Stem Cell Guide

The Stem Cell guide is integrated with the Genetizen – a blog authored by experts in the field of bioethics, genetics, and healthcare who comment on and analyze current developments in the field.

A key feature of this guide is its peer-review capability i.e., the ability for visitors to contribute and interact with the content. Comments are enabled at that bottom of every page. However, if you'd like to submit your own story click Your Stories on the menu bar.

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

65 diseases/conditions treated by adult stem cells

Here are the categories and specific diseases/conditions that www.stemcellresearch.com states are successfully treated by adult stem cells.

Cancers:

  • Brain Cancer
  • Retinoblastoma
  • Ovarian Cancer
  • Skin Cancer: Merkel Cell Carcinoma
  • Testicular Cancer
  • Tumors abdominal organs Lymphoma
  • Non-Hodgkins lymphoma
  • Hodgkins Lymphoma
  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Chronic Myelogenous Leukemia
  • Juvenile Myelomonocytic Leukemia
  • Cancer of the lymph nodes: Angioimmunoblastic Lymphadenopathy
  • Multiple Myeloma
  • Myelodysplasia
  • Breast Cancer
  • Neuroblastoma
  • Renal Cell Carcinoma
  • Various Solid Tumors
  • Soft Tissue Sarcoma
  • Waldenstrom's macroglobulinemia
  • Hemophagocytic lymphohistiocytosis
  • POEMS syndrome

Auto-Immune Diseases

  • Multiple Sclerosis
  • Crohn's Disease
  • Scleromyxedema
  • Scleroderma
  • Rheumatoid Arthritis
  • Juvenile Arthritis
  • Systemic Lupus
  • Polychondritis
  • Sjogren's Syndrome
  • Behcet's Disease
  • Myasthenia
  • Autoimmune Cytopenia
  • Systemic vasculitis
  • Alopecia universalis

Cardiovascular

  • Heart damage

Ocular

  • Corneal regeneration

Immunodeficiencies

  • X-Linked hyper immunoglobuline-M Syndrome
  • Severe Combined Immunodeficiency Syndrome
  • X-linked lymphoproliferative syndrome

Neural Degenerative Diseases/Injuries

  • Parkinson's disease
  • Spinal cord injury
  • Stroke damage

Anemias/Blood Conditions

  • Sickle cell anemia
  • Sideroblastic anemia
  • Aplastic Anemia
  • Amegakaryocytic Thrombocytopenia
  • Chronic Epstein-Barr Infection
  • Fanconi's Anemia
  • Diamond Blackfan Anemia
  • Thalassemia Major
  • Red cell aplasia
  • Primary Amyloidosis

Wounds/Injuries

  • Limb gangrene
  • Surface wound healing
  • Jawbone replacement
  • Skull bone repair

Other Metabolic Disorders

  • Osteogenesis imperfecta
  • Sandhoff disease
  • Hurler's syndrome
  • Krabbe Leukodystrophy
  • Osteopetrosis
  • Cerebral X-linked adrenoleukodystrophy

The majority of these are treated by bone marrow transplants, the category of stem cell treatment discussed previously in 7 parts in this blog.

Marie Godfrey, PhD 

Using adult stem cells for heart problems

A recent news article reminded me that "adult" stem cell research continues while the issue of federal funding of embryonic stem cell research remains unchanged. The article I saw came June 2 from WTAE Channel 4 Action News in Pittsburg and highlights Richard Howell's receipt of stem cells in an effort to reverse the heart failure that "left him too weak to leave his living room and at risk for complications, including organ failure."

Howell is one of a number of patients in experimental stem cell studies. This one is taking place at the Cleveland Clinic, recently a recipient of a $24 million grant--along with Case Western Reserve University (Case) and its partners, University Hospitals of Cleveland (UHC), and Athersys, Inc.

According to Dr. Stephen Ellis of The Cleveland Clinic: "Mr. Howell received 18 separate injections encompassing about 200 million cells. By giving these cells, the hope is the heart muscle will function better, contract better." The cells came--not from bone marrow, as might have been expected, or even from peripheral blood cells, but--from thigh muscle cells.

One of the fascinating aspects of the source of the stem cells is that cardiac muscle and thigh muscle cells are different types and designed for different functions. One type does not generally convert into the other. The news article did not explain how stem cells--rather than fully developed muscle cells--were identified and removed for transplant.

