Approved Stem Cells' Potential Questioned

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Washington Post reports: (full story here http://www.washingtonpost.com/wp-dyn/articles/A7420-2004Oct28.html?nav=rss_nation )

Approved Stem Cells' Potential Questioned

By Rick Weiss
Washington Post Staff Writer
Friday, October 29, 2004; Page A03

All of the human embryonic stem cells available to federally funded scientists under President Bush's three-year-old research policy share a previously unrecognized trait that fosters rejection by the immune systems, diminishing their potential as medical treatments, new research indicates.

A second study has concluded that at least a quarter of the Bush-approved cell colonies are so difficult to keep alive they have little potential even as research tools.

The two studies -- the second still incomplete and the first one provisionally accepted for publication in a top-tier scientific journal but not yet published -- add new elements to the escalating debate over U.S. stem cell policy.

Embryonic stem cell research has become an unexpected wedge issue in the neck-and-neck race for the White House, with Bush insisting that it would be immoral to expand the research to include new cell colonies and Democratic challenger John F. Kerry promising to loosen the restrictions that today limit federal funding to 22 of the more than 150 known cell colonies.

The first study, led by Fred Gage of the Salk Institute in La Jolla, Calif., and Ajit Varki of the University of California at San Diego, focused on a peculiar aspect of the federally approved cell lines: Unlike colonies being derived using newer techniques, all the Bush-approved colonies were initially cultivated in laboratory dishes that also contained mouse cells.

Scientists and the Food and Drug Administration have already expressed concern that animal viruses lurking in those mouse cells might infect the human cells and cause trouble when they are transplanted into patients, as doctors hope to do.

With adequate testing, those cells may yet gain approval for use in patients, the FDA has said. But the new work suggests that the mouse-exposed cells have an additional drawback.

At the heart of the problem is that all mammalian cells -- with the exception of human cells -- bear certain molecules on their surface, known as N-glycoylneuraminic acid. (Human cell surfaces bear a different but related molecule, N-acetyl neuraminic acid.)

Varki had previously demonstrated that the vast majority of people have antibodies against this molecule, perhaps as a result of eating mammalian meat such as beef. The new work shows that human embryonic stem cells grown on mouse cells "consume" the mouse molecules and then display them on their own surfaces.

When human blood serum was added to the mouse-cultivated human stem cells in lab dishes, antibodies attacked the stem cells and killed them. In the eyes of the immune system, "these human cells look like animal cells . . . which leads to [their] death," Gage said at a recent scientific meeting.

Details of the experiment are embargoed until the research report is published, but Gage described the work on Oct. 12 to a panel of experts at the National Academies of Science, which is drawing up policy recommendations on stem cell research.

Several teams around the world have lately had success growing human embryonic stem cells without mouse cells, and proponents of stem cell research said yesterday that the findings strengthen the case for letting federally funded researchers work on newer stem cell colonies..........

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IMO, the only way that science is to make headway with stem cell research, is if new, untainted lines are made available. Obviously, George Bush is not going to permit this, so it is up to private foundations to provide scientific grants to enable this most crucial work to move forward.

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From "Chemical & Engineering News", the weekly publication of the American Chemical Society, October 18, 2004, p 36 (emphasis mine):

"Policies on the conduct of embryonic stem cell research sharply divide Bush and Kerry. The issue is extremely controversial because the creation of some new cell lines would involve the use and destruction of human embryos. Bush severly restricted federally supported research in August 2001 to only those cell lines started by that date. He has not wavered from the policy since then, despite scientists' concerns that actual usable cell lines under this policy are too few to enable much research. Before Bush allowed this limited support, there was no federal spending on embryonic stem cell research.
At the AAAS forum, Walker [a Bush spokesman] argued that Bush has taken a moderate path, funding embryonic stem cell research in such a way that it avoided a serious confrontation in Congress, where even tighter restrictions might have been imposed. 'Without his leadership, there could have been a firestorm on Capitol Hill that would have retarded progress,' he said. Walker also noted that considerable advances have been made in using other stem cells, such as umbilical cord blood stem cells, in treatment of diseases. Bush has stated that he remains committed to fully exploring the promise and potential of stem cell research without violating ethical principles and while maintaining respect for all human life. Bush has also repeated his opposition to all forms of human cloning, even if for research purposes."

