Dolly's anniversary--Is human cloning still a realistic fear?

I missed the 10-year anniversary of Dolly-the-sheep's birth last week (on the 21st of February). Maybe you did, too. Wonder what happened to the supposed cloned babies born to the alien-spawned wierdos?

Anyway, cloning--we learn in a free article from Nature online--"is beginning to change tact."

But as the decade passed and a menagerie of other mammals was cloned , no cloned human babies appeared. What did occur, and what moved the ethical debate in an unforeseen direction, was the isolation of human embryonic stem-cell lines by James Thomson and his colleagues at the University of Wisconsin, Madison.

With that achievement, it became clear that broad research avenues could be opened up by cloning human embryos to extract stem cells from them. These could then be used as disease models and drug targets, or to develop therapies involving tissue transplantation.

But as quickly as scientists recognized the potential of such opportunities, political and ethical opponents seized on the notion that allowing cloning in research would only ensure that it would one day be used for reproductive purposes. What's more, they argued, research cloning was a fundamental assault on human dignity, because it creates, manipulates and destroys human embryos for scientific ends.

"What really took place is that the stem-cell debate replaced the cloning debate," says Caplan. "Because there was — and is — a tremendous interest in trying to clone embryos, not people."

In spite of the South Korean scandal, where fradulent claims of cloned human embryos caused considerable concern, reproductive cloning still is the center of hopes for embryonic stem cell research. The research, most of it taking place with private money because of bush's halting of the production of new stem cell lines with federal money, continues. Meanwhile, according to Nature,

. . . opposition to cloning babies has remained firm through a decade of polling, at about 90%, but polls in recent years have shown that 60–70% of the public supports research using stem cells obtained from discarded embryos in fertility clinics.

"As people learn about the possibilities for new approaches to disease, they see the embryonic stem-cell issue in a different framework," says Jonathan Moreno, a bioethicist at the University of Pennsylvania, who co-chaired a committee that crafted 2005 research guidelines for the US National Academies. "They see it as medical research that could help them or their families."

The notion of cloning embryos to be a source of stem cells — as opposed to using embryos left over from fertility treatment that are slated for destruction anyway — is much more controversial. It remains a touchy political issue in many countries, including the United States, and is approached gingerly by public and private funders alike.

In the near term, "I rather doubt that we will see very much [cloning] in the context of embryonic stem-cell research in the United States", says Moreno. But he thinks advances are likely to come in countries where the work is seen as more acceptable, such as Britain, where groups led by Wilmut at the University of Edinburgh and Alison Murdoch at the International Centre for Life in Newcastle upon Tyne have been given permission to pursue it. (Murdoch's group has already cloned at least one human embryo, but has had no luck extracting stem-cell lines.)

The research, and the interest, goes on. If you wonder what animals have been cloned--famous and not--check out the excellent cloning timeline in the Nature article, with photographs of cloned animals. 

Marie Godfrey, PhD

 

 

 

Mitt Romney and stem cell research

In at least one of the sources I read about Romney's latest speech on stem cells, he was quoted as supporting the stem cell lines "approved" by President Bush in 2001. Romney stated that these lines did not come from embryos. Thus, presumably, they didn't violate his anti-abortion position.

Mr. Romney, you're wrong. The approved stem cell lines--the ones identified by Bush as being created before August 2001--ARE embryonic stem cell lines. They were derived from embryos "discarded" by families who did not want to use them for implantation and possible development into a human being.

Perhaps some of Romney's campaign staff should be reading this Genetizen blog. There's lots of accurate information on stem cells available here.

Marie Godfrey, PhD

 

Newest stem cell developments

I learned about the newest stem cell advance--converting human skin cells into stem cells--the day before the news was released. I didn't write about it as the news was breaking because I needed time to digest what the newspapers and online news sources were saying. So, now I'm ready.

I'm pleased to see that almost all articles inserted at least one note of caution about how long it will be before the discovery could translate into treatments for human conditions. Typically, however, the caution appeared in the "weakest" position in the articles, at the end of the carryover to an inner page. This, of course, is the place readers rarely reach.

I did find one of Yamanaka's comments particularly appropriate. He was quoted in an Associated Press article as saying:

We need to come up with some sort of rules about what kinds of cells can be used and to what ends. Otherwise someone may put this technology to use in troubling ways.

You can help be part of that "rule-making" by reading trustworthy news releases and asking questions. You may not think all this relates to you now, but I can assure you that you will be deeply interested some time in the future.

Many articles declared the breakthroughs a vindication of Bush's policy halting federal funding for research with "new" stem cell lines, as well as his refusal to approve bills returning all or part of the funding. Some are surely saying, "See, I knew all along that adult stem cells are the way to go." Meanwhile, the scientists working with embryonic stem cells--for example, those recently produced from the monkey--are saying that the research must continue. Their general message is that no one knows which path will be successful in producing the "cure" for paralysis, diabetes, or other conditions.

This research says nothing about adult stem cells, including stem cells extracted from umbilical cords. Although the cells that became stem cells started out as adult skin cells, they were genetically altered by transferring into them 4 genes known to turn cells "on" or "off". A virus was used to make the transfer. After the genes had been inserted into the cells, the cells changed in some as-yet-undetermined way, becoming capable of differentiating into cells other than skin cells. How far these cells have been grown was not discussed in the general media.

Because these cells now contain new genes, not to mention the viral genetic material that probably is no longer intact or capable of producing a virus, we don't know how they would behave if injected into a human--even the human from which the cells came in the first place. And, no one's likely to try introducing similar cells into humans until much more research has been done. Also, there's some destruction of the DNA in the process of conversion, so this may affect future development of the new stem cells.

So, the titles such as "Long Wait for a New Hope" and "Ethicists hail stem cell breakthrough" have to be tempered, as usual, with reality. Meanwhile, let's celebrate the fact that human stem cells have been created--in two different laboratories working independently--without destroying human embryos. This feat is truly a wonder in itself!

To read more about the research, consult a newpaper or online source you trust for accurate reporting or go directly to the articles in the peer-reviewed professional journals Cell (click on Yamanaka under Announcements at top right of home page) and Science News (only the abstract is available without cost).

Marie Godfrey, PhD

Stem-cell issue more about politics than science

Normally, I expect a very conservative viewpoint from the Deseret News, one of Utah's church-owned newspapers. That's why I was surprised to see a liberal op-ed piece yesterday. Even more interesting, it came from Ellen Goodman in Boston--another conservative place. Perhaps minds are opening in the US. Here's what Ellen had to say:

“By now you may be forgiven for suspecting that science is tinted — if not entirely tainted — by politics. The arguments over evolution and global warming alone are enough to make anyone believe that we have red and blue science as well as red and blue states.

But nothing has been quite as polarizing over the past six years as the controversy over embryonic stem cells. Stem cells have been a defining issue even among politicians who can't define them.

So it is no surprise to see a genuine, bona fide scientific breakthrough put through the political spin cycle. Last week, a trio of competing labs from Japan to Massachusetts rolled back the biological clock in mice and turned ordinary skin cells into the equivalent of embryonic stem cells. The research raised the possibility that we might eventually be able to make stem cells without destroying human embryos.

This announcement came on the eve of a House vote to allow federally funded scientists to study cells from leftover frozen embryos at fertility clinics. And this disharmonic convergence put the politicians into orbit.

