The Cloning Debate Rolls On

With Frist recently announcing his support for expanding embryonic stem cell research, many people probably believe that the cloning and embryonic stem cell debates are over, but they are wrong. Bush signing H.R. 810 into law wouldn't end the debates, either.

Sufficiently funding somatic cell reprogramming—dedifferentiation and transdifferentiation—would.

One of the primary benefits of embryonic stem cell lines, as claimed by researchers, is the ability to create and study the disease process in affected cell lines to watch how the disease develops and to test potential drugs against. There are currently three main ways to obtain diseased stem cell lines:

1. Deriving diseased cell lines from cryopreserved embryos at IVF clinics.
2. Therapeutic cloning.
3. Cell reprogramming.

The first option, while statistically improbable, is the only way of obtaining diseased embryonic stem cell lines made possible by H.R. 810. Assuming enough cell lines could be obtained this way, there would likely be a lack of diversity to make this an attractive option with the current state of technology. Given these (and other) deficiencies, researchers will not find H.R. 810 acceptable.

The most well known and widely debated option is second: therapeutic cloning. As therapeutic cloning creates an embryo, this option is not a realistic option.

The final option, cell reprogramming, removes both cloning and destroying embryos from the debate. Directly reprogramming an adult cell from one type to another is known as transdifferentiation, while reprogramming an adult cell to a more pluripotent state is known as dedifferentiation.


An example application of transdifferentiation would be biopsying skin cells from a person, directly converting them into islet cells, and then transplant them back into the same person to treat Juvenile Diabetes. Not only does transdifferentiation avoid creating an embryo, it also avoids potential immune rejection problems.

The one problem with this technique is that people with diseases caused by genetic abnormalities may not be able to be their own donors, as the genes would be the same. Two options exist to solve this problem: the first being gene therapy, and the second being obtaining cells from a donor.

An example application of dedifferentiation would be biopsying skin cells from a person and culturing the cells directly into embryonic stem cells. (This should sound familiar, as dedifferentiation is just a specific form of transdifferentiation.) These stem cells could then be grown, cultured to become islet cells, and then transplanted to treat Juvenile Diabetes.

The dedifferentiated stem cells could also be used in labs to allow researchers to study disease processes.

Transdifferentiation, including dedifferentiation, will allow researchers a way to obtain the cells they need to study the early stages of disease processes without destroying embryos or subjecting women to risky hyperovulation sessions, as eggs would not be required.

With Bill Frist making references to cell reprogramming and the President's Council on Bioethics endorsing somatic cell reprogramming, the research has been acknowledged as legitimate on a federal level. All it needs to achieve reality is significant funding.

During this August recess, please contact your Congressmen and ask them to support research into cell reprogramming. Without proper funding, we will stay mired in a needless debate.

Please, contact your Congressmen.

Bill Frist's Floor Speech on Stem Cells. Politics or Not?

PBS is streaming Frist's Speech (RealAudio) on their Online NewsHour Stem Cell page. Some excerpts from the speech:

Right now, though, let me say this: I believe today -- as I believed and stated in 2001, prior to the establishment of current policy -- that the federal government should fund embryonic stem cell research. And as I said four years ago, we should federally fund research only on embryonic stem cells derived from blastocysts leftover from fertility therapy, which will not be implanted or adopted but instead are otherwise destined by the parents with absolute certainty to be discarded and destroyed.

Let me read to you my 5th principle as I presented it on this floor four years ago:

No. 5. Provide funding for embryonic stem cell research only from blastocysts that would otherwise be discarded. We need to allow Federal funding for research using only those embryonic stem cells derived from blastocysts that are left over after in vitro fertilization and would otherwise be discarded (Cong. Rec. 18 July 2001: S7847 [ed: PDF]).

I made it clear at the time, and do so again today, that such funding should only be provided within a system of comprehensive ethical oversight. Federally funded embryonic research should be allowed only with transparent and fully informed consent of the parents. And that consent should be granted under a careful and thorough federal regulatory system, which considers both science and ethics. Such a comprehensive ethical system, I believe, is absolutely essential. Only with strict safeguards, public accountability, and complete transparency will we ensure that this new, evolving research unfolds within accepted ethical bounds.

In a prior post, I stated that I believed Frist's recent announcement is "purely political." Given the full-text of his 2001 statements on stem cell research, do I still believe this?

Well, let's take a look at his rather persuasive reasoning for why he now feels "It’s time for a modified policy."

When the President announced his policy, it was widely believed that 78 embryonic stem cell lines would be available for federal funding. That has proven not to be the case. Today only 22 lines are eligible. Moreover, those lines unexpectedly after several generations are starting to become less stable and less replicative than initially thought (they are acquiring and losing chromosomes, losing the normal karyotype, and potentially losing growth control). They also were grown on mouse feeder cells, which we have learned since, will likely limit their future potential for clinical therapy in humans (e.g., potential of viral contamination).

To address the first point, at a committee hearing on September 5, 2001 (PDF), NIH Secretary Tommy Thompson said that there were only 24 or 25 fully developed cell lines available at the time for funding. While President Bush had stated that over 60 cell lines were available for funding, Secretary Thompson suggested that the remaining cell lines would be available for research purposes within eight or nine months (ie, by June 2002). This turned out to not be true.

Frist's second and third concerns about the existing stem cell lines were also raised in the September 2001 meeting.

Frist also made a reference to "promising research not even imagined four years ago" in his recent speech, such as reprogramming an adult stem cell to become more pluripotent. Four years ago, Frist made reference to "recent" research suggesting "adult stem cells may have more plastic properties than previously believed." (page S7848)

Based on the evidence presented, I do still believe that Senator Frist's statements are purely political.

With that said, there's no reason to cry over spilt milk. Instead, let's use this as a history lesson.

What did we learn? Unnecessary debates prolong cure research, which prolongs suffering. If we can avoid debates in the future, let's do so. Supporting dedifferentiation research avoids the debate—no embryos created, none destroyed—so let's support it. :)

Frist Supports ESC Research; Bush Takes One for the Team

Senator Bill Frist has now come out in support of embryonic stem cell research. Is he telling the truth?

Frist needs this to appeal to the Centrists, and Bush's guaranteed veto allows him to take this stand on the issue. Bush maintains his appeal with the Right, Frist gains approval from the Centrists, Bush campaigns for Frist in 2008 (if he gets the nod, which is likely) and hands the Right to Frist. This is purely political.

From the New York Times:

But, Mr. Frist says the Castle bill has shortcomings. He says it "lacks a strong ethical and scientific oversight mechanism," does not prohibit financial incentives between fertility clinics and patients, and does not specify whether the patients or the clinic staff have a say over whether embryos are discarded. He also says the bill "would constrain the ability of policy makers to make adjustments in the future."

This is inaccurate. The Senate companion bill (S. 471) to Castle's bill (H.R. 810) explicitly states under Section 498D:

`(1) The stem cells were derived from human embryos that have been donated from in vitro fertilization clinics, were created for the purposes of fertility treatment, and were in excess of the clinical need of the individuals seeking such treatment.
`(2) Prior to the consideration of embryo donation and through consultation with the individuals seeking fertility treatment, it was determined that the embryos would never be implanted in a woman and would otherwise be discarded.
`(3) The individuals seeking fertility treatment donated the embryos with written informed consent and without receiving any financial or other inducements to make the donation.

These subsections address both of the issues raised by Frist: it prohibits patients from being financially compensated for donating the embryos and it states that the decision is made, with informed consent, by the "individuals seeking fertility treatment".

If Republicans can maintain their hold through the 2008 elections, embryonic stem cell research will still not be allowed and Frist can set forth an "ethical" ESC policy that pacifies all sides. (Assuming we don't know how to reprogram somatic cells into ESCs by then.)

Update: From the Congressional Record (PDF):

Mr. FRIST. Mr. President, I very much appreciate the question. It gives me the opportunity to show the work and the challenge it is to address an issue that strikes at the science and ethical concerns.

My approach has been to include what I think the Senator from Iowa wants, and that is a clean up-or-down-vote on this bill. I have real concerns with how that bill is written, and I will give several examples of why it bothers me a bit the way it is written and passing as a clean bill. But I am willing to do that if I can take into consideration the moral concerns and scientific concerns of others in this body and give them the same opportunity that the Senator from Iowa is asking for, and, thus, put together a group, a defined group, but not an unlimited group--we will be voting up or down on all sorts of votes--but see where everybody is on alternative ways: You do not have to destroy embryos to get the same cells you get from embryos, the cord blood bill, H.R. 810, and the cloning bill. It is a separate issue but involves the creation of embryos and ultimately the destruction of embryos.

That is what we are talking about. That is my attempt. It is going to take a while on the floor of the Senate because of the fact of it not having gone through the committee process and the fact everybody does stand in little different positions, from an ethical standpoint, on any of the bills.

On H.R. 810, the consent process is inadequate, from my standpoint. There is not an ideal ethical construct. It says informed consent, but it does not specifically talk about the potential for financial incentives between, say, a physician and an in vitro fertilization clinic. That is not addressed specifically in the bill. Instead of voting up or down, I would like to at least discuss those issues.

Another issue--there is informed consent and the financial incentives--would be if we pass it, it is passed forever; there is no opportunity to come back and look at it on a periodic basis, say, every 4 or 5 years.

I mention those concerns because I am willing to step back and give a clean vote on that if we can take into consideration other people's issues or their particular bills. I am a little surprised my colleagues have not taken me up on that opportunity, but since they have not, we will have to come back and figure the best way to address it when we get back after the recess.

"Stem Cells" in Portugal; an Urban Legend?

Various news outlets are often found reporting on people with spinal cord injuries going to Lisbon, Portugal for what the outlets usually (mistakenly) refer to as an "adult stem cell" treatment. As of early May, 52 people have traveled to Portugal to have this surgery, with anecdotal reports of mixed amounts of recovery. (Primarily sensory, with modest one-to-two functional levels of return at best; not average or minimal levels of return, but maximum.)

What do we really know about the treatment?

We know that Dr. Lima extracts the nasal mucosa which (when unpurified) contains olfactory ensheathing cells, mucosal glands, cilia, fibroblasts, and a number of other cell types. Dr. Lima then cuts out a part of the spinal cord to remove scar tissue (which may also contain surviving axons) and transplants the extracted nasal mucosa across the site of injury.

Why is he transplanting the nasal mucosa?

The nasal mucosa is a component of the olfactory system, which is a part of the central nervous system known to perpetually regenerate itself throughout our lifetimes. The belief is that cells of the nasal mucosa produce growth factors that will allow nerves in the spinal cord to overcome native inhibitory signals and regenerate.

Are there really stem cells in there?

A recent study from Brisbane, Australia reports that there are.

Are the stem cells responsible for the reported recovery?

This is the tricky question, which requires a small amount of background knowledge before answering.

Nerve cells transmit information through the spinal cord by electrical impulses called action potentials. Nerve cells are insulated by a fatty substance known as myelin that allows action potentials to travel long distances.

Spinal cord injuries that do not sever the spinal cord usually cause cells around the site of injury (that survive the injury) to lose their myelin insulation. As unmyelinated cells cannot pass on action potentials, simply restoring the myelin in a sufficient number of cells can result in functional recovery.

With that as background, the primary function of olfactory ensheathing cells in the nasal mucosa (and elsewhere) is to myelinate cells. Therefore, the recovery noted in those who received such transplants may be due to the olfactory ensheathing cells, and not any stem cells that may survive the transplant.

So, are the stem cells responsible for the recovery? Yes or No?

Without further information, it is impossible to know. The recovery may be the result of the stem cells, the olfactory ensheathing cells, a combination of the two, or something else entirely such as the removal of the scar tissue or the intensive rehabilitation after the surgery.

Is anyone currently working to find out what causes this recovery?

Yes.

The Australian team mentioned earlier began a human clinical trial earlier this year to determine whether the recovery is due to the olfactory ensheathing cells.

Would embryonic stem cells work better?

No.

A direct embryonic stem cell transplantation would likely show a lower, or a comparable, degree of recovery. Such a transplantation would have a risk of forming a tumor in the spinal cord, which wouldn't be pretty.

Any future therapy involving embryonic stem cells will require that they be grown into specific cell types prior to transplantation. Geron is working on a treatment based on these principles and are hoping to initiate a clinical trial in 2006.

Is the "Adult stem cells cure paralysis" claim an Urban Legend?

Yes.

While the reported benefits are helpful, they are by no means a cure for all the issues involved with paralysis. As mentioned above, the stem cells may not even be responsible for the limited recoveries that have occurred.

Stem Cell 'Alternatives' Raise the Debate

(An excellent editorial appeared at Wired News today that discusses this in more depth. I will try to avoid duplicating too many points.)

Noted Professors Paul Berg, George Q. Daley, and Lawrence S.B. Goldstein penned an Opinion piece for the Washington Post entitled Stem Cell 'Alternatives' Fog the Debate, in which they argue that the Senate is facing a decision pitting themselves against the will of the House and delaying "vital medical research." Unfortunately, the basis of their argument is a bit misplaced, as the bill they are supporting (H.R. 810/S. 471) has effectively been declared dead-on-arrival by President Bush. Without a veto-proof margin in both the House of Representatives and the Senate, any Senate action on the bill will be largely symbolic and ineffective.

Berg, et. al continue on to discuss the 'Alternatives' Bill (H.R. 3144) proposed by Rep. Roscoe Bartlett (R - MD) and its efforts to divert support away from H.R. 810 "by promoting dubious approaches to obtaining stem cells that even their supporters concede are scientifically and ethically problematic." While three of the four suggested approaches are ethically dubious, the fourth approach (somatic cell reprogramming, a.k.a. transdifferentiation, of which dedifferentiation is a specific type) presents no ethical concerns, provided you outlaw the creation of an embryo through its use.

The trio then say "Research on these proposed alternatives is already legal and can be funded by existing mechanisms. ... Interested scientists need only write a grant proposal and pass the scientific peer review process for technical merit to secure funding for the research." While this is true, this argument against the need for H.R. 3144 is—to borrow a term—dubious, as bills have long been used to allocate funding for and attract scientists to emerging areas of research.

Professors, Researchers, Scientists, and Advocates who support H.R. 810 should not be afraid of also supporting H.R. 3144. The debate over when life begins (embryonic stem cell opponents oppose the research because they believe an embryo is a life; proponents don't) is an ideological one that has long divided the country, and it will not stop because of stem cell research. H.R. 3144 offers a chance to remove ideology from the debate and satisfy both sides.

If Roe vs. Wade participants were given the opportunity to remove ideology, they would have taken it. We are being given that opportunity with H.R. 3144 and we should take it, not waste it.