Stem Cell Research
Tuesday, November 20, 2007; 1:00 PM
Washington Post science writer Rick Weiss was online today to discuss the latest in stem cell research, including the recent achievement of converting human skin cells into embryonic stem cells and its potential implications.
Click here for more Washington Post coverage on stem cells.
A transcript follows.
Rick Weiss: Welcome, everyone, to today's chat on the latest discovery in the field of stem cell science. Every new discovery comes with caveats, of course, or at least should - especially when they come laden with promises of cures. But I have to say that, despite the predictable caveats, I have rarely seen scientists so excited about a new finding. As one of them put it, it is like the alchemist's dream come true, but instead of turning lead into gold they are turning skin cells into stem cells. The latter, of course, have all kinds of biomedical and therapeutic potential. I'll do my best here to explain the work, its limits and its practical potential.
West Palm Beach, Fla.: Question! Exciting news. In your reporting did you get the sense that the researchers' interest evolved in part from the heated debate over embryonic stem cells? In other words, did the researchers pursue inquiries about other types of cells more fervently because of the uproar and stalemate over the use of embryonic stem cells in research? Did the stem cell debate and political controversy actually lead them to this breakthrough using other types of less controversial cells?
Rick Weiss: Some opponents of embryo research are making the case that, had President Bush not stuck to his guns, scientists would not have pursued alternatives so actively.
For the most part, all the scientists I spoke to denied this. They said science always looks for better and simpler ways of doing things.
The truth might lie somewhere in the middle. If nothing else, it's hard to believe that the lack of funding for embryonic cells had no effect on scientists' decisions about what to pursue.
Seattle: Isn't it true that these "modified stem cells" are not truly adaptable, and only have limited usage for experimental purposes?
And is it also not true that many of the people who have religious objections to the use of stem cells in research also have objections to the use of any human cells in research?
Rick Weiss: The new cells do have limitations for their applicability in medicine, but so did the old, original es cells. In this case the limit is that they have viruses inside of them -- that's how scientists got them to turn from skin cells into stem cells. And the viruses can make the cells become cancerous. But that is not an insurmountable problem. Researchers are already figuring out how to do this without viruses. They say it will be done, probably pretty soon. Regular es cells have their own problems -- they can cause tumors too, which is why the ones being looked at for use in medicine are not really es cells but es cells that have been coaxed to differentiate partly into adult cells.
As for your other question, I don't know of any groups or religions that oppose the use of human cells in research generally.
Washington: How long?
How long until this process is successful enough that those using 'ethically suspect' stem cells can give up and switch to these 'ethically cleared' stem cells? Six months, a year, or will there always be a 'need' in some people's mind for fetus-based stem cells?
Rick Weiss: Scientists are saying that it is way too soon to talk about 'dumping' es cells. If nothing else, they remain for now the 'gold standard' against which all other candidate therapeutic cells can be compared against. It may well turn out in the end that es cells are best for some applications, and ips cells (the new kind) are good for others. Time will tell. Certainly more is known about es cells at this point, and one or two clinical trials of therapies involving them could start next year.
Springfield, Va.: There is a good chance that all the new discovery will do is shift the conservative Christian and the President's objection from "destroying human life" to "playing God and experimenting with human life." The objection is a religious objection to any research that is deemed to encroach on God's prerogatives.
Rick Weiss: Everyone has their own line that determines when we have gone from being people to playing god. But I don't know why manipulating cultured cells would be any more of a line than any other. Do the people you are talking about not take medicine? Not wear clothes? Not heat their homes? The isolation of these cells does not interfere with the development of a nascent life form, which was the big ethical line in the sand. But sure, it will be interesting to see if any groups do jump on this as a step too far, and if so, what exactly the rationale is for opposing it. It's a big, diverse country out there.
Charlotte, N.C.: Hi, thanks for hosting this and for great coverage of this ground breaking research. I've been following stem cell research for some time and this recent announcement suggests substantial progress has been made and the 'holy grail' is within view.