So far, Howell--who couldn't walk to the mail box--is "out of his living room and on the beach" 6 weeks after surgery. Howell agreed to take the risks--including possible arrhythmias or potentially lethal rapid heart rhythms--even though it may take months, or even years, before anyone knows if the experiment was successful.

The news article can be found at http://www.thepittsburghchannel.com/health/9314174/detail.html Details about the Cleveland Clinic are accessible from their home page: www.clevelandclinic.org

Marie Godfrey, PhD

Using cardiac adult stem cells to repair heart tissue

One of the strong messages from the stem cell meeting in San Francisco over the weekend was that stem cell research needs to show some new successes soon. For many reasons, embryonic stem cell research is unlikely to provide new treatments or curescat least not in humanscwithin the next couple of years. Even though some clinical trials are planned, these are generally Phase I trials, which are intended to test the safety not the efficacy of stem cell treatments.

A new federal program focused on cell-based therapies that could be ready for clinical trials testing within two years announced Sept 29 that my favorite institution Johns Hopkins is one of three centers to receive five-year funding ($12 million) from the National Heart, Lung, and Blood Institute as a Specialized Center for Cell-Based Therapy for Heart, Lung and Blood Diseases (SCCT). Hopkins is the only center dedicated to new therapies for heart problems. The SCCT initiative will focus on two major projects.

Marbin's group will study the potential of using a patient's own cardiac stem cells to repair heart tissue soon after a heart attack, or to regenerate weakened muscle resulting from heart failure. By using a persons own adult stem cells instead of those from another donor, there would be no risk of triggering an immune response that could cause rejection. Marb¡n was recently successful in replicating large numbers of cardiac stem cells in the lab within a very short time, as little as four weeks. The stem cells, extracted from healthy parts of hearts not otherwise damaged by heart attack, grew to form clusters, called cardiospheres, which contain cells that retain the ability to regenerate themselves and to develop into more specialized heart cells that can conduct electrical currents and contract like heart muscle should.

Hare's group will evaluate adult mesenchymal stem cells (the stem cells in bone marrow that do not form blood cells) as a potential therapy to heal damaged hearts. Last year, his research in animals showed that stem cells harvested from one pig's bone marrow and injected into another pig's damaged heart restored heart function and repaired damaged heart muscle by 50 percent to 75 percent after just two months of therapy. In March 2005, Hare and other researchers began a Phase I clinical trial to test the safety of injecting adult stem cells at varying doses in patients who have recently suffered a heart attack. In total, 48 patients will participate in this study, which involves several sites across the country, including Hopkins. Results are not expected until mid-2006. Because mesenchymal stem cells are in an early stage of development, they, too, avoid potential problems with immune rejection, in which every humans immune system might attack stem cells from sources other than itself.

Marie Godfrey, PhD

Embryonic stem cell lines accumulate changes in their genetic material over time

Wow! Google Alerts finally sent me an article that discusses both the genetics of stem cells and my alma mater, The Johns Hopkins University. At the same time, the article feeds into my current discussion of the usability of adult vs. embryonic stem cells.

The notice I received connected to http://www.newswise.com/articles/view/514125/ and was summarized with the following clip:

An international team of researchers has discovered that human embryonic stem cell lines accumulate changes in their genetic material over time.

The researchers' work is described in the Sept. 4 online edition of Nature Genetics.

Anirban Maitra and Dan Arking, two of the authors and members of the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins state:

Embryonic stem cells are actually far more genetically stable than other stem cells, but our work shows that even they can accumulate potentially deleterious changes over time. Now it will be important to figure out why these changes occur, how they affect the cells' behavior and how time affects other human embryonic stem cell lines.

So, should we continue restricting funding of embryonic stem cell research to lines existing 4 years ago? Should all stem cell transplants be freshly-harvested adult stem cells? What happens with stem cell lines developed from stored umbilical cord cells? Hmmm, once again, more questions than answers.

