TGIF: Recommended Science & Medicine Weekend Reads

Happy The Elephant

Happy The Elephant. Image JULIE LARSEN MAHER / WILDLIFE CONSERVATION SOCIETY

With these recommendations I’m aiming for a diverse range of content and perspectives, some of which I may not agree with, but all of which are interesting.

Prostate Organoid from Stem Cells. More organoid news.

Why Do Glowing Sharks Glow? A cool piece from Ed Yong.

Damn. Inquiry into duplications reveals “multiple” image problems in tumor study in Cell Stem Cell.

Comment on Proposed Framework for NIH-Wide Strategic Plan from NIGMS’ Dr. Jon Lorsch

BioPolitical Times (CG&S). The Facts Behind #CRISPRfacts and the Hype Behind CRISPR

Stanford now offering an on-line stem cell course. Check it out.

Regulation of unproven stem cell therapies – medicinal product or medical procedure? from MacGregor, Petersen, and Munsie.

NYT journalist: I am not a neutral observer–can I still be a fair reporter? The Loneliest Elephant, by Tracy Tullis on Happy the Elephant (image above).

Applicant fantasizes about visiting the study section meeting during discussion of his grant application. DrugMonkey Blog Humor.

Judge dismisses cardiac stem cell researchers’ lawsuit against Harvard Anvsera suit.

Fantastic organoid voyage: views from inside a mini-organ

Fantastic VoyageDid you ever see the classic sci-fi movie, Fantastic Voyage?

In it, the heroes travel inside of the human body in a craft, observing all kinds of awesome biology in an up close and personal kind of way on route into the brain with the goal to do microsurgery of a sorts.

Even though this movie came out a year before I was born, I saw it later as a kid and found it captivating.

“What if we could travel inside the body or even inside organs?” I thought back then. It seemed like we could learn amazing things first hand.

A new technology called organoids or mini-organs kind of makes this possible today.

In fact, organoids are extra exciting because this technology allows us to make miniature version of organs and then do science on them. The organoids can be differentiated and grown, depending on the type you want to make, from pluripotent or adult stem cells or other sources of tissue.

Even though we cannot literally climb inside to take a look, we can do the next best thing using histology and advanced microscopy even on “living” organoids. In a great piece of science writing, Cassandra Willyard, talks us through all the various new kinds of human organoids: liver, kidney, brain, pancreas, stomach, lung, breast, and the list goes on including “guts” as per the quote from Hans Clevers at right from Willyard’s article. I love this quote.Hans Clevers

If we could shrink ourselves down and literally climb inside a human organoid, what would we see? What amazing things might we report on from this voyage?

In mini-brains we’d see neurons, synapses, glia, oligodendrocytes, and fiber tracts. We even might be witness to electrical activity in this mini-brain that represents actual rudimentary thought of a kind. Imagine seeing that “in person” from the inside.

Cerebral organoidsIn a mini-kidney or liver organoid, we might see all different kinds of cellular and tissue activities. If we dropped the equivalent of a micro bottle of vodka or tiny firecracker inside as a model of injury, we might see the organs kick into action to repair themselves.

In a breast organoid we might see milk production from the inside or the first signs of breast cancer formation. In a mini-lung, we could possibly see lung cancer germinate too or hike around inside airways such as bronchi, bronchioles, and alveoli. A bio-spelunker.

Exploring inside a heart organoid you could feel what it is like to be inside of something very similar to a beating heart. Would you like the rhythm and beat or feel like there’s a constant earthquake?

Inside the organoids in the lab you don’t have to worry about some nasty immune cell trying to knock you off either.

Some of the labs focusing on organoid research have discovered important things about normal human development and disease from this work. The Madeline_Lancasterresearchers include teams from the labs of Drs. Hans Clevers, Jürgen Knoblich, Melissa Little, Takanori Takebe, and a growing number of others. The late Yoshiki Sasai did pioneering work in this area as well.

The postdocs and other trainees in these labs have done work that has changed our visions of what is possible in stem and developmental biology in a dish. For instance, Dr. Madeline Lancaster’s work on mini-brains has opened a lot of minds to all that is possible in brain neuroscience in a dish (see images above of a mini-brain and of Dr. Lancaster at right).

An organoid is not just a model system either, but also might have therapeutic potential. Tissues grown in 3-D that take on the form and function of real human organs even if in miniature form could form the basis of innovative therapies in the future as well.

I would say that so far in 2015 organoids are the most exciting development and some have argued they are most important new thing in the stem cell and developmental biology fields.