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I must admit I'm not as well-read in this subject as I should be. A few of the points I've heard, though, include:
* Bush didn't ban embryonic stem cell research; he just limited federal funding.
* Alternative stem cell sources--such as umbilical cord--have not been fully explored and may offer just as much promise as embryonic stem cells without the ethical controversy.

Regarding the first point, some people argue that a block on federal funding is essentially a ban. My view as a researcher, though, is that federal funding is generally only "required" for topics where there is no industrial interest/relevance. If there is any likelihood of useful products (i.e., $ to be made) in a technology, as is purportedly the case with embryonic stem cells, a big-money industry like pharmaceuticals will have no difficulty funding research & development.
Also from my experience as a researcher, it is not at all unusual for something to look extremely promising in initial trials, only to be a complete dud once more is understood. I can certainly understand someone like Bush not wanting to cross ethical boundaries for something that isn't even a sure thing, particularly when there are more palatable alternatives (umbilical stem cells) available.

(Again, I'm not an expert--this is just my $0.02)

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Interesting views Lab Rat.

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Bush essentially shut down fetal stem cell research in the US. How did he do it? By limiting the federal funding. In addition the stem cell lines that he agreed to fund for research were not only inadequate but as you have read are virtually unusable.
Arnold S has thankfully appropriated $3 billion for the research in Calif.
I should note that Bush's actions are contrary to the wishes of a large majority of Americans. Both Democrates,Republicans, and Independents. It would seem that Bush's religious beliefs however have more weight than the wish's of a majority of the American people. That is the way it is in a theocracy

For me it is just another reason to despise the creep in the White house.

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Lab rat wrote

Quote:

Regarding the first point, some people argue that a block on federal funding is essentially a ban. My view as a researcher, though, is that federal funding is generally only "required" for topics where there is no industrial interest/relevance. If there is any likelihood of useful products (i.e., $ to be made) in a technology, as is purportedly the case with embryonic stem cells, a big-money industry like pharmaceuticals will have no difficulty funding research & development

If you are a researcher as claimed you know that there is no pharmaceutical corp. that will fund the billions needed in this research. Furthermore much research of that nature is carried on at universities and labs of this nation funded by federal grants.
Lab rat wrote.

Quote:

Also from my experience as a researcher, it is not at all unusual for something to look extremely promising in initial trials, only to be a complete dud once more is understood. I can certainly understand someone like Bush not wanting to cross ethical boundaries for something that isn't even a sure thing,

Again if you are as claimed a researcher you should know there is no such thing as a sure thing. If all research was limited to sure things we would still in caves sitting around a fire.

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au1929 wrote:

Bush essentially shut down fetal stem cell research in the US. How did he do it? By limiting the federal funding. In addition the stem cell lines that he agreed to fund for research were not only inadequate but as you have read are virtually unusable.
Arnold S has thankfully appropriated $3 billion for the research in Calif.
I should note that Bush's actions are contrary to the wishes of a large majority of Americans. Both Democrates,Republicans, and Independents. It would seem that Bush's religious beliefs however have more weight than the wish's of a majority of the American people. That is the way it is in a theocracy.

<nodding> Amazingly, Spain has just opened up Embryonic Stem Cell Research (according to today's NYTimes)

Quote:

Spain's Socialist government approved new conditions governing research with embryonic stem cells Friday, allowing scientists to investigate using frozen embryos while seeking cures to diseases such as Parkinson's, Alzheimer's and diabetes.

The measure was approved after a weekly cabinet meeting and announced by Deputy Prime Minister Maria Teresa Fernandez de la Vega and Health Minister Elena Salgado.

"It's an important step for investigation with stem cells, which is one of the most promising fields to fight incurable illnesses," said Salgado in the press conference after the cabinet meeting.

The bill will allow research with stem cells after approval has been given by parents to use remaining embryos obtained through in-vitro fertilization and which have been frozen for more than five years.