Marie Godfrey, PhD

Leads on question of adult vs. embryonic stem cell potential

Since I have not yet created a template for my blog entries, I return to old ones to make the font, spacing, etc. the same. Today, I happened to stumble on my July 3 blog and see that I have been wrong about Frist's changes of mind and when they occurred. His most recent to back the removal of federal funding restrictions on embryonic stem cell research is his second switch, as I have been saying. But, the first switch from support to banning occurred back in 2001 after Bush restricted federal funding, not in April of this year. I had the date incorrect.

This morning's (6 August 2005) Google Alerts brought me an article from WorldNet Daily, Grants Pass Oregon, written by Kelly Hollowell, JD, PhD, Senior Strategist at the Center for Reclaiming America. The alert read: A detailed list of supporting references is available on request to my e-mail address below, as is a list of adult stem cell applications for 65 human diseases. Had another portion of the article been chosen for the alert, such as her quotes from Frist, I might never have checked out the article. As it was, I read it finding a discussion countering Frist's use of unique to describe embryonic stem cell capabilities. Hollowell states:

According to more than 15 recent publications in leading and peer-reviewed scientific journals, adult stem cells have the same pluripotency and/or capacity to multiply as embryonic stem cells.

The most recent and groundbreaking publication, by Dr. John Huard, director of the Growth and Development Laboratory at Children's Hospital of Pittsburgh, confirms that adult stem cells have the same ability as embryonic stem cells to multiply. This publication appears in the July 2005 edition of Molecular Biology of the Cell. The paper is appropriately under consideration for Molecular Biology of the Cell paper of the year.

Other data clearly demonstrate the ability of adult stem cells to form heart, liver, kidney, muscle, brain, nerve, insulin-producing, hair, skin, lung, retina, intestinal and spleen cells. The data also demonstrate that adult stem cells have the ability to regenerate damaged tissue.

I responded to the article immediately, adding some comments of my own, and requested the list of references, which she promptly sent. Of course, I also invited her to check out Geneforum and add her comments to the discussion.

I'll be reviewing as many articles as I can, so I can digest the information she references and bring you a summary of what I find. These references are a perfect source for my last blog entry question: how do adult stem cells and embryonic stem cells compare in potential? Unfortunately, searching MedLine or Google scholarly for successful stem-cell treatments has been frustrating. Thank you, Dr. Hollowell.

Marie Godfrey, PhD

Opposition to embryonic stem cell research cites 65 diseases cured by adult stem cells; are they right?

David A. Prentice, a scientist with the conservative Family Research Council is one of the people advocating tight restrictions on embryonic stem cell research. According to an article in the July 15th Washington Post and a letter to the editor of Science magazine, Prentice's claims that adult stem cells have at least as much medical potential as embryonic cells are not supported by even the references he gives in his examples.

Shane Smith of the Children's Neurobiological Solutions Foundation in Santa Barbara, Calif.; William B. Neaves of the Stowers Institute for Medical Research in Kansas City, Mo.; and Steven Teitelbaum of Washington University in St. Louis went through Prentice's footnoted documentation and concluded that most of his examples are wrong. For example:

  • A study cited by Prentice as evidence that adult stem cells can help patients with testicular cancer is in fact a study that evaluates methods of isolating adult stem cells.
  • Similarly, a published report that Prentice cites as evidence that adult stem cells can help patients with non-Hodgkin's lymphoma does not address the medical value of those cells but rather describes the best way to isolate cells from lymphoma patients and grow them in laboratory dishes.
  • And Prentice's reference to the usefulness of adult stem cells for patients with Sandhoff disease -- a rare nerve disorder -- is "a layperson's statement in a newspaper article".

"All told, the scientists concluded, there are only nine diseases that have been proved to respond to treatment with adult stem cells." (Washington Post).

The Post quotes from the Science letter as follows:

By promoting the falsehood that adult stem cell treatments are already in general use for 65 diseases and injuries, Prentice and those who repeat his claims mislead laypeople and cruelly deceive patients.

Prentice, in a brief voice message left for a Post reporter, is quoted as saying, "I appreciate them pointing out some of the things . . . that need to be changed and updated." But, the Post reports that "he accused the letter writers of 'mental gymnastics' by focusing narrowly on proven therapies, as opposed to the large number of diseases for which the value of adult stem cells is now being tested."

The issue of adult vs embryonic stem cell research has been discussed here in the Genetizen blog several times. To see these entries, adult stem cells in the search box on this page.

