The first chimeric monkeys

February 5, 2012

A chimera is an individual that contains a mixture of genetically different cells -- from different zygotes. I suppose that a person who has received an organ from another individual is a chimera. In modern biology, making chimeric mice is common. To do that one injects embryonic stem cells (ESC) into an early stage embryo, called a blastocyst. (The movie listed below with the article illustrates this.) The injected cells mix with the blastocyst cells, resulting in a mouse containing cells of both types. This is useful because one can introduce new features by modifying the ESC before using them. The chimera itself, as a mixture, is not useful; however, gametes are of one cell type or the other, so breeding of the chimera leads to some animals carrying the modification. Thus making chimeras is one step in lab work introducing new mutations into mice.

Attempts to carry out the same procedure in monkeys have largely failed. A new paper confirms that, but shows that one can make chimeras in rhesus monkeys by going to an earlier stage of development. Their basic procedure is to fuse embryos at the 4-cell stage. In various experiments, they fused 3-6 such embryos. They did various analyses on them, but some were implanted in a surrogate mother, and two such mothers gave birth to live offspring: those results are shown in the picture above.

How do we know that these animals are chimeras? Of course, that was the intent -- the experimental design. Multiple embryos were fused; the idea is that the cells of those multiple embryos somehow form one animal. But how do we tell what actually happened? The key idea is that the embryos used to form the chimera can be distinguished; they test the resulting chimeric animal, and show that it has features from multiple parents. For example, embryos might contain different DNA markers.

It is not at all clear what the implications are of this work. Making chimeras per se is not a particularly useful result. What makes the work with mouse chimeras so useful is that it uses ESC, which can be grown and modified in the lab while still preserving their ability to function normally when returned to a blastocyst. So far, this cannot be done with the monkeys. Can the cells from the 4-cell stage be similarly grown and modified, and still preserve their ability to resume normal growth? Perhaps, but probably not. Will further analysis of this system, which now includes one way that does work to make a chimera, lead to better understanding of the entire reproductive system, and then to the ability to make chimeras using ESC? We'll see.

News stories:
* Three monkeys a genetic mishmash -- Feat suggests stem cells may have less potential than hoped. (Science News, January 5, 2012.)
* World's first chimeric monkeys are born. (PhysOrg, January 5, 2012.)

* News story accompanying the article: Chimeric Primates: Embryonic Stem Cells Need Not Apply. (A Trounson & U Grieshammer, Cell 148:19, January 20, 2012.)
* The article: Generation of Chimeric Rhesus Monkeys. (M Tachibana et al, Cell 148:285, January 20, 2012.)

There is a video file with the article; look for "Supplementary Content", at upper right. The movie has two parts. The first shows how one injects embryonic stem cells into the blastocyst. Remember, this method did not work for the monkeys. Nevertheless, the method is used with other animals, and what the movie shows is useful. The second half of the movie shows another injection.

Other posts about chimeras:
* On his right side, he is female (April 24, 2010).
* Children with two fathers (January 3, 2011).

Other posts about monkeys:
* Prejudice against outsiders -- in monkeys (May 10, 2011).
* Speech: Taking turns (August 17, 2011).

Were comets the source of Earth's water?

February 3, 2012

There is a lot of water on Earth. Where did it come from? The common view is that any water on the nascent Earth would have been lost, due to the high temperature during the early phase of Earth formation. That leaves "elsewhere" as the source: bombardment of the Earth with water-bearing objects, such as comets or asteroids. Such collisions occur, and were more frequent in the old days.

Planetary scientists have tried to figure out whether comets or asteroids were the major source. The evidence has not been consistent. A new paper makes the argument even more wide open.

The key idea is to measure the hydrogen isotope ratio of water: Earth water, and water from various possible sources. On Earth, we do that with a mass spectrometer. ESA's Herschel Space Observatory does it by measuring spectral bands in the infrared. In any case, one measures the ratio of ²H to ¹H -- the D/H ratio. (²H is known as deuterium, symbolized as D.) What is it we should measure? Well, "ocean" is simple enough for Earth water -- and we have lots of data for that. And we can collect meteorites, many of which are thought to have the same composition as asteroids, so we measure their water.

