When I say “stem cell”, the first thing most people will think of is controversy. Whether from uproar in politics about human embryos or from scams out of foreign countries, stem-cell research has had a short and rocky history. Before I began my internship working with these cells this summer, I wasn’t quite clear on what they were, where they came from or why they might be useful.
So what’s the truth about stem cells? There are three distinct types of stem cells, Embryonic, Induced Pluripotent, and Adult. We’ll begin with the first and most controversial, embryonic stem cells. These were the first to be harvested, initially from mice in 1981 and then from humans in 1998. They possess a variety of useful characteristics, namely, these embryonic stem cells are “pluripotent.” This means that they can become any cell type in the human body. Think of them like the trunk of a tree; they are the base from which all cell types branch and grow. Through a process called directed differentiation, scientists can nudge a pluripotent cell up a specific branch, into neurons, heart cells, blood cells, or whichever cell type they would like to study.
Because of this pluripotent property, stem cells hold immense promise for both basic research and clinical therapies. By creating a neuron in a dish, a scientist could study human processes at a microscopic level, opening the gateway to thousands of potential new insights about our species. This technique could also eliminate the need for animals in research, allowing scientists to make more accurate predictions about how new drugs may work, and achieve a greater knowledge of human biology. In therapy, stem cells could be used to grow new organs, or be grown into different cell types and injected into a failing organ to reverse damage. Because the promise of pluripotent stem-cell research was so immense, scientists were eager to study the new technique.
In the early days of stem-cell research, the only way to obtain these pluripotent stem cells was from embryos left over from in-vitro fertilization treatments. When a parent decides to undergo in vitro fertilization, more fertilized eggs are created than can be implanted. After a successful pregnancy, the parent is given a choice for what she would like to do with the excess eggs. They can choose to store them, discard them, or donate them to science. Scientists cannot pay a parent for use of embryos. If the parents choose to donate the fertilized egg, it is grown in a lab for approximately five days. At this stage of development, the embryo is called a blastocyst, and contains 50-150 cells. The inner cell mass, where the stem cells are found, is then extracted, and the remainder of the blastocyst is discarded.
In 2001, three years after this technique was first done successfully, Congress placed severe limitations on stem-cell research. The Dickey-Wicker amendment banned using federal funds for any research that creates a human embryo, the process routinely done in private fertilization clinics, or destroys an embryo. Because the creation of embryonic stem cells results in the destruction of the original blastocyst, the amendment effectively banned the NIH from supporting stem-cell research. The argument for the amendment came from an ethical argument about using human beings for research. It is an argument that shares many similarities with that of anti-abortion proponents: the belief that human life begins at conception. Proponents of the bill argued that a five-day-old cluster of cells was in fact an independent life, whereas opponents contended there was no thought and therefore no consciousness to destroy. The ensuing ethical debate continued throughout the 2000s, with some states, including California and New York, overriding federal laws by creating their own stem-cell agencies with state funding. Due to the limits on available funding and the ethical concerns, researchers began to look towards alternatives to embryonic stem cells.
At first adult stem cells seemed like a solution. These are the cells that are contained in every adult human within the bone marrow. They can create new red blood cells and various cells of the immune system. All adult stem cells are considered multipotent. Think of them like a big branch on a tree; they can become any type of immune cell, but cannot become a heart cell or a brain cell. This characteristic severely limits their growth and their potential. What scientists needed was a pluripotent stem-cell type, one that was identical to embryonic stem cells but could avoid the ethical issues.
In 2006, the dream of such an ideal cell became reality. Called induced pluripotent stem cells, this discovery heralded a new age in stem-cell research. Using skin cells from adults, a scientist named Shinya Yamanaka was able to reprogram or “trick” the cells into believing they were pluripotent stem cells again. By utilizing four dominant master regulator genes, he turned back the clock on these skin cells, so that they expressed all the same characteristics of embryonic stem cells, without using an embryo. Now, scientists are able to take cells from adults and recreate a cell type with biologically powerful properties. In addition to being identical to embryonic stem cells, induced stem cells can be derived from a living adult patient, opening the door to personalized immune matched medicine, “disease in a dish” drug modeling, and a variety of new and useful applications. In an unprecedentedly short amount of time, a mere six years after the discovery, last year the Nobel Committee recognized the significance of Yamanaka’s work. They awarded him, along with Cambridge biologist Sir John Gurdon, the Nobel Prize for Medicine.
The laws surrounding stem cell use for research still vary from state to state, as Congress debates how to use federal funds in consideration of this new kind of non-embryonic stem cells. As the legislation begins to change and research takes leaps and strides towards clinical trials, stem cells will once again come into the public perception, and assuredly the public debate.