It tweaked conspiracy theories by embryonic stem-cell proponents such as Democratic Rep. Rahm Emanuel, who suggested the irony of having a breakthrough announced every time a bill comes up for a vote. Opponents such as Richard Doerflinger of the U.S. Conference of Catholic Bishops speculated on a higher intervention in his favor. As he said, half-jokingly, "God is telling us he is there!"

The bill passed anyway and now heads to the White House. If the president goes through with his veto, you can bet he'll cite this research as proof that, see, told you so, we don't actually need to use human embryos.

Before this happens, let me offer a brief refresher course in Stem Cells 101. What scientists are trying to do is to take an ordinary cell from the human body and persuade it to become, say, a heart muscle cell or a brain cell or a liver cell to fix whatever ails us. But they don't know how to do it.

The reason researchers use embryos is not because they want to run a recycling program for IVF clinics. Nor because they have a passion for wedge issues. It's because the embryo can do what scientists can't do yet. The embryo contains signals that tell the cell to switch on the program of development. But to harvest stem cells, the embryo has to be destroyed.

If, as this latest breakthrough suggests, researchers can reprogram ordinary body cells to act like stem cells in the friendly laboratory mouse, they may eventually be able to avoid the use of embryos at all. Which would be good news all around.

But anyone who says we don't need human embryos in this scientific pursuit has forgotten a couple of things. First of all, we don't know if the new research will work with people. Second, this breakthrough actually began with scientists studying the genes in mice embryos. Anybody who wants to repeat the work in humans will have to use human embryos to learn the same mechanics.

In short, we'll need to use human embryos even to help us eventually stop using human embryos. Pop quiz, anyone?

The stem-cell debate has been embedded in abortion politics from the get-go, locked into an argument over the moral status of an embryo. Even as science progresses, the politics stay stuck.

Today, as cell biologist Kenneth Miller notes, one side claims "we can do everything we need with adult stem cells." The other side says that "only embryonic stem cells have the full therapeutic potential that we need to save lives." In fact, adds Miller, "Neither side is right. We are far too early in the game to know."

How early? Bioethicist Art Caplan compares us to folks "standing at Kitty Hawk watching the Wright brothers and asking if you can ever get to the moon." Didn't we need a little federal help for that liftoff?

At this early stage we should be pursuing every promising route of research. As Caplan says, "If I were in a wheelchair, I'd want to put my chips on as many numbers as possible."

As the bill heads to the White House, the question is not whether research on embryonic stem cells will go forward. It is going forward in foreign countries and private companies and states that support it from Massachusetts to California. It's whether it will go forward with federal funding and oversight and accountability.

For once in this administration it would be swell to see science trump its bully of a brother: political science.”

I don't normally quote an entire piece from the media, but this one seemed particularly easy to read. I thought you might enjoy reading it.

Marie Godfrey, PhD

The commercial side of stem cell R & D

Yesterday, I wondered what has been happening in stem cell research and development (R & D) during the past few years. Today, I was reading about a stem cell conference to be held in San Diego in February and found a Stem Cell Market Analysis Fact Sheet. The document is intended for investors, physicians, and comapnies involved in stem cell research.

Consistent with my self-imposed rule of not advertising specific companies, I won't name any here; but I will post the entire fact sheet in the Stem Cell Forum section of the website. You can find it by searching for "stem cell market analysis" from the home page. I'm intentionally not providing a link here.

So, here's some of what the fact sheet includes:

Stem Cell Company Revenues:

2005: $ 974,000

2006: $ 16,405,000

2007: $ 36,856,000 estimated

2016: $8.5 billion estimated (new forecast to be released at Stem Cell Summit on Feb. 12)

Estimated number of c ompanies developing stem cell products: 200+ worldwide

Market value of all public stem cell companies: $1.655 billion

Current applications for stem cell products

• Replacement for bone harvesting in spine fusion surgery
• Bone growth and void fill in fresh fractures
• Bone growth and void fill in non-union fractures

Stem cell products expected to be approved by the FDA in the coming 36 months

• Prochymal (treatment for graft vs. host disease)
• Two (possibly three) treatments for damaged heart muscle due to heart disease
• Chondrogen (repair of knee cartilage)

Other details:

• A single dose of adult stem cells for therapeutic use usually has a minimum of 104 million viable stem cells.
• The most common source of commercial stem cells in the United States is donor-derived adult stem cells.
• Donor-derived adult stem cells are available as either minimally manipulated donated tissues or as cultured donor cells.

The fact sheet also describes projected sales figures, number of people likely to be customers, and what other types of treatements serve as competition.

So, we know there's money out there. Now, what's the scientific evidence that these treatments work?

Marie Godfrey, PhD

 

US Senate passes stem cell bill

The Senate has once again passed a stem cell bill whose primary function is to allow federal funding of stem cell lines created after August, 2001. The ban was placed by President Bush and has been upheld since then, limiting federally-funded embryonic stem cell research to approximately 24 or fewer stem cell lines.

President Bush is expected to veto the bill.

I recently found a 2005 edition of National Geographic in which the subject of stem cell research was thoroughly discussed--with the usual excellent photographs. I think what surprised me most was that only one item dated the article: Hwang's announcement of producing a stem cell line from adult cells by nuclear transfer had not been made or declared completely false. Other than that, not much seemed to be new.

Whether the slow progress in embryonic stem cell research is because of the science itself or the lack of federal funding cannot be clearly determined. Two facts have held up though:

• Adult stem cell research is producing few instances of "cures" of debilitating diseases in spite of a number of tests. Success is still based on individual cases, but there is promise.
• Embryonic stem cell research, still  controversial and abhorent to many, has a long way to go before it can fulfill the promises made--if it ever does.

What's your opinion???

Marie Godfrey, PhD

Stem cells hot again

The US House of Representatives passed a bill January 24th very much like last year's bill to allow federal funding for embryonic stem cells derived from embryos that might otherwise be discarded.

The usual rhetoric reined on the Hill. The only development identified as new was the recognition that stem cells have now been derived from amniotic fluid. These cells presumably come from the developing embryo and would thus be as "potent" as any embryonic stem cell.

Again, we're into rhetoric and into the subject I am accused of always focusing on--words. In this case, the questions are two:

1. How can someone tell whether the cells removed from the amnionic fluid belong to the embryo/fetus and not the mother (adult)? Inaccurate identifications are not uncommon in pre-natal diagnosis.

2. Are the cells more embryonic earlier in development--as opposed to later? Where is the boundary between embryo and fetus? After all, fetal stem cells derived from the umbilical cord are actually adult cells, not embryonic (

What really are the differences between embryonic and adult stem cells?

All the old arguments are being brought out. Which makes me wonder: hasn't anything new happened in embryonic/adult stem cell research in the year and a half since the previous stem cell funding bill was introduced and passed in the House? Besides the Hwang problems in South Korea, has anything new happened since President Bush first imposed the ban on federal funding for embryonic stem cells derived after whatever date it was years ago?

Hmmmmmm..............

Let me check into that again. All I see is a new adult-stem-cell cure number--73 vs. the older 65. If adult stem cells are so much better than embryonic stem cells, why so few new cures (if, in fact, the cures are anything more than cancer recovery treatments not on the earlier list)? If embryonic stem cells are so much better than adult stem cells, why no progress in the the past five or so years? I can't believe federal funding has all that much to do with it. After all, federal funding has continued on the embryonic stem cell lines "approved" by Bush.