The big problem is comets. Getting our hands -- or our instruments -- on cometary material is difficult, and only a few comet samples have been analyzed. The first few comet samples that were analyzed gave D/H ratios very different from that of Earth water. Thus, comets as a source of our water has gone out of favor.

Now we have a new cometary analysis -- and it fits right with Earth water. Comets are "in" again. What makes this result especially interesting is that this is a different type of comet than those measured previously; perhaps the new result reflects that type of comet, not just the individual comet.

Here is a summary of what we now know about the D/H ratio from various sources:

You can see that most of the values shown are about the same, with D/H about 1.5x10^-4. However, the value shown for the Oort cloud comets is twice that. Until this new work, those were the only measurements we had for cometary water. Now, we have a new measurement, which shows that at least this one comet has water like ours. The significance of this new result remains to be seen, but for now comets are "in" again as a possible source of Earth water.

News story: Herschel finds first evidence of Earth-like water in a comet. (Space Daily, October 6, 2011.)

The article: Ocean-like water in the Jupiter-family comet 103P/Hartley 2. (P Hartogh et al, Nature 478:218, October 13, 2011.) The data table above uses information in the abstract of this article.

Musings looked at another aspect of this question in the post Where did our oceans come from? (January 4, 2011). That post deals with the possibility that our water was actually homemade. That is, it questions the assumption made above that our original water was all lost.

More from the Herschel mission, also on water measurements: A water fountain for Saturn (October 23, 2011).

Restricting excessive use of antibiotics on the farm -- follow-up

January 30, 2012

Original post: Restricting excessive use of antibiotics on the farm (September 25, 2010). That post presents the issues: how use of antibiotics on the farm may be causing increased antibiotic resistance in human pathogens. That statement is disputed by some, especially in the farm industry. Nevertheless, there is a move toward restricting antibiotics used for humans from use on the farm. The New York Times story in that post is still a good introduction.

The US FDA (Food and Drug Administration) has now issued a rule. It makes a small step in the direction of restricting such antibiotics on the farm. Those on one side will be disappointed by the announcement, but at least it is in the right direction.

The announcement: FDA to protect important class of antimicrobial drugs for treating human illness. (FDA, January 4, 2012.)

News stories:
* FDA limits some livestock antibiotics. (The Hawk Eye (Burlington, Iowa), January 5, 2012.) This is from a farm-state newspaper, but the story is reasonably well balanced.
* Public health: Rules tighten on use of antibiotics on farms. (N Gilbert, Nature 481:125, January 12, 2012.)

A parasitic fly that causes hive abandonment in bees: Is this relevant to CCD?

January 27, 2012

This post makes a connection between two ideas that have come up before. One is a serious and poorly understood problem of economic importance; the other is a fascinating behavioral issue involving parasites.

Bee colonies are being lost at an alarming rate, in a phenomenon known as colony collapse disorder (CCD). Various causes have been suggested, but none has been shown to be a key factor. In particular, nothing suggested so far explains a key observation of CCD: the bees seem to simply disappear. Here is a post on CCD: US Army attacks colony collapse problem -- and an ethics story (October 25, 2010).

We have also noted cases where a parasite seems to control the behavior of its host; sometimes we say that the host has become a zombie. A recent such post is Wasp hides under ladybug (January 3, 2012).

The main finding in the new work is that a particular parasitic fly can parasitize honeybees, and one of its effects is to cause hive abandonment. That is, the bees just leave the hive. This may be a zombie-type effect, with the fly controlling the behavior of the bees. (However, other explanations are possible. For example, it may be that the bees are sensed to be abnormal by their hive-mates, and are ejected from the hive.) Whatever the explanation, this behavior is reminiscent of a key aspect of CCD.

So, is this parasitic fly responsible for CCD? Not so fast. First, the distribution of the fly does not seem to correspond to the distribution of CCD. Second, fly-infected bees were often found to be infected with other agents. This finding might suggest that the disorder is due to a combination of agents.

