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Stem cells and endangered livestock breeds

A group of scientists at the Massachusetts Institute of Technology has managed to turn fibroblasts, cells abundant in connective tissues, back into pluripotent, i.e. non-differentiated, stem cells. ((Wernig et al. 2007. In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state. Nature.))  This has caused quite a stir — and for good reason.

Because stem cells are pluripotent, they can in theory be turned into virtually any cell type in the body. Needless to say, such cells have tremendous potential for therapeutic intervention in all sorts of human maladies that result from cellular death or injury. Until now there have been mainly two ways to obtain stem cells: one involves the generation and subsequent destruction of  an embryo to extract embryonic (ES) stem cells,  the other relies on  isolation of adult stem cells, which have been found in all sorts of locations from the spinal chord to dental pulp.

But there are limitations and issues with both approaches: the derivation of ES cells evokes moral objections from many quarters because it necessitates the destruction of an embryo, while the use of adult stem cells is at present fraught with doubts about whether such cells are truly pluripotent. This is why this new development is considered such a breakthrough.

Why would a method to generate stem cells be relevant for saving endangered animal breeds? What if it were possible to turn pluripotent stem cells into eggs and sperm cells? Impossible, you say? Well, consider this: an article appeared in 2003 in the journal Science claiming that scientists had, indeed, managed to generate what seemed to look like egg cells from embryonic mouse stem cells. ((Hübner et al. 2003. Derivation of oocytes from mouse embryonic stem cells. Science 300:1251-56.)) Several other groups meanwhile seem to have coaxed stem cells to turn into primitive sperm cells, and at least one report has described the use of such sperm cells to generate live mouse offspring. ((Nayernia et al. 2006. In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice. Developmental Cell 11:125-32.))

Much of this remains to be worked out and confirmed by other scientists, and given the incredibly complicated process of meiosis and maturation that egg and sperm cells have to undergo before becoming truly functional, many doubt this kind of approach will ever be feasible. Even the conversion of fibroblasts into stem cells is at present still very complicated and this recent report represents mostly a proof of principle. 

But just imagine if this were all to work: it might then be possible to go out into a field, pick a few small chunks of ear tissue from as many endangered cattle, goats or pigs as you want,  isolate the fibroblasts, turn them into stem cells, coax those into becoming eggs and sperm, make embryos, and put them into your freezer, where they could remain indefinitely. You could do this probably with a lot less effort than it often takes to ensure preservation of  rare animals in situ and would, moreover, be able to bank as much of a breed’s genomic variation as you’d like.

Maybe this will remain science fiction. Then again, nobody thought a sheep could be cloned either…. ((Contributed by H. Michael Kubisch))

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Cacao and maize tell similar stories

Playing catch-up, I note from Cacaolab an article in the New York Times, saying that archaeologists reckon that people first used the pulp in cacao pods as the basis for a fermented beverage, only later figuring out that the seeds might be good to eat too. Cacaolab says this makes sense. I’ll take their word for it.

I like the idea of one thing leading to another because it gives weight to my favourite theory on the domestication of maize. All the evidence suggests that the original mutation that turned teosinte into maize happened only once. So how come somebody noticed it? Because people were cultivating teosinte. But why? They weren’t using the seeds, as far as we know. Hugh Iltis advanced the idea that people were growing teosinte as a source of sugar, chewing on the stalks rather like sugarcane. And they were also harvesting corn smut, Ustilago maydis, a fungus that grows on the seeds and that is known locally as huitlacoche (which, by the way, is absolutely delicious). So they had every reason to pay attention to teosinte’s miserable ears of grain, and to notice the changes that created maize.

Speaking of which … geneticists have recreated the rare events that gave rise to wheat, giving us synthetic wheat (incredibly useful for breeding) in the process. They know all about the mutations that make maize. But as far as I know they have not yet made synthetic maize. Why not?

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Search for rust-proof wheats proceeds

Scientists at the USDA Small Grains and Potato Germplasm Research Unit at Aberdeen, Idaho, have been combing old records in their search for wheat that may be resistant to UG99 and other types of stem rust. Nearly 8500 accessions from all around the world have been tested since 1988. Those tests did not include UG99, of course, which first emerged in 1999, but they are still useful to identify likely candidates. Farmers’ varieties from Chile, Ethiopia, Turkey and Bosnia and Herzegovina are showing promise, and several are being shipped out to east Africa to be trialled in the real world where UG99 runs riot.

The article in the USDA’s magazine is just one of several that discuss cereal breeding. There’s an editorial on the need for global cooperation ((Doh! It’s a global problem.)), an overview of UG99 (which we blogged earlier) and others on breeding soybeans and common beans.

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Happy birthday, chicken

edm-broilers.jpg Those chickens give me the willies. Like the mythical boiled frog, I hadn’t been really aware of what has been done to the broiler chicken in the past 50 years. I knew, of course. But I didn’t know. Now, thanks to an almost incidental image on the web site of CBC news in Canada, I do. ((The photo is by Martin Zuidhof, a researcher at the University of Alberta. I wish I could find a bigger version.))

The reason for the CBC story, amplified in a press release from the University of Alberta, is that it is 50 years since the Poultry Scientists at the University of Alberta decided “to preserve a strain of broiler chicken to ensure it would live on”. The lovable boffins decided to celebrate with a bit of a party, which included a special feed for the hens, “topped off with birthday candles”. There is, of course, a serious point to all this: birds back then may have been five times smaller, and much slower growing, but they had some fine genes that the far-sighted scientists deemed worth preserving.

“At the time, it was thought by Agriculture Canada that genetic progress was happening pretty quickly and that a random-bred standard should be maintained to preserve those genetics,” said Doug Korver, a professor of poultry nutrition in the Faculty of Agriculture, Forestry, and Home Economics. “Preserving genetic stocks is important in poultry, because we use so few individual strains to produce a lot of the poultry in the world.”
“If we ever have to fall back on some traits that have been lost in the commercial genetic selection process, then we have that resource available to us to rely on again,” Martin Zuidhof told CBC News.

The crucial phrase is “random-bred”. Each year the scientists choose 400 eggs from 300 hens and use them to rejuvenate the flock. There is no selection, so the chances are good that all the genetic diversity is being preserved. Indeed, at a visible, phenotypic level, diversity is increasing. The original flock was all-white. Fifty years on, coloured birds stroll among their white brethren.

Among the invisible differences between the random-bred flock and modern selections is the response to infection. Modern birds do not divert many resources away from growth and into an immune response. “Old” birds mount a vigorous immune response, but at the expense of growth. It is this shift in priorities that underlies the almost unbelievable progress of the modern bird; it is selected to grow, quickly and efficiently, and infections are a distraction. The day may come when modern flocks need a better immune response, or maybe just resistance genes.

One of the issues is food security, said Zuidhof, citing the threat of bird flus, which wipe out entire flocks of chickens almost overnight. “Should something happen in the industry that caused a major loss of numbers, we have a strain that is unselected and closer to the indigenous chicken. It is just one more approach to securing the food supply going into the future.”

So how much has the modern bird changed? It is ready for the table in 35 days — that’s five weeks — versus the 90 days, almost 13 weeks, of its ancestor, which was already pretty well selected. Zuidhof reckons about 80% of the increase is down to genetics and just 20% to better nutrition and housing.

“People often assume that because chickens are so different from how they were 50 years ago, it must be to some technology like hormones. It’s all based on traditional selection of the best individuals and nutrition.”

Nevertheless, the scientists know that they don’t know when they might need to go back to the relatively unselected founder stock, hence the happy birthday to that genepool. And if its worth preserving the basis of the modern broiler flock, how much more important might it be to preserve the rest of the chicken’s genetic diversity?