________ ____________________ Clinton Biltucci Brandon Cooney ____________________ ____________________ Thomas Fonteccio Thomas Izzo August 27, 2010 APPROVED: _________________________ Prof. David S. Adams, Ph.D. Project Advisor ABSTRACT The purpose of this IQP is to compile information regarding the topic of stem cells, and then draw conclusions about this new technology and its effects on society. Stem cells are undifferentiated cells with the ability to renew and divide indefinitely to generate specialized cells. The seemingly unlimited potential of stem cell research has several medical applications and has founded the new field of regenerative medicine. However, their use draws strong ethical concerns for embryonic type stem cells, which leads to the creation of legislation to dictate the boundaries of this new technology. 2 TABLE OF CONTENTS Signature Page …………………………………………………………………….. 1 Abstract ……………………………………………………………………………. 2 Table of Contents ………………………………………………………………….. 3 Project Objectives ……..……………………………...…………………………… 4 Chapter-1: Stem Cell Types …………….……...………………………………… 5 Chapter-2: Stem Cell Applications ..…………………………………………….. 24 Chapter-3: Stem Cell Ethics ……………………………………………………… 32 Chapter-4: Stem Cell Legalities ……………………………….…………………. 45 Project Conclusions …………………………………………….………………… 58 3 PROJECT OBJECTIVES The objective of this IQP project was to investigate the controversial topic of stem cells, and to discuss the progression of this new technology and its influence on society. The purpose of chapter-1 is to define the various types of stem cells, where they are found, and how they can be distinguished via potency. Chapter-2 describes how these stem cells are applied in practical experiments that have generated success not only in animal studies but in human clinical trials. The purpose of chapter-3 is to confront the moral concerns surrounding this controversial topic, while chapter-4 dives into U.S. and international laws that govern this growing field. Finally, the author‘s conclusions are discussed based on the research gathered for this project. 4 CHAPTER-1: STEM CELL TYPES Thomas Fontecchio Stem cells are the foundation for every organ, tissue, and cell in the body. Stem cells are a class of undifferentiated cells that are able to differentiate into a specific cell type. The major function of stem cells is to maintain homeostasis in the body in terms of replacing dead or injured cells with new ones that function properly. A common misconception is grouping stem cells into one large category even though there are a number of different types. When stem cells are brought up in conversation, most people associate the term with the infamous embryonic stem cells, but not all stem cells are the same and some are far less controversial than others. Recent advances in technology and science have provided health care professionals with new opportunities and alternatives to conventional techniques that only treat the symptoms of a disease or injury. These cells have the ability to continuously multiply and develop into various types of cells in the body founding the new field of ―regenerative medicine‖. The purpose of this chapter is to document the various types of stem cells and to lay the foundation for our later chapter discussions on their ethics and legalities. Stem Cell Potency The primary defining feature of a stem cell is potency, or its ability to become other cell types. Stem cells divide asymetrically, producing one cell that retains the ability to divide indefinitely and another cell that is more specialized than the first. The function of the indefinitely dividing population is to serve as a reservoir of long lived cells, while the more differentiated cells replace damaged or aging tissues. The less potent a stem cell is, the fewer 5 tissues it can form. There are four varying degrees of potency. Totipotency is the ability of a cell to produce all the differentiated cells that form an entire organism, plus the extra-embryonic tissue such as the placenta. Newly fertilized eggs are totipotent. As the cells of the embryo begin dividing, the cells through the embryo 8-cell stage (48 hrs) also remain totipotent, but not thereafter. Embryonic stem cells (ESCs) constitute the inner cell mass of the 5-day old blastocyst, and are termed pluripotent because they have the ability to differentiate into any of the three germ layers (endoderm, mesoderm, and ectoderm), and can give rise to any adult tissue. Multipotent cells can form multiple related types of cells, but with a limited number of lineages. An example of multipotent stem cells are hematopoietic stem cells that can develop into several types of blood and marrow cells, but which normally lack the ability to develop into brain or nerve cells. Stem cells which are almost fully differentiated are known as unipotent cells, which are locked into specific cell fates, depending on the tissue origin. Stem Cell Background Recent developments in stem cell