retrovirally transforming pancreatic cells from adult mice into insulin-producing beta cells
August 27, 2008 7:51 PM   Subscribe

Scientists Repurpose Adult Cells - "Scientists have transformed one type of fully developed adult cell directly into another inside a living animal, a startling advance that could lead to cures for a variety of illnesses and sidestep the political and ethical quagmires associated with embryonic stem cell research." [nature abstract, nature writeup, audio announcement]
posted by kliuless (21 comments total) 5 users marked this as a favorite
It is about time. I was really getting tired of religious issues getting in the way of medical progress in this area. If it wasn't for religion we would be able to regrow limbs by now.
posted by Mr_Zero at 8:17 PM on August 27, 2008 [1 favorite]

It is about time.

Well not yet. This will takes many years before it becomes viable, if at all, there are lots of ways it could be a dead end as a treatment.
posted by stbalbach at 8:41 PM on August 27, 2008

This kind of news will be used by the Right another reason to oppose stem cell research. This is good news for the Right, not for the sick people who need help now.
posted by null terminated at 8:51 PM on August 27, 2008 [2 favorites]

If it wasn't for religion we would be able to regrow limbs by now.

Or women from our ribs. That'd be cool.
posted by weapons-grade pandemonium at 9:09 PM on August 27, 2008 [6 favorites]

I was really getting tired of religious issues getting in the way of medical progress in this area

Do you honestly think the wackjobs can't come up with some psychotic explanation of why this is against God's will but penicillin and nosejobs are fine?
posted by dirtynumbangelboy at 9:30 PM on August 27, 2008

"I see no moral problem in this basic technique," said Richard Doerflinger of the U.S. Conference of Catholic Bishops, a leading opponent of embryonic stems cell research. "This is a 'win-win' situation for medicine and ethics."

If the Catholic Church, (at least in the US) won't object because no embryos are destroyed, maybe "the wackjobs" won't try to head off any Federally funded work in this new area.

Of course the annoncement comes with the seemingly mandatory caution for medical breakthroughs that human trials are five years away.
posted by longsleeves at 9:59 PM on August 27, 2008

There's no ethical quagmire related to embryonic stem cell research. There's certainly a political and religious one, though.

But hey, if this works, I guess that's good news. Just as long as normal embryonic stem cell research and treatments aren't delayed until this works.
posted by Joakim Ziegler at 10:21 PM on August 27, 2008

There's certainly a political and religious one, though.

No.. there's only a religious quagmire, which is forced to be political because people don't understand that they have to keep their Gods out of our government.
posted by dirtynumbangelboy at 10:27 PM on August 27, 2008 [2 favorites]

How many concurrent discussions of strident atheists and their overstated cases do we need? Can't you guys get a room? Or do this in the electionfilter threads instead?

Anybody want to discuss the post? It strikes me that there is (a) little control over which cells get converted and (b) they're not the best beta cells to have if they don't respond to glucose. It seems that clinical trials would be a long long way off. What possibilities are there for a more targeted delivery system? Retroviruses and gene therapy always sounded like a recipe for cancer to me.
posted by nowonmai at 11:03 PM on August 27, 2008 [1 favorite]

Retroviruses and gene therapy always sounded like a recipe for cancer to me.

For in vitro transduction, I hold the same cynical view. For in vivo delivery, such as was used in this paper, I see widespread immune activation and systemic organ failure.
posted by kisch mokusch at 11:23 PM on August 27, 2008

So it's win-win, really?

I get really worried when we start fiddling with viruses and genes. I know we know a lot. But we also thought we knew a lot about a great many things.
posted by dirtynumbangelboy at 11:38 PM on August 27, 2008 [1 favorite]

So, it's been thirteen years since I graduated with a degree in Genetics, and eight years since the Human Genome Project. Why aren't we just running the DNA through a protein model builder?

OK, so that's far too difficult: can't model what the results of the protein are, transcription factors, RNA changes and post transcription. But are we really still just chucking things in there and seeing what we can do? (That sounds like I'm denigrating this particular achievement: I must stress that "chucking things in there" is great science.)

