Of Stem Cells and Neanderthals

January 24, 2005 10:33 AM

Come out, experts from the woodworks!Neu5Ac and Neu5Gc are sugars found on cells present in nearly every mammal, from chimps to pigs. When scientists altered the genes of mice so that they couldn't produce them, the mice died. However, unlike our closest relatives, humans lack a gene that makes Neu5Gc. The gene is not gone, but rendered silent by a fatal mutation, one that occured approximately 500,000 ago. Now, note that it is illegal to produce any new embryonic stem cell lines. Any scientist will tell you that extant and legal human stem cell lines have been existing in calf serum and often on layers of mouse "feeder" cells for growth. As such, they are immersed in a bath of antigen and if re-introdcued would elicit a strong immune response. I.e. although of human origin, they would be treated as foreign cells if injected. It is likely they would be rejected if injected with today's techniques anyway, but this may represent another significant hurdle for research, one that could be sidestepped with more progressive policy. (Via The Regular)
posted by willns (32 comments total)

here's another good synopsis...
posted by willns at 10:35 AM on January 24, 2005

Illegal in the US. Much of the rest of the world can still do this research. Call me when you guys hit 50% agreement with evolution. *snicker*.
posted by i_am_joe's_spleen at 10:37 AM on January 24, 2005

Illegal, or just not something that can be done with federal funds?
posted by alms at 10:48 AM on January 24, 2005

Important bit from the link in willn's comment:

"The human embryonic stem cells remained contaminated by Neu5Gc even when grown in special culture conditions with commercially available serum replacements, apparently because these are also derived from animal products,"

Even if the U.S. did allow new stem cell lines to be developed, they would be contaminated with Neu5Gc too, because all currently available culture media contain Neu5Gc.

The solution has to be to develop Neu5Gc-free media, but once you've done that, you can grow existing cell lines in it, which will become Neu5GC-free when grown for a sufficient number of generations.
posted by DevilsAdvocate at 10:53 AM on January 24, 2005

It is not illegal in the US, actually. It just isn't allowed with federal funds. Researchers can and do produce new cell lines in the US. However, having government funding could do a lot to speed up research...
posted by unreason at 10:55 AM on January 24, 2005

Devil's advocate- it should not be difficult to remove the contaminent from animal serum (making human serum is probably out of question). But it's not just media- we use mouse cells to culture the stem cells, knockout "feeder cells" will need to be made. Again though, this should not be too hard. It is however, unclear how quickly the cell lines will need in that environment to shed the sugar or that the sugar's presence has irrevocably altered the cells (an unfortunate possibility). Also, small levels of the sugars certainly make it into our bodies (food we eat), but there are certain areas of the body that are behind serious filteration and purification systems (the infamous "blood brain barrier" for example) that may have little tolerance for the sugar. The point is, stem cell mediated neuron replenishment (which gets the most press for stem cell research in my opinion), could be a lot harder unless scientists can work with pure human lines.
posted by willns at 11:30 AM on January 24, 2005

Now, note that it is illegal to produce any new embryonic stem cell lines.

No, it isn't. Man, every time we discuss this, I'm amazed by how poorly the otherwise well-informed denizens of Metafilter understand this issue.

As for government funding, come to California, ye biotech companies! The state is pumping $3 billion over the next 10 years into embryonic stem cell research. Other states are talking about following suit. Hurray for Federalism!
posted by mr_roboto at 11:31 AM on January 24, 2005

BRING YOUR STEM CELL BUSINESS TO CAL-EE-FORN-YA. MARS WE NEEDS WOMENZ.
posted by basicchannel at 11:43 AM on January 24, 2005

It is also illegal for me to pave my driveway. I'm getting sick of only having rocks. They end up on the lawn, in the road, and pretty much everywhere BUT my driveway. I think the federal government should pay to have my driveway paved immediately.