research have been considered breakthroughs for science and the field of biology, so with all the press coverage and ethical debates, the layperson might think stem cells are a recent discovery. Stem cell work actually has a long history that dates back to the late 1800s. In 1886, William Sedgwick used the term ―stem cell‖ to describe the regenerative properties of plants (Chamany , 2004). A decade later, E.B. Wilson applied the term to cells in the roundworm that retained genetic material and appeared to regenerate. Contemporary stem cell techniques also arose from embryology work of the late 1800s and early 1900s. In 1912, Jacques Loeb successfully achieved artificial parthenogenesis, the process by which unfertilized eggs undergo chromosome duplication and rapid mitosis to establish a 6 developing embryo (Chamany , 2004). Loeb subjected sea urchin eggs to various concentrations of salt, stimulating them to undergo cell division as if sperm had fertilized them. The ability to induce an organism that does not naturally reproduce via parthenogenesis was groundbreaking. The work was heralded in newspaper headlines as ―The Creation of Life‖, and made accessible to the public through literature. More recently in the 1950‘s and 1960‘s, in vitro fertilization (IVF) techniques were developed for animals, and were later applied to humans in IVF clinics in the late 1960‘s (Deech, 2008). IVF clinics provided a boost to stem cell knowledge from the research performed with extra discarded embryos that were not reimplanted for reproductive purposes, eventually leading in 1998 to the isolation and growth of human ESCs from 5 day old blastocysts (Thomson et al., 1998). The use of embryos in research has always been a topic of ethical debate, and will be discussed in detail in Chapter-3. Embryonic Stem Cells With the discovery of IVF, scientists were able to study the developmental pathways beyond the first stages of embryogenesis and chart the fate of each cell in the developing organism. It was established that all adult cells arise from three primary germ layers: the endoderm, mesoderm, and ectoderm. These cell layers arise early in embryonic development about day-5 when a cavity called the archenteron forms the blastula. The blastula (Figure-1) is a hollow ball of cells consisting of the inner cell mass (ICM) which contains ES cells and forms the embryo, and the trophoectoderm which forms the placenta. The ICM over time reorganizes into the three primary germ layers. 7 Figure-1: Photograph of a Human Blastocyst at Day-5. The cells of the inner cell mass (ICM) contain ES cells, and eventually become the embryo. The cavity or blastocoel is marked with a C. The outer layer is the trophoectoderm that will form the placenta. (Advanced Fertility Center, 2007) The endoderm is the first embryonic layer to form, and begins in the human embryo at about two weeks after fertilization. By the fifth week, the endoderm will differentiate into internal structures such as the liver or pancreas. The mesoderm is the next layer to grow. From the mesoderm comes the intermediate organs such as muscle, bone, connective tissue, and the reproductive and urinary systems. The ectoderm is the final germ layer to form, and consists of three separate parts: surface ectoderm, neural ectoderm, and neural crest. The surface ectoderm is responsible for developing skin and other tissue such as eyelid epidermis, tooth enamel, and the mucous membrane of the mouth. The neural ectoderm acts to form the retina, optic nerve fibers, and retinal pigment. This part of the ectoderm contains the neural tube, which is responsible for developing the central nervous system. The cells in the neural crest develop into parts of the skeletal system, autonomic nervous system, and produce hormones (Shiraki et al., 2009). 8 A fourth set of embryonic cells specifically give rise to the reproductive organs and are called the primordial germ cells (PGCs). During the 1950‘s and 1960‘s, work by cancer specialist Leroy Stevens first suggested that some of these PGC cells might be pluripotent and that surrounding cells provide the necessary environmental signal needed to stimulate differentiation (Chamany , 2004). Stevens conducted a series of experiments and found that such cells exist and share similar characteristics with cancer cells. Stevens came across some cells which originate from primordial germ cells and found that they formed teratomas. A teratoma is an encapsulated tumor with tissue or organ components resembling normal derivatives of all three germ layers (Baker, 2009). PGCs normally go on to develop into the cells of the ovaries or the testes in the adult organism, but some cells maintain the capacity to become a variety of cell types, and others can become malignant which develop into tumors. Stevens decided to conduct an experiment with early embryonic cells from the inner cell mass and found that they went on to develop into teratomas upon injection into mice testes.