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

Bush vetoes bill intended to remove restrictions on federal funding of stem cell research

Bush's veto of the bill known as H.B. 810, or the stem cell enhancement bill, is the first veto cast by the President of bills delivered to him from Congress. The New York Times online reported the veto about an hour ago.

Bush, "surrounded by scores of children born as a result of an embryo-adoption program and their parents", made the following statement:

This bill would support the taking of innocent human life. Each of these human embryos is a unique human life with inherent dignity and matchless value. These boys and girls are not spare parts.

In an interesting note, the Times reported:

. . . one element was missing [from the White House ceremony]: a flourish of the pen that Mr. Bush typically uses to sign a measure that he likes. The president had already signed his name on the veto before appearing in public. The actual signing was not photographed because, Mr. Snow said beforehand, Mr. Bush did not think it would be appropriate.

No official statement was made on whether an override vote would be taken.

Marie Godfrey, PhD

All 3 stem cell bills pass Senate

Just a few minutes ago, the last (H.B. 810)--and most controversial--of the three stem cells debated in the Senate passed 63 to 37. According to the summary shown on the C-SPAN2 screen, this bill "broadens spending for embryonic stem cell research". Actually, what it does is remove the limitations now in force; no additional money is allocated in the bill. Since the House had already passed this bill (14 months ago), the bill now goes to President Bush. If he vetoes it, as he has declared, the 63 votes would not be enough to override the veto; 67 votes are needed.

The other two bills relating to stem cell research (no fetal farming and investigate alternative ways of making embryonic stem cell lines), as expected, passed-- unanimously. These will now go to the House, where they are also expected to easily pass. President Bush will likely sign these two bills.

One question arose in my mind as I was watching the voting: if so many spoke in favor of retaining the limits on federal spending for embryonic stem cell research why did so few (zero) vote against the bill that directs NIH to investigate alternative ways of creating embryonic stem cell lines? Wouldn't this money also be "taken away" from adult stem cell research"?

Anyway, the drama is over in the Senate. Let's see what President Bush does.

Marie Godfrey, PhD

ALL the bills

Just in case you think the list of active bills (in the previous blog entry) covers everything, here is the full list of bills relating to stem cells and cloning introduced into the House (ih) or Senate (is) and the actions taken since then. Each abbreviation, eg (ih), is defined after each title. The ones marked with * are on the current active legislation list.

H.Con.Res. 166 (ih) Expressing the sense of the Congress that the Federal Government should not infringe on State or private programs that fund embryonic stem cell research. [Introduced in House]

H.R. 162 (ih) To authorize the use of Federal funds for research on human embryonic stem cells irrespective of the date on which such stem cells were derived, and for other purposes. [Introduced in House]

H.R. 222 (ih) To prohibit the expenditure of Federal funds to conduct or support research on the cloning of humans, and to express the sense of the Congress that other countries should establish substantially equivalent restrictions. [Introduced in House]

H.R. 596 (ih) To amend the Public Health Service Act to establish a National Cord Blood Stem Cell Bank Network to prepare, store, and distribute human umbilical cord blood stem cells for the treatment of patients and to support peer-reviewed research using such cells. [Introduced in House]

H.R. 810 (eh) To amend the Public Health Service Act to provide for human embryonic stem cell research. [Engrossed in House]

H.R. 810 (ih) To amend the Public Health Service Act to provide for human embryonic stem cell research. [Introduced in House]

H.R. 810 (pcs) To amend the Public Health Service Act to provide for human embryonic stem cell research. [Placed on Calendar Senate]

*H.R. 810 (rds) To amend the Public Health Service Act to provide for human embryonic stem cell research. [Received in the Senate]

*H.R. 1357 (ih) To amend title 18, United States Code, to prohibit human cloning. [Introduced in House]

H.R. 1650 (ih) To amend the Internal Revenue Code of 1986 to allow tax credits to holders of stem cell research bonds. [Introduced in House]

*H.R. 1822 (ih) To prohibit human cloning and protect stem cell research. [Introduced in House]

H.R. 2520 (eh) To provide for the collection and maintenance of human cord blood stem cells for the treatment of patients and research, and to amend the Public Health Service Act to authorize the C.W. Bill Young Cell Transplantation Program. [Engrossed in House]

