Your living flash drive
A news article from Computerworld:
A Japanese university announced scientists there have developed a new technology that uses bacteria DNA as a medium for storing data long-term, even for thousands of years.
Keio University Institute for Advanced Biosciences and Keio University Shonan Fujisawa Campus announced the development of the new technology, which creates an artificial DNA that carries up to more than 100 bits of data within the genome sequence, according to the JCN Newswire.
The universities said they successfully encoded "e= mc2 1905!" -- Einstein's theory of relativity and the year he enunciated it -- on the common soil bacteria, Bacillius subtilis.
I like the exclamation point!
This isn't at all a new idea. I've long predicted to my classes that people would take advantage of DNA design to implant messages in their children's DNA.
Usually they look at me like I'm a raving loon. Which, I have to admit, isn't so different from any other day.
"Why would anybody want to do that?" Well, why would somebody want to get a tattoo? There are lots of reasons. Vanity. A memorial of someone they loved. Self-actualization.
Unlike the bacterial genome, the human genome makes room for a lot of cruft. Which means that the messages can be long -- maybe megabases -- without causing biological problems. And the permanence of the messages is a lot longer per copy, since the DNA repair mechanisms are vastly better and the human lifespan is so much longer.
Imagine a implanting a copy of all your known genealogical information into your children's DNA.
Or an encoded version of your preferred religious book.
Or maybe a short video message. OOOOHH -- it could be the clue to a crime in some futuristic novel!
DOE genomics
Linked on Evolgen, I found this post from Nobel Intent that gives a quick summary of reasons the U.S. Department of Energy is in the genomics business. It's a good rundown, including radiation research into mutations and research into new biofuels. It might also mention the interest in finding microbial agents to clean up chemicals of various kinds. As the Neandertal metagenomics stuff starts coming online, some folks might be interested in the history of DOE involvement in genomics, and this is a good place to start.
They didn't sign on for this
I got pointed to this Ronald Bailey article in Reason, which describes the approaches of some ethicists to the prospect of "genetic enhancement" of humanity. I'm pasting this passage for the links, and for the sheer magnitude of efforts already underway to limit alterations to the genome:
Far from there being a "right" to enhance oneself and one's progeny, some institutions and activists currently aim to outlaw various biotech interventions. For example, the European Convention on Human Rights and Biomedicine prohibits the introduction of "any modification in the genome of any descendants." While it does not have the force of law, UNESCO's Universal Declaration on the Human Genome and Human Rights urges nations to ban "practices which are contrary to human dignity" and specifically points to reproductive cloning. Bioethicist George Annas wants to go further and have the United Nations adopt a a Convention of the Preservation of the Human Species that would make efforts to enhance human beings by making heritable changes in people's genomes a crime against humanity.
Who knew they had time? I can't help but think that all this regulating and forbidding won't come to anything. There will be little sense that these are really negotiated political solutions. It's like a gold rush of regulation, and the people in a position to actually make changes to genomes haven't gotten off the line yet.
Anyway, I thought there was a certain amount of silliness in this description of ethical vs. unethical genetic changes:
Philosopher Fritz Allhoff from the University of Western Michigan speaking on a conference panel about "Democratizing the Genome" grappled with the issue of consent. Allhoff offers a principle derived from the second formulation of Kant's categorical imperative that "genetic intervention would be morally permissible only if every future generation would rationally consent to the genetic alterations made in the germ-line."
The article goes into some detail about what kinds of genetic alterations might fit this criterion.
My comment is this: The notion that genetic changes require consent of future generations presupposes the wrong baseline. The alternative to intentional changes is not no change, or stasis. Stasis is not an option, regardless of what we do. The genetics of our species have been changing for some time, and they continue to change even now. Many of those changes have been (or will be) direct consequences of cultural traditions.
Further, our genetic nature today is not one that past generations of humanity could have possibly predicted. Consider a well-known genetic adaptation of our species, like the sickle-cell trait, which confers resistance to malaria in heterozygotes but is deadly to homozygotes. Clearly on the basis of survival and reproduction, that trait has survived and proliferated in malarial West Africa over the last several thousand years. It certainly benefited the first people who carried it. But today its benefit has been eliminated in many of the descendants of those first carriers -- in malarial Africa, it causes as many deaths from the sickle-cell trait as it saves from malaria, and in African-Americans very few people are saved from malaria, so it only has costs.