In summary, then, we have an agent -- a parasitic fly -- which seems to cause a behavior something like what is seen in CCD. However, it is questionable that it is what is actually causing the current CCD disease. This is still a useful finding, even if it is not "the answer". The implications of this finding will be the subject of future work. For example, studying how this fly causes hive abandonment may be useful.

News stories:
* Deadly fly parasite spotted for first time in honey bees. (PhysOrg, January 3, 2012.)
* Parasitic Fly Dooms Bees to Death by Maggots. (Science Now, January 3, 2012.)

The article, which is freely available: A New Threat to Honey Bees, the Parasitic Phorid Fly Apocephalus borealis. (A Core et al, PLoS ONE 7(1):e29639, January 3, 2012.)

Snakes and humans: who eats whom?

January 23, 2012

We've all heard of food chains. Big fish eats small fish, and that small fish eats smaller fish -- and so forth. Of course, in the real world, the patterns may be more complex, and we have food webs. It is not often that we talk about food webs involving humans.

Where are we going with this? A group of scientists has studied a hunter-gatherer tribe in the Philippines, a tribe that is thought to represent an early type of human society. In particular, they study the relationship of the people to snakes. And what is that relationship? Complex! People eat snakes, as the figure above suggests. And snakes eat people. And people and snakes compete for other small animal prey.

It's a fascinating story, even if a bit gruesome at times.

Are we really supposed to believe all the stories told in the paper? It's an interesting question, one that the authors address. It is plausible that the subjects might "enhance" some stories. The problem is not unlike interviewing witnesses to a crime. The authors note some of the precautions they took to try to minimize enhancements.

Announcement: Study of man-eating snakes: Snakes are predators on, prey of, and competitors with primates. (Cornell University, December 13, 2011.) Good overview of the work.

The article: Hunter-gatherers and other primates as prey, predators, and competitors of snakes. (T N Headland & H W Greene, PNAS 108:E1470, December 27, 2011.)

More about pythons: Heart health and python blood (December 28, 2011).

Schmallenberg virus

January 20, 2012

A new virus has appeared -- and is causing fairly serious problems with milk production and fetal development in farm ruminants in Germany, Belgium, and the Netherlands. The virus was identified in November 2011. It is probably transmitted by midges.

Scientists have the genome sequence, and thus know the general type of virus. They can grow the virus in the lab. Beyond that, little is known. The good news is that they are fairly sure they have the right virus.

They briefly address the question of whether this new "Schmallenberg virus" (named after the German town where it was first discovered) infects humans. They suggest that it does not, because midges do not bite humans much. I find that less than reassuring. By the same argument they use for cattle, if pregnant humans were infected last summer, the results remain to be seen.

News story: New Animal Virus Takes Northern Europe by Surprise. (Science Now, January 13, 2012.) I suspect this tells most of what is known at this point. Nevertheless, it is remarkable that within weeks of a new virus emerging, we have this much information. It will be interesting to follow this story. Some might hope that it is not too interesting a story. In any case, it is an example of an emerging disease that we can watch from very near the beginning; as a matter of public health, biologists will follow it closely.

In the meantime, beware the midges.

More about emerging diseases is on my pages for Biotechnology in the News (BITN): Emerging diseases. That discusses some general issues, and also links to some specific diseases that have emerged in recent decades.

A Musings post on the broad issue of diseases: One health (November 15, 2010).

Several posts on the new flu strain that emerged in 2009, plus others about flu, are consolidated on the page: Musings: Influenza (Swine flu).

We'll add selected new developments from time to time, often with little comment...

Added January 26, 2012. Schmallenberg virus confirmed on farms in the UK. (Guardian, January 23, 2012.)

Musici Ambulanti: Ancient art and ancient microbiology

January 17, 2012

Each month the cover of EID (Emerging Infectious Diseases) has a work of art. The editor writes an essay about the art, and somehow ends up connecting it to the journal content.

