Monday, October 17, 2005

New Methods to Derive Embryonic Stem Cells

New Methods to Derive Embryonic Stem Cells

If you are interested in stem cell research, you have probably already heard by now about the studies published in this week’s issue of Nature involving new ways to derive embryonic stem cells in mice. These have been widely covered by the media, so in this post I’ll give you several brief summaries as they have appeared in different sources. The story will probably continue to circulate for some time.

The nature.com website reports on the two studies. The article lays the background about the ethical concerns regarding creating and destroying an embryo for the purpose of obtaining stem cells, then discusses the two studies on mice. In the first study, researchers at MIT performed an SCNT variant called “altered nuclear transfer” (ANT) in which a gene in the donated egg is switched off. The result is the growth of a blastocyst from which embryonic stem cells can be derived but which is unable to implant in a uterus and develop into a fetus. In the second study, researchers at Advanced Cell Technology in Massachusetts took single cells known as blastomeres from eight-cell embryos. The blastomeres were used to derive ES lines, while the embryos went on to develop into healthy mice. This technique is similar to one already used in IVF procedures, known as preimplantation genetic diagnosis (PGD).

The article then goes on to give some opinions of other researchers on the studies. The PGD method has the disadvantage that the cells derived are only a genetic match for the couple who underwent IVF treatment, not for the prospective patient. Some people are also concerned that the blastomere also has the potential to develop into a viable embryo on its own. Another concern that has been voiced is potential damage to the baby which develops from the embryo from which the blastomere was removed.

The ANT method, on the other hand, is seen by some as destroying the embryo through engineering a mutation. So to the question of “What is a human?” has now been added the question of “What is an embryo?”

The Christian Science Monitor reports on the study as well. The article begins by addressing the ethical concerns and the quest for a way to resolve them, and includes the following:
This broad lab-based approach "is encouraging," says the Rev. Tadeusz Pacholczyk of the National Catholic Bioethics Center in Philadelphia, who holds a doctorate in neuroscience from Yale University. "You're using the power of science to develop a solution that gets around a very grave moral objection."

The article repeats the methods and results of the studies and summarizes opinions of several other un-named scientists, who believe that the ANT method would take away money from SCNT research. The scientists “added that the approach doesn't solve any ethical dilemma because in their view it incorrectly presumes that the ethical standing of an individual hinges on the action of a single gene.”

The English language version of the Chinese Xinhuanet reports a few more details on the ANT procedure; the researchers used RNA interference to target the Cdx2 gene. They then had to repair this and re-enable the gene in the derived stem cells.

Forbes picked up the HealthDay News version of the story, which included a number of quotations from various scientists, including Dr. Robert Lanza, one of the researchers in the PGD method. The article also had the following:
A statement from Dr. Robert Schenken, president of the American Society for Reproductive Medicine, added a cautionary note.

"The research by Professor Jaenisch and Professor Lanza and their colleagues announced today represent important steps forward in the rapidly evolving field of stem cell science," the statement read. "It is essential to note that both of these studies, while potentially very important, are also very preliminary. There is much work to do before any of this might be applied to human beings. Thus far, our work in many other areas has taught us that in reproductive medicine, what works in animals may not translate well to humans."

An AP story picked up by the Columbus Dispatch quoted Richard Doerflinger, deputy director of pro-life activities for the Catholic bishops conference, as saying that the PGD method was a way “to select out genetically imperfect embryos” and also posed a risk of harm. Doerflinger also said that the ANT method was creating an embryo and then destroying it. However, the AP story quoted the Rev. Pacholczyk as saying that it was a step in the right direction.

The Australian reported on the PGD method, including a quote from parliamentary health secretary Christopher Pyne: "I object to the idea that embryos are available for research where I think they should be treated with some respect, rather than treated as a resource upon which human beings can experiment and interfere with.”

The study is also reported, with a number of different people weighing in, in the San Francisco Chronicle, the Boston Globe, Science Daily (UPI), the Washington Post, Reuters, the BBC, the Sydney Morning Herald, and others. The studies appear to have raised as many issues as they might resolve on the ethical front. It is still of course unknown how well either procedure would work on humans as opposed to mice.