Now, suppose we asked prehistoric Africans whether future generations would consent to the sickle cell allele. What would they say? The genetic situation is very clear -- the first few generations that carried the allele had huge advantages in survival and faced few costs, because it was unlikely to mate with another carrier and have children with the sickle-cell trait. Over time, as the allele became common, the costs rose to match the benefits. But also over time, the relatedness of further generations to the original carriers declines. After 20 or 30 generations, the original carriers have certainly won out -- they have become ancestral to a much higher proportion of the population than they would have otherwise, but the
What is the primary good here? Giving people the chance to live longer in the face of malaria? On that basis, the sickle-cell allele had an early initial success and a long-run failure. Giving people the chance to have more children? Again, that worked incredibly well early on for carriers -- but its benefit ultimately disappeared. And it came at the cost of the reproduction of all the initial population that lacked the allele.
Or maybe the primary good is allowing the population to exist at all. It is far from clear that human occupation of high-malaria regions would even have been possible without genetic adaptations to resist malaria. The sickle-cell allele is not the only one of those, but it is an important one.
So it is nonsensical to pose the question of whether future generations would consent to our changes. For most changes, we can predict pretty surely that if the change has a short-term positive effect, the competitive advantage given by that effect will disappear once everyone has it. Now maybe you could argue that some such changes would be good on their own merits in any context -- like genetic changes that make people live longer but don't kill children in the process. But not everybody wants to live longer today, and if those effects are viewed as good in the future, it will be in terms of cultural values that we today are ill-equipped to predict.
And the entire question removes our relevance as actors. The only way that our actions can have lasting importance is by virtue of their effects on the future. If we take away our own possibility of action, then we eliminate our relevance. If we refuse to take actions that we believe will be good for our children, then we leave them to the genetic changes that will occur without us.
Well, anyway, some philosophers construe the rules to allow some kinds of genetic alterations:
Philosopher Martin Gunderson from Macalester College offered the notion that perhaps permissible genetic interventions might be limited to those which enhance a person's moral capacities including the ability to reason based on principles, conform to moral rules, be morally perceptive, and have a certain kind of moral empathy.
In other words, if they were more likely to major in philosophy....
Belt on up to the smart bar
I draw your attention to an essay by neuroscientist Michael Gazzaniga in the current Scientific American Mind. It's a long and thoughtful consideration of the ethics of cognitive enhancement drugs:
Smarter on Drugs
We recoil at the idea of people taking drugs to enhance their intelligence. But why?
By Michael S. Gazzaniga
Any child can tell you that some people are smarter than others. But what is the difference between the brain of a Ph.D. student and the brain of the average Joe? If we can figure that out, then a bigger question follows: Is it ethical to turn average Joes into geniuses? Evolutionary theory suggests that if we are smart enough to invent technology that can increase our brain capacity, we should be able to use that advantage. It is the next step in the survival of the fittest. As noted psychologist Corneliu Giurgea stated in the 1970s, "Man is not going to wait passively for millions of years before evolution offers him a better brain."
That said, gnawing concerns persist when it comes to artificially enhancing intelligence. Geneticists and neuroscientists have made great strides in understanding which genes, brain structures and neurochemicals might be altered artificially to increase intelligence. The fear this prospect brings is that a nation of achievers will discard hard work and turn to prescriptions to get ahead.
Enhancing intelligence is not science fiction. Many "smart" drugs are in clinical trials and could be on the market in less than five years. Some medications currently available to patients with memory disorders may also increase intelligence in the healthy population. Likewise, few people would lament the use of such aids to ameliorate the forgetfulness that aging brings. Drugs that counter these deficits would be adopted gratefully by millions of people.
Over 4000 human genes patented
National Geographic News has a story about the ubiquity of gene patenting, following on an analysis in Science (subscription required) by Kyle Jensen and Fiona Murray.
