[An original, shorter version of this post first appeared at Lifenews.com!]
Turning a blind eye toward both good science and good ethics, the embryonic stem cell and cloning company, Advanced Cell Technology (ACT), has published a very preliminary online report regarding their first two patients injected with embryonic stem cell derivatives. The two patients, one who has age-related macular degeneration, the most common cause of blindness, and the other with a rare form of blindness called Stargardt's disease, were injected with retinal cells made from human embryonic stem cells only 4 months before the report was submitted. This makes it far too early to know whether these embryonic stem cells will actually be safe or effective. In fact, it's surprising that any reputable scientific journal would publish such very preliminary data, given the early stage of the clinical trial (which is supposed to last at least two years), the short period of time after the patients were injected, and the low numbers of patients and lack of controls.
Dr Martin Friedlander, Professor of Ophthalmology at Scripps Health in La Jolla, California pointed out the deficits and dangers of such early and incomplete reporting:
To reach any conclusions on the safety or efficacy of two patients treated for four months without a control population for comparison is unreasonable. This is why anecdotal reports like this are not published. This falsely raises the hopes of millions of individuals suffering from these diseases.
The paper published in the journal Lancet clearly reveals that the data are preliminary and uncertain. It mentions that one patient who showed improvement in her eye that was injected with the cells, also showed improvement in her eye that was NOT injected with the cells. The authors admit in the paper that there is a general lack of hard data:
"At present, we do not know if the transplanted cells have reduced immunogenicity or whether they will undergo rejection without immunosuppression in the long term. Similarly, we are uncertain at this point whether any of the visual gains we have recorded were due to the transplanted cells, the use of immunosuppressive drugs, or a placebo effect."
First author Dr. Steven Schwartz has noted the likelihood of the placebo effect in several interviews. Dr. Schwartz conceded that it was extremely unusual for researchers to publish a study after treating only two patients out of a planned 24. But he said that was justified by the huge interest in the stem cells. ACT has been criticized in the past for overstating results, in part because it has been desperate to raise money to stay in business. The companys stock rose 3.4 cents, or 23 percent, to 18 cents on Monday.
The safety of the patients is also still very much in question. Humans can take much longer to develop a tumor than lab mice, sometimes years. Previous research has shown that as few as two growing embryonic stem cells among millions of injected cells can lead to tumors, even if the cells are supposedly pre-differentiated. The concern regarding potential tumor formation and need for continued surveillance was noted by Dr. Sheng Ding of the Gladstone Institute:
If just a few undifferentiated stem cells are injected, you may not see [an effect] at all, or you may be able to see it over a much longer period of time. The 4-month follow-up received by the trial patients thus far is very short in this regard, and I think the patients need a much, much longer-term follow up to make sure theres no tumor cells.
It is indeed surprising that this paper was published. The preliminary nature of the paper reinforces the image of ACT noted in a recent story in Nature:
"Since the late 1990s, ACT has gained a reputation as a renegade company, accused of overhyping results to raise attention and money. Critics say that the company has damaged the field more than once with its high-profile, controversial announcements, such as one describing the companys attempts to clone a human embryo in 2001..."
The embryonic stem cells (line MA09, currently pending review for NIH approval of taxpayer funding) used for injections into patients in the current trials are part of another embarrassing moment for ACT. Their derivation was described in a 2006 paper in which ACT claimed that they arose from single blastomeres that had been removed from human embryos, without destroying the embryos. However, the embryos had indeed been destroyed cell by cell, leading to several "corrections" to their published information. In a subsequent 2008 paper they again claimed to have accomplished derivation of embryonic stem cells without destroying an embryo, creating what they termed their NED (no embryo destruction) lines, but their own published data showed only 80-85% of the embryos survived the laboratory manipulation, falsifying their claim.
There are certainly better alternatives to embryonic stem cells. Similar stem cells--iPS cells--can be derived without any use of embryos; their potential is noted in the accompanying published comment. In fact, ACT scientist Bob Lanza has already said that they are planning to use iPS cells in the future, which potentially could remove the need for immunosuppressive drugs and provide an ethically-derived source of cells. However, since iPS cells are pluripotent, with a penchant to grow and make lots of cells, they face the same practical problem of tumor formation as embryonic stem cells.
A practical, as well as ethical solution, would be the use of adult stem cells. Preliminary work has shown that retinal repair could be accomplished using adult stem cells from bone marrow, or possibly even adult stem cells from within the patient's own eye. Adult stem cells from the patient's own eye have already been used successfully to treat corneal blindness in people.