H.R. 2520 (ih) To provide for the collection and maintenance of human cord blood stem cells for the treatment of patients and research, and to amend the Public Health Service Act to authorize the C.W. Bill Young Cell Transplantation Program. [Introduced in House]

*H.R. 2520 (rds) To provide for the collection and maintenance of human cord blood stem cells for the treatment of patients and research, and to amend the Public Health Service Act to authorize the C.W. Bill Young Cell Transplantation Program. [Received in the Senate]

*H.R. 2541 (ih) To amend the Public Health Service Act to provide for the expansion, intensification, and coordination of the activities of the National Institutes of Health regarding qualifying adult stem cell research, and for other purposes. [Introduced in House]

H.R. 2574 (ih) To amend the Public Health Service Act to provide for a program at the National Institutes of Health to conduct and support research on animals to develop techniques for the derivation of stem cells from embryos that do not harm the embryos, and for other purposes. [Introduced in House]

H.R. 3144 (ih) To amend the Public Health Service Act to provide for a program at the National Institutes of Health to conduct and support research in the derivation and use of human pluripotent stem cells by means that do not harm human embryos, and for other purposes. [Introduced in House]

H.R. 3444 (ih) To amend the Internal Revenue Code of 1986 to provide credits against income tax for qualified stem cell research, the storage of qualified stem cells, and the donation of umbilical cord blood. [Introduced in House]

*S. 471 (is) To amend the Public Health Service Act to provide for human embryonic stem cell research. [Introduced in Senate]

*S. 658 (is) To amend the Public Health Service Act to prohibit human cloning. [Introduced in Senate]

S. 681 (is) To amend the Public Health Service Act to establish a National Cord Blood Stem Cell Bank Network to prepare, store, and distribute human umbilical cord blood stem cells for the treatment of patients and to support peer-reviewed research using such cells. [Introduced in Senate]

S. 876 (is) To prohibit human cloning and protect stem cell research. [Introduced in Senate]

S. 1317 (is) To provide for the collection and maintenance of cord blood units for [Introduced in Senate]

*S. 1317 (rs) To provide for the collection and maintenance of cord blood units for [Reported in Senate]

S. 1520 (is) To prohibit human cloning. [Introduced in Senate]

S. 1557 (is) To amend the Public Health Service Act to provide for a program at the National Institutes of Health to conduct and support research in the derivation and use of human pluripotent stem cells by means that do not harm human embryos, and for other purposes. [Introduced in Senate]

*S. 1557 (is) To amend the Public Health Service Act to provide for a program at the National Institutes of Health to conduct and support research in the derivation and use of human pluripotent stem cells by means that do not harm human embryos, and for other purposes. [Introduced in Senate]

In Thomas (the source of the list), the list is identified as Last updated: January 14, 2005, however the list includes actions in response to Hurricane Katrina, so it is probably up-to-date.

Marie Godfrey, PhD

Stem cell bills to be debated in Senate July 17

Here are the summaries of the bills being considered:

S.3504

Title: A bill to amend the Public Health Service Act to prohibit the solicitation or acceptance of tissue from fetuses gestated for research purposes, and for other purposes.
Sponsor: Sen Santorum, Rick [PA] (introduced 6/13/2006) Cosponsors (2)
Related Bills: H.R.5719
Latest Major Action: 6/13/2006 Referred to Senate committee. Status: Read twice and referred to the Committee on Health, Education, Labor, and Pensions.


SUMMARY AS OF:
6/13/2006--Introduced.
Fetus Farming Prohibition Act of 2006 - Amends the Public Health Service Act to prohibit any person or entity involved in interstate commerce from: (1) soliciting or knowingly acquiring, receiving, or accepting a donation of human fetal tissue knowing that a human pregnancy was deliberately initiated to provide such tissue; or (2) knowingly acquiring, receiving, or accepting tissue or cells obtained from a human embryo or fetus that was gestated in the uterus of a nonhuman animal. Imposes fines and/or imprisonment for violations of this Act.