Could you speculate on timelines, necessary advances, and possible techniques that could be used to bring this research into wider practical use? Many Thanks, -Victor M. Virreira
Rick Weiss: The big next step is to find better ways of turning on the right genes to get cells to become embryonic -- ways that don't involve retroviruses. Many scientists are talking about using "small molecules" that can get to a cell's DNA and affect which genes are turned on or off. Also important: What other gene combinations can accomplish that (the two teams used four genes each, but two are different between them and other combinations with other genes may work, too). The thinking right now is that different genes in different doses might result in stem cells that have slightly different potentials to become different kinds of tissues. Then of course there will be years of safety testing, first in animals, then in people. And then, at least, some efforts to treat diseases. Meanwhile they will be used by many scientists to study diseases in lab dishes.
Washington, D.C.: What can those suffering from the diseases that are often mentioned as likely to benefit from stem cell research -- Parkinson's, for example -- realistically hope for from this breakthrough? There are many caveats noted, which are followed by comments that the obstacles are likely to be overcome quickly. What effect does this development have on the outlook for coming up with treatments and cures?
Rick Weiss: Even as the cells are studied for possible use in people, they will be invaluable as lab tools. Say you have Parkinsons: The disease manifests mostly in the brain, but the genetic underpinnings of it are in every cell in your body. That means scientists can take some skin cells from a patient with PD, grow them into stem cells, differentiate those into brain cells and see what goes wrong with them in a dish. That's a lot easier than studying the development of PD in a person's brain. It also provides a great way to test potential treatments -- either on the nerve cells themselves in a dish, or on mice into whom these human PD brain cells have been injected.
Seattle: My question is on the yields. Don't we get a yield of perhaps 100 modified skin cells with mutable characteristics for every million cells used for this? And isn't this yield fairly low and very expensive?
Rick Weiss: That's a fine yield when you consider how easy it is to grow millions of skin cells from a tiny biopsy.
Cell culture is cheap and easy.
Philadelphia: What seems to be overlooked in the headline although I have read it in various articles is that this process causes DNA damage, which could lead to cancer. Although a breakthrough I think the enthusiasm should be tempered because these cells ARE not the same as embryonic stem cells which are normal healthy cells. Unless they can solve this problem these cells will be useful in the lab but not in humans. What do you think of this aspect?
Rick Weiss: I would not call embryonic stem cells "normal healthy cells." They have their own "issues." As I mentioned above, they like to become tumors if given the chance -- the same downside as these new ips cells (for slightly different prooximate reasons), which is a telling thing. After all, much of the beauty of stem cells generally is that they can replicate indefinitely, which, when you think about it is what cancer does. Multicellular life is a very delicate balance between cell proliferation and cell senescence, just as the circulatory system is a very delicate balance between fluidity and clotting. The trick is going to be in the fine tuning.
Seattle: But doesn't PD have two basic theories for causation? One is mitochondrial - and the reason under that theory that brain cells are most impacted is that they use the ATP power from the mitochondrial energy factories. So, to study that, we need to actually use the female-inherited mitochondrial sections of the DNA in human cells ... and the other theory involves pathways. It seems we need stem cell lines which can form eternal cell lines to provide study samples, and this method won't provide that, since it's a one-off harvesting using viral manipulation ...
Rick Weiss: This is a little detailed for this discussion, but suffice it to say for now that some of the donor cell's mitochondrial DNA gets integrated into these new cells, so at least the potential to study mtDNA-related diseases is there with ips cells.
NW D.C.: Would stem cells ever possibly be of help to nervous system disorders such as multiple sclerosis?
Rick Weiss: To the extent a disease is caused by a person's immune system attacking its owner, stem cells and regenerative medicine generally are less promising, as they would simply add more fodder to be attacked. That said, I can imagine that some kinds of stem cells might be able to be injected into bone marrow to rewrite some of those faulty immunological instructions. I think in general the field is limited only by the imagination for now, as these cells do represent the most basic building blocks of human life. Of course, imagination is just imagination. Whether and when scientists will learn how to control these cells is an open question. Some tasks will probably be relatively easy. A lot of others will no doubt prove impossible or nearly so.
Bethesda, Md.: Are there any publicly traded companies out there such as Advanced Cell Technology that might really benefit from this breakthrough?
Rick Weiss: Looking for stock advice?
How about Washington Post company?
I know nothing.
Washington, D.C.: Today's article contains very exciting news. But I would like to know if you have any sense of how long it might take for applications of today's basic stem cell research to be available for use in humans. I know that medical trials take years, and sometimes decades, given the need for animal testing even before human trials can begin. Thanks.
Rick Weiss: Regular human embryonic stem cells will almost certainly beat these new cells into the clinic. Geron in Calif. says it hopes to start human tests of an es cell-based therapy in people with spinal cord injuries next year. Advanced Cell Technology in Mass. says it hopes to file with the FDA next year for permission to try an es-based therapy for retinal degeneration.
North Potomac, Md.: You mentioned in your piece that the two groups could use different genes to make the skin cells into stem cells. How many combinations do they think there could be, and how can they sort out which one is best?
Also, if they turn on these genes to make stem cells, how do they turn them off?
Rick Weiss: Your second question is key. You want the genes turned on long enough to make the transition to stem-ness, then have them turn off. One problem with using retroviruses is that it is hard to turn them off (though in these experiments, most of them did turn off spontaneously -- most of the time. Of course, they can turn back on spontaneously too, so personally I would never quite relax with these things in me). Other methods of turning genes on or off are more stable -- adenoviruses, for example, though they have potential problems of their own. This is a great example of how different fields of science complement each other though. There has been great basic research in recent years on gene expression and control, in part through the field of gene therapy and in part from basic biomedical research. All of that will come into play now. It is hugely complex, but the fact that these teams got it down to just four genes -- four genes that that run the whole show from there on their own! -- is really astonishing and a wonderful example of the progress being made in understanding what could only be seen as an impossibly complex black box even five years ago.
Annandale, Va.: There are many steps between what works in the lab and practical treatments for disease. Have any of the researchers applied for patents on their discoveries?
Rick Weiss: The Wisconsin team has applied for patents. I presume (but don't know) that the Japanese team has as well. Their approaches are similar but the details are different. I suspect that as more labs get onto this, even better ways will be found, generating newer patent claims, though the foundational Intellectual Property claims may stick for one or both of these teams.
Boston: Stem cells seem to be the new "miracle cure" for everything. But is it feasible to treat millions of people with stem cells given that creating them is both time and labor intensive?
Rick Weiss: Biological therapies in general pose problems far more complex than conventional chemical therapies, ie. drugs. For one thing they tend to be very variable. They are (or at least were) alive, after all. And biology is a lot squishier than chemistry when it comes to batch-to-batch consistency. This has been one of the big issues that Geron (mentioned above) has been dealing with in its conversations with the FDA. The FDA wants assurance that stem cell therapies will have lot-to-lot consistency the way pills do. That is hard to do, but not impossible, especially if you have a starter batch of cells (kind of like sourdough bread) that you can keep tapping into, and if your methods are straightforward enough to minimize variability along the production line and if you have good methods for quality control testing along the way.
Ballston, Va.: We are expecting our first child next month and are debating whether we should spend the money (upwards of $2000) to preserve our child's cordblood.
Could the findings of the recent study on stem cells have any implications on making cordblood banks obsolete?
Rick Weiss: In the long run, yes. In theory you could get whatever you needed from your own skin cell and not need cord blood. But there are still a lot of unanswered questions about the different capacities of cord blood, es cells, ips cells etc. I noticed recently (where? I don't recall right now!) a report calling for the establishment of publicly funded cord blood banks, upon which all could draw as needed. I wonder if any of these are available yet, to bypass the expensive commercial route. I have seen experts express doubts about the value of some of these commerical ventures, but I am not well informed enough to chime in more than that today.
Boston: Isn't it true that some of the scientists who have spent many years doing research on stem cells from embryos tend to send out press reports dismissing the recent breakthroughs in order to preserve funding for their own research as well as to "finish off" the ethical/moral arguments of those in opposition to embryo research?
Rick Weiss: Some es cell scientists have warned against jumping to the new cells, saying the work is still pretty young, which may sound self-interested -- and may in part be -- but is also a very reasonable statement, it seems. Others have dropped their work with embryo cells to take up with the newer ips cells, notable among them Ian Wilmut, a leader in the work that led to the creation of Dolly the cloned sheep. He said the other day he is not going to slog through the es cell field anymore, with its difficult science and politics, when a more promising (to him) and seemingly simpler approach (certainly simpler politically) is now available. So even scientists with a big stake in one field (he worked for years to get permission from the U.K. govt to work with embryonic stem cells) can change their minds when they see a better opportunity for progress elsewhere.
Rick Weiss: OK folks, it's been fun chatting but I have some actual work to do! And remember, there is no stem-cell cure for obesity yet, so take it easy on the stuffing on Thursday.
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