Researchers will also need the approval of a commission that will study each case individually.

The bill also states that parents must renounce any possible financial benefits that might result from such research, including possible patents.

Many scientists believe that stem cells, which can potentially grow into any type of human tissue, may one day be used to treat a series of diseases.

In July 2003, the former conservative government of Prime Minister Jose Maria Aznar authorized the use of embryonic stem cells for research but imposed many restrictions on the use of frozen embryos and forbade investigation with embryos that were more than five years old.

"It's all about making things easier for scientists to research with stem cells," said Fernandez de La Vega. "It's pure common sense," she added.

Ah-ha, a limited resource 'round about Washington D.C.

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Piffka
Religious fanatic sitting in the White House. He does not believe in separation of Church and State.

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I know... I just posted somewhere else that one of my two big reasons to vote for Kerry and against Bush is that I'm tired of Texas Baptist beliefs taking precedence over Science.

The other is I truly believe Kerry will help us regain trust with the rest of the world.

The third is that Bush is a corporate pandering monkey. <smiles>

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au1929 wrote:

Bush essentially shut down fetal stem cell research in the US. How did he do it? By limiting the federal funding. In addition the stem cell lines that he agreed to fund for research were not only inadequate but as you have read are virtually unusable.

Arnold S has thankfully appropriated $3 billion for the research in Calif.

I'll have to say a yes and a no to your last statement au. Here in California, we do have a proposition on our ballot (Prop 71) that would, if passed:

* Establish "California Institute for Regenerative Medicine" to regulate stem cell research and provide funding through grants and loans, for such research and research facilities.

* Establish the constitutional right to conduct stem cell research: prohibits Institutes funding of human reproductive cloning research.

* Establish an oversight committee to govern the institute.

* Provides for a General Fund LOAN up to $3 million for the Institutes initial administration/implementation costs.

* Authorizes the issuance of General Obligation Bonds to finance institute activities up to $3 billion subject to an annual limit of $350 million.

* Appropriates monies from the General Fund to pay for Bonds.

Fiscal Impact?

* State cost of about 6 billion over 30 years to pay off both the principal ($3 billion) and interest ($3 billion) on the bonds.

* Unknown potential state and local revenue gains and cost savings to the extent that the research project funded by this measure result in additional economic activity and reduced public health care costs. Note however, this measure would allow the state to receive patents, royalties and licenses resulting from the research funded by the institute. The amount of revenues the state would receive from those types of arrangements is unknown but could be significant.

I guess my point is, the Proposition must first pass on November 2nd before any appropriations or loans are made.

I do know for a fact, it has at least 1 vote in its favor from me! It's a subject very near and dear to my own heart and had only wished it would have been on any ballot 5 years ago

Did you know that at first Arnold was against this?

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Interesting debate - don't stop!!!

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Lady J
Thanks for the update. The way it came over on the news media made me believe it was a done deal. What does the sentiment look like for or against? As for Arnold I wonder how much influence his wife had in that change of heart.

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Au,

You are very welcome. The most recent poll figures that I have heard about favor Proposition 71. Of the likely voters, it shows 58% approval to 34% opposed. (plus or error margin of 4.3%) The remainder I guess are undecided.

Supporters of the campaign are growing daily with donations from the private sector alone have topped the 25 million, while opponents donations are about 150,000.

It looks like a slam dunk, but no one can be certain until the election is over....

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au1929 wrote:

If you are a researcher as claimed you know that there is no pharmaceutical corp. that will fund the billions needed in this research. Furthermore much research of that nature is carried on at universities and labs of this nation funded by federal grants.

Again if you are as claimed a researcher you should know there is no such thing as a sure thing. If all research was limited to sure things we would still in caves sitting around a fire.

Two points:
1) Pharmaceutical corp's also fund university research. A federal handout isn't a prerequisite for good research--on the contrary, many federal handouts go to projects with no practical relevance. Regarding stem cell research, what is needed initially is exploratory, proof-of-concept type work--a common setup would be an industry-sponsored grant funding either a particular professor and his/her group or funding a specific project involving multiple professors/groups. This is relatively cheap for the industry, as they get dedicated graduate students (low cost but qualified labor) performing the initial studies. The industry obviously does not commit "billions" until they get a reasonable amount of experimental data suggesting some likelihood of success; yet this model is very effective at screening potential technologies. Thus, if the technology has promise, federal funding is irrelevant.
2) I did not mean to imply we should only fund "sure things". However, given a choice between two technologies of questionable potential, I support Bush's choice to go with the less ethically controversial option. The ONLY reason it might be justified to choose/fund embryonic stem cells over umbilical cord stem cells would be if the embryonic stem cells clearly showed a high likelihood of success (more of a "sure thing") while the umbilical cord cells did not. This is not the case.

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This subject has been discussed on a2K previously. Refer to the following referenced links

http://www.able2know.com/forums/viewtopic.php?t=31342

http://www.able2know.com/forums/viewtopic.php?t=26415

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Good News

Israeli Stem-Cell Research Heals Hearts
21:42 Oct 03, '04 / 18 Tishrei 5765

A successful Israeli experiment has injected stem-cells into the failing hearts of pigs to correct faulty heart rhythms.

The study, reported by Israel21c, raises hopes that the method will eventually serve to enable natural biological pacemakers.

Heart disease is a leading cause of death worldwide. Heart attacks cause tissue to be permanently destroyed when blood is temporarily cut off to sections of the heart.

The implications of the Israeli study could eventually result in relief for the hundreds of thousands of people around the world who now use artificial pacemakers to regulate their hearts. Pacemakers are typically inserted because the normal rhythm-generating cells work irregularly, or because they have a break in the cell system of the heart used to spread the natural pacemaking nerve signal.

The Israeli experiment used human embryonic stem cells, taken from five-day-old embryos, which have the ability to grow into almost all of the hundreds of kinds of cells in the body. Researchers are currently focused on discovering methods of integrating stem-cells to regenerate various organs.

The research team from Israel’s Technion Institute of Science, which was headed by Prof. Lior Gepstein of the Bruce and Ruth Rappaport Institute of Medical Sciences at the Technion Faculty of Medicine, and including leading stem cell researcher Prof. Joseph Itskovitz-Eldor of Rambam Medical Center's obstetrics and gynecology department, showed that the cardiomyocytes (heart muscle cells) created from tiny human embryos integrated functionally into the pigs' hearts.

"This has been a long process," Gepstein told Israel21c. "Our first step was generating cell types from stem cells in the lab. We then succeeded in generating heart cells a few years ago. The next step was not only to generate but to show that these cells could function in vivo, and integrate with other networks of cells, and we have now done that."

"This is extremely important research," David Gutterman, associate director of the Cardiovascular Research Center at the Medical College of Wisconsin in Milwaukee said. "This could lead to a replacement of the mechanical pacemaker, which requires surgery to replace the battery every few years. We could also replace beating cells in patients who have had heart attacks."

Technion scientists are widely recognized as pioneers in stem cell research. Itskovitz-Eldor was among the team that first discovered in 1998 the potential of stem cells to form any kind of tissue.

Gepstein's team started with masses of stem cells growing in laboratory dishes, from which they isolated those few that were spontaneously developing into heart cells. Pulsing in unison, as heart cells do, they were easy to spot.

The team threaded a probe into the hearts of the 13 pigs and made a small burn in the area that regulates heartbeat, causing a permanent severe slowing of those animals' heart rates. The injury mimicked a human heart rhythm disorder that could be caused by disease or a small heart attack.

Then they injected about 100,000 of their human embryo-derived heart cells into the pig hearts. Eleven of the 13 returned to faster heart rates, the team reported in the Nature Biotechnology journal.

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Good news!!! Thank you for sharing au! Smile

While too late to save my sis, I want to see every bit of good that can come from stem cell research realized. I am definitely opposed to human cloning, but dang...I would have given every last egg of my own to be used for blastocysts just to have one more day with my sister.

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Approved Stem Cells' Potential Questioned

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