S.2754

Title: A bill to derive human pluripotent stem cell lines using techniques that do not knowingly harm embryos.
Sponsor: Sen Santorum, Rick [PA] (introduced 5/5/2006) Cosponsors (4)
Related Bills: H.R.5526
Latest Major Action: 6/27/2006 Senate committee/subcommittee actions. Status: Committee on Appropriations Subcommittee on Labor, Health and Human Services, Education, and Related Agencies. Hearings held.


SUMMARY AS OF:
5/5/2006--Introduced.
Alternative Pluripotent Stem Cell Therapies Enhancement Act - Amends the Public Health Service Act to require the Secretary of Health and Human Services to develop techniques for the isolation, derivation, production, or testing of stem cells that are capable of producing all or almost all of the cell types of the developing body and may result in improved understanding of treatments for diseases and other adverse health conditions, but are not derived from a human embryo.

Requires the Secretary to: (1) provide guidance concerning the next steps required for additional research; (2) prioritize research with the greatest potential for near-term clinical benefit; and (3) take into account techniques outlined by the President's Council on Bioethics and any other appropriate techniques and research.

H.R.810

Title: To amend the Public Health Service Act to provide for human embryonic stem cell research.
Sponsor: Rep Castle, Michael N. [DE] (introduced 2/15/2005) Cosponsors (200)
Related Bills: S.471
Latest Major Action: 6/6/2005 Read the second time. Placed on Senate Legislative Calendar under General Orders. Calendar No. 119.


SUMMARY AS OF:
5/24/2005--Passed House, without amendment. (There is 1 other summary)

(This measure has not been amended since it was introduced. The summary has been expanded because action occurred on the measure.)

Stem Cell Research Enhancement Act of 2005 - Amends the Public Health Service Act to require the Secretary of Health and Human Services to conduct and support research that utilizes human embryonic stem cells, regardless of the date on which the stem cells were derived from a human embryo, provided such embryos: (1) have been donated from in vitro fertilization clinics; (2) were created for the purposes of fertility treatment; (3) were in excess of the needs of the individuals seeking such treatment and would never be implanted in a woman and would otherwise be discarded (as determined in consultation with the individuals seeking fertility treatment); and (4) were donated by such individuals with written informed consent and without any financial or other inducements.

Requires the Secretary to: (1) issue final guidelines to carry out this Act within 60 days; and (2) submit annual reports on activities and research conducted under this Act.

H.R.810
Title: To amend the Public Health Service Act to provide for human embryonic stem cell research.
Sponsor: Rep Castle, Michael N. [DE] (introduced 2/15/2005) Cosponsors (200)
Related Bills: S.471
Latest Major Action: 6/6/2005 Read the second time. Placed on Senate Legislative Calendar under General Orders. Calendar No. 119.


SUMMARY AS OF:
2/15/2005--Introduced. (There is 1 other summary)

Stem Cell Research Enhancement Act of 2005 - Amends the Public Health Service Act to require the Secretary of Health and Human Services to conduct and support research that utilizes human embryonic stem cells, regardless of the date on which the stem cells were derived from a human embryo. Limits such research to stem cells that meet the following ethical requirements: (1) the stem cells were derived from human embryos donated from in vitro fertilization clinics for the purpose of fertility treatment and were in excess of the needs of the individuals seeking such treatment; (2) the embryos would never be implanted in a woman and would otherwise be discarded; and (3) such individuals donate the embryos with written informed consent and receive no financial or other inducements.

You can check out additional details by going to www.senate.gov and making your selection of the bills on the righthand side of the screen (schedule for Monday, July 17).

Marie Godfrey, PhD

Was stem cell action in Senate strictly political?

I watched many hours of the stem cell debates in the Senate Monday and Tuesday, taking a break mainly when the Senate went to lunch on Tuesday.

Actually, one had to watch only once in a while, because much of the information presented was repeated over and over. I believe the whole discussion was strictly a political move on the part of both Democrats and Republicans. Democrats and Republicans alike pushed to have the measure discussed so that the public could see them on stage making their pitch. All are eager to look good to their constituents and others and most really believe what they were saying.

The "deal" to put 3 bills together and to vote on the newer ones before the older H.B. 810 gave everyone an opportunity to speak on behalf of two bills considered not controversial. Then, each could give their spin to the controversial bill. Meanwhile, though, everyone "knows" that President Bush will rescue the millions or billions that might be spent on stem cell lines created after August, 2001 by vetoing the bill.

The following statements have been around for a long time (certainly since 2001):

  • Treatment with adult stem cells (and cord blood stem cells) has shown positive results for 65 (68, 70, 72?) diseases [the number varies, but no one ever mentions that almost all represent infusions of blood-forming cells in patients treated for cancer]
  • Embryonic stem cell research has not "cured" a single disease [note the difference between "positive results"--the new mantra--and "cure". This statement is true; however, clinical studies of embryonic stem cells are just beginning, and those funded by the federal government can only be done with 6 (4?) "healthy" but mouse-contaminated cell lines. Studies with adult stem cells (eg, bone marrow) have been going on for decades.]
  • Creation of embryonic stem cells requires the killing of embryos. [Yes, removal of the inner cell mass from a very early embryo does mean that the embryo will never develop into a human being. If you agree that this is killing an embryo, the rest of the text here doesn't apply. However, no blastocyst is guaranteed life: many embryos do not succeed in implanting when they are put into a woman's uterus; some embryos are "killed" when too many embryos implant and develop, and a multiple-birth is risky; many embryos are allowed to die (from storage beyond a couple of years); many embryos are discarded because they are not needed by the people who supplied the egg and sperm.]
  • Some people have adopted embryos (having one or more introduced into a woman's uterus and allowed to develop). These are the Snowflake children. [The numbers naturally have increased since 2001.]
  • Stem cells from a source other than the person receiving them can cause immune reactions in the recipient. [Speakers generally accused the non-favored type of stem cells of causing this problem. Yes, there is always a chance of rejection, graft-vs-host reaction, and other immune problems when foreign cells are introduced. However, The stem cells taken from a person and injected back into that person have the same genetic components; if the person developed a genetically-influenced condition, giving back the same genes cannot help forever. Cord blood cells are not the answer: Most adults didn't save their umbilical cord cells, and if they did, the cells wouldn't be healthy in storage over more than 5 years or so. There are very few stem cells in the umbilical cord, so even an infant or child who was originally attached to the cord cannot get more than one stem cell treatment without growing the cells in test tubes.]

Here are some of the newer arguments for and against embryonic stem cell research:

  • Stem cell lines have been created by "alternative" means--one of the three bills requires Congress to spend money to further research these methods. [Did you know that one method creates a defective embryo and then uses it as a source for stem cells and that another method removes one cell from an 8-cell embryo and uses this to develop a stem cell line? Both techniques are new, not fully tested, and other possibilities certainly exist.]
  • Embryonic stem cells injected into mice create teratomas (cancers). [One speaker said, "that's how scientists tell the cells are stem cells, because they are capable of growing in the new location"; another said "we can never control these teratomas, which will kill the recipient"--these are not direct quotes.]
  • Adult stem cells have been used to create new heart tissue and repair damaged spinal cords. [This work is still early, only on individual patients generally outside the U.S. and not in controlled clinical studies, and neither is a "new" use of stem cells. The stem cells used--either hematopoietic (blood-forming) or connective tissue (also generally from bone marrow)--could be expected to develop into the resulting tissues.]
  • Stem cell lines have been created from eggs and sperm (germ cells). [I need to research this one further; since eggs and sperm have only 1/2 the chromosomes of other cells, this statement cannot be totally true. The research must refer to cells in the body that can develop into eggs and sperm. Also, in women, all egg cells have already been formed at birth so it is hard to tell what cells are being described.]

I think that list gives you enough-perhaps more than you wanted to know--about some of the arguments presented during Senate presentations. You can read everything, including all information a Senator asked to have "put into record" by going to www.senate.gov and accessing the Daily Digest--and then the detailed text--for each day.

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

Audrey R. ChapmanSince 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).

Letter from Insoo Hyun and Kyu Won Jung, World Stem Cell Hub Ethicists

The following letter just appeared in the American Journal of Bioethics:

Letter to the Editor Concerning Oocyte and Stem Cell Procurement for Stem Cell Researchby Insoo Hyun, Kyu Won Jung
2005. The American Journal of Bioethics 5(6):Wxx

To the Editor,

In our article, Oocyte and Somatic Cell Procurement for Stem Cell Research: The South Korean Experience, we outlined and defended the informed consent procedures that we reported that Dr. Jung designed for the Hwang team's 2005 patient-specific stem cell study. In our article, we claimed that the Hwang team followed these rigorous informed consent procedures to procure eggs and somatic cells for their 2005 stem cell research.

However, on December 16, 2005, we began to doubt whether the Hwang team had actually used any of these eggs and somatic cells to generate data for their 2005 Science study. Our doubts were raised by some of Dr. Hwang's remarks during his press conference that same day and also by the two to three month timeline now widely acknowledged by scientists to be necessary to culture new stem cell lines.

Our first concern was that the timeline for the volunteers egg and somatic cell donations did not match the timeline necessary for the Hwang team to produce data for their March 15 article submission to Science. The process we described was not in place prior to January 23, 2005.

Furthermore, Dr. Hwang publicly declared that several patient-specific stem cell lines were contaminated on January 9, 2005, which would suggest that the team performed some of their cloning research well before to the activation of Jung's informed consent procedures. We reported our concerns immediately to a member of the Hanyang Hospital IRB and the leadership of the International Society for Stem Cell Research (ISSCR) and its bioethics committee.

On December 23, 2005, the SNU investigative body announced not only that the Hwang team had fabricated their data, but that they had also used far more eggs than they had initially reported to Science. These extra eggs most certainly were not procured through our described informed consent procedures. Indeed, we wonder whether any of the eggs and somatic cells donated through our informed consent procedures were ever used for research. If not, then Hwang and colleagues may have allowed egg donors to expose themselves to risk needlessly. So, in addition to the problems of the Hwang team's scientific integrity, serious ethical charges of informed consent must now be explored.

We are extremely disappointed by the evidence of the Hwang team's scientific and ethical misconduct. However, we remain steadfast in our belief that the informed consent procedures we describe in our article are ethically rigorous and that they provide a useful starting point for developing tough guidelines for tissue procurement for stem cell research. Unfortunately, we were lead to believe that the Hwang team had actually used these procedures to produce the patient-specific stem cell lines they reported to Science.

Insoo Hyun and Kyu Won Jung

Geneforum's interview with Dr. Hyun appeared some time ago in this blog. We have a second interview, which should be posted soon.

The full article on oocyte donation is the following:

Oocyte and Somatic Cell Procurement for Stem Cell Research:by Kyu Won Jung, Insoo Hyun
2005. The American Journal of Bioethics 5(6):W17

The article has free access.

Marie Godfrey, PhD

Wish and WSCH--the difference is a human being

When the World Stem Cell Hub (WSCH) in Seoul, Korea announced that it was accepting applications from people interested in participating in stem cell research on spinal cord injuries and Parkinsons, the website was flooded with applications. I want to introduce you today to someone who is among those who applied to WSCH.

Steven Edwards describes the emotional aspects of his application in Stem-cell Hopes Hit Home, published online in Wired Magazine, at http://www.wired.com/news/medtech/0,1286,69470,00.html. "I knew my odds were slim. When the call for subjects came out, the website for the World Stem Cell Hub crashed under the traffic load. If I volunteered, I would be one among thousands" he tells us.

He views the implications of a embryo made with his DNA and wonders, "What would the embryo that was used to cure me be like, if it were instead allowed to develop?" This is a question much more personal than asking whether an embryo in a test tube is human. Would he be committing a form of suicide or just using part of his own tissue to create cells that might repair his paralyzed body?

What would you think, if WSCH could fulfill wishes? Please check out Steven's article.

Marie Godfrey, PhD

House passes stem cell research bill

On January 11, the House of Representatives passed the Stem Cell Research Enhancement Act of 2007 (H.R. 3) by a vote of 253 - 174. This bill requires the Secretary of Health and Human Services to conduct and support research that utilizes human embryonic stem cells, regardless of the date on which the stem cells were derived from a human embryo. It also places limits on such research based on ethical requirements.

Looks like the Democrats are trying to get things moving again. You may remember that the House passed a number of such bills last year, but none of them made it through the Senate. I'll keep following the progress. You can always make your own opinion known -- whether you support stem cell research in general, or wish to place limitations -- by writing or calling your representatives in Congress.

Click here to learn more about this legislation, and type "H.R. 3" in the bill number search box.

Marie Godfrey, PhD

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