I'm eager to learn what questions and opinions others have. Won't you add a comment to this entry?

Marie Godfrey, PhD

 

Adult vs. embryonic stem cells

Everyday I scan many pages of information on stem cells, including the Google Alerts I get 5-10 times a day. Sometimes, I get fired up enough to send my own comment to an article or opinion. Yesterday, I responded to an opinion claiming that 65 diseases can be successfully treated with adult stem cells and referring to an article in the Washington Post. Since I have been diligently exploring the comparison of adult and embryonic stem cells, I read the referenced article only to find no reference to 65 diseases. My opinion was posted (I guess), but I received no response to my comment that statements with faulty or no corroboration are what make ordinary people so confused about stem cell research.

Today, while following leads, I tripped over a site I should have found long ago (http://www.stemcellresearch.com). For some reason, it didn't turn up on Google or Yahoo searches. Anyway, lo and behold, the right side of the screen has 65 vs. 0 for adult stem cells vs. embryonic stem cells. The list of diseases/conditions successfully treated by adult stem cell transplants looked very familiar and, as I linked to the reference list, I knew why. These were the very references sent to me as her own by the head of an organization opposed to embryonic stem cell research. Funny thing, none of the pages had their original footers identifying the real source of the references.

We at Geneforum have been using a blog--rather than just posting chunks of information or providing a list of today's 15 news releases for several reasons. Among them is the comments capability. Anyone reading the blogs can comment or ask questions. Another is to provide an experts analysis of the voluminous, often contradictory, information available primarily through the Internet. I try, as much as possible, to give you the source of the information unless its available from many different sources. And what I write, unless I add a statement such as taken directly from, is original. I read, dig, and read some more until I am fairly confident that what I am posting is accurate and untainted as much as possible by my personal opinions.

Thanks for reading, and please refer others to this site.

Marie Godfrey, PhD

Alternative sources of stem cells doesn't pass House

Overlooked in the hype about Bush's veto of "stem cell enhancement bill", which started out as H.B. 810, is the third of the stem cell bill package: S.2754. This bill is intended to direct NIH to fund research to derive human pluripotent stem cell lines using techniques that do not knowingly harm embryos. S.2754 is also known as the Santorum bill.

The Senate passed this bill unanimously (by counting yeas and nays) and turned the bill over to the House for its first consideration. On 18 July, the bill failed to pass, not being agreed to in the House. A motion was made to suspend the rules and pass the bill failed by yeas and nays 273 to 154 (a 2/3 majority is required).

I cannot tell whether the Senate-passed bill is still alive.

One possible reason for problems in the House maybe the bill (HR 5526 IH) the House introduced 6 June with a similar purpose, although--as far as I can tell, the bills are identical.

Marie Godfrey, PhD

Creating stem cell lines without destroying embryos

The recent announcements that a commercial company has been able to create stem cell lines without destroying embryos has hit most of the news programs and other outlets--with the expected feedback.

The technique involves the removal of a single cell from an 8-cell embryo (outside the human body) and culturing this cell to produce stem cells. The arguments against "destroying embryos" presumably do not apply because the embryo is not harmed in the process. You may remember that harvesting cells from a more-developed blastocyst--after the embryo has developed into a hollow ball with an inner cell mass--does destroy the embryo.

So, why 8 cells?

• The previous cell division--which doubles the number of cells in the embryo--was made by a 4-cell embryo. One cell of an embryo at this stage could become a fetus--with perhaps 3 other babies created from the other 3 cells, giving the parents quadruplets.
• Cell division is so rapid in the newly fertilized egg that "catching" an embryo at the 8-cell stage requires careful attention. Presumably, some of the embryos could be any number of cells prior to formation of the blastula. This is why the news reports tend to say "8-to-10-cell stage". Also, the cells do not necessarily divide simultaneously.
• There are many reports that cells at early stages of division may not be genetically identical. Rapid cell divisions in the embryo may sometimes produce cells with very slightly different DNA content.
  
• In pre-implantation genetic diagnosis, cells have been successfully removed from embryos of 8 cells or more without harming the embryo. This one is a bit tricky to prove, though, since more than one embryo so examined is usually introduced into the uterus for development into a fetus. If only one of 2-4 embryos develop into a fetus, there's no way of knowing why the others did not so develop.
• Smoke and mirrors--there appears to be less public concern about an embryo with one cell removed than there is about a blastula with its germ cells removed. Good publicity for a commercial company and eventually great profits from newly-created cell lines.

Here are some considerations you might not have thought of--whatever your opinion about embryonic stem cells and their creation:

• What will happen to the rest of the embryo? If it will be discarded, or used for potentially creating additional stem cell lines, this technique is no different from any technique that destroys an embryo.
  
• Is the technique useful only for people planning in vitro fertilization and pre-implantation genetic diagnosis? If so, would two cells have to be removed--one for the genetic diagnosis and one for the stem stem line? Will removing two cells damage the embryo?
• Will there be a market for embryos created solely for generating stem cell lines?
• How will stem cell lines be created for diseases such as Alzheimers or other adult-onset conditions generally occurring when a person is no longer fertile?
• If the embryo is yours, do you get the rights to any money made from the stem cell line(s) developed from that embryo?
• If the method is so successful, how come only 2 cell lines could be created from 81 embryos?

Want to add some comments of your own? Please do.

Marie Godfrey, PhD

Geneforum Interview with Audrey Chapman: Bridge Over Troubled Waters

An Interview with Audrey R. Chapman
Director, Science and Human Rights Program
American Association for the Advancement of Science

by Mark Compton

Since late in the Clinton Administration, the public debate over stem-cell research has often seemed less a dialogue than a shouting match between scientists and religious leaders. There are still some, however, who persevere in trying to keep communication channels open. And Audrey Chapman, Director of the AAAS Science and Human Rights Program, can certainly be counted as one of those.

As an ordained minister in the United Church of Christ who also happens to hold a Ph.D. in Political Science from Columbia University and serve on the staff of a major scientific organization, Chapman herself has a foot in either camp. And perhaps because of that, her extensive writings on genetics, stem-cell research and human rights strike a balance between a wide—and sometimes wildly varied—range of topics and perspectives.

Chapman's most recent book, Unprecedented Choices: Religious Ethics at the Frontiers of Genetic Science drew praise both from scientists and theologians. She also served recently as one of the lead authors of a report on stem-cell research co-published by the AAAS and The Institute for Civil Society. And later this year, she has another book scheduled for release: Designing Our Descendants: Potential and Limitations of Genetic Modifications.

[The views and opinions expressed by the participants in this interview are not necessarily those of Geneforum, and the publication of this interview should in no way be construed as an endorsement of those views.]

[Mark Compton]: Last September, in testimony before the Senate Appropriations Subcommittee on Labor, Health and Human Services, adult stem-cell researcher Dr. Curt Civin of the Johns Hopkins University School of Medicine observed: "Embryonic stem-cell research is crawling like a caterpillar. It may hold the key to expanding proven adult stem-cell therapies to many more patients, but administrative and technical barriers are impeding the progress of this vital research." How do you view that assessment?