Oh, wait. It's not illegal? But if it isn't illegal, why won't the federal government pay for it? It is in the best interest of my family, my neighbors, and everyone that drives on the road that might get hit by an errant rock. If someone might get a cracked windshield from a flying rock, the federal government should step in and take care of this problem immediately. I'm sure that the taxpayers would be willing to foot the bill.
posted by bh at 11:59 AM on January 24, 2005

Point taken robot, should I have said, "illegal in all states except California?"
posted by willns at 12:02 PM on January 24, 2005

Come out, experts from the woodworks!

Erm, willns: no, you should have said "it's illegal to use federal funds, but legal otherwise everywhere in the US."
posted by koeselitz at 12:07 PM on January 24, 2005

Another problem with existing cell lines is sensecence. After a stem cell divides a number of times in culture, it'll stop dividing. There are some interesting telomerase work being done, but "imortalized" cells aren't, really.
posted by PurplePorpoise at 12:08 PM on January 24, 2005

Are you (obtusely) suggesting the government shouldn't fund scientific research, bh? I suppose you could make an idealistic minimal government case for this position, but in real terms it would mean a train wreck for the U.S. economy and university system.

Point taken robot, should I have said, "illegal in all states except California?"

No. It is legal throughout the U.S. Federal funding agencies, however, have been directed not to fund embryonic stem cell research. Researchers must therefore find their funding elsewhere (private investors, state governments, etc.) This is a major barrier for academic investigations of embryonic stem cells, as the vast majority of funding for academic research comes from the federal government.
posted by mr_roboto at 12:10 PM on January 24, 2005

Koeselitz, generating new lines canont "be pursued under existing rules for the use of federal grant dollars." Researchers rely on federal grants for funding. By removing federal funding policy makers have made it effectivedly illegal.
posted by willns at 12:10 PM on January 24, 2005

There is this one incidence, that always intrigues me. I have read that, according to the human genome project, within the last 50,000 years, the population of humans on this planet, dropped to around 2,500 due to some happening that is not known. That is all populations of humans. An infection that wiped out all humans with the now-toxic sugar, leaving behind only the mutants, might account for something like that. I assume that humans lived all over the world, as we do now. It is hard to imagine that a predator bacterium or virus could travel like that, but with the new bird flu and the way birds get around, maybe that could have happened.

You have to wonder if there is a link to that sugar, and any or all Auto Immune Diseases? If that sugar is never found in the human brain, as far as the scope of this research goes, what if it is in the brains of people with MS, or Alzheimers, or Mad Cow? My father always says, "Some people get all their exercise, jumping to conclusions", I think he made that up, to describe how my mind works.
posted by Oyéah at 1:16 PM on January 24, 2005

Neu5Ac and Neu5Gc are sugars found on cells present in nearly every mammal, from chimps to pigs. When scientists altered the genes of mice so that they couldn't produce them, the mice died. However, unlike our closest relatives, humans lack a gene that makes Neu5Gc. The gene is not gone, but rendered silent by a fatal mutation, one that occured approximately 500,000 ago.

Damn interfering aliens—keep your grubby tentacles off my genome!
posted by rushmc at 1:18 PM on January 24, 2005

Great article, willns. Thanks.
posted by homunculus at 1:27 PM on January 24, 2005

Some other things to gloss.
posted by homunculus at 1:28 PM on January 24, 2005

PurplePorpoise: Another problem with existing cell lines is sensecence. After a stem cell divides a number of times in culture, it'll stop dividing. There are some interesting telomerase work being done, but "imortalized" cells aren't, really.

My understanding is that that's only true for multipotent stem cells (roughly, adult stem cells) but it's not an issue for pluripotent or totipotent stem cells (roughly, embryonic stem cells). This seems to agree.

bh: That's certainly the classic libertarian argument against government funding of scientific research, but it would apply to all research equally (with the possible exception of defense-related research). That argument certainly doesn't support a specific prohibition against government funding of stem cell research only.
posted by DevilsAdvocate at 1:30 PM on January 24, 2005

People claiming that it is illegal to do stem cell research in the US are, of course, wrong. But all those people above who are patting themselves on the back and saying that it is only illegal to "use federal funds" are also being disingenuous. Not purposefully, I think, but still being inaccurate.

Here is the truth:

It is not only illegal to use federal funds to do stem cell research, it is illegal for any organization that receives federal funds for *any reason at all* to do stem cell research. In other words, it's not that you can't use federal money, it's that if you receive any federal money at all even for things completely unrelated to stem cell research you can't do any stem cell research. Care to take a guess how many serious research organizations don't receive any federal money at all. The answer is: pretty much every serious group receives some federal money.

So while the statement "it is illegal to do stem cell research in the USA" is false, simply replying that "you can't use federal money" is just about as wrongheaded... and the people doing it are more annoyingly proud of themselves. The effect of Bush's policy is very close to a blanket ban since virtually every significant research organization receives some federal money. So cut it out with the "you just cant use federal money" stuff.

California is trying to change this, of course.
posted by Justinian at 1:50 PM on January 24, 2005

Are you (obtusely) suggesting the government shouldn't fund scientific research, bh? I suppose you could make an idealistic minimal government case for this position, but in real terms it would mean a train wreck for the U.S. economy and university system.

Mr_Roboto: Yes, actually I am making a case for that. It is not the federal government's job to support the university system. It is not the federal government's job to support anything, actually. While I realize that I hold a very unpopular view here, I've yet to see or hear an argument that compels me to think differently.

On preview: DevilsAdvocate, I agree. Restrictions like these are a waste of time and money. I wish there was less funding across the board. However, I can see how some people have a strong moral issue with this, just like I could see people complaining if the government wanted to fund studies on which religion is more correct. Ideally, they would fund neither.

Justinian: Any company that is receiving federal funding is taking money from everyone in this country. Personally, I equate this with stealing.
posted by bh at 1:57 PM on January 24, 2005

I've yet to see or hear an argument that compels me to think differently.

I think success speaks for itself. Is there a country on the face of the planet without governmental support for its university system that has a successful university system? I know that sounds horribly pragmatic of me, but pragmatism gets things done (and gets diseases cured, as the case may be).

It is not only illegal to use federal funds to do stem cell research, it is illegal for any organization that receives federal funds for *any reason at all* to do stem cell research. In other words, it's not that you can't use federal money, it's that if you receive any federal money at all even for things completely unrelated to stem cell research you can't do any stem cell research

That's simply not true. I'm not sure where you came up with that, but it's not true. Seriously, did you just make that up?

Here's the NIH FAQ on federal funding and the use of embryonic stem cells. It turns out that not only can non-federally fundable lines be used in institutions receiving federal funding, but they can even be used by individual researchers receiving federal funding. The only proviso is that:

Scientists who receive federal funds and study both federally fundable and non-federally fundable human embryonic stem cells must charge research costs for study of non-federal lines only to non-federal sources of funding. With respect to indirect costs, such as facilities and administrative (F&A) costs, scientists should adhere to the guidelines in applicable federal cost principles such as OMB Circular A-21 (Colleges and Universities). These documents describe how to keep budget and accounting records so as to prevent federal funds from improperly subsidizing non-federally supported research.

In other words, you can receive federal funds and research non-federally fundable cell lines; you just need to do your bookkeeping well to make it clear that no federal funds are going to work on these non-fundable lines.

In fact, researchers currently receiving federal funding are even allowed to derive new embryonic stem cell lines, using their existing laboratories, provided they meet the following criteria:

You may do the derivation in your university laboratory as long as: 1) you carefully and consistently charge all direct costs of doing the derivation to a non-federal funding source and 2) your university or research center has in place a method of allocating the costs of supporting your laboratory so that this activity's appropriate facilities and administrative (F&A) costs are charged to non-federal accounts.
posted by mr_roboto at 2:28 PM on January 24, 2005

bh - No time, but the public goods argument points very strongly toward gov't funding for basic research. The benfits accrue to everybody, and it's impossible to internalize the benefits of basic research. The market would under-invest in basic research, and over-withhold the benfits from the public.
posted by thedevildancedlightly at 2:28 PM on January 24, 2005

thedevildancedlightly - No time here, either. But one thing worth mentioning - If the government could spend money on research that actually helped the public at large, and didn't benefit specific interests and certain drug companies, then I can see that argument holding water. Any research done with government money should be in the public domain. As long as taxpayers fund anything that benefits only large corporations, I'm against all funding.