Here is the key graf from the Science study:
Our results reveal that nearly 20% of human genes are explicitly claimed as U.S. IP. This represents 4382 of the 23,688 of genes in the NCBI's gene database at the time of writing (see figure, right). These genes are claimed in 4270 patents within 3050 patent families (28). Although this number is low compared with prior reports, a distinction should be made between sequences that are explicitly claimed and those that are merely disclosed, which outnumber claimed sequences roughly 10:1. The 4270 patents are owned by 1156 different assignees (with no adjustments for mergers and acquisition activity, subsidiaries, or spelling variations). Roughly 63% are assigned to private firms (see figure, above). Of the top ten gene patent assignees, nine are U.S.-based, including the University of California, Isis Pharmaceuticals, the former SmithKline Beecham, and Human Genome Sciences. The top patent assignee is Incyte Pharmaceuticals/Incyte Genomics, whose IP rights cover 2000 human genes, mainly for use as probes on DNA microarrays.
Gene patents are not unequivocally a problem -- they have benefits and costs. But there is at least one sense in which the patent grab may not be such a good idea. From the NG article:
"You can find dozens of ways to heat a room besides the Franklin stove, but there's only one gene to make human growth hormone," said Robert Cook-Deegan, director of Duke University's Center for Genome Ethics, Law, and Policy.
"If one institution owns all the rights, it may work well to introduce a new product, but it may also block other uses, including research," he said.
In five or ten years when somebody tries to market a "tricorder"-like device that can spontaneously probe a person's genome for any known genetic variant, what happens when all these companies and universities try to enforce their DNA microarray patents on each variant?
References:
Jensen K, Murray F. 2005. Intellectual property landscape of the human genome. Science 310:239-240. Full text (subscription)
Genes for the masses
The Boston Globe has a story about geneticist George Church and his quest to bring whole-genome sequencing below $1000.
Church knew that a key to making gene sequencing fast and affordable lay in miniaturizing the process. He coats a slide with millions of microscopic beads, each impregnated with chemicals that light up when exposed to DNA base pairs. A digital camera fitted to a microscope photographs the pattern, and software decodes the results. His process is more than 250 times faster than conventional technology. In short, rather than take seven years to sequence the human genome, Church's machines can theoretically do it in less than a week. He says "theoretically" because he and his students have only decoded the DNA of E. coli, which is 1/1000th the size of the human genome. Based on his current costs, he thinks he could decode a human genome for about $2.2 million.
I wrote about this technology last year, but the Globe article is pretty informative about the work behind it.
And it has this hint:
Meanwhile, at least half a dozen well-funded labs across the country are shooting for that $1,000 target. One, a Connecticut firm called 454 Life Sciences that runs a somewhat different microscopic technology, rivals Church's so closely that no one can predict who will reach the goal first.
My question is, why are they shooting for $1000? It seems to me that if you can go from $2.2 million to $1000, it won't take very much longer to go to $100, or even less. The materials cost and computational resources certainly won't cost that much in volume.
They are framing the cost in terms of the cost of a personal computer, but it wasn't so long ago that the "accepted" cost of a PC was over $3000, and now most buyers spend a lot less than $1000. So that's arbitrary too.
My guess is that the magic $1000 figure that keeps getting quoted is an attempt to prime insurers to expect that billing amount when the process becomes common. The question is not how much you would pay for a genome, but how much an insurance company would pay on your behalf. A lot of diagnostic procedures approach that billing amount, so it is a convenient pricing hook.
If I'm right, then you can place the $1000 genome in the same category as MRI scans and X-rays, neither of which is priced at what it is worth in materials or energy, but in terms of amortization of equipment and expert interpretation.
Except for genome sequences, the fixed investment may be a whole lot less than for any radiographic equipment. After all, with an MRI machine, you have to have it on site (in the basement, since no floor can hold it!), and you can only run people through at a slow rate. More patients per hour and you need more machines.
With genomes, you can always send material away to a central lab -- it doesn't have to be on site, and with enough miniaturization and automation there may be no hard limit on the speed of sequencing.
What we are not seeing is much in the way of justifying the value of the genome sequences in terms of medical cost savings. So far, the benefits are purely hypothetical -- if you know your alleles, you can take measures to prevent disease early, or you can avoid harmful drug interactions, etc.