[Audrey R. Chapman]: I'd say that's a fair assessment. Among those researchers who are particularly interested in tapping the potential of human embryonic stem cells, you'll find many who hold similar views. When President Bush first announced his policy on stem-cell research in August 2001, he indicated there were over 60 stem cell lines available, but it turns out there actually are far fewer than that. Many of the sources the President and the National Institutes of Health identified are in a very preliminary stage of development and may not even be valid human embryonic stem-cell lines. Secondly, many of the non-American sources—and the overwhelming majority of the lines President Bush identified as available come from outside this country—are quite reluctant to share their material in the US because of concerns over the possibility that the University of Wisconsin Alumni Association, which holds patents in this country on both the stem-cell research process and the products yielded by that process, might sue them for patent infringement. In fact, the estimates I've seen indicate that only between five and nine of the sources President Bush identified are actually available to scientists in this country. And there also have been delays in completing the reviews required as part of any application for federal funding. That's all gone quite slowly. So here we have a very promising area of research and a great many scientists interested in doing the work. And yet it's been very difficult to actually get any serious research initiated in laboratories throughout the country.

In amplification of your last comments, I'd like to observe that many advocates within the research and medical communities—as well as many patients' rights groups—argue that stem-cell research appears to represent our greatest hope for realizing advances in the prevention, diagnosis, and treatment of a broad range of devastating human diseases...most particularly, heart disease, cancer and various diseases of the nervous system, such as Parkinson's Disease, Alzheimer's Disease and Multiple Sclerosis. Do you consider those hopes to be well-founded? Or are they more the product of wishful thinking?

I certainly think the potential is there, but when you're at a preliminary stage of developing a technology, it's hard to know exactly what the results will be. And, by the way, I'd add diabetes to your list since juvenile diabetes is one of the few areas where it's been possible to raise substantial sums of money to fund private research. As a result, there's been a considerable effort to use embryonic stem-cell lines in an attempt to develop pancreatic-like cells capable of producing insulin.

It sounds as though you can appreciate and understand the frustration being expressed throughout the research community right now.

I can, and of course, I also recognize that we have a public policy, ostensibly, that allows federally funded research to proceed on those stem-cell lines isolated and made available prior to the President's August 2001 address. So I think another question that has to be asked is: Even if more such lines were available, would that be sufficient to allow researchers to develop these long-awaited cures? And there are numbers of scientists who say, "No."

But, as I see it, there are two major problems with the current guidelines for federal funding. The first is that the number of stem-cell lines currently available under those guidelines doesn't appear to offer sufficient diversity. Secondly, all the stem-cell lines that qualify under President Bush's policy were developed on mouse feeder layers—and that creates problems when it comes to using them in clinical trials for human therapies. There are approaches that have been developed subsequent to August 2001 that eliminate the need to use a mouse culture as a growth medium. So the more recently developed lines created with the help of those approaches aren't potentially contaminated with mouse viruses in the same way. But since they were derived after August 2001, they're ineligible for government-funded research.

In announcing those policy guidelines in August 2001, President Bush made it quite clear he didn't want the government to support the destruction of any further human embryos. That position, I take it, is one that's rooted in the religious view that human life begins at conception.

I wouldn't say "religious view." There actually is a wide diversity of viewpoints within the religious community about the moral and theological status of an early-stage embryo.

But I think we can probably agree that this particular view is rooted somewhere in the religious community.

Yes, among certain parts of the religious community.

Understood. So I wonder—at least where the question of stem-cell research is concerned—wouldn't that position tend to assign greater moral weight to the rights of the unborn than to those of the already born?

Yes, but I wouldn't even say "unborn." I find that to be a very problematic label when applied to frozen embryos in fertility clinics, which have a very, very low probability of ever being born. The embryos that are being proposed for derivation of embryonic stem-cell lines are ones that would otherwise likely be discarded. They're leftovers from couples' efforts to have children or they're of too low a quality to be implanted. The prospects that any of these would, at some subsequent date, be the basis for a pregnancy are almost nonexistent. So to even call them "potential human lives" is, I think, misleading.

I quite agree that any test that holds as absolutely sacred anything with even the slightest potential for life could only be fraught with all manner of problems and inconsistencies.

And for those who are really concerned about it, perhaps they should think about focusing their energies on regulating the fertility industry. There are already over 100,000 embryos in storage, with more likely to be created and stored.

Right. The vast preponderance of which are earmarked for disposal at some point.

Yes. Well, in Britain, in fact, there's a law that requires the destruction of any frozen embryos kept in storage longer than a few years. In the US, there don't appear to be any clear laws instructing clinics what to do. In many cases, the embryos just sit there because the fertility clinics have not been given any clear directives. And what has been suggested is that at the time couples first create the embryos, they should be offered protocols that allow them to indicate—should they end up deciding not to use some of the embryos for the purpose of starting a pregnancy—what's to be done with those leftovers. And one of the options such protocols could offer would be for donating the embryos for research purposes. But as far as I know, protocols of this type are not currently in widespread use.

I have to confess that I'm a bit confused about government policies that oppose research uses of leftover embryos from fertility clinics, but at the same time effectively turn a blind eye to the commonplace practice of discarding those very same embryos. Is that just ignorance on the part of the government? Or simply the function of a terribly convoluted moral position?

No. I think for a whole variety of reasons, legislators have been quite reluctant to even broach the topic of regulating the assisted fertility industry. And I consider that reluctance very unfortunate. As any regular reader of the news is undoubtedly already aware, there are many serious problems within that sector. We've had many instances, for example, where technologies have been introduced even though they haven't been adequately tested. As a result, humans and human reproduction are effectively being used as subjects for experimentation. And there also are all kinds of other unsavory practices that go on—which do a great disservice to those researchers who are totally honorable and moral about how they proceed on these matters. And as the assisted fertility industry continues to grow, those problems are just going to become larger and more complex.

So public health and the industry itself would probably benefit from a bit of regulatory oversight?

Definitely. Some of the current practices are chilling. For example, one fertility clinic in New Jersey has apparently taken women with mitochondrial disease or various mitochondrial deficiencies and then employed a technique that takes cytoplasm from a donor and uses it to augment the woman's own cytoplasm. By virtue of this approach, at least 30 children have apparently been born who have genetic resources derived from three sources—the mother, the father and the donor. Now, all of this has been done without first attempting careful experiments on animals to evaluate the procedure. And also bear in mind that the results are inheritable. So if these children grow up and have children of their own, they're going to be passing this genetic material—with all its unknown properties—onto generations of descendants.

Truly, this is the stuff of science fiction.

It really is the stuff of science fiction. And there are no regulations whatsoever to prevent people from doing this kind of thing.

And while we're on the subject of conflicted, inexplicable—and perhaps inexcusable—government stances, I'd like to ask about the controversy over the research uses of gonadal tissues derived from aborted fetuses. Although I understand that there are many who stand morally opposed to abortion, the fact is that there continues to be a regular and apparently unending supply of aborted fetuses. That said, why is there any opposition to utilizing stem cells derived from those fetuses for research applications? I mean, nobody seems to raise a ruckus over the use of tissues from other cadavers for research purposes.