If (not when) the government can clean things up, I'm willing to re-evaluate.
posted by bh at 2:36 PM on January 24, 2005

MetaFilter: I've yet to see or hear an argument that compels me to think differently.
posted by homunculus at 2:38 PM on January 24, 2005

bh - I used to work at the NIH - you can take that as potential bias or as insight. Your call. But we were researching basic cell transport mechanisms. Eventually many drugs for Alzheimer's and Parkinson's may use the insights that we gained, but not for many years. The information we put out is in the public domain - what proteins are involved in cell transport. It's published, free, without limitaitons. Go to PubMed and search for "Paul Blank". That's as public domain as it gets.

Yes, a pharmaco will be involved before a drug is made, but figuring out what transport proteins are involved is a far cry from being ready for a drug. The information is available to all drug companies, and equally to all of them. They are being rewarded for taking basic information and transforming it into useful therapies. They wouldn't conduct this type of basic research (or conduct it in overlapping races) without the NIH.
posted by thedevildancedlightly at 3:01 PM on January 24, 2005

PubMed note - the format is to search for "Blank P", look for the articles on calcium-mediated exocytosis. Full-text articles available.
posted by thedevildancedlightly at 3:08 PM on January 24, 2005

the public goods argument points very strongly toward gov't funding for basic research

This used to apply, but in the current era of patent and copyright insanity, I'm not sure how much it does anymore. Let the benefits actually accrue to the public and I'm all for funding of basic research; pay the corporations to do research which they roll over into billions of dollars of private profit and proprietary intellectual property and it suddenly becomes a lot less attractive.
posted by rushmc at 3:56 PM on January 24, 2005

rushmc - It feels like a cop-out, but here's the short summary:

Even with patent and copyright craziness there is still public benefit to pharmaco patents. Four sources of public value:

1 - Pharmacos can never extract 100% of the value of medicines to the consumers (a drug that costs $5 might be worth $20 to you and they'll never get it all out of you)

2 - Devopment of one drug and a publicly published patent encourages development of later drugs (which will also produce spillover benefits)

3 - Human capital is developed in drug development and can't be controlled. Most states with big high-tech industries (eg, California) don't enforce covenants not to comepete, so pharmacos can't prevent employees from taking advantage of the investment in human campital

4 - Spillover from creating a high-tech center. Basically it's a Good Thing to have a high-tech corridor (eg, Silicon Valley) as it produces a lot of high-paying intellectual jobs.

So, tons of spillover value. Public research does at least one of the following:

1 - Reduces overlap. If Merck and Pfizer exist in a vacuum (no NIH) they'll both research on a lot of the same basic research issues, which is a total waste and raises drug prices for consumers and reduces the availability of capital in other markets

2 - Corrects for under-investment. Again, if there is no NIH then Merck and Pfizer will be hesitatnt to invest in basic research (very costly relative to reward) since it's possible that the other competitor will get the prize first. So, the NIH solves the under-investment problem.

Those are the quick highlights. The long version has a long micro and macro economic explanation with lots of risk-efficient investment and supply-and-demand charts.
posted by thedevildancedlightly at 4:25 PM on January 24, 2005

Yes, it's a pretty good summary of the benefits. I still maintain they are outweighed by the negatives in the current system.
posted by rushmc at 5:27 PM on January 24, 2005

rushmc - Problems with the patent law don't imply (at least to me) an argument against public support for basic research. Patent law is defintiely an interesting issue... Next time it comes up I'd love to debate more fully.
posted by thedevildancedlightly at 6:07 PM on January 24, 2005

Interestingly, I often lie on a on layers of mouse "feeder" cells for growth also. I'm currently 16 feet tall.
posted by nanojath at 8:18 PM on February 23, 2005