Scientific progress is so fast at a distance (flight to moon in sixty years!) and so very slow at close up (where's my anti-aging drug? I'm 34 now!) More money for science!
posted by alasdair at 12:10 AM on August 28, 2008 [1 favorite]

To the OP: thanks for the article! Wonderful stuff. Truly great... I love seeing the boys from Harvard working hard.

To the rest of you:

Another atheism fight on metafilter... must be Thursday.

You should really read some of the other ones before you (badly) re-hash stuff that we just went through yesterday.
posted by chuckdarwin at 1:26 AM on August 28, 2008

I think that anyone who believes in an imaginary being, no matter what its name is, should be labeled mentally ill.

It's hardly radical to state what a left-wing, anti-religious place MeFi is - it's actually the reason I stopped coming here. But, I guess the only thing that believers like myself can do about it is to report - honestly, and without casting judgement on others - how we met God in our own lives. I actually met him in a pub - which will probably surprise some of you faithless, sinful bastards.

It was one of the darkest and most stressful times in my life, when I was searching for meaning and finding none. Like many of the hopeless, I'd turned to alcohol as a crutch - but the addiction only robbed me of my friends, the love of my family, and, ultimately, my self respect. And then, one day, I saw God!

He was sitting in the local boozer, reading a newspaper, just quietly glowing with infinite golden power. He was 9 foot tall and totally naked, and he had a Donkey's head so I guess he musta been an Egyptian God. Of course, we still don't know whether there is one God or many - it's cause God-language has no word for "a" or "the," much like Japanese. Actually it's pretty fucking imprecise all round is God-talk - people are always, "Ooh ooh the language what's spake in Heav'n's vaults! Must be all bitchin' and shit!" But Gods are omniscient, all-subtle and maximally puissant, so they can afford to be vague.

Anyway, there God was, ass-naked at both ends, and he had a HUGE cock that lay on the table in front of him, and it had two eyes and a little mouth and was sucking a vodka mule through a straw.

I'm a renowned Egyptologist because I read some Erich von Däniken, so I thought I'd say hello. "Hail, Hee-Haw, great Donkey-headed God of Egypt, whose piss succours the Blue and White Niles, fecund mother of the delta that gives life to all beings!" I said.

"I acknowledge thee, petitioner," he replied, and Lo! It was thus, for I found in my hand a petition signed by all rational beings to recommission The A-Team for prime time TV, with Owen Wilson playing the role of "Face Man". Thus I presented it to him, and he thanked me and gave it unto a divine assistant for numinous filing, and promised that he would give it due consideration.

Of course, I realised that this was also the chance I'd been waiting for throughout my down-spiral of depression, so I asked him: "Great Lord, what is the meaning of existence, and how can mortals live just and happy lives for their brief time, which flees from their grasp like sand through the fingers of an open hand?"

"I pity the fool who does not know the answer," spake he - and then he told me.

And now? Well, I travel the internet, lonely as a prophet, going from website to website to spread the good news. I'm off to Little Green Footballs now to tell the same story, word-for-word, except I'll swap every noun for the one two places along, and the only verb I'll use is "to ovulate". So long!
posted by the quidnunc kid at 1:57 AM on August 28, 2008 [6 favorites]

Model? Bah, we need to just do the experiments. With 1400 transcription factors, assuming 50% are not involved in differentiation, 700 remain. Assuming transfecting 3 factors can lead to a discernable phenotype, that leaves about 57 million combinations to choose from. Existing tissue surveys can further narrow the possible pools by eliminating combinations that never occur naturally, and better molecular dissection of early embryonic development transcription factors (still requiring early stage embryos) would point to the major players. Stembase seems to be doing some of the analysis portion. A major screening transfection effort using all the TFs (already cloned, available from a human gene expression vector vendor) would get most of the simple tissue transformations for a couple million bucks. I'm sure this is being done now.
posted by benzenedream at 2:03 AM on August 28, 2008

We've had a lot of these gene therapy-based-scientific-breakthrough-posts of late, and a lot of media hype in general these last 10 years about gene therapy, so I want to take the opportunity to mention a few reasonably sized obstacles that are keeping promising mouse studies such as this one from the clinic.

Firstly, gene therapists eventually have to overcome the immunological challenges associated with retroviral and stem cell-based treatments. If you transplant stem cells from one individual into another, they will be rejected as foreign. That is the major issue with regards to the potential therapeutic use of embryonic stem cells especially, and presents a bigger obstacle than any religious issues, because religious issues can at least conceivably be surmounted (even if it means doing it all in China!), while transplant tolerance has remained little more than a pipe dream for half a century. Admittedly, the "de-differentiation" of skin cells (posted previously) gets past this issue, and will probably be the way of the future. I should note that transplant rejection is not an issue with this particular study.

Currently, we directly target the cells from patients with the aim of correcting a defective gene somehow (or to potentially "re-program" the cells as in this case). This is inevitably achieved using a viral vector to insert a gene into the DNA of target cells. Now most of the time we have no idea where it gets inserted (particularly if it's done in vivo), which is where your cancer risk comes in. Smack the gene right into the middle of p53 or some other oncogene and you have a cell that could very easily become cancerous. If the inserted gene(s) gives that cell a competitive edge (such as in SCID), it further increases that risk.

But here you are presented with a bit of a problem: Because if you don't give the cells a competitive edge there can be a failure of the cells to engraft well enough to affect the desired change. (These cells will also have viral antigens inside them, which potentially makes them a target for immune-mediated destruction, but I don't hear too much discussion regarding this point).

Then there's in vivo delivery: Program the virus to go where it needs to go, inject it into the patient, and let it do its thing. But it's amazingly hard to get virus into the right place by this method (adenoviruses, for example, seem to routinely end up in the liver, regardless of what they're supposed to do). Even if you can get them into the right region (by, say, direct injection into the target organ as was done here), you still have the efficiency hurdle. Enough cells need to be transformed to get an effect. Transduction efficiency is not a small hurdle, especially in vivo (although I've gotta say it's pretty impressive how high they can get it in vitro). The bar is set differently here depending on what needs to be achieved, but the easiest way to increase transduction efficiency is to add more virus. However, if you directly administer a lot of virus to an individual, you will most definitely get the attention of the host immune system. And humans seem to be especially prone to producing cytokine storms (much more so than rodents, as has been abundantly shown by the monoclonal antibody TGN1412), which can be fatal (see the recent NYT article The Biotech Death of Jesse Gelsinger).

And finally, let's have a look at the implied therapy for this paper: Replacing lost beta-cells in diabetes. In Type 1 diabetes, where beta-cell destruction is most apparent, this therapy would be akin to sending freshly minted ferraris into a demolition yard. More specifically: The pathological process that is mediating the destruction of beta-cells would not be prevented by the presence of newly formed beta-cells. They would simply become another (short-lived) target. This holds true for any other autoimmune or chronic inflammatory disease, neurodegenerative disorder, or any other disease in which there is ongoing pathology that we have no idea how to stop.

From a pure scientific perspective, I think this paper is pretty amazing. But the potential therapeutic applications are overstated, as are most of these gene-therapy discoveries. As Ruth Macklin says in the NYT link "Gene therapy is not yet therapy."
posted by kisch mokusch at 4:24 AM on August 28, 2008 [2 favorites]

1. When science and imagi-faith-ion meet on the road, one must yield. Is it a coincidence that America, founded on a freedom of religion principle and thus freed from the chains of a State Religion, is the science leader - not just of the world - but of all times?

2. Those believing in the irrational - are they any different than those committed to asserting the unknowable?

3. What any of us believe as citizens of this nation... is fundamentally the business of all of us as citizens of this nation. We stand together. That is our strength.

4. We have not escaped ethical dilemmas with this step, we have merely advanced to a new plateau of ethical dilemmas. When science allows us to extend life indefinitely, what is a "life sentence" for criminals who never age? When science allows us to repair the human body at any level, when can a person opt out?
posted by ewkpates at 4:37 AM on August 28, 2008

altho the wired link notes that "Another [stem cell] technique, known as de-differentiation, can turn skin cells to stem cells -- but tends to introduce cancer-causing mutations."

also btw "A Challenge to Gene Theory, a Tougher Look at Biotech" :P

posted by kliuless at 6:12 AM on August 28, 2008

Mod note: a few comments removed - take fighty name-calling to email or metatalk and don't crap in a brand new thread pls.
posted by jessamyn (staff) at 6:34 AM on August 28, 2008

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