For past posts on this blog highlighting organoids you can read here.

Nita Farahany Interview on Human Germline Modification: Defining A Road Forward

Nita FarahanyThe topic of heritable human genetic modification has been heating up recently. Prominent scientists, ethicists, and legal scholars have being weighing in, and there is a range of attitudes. Some favor a complete, moratorium including even lab work, while on the other end of the spectrum there are those who have a more liberal perspective. Many of us fall in the middle somewhere.

I have been interested in having conversations with people with diverse views and posting them on this blog. You can see past interviews with Jennifer Doudna here and George Church here.

Duke Professor Nita Farahany, J.D., Ph.D has been one of the more prominent, public proponents of some forms of human germline modification. She has been in a number of debates arguing on the “pro-human modification side”, including just to cite one debate this one where she argued against prohibitions on genetically modified babies. I also recommend watching the video below where she debated Marcy Darnovsky of CG&S  and advocated for allowing human genetic modification. The way the debate framed it was, “Should we design our babies?” and Farahany argued the “yes” side. She has mainly focused on three-person IVF rather than nuclear editing such as by CRISPR-Cas9, but the latter has become increasingly feasible on a technical level and important as an area of discussion.

I reached out to Professor Farahany, who is also a member of the prestigious Presidential Commission for the Study of Bioethical Issues, to have a conversation about human germline modification. I found many of her answers to be intriguing and surprising.

PK: You’ve been characterized in various debates, to put it simply, as being on the side arguing the “pro-designer baby” case. Is that correct? And why?

NF: No. I’m in favor of mitochondrial transfer, but not nuclear gene editing at this time. We haven’t reached a point in the technology where nuclear gene editing could be done with an expectation of safety and efficacy. Still, the bright line between somatic and germline modification – it’s not tenable. Could I be convinced on nuclear modification in the future if there’s more information? Possibly. I’m not opposed to germline modification ever happening.

PK: What has made you more supportive of mitochondrial transfer compared to nuclear gene editing?

NF: The UK has taken the appropriate approach on mitochondrial transfer. They held meetings and hearings. They involved the public. The HFEA provided information. They engaged the Nuffield Bioethics Commission. Their process was thoughtful and considered. They made the right choice at the end of the day. I’d like us (in the U.S.) to follow that lead. We need to reconsider. I’m concerned that the alternative is people facing mitochondrial disorders turning to risky medical tourism.

PK: What specifically makes you feel differently about mitochondrial transfer versus CRISPR of nuclear genes?

NF: CRISPR is newer. And editing of nuclear genes raises greater ethical concerns. That being said, I don’t draw a bright line around it. The difference is where the technology is today. A place I could imagine nuclear gene editing being appropriate is if we know that there is a particular single polymorphism that creates an unhealthy condition and that with CRISPR technology we could replace the unhealthy portion with a healthy portion. We aren’t introducing any new traits in that case. I could imagine that could be a place for gene editing and if we also had adequate safety and efficacy information, I could possibly support that.

PK: Is mitochondrial transfer a form of heritable genetic modification? Some have argued it isn’t.

NF: Yes, it is germline genetic modification. The controversy has had less to do with the technology than to crossing the line to germline modification.

PK: A few months ago the first human embryo editing paper was published. One can fault the specific form of CRISPR methods they used, but they still found numerous problems such as off-target effects and mosaicism. What was your reaction to that paper?

NF: I’m unsurprised about the effects and that’s part of why it is too soon. We need to really understand the technology better. I’m in favor of using it in animal models. Then we could consider human work later based on what is found.

PK: Does the non-viable embryo aspect of that study make it less problematic?

NF: I wouldn’t be doing human embryo work at all today even in vitro in the lab. What would be reason to use human? There hasn’t been adequate democrat deliberation. Making the leap to humans is problematic. At this point we need to focus on animal studies. Even in nonviable human embryos there are ethical concerns.

PK: Let’s say we get to a point where we know CRISPR is safe in humans. Even if it is safe and effective, are there still other ethical issues?

NF: I personally would probably be in favor of it, but my opinion is not the basis of deciding as a whole whether we as a society do it. It’s already happening elsewhere. It’s figuring out how to enable progress.

PK: Some have raised the issue that the future genetically modified children cannot consent to being edited. Is that a valid issue?

NF: We can’t consent future children to be born to begin with. Children also don’t consent to parenting strategies. The idea that children cannot consent to gene editing is a bit of a red herring. It’s less about consent and more about the impact on that child and on the human population more generally.

