genetics biology

G e n e t i c s , t e c h n o l o G y , a n d s o c i e t y

stem cell Wars

Stem cell research may be the most controversial research area since the beginning of recombinant DNA technology in the 1970s. Although stem cell research is the focus of presiden- tial proclamations, media campaigns, and ethical debates, few people understand it sufficiently to evaluate its pros and cons.

Stem cells are primitive cells that rep- licate indefinitely and have the capacity to differentiate into cells with special- ized functions, such as the cells of heart, brain, liver, and muscle tissue. All the cells that make up the approximately 200 distinct types of tissues in our bodies are descended from stem cells. Some types of stem cells are defined as totipotent, mean- ing that they have the ability to differenti- ate into any mature cell type in the body. Other types of stem cells are pluripotent, meaning that they are able to differentiate into any of a smaller number of mature cell types. In contrast, mature, fully differ- entiated cells do not replicate or undergo transformations into different cell types.

In the last few years, several research teams have isolated and cultured human pluripotent stem cells. These cells remain undifferentiated and grow indefinitely in culture dishes. When treated with growth factors or hormones, these pluripotent stem cells differentiate into cells that have the characteristics of neural, bone, kidney, liver, heart, or pancreatic cells.

The fact that pluripotent stem cells grow prolifically in culture and differen- tiate into more specialized cells has cre- ated great excitement. Some foresee a day when stem cells may be a cornucopia from which to harvest unlimited numbers of specialized cells to replace cells in dam- aged and diseased tissues. Hence, stem cells could be used to treat Parkinson dis- ease, type 1 diabetes, chronic heart dis- ease, Alzheimer disease, and spinal cord injuries. Some predict that stem cells will be genetically modified to eliminate trans- plant rejection or to deliver specific gene products, thereby correcting genetic de- fects or treating cancers. The excitement about stem cell therapies has been fueled by reports of dramatically successful ex- periments in animals. For example, mice with spinal cord injuries regained their

mobility and bowel and bladder control after they were injected with human stem cells. Both proponents and critics of stem cell research agree that stem cell therapies could be revolutionary. Why, then, should stem cell research be so contentious?

The answer to that question lies in the source of the pluripotent stem cells. Until recently, all pluripotent stem cell lines were derived from five-day-old embryonic blas- tocysts. Blastocysts at this stage consist of 50–150 cells, most of which will develop into placental and supporting tissues for the early embryo. The inner cell mass of the blastocyst consists of about 30 to 40 pluripotent stem cells that can develop into all the embryo’s tissues. In vitro fertilization clinics grow fer- tilized eggs to the five-day blastocyst stage prior to uterine transfer. Embryonic stem cell (ESC) lines are created by taking the in- ner cell mass out of five-day blastocysts and growing the cells in culture dishes.

The fact that early embryos are de- stroyed in the process of establishing human ESC lines disturbs people who believe that preimplantation embryos are persons with rights; however, it does not disturb people who believe that these embryos are too primitive to have the status of a human being. Both sides in the debate invoke fundamental ques- tions of what constitutes a human being.

Recently, scientists have developed several types of pluripotent stem cells without using embryos. One of the most promising types—known as induced plu- ripotent stem (iPS) cells—uses adult somatic cells as the source of pluripotent stem cell lines. To prepare iPS cells, scientists iso- late somatic cells (such as cells from skin) and infect them with engineered retrovi- ruses that integrate into the cells’ DNA. These retroviruses contain several cloned human genes that encode products re- sponsible for converting the somatic cells into immortal, pluripotent stem cells.

The development of iPS cell lines has generated renewed enthusiasm for stem cell research, as these cells bypass the ethical problems associated with the use of human embryos. In addition, they may become sources of patient-specific pluripotent stem cell lines that can be used for transplanta- tion, without immune system rejection.

At the present time, it is unknown whether stem cells of any type will be as miraculous as predicted; however, if stem cell research progresses at its current rap- id pace, we won’t have long to wait.

Your Turn

Take time, individually or in groups, to answer the following questions. Investigate the references and links to help you understand the technologies and controversies surrounding stem cell research.

1. What, in your opinion, are the scien- tific and ethical problems that still surround stem cell research? Are these problems solved by the new methods of creating pluripotent stem cells?

You can find descriptions of some new methods of generating pluripotent stem cell lines, and the ethical issues that accompany these meth- ods, in Kastenberg, Z. J. and Odorico, J. S. 2008. Alternative sources of pluripotency: sci- ence, ethics, and stem cells. Transplantation Rev.22: 215–222.

2. What are the current stem cell re- search laws in your region, and how do these laws compare with national regulations?

A starting point for information about stem cell research regulations can be found on the Stem Cell Information Web site of the National Insti- tutes of Health (http://stemcells.nih.gov).

3. Do you oppose or support stem cell research? Why, or why not?

An interesting online poll, along with argu- ments for and against stem cell research, is offered by the Public Broadcasting Corpora- tion, at http://www.pbs.org/wgbh/nova/ body/stem-cell-poll.html.

4. What, in your opinion, is the most significant development in stem cell research in the last year?

Some ideas to start your search are: the PubMed Web site (http://www.ncbi.nlm.nih.gov/ sites/entrez? db=PubMed) and the New York Times online Stem Cell page (http:// topics.nytimes.com/top/news/health/ diseasesconditionsandhealthtopics/ stemcells).