An Editorial Supporting Stem Cell Research in Florida

An Editorial Supporting Stem Cell Research in Florida

In an opinion piece appearing in the Palm Beach Post, the author Eve Herold argues that Floridians need to support embryonic stem cell research. She points out the number of elderly Floridians with some form of a degenerative disease which might be treated by stem-cell therapies and argues that embryonic stem cell research in addition to adult stem cell research is necessary for the following reasons:

Adult stem cells can only generate a limited number of stem cells, while embryonic stem cells “hold the entire blueprint for the human body”; for scientists to learn how to “reprogram” adult stem cells, they need to understand how it occurs in embryonic stem cells and what the factors are; existing embryonic stem cell lines have mutated and also have been contaminated by the feeder mouse cells; the only way to create a stem cell match to avoid an immune system response is by using SCNT technology to put a particular patient’s DNA into the embryo to create the new cells; and that many of the existing federally-funded embryonic stem cell lines can only be used for research and teaching and patent restrictions limit scientists’ experimenting all the way to treatment. She also argues that the United States will continue to fall behind other countries, but the state of Florida can maintain global competitiveness.

This is a through, 2 page single-spaced opinion piece that seems well grounded in science.

Summary of a Right-to-Life Editorial

I’m providing this summary because the editorial refers to some existing research, and because I’m following what happens in the Wisconsin debate. The editorial itself does not provide any research news.

An opinion piece appearing in the Milwaukeee Journal-Sentinel on-line argues that therapeutic cloning will lead to cloning of human embryos to live through the fourth or sixth month of gestation so that more stable cells can be used to create organs and tissue as needed. She refers to a study on cows where livers from cloned fetal cows were put into adult cows; she also refers to “artificial womb” studies. The conclusion is to urge Governor Jim Doyle not to veto the recent legislation regarding SCNT.

A copy of the article she refers to by Robert Lanza can be found on the website of Advanced Cell Technology; download the PDF “Long-Term Bovine Hematapoietic Engraftment with Clone-Derived Stem Cells.” Lanza has also done work cloning endangered species, such as the guar. The “artificial womb” study by Hung-Ching Liu was reported in 2002, one source being the British newspaper The Guardian. Liu’s work is to help women who are unable to carry a baby to term.

Australian Editorial About Stem Cell Research

Australian Editorial About Stem Cell Research

The Age printed an opinion piece by Alan Nichols, an Anglican priest and writer, and director of the Centre for Applied Christian Ethics at Ridley College, Melbourne University, on October 16. Nichols argues for preserving the status quo in the Australian stem cells debate:

But there is a middle way - to support the status quo, which would allow further research on embryo stem cells to see what benefit it can bring, but continue the legislative ban on therapeutic cloning because the arguments to lift the ban are not conclusive. The effect of this would be to simply extend the two pieces of legislation, and insert another sunset clause three or five years hence.
He argues for preserving the status quo for the following reasons: adult stem cell research has already shown very promising results; only a few embryonic stem cell research trials have been done in Australia but the results show good potential; but he sees therapeutic cloning as close to eugenics or Nazi attempts to create a master race. He says that he would need to see first that the research on existing, donated embryos has been fruitful, and then if it has used up the entire existing embryos before creating new ones.

Nichols says he regards the moment 14 days after conception (a period when 25 % of pregnancies still end in spontaneous abortion) as the important moment in the embryo becoming human life. He acknowledges that other people who are pro-life have different opinions and says,

We support medical research to achieve public good, but give us time for our understanding and ethics to catch up. Give us time to see what happens.
He concludes with a request to not treat embryos as a commodity or to makes business-based arguments for research; “they said this about the slave trade.”

I found this piece to be generally well-written and though provoking, precisely because it struggles with the issue instead of offering a dogmatic response on either side. I do think that comparing therapeutic cloning to eugenics or Nazi experiments is a good way to increase the temperature of the rhetoric without thinking through the scientific issues carefully. While the technology to create a “better” human being may come along at some point, and will certainly be a hotly debated issue, SCNT is not it.

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