Surprise! Approved Lines Contaminated, Undesirable

I knew it wouldn't be long before my suspicion was confirmed - scientists don't want to work on the contaminated cell lines the government has to offer. John D. Gearheart, a Johns Hopkins developmental biologist and stem cell pioneer is quoted below during his testimony at a hearing held by the Senate Special Committee on Aging yesterday.

"Gearhart, who conducts research on stem cells from embryonic and adult tissues, said the lines available for research under the president's policy lack genetic diversity, are not disease-specific, are not adequate for researchers to apply to a wide variety of diseases and are contaminated with animal cells.

Earlier embryonic stem cell lines, including the 22 available for federal research, were grown with mouse "feeder" cells that helped the stem cells grow but also made them unsuitable for use in human therapies.

Gearhart said colleagues at the University of California, San Diego and the University of Wisconsin, Madison recently published methods for growing embryonic stem cells without such mouse cells.

"We'd rather work on lines that have no feeder layers," he said of the new, "cleaner" cell lines. "These are now available. This is extremely valuable and should be eligible for federal funding if we want to progress."

Here is the link to the article, but be warned, you might have to "register' with the baltimore sun in order to view it - it is free to register. Alternatively, you could go to baltimoresun.com and search on Gearhart - for some reason I didn't have to register when I did it that way.

Scientists back bill on stem cells, Baltimore Sun, 6/9/05

How Many Stem Cell Lines Was That, Again?

On August 9, 2001, President George W. Bush announced his policy on federal funding for embryonic stem cell research, stating that “more than 60 genetically diverse stem cell lines already exist… we should allow federal funds to be used for research on these existing stem cell lines.” He limited federal funding to “existing” lines because the embryos that were the sources of those lines had already been destroyed, so in funding only those lines, no one’s tax dollars would be spent on further destruction of embryos to create new lines.

Now, the way a stem cell line is created goes something like this (in extremely basic layman’s terms): 4-5 days after fertilization, what is commonly referred to as an embryo is known as a blastocyst and it contains embryonic stem cells. The first step toward deriving a stem cell line from a blastocyst is to extract the stem cells from it. At this point, those cells do not constitute a “stem cell line.” There are several more steps that must be taken, including “expanding” the cells (getting them to start dividing) before they can be said to constitute a line, and in the end, if the process works, the researcher will have created a “a permanently established cell culture that will proliferate indefinitely given appropriate fresh medium and space,” (www.biology-online.org) i.e., a stem cell line.

Today, almost four years after Bush’s announcement, only 22 of the over 60 existing cell lines are available for research. There are those who defend this low number by pointing out that Bush did not say that the lines were available, he said they existed, and indeed, that is what he said. However, not only could it be argued that the clear implication was that they either were or would someday be available (otherwise, how could they be “used for research?”) but that, in fact, a full 26 of the alleged “lines” were not, in fact, “lines” at the time of his announcement, and, further, these 26 and an additional 11 either definitively would never be available (27) or most likely would never be available (10).

In reality, 19 of what Bush called “lines” had not yet undergone the process of expansion and the subsequent steps necessary to establish a cell line (BresaGen, CyThera, Karolinska University, National Center for Biological Sciences in India), and therefore were not lines at the time of Bush’s announcement; as it happens, 16 of them failed to expand and so will never become lines; the status of the other three is unclear, except for the fact that it is illegal to export them from their country of origin. In the case of seven more of the alleged “lines,” they simply didn’t exist at all, in any form (Geron – these lines were attributed to both Geron and two academic institutions – i.e., seven lines were counted as 14). That means a total of 26 out of “over 60” “existing stem cell lines” were not, in fact, “existing stem cell lines” at the time of Bush’s announcement.

Of the 26 that did not exist, 23 will never be available (16 failed to expand, seven never existed at all). There are also an additional four that will never be available (1 was withdrawn by the donor, which would actually strongly suggest that this was also not yet a line… in fact, it would suggest that the derivation process had not even begun because it wouldn’’t make much sense for a donor to withdraw anything but an intact blastocyst, would it?; and three are only available to Korean researchers), bringing the total to 27 alleged “lines” that will never be available to be used in federally funded research,

Finally, there are 10 lines in India that will most likely never be available for research since the Indian government has prohibited the export of human cells, bringing the grand total of lines that either never existed or will never be or most likely never be available to 37, out of “over 60” “existing stem cell lines.”

Of the remaining 30 lines, eight are "not yet available for shipping," which, after four years, begs the question, will they ever be ready for shipping?

that leaves 22 that are actually lines and are available for shipping. However, all of these have been contaminated with mouse feeder cells. According to Dr. Ajit Varki of UCSD, they are still suitable for “in vitro or animal studies in the lab,"* but they are unsuitable for any human clinical applications, i.e., any studies involving human subjects. I suspect scientists will be less likely to use these lines as a result of the contamination, but I have not found corroboration of that suspicion anywhere as yet.

*http://www.healthfinder.gov/news/newsstory.asp?docID=523557

How Many Stem Cell Lines Was That, Again? (continued)

With reference to the post above, have a look at the table below, and the sources I have listed below it.

	Total # lines ever claimed "existing"	#  lines acctd for	# lines avail	# lines not avail			Explanation
				not avail for shipping	will never be available	did not exist 8/9/01
BresaGen, Inc., Athens, GA	4	4	3	-	1	1	failed to expand into undifferentiated cell cultures (i.e., did not become a stem cell line)*
Cell & Gene Therapy Research Institute, Korea	2	2	-	2	-	-	none
Cellartis AB, Sweden	3	3	2	-	1	-	withdrawn by donor**
CyThera, Inc., San Diego, CA	9	9	-	-	9	9	failed to expand into undifferentiated cell cultures (i.e., did not become a stem cell line)*
ES Cell International, Singapore	6	6	6	-
Geron Corp, Menlo Park, CA	7	7	-	-	7	7	Geron Corp. of Menlo Park, Calif., does not, and did not at the time of the pronouncement, have seven cell lines. The cell lines attributed to Geron are the same lines attributed to WiCell and UCSF, and a full 8 days before Bush's announcement, testimony was given before the Senate Appropriation's committee that made this very clear. It was also confimed two years later by Geron in its response to NIH's' query about its cell lines.***
Goeteborg Univ, Sweden	16	1	-	1	?	?	none - 15 "lines" no explanation
Karolinska University, Sweden	6	6	-	-	6	6	failed to expand into undifferentiated cell cultures (i.e., did not become a stem cell line)*
Maria Biotech Co., Korea	3	3	-	-	3	-	only available to Korean scientists****
MizMedi Hospital, Seoul N. Korea	1	1	1	-		-
National Centre for Biological Sciences, India	3	3	-	-	3	3	as of May 2002, India had prohibited the export of human cells until it developed a national policy for doing that sort of business, but in the case of these three "lines," as of 2003, NCBS had not yet even attempted to expand these cells, therefore they could not have been "lines" in 2001.*****
Reliance Life Sciences, India	7	7	-	-	7	-	as of May 2002, India had prohibited the export of human cells until it developed a national policy for doing that sort of business******
Techion Israel lnstitute of Technology	4	8	3	5	-	-	none
UCSF	2	2	2	-	-	-
WiCell Research Institute, WI	5	5	5	-	-	-
TOTALS	78	67	22	8	37	26

Sources as of 6/5/04

*NIH classification which means that these stem cells failed to become "lines," and a line is defined as "a permanently established cell culture that will proliferate indefinitely given appropriate fresh medium and space." Obviously, if they have failed to become lines since 8/9/01, they were not lines at that time. . http://stemcells.nih.gov/research/registry/ and http://stemcells.nih.gov/research/registry/unavailable/

**http://stemcells.nih.gov/research/registry/cellartis.asp

***http://stemcells.nih.gov/research/registry/unavailable/geron.asp, http://appropriations.senate.gov/releases/record.cfm?id=177851

****http://stemcells.nih.gov/research/registry/unavailable/maria.asp

*****http://stemcells.nih.gov/research/registry/unavailable/ncbs.asp, http://www.genomenewsnetwork.org/articles/10_03/stem_cell_us_lines.php, http://www.washingtonpost.com/ac2/wp-dyn?pagename=article&contentId=A24621-2004Mar2¬Found=true, http://www.mult-sclerosis.org/news/May2002/StemCellResearchRunsIntoRoadblocks.htm

******http://stemcells.nih.gov/research/registry/unavailable/, http://www.genomenewsnetwork.org/articles/10_03/stem_cell_us_lines.php, http://www.washingtonpost.com/ac2/wp-dyn?pagename=article&contentId=A24621-2004Mar2¬Found=true, http://www.mult-sclerosis.org/news/May2002/StemCellResearchRunsIntoRoadblocks.html

Total # of lines ever counted as existing:
http://stemcells.nih.gov/research/registry/eligibilityCriteria.asp

# of lines listed as either available or not available (# of lines accounted for):
http://stemcells.nih.gov/research/registry/index.asp
http://stemcells.nih.gov/research/registry/unavailable/