PK: What about using genetics technology for prediction of offspring traits? I read that you and your husband had used the 23andMe genetic predictive tool for future offspring. What was that experience like?

NF: We thought it was interesting. It was very limited though. They predict traits such as lactose intolerance, eye color, wet earwax, and things like that. We now have a 6-month old daughter and we did compare the 23andMe predictions to what she is really like. If we could have had it be much more predictive we would have liked that. As it was, it was just more a novelty and fun.

PK: Lee Silver’s GenePeeks and other groups are already offering gamete screening kinds of tools in part based on predictive genetics. What’s your reaction?

NF: There are some ethical concerns there, but compared to gene editing it is relatively less problematic. If you are able to select between embryos and find the one that is the healthiest, that is appropriate. It’s about selection for health versus editing.

PK: How about the selection that is already happening of certain kinds of embryos based on genetic information? For example, what’s your view of PGD for embryo sex selection?

NF: I’m not troubled by sex selection in this country. In other countries it can be more problematic. For example, if there’s a one-child policy or gender imbalances in a society, sex selection can be much more of an issue. I think sex selection can be valuable and if, for example, a couple wouldn’t get pregnant with a child of a certain gender, but they will have another child of the other gender with the help of sex selection then that is positive.

PK: What about for PGD for trait selection?

NF: We already do this. We look for embryos without a heart condition or for ones without other conditions such as Tay-Sachs. What you probably mean is trait selection for things like eye color?

PK: Yes, that’s more the kind of trait selection I was meaning.

NF: Am I concerned about it? It’s a little weird. I have a hard time imaging I would care about my future child’s eye color. But if it really matters for someone, then I don’t find it problematic. If there are five embryos that are all healthy and one has brown eyes and the parents wants to choose that one, I don’t see that being a problem.

PK: But what if it goes further to say height, body mass, musculature, facial features, and such?

NF: Even if people do that (e.g. select for certain features), we won’t end up with eugenics. When people are given choices, they tend to choose to have children who look like them but a little better. Do we already have high expectations of our children? I think so.

PK: You mentioned eugenics. Does gene editing raise the risk of eugenics?

NF: We don’t have a pretty history of eugenics. It’s an appropriate concern to have in mind when we start talking about gene editing. Genetics is not so simplistic as we once thought. The ability to have an “effective eugenics” policy is much less likely than previously thought. I don’t think heritable human genetic modification will reawaken genetic determinism. It may reawaken a desire to improve the heath and prospering of future generations. Still we have to make sure it happens in a way that doesn’t create a society that favors determinism.

PK: What about not just selecting for certain traits, but actively using genetic modification for specific trait enhancement? Not just for genetic disease prevention, but for human “enhancement”?

NF: We are nowhere close to that being okay. But if we can show it is safe and efficacious…if we as a society are okay with editing, am I going to be the one to draw the line there? We’ll have to see. It also depends on the type of traits. Consider traits in the existing population versus totally different traits. For instance, if we can correct a person’s vision to 20-20 vision that is positive and different than say giving them UV vision or something else that is entirely outside the range of the normal human population.

PK: Looking to the future, there is slated to be an upcoming NAS meeting on germline human modification. Will that be sufficient to engage the public on this issue?

NF: What does democratic deliberation look like? A NAS meeting doesn’t engage a broad public audience. The NAS meeting will be positive, but more is needed. This issue (germline genetic modification) touches on pro-life, pro-choice, and people have concerns on “designer babies”. There are many issues here. What does society look like when we starting germline editing, traits start being edited, etc.? This justifies the need for a broader public audience.

Scientists and suicide

suicide symbolsWhy do some scientists kill themselves and can such suicides be prevented?

Clearly it can be hard or even impossible to tell from the outside what things may be like on the inside for anybody whether they are a scientist or not.

Last year the world of science, and in particular the stem cell and developmental biology fields, were stunned when noted RIKEN scientist Yoshiki Sasai committed suicide. At least in part that death was linked to the STAP cell fiasco.

More recently the CEO of Cambrian Genomics, Austen Heinz, died of suicide as well some time in the last two months. There are no concrete details on this death and no public indications of a reason for the suicide. An obituary can be read here.

I interviewed Austen and posted the discussion on this blog just a few months back. The focus was on Cambrian and his enthusiasm for human genetic modification. I viewed Austen as a very confident scientist working on cutting edge research who was unafraid to push the boundaries to the extreme. I was surprised and very sad to learn that he had taken his life.

Many scientists over the centuries have committed suicide (see partial list here on Wikipedia).

A 1990 study of scientists who committed suicide (why only male?) concluded that they faced intense stress and for some it was too much leading to the suicide. Coverage of that study in The Scientist noted a few key reasons thought to be linked to scientist suicide:

“The leading contributing factors were: isolation, 50 percent; physical illness, 47 percent; politics as both a precipitating and background factor, 42 percent; and depression (sometimes hereditary), 31 percent. The percentages add up to more than 100 because most suicides had more than one cause.”

Minor contributing factors were defined as the following:

“Minor precipitating factors were: death of a close relative, 17 percent; overwork, 14 percent; business or legal problems, especially common among inventors, 11 percent; grant problems, 8 percent; problems with the administration or boss, 3 percent.”

What do you think are the most important factors?

Of course women scientists commit suicide too and at one point it seemed that women chemists were far more likely than their male colleagues to kill themselves.

Scientists of any gender or age can find themselves in a pressure cooker of stress. Could the perception that a higher proportion of scientists are shy have any role or is scientist shyness a myth? For some if there is a perception of being outside the stodgy norm for almost any reason that stress can be strongly amplified. Some scientists who committed suicide in the past had faced discrimination of various kinds such as for race or sexual orientation. The amazingly gifted 20th century scientist Alan Turing may have committed suicide after being persecuted for a relationship with another man.

Can anything be done to make a positive difference?

There’s not a whole lot of compassion in the community of science for scientists as actual people. I’m not sure if there’s a way to change that. It would be helpful if there were less stigma for scientists who have mental health issues. Science needs more resources available to scientists who may feel in a particularly hopeless situation at a certain time with nowhere to turn.

More research on suicide by scientists is needed as well. Remarkably there are almost no scientific articles on suicide by scientists. For instance, see this PubMed search result, which yielded just 4 articles out of the >23,000 with the title word “suicide”. So we are pretty much in the dark in terms of scientist suicides, trends, causes, and such. It seems to be one of those taboo topics that in reality needs more open and thoughtful discussion.

If you are feeling possibly suicidal, please look for help. For instance, you can contact the National Suicide Hotline in the US at 1 (800) 273-8255, toll-free, 24/7, in both English and Spanish.

Tale of 7 stem cell stock woes: how low can they go?

To get from point A of a stem cell discovery to point B of a patient actually receiving a treatment based on that discovery is a long and non-linear road.

Stem cell biotech companies including publicly traded companies are an integral part of the field making that journey. How those companies fare financially is not just of interest to investors, but also should be on the radar screen of scientists and advocates too.

Lately, stem cell companies have not been doing so well financially to put it mildly and their stock prices have generally been going down, down, and down further. A lower stock price and market capitalization are not just a headache for investors and bad for the companies, but they also strongly interfere with the progress of the clinical science.

Today I’m looking at 7 stem cell biotechs. To be blunt, why are their stocks doing so miserably?

Ocata

Ocata Therapeutics (OCAT, formerly ACTC) is the only biotech discussed in this post in which I hold a financial stake and it is a small stake…growing smaller by day as the stock spirals down. If you look at the chart you can see what a terrible 6-months it has been for OCAT.

BioTime (BTX) is another stem cell biotech company often discussed on this blog. Like Ocata, I’m a fan of the science in this company and the scientific leadership. The stock has been seriously roughed up in the last three months after a good period prior to that.

The stock price of StemCells, Inc (STEM) has really been struggling since March, when it took a nose dive and then another precipitous drop in late June.

Caladrius (CLBS), which was formerly NeoStem, is basically at its 52-week low.

Athersys (ATHX) stock dropped off a cliff in April of this year (down more than 50%) and has not recovered at all.

Cytori (CYTX) stock is at a fraction of the price it was a year ago.

Neuralstem (CUR) stock cratered in March and remains way down.

One exception (and I’m sure there are others) I found is Osiris (OSIR), which has had a good run of late.

NASDAQ Biotech index

The NASDAQ Biotech Index (above) has done great in the past year so this trend in stem cell stocks is definitely going against the overall biotech trend.

Stem cell biotechs constitute a volatile area for sure, but in some cases the companies have reported encouraging results and progress. Good news seems to be accompanied by no positive change in the stock price.

If this trend continues at some point are some of these companies going to fold?

Overall, why all the stem cell biotech stock woes of late?

Disclaimer: this post is not financial advice.