Well, there are a number of problems with stem cells derived from aborted fetuses. First of all, you have to understand that there are two forms of aborted fetuses. Naturally aborted fetuses are aborted for a reason and that often proves to be related to abnormalities, including genetic problems. Developing embryonic stem-cell lines from an aborted fetus with irregular genetic composition would be very dangerous for future patients. Secondly, there's only a very narrow window of opportunity—of just a few days within the first eight weeks of conception—in which to obtain embryonic stem-cell lines from aborted fetuses. That means the woman would have to have the abortion in a hospital to allow the stem cells to be harvested from the fetus. Most spontaneous abortions do not take place in a clinic or hospital where the tissue could be recovered. And, in any event, the very little research that has been done with stem-cell lines from that source suggests they may be less plastic than the embryonic stem-cell lines derived from embryos that are only a few days old.

So the embryos look to be a more promising source?

Much more promising. Yes.

Bush's policies have caused some people to question the role that religious views should play in the formation of public policy—particularly in a country such as ours where the notion of a separate Church and State is central to our Constitution. In your estimation, what rights do you believe religious leaders should be free to exercise in the shaping of public policy?

I think they have a very important role to play. That may not be the answer you expected. But I am an ordained minister and I worked for the United Church of Christ national office for several years. In a country such as ours I think no single religious group should have veto power over public policy, but I believe that the wide range of religious communities should be consulted and that their voices should be heard. And then public policy should be made, taking those views into account. Right now, the religious community is one of the few sources of thoughtful, ethical viewpoints on new genetic and reproductive technologies. And they also represent concerns shared by many throughout the American population. What I find problematic is the fact that one perspective, for entirely political reasons, seems to enjoy veto power over policy. There are many groups within the religious community that are supportive of embryonic stem-cell research and do not believe that an early-stage embryo should be treated as having the same moral status as a fully formed human being.

Alright, so with reference to that veto power you say one group currently enjoys, what safeguards do you believe should be vigilantly observed so as to prevent certain religious leaders from exercising disproportionate influence?

It's not that religious leaders exercise disproportionate influence. There's just one narrow segment of the religious community that's managed to insinuate its way into political power. And, in our system, the only way to overcome that sort of thing is to try to counter that influence. I think there's just no other way. You can't start regulating who does and who doesn't participate in the political process. And when people find that they take strong issue with a particular stand, I see it as their responsibility to voice their objections and take action.

What would you see as the mechanism for that sort of expanded public involvement? We're talking about something larger than town hall meetings, I presume.

Actually, I think that would be an excellent place to start.

Any other mechanisms come to mind? Use of the Internet?

That would be a possibility, but what I think we really need is a crash effort to educate people. I would be very nervous about having a public debate based on misinformation. There are many opponents of genetic technologies who have sensationalized what they entail and have grossly misrepresented the implications of going forward with them. And this is very much in keeping with the way the abortion debate has proceeded. So I think it's important that you link public education with public discussion.

Agreed. But how best to plug public officials into the values and ideas their constituents ultimately manage to express through various forums? There seems to be quite the disconnect there, don't you think?

Well, I'm very pleased about the work that Geneforum is doing, both in terms of educating the public and informing policymakers about the core values expressed by their constituents. All of that, I think, represents an important step in the direction of trying to accomplish the sort of public involvement that's vital to the workings of a participatory democracy.

Great...and here's a topic that's certainly worthy of robust public debate: Just after this past Christmas, Dr. Brigitte Boisselier, the scientific director of Clonaid, announced the birth of what she claimed to be the first human clone. A cloud of suspicion has hung over that announcement since there's been no opportunity for independent corroboration and because Clonaid itself has the rather dubious distinction of being part of a religious sect which contends the human race was created by a group of space travelers who cloned themselves. That said, there are also some other perhaps more serious reproductive cloning efforts reportedly afoot in the labs of Italian doctor Severino Antinori and former University of Kentucky researcher Panos Zavos. All of which serves to raise a raft of questions. But first, let's just focus on the ethics of reproductive cloning itself. Your views on that?

I'm very opposed, as most people in the religious community—and, in fact, most Americans—are. When you realize the very low rate of success with all the species of animals that have been cloned to date, you begin to appreciate just how risky these efforts really are. Also, there are experts who believe that there has never been such a thing as a normal mammalian clone—even among those that have been carried through to birth and have survived. And that's because it's not only a matter of the clone having a full genetic complement. During the process of a natural union between an egg and sperm, an imprinting process is triggered by which instructions are given to the new conceptus as to which genes should be turned on and which should be turned off under certain circumstances. And we cannot replicate that process in cloning experiments.

Also, clones tend to be of a very large size in comparison to normal pregnancies, so they can be quite dangerous to the mother. That large size also seems to contribute to a low likelihood that any such pregnancy will actually survive to term. So I think it's scientifically irresponsible to be doing any human cloning at this point. Having a child be born through that process raises all kinds of moral and ethical issues. Personally, I don't think human society is ready to deal with those issues. I'm particularly concerned with the tendency cloning would have to commodify human life. It would also encourage parents to view reproduction as something that can be controlled according to design specifications of their own choosing.

So if I understand you correctly, you believe it would be scientifically irresponsible to proceed with reproductive cloning because there's so much about fundamental human biology that is not yet understood?

Yes. That's true. But even if it was understood, it couldn't be controlled. So my concerns actually have to do with both of those aspects.

OK. But with regard to understanding, wouldn't continued research on embryonic stem cells help us to gain a richer, fuller appreciation for fundamental biological processes? Isn't that the hope anyway?

Well, certainly, one of the reasons scientists want to proceed is that they believe they'll learn a great deal more about basic human biology at the early stage of life.

Another consideration is that given all the buzz these various efforts at human cloning are likely to create, what do you see as the potential implications for therapeutic cloning research programs? Are they likely to suffer collateral damage as a consequence of a furious backlash against reproductive cloning?

Yes, they almost certainly will. But I think that research would be less likely to suffer damage if we had regulatory safeguards in place to assure that therapeutic cloning cannot metamorphose into reproductive cloning.

There's a school of thought that holds that anything developed initially for therapeutic purposes can—and usually will—be put to more bastardized ends at some later point.

That's a valid sense of apprehension. So I certainly think it would be wise to put an appropriate regulatory structure in place before we proceed down the path of therapeutic cloning.

Do you feel the people in Congress and the White House currently have enough of a grasp on the distinctions between reproductive and therapeutic cloning to be able to formulate informed, balanced policy guidelines?

No. But, in any event, I think the White House is more inclined to make decisions on a political basis than a scientific basis.

What ethical distinctions would you yourself draw between reproductive cloning and therapeutic cloning?

Therapeutic cloning, of course, is never intended to result in the full development of a human being, but only to enable an early stage embryo to proceed far enough for the purposes of harvesting stem cells that can be directed to develop into a specific kind of tissue. And so the ethical issues about a child being born with any expectations of a predetermined future are not really in question. Also, there are few scientific risks. You don't have the problem of assuring that the conceptus can transit through the various stages of development to an actual birth. But some of the same ethical concerns that have been raised about reproductive cloning apply—for example, the possibility that this process will diminish our sense of the sacredness of life or accelerate the commodification of human life. Those concerns have been raised by ethicists in both the secular and religious communities in response to potential human reproductive cloning. Still, you could say the risks associated with therapeutic cloning are smaller and the benefits are potentially greater. So that would certainly tend to change the calculus.

And here's another consideration to weigh in the balance: We've already established that current US policy bars the use of public funds for much of the stem-cell research currently under way. But by leaving that research largely in private hands, aren't we ensuring that the therapeutic benefits of stem-cell research will ultimately be distributed in an inequitable fashion?

Definitely. Because private investors are going to put their money wherever they think the potential for reaping a financial reward is greatest, we may find that our current restrictions on public funding end up skewing the types of therapeutics that are ultimately developed. Also, because the tendency in the private sector will be to patent most of those therapies, providers will be free to drive up prices—which will effectively reduce the availability of any therapeutic applications.

Specifically with regard to the potential for skewing the research itself, it's long been held that pharmaceutical companies tend to drag their feet when it comes to the development of vaccines, since curing a disease almost never proves to be as profitable as treating a disease.

Right. And the other problem is that because so much of the current stem-cell research is being done in the private sector, there's likely to be a strong sense of proprietary control that may impede access to future data and stem-cell lines—which may have the effect of slowing progress across the board. In this country, we don't have a strong research exemption codified in law that would protect researcher access to the material so long as it's not used for commercial development purposes.

So the net effect, if I understand you correctly, is that we may end up retarding research as a whole, and that certain promising therapies may never be developed simply because they don't appear likely to yield obscene profits.

That's right. Also, I think you shouldn't underestimate the implications of not sharing the results of private research with others throughout the research community.

Are you optimistic that policymakers can be educated sufficiently well to allow for enlightened thinking in this area?

I think they can be educated, but I think most decisions in this area are made on political rather than scientific grounds. And that, of course, is bound to have major repercussions.

I'm inclined to think of that, actually, as little more than just the typical populist pandering for political gain...business as usual, in other words. That said, what role do you feel ordinary citizens ought to start playing in the debate?

The AAAS has strongly advocated educating people and finding ways to involve them in meaningful public discussions. We have a democratic and representative form of government. And we are making very important decisions currently on some very substantial technical and scientific matters. Unless people can become more scientifically literate and start participating on that basis in public debates, it's going to weaken our whole representative, democratic order.

About the Interviewer

Mark Compton monitors trends in information technology and biotechnology from a comfortable perch midway between the Silicon Valley and Oregon's Silicon Forest.

Geneforum Interview with Insoo Hyun: Ethical thinking guides new South Korean World Stem Cell Hub

As the embryonic stem cell debate rages in the United States, the South Korean World Stem Cell Hub has deployed a more practical and less acrimonious approach for guiding advancements in this area of research. In an interview conducted by Geneforum, Korean-born Insoo Hyun, Ph.D., a bioethicist at Case Western Reserve University and co-chair of the South Korean World Stem Cell Hub Ethics Working Group, describes how a cooperative and open dialogue between the Hub and the South Korean government has allowed him, at the onset, to train researchers to think ethically about embryonic stem cell research. "If you don't think about the ethical issues, there will be a time when it will hinder your basic science research, like what's happening in the U.S," says Hyun in the interview. "You really need to be involved in the ethical discussion from the start." The interview with Marie Godfrey, writer of Geneforum's blog, Genetizen, tells about the innovative ways ethics, preclinical/in vitro science, and clinical studies are being integrated in South Korea. UPDATE: There are a number of news stories today about the announcement of the World Stem Cell Hub in South Korea. See articles in the San Francisco Chronicle and the New York Times (subscription required).

House passes stem cell research bill

Interpreting stem-cell research

In general terms, a stem cell is any cell that can multiply indefinitely and has the capacity to differentiate into more than one cell type. A stem-cell line is a group of stem cells in laboratory conditions (i.e., in vitro), continually producing new cells of the same type. Stem cells can be derived from embryos, from adult cells, from umbilical cords that are discarded after babies are born, and from human placentas. Under special laboratory conditions, stem cells can be encouraged to produce a variety of human cell types, including nerve cells, liver cells, and heart cells.

To more accurately interpret media references to stem-cell research ask the following questions:

What animal is involved? Research conducted with mice often provides insight into human systems and the research has fewer moral and regulatory issues attached. Because of current limitations in the U.S., federally-funded studies on embryonic stem cells can only be conducted with non-human animals or existing stem-cell lines. There are no limitations on privately-funded studies other than the restriction that cloning cannot be used as a source of stem cells. Research is also being conducted with tissues cultured from humans or other organisms.

Where is the work being done? Much of the current human embryonic stem-cell research is being conducted outside of the U.S. Inside the U.S., work on non-adult stem cells is limited to the few institutions who have, or can obtain, existing embryonic stem-cell lines. There are currently no U.S. limitations on non-embryonic stem-cell research, other than those already in place for any human clinical study.

What was the source of the cells?

Non-embryonic, or adult, stem cells are relatively undifferentiated cells removed from an adult and allowed to multiply in vitro. Bone marrow cells, grown in vitro before being injected into a recipient, are one type of stem cell. Non-embryonic stem cells have been tested in the treatment of cancer, Crohn's disease, and multiple sclerosis.

Embryonic stem cells are cells harvested from a special part of a late blastocyst --a layered ball of cells resulting from multiplication of a fertilized egg. Under special conditions, embryonic stem cells can develop in vitro into any tissue of the body. Muscle, nerve, and heart (cardiac) tissues have been grown this way. While the entire blastocyst, under proper conditions, can develop into a human being, embryonic stem cells cannot.

Umbilical cord blood contains neonatal stem cells. These cells are capable of differentiating into various cell types; such as hematopoietic cells (blood and immune system-forming cells), mesenchymal cells (muscle, cartilage, bone and fat cells), and neural cells (brain and central nervous system cells). These properties of cord blood stem cells are similar to those shown by embryonic stem cells. However, unlike embryonic stem cells, umbilical cord blood stem cells are abundant, easily collected and are non-controversial.

Who was the source of the genetic material? Non-embryonic stem cells can come from the same person who later receives the injected stem cells (autologous transplant), a closely related person (allogenic transplant), or an immunologically matched but unrelated person (Matched Unrelated Donor or MUD transplant). Syngenic bone marrow transplants are performed from one identical twin to the other. Prior to receiving the newly grown cells, the recipient is treated to decrease their own immune system's cells to as few as possible. After receiving transplanted cells, the recipient may be given drugs to prevent rejection of the new cells and possible graft-versus-host disease. Once begun, anti-rejection drugs must be continued throughout the recipients life. Embryonic stem cells can be harvested from an embryo that has developed to the blastocyst stage (14 days and about 150 cells) from a naturally-fertilized egg, an artificially-fertilized egg, or an egg whose genetic material was replaced by genetic material from another cell. Genetic material from the intended stem-cell recipient can be used to replace genetic material of a fertilized egg.

Stem cells can also be identified by the terms pluripotent, totipotent, and multipotent:

Totipotent stem cells form when a fertilized egg first divides. Totipotent stem cells can develop into a complete individual.

Pluripotent stem cells are also called embryonic stem cells. A few days after a fertilized egg divides, the totipotent stem cells form a blastocyst, or a ball of cells. The inner layer of this blastocyst contains pluripotent stem cells, which are capable of developing into any tissue in the body. Pluripotent stem cells cannot, however, become a complete individual.

Multipotent stem cells are sometimes called somatic or adult stem cells. These stem cells are found in mature tissue and are maintained by the body to replace worn out cells in tissues and organs. Stem cells from bone marrow, called hematopoietic stem cells, form the various kinds of blood cells. Neural stem cells form the brain and central nervous system. Mesenchymal stem cells form fat, bone, muscle and cartilage.

Marie Godfrey, PhD

Is embryonic stem cell research necessary?

If--according to the last entry I posted--adult stem cells can treat 65 different diseases/conditions and embryonic stem cells 0, why is research being conducted with embryonic stem cells and why is there a debate about federal funding of same? A number of possible reasons have been proposed:

• Media hype, hope, and promises
• Terminology is confusing, so few know what is going on
• The limitations of adult stem cells
• The National Academies of Science (and NIH) said so

Media hype, hope, and promises

The first embryonic stem cell was created in 1998. Seven years is plenty of time for media hype, but not enough to cure the many diseases/conditions promised daily in newspapers and television. Over the Labor Day weekend, Robert Winston, a leading fertility expert in the UK where embryonic stem cell research is legal and funded stated that he believes that the benefits of stem cells have been overhyped. His announcement has received almost as many Google alerts as Senator Frist's change of mind, indicating that sensational news whether good or bad tends to get transmitted around the world very quickly.

Testimony by famous people such as Christopher Reeves and Nancy Reagan help keep the widest possible options active.

Terminology is confusing, so few know what is going on

Perhaps embryonic stem cell research is still in the news because people are so confused about the language used that the most controversial keeps hogging the spotlight. The phrase stem cell alerts readers to interesting and perhaps controversial news, as does the word cloning. Even embryonic is not specific enough. Reiterating some of the confusion may show how complex the terminology problem is.

An adult cell is one that has fully differentiated into its functional state in the body for example, the rods and cones of the eye are adult cells even if they are found in a child or a fetus. An adult stem cell is, presumably, a cell in a cell in a human body that produce a copy of itself under some conditions and a more differentiated cell in other conditions these are the hematopoietic (blood-forming) and mesenchymal (connective-tissue forming) cells of the bone marrow and other clusters of cells elsewhere in the body.

Stem cells taken from the umbilical cord of a newborn human infant or from the fluid around a developing fetus or from other amniotic tissues (including a portion of the placenta) are also called adult stem cells. These are sometimes called stem cells with embryonic potential or embryonic-like stem cells, since they are believed to be capable of developing into more tissue types than adult stem cells from a particular adult tissue.

Generally, the name embryonic stem cell is reserved for cells derived from the inner cell mass of the blastocyst stage of early embryonic development. By the way, the outer layer of the blastocyst is necessary for implantation and for development of the placenta and umbilical cord.

A stem cell derived by transfer of adult DNA into an unfertilized egg (the Korean stem cell lines) or into an embryonic stem cell (the Harvard stem cell) is also an embryonic stem cell even though it may not have been taken from an embryo and certainly could not have developed into a human being.

The earlier blog entry, Interpreting stem cell research, provides a clear way to analyze reports in the media and--perhaps--to deal with confusing terminology

The limitations of adult stem cells

Some argue about it, but there is strong support of the conclusion that adult stem cells are not as versatile as embryonic stem cells. One limitation is that most of the diseases/conditions treated with adult stem cells (bone marrow source) are related to rescuing the body's ability to make blood cells and fight infections. Many of those who argue against embryonic stem cell research include umbilical cord blood cells in the category of adult stem cells. We are learning, as expected, that the manipulation of stem cells into tissues in the laboratory differs from the same differentiation in the body and that the milieu in which the cells live matters greatly. Perhaps adult stem cells are not as limited as they seem and we only need to figure out what's needed to make them more versatile.

At the same time, adult stem cell transplants have been around for 40 years and have yet to cure Parkinsons, Alzheimers, muscular dystrophy, spinal cord paralysis.

The National Academies of Science (and NIH) said so

In 2002 the National Academies report Stem Cells and the Future of Regenerative Medicine called for human stem cell and human embryonic stem cell research to move forward. The report argued for federal funding of research deriving and using embryonic stem cells from a variety of sources, including those from nuclear transfer. The reasons for federal funding were that progress in the field is less likely to be hindered and there's greater opportunity for regulatory oversight and scrutiny of the research. Bush's later Presidential Directive limited the stem cell lines to those in existence in August, 2001. The National Research Council and the Institute of Medicine recently released their Guidelines for Human Embryonic Stem Cell Research, which are intended to provide some consistency in how embryonic stem cell research is conducted.

Marie Godfrey, PhD

My opinion on stem cell research

Although I am extremely reluctant to do so, I've been encouraged by some others in Geneforum to share my personal opinion of stem cell research. I suspect they will be surprised. In the stem cell poll that appears in the left column of the home page for Geneforum, my vote is among those in the 3rd category--my opinion on federal funding of stem cell research is based mostly on economic grounds. Even before the two hurricanes that hit the Gulf Coast, I have been among those who feel that the U.S. federal government is spending our money inappropriately. There are so many other things we need to spend our money on--things that support life today. The opening of the World Stem Cell Hub in Korea has been of special interest to me because it means that another country, who deserves the economic boost, is focusing on research that is likely to provide amazing and unimagined applications in the future. We really need to operate as an international community, not just as one country. I agree with Insoo (see my interview with Insoo Hyun, a bioethicist) that the focuses of embryonic and adult stem cell research are different and that embryonic stem cell therapies for human diseases with a genetic component (for example, Type I diabetes) are a long way off in the future. There's no strong scientific reason to discard one type of research in favor of the other. I really don't know what I think about "true" embryonic stem cell research, where a human embryo, created by fertilization of an egg with a sperm, is destroyed. For somatic cell nuclear transfer (SCNT)--at least the type performed by Hwang in Korea--I tend to think the way Hwang does (according to Insoo). It's a very special form of tissue culture, providing an opportunity for advancing our knowledge of disease therapy and our understanding of cells in a way simply not possible with adult stem cells. As I read about the long-term effects of bone marrow transplant--especially for young children--I am excited to think that there may be a way to avoid graft-versus-host disease that is all too common when cells are transferred between two different people. Wouldn't it be great to have cells immunologically identical to the recipient? If SCNT is the only way to get that, then I support the research. I have wondered, as a scientist and geneticist, what if blastocysts created in SCNT are not capable of developing into human beings? Human fertilization and implantation are such complex processes--often failing even in the best of conditions. Why have we automatically believed that the product of joining a somatic cell and an enucleated egg cell is a viable human embryo? Just because animals can be cloned, it doesn't mean that's what's being done in SCNT. And no, I definitely do not support human cloning! Please note, these are my opinions only, and may not reflect those of other members of Geneforum or its board. Your opinions are also welcome; use the comment mode in this blog to let others know what you think--and why. Marie Godfrey, PhD

Regulatory hurdles for stem cells

One of the big surprises to me from the stem cell meeting in San Francisco over the weekend was the academic's astonishment at how much work is involved in getting a treatment approved by the Food and Drug Administration (FDA). If stem cell treatments are to be patented and sold like prescription drugs which is a likely commercial goal then a very long process is involved and the steps are many. The steps are also highly regulated by authorities, including the U.S. FDA, the European Agency for the Evaluation of Medicinal Products (EMEA), and the Korean Food and Drug Administration (KFDA).

Human clinical studies can begin in another country or in a U.S. state as long as no international or interstate commerce is involved an unlikely situation given the limited sources of stem cells. To conduct studies that may eventually be used to support a marketing application, an Investigational New Drug Application (IND) is necessary and this requires extensive, highly regimented animal (preclinical) studies. Essentially, the group planning to introduce the stem cells into humans has to 1) characterize the material to be used, 2) demonstrate that the material is unlikely to cause safety problems, and 3) provide a plan for Phase I clinical studies.

A natural question to be asked here is, why hasn't this been necessary with bone marrow transplants? The issue is profit. A group, such as a particular hospital, can perform medical procedures considered beneficial for patients without all the FDA regulatory process as long as the procedure is not patented and sold for profit. That the facility performing the procedure is likely to make a profit because patients will go there rather than elsewhere is a different issue. Thus, we have bypass surgery for heart conditions as an accepted medical procedure, but balloons inserted into blood vessels to increase blood flow were patented and met FDA regulations as medical devices.

So, as we consider the future of stem cell research we also have to include the American free-market system and the need for companies to make a profit. What I don't know and perhaps a reader can tell us what regulations companies that offer fetal stem cell treatments or cord blood cell treatments have to follow.

Marie Godfrey, PhD

Research results vs. breakthroughs the Scientific Method vs. media hype

I live in Utah the home of cold fusion (which was greatly hyped before its bubble burst) and, as a scientist, I'm always eager to see confirmation of new breakthroughs before I fully believe. Meanwhile, media hype is eager to report the first or the best whatever. The addition of money and politics to the picture has enhanced the conflict.

The latest accusations in the Hwang stem cell controversy are not surprising. Hwang's work has not yet been duplicated by others. One of the key steps of the Scientific Method is confirmation of results by outside sources. While Hwang could be accused of going after the glory before the confirmation, I can't help but wonder what Shatten and the others in the group were doing at the time. Could they have attached their names to a paper without agreeing with the information in the publication?

Science contains "refereed research reports, submitted by their authors for free, with the sole objective of making the research findings available as broadly as possible once they have met Science's rigorous standards of peer review" as well as articles by salaried staff writers and commissioned articles written for a fee. The Hwang article, published in Science 17 June 2005 308:1709 (online in Science Express on 19 May 2005) presumably was peer-reviewed. Could the peer reviewer(s) and the editors (copyeditors, proofreaders, etc.) not note that two figures were identical when they should not have been?

Perhaps the greatest message in the Hwang conflict is that we all have to be critical of information released by scientists to the public. I have worked as a scientist writing peer-reviewed publications, a medical writer for pharmaceutical companies, and now a blogger. Each of these areas is and should be subject to public scrutiny. You, as a reader of this blog, can hold me accountable by challenging anything I write and I really appreciate those who take the time to comment on blog entries, whether the comments are positive or negative. The only comments I do not publish are the obvious spam messages that slip through.

So, view news reports and even scientific articles critically. You do not have to understand the science to be critical of its reporting. In fact, for another publication I write for, we prefer critics who know nothing about the subject in question. We ask them to read an article and tell us whether it is believable and coherent. We can all do the same.

Marie Godfrey, PhD

Stem cells from primates

I just put my new Oregon license plates on my car and am proud to identify myself as an oregoniutahn (probably sounds like some commercial you've seen lately). Today's Oregonian included more on its front page about Shoukhrat Mitalipov's ability to cconvert monkey skin cells into heart, nerve and other adult cells. Before this, no one had been able to get the right combination of techniques and chemicals to complete the process. The journal Nature published a study detailing the breakthrough. According to the Oregonian, "Mitalipov and his colleagues had cloned cells scraped from a monkey's skin, transforming them into embryonic stem cells by incubating their DNA inside an egg cell. Researchers "turned the resulting line of stem cells into heart cells, nerve cells and other adult cells." "A Russian native, Mitalipov has worked at the Hillsboro lab since 1998 with retired scientist Don Wolf and others. Despite scientists and politicians promising that sick people could be treated with cloned stem cells, many researchers thought primates' complex biology would make that technically impossible." "Basically, the Oregon scientists figured out a better way to run an experiment that had been done many times without success. Cloning monkey stem cells involves harvesting an egg, emptying material from the egg's nucleus, then inserting DNA from an adult cell. But the tools and methods previously used damaged the cells, so they rarely grew into early stage embryos and never yielded stem cell lines." "Genetic tests proved the resulting cells genetically identical to the adult DNA donor, not the female egg donor, right down to having Semos's (the donor monkey) male sex chromosome. At least one major problem remains: "The technique is not terribly efficient. The Oregon crew used 304 eggs to make two stem cell lines." Check out http://www.oregonlive.com/news/ oregonian/index.ssf?/base/news/1195102503309700.xml&coll=7&thispage=1 for more details. Marie Godfrey, PhD

The end of stem cell research? Hardly

My thanks today to Arthur Caplan, PhD, for his comments on stem cell research--in direct contrast to mine yesterday about stem cell research fizzling. His article--whose title I stole for this blog entry--can be accessed at http://msnbc.msn.com/id/10683107/

In addition to discussing the demise of Hwang and his research, Caplan comments on a fact well-known among scientists but not always effectively transmitted to the public:

In fact it has proven very hard to clone many animals including most monkeys and primates. While human embryonic cloning will happen it may not happen for years.

People wanted to believe--including those who flooded the World Stem Cell Hub website with applications to participate in stem cell studies. Caplan suggests Hwang got away with the hoax--admittedly it was for only a short time--because people are so convinced that stem cells and the "cloning" needed to create them are possible.

Thanks, Arthur for your thoughtful contribution to the latest news.

Marie Godfrey, PhD

What is a cell?

Ever so often, we need to repeat the basic questions before we can go on to the more difficult ones. So, what's a cell?

The cell is the smallest complete unit of a living organism. Bacteria are one-cell organisms; humans have many millions of cells. For multicellular organisms, the cell (zygote) created by the fertilization of a egg by a sperm can multiply, differentiate into many different tissue types (e.g., muscle, nervous, cardiac), form different organ systems (e.g., cardiovascular, skin, digestive tract), and become an entire human being. In humans, as with all mammals, development into an independent living organism is only possible if the zygote implants itself in a female's uterus within a limited number of cell disivions after fertilization.

During differentiation, most cells follow a one-way path towards one of the many different tissue types needed by the body. Although nearly all cells of a human being contain the same genetic information (genotype), cells of one tissue type (e.g., muscle) are different in appearance and function (phenotype) from all cells of other tissue types (e.g., nerve and skin).

Because the body often needs different numbers of certain cells, the body's remarkably efficient construction system maintains a supply of cells that have not completed their differentiation. In particular, stem cells in bone marrow can produce lymphocytes, leukocytes, and other blood cells. Except for these "undifferentiated" cells, one tissue type cannot produce another tissue type; e.g., muscle cells cannot produce nerve cells.

Two cell types of the human body are "special". The sex cells -- oocytes and spermatocytes -- produce specialized reproductive cells -- eggs (ova) and sperm -- which have only half the genetic material of other body cells. Human females produce all their egg cells before birth; males produce their sperm cells over many years. An egg or sperm must combine with its matching type (forming a zygote) before it can multiply. The other special type of cell is red blood cells (erythrocytes), which have differentiated so far they no longer contain any genetic material and can no longer produce new cells.

Marie Godfrey, PhD