The figure here is from the cover of the January 2012 issue of EID. The essay about it is: Tough Art and Microbial Drama. (Polyxeni Potter, EID cover story, January 2012.) EID, a publication of the US Centers for Disease Control, is entirely open access. (The figure is in color only in the web page version, not in the pdf. Also from the web page version... you can directly link to the articles that are listed as References, or to the journal Table of Contents for a complete listing.)

Another EID cover story: Why are musical instruments featured on the cover of EID? (June 7, 2010).

Synesthesia: the good side?

January 14, 2012

Synesthesia might be thought of as a cross-talk between the senses. For example, people with a certain kind of synesthesia would see the number 4 as blue.

Is this "bad"? As so often when we are faced with the variability of humans, it can be hard for us to understand how people who are different might be "ok". In the case of synesthesia, some have argued that the cross-talk is a special feature, allowing such people to make connections that the rest of us would not make. They would suggest that there is some analogy between synesthesia and creativity, with both involving a "skill" of making connections between things that most would not consider related. Is this an innate skill for certain people, based on how their brains are wired, or is it a learned skill? Much evidence points to it being innate. For example, the connections that a person makes are stable over time, and study of the brain suggests that they are due to real brain activity in the expected regions.

The following figure suggests that heredity is involved in synesthesia. This is Figure 2 from the paper.

If a tendency towards synesthesia is inherited, does that mean it is good -- that nature has selected for it? Or has this characteristic just come along for the ride, along with some other trait that is good? We don't know, but the data says we should ask the question.

News story: Why has synesthesia survived evolution?. (Medical Xpress, November 22, 2011.) A short but useful overview of the ideas from the article.

The article, which is freely available: Survival of the Synesthesia Gene: Why Do People Hear Colors and Taste Words? . (D Brang & V S Ramachandran, PLoS Biology 9:e1001205, November 22, 2011.) The article is good for browsing. It is classified in the journal as "Unsolved Mystery". The final section, "Towards a Solution", is a useful overview -- and emphasizes that the big story here is asking questions about this interesting condition.

We have noted synesthesia in the post: What does blue light smell like? (July 18, 2010).

Split brains and yellow submarines

January 9, 2012

A recent "Profiles in Science" story in the New York Times is about neuroscientist Michael Gazzaniga. Gazzaniga is not only a leading scientist, but a fine communicator. The article is both fun and informative. Have a look!

The story: Decoding the Brain's Cacophony. (New York Times, October 31, 2011.)

I have recommended another book by Gazzaniga on my page of Book Suggestions: Gazzaniga book. That book was noted in the post: The animal mind (July 23, 2009).

Gene therapy: Could we now treat Queen Victoria's sons? The FIX Fix.

January 6, 2012

Hemophilia -- the failure of blood to clot properly -- is most often due to defects in the gene for coagulation factor VIII or IX, resulting in hemophilia A or B, respectively. Both genes are on the X chromosome, which means that the disease is common only in males. Several of Queen Victoria's male descendants, some on one or another European throne, suffered from the bleeding disease. The basis of the royal bleeding was not known at the time. However, modern genetic analysis of the remains of Alexei Romanov, son of the Russian Tsar and in the Victoria lineage, revealed a mutation in the gene for Factor IX (FIX). We thus infer that Queen Victoria carried a mutant FIX gene.

A new report shows that gene therapy -- adding a proper gene for the FIX protein -- shows promise in treating hemophilia B.

This is not a new idea. However, previous attempts to do such gene therapy have yielded limited benefit. Now, they have made technical improvements to the gene delivery system, and try again. Work with six patients is reported. The dose was escalated during the study: the first two patients received a low dose, the second two a medium dose, and the final two a high dose. Here are the results reported for the 6th patient.

