Best case in favor of germline human genetic modification?

Human genetic modification

Flying out of Portland Airport yesterday, I saw these magazines side by side.

Hmmm.

That’s a humorous juxtaposition and the two covers are oddly similar in design.

It go me thinking…

Could using germline human genetic modification be a wise thing to do in some cases?

After all, humanity in many ways has serious flaws. Could we try to make Homo sapiens a better species via, for instance, CRISPR’ing embryos for “better” traits and removing possibly negative traits?

Of course attempts at making “better” people could yield worse results than already naturally occur.

So have I been wrong about supporting a moratorium against heritable human modification?

I don’t think so.

Still, this peculiar pairing of magazine covers made me laugh and think.

Stem cells “wild ride” in space capsule

stem cells space

Engineers work on capsule. Credit: Terminal Velocity Aerospace

Stem cells took a trip near to space in a test capsule and reportedly returned alive and apparently well.

What was the story with the stem cells being tested in this way for future time in space? Space.com reports:

The RED-4U capsule was created by Terminal Velocity Aerospace (TVA) to return science experiments to Earth and carried a cargo of adult stem cells, which can grow into any cell type. The cells, provided by the Mayo Clinic, are thriving despite a parachute’s deployment issue, the company’s CEO said. The failure’s cause is being investigated, but is not related to the parachute design.

Sound pretty cool despite the parachute glitch, but what comes next is a quote in the piece from the TVA CEO that seems to either be a mistake or hype:

“There is evidence, from prior testing, that they will grow up to 10 times faster in space and have higher purity and other advantages as well.”

Ten times faster? I don’t think a ten-fold increase in adult stem cell growth is probably even possible unless the cells were unusually slow to grow in the first place. For instance, if the stem cells doubled ever two days or 48 hours normally, a ten-fold boost in growth would mean doubling every 4.8 hours. I don’t see how that’s possible given what we know about cell biology and division. Even cancer cells in general do not grow that fast.

More on this project sounds very cool though:

“The Mayo Clinic has a $300,000 grant from the Center for the Advancement of Science in Space (CASIS) to develop techniques for growing stem cells in space, but a flight date has not been announced. CASIS manages the International Space Station U.S. National Laboratory.”

I hope they can get the project into space sooner rather than later and am excited to see what they learn from the experiment. There have been past trips for stem cells into space that were quite interesting and CASIS has had a funding program for this kind of research, which is great.

Did NHK, Japan’s PBS, Violate Human Rights of Obakata (小保方 晴子) over STAP?

Obokata press conference

Obokata late press conference

The Japanese public broadcasting system, NHK, has been accused by scientist Haruko Obokata of violating her human rights.

Obokata was the primary researcher involved in the STAP cell fiasco in which two ultimately retracted Nature papers contained duplicated, plagiarized, and manipulated data. She was certainly not the only researcher on those papers, but overall she has been accused of having the most central role in the STAP problems. Obokata left RIKEN late in 2014.

During the height of the STAP cell mess the Japanese media hounded Obokata and other STAP cell authors including Yoshiki Sasai, who ultimately committed suicide. From accounts in Japan, the STAP cell story was on the equivalent of the nightly news and on the front of national newspapers and tabloids almost every day for a time.

For instance, NHK was incredibly persistent with pursing Obokata and now Obokata has said that they violated her human rights in a complaint to the Japanese Broadcasting Ethics & Program Improvement Organization or BPO. Obokata asserts that NHK violated her rights in numerous ways including accusing her of stealing embryonic stem cells and she sustained injuries while being pursued by NHK. BPO will be investigating these and other assertions by Obokata against NHK.

During the STAP cell mess last year, it seems because I was covering the STAP cell claims and science here on this blog, many members of the Japanese media emailed and called me. I can understand that they were looking for information and perspectives, but it went out of control in certain cases. Some, including reporters saying they were from NHK, were very aggressive with me. They some persistently called me at work and even at home in the middle of the night.

I had decided to not talk with them because of their aggressiveness and their tendency to focus on negative, personal stories rather than the science and facts, but they wouldn’t take “no” for an answer. Several pursued me for comment at conferences too. I don’t have direct knowledge of what happened with Obokata and NHK, but my sense is that the media went way out of bounds on STAP and made it personal.

New Paper on IPS Cell Immunogenicity, Clinical Insights, & Possible Solutions

打印Can cells produced from autologous induced pluripotent stem cells (IPSC or IPS cells) sometimes be immunogenic in patients?

This key question has remained somewhat unsettled due to varied findings over the years (e.g. see here), but many of us had generally felt in the last couple years that immunogenicity in an autologous context wouldn’t be a major problem.

This is a big deal because if human IPSC (hIPSC) and in particular their derivatives are immunogenic (sparking a major immune response once transplanted that destroys them) even in an autologous setting that could necessitate the use of immunosuppression with their clinical use. In turn this would substantially reduce their potential advantage over human embryonic stem cells (hESC) for various clinical applications. Immunosuppressive therapy can be expensive and has its own potential side effects too for patients.

A new, very important Cell Stem Cell paper from a team led by Professor Yang Xu sheds significant new light on this key issue, but interestingly leaves the question answered so far at least as both “yes” and “no”. In short, autologous hIPSC derivative immunogenicity is present in some instances and not in others. The researchers used an innovative humanized mouse (Hu-mice) immunological model system. You can see a summary in image form from the paper above. They found that hIPSC derivative immunogenicity depends on the type of differentiated cell that is produced and the specific, associated antigens.

For instance, while hIPSC-derived retinal pigmented epithelial cells (RPE) were not significantly immunogenic in this system, smooth muscle cells (SMC) make from hIPSC did spark a substantial immune response. The rejection of the hIPSC-derived SMC was thought to be due to misexpression of immunogenic peptides that sparked a T cell response. The immunogenic factors are not normally expressed in SMC suggesting that tweaking hIPSC production protocols could be helpful here as the authors indicate:

“While SMCs differentiated from hiPSCs exhibit functionalities and global gene expression profiles highly similar to those of normal human counterparts, the finding that the immunogenic antigens expressed in hiPSC-derived SMCs are not expressed by normal human SMCs suggests that further improvement of the robustness of the differentiation process of hiPSCs could help to reduce the immunogenicity of hiPSC-derived cells.”

Therefore, how IPSC are made will impact their immunogenicity.

The data in this paper on RPE is encouraging, but the observations with SMC raise broader awareness that hIPSC derivatives cannot simply be assumed to be non-immunogenic in an autologous setting. What about liver, kidney or neural derivatives of hIPSC? Lung, heart?

It is also possible, since everybody’s immune system is different, that immunogenicity of any given hIPSC-derivative will vary depending on the patient.  If the immunogenicity of every patient’s hIPSC-derived cells ideally would be tested prior to transplantation, how would we do that? We’d need some kind of robust, high-throughput system like the teratoma and gene expression assays that are now used to screen human pluripotent stem cells for potency. Could the Hu-mice be used for this? The Hu-mice used here are indeed an elegant system, but how things play out in actual human patients with their own immune system could be different. Still they or some adaptation of that technology could prove very effective as an initial screening system.

Overall the findings of this new paper along with the recent news of the halt on the hIPSC trial for macular degeneration, together are signs of a more complicated road ahead to the beside for IPSC. They are not insurmountable hurdles, but rather indications of the IPSC field maturing to have a clearer understanding of the challenges facing it. This is a good thing, even if a bit bitter sweet, because it means we can find solutions and move forward.