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Its a shame that National Geographic has become part of a corporate empire that is not always consistent, to put it nicely, with data-based reality. Can NatGeo maintain its credibility and impact, when it is owned by a climate change denier (quoted for example as dissing folks as extreme greenies) who also has other verynon-scientificpriorities?

Theres been an increasing amount of discussion of the technology that could produce GM humans. This dialogue includes the new Hinxton Statement (my take on that here) and George Churchs quoted that Hinxton (which BTW did not call for a moratorium of any kind) was being too cautious nonetheless. Church is quoted:

seems weak on addressing why we should single out genome editing relative to other medicines that are potentially dangerous

Should we push pause, stop, or fast-forward on human genetic modification? asks Lisa Ikemoto.Is there a rewind or edit button too?

The NEJM published a new piece on stem cell clinics run amok and the lack of an effective FDA response. Sounds awfully familiar including the use of Wild West in the title, right? My gripe with these authors is that they didnt give credit where credit is due to those of us on the front lines of this battle and in particular to social media-based efforts to promote evidence-based medicine in the stem cell arena. Still, their message was on target.

Are men more likely to commit large-scale scientific fraud? Check out RetractionWatchs leaderboard.Of course the sheer number of retractions does not take into account the impact of any one or two given retractions that had a disproportionate toxic effect like the STAP pubs. Maybe another calculation to do is the # of citations to a retracted paper.

DrugMonkey talks about perceived scientific backstabbing.

The international stem cell policy and ethics think tank, the Hinxton Group, weighed in yesterday on heritable human genetic modification with a new policy statement.

The Hinxton statement is in many ways in agreement with the Baltimore, et al. Nature paper proposing a prudent path forward for human germline genetic modification, which came out of the Napa Meeting earlier this year.

However, while several of the Napa authors have now thrown their public support behind a clinical pause or moratorium on heritable human modification (e.g. Jennifer Doudnaas well asDavid Baltimore and Paul Berg in a later piece in the WSJ), Hinxton didnt explicitlyaddress either positively or negatively the question of a moratorium.

My initial reading of the Hinxton statement is that I mostly agree with it. In my own proposed ABCD planon human germline modification from earlier this year, however, I included at least a temporary clinical moratorium.

I also would have appreciated a more detailed risk-benefit analysis in the Hinxton statement. For instance, I didnt see a discussion of specific possible risks in their statement. Via myown risk-benefit analysis, I come to the conclusion that on the whole a temporary clinical moratorium has the potential for far more benefit than harm.

What would be the specific, possible benefits of a moratorium?

If the scientific community has united behind a moratorium on clinical use not only will that discourage rogue or potentially ill-advised stabs at clinical use, but also if a few such dangerous efforts proceed anyway (which is fairly likely) and come to public light, these unfortunate events will be placed in the appropriate context of the scientific community having a moratorium in place. Therefore, a moratorium both discourages premature and dangerous clinical use as well as putting potential future human gene editing clinical mishaps into the proper context for the pubic.

Another potential benefit of a moratorium is that it could discourage lawmakers from passing reactionary, overly restrictive legislation that bans both clinical applications and important in vitro research. It would give the politicians and the public the right sense that the scientific community is handling this situation with appropriate caution. If you dont think that a law on human germline modification is likely in the US, consider that conservative lawmakers have already proposed such a law be included as part of the pending appropriations bill and Congress a few months ago held a hearing on germline human modification.

Other benefits of a moratorium include that it would a) demonstrate to the public that the research community is capable of reaching consensus aboutimportant ethical issues and b) increase accountability within the research community. Any rogue researchers or clinicians who would violate the moratorium, even if it were not illegal for them to do so, would at least be subject to the disapproval and possible sanction of their professional peers or institutions. Without a moratorium in place, it is far less likely there would be these kinds of consequences.

What about risks to a clinical moratorium?The primary possible risk of a clinical moratorium is that it could, should human heritable genetic modification someday down the road be viewed as a wise course to pursue directly, impede clinical translation. This warrants discussion, but in my view the risk here is somewhat reduced by the possibility that continuing basic research develops a compelling case that a blanket clinical moratorium might no longer be needed.

The other risk here is that amoratorium on clinical use also might in theory discourage some potentially valuable pre-clinical research as well. In other words, some researchers may adopt the mindset that if they cannot get to their ultimate goal of making clinical impact, why do the preclinical studies? I expect that many researchers would instead go ahead and do the preclinical work with the expectation that a clinical moratorium could be lifted and in fact their own preclinical work might help build a case for moving beyond a moratorium.

I agreestrongly with Hinxton on the need for continuation of basic science on CRISPR and other gene editing technologies limited to the lab. In my view, we should have a nuanced policy though, whereby we support continuation of gene editing research in human cells and even in some cases human embryos in the lab under specific conditions (see again my ABCD plan for details), but in whichwe also put an unambiguous hold onclinical applications at this time.

In the absence of a framework that includes a clinical moratorium, we probably do not have the luxury of a reasonably long time frame (e.g. measured in a few years) for open discussionto sort things out carefully. To be clear, open and diverse discussion is crucial, but we just do not have a whole lot of time to do it as things stand today. Why? In the mean time absent a moratorium, I believe that some will go ahead and do clinical experiments on human germline editing. This would not only put individual research subjects at risk, but also pose dangers in terms of public trust and support to the wider scientific community. In a relatively permissive environment lacking a clinical moratorium, one or two instances of rogue researchers clinically using gene editing in a heritable manner could end up leading to a backlash in which even in vitro gene editing research is stymied.

Stemcentrx scientists working with targeted molecules that can kill some types of lung cancer. MIT Tech Review Image.

A stem cell biotech in the news this week was one thathad mostly flown under the radar previously.

Stemcentrx hasa focus on killing cancer stem cells as a novel approach to treating cancer. Antonio Regalado had a nice articleyesterday on the company. He reports that Stemcentrx has around a half a billion in funding. It is valued in the billions. These are very unusual figures for a stem cell biotech.

Stemcentrx isdeveloping novel cancer therapeutics such as antibodies that target cancer stem cells. Their development pipeline at least in part uses a model of serial xenograft tumor transplantation in mice.Cancer stem cells are also sometimes called tumor initiating cells (TIC). As a cancer stem cell researcher myself, I find Stemcentrx intriguing.

The company published an encouraging bit of preclinical data recently in Science Translational Medicinewith a team of authors including leading company scientist, Scott Dylla. In this paper the team presented evidence that they have a product in the form of a loaded antibody (conjugated to a toxin) against a molecule called DLL3 important to TIC biological function and survival. DLL3 is part of the Notch signaling pathway. Stay tuned tomorrow for my interview with Dr. Dylla.

They showed that this anti-DLL3 antibody,SC16LD6.5, exhibited anti-tumor activities in xenograft models of pulmonary neuroendocrine tumors such as small cell lung cancer. The company also has a clinical trial ongoing but not currently recruiting using this drug, and they have another trial for ovarian cancer based on antibody targeting as well.

SC16LD6.5 also exhibited some degree of toxicity in rats and a non-human primate model so thats a possible issue moving forward, but the toxic effects were at least partially reversible and when youre dealing with a deadly disease some toxicity for treatment is kind of to be expected.

Can Stemcentrx survive and hopefully even thrive as a company selling products that kill cancer stem cells? Well have a clearer picture on this in a few years, but in general biotechs of this type in this arena have a high failure rate. We need to keep in mind the long, sobering path ahead between these kinds of preclinical result and getting an approved drug to patients.

At the same time, this team has the money and talent to potentially succeed, and again, theres that half a billion in funding, which all by itself makes this stem cell biotech noordinary company. Theres another unique thing going on here: famed tech investor Peter Thiel is one of the major funders of the company.

Those of us in the cancer stem cell field have long been engaged in the debate overwhether these special cells exist in specific solid tumors and their functions in tumorigenesis. I believe they are present and important in some, but not all of such tumors. The controversial nature of TICs in lung cancer specifically makes SC16LD6.5 a high-risk, high reward kind ofproduct.

More weapons against lung cancer will be of coursea good thing and targeting cancer stem cells is an innovative approach. The company isrecruiting for many positions including scientists so if you are interested take a look.

I hope Stemcentrx succeeds and I look forward to reading more of their work as the years go by.

The winner of the inaugural Ogawa-Yamanaka Prize is Dr. Masayo Takahashi, MD, PhD.

According to the Gladstone Institutepress release, Dr. Takahashi was awarded the prize for her trailblazing work leading the first clinical trial to use induced pluripotent stem (iPS) cells in humans.

The prize, including a $150,000 cash award, will be given at a ceremony next week at the Gladstone on September 16. If you are interested in listening in, you can register for the webcast here.

Dr. Takahashi started the first ever human clinical study using iPS cells, which is focused on treating of macular degeneration using retinal pigmented epithelial cells derived from human iPS cells.

Congratulations to Dr. Takahashi for the great and well-deserved honor of the Ogawa-Yamanaka Prize.

As readers of this blog likely recall, Dr. Takahashi received our blogsStem Cell Person of the Year Award last year in honor of her pioneering work and that included a $2,000 prize.

Otherpast winners of our Stem Cell Person of the Year Award have gone on to get additional awards too.

The 2013 Stem Cell Person of the Year, Dr. Elena Cattaneo, went on to win the ISSCR Public Service Award in 2014 along with colleagues.

And our 2012 Stem Cell Person of the Year Award winner, stellar patient advocateRoman Reed, went on in 2013 to receive the GPI Stem Cell Inspiration Award.

The more we can recognize the pioneers and outside-the-box thinkers in the stem cell field, the better.

I recently ran a poll on my blog about how the FDA is doing on handling stem cell clinics.

There is substantial debate in the stem cell arena about how the FDA handles stem cell clinics ranging from the view that the agency is far too strict to excessively lenient.

The results of the poll reflect a great deal of dissatisfaction with the job that the FDA is doing on stem cell clinics.

Only 9% of respondents felt that the FDA is currently do things just about right.

While the top 2 answers were polar extremes, by a large margin the top answer was that the FDA was much too lenient.

Although Internet polls of this kind are not scientific, they can reflect sentiments of a community.

Read the original here:
Knoepfler Lab Stem Cell Blog | Building innovative ...

This entry was posted on September 11, 2015 at 8:41 pm and is filed under Cell Medicine. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |