And Oh Yeah, Those Other Guys Won, Too

Thursday, January 17, 2008
In all the hoopla over Al Gore and the IPCC winning the 2007 Nobel Peace Prize, I believe not enough attention was paid to the other winners. Yes, there are other winners, because the sun and moon do not rise and set on Al Gore or the IPCC, despite the media coverage.

The one that excited me the most was the 2007 Nobel Prize in Physiology or Medicine. It was jointly awarded to Mario R. Capecchi, Martin J. Evans and Oliver Smithies for "their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells." From the public information: "This year's Nobel Laureates have discovered how to use embryonic stem cells to create precise and permanent genetic changes in mice. The mice generated in this manner are known as 'knockout mice' because the change can lead to elimination ('knock-out') of a gene function." How cool is that?

And to quote Family Guy, "Why are we not funding this?"

Thanks, Doctors Capecchi, Evans and Smithies, for your diligence in helping us live longer, healthier lives. You guys rule.

17 comments:

Jim Wright said...

Cool.

Jeri said...

Are you sure it isn't "Smart Chicks Dig Hot Men?"

Seriously, very fascinating research. I'm glad that at least on the international front it's respected and rewarded.

Janiece Murphy said...

Jeri, part of being "Hot" is being "Smart."

Get with the program, girl.

John the Scientist said...

Guys, don't go off half-cocked. Mario R. Capecchi and Oliver Smithies are US researchers. Only Sir Martin Evans is English. At least 2/3 of this work was conducted in the USA, and paid for grant monies from the US NIH and / or NSF.

Not only is Capechi American, he works in the heart of Mormon country. Capechi's work was funded by the NIH:

"In 1980, when Capecchi submitted a grant application to the National Institutes of Health that included experiments testing the feasibility of gene targeting in mammalian cells, peer reviewers were skeptical about the probability of success for this part of his proposal and thought that other experiments he planned would be more fruitful. But Capecchi, distinguished professor of human genetics at the School of Medicine, investigator at the Howard Hughes Medical Institute and distinguished professor of biology, had been drawn to molecular biology because of the aura of possibility. He received NIH funding for all of the projects, which enabled him to carry out the mammalian gene targeting experiments, and persevered."

Oliver Smithies is at UNC, and is primarily funded by the NIH, but also has NSF grants. I have to look up his seminal paper with H.S. Kim when I get back to the office to see who funded the intial research.

A couple of points. One, this was not human embryonic stem cell research. Two, some of this was not even embryonic stem cells, but adult ones. Neither of those are opposed by the current administration.

I don't agree with the current administration's stance on human ambryonic stem cell research, but don't confuse this result with that issue. The US leads the wya in knockout mouse research. Your tax dollars do fund this.

Janiece Murphy said...

John, as usual, I appreciate your expertise in these matters, since it's apparent that of the regular commenters around here, you're the best qualified to comment on this issue.

I was aware that some stem cell research had been funded by the NIH and the NSF, and I thought the post (and the links) were pretty clear about this being research about mice and not humans.

I can't speak for Jeri, of course, but I think her comment meant that the recognition was given by an international entity, rather than a domestic one. At least that's the way I read it.

And regardless of the winners' national origin and where the money came from, I still stand by my original comment - this is cool, and these guys rule.

I just couldn't resist the Family Guy reference, 'cause, you know, satire is always appropriate. Hehe.

Jim Wright said...

John, what's your take on the pig heart scaffold reanimation/ reconstruction from stem cell manipulation (Don't have a link handy, but it was all over the news last week). I thought that was pretty incredible - I had no idea the field had advanced so far. My understanding was that the stem cells were derived from adult animals and not from embryos. And the news claimed that the researchers were within a stone's throw of doing it with human tissue (of course, that was the news' spin, I'd be surprised if that was an actual quote from the researchers themselves).

Janiece Murphy said...

John, what Jim asked. You're the only person I "know" who can really give us an informed opinion.

Or if you've blogged about it, please provide the link.

John the Scientist said...

Y'all mean this, right?

It's a significant Proof of Concept. I wouldnt call it Nobel worthy, but it's pretty important. If you have access to a University library, you can check this 2005 article out to see what's been done. Indeed, heart valves had already been made this way, as well as organs such as kidneys and pancreases in animals, so to answer Jim's question, this is a little more complex, but yes the technology had evolved to nearly this point by 2004 or so.

The heart is a bit more complex, because a pancreas is little more than a chemical factory, and a kidney is little more than a filter - there are no moving parts in those organs. The exciting thing about making a heart is that it's got moving parts, and those parts have to move in a certain sequence. What most impresses me is that those cells on the scaffold can beat in the right sequence and generate a blood pressure.

Note that although Taylor used neonatal rat heart cells, the human therapy would use adult stem cells from the patient themselves to prevent tissue rejection (investigational stem cell therapies in MS and Parkinsons often degrade when immunosuppressive drug regimens are stopped).

I only know of a couple of trials going on right now using embryonic stem cells, but researchers in Parkinson's have been using fetal tissue for a while. They find that the implanted tissue works as long as you keep the patients on the same drugs you use to prevent rejection of kidney and liver transplants, but once you stop those drugs, the cells quit working. This is where I find some of the hysteria about Bush's stance on stem cell research to be a bit specious, at least the "oh my God, we're going to miss a cure for ____". I find it highly unlikely that fetal stem cell transplants are not going to have the same problems as an organ transplant, at least in the near future. Adult stem cell transplants taken from the patient's own stem cells and cultured, are going to probably be the near term wonder therapies (and remember that near term to a medical researcher is a decade or two).

What I don't like about Bush's stance on stem cell research is that it slows down our use of those cells in basic research. We can learn a lot from growing fetal cells in a petri dish and watching how those cells differ from adult ones. That's the real impact of the NIH ban.

That being said, there are ways and ways of paying for research. Now, I'm not advising anyone might do this but, let's just say that a grad student wanted to mess about with something that wasn't covered in a grant.

First of all you need equipment. But that equipment was already purchased by the lab on other grants. Once in the lab, it can be used by anyone for any research conducted in the lab, the NIH never told my boss “only use that laser to study those proteins you said you were looking at for us”. Once we finished that grant we used the laser to look at all kinds of stuff for the NIH, DoD, NSF, etc.

Next, salaries. A grad student works 60 – 90 hours per week on all kinds of stuff. I was paid out of all kinds of grants, but no one tracked my time. No worries there. My advisor usually had 4 – 5 grants open at any single instant, and I was working on at least 2 at any given time, but I’d help out on others. I’m a co-author on one of my wife’s papers (and she on one of mine), and we sure as hell didn’t work off of the same grants (she was an NIH laser jock, I was a DoD materials guy, and I rarely touched lasers, and she never did any polymer chem).

Finally, supplies, such as reagents – often common to everyone in a lab, working on whatever grants were there. What’s left? The purchase of the embryonic stem cells themselves – the one thing you can’t fudge on an NIH grant. That’s all the private investors, philanthropists, or state governments really have to pay for, because the infrastructure, equipment and people are already there in the Universities.

So the people yelping about how much a study costs – they have no clue about how real researchers rob Peter to pay Paul as one grant finishes and the renewal grant hasn’t started yet – that’s why you have multiple grants running. That same mechanism will allow US researchers to work on human embryonic stem cells.

Now, as to the question, should they have resort to these kind of tactics? Hell no. I’m not in favor of creating and killing embryos just to harvest stem cells, but embryos that are going to be deep-sixed by fertility clinics anyway? What a waste NOT to use them.

John the Scientist said...

Wow, that was a long comment. Sorry for chewing up oyur bandwidth. On a lighter note, did I tell you that I once had dinner with this year's Chemistry Prize recipient.

John the Scientist said...

Oh yes, you can also create a human / mouse hybrid by planting a humna gene in a mouse (let's say you want to study a drug that hits a protein that humans make but mice don't). Those are called "knock-in" mice.

Janiece Murphy said...

John, thanks very much for the synopsis. Because I'm a technologist and not a scientist, I'm sure the papers you reference would just induce me to drool all over my ignorance, but it's nice to have someone who can translate it for me without giving me a case of the snoozies.

And I believe John Scalzi already did that "knock in" thing in The Android's Dream.

Fact is stranger than fiction!

Jeri said...

Janiece, you were being charitable, but mostly, my comment was fairly ignorant in light of John's comments. :) And that's ok, because learning is good!

John, thank you for the really great explanations, they help provide context a lot more effectively than media sensationalism.

John the Scientist said...

Yeah, the sheep mother in Android's Dream was a knock-in. As of now, we can only knock-in a few genes at a time, so fetting a human organ in a sheep is way beyond our capabilites right now. Knocking in a whole organ whould cause all sorts of downstream consequences in the immune system, just like putting someone else's kidney does in a human-to-human transplant. The immune system of a sheep would recognize human uterine tissue as foreign even faster htan it owuld recognize a uterus that has been transplanted from another sheep.

John the Scientist said...

I'm curious - has anyone here ever met a Nobel Winner? It's pretty common for scientists to have met one or more.

I'd like to see them get out to the lay public more, though.

Janiece Murphy said...

I haven't, but as previously noted, I'm a technologist, not a scientist.

I donate money to Doctors Witout Borders...does that count?

No?

::Slinks off::

John the Scientist said...

I just think that since the space program is such a shmables, these guys ought to be the public face of US science and get out there a bit more.

Janiece Murphy said...

John, I tend to agree. I'm so sick of people like Britney getting all the press, when we should be talking about people like Drs. Capecchi, Evans, Smithies and Haile.

These are the people that are pushing the limits of human understanding, and deserve our respect and support.

::climbs down from soap-box::