So far, "personalized medicine" is a race where the only competitors want to add drugs (or other patented compounds) to the normal regimen of people we now consider healthy. The promise is that this addition will evade problems later in life.
But what would be really nice (and quite possibly necessary given the explosion in health costs) is for genomes to decrease the cost of medical care. Know your genome, and avoid expensive problems. Or other unnecessary tests.
Maybe a long life of taking cheap prophylactic drugs will save many expensive hospital stays in the long run. Maybe enough harmful drug interactions will be avoided to create net savings.
But I'd like to see the other competitors in the race, if there are any.
Hepatitis B and sex ratio at birth in Asia
After yesterday's post on sex selection, a reader sent me a link to a BusinessWeek article from earlier this year that discusses a new hypothesis for the elevated proportion of males in many populations:
Many people think the reason [for reduced female birth ratio] is abortion and the killing of newborn girls. But new research suggests another reason. Harvard economist Emily Oster, in her PhD thesis "Hepatitis B and the Case of the Missing Women," suggests that biology explains a good deal of the missing-women puzzle.
The idea is that hepatitis B infection appears to affect sex ratio at birth among infected vs. noninfected people:
There is much evidence that parents infected by HBV are more likely to have male children. Places with substantial HBV -- Asia, Alaska, and parts of the the former Soviet Union -- tend to have high male-female birth ratios. Studies in Greece and France show that HBV-positive parents had male-female ratios for offsprings of 1.7 to 1.8, vs. 1.1 to 1.2 for those who are HBV-negative. This pattern also shows up among immigrants, with those from high HBV areas, such as China, having high male-female offspring ratios in the U.S.
The biological explanation for the HBV effect is unclear, though it may involve more frequent spontaneous abortion of female fetuses. But the effect is large, concentrated in certain regions, and susceptible to elimination via the HBV vaccine. In Alaska, the use of the HBV vaccine in 1982 led to a sharp decline in high male-female birth ratios.
Among Asian countries, the HBV influence is greatest in China, explaining 75% of Coale's missing women. In India, the adjustment is less important, explaining only 17%. For Asian countries in general, Oster locates 46% of the absent women, ending up with 33 million missing, rather than Coale's 60 million or Sen's 107 million.
The research paper is available online.
This post by Peter Gallagher (no not the While You Were Sleeping actor) raises some skepticism about Oster's conclusions. Although the argument accepts that hepatitis B may explain some of the effect, it gives some reasons to think the influence of hep B is not as strong as Oster predicts.
You may also notice the BusinessWeek column is by a Harvard economist hyping the Ph.D. thesis of new Harvard economics graduate! But there are more interesting reasons for nepotism favoring this particular graduate student, the child of two economists. This Slate article by the Freakonomics guys tells the story with a fascinating connection at the end:
In the early 1980s, a group of psychologists and linguists banded together to write Narratives From the Crib, a study of how children acquire linguistic skills. Narratives was built around the speech patterns of one child, a 2-year-old girl. Her parents had noticed that she often talked to herself in the crib after they said good night and left her room. They were curious to know what she was saying, so they began to record her chatter. They turned on the tape recorder while they were tucking her in and then left it running. Eventually they gave the tapes to a psychologist friend, who shared it with her colleagues. The big surprise to these experts was that the girl's speech was far more sophisticated when she was alone than when she was speaking with her parents. This finding, as Malcolm Gladwell would later write in The Tipping Point, "was critical in changing the views of many child experts."
The 2-year-old girl in question was referred to as Baby Emily. Her full name? Emily Oster.
Human Genome Project afterglow
I was reading The Scientist because RPM sent me to this article, titled "The Human Genome Project +5".
And yet the last five years, in Olson's view, have been "a period of a great grinding of gears, kind of shifting of gears." In the terms of the science historian Thomas Kuhn, it's been "a period of consolidation and more normal science." Others, such as Sydney Brenner of the Salk Institute, the Nobel Prize-winning pioneer of the worm, Caenorhabditis elegans, go further, worrying that the genome sequence and the growing lists of sequences and proteins and protein interactions and functional elements don't get very deep into such core problems of biology as the operations of the cell, of development from egg to adult, or the problem of consciousness. "We've become very geno-centric," says Brenner. "The cell must become the focus."
I would say this is pretty much correct -- there has been a long period of normal science in genetics lately, with new findings pretty much following one after another. There have been no revolutions coming out of the HGP.
But I think this scale of examination is a bit misleading. The HGP opened the deep end of the data pool, and we are still swimming in the toddler tank.
Consider what is happening in terms of new data:
One of the most dramatic efforts to push genomics into the realm of complex, multi-genic diseases is the five-year, $138 million haplotype map (HapMap) project, involving samples donated by Japanese, Han Chinese, Yoruba, and Americans of European descent. The project takes advantage of the fact that the millions of single nucleotide polymorphisms (SNPs) found in at least one percent of humans tend to pass between generations in blocks of DNA called haplotypes. The project announced its Phase 1 analysis in October 2005, and said that the analysis of Phase 2, already completed, would be published in 2006. Despite successes, such as using HapMap data to pinpoint a gene for macular degeneration, there remains controversy over HapMap's reach into domains such as rearrangements like deletions and reversals, or the numerous rare mutations that may be involved in diseases.
The minor variations are of central interest to Bentley of Solexa, who has specialized in rare variations. The HapMap, he says, has limitations, capturing only common variations in three target populations, missing the rare mutations. But it may provide a quick way to find more disease genes. Still, in three to five years, he says, the new sequencing machines should open the option of going after virtually all the many genes involved in a disease like diabetes. To be sure, the multiple sequences of patients and "controls" will have to square with what HapMap has found. "Everything that a HapMap captures should also be captured by a technology that aims to do better." Bentley, an early proponent, calls the HapMap "a real benchmark."
There seems to be a "Moore's law" for genome sequencing:
The workhorses of the 2001 human drafts have kept doubling their throughput about every 22 months over 15 years. In September, 454 reported that, in a single run, its system did a shotgun sequence and assembly of the microbe, Mycoplasma genitalium, in four hours. Claire Fraser's team at the Institute for Genomic Research took three months to work out Mycoplasma's sequence in 1995.
And there are gene expression microarrays and microRNA assays, as described in the article. For people who want to know about gene activity at every stage of life, in every type of cell, and in response to every external stimulus, the tools are in place to figure those things out.
As for myself, I think the accumulating data will have some revolutionary effects. These won't be in genetics itself -- I think the paradigms in place now in terms of gene interactions and regulation are very powerful. No doubt some new twists in gene sequence and function will be found, but I would guess that the current picture will expand rather than being overthrown.
But for other fields, I think genetics has some revolutionary power. Obviously genomic medicine has the potential to radically change the way we approach chronic conditions. And metagenomics is already changing the way biologists study microbial communities in all kinds of environments. It wouldn't surprise me if scientists working in places like the Foja Mountains work with DNA tag samples before they do traditional taxonomy on new species.
What will happen to anthropology as a result of the HapMap? There are surprises in store...
Mozart and mammoth metagenomic manipulation
OK, I just think the Mozart skull DNA extraction is creepy. Not because identifying dead skulls is creepy in itself -- hey, I like forensic anthropology a lot more than the random person on the street.
No, I think it's creepy because of the mammoths. I got ahold of the mammoth DNA paper by Poinar and colleagues a couple of weeks ago; it's on Science Express.
Can I just say, Science Express is super-lame? I mean, a subscription wall inside a subscription wall!
The paper, on the other hand, is decidedly not lame. Here is the abstract:
We sequenced 28 million base pairs of DNA in a metagenomics approach using a woolly mammoth (Mammuthus primigenius) sample from Siberia. Thanks to exceptional sample preservation and use of a novel emulsion polymerase chain reaction and pyrosequencing technique, 13 million base pairs (45.4%) of the sequencing reads were identified as mammoth DNA. Sequence identity between our data and African elephant (Loxodonta africana) was 98.55%, consistent with a paleontologically based divergence date of 5 to 6 million years. The sample includes a surprisingly small diversity of environmental DNAs. The high percentage of endogenous DNA recoverable from this single mammoth would allow for completion of its genome, unleashing the field of paleogenomics.
Of course, they were helped a lot by the unique preservation in the sample, which was found in optimal cold conditions at the shore of Lake Taimyr. That probably cut down substantially on extraneous microbial and fungal DNA.
But the metagenomic approach makes these kinds of contaminants mostly irrelevant. In metagenomics, researchers sequence every last piece of DNA in a sample, and then figure out what all the pieces are by comparing them to genome databases. What you get is illustrated by this pie chart:
Proportion of DNA sequence from different sources in the mammoth sample of Poinar et al. (2006).
There are two beautiful things about this graph. One is that, although there happens to be a lot of mammoth DNA in the sample (over 50 percent), there doesn't have to be. The fact is, it doesn't really matter how much of the original stuff is there or how much junk there is; if there is any minimal level of DNA preservation from the original beast, you are going to be able to find it.
The other beautiful thing is that the ability to recognize sequence is determined not by your own work on a fossil, but by the completeness of genome databases. This means that unknown sequences just sitting on your computer after an extraction gradually, inexorably, will be identified when science gets around to sequencing the organism they came from. The 18.42 percent "unidentified" in the graph will slowly reduce over time. Now, almost none of that will be mammoth-relevant information, but it's still pretty cool.
There are two problems. One is, if the DNA preservation is poor, you are going to have to grind through an awful large amount of bone to get any kind of good genome coverage. In this case, a small sample of mammoth bone was sufficient to sequence 13 million base pairs of mammoth DNA. But there might or might not be anything interesting in those 13 million base pairs. It is certainly possible to sequence more from more samples, and that is the point: if preservation was not as good as in this particular sample, you would have to mill major mammoth mandible to get a full genome sequence.
For mammoths, I don't see that as much as a problem. Remember the Explorers' Club, after all. I imagine a large woodchipper in some DNA lab standing ready to chomp the frosty mammoth meat.
For hominids, that will be a bit more troubling. Will we be willing to put an entire skull in the blender for a complete Neandertal genome? Or if Neandertals are well-enough preserved and we are willing to settle for less-than-full genome coverage, what about more ancient or more marginally preserved fossils, like an Atapuerca femur? Does a genome have more scientific value than a fossil object itself, if we can preserve its anatomical detail with microCT or other techniques?
Then there's the other problem: degradation. How good is the sequence? Even in the exceptionally well-preserved mammoth sample, there was substantial evidence for degradation of sequence, with around twice the number of expected C -> T transitions compared to elephant and a third or so more G -> A transitions. That's an awful lot of potential noise for anyone looking at gene function and evolution. I'm guessing what will have to be done is to simply ignore certain classes of mutations that are likely to derive from postdepositional diagenesis (that is, DNA rot). Even so, some remaining diagenetic changes will remain hard to figure out.
The best approach may be to simply grind up more bone; making sure that each genome section is covered by multiple copies. The multiple copies allow for error correction, since it is relatively unlikely that any single diagenetic change will occur in multiple copies of a gene. The really, really good news is that given enough sample, we are very likely to get accurate genome sequences from ancient humans.
But the whole thing raises a fairly hairy problem concerning fossil humans. It's like that commercial with the owl and the Tootsie Pop -- how many samples does it take to get the genome? CHOMP!
So what about Mozart?
Something we can do to a Neandertal, we can certainly do to bones from any historical figure. The Mozart genome, the King Tut genome, the Lincoln genome, the John Wilkes Booth genome -- we can have them all!
Today, you can have your Y chromosome sent away to find out if you are a descendant of Genghis Khan. Tomorrow, you'll be able to compare every one of your genes to Mozart. In all likelihood, some genetic variants will be associated with musical talent. The obvious next Austrian TV special will be the Mozart genotypes for any music-related genes. The less obvious step will be screening your young Julliard candidate for genetic similarity to Mozart.
There's no way Mozart can cash in on the process. But what about living celebrities, or athletes? Subscribe to iGenes and you can find out whether your kid's genes might give him the chops for the NBA (with proper work and training, of course) or whether he should start hitting the links instead.
That's what I find creepy. And there are an awful lot of composers buried in well-known locations that could be dug up for genetic comparisons.
References:
Poinar HN et al. 2006. Metagenomics to paleogenomics: large-scale sequencing of mammoth DNA. Science (online early) doi:10.1126/science.1123360.
How much sex selection is there?
I discuss biotechnology and society in my genetics course, and today I wandered across this working paper discussing sex control of offspring, including selective abortion in the US and abroad, preimplantation and prefertilization screening, and possible future effects of the technologies. I'm noting it here because of its inclusion of some numbers:
Even in just the short time that these various methods of sex control have been available, they have had dramatic effects on sex ratios in many parts of the world. Generally, any variation in the sex ratio exceeding 106 boys born per 100 girls born can be assumed to be evidence of sex control. Here are just a few examples of skewed sex ratios around the world today (most recent figures provided). The sex ratio in Venezuela is 107.5, in Yugoslavia 108.6, in Egypt 108.7, in Hong Kong 109.7, in South Korea 110, in Pakistan 110.9, in Delhi, India 117, in China 117, in Cuba 118, in the Caucuses nations of Azerbaijan, Armenia, and Georgia, the sex ratio has reached as high as 120. While the sex ratio in the United States has remained stable at 104.8, certain American ethnic groups have seen a statistically significant rise in their sex ratios. In 1984, the sex ratio for Chinese Americans was 104.6 and for Japanese Americans 102.6; in 2000, these ratios had risen respectively to 107.7 and 106.4 (citation elided).
On the subject of commercial application of sex control technologies, there is this:
Today, sex-control services are openly advertised on the Internet, and sex control could in the future become a big business. Here's how Fortune magazine recently summed up at least the potential market for MicroSort alone: "Each year, some 3.9 million babies are born in the U.S. In surveys, a consistent 25 percent to 35 percent of parents and prospective parents say they would use sex selection if it were available. If just 2 percent of the 25 percent were to use MicroSort, that's 20,000 customersÉ. [and] a $200-million-a-year business in the U.S. alone." (Wadman M, "So you want a girl?" Fortune, Feb. 9, 2001)
And I was actually quite taken by this almost poetic evocation of parenthood:
The salient fact about human procreation in its natural context is that children are not made but begotten. By this we mean that children are the issue of our love, not the product of our wills. A man and a woman do not produce or choose a particular child, as they might buy a particular brand of soap; rather, they stand in relation to their child as recipients of a gift. Gifts and blessings we learn to accept as gratefully as we can; products of our wills we try to shape in accordance with our wants and desires. Procreation as traditionally understood invites acceptance, not reshaping or engineering. It encourages us to see that we do not own our children and that our children exist not simply for our fulfillment. Of course, parents seek to shape and nurture their children in a variety of ways; but being a parent also means being open to the unbidden and unelected in life (emphasis in original).
I think that pretty much sums up my feelings about children.
Yet it is one way of looking at the issue that comes into direct conflict with other cultural forces, such as the intense pressure to have a son, at least for many families. Those pressures differ with different cultural backgrounds, but they are pretty much present at some level everywhere. People's attitudes about biotechnology ultimately reflect deep cultural divisions between different -- sometimes irreconcilible -- goals (via Althouse).
UPDATE: This later post discusses the alternative hypothesis that the elevated male sex ratio in many populations may be explained by hepatitis B infection rates. That hypothesis came after the 2003 working paper discussed in this post, and the issue at present seems to be unresolved.
Another reason for paranoia about genetic testing
I'm usually very skeptical of claims that widespread DNA testing will result in bad effects -- "Big Brother" finding out your genotype and discriminating against you, for example. A lot of people are afraid of it, but there has been a lot of unnecessary scaremongering.
But today I read this New Scientist story by Alison Motluk:
Anonymous sperm donor traced on internet
LATE last year, a 15-year-old boy rubbed a swab along the inside of his cheek, popped it into a vial and sent it off to an online genealogy DNA-testing service. But unlike most people who contact the service, he was not interested in sketching the far reaches of his family tree. His mother had conceived using donor sperm and he wanted to track down his genetic father.
Now, that doesn't sound so bad, does it? The biological father must have also submitted his DNA to some genealogy database, which came up as a match, right?
Wrong!The boy paid FamilyTreeDNA.com $289 for the service. His genetic father had never supplied his DNA to the site, but all that was needed was for someone in the same paternal line to be on file. After nine months of waiting and having agreed to have his contact details available to other clients, the boy was contacted by two men with Y chromosomes closely matching his own. The two did not know each other, but the similarity between their Y chromosomes suggested there was a 50 per cent chance that all three had the same father, grandfather or great-grandfather.
Importantly, the men both had the same last name, albeit with different spellings. This was the vital clue the boy needed to start his search in earnest. Though his donor had been anonymous, his mother had been told the man's date and place of birth and his college degree. Using another online service, Omnitrace.com, he purchased the names of everyone that had been born in the same place on the same day. Only one man had the surname he was looking for, and within 10 days he had made contact.
The implication is very simple: no one is anonymous. Suppose you let your DNA slip anywhere. Everyone does to the tune of 36 million cells per day, not to mention the occasional lucky sperm. Now if one of your relatives is careless enough to have his name and DNA sequence associated in a public database, then your entire genetic profile may be available to anyone who's interested.
This seems like a pretty simple way to find out the surname of any unknown DNA sample you might have. Most relatively common US surnames already have entries at one or more genealogy registry. If a motivated fifteen-year-old can do it once, the CIA can certainly do it indefinitely many times. All that is needed is for somebody to want to find you.
Better not give them a reason.
Venter patents synthetic life?
Jocelyn Kaiser writes:
The work involves a simple bacterium called Mycoplasma genitalium that Venter's eponymous institute in Rockville, Maryland, has been tinkering with for years. An early goal was to determine the minimum number of genes for life, and in 1999, scientists there published a rough tally. Now, they want to synthesize this "minimal genome" from scratch, get it working inside a cell, then add genes that would enable the bug to crank out hydrogen or ethanol to produce cheap energy (Science, 14 February 2003, p. 1006). The Venter Institute describes this plan in a patent application filed last October and published on 31 May by the U.S. Patent Office.
The ETC Group, a technology watchdog group based in Ottowa [sic], Canada, is alarmed. They compare Venter's plans to patent a platform for building designer microbes to Microsoft's domination of personal computer software, suggesting that it's "the start of a high-stakes commercial race to synthesize and privatize synthetic life forms." ETC is calling for Venter to withdraw the application and for the U.S. and international patent offices to reject it so that societal implications can be considered.
World Science also has a writeup that includes this Venter quote:
"If we made an organism that produced fuel, that could be the first billion- or trillion-dollar organism," said Venter in the June 4 issue of Newsweek magazine.
On the one hand, there's nothing all that unusual about this -- it's already routine to patent strains or organisms based on recombinant DNA. The synthetic bacterial platform may produce greater license fees, since anyone who wanted to develop an application would have to buy a license. But it's not fundamentally different from the status quo.
On the other hand, Venter is starting to seem a lot like that creepy guy in Blade Runner who owns the android-making corporation. You know, the guy with the Coke-bottle glasses who has his office in the big sunny pyramid building. Except, with Venter it's a boat.
Zimmer on bioinformatics
Carl Zimmer has a very nice post describing recent work in bioinformatics, with a view toward explaining what the field is and how it works.
Here's a quote:
The classic method for figuring out what a gene is for is good old benchwork. Scientists use the gene's code to generate a protein and then figure out what sort of chemical tricks the protein can perform. Perhaps it's good at slicing some other particular protein in half, or sticking two other proteins together. It's not easy to tackle this question with brute force, since a mystery protein may interact with any one of the thousands of other proteins in an organism. One way scientists can narrow down their search is by seeing what happens to organisms if they take out the particular gene. The organisms may suddenly become unable to digest their favorite food or withstand heat, or show some other change that can serve as a clue.
Even today, though, these experiments still demand a lot of time....
This dilemma has helped give rise to a new kind of science called bioinformatics. It's an exciting field, despite its woefully dull name. Its mission is to use computers to help make sense of molecular biology--in this case, by traveling through vast oceