Embryo Project Encyclopedia

Human pluripotent stem cells are valued for their potential to form numerous specialized cells and for their longevity. In the US, where a portion of the population is opposed to destruction of human embryos to obtain stem cells, what avenues are open to scientists for obtaining pluripotent cells that do not offend the moral sensibilities of a significant number of citizens? It is this question that the official position paper, or white paper, "Alternative Sources of Human Pluripotent Stem Cells," published in May 2005 by the President's Council on Bioethics under the chairmanship of Leon Kass, seeks to answer. Three experts external to the council, Andrew Fire from the Stanford University School of Medicine, Markus Grompe of the Oregon Health and Science University, and Janet Rossant from the Samuel Lunenfeld Research Institute in Toronto, also reviewed the white paper prior to publication.

Matthew Kaufman was a professor of anatomy at the University of Edinburgh, in Edinburgh, UK, who specialized in mouse anatomy, development, and embryology during the late twentieth century. According to the The Herald, he was the first, alongside his colleague Martin Evans, to isolate and culture embryonic stem cells. Researchers initially called those cells Evans-Kaufman cells. In 1992, Kaufman published The Atlas of Mouse Development, a book that included photographs of mice development and mice organs over time. Kaufman also wrote books about UK medical history, phrenology, or the study of craniums as an indicator of character or mental ability, and medical teaching in the eighteenth and nineteenth centuries. Kaufman’s anatomical records and experiments in mouse development contributed to genetic engineering, embryology, and anatomy.

In the twentieth and early twenty-first centuries, Gail Roberta Martin specialized in biochemistry and embryology, more specifically cellular communication and the development of organs. In 1981, she named any cell taken from inside a human embryo at the blastocyst stage an “embryonic stem cell”. During development, an embryo goes through the blastocyst stage just before it implants in the uterus. Embryonic stem cells are useful for experiments because they are self-renewing and able to develop into almost any cell type in the body. Martin later identified a key chemical component in limb development and continues to study embryogenesis, or the growth of embryos over time. Martin’s work on embryonic stem cells has allowed scientists to further research and treat human diseases, and her study of how organs form has helped scientists learn about the healthy growth of embryos.

In April 1953, James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure of Deoxyribose Nucleic Acid” or “A Structure for Deoxyribose Nucleic Acid,” in the journal Nature. In the article, Watson and Crick propose a novel structure for deoxyribonucleic acid or DNA. In 1944, Oswald T. Avery and his group at Rockefeller University in New York City, New York published experimental evidence that DNA contained genes, the biological factors called genes that dictate how organisms grow and develop. Scientists did not know how DNA’s function led to the passage of genetic information from cell to cell, or organism to organism. The model that Watson and Crick presented connected the concept of genes to heredity, growth, and development. As of 2018, most scientists accept Watson and Crick’s model of DNA presented in the article. For their work on DNA, Watson and Crick shared the 1962 Nobel Prize in Physiology or Medicine with Maurice Wilkins.

According to the US National Institutes of Health (NIH), the standard American source on stem cell research, three characteristics of stem cells differentiate them from other cell types: (1) they are unspecialized cells that (2) divide for long periods, renewing themselves and (3) can give rise to specialized cells, such as muscle and skin cells, under particular physiological and experimental conditions. When allowed to grow in particular environments, stem cells divide many times. This ability to proliferate can yield millions of stem cells over several months. As long as the stem cells remain unspecialized, meaning they lack tissue-specific structures, they are able to sustain long-term self-renewal.

Max Ludwig Henning Delbrick applied his knowledge of theoretical physics to biological systems such as bacterial viruses called bacteriophages, or phages, and gene replication during the twentieth century in Germany and the US. Delbrück demonstrated that bacteria undergo random genetic mutations to resist phage infections. Those findings linked bacterial genetics to the genetics of higher organisms. In the mid-twentieth century, Delbrück helped start the Phage Group and Phage Course in the US, which further organized phage research. Delbrück also contributed to the DNA replication debate that culminated in the 1958 Meselson-Stahl experiment, which demonstrated how organisms replicate their genetic information. For his work with phages, Delbrück earned part of the 1969 Nobel Prize for Physiology or Medicine. Delbrück's work helped shape and establish new fields in molecular biology and genetics to investigate the laws of inheritance and development.

In 1954 Max Delbruck published On the Replication of Desoxyribonucleic Acid (DNA) to question the semi-conservative DNA replication mechanism proposed that James Watson and Francis Crick had proposed in 1953. In his article published in the Proceedings of the National Academy of Sciences, Delbrück offers an alternative DNA replication mechanism, later called dispersive replication. Unlike other articles before it, On the Replication presents ways to experimentally test different DNA replication theories. The article sparked a debate in the 1950s over how DNA replicated, which culminated in 1957 and 1958 with the Meselson-Stahl experiment supporting semi-conservative DNA replication as suggested by Watson and Crick. On the Replication played a major role in the study of DNA in the 1950s, a period of time during which scientists gained a better understanding of DNA as a whole and its role in genetic inheritance.

In 1956, Gunther Stent, a scientist at the University of California Berkeley in Berkeley, California, coined the terms conservative, semi-conservative, and dispersive to categorize the prevailing theories about how DNA replicated. Stent presented a paper with Max Delbrück titled “On the Mechanism of DNA Replication” at the McCollum-Pratt Symposium at Johns Hopkins University in Baltimore, Maryland. In response to James Watson and Francis Crick’s proposed structure of DNA in 1953, scientists debated how DNA replicated. Throughout the debate, scientists hypothesized different theories about how DNA replicated, but none of the theories had sound experimental data. Stent introduced DNA replication classes that, if present in DNA, would yield distinct experimental results. Conservative, semi-conservative, and dispersive DNA replication categories shaped scientists' research into how DNA replicated, which led to the conclusion that DNA replicated semi-conservatively.

In 2015, biologist Helena D. Zomer and colleagues published the review article “Mesenchymal and Induced Pluripotent Stem Cells: General Insights and Clinical Perspectives” or “Mesenchymal and Induced Pluripotent Stem Cells” in Stem Cells and Cloning: Advances and Applications. The authors reviewed the biology of three types of pluripotent stem cells, embryonic stem cells, or ESCs, mesenchymal stem cells, or MSCs, and induced pluripotent stem cells, or iPS cells. Pluripotent stem cells are a special cell type that can give rise to other types of cells and are essential for development. The authors describe the strengths and weaknesses of each type of stem cell for regenerative medicine applications. They state that both MSC and iPS types of stem cells have the potential to regenerate tissues among many other therapeutic possibilities. In their article, Zomer and colleagues review the potential for MSCs and iPS cells to reshape the field of regenerative and personal medicine.