The figure above is Figure 1F from the paper; the complete Figure 1 shows such data for all six patients. Observations range out to 70 weeks (18 months) for patient 1 (lowest dose) down to the 20 weeks seen above for patient 6. There is much variability, but here are some general observations...
* All patients showed a rise is FIX levels, and clinical benefit. The latter is judged, for example, by a reduced need for taking the FIX protein.
* The level of FIX increased as the treatment dose increased.
* Liver toxicity, as noted above, was seen only for the two patients at the highest dose. In both cases, treatment of the liver damage seemed successful.

That's where it stands. Six patients, various doses, observations from 20-70 weeks. All show benefit -- sustained benefit. It's the best yet. Long term? We'll see.

News stories:
* Treatment for Blood Disease Is Gene Therapy Landmark. (New York Times, December 10, 2011.)
* Gene Therapy Achieves Early Success Against Hereditary Bleeding Disorder, Study Suggests. (ScienceDaily, December 11, 2011.)
* ASH: Gene Therapy Puts Merry in 'Christmas' Bleeding Disease. (MedPage Today, December 10, 2011.) (ASH refers to this being, in part, a report of a presentation at a meeting of the American Society of Hematology. The term 'Christmas' disease refers to the name of an early patient.)

* Editorial accompanying the article: Merry Christmas for Patients with Hemophilia B. (K P Ponder et al, New England Journal of Medicine 365:2424, December 22, 2011.) Includes a discussion of the likely merits of gene therapy with the FIX gene vs the conventional treatment with the FIX protein.
* The article: Adenovirus-Associated Virus Vector-Mediated Gene Transfer in Hemophilia B . (A C Nathwani et al, New England Journal of Medicine 365:2357, December 22, 2011.)

For another gene therapy approach to treating hemophilia, see Gene therapy: Curing an animal using a ZFN (August 9, 2011). This, and another gene therapy post referred to there, involve mice. It's important to note that the current work is gene therapy in people -- real patients.

For another story about a sex-linked gene, see Quiz: The monkey-cat (October 26, 2011).

For more on gene therapy, see my page BITN: Agricultural biotechnology (GM foods) and Gene therapy.

Vox Balaenae

January 4, 2012

This accompanies the post on whale songs, immediately above. Vox Balaenae is a piece of music inspired by whale songs. It was composed in 1971 by the rather radical American composer George Crumb (1929-). The title is sometimes translated as Voice of the Humpback Whale.

Video: George Crumb - Vox Balaenae. (10 minutes.) The performance is identified on the YouTube page, and on the video itself.

Other music posts include: Quiz time... (June 15, 2011).

European journal open to authors around the world -- and beyond

January 2, 2012

A new journal article is on work done on the International Space Station (ISS) -- and was submitted from there, ~350 km (~200 miles) beyond our planet. The journal claims that this is the first paper to be submitted by an author not on Earth.

Some ages ago, there must have been a first scientific paper based on looking upward from the Earth's surface and viewing the heavens. We have noted a 1781 paper by William Herschel: The first report of a new planet (March 13, 2011). Of course, many preceded him -- whether or not they wrote what we would now call scientific papers. [We also noted books from the early 17th century by Kepler and Galileo, based on their observations of the heavens: Book review: Galileo (October 6, 2010) -- and linked post.] In the 20th century, we began to get papers based on observations made in outer space. Now we have a paper written there and submitted from there.

What is the next event in this series? When will it happen?

News story: Journal receives its first paper from space. (EurekAlert, November 11, 2011.)

* Editorial accompanying the article: Is EPL a global journal? No, more!. (M Schreiber, Europhysics Letters, December 2011.) The editorial tells the somewhat amusing background story behind the paper.
* The article, which is freely available: Direct measurement of the speed of sound in a complex plasma under microgravity conditions. (M Schwabe et al -- including S Volkov, Europhysics Letters, December 2011.) Check the author affiliations -- especially the current address for the last author. I should note, however, it is not at all clear from the paper per se that he is the one who submitted the paper, from that address. Oh, you can find out what the paper is about here; at least, peek at the abstract. But the content of the paper is not what this post is about.

The following page suggests that the claim made above is not quite right. I'll let folks check it for themselves as they wish. A letter from space. (Physics World blog, November 11, 2011.)