Secular Service: Feb 22 2010
Red Sox Steve
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February 22, 2011
February 14, 2011
Stem Cell Research and Federal Funding - A Brief Overview
By Red Sox Steve
Vagabond Guru
Last time, we examined the science behind DNA and stem cells. DNA is an instruction manual for the assembly of proteins that make up the human body, and stem cells are the earliest distinct units that make up specific parts of the human body. The potential to use DNA and stem cells for therapeutic purposes is the main driving force behind stem cell research in laboratories around the world. One of the key sources of funding for this research has been the US government, subject to policy distinctions made by each presidential administration starting around 1975.
In 1975, a US government entity called the Ethics Advisory Board (EAB) had been the only regulatory body with the power to award federal funding for In-Vitro Fertilization (IVF) research. At the time, IVF research was at the cutting edge of investigation into human embryos. Under Presidents Reagan and George H.W. Bush, the EAB was disbanded, and no embryotic research was funded. By 1994, the NIH, under President Clinton, had developed research guidelines for investigation of human embryos. In 1995 however, congress returned to Republican control, and a ban on both federal funding to create embryos for research and destructive embryotic research has been in place ever since. This was done via an amendment to the annual appropriations bill called the Dickey-Wicker amendment, and it has been attached to every appropriations bill since then.1
In 1998, in Wisconsin, human stem cells were isolated and grown in a cell culture (under man-made and artificially controlled, external conditions) for the first time. The following year, the Department of Health and Human Services released a memo2 to the NIH which stated that because stem cells extracted from human embryos were "pluripotent", they are not considered to be part of a living human embryo. As a result, the pluripotent stem cells which are extracted from human embryos do not fall under the federal ban on research funding, and any related research is eligible for federal funds.
To quickly revert to our earlier discussion, the term "pluripotent" (or, "pluripotency") refers to the fact that certain cells, in this case, stem cells, can differentiate into any type of cell needed by the human body; most immediately, they can form the three germ layers we discussed last time: the ectoderm, endoderm and mesoderm. Pluripotent stem cells, however, cannot form a fetus or human by themselves because they lack the ability to form a placenta, the organ within the womb that enables the uptake of nutrients by the fetus from the mother.
On August 9, 2001 President Bush made a speech3 in which he delineated his administration's policy on stem cell research: the government will permit funding on any embryonic stem cells that already exist as a result of IVF; however, no federal dollars will be set aside for research based on the extraction of new stem cells from embryos. In 2005 and 2006, a bipartisan bill passed both houses of congress to allow federal funding of research on stem cell lines from new embryos, but was vetoed both times by President Bush. The scientific rationale for Bush's opposition is that by removing stem cells from the embryo, scientists are destroying the possibility that those stem cells will go on to produce a living organism.
In March 2009, President Obama changed the policy again4, repealing the ban on funding of research with new stem cell lines. Similar to his predecessors, he wouldn't approve spending federal funds on work that would destroy the embryo solely for research purposes, or where ESCs were obtained from embryos created by processes like nuclear transfer (cloning) or parthenogenesis (reproduction).
Nuclear transfer requires the manual exchange of a nucleus (where the DNA is located) in an unfertilized egg for a nucleus containing DNA scientists wish to replicate. Parthenogenesis involves embryotic development without fertilization. In both cases, any extraction of stem cells would interrupt the growth and development of the embryo. Further, Obama's policy would ban federal funding where ESCs or induced pluripotent cells are introduced into "non-human primate blastocysts" or in animals where ESCs contribute to the germ line (recall our brief summary of the germ layers from last time).
Federal funding policy for stem cell research changes every time the White House changes parties, which stunts the growth of knowledge we can glean from research efforts. Currently, stem cell research has the federal funding it needs from the Obama administration, and new stem cell lines can be used for research. As we look forward in our discussion, we will explore the scientific challenges that researchers face, and take a look at potential therapies with ties to stem cell research.
Sources:
1) Journal of Law, Medicine & Ethics; Summer2010, Vol. 38 Issue 2, p191-203, 13p
2) 1999 memo: http://news.sciencemag.org/scienceinsider/Implementing%20New%20Federal%20hESC%20Research%20Policy.pdf
3) August 9, 2001 speech by G.W. Bush: http://www.c-spanvideo.org/program/CellResea/start/35/stop/679
4) March 9, 2009 speech by B. Obama: http://www.c-spanvideo.org/program/SSci/start/0/stop/1005
February 01, 2011
The Science of Stem Cells
By Red Sox Steve
About a decade ago, both Celera Genomics, a private company led by Craig Venter, and The Human Genome Project, a government-funded effort headed by Eric Lander, were able to code the entire human genome. That is, both projects, simultaneously, were able to identify every base pair, in order, in human DNA. In one case, the DNA came from an unknown individual from Buffalo, New York and in another, from Venter himself.
Why is this important, and where does science take us from here?
The genetic code of a living thing, that is, the sequence of DNA molecules that are the "building blocks" of all life on earth, is the most basic information passed from one generation to the next. For the purposes of this discussion, animals, plants and humans appear and behave the way they do because of the DNA contained in their cells. DNA is considered our "instruction manual" for life. To carry the analogy further, the sequence of base pairs in a DNA molecule tells the body which parts should exist, and how they should fit together.
DNA is short for "Deoxyribonucleic Acid", and there are four different molecules that form the building blocks mentioned above:
1) Adenine
2) Cytosine
3) Guanine
4) Thymine
Each of the four molecules can only pair with one other. In other words, only Adenine and Thymine bind together, while only Guanine and Cytosine bind together, each forming what is called a "base pair". All 46 chromosomes (23 pairs) found in humans make up the entire genome, and together contain 3 billion base pairs of DNA.
It may surprise you to learn a few things about DNA and our genetic makeup:
1) We have nearly the same genetic makeup as our oldest human ancestors from billions of years ago.
2) Half of human DNA is similar to that found in a banana.
3) Every baby born today has 99.9% of its DNA in common with every other baby.
4) Only 1-2% of our entire genetic code is used to make up every cell in the human body.
5) Humans have 20-30,000 genes, about the same number as that found in a fly.
Based on the relative positions of the four base pairs in our genetic code, there exists enough information to make all the proteins a human organism needs to exist. When the sperm cell meets the egg, the DNA from both cells combine and replicate and a process known as "embryogenesis" has begun. This, however, is the most fundamental view of cell and reproductive biology. Stem cells take these fundamentals a bit further.
A "stem cell" is a particular type of cell that has the ability to replicate and differentiate to form almost any type of cell needed in the human body. There are two main types of stem cells:
1) Embryonic stem cells - these cells make up what is called the "embryo", which appears soon after fertilization
2) Adult stem cells - more specialized cells that can either regenerate in response to an injury or function normally in organs that require cells with regenerative capabilities like blood or digestive cells.
Embryonic stem cells ("ES" cells) are found in what is called the blastocyst. 5 days after fertilization of the egg by a sperm, the blastocyst forms as a distinct structure, during the earliest stages of embryogenesis. The blastocyst has an outer layer of cells called the trophoblast, which assists in attaching the embryo to the uterus and forms part of the placenta. The blastocyst also contains what is known as an "Inner Cell Mass" (ICM). The ICM is where ES cells used in stem cell research first appear as a distinct group.
Following the formation of the blastocyst, the next stage in embryogenesis is called gastrulation. The blastocyst forms into what is called the gastrula around 16 days after fertilization in mammals. When the gastrula is formed we start to see a connection between the embryo and a fully formed human. From the ICM are produced three distinct groups of cells - or "germ layers" - in the gastrula: the endoderm, the ectoderm and the mesoderm. A process of chemical signaling between adjacent cells called "primary induction" assists in the formation of separate germ layers. From these three germ layers, all the cell types needed by humans are formed. The three types of germ layers and examples of the cells they form are below:
1) Ectoderm: cells of the nervous system, neurons, lining of mouth and nostrils, and hair and nails.
2) Mesoderm: bone, cartilage, muscle, connective tissue, and reproductive cells
3) Endoderm: lung, thyroid and pancreas cells
After formation of the gastrula, secondary and tertiary induction help form the neural system and eventually other organs.
This is where stem-cell science has come into play. In normal embryogenesis, a blastocyst attached to the uterine wall has both the gastrula and trophoblast working together to eventually form a human embryo. Because of the presence of the trophoblast and the role it plays in induction, the three germ layers can successfully mature, forming the cells needed by a human. Further, when ES cells are removed from the blastocyst and placed in a test tube or on a plate without the trophoblast, differentiation can still occur. The ES cells will aggregate to form a gastrula and are still capable of forming three germ layers and any of the 200 types of cells needed by humans. Seen in this light, ES cells are thought to be "immortal".
In culture, and without the trophoblast, ES cells form what is called an "embryoid body". ES cells aggregate, due to the requirement of inter-cellular signaling, and attempt to form germ layers and an embryo. Unfortunately, the independent ES cells aggregate to form a hollow ball (called a "cystic embryoid body") and also produce a disordered and irregular collection of various types of cells including neurons, skin cells and muscle tissue.
What if scientists take ES cells from the blastocyst of one pregnant mouse and put them into the blastocyst of another pregnant mouse? Will they assist in the development of the fetus when surrounded by a "foreign" trophoblast? Again, injected ES cells have shown that they are capable of aggregating into germ layers, and forming various types of cells needed by their host mammal; however, they still form embryoid bodies (also called "teratomas"), and are considered benign tumors rather than helpful cells.
Essentially, ES cells are capable of forming every type of cell needed by the mammalian species they come from, however without proper guidance from their surroundings, they are "flying blind". They have the potential to form every type of cell, however they have no way of knowing how they assemble or where they should go.
The foundation of stem cell research is based on the idea that ES cells each contain sufficient DNA to code every protein needed in a human or other mammalian body. Therefore, scientists work from the standpoint of differentiation, attempting to promote the growth of specific proteins, neurons, and organs - essentially seeking to direct the growth of an ES cell to replace or bolster the function of cells already in a person's body. In later writings, I will expound on the specifics of stem-cell research and discuss how scientists are overcoming the challenges presented by trying to promote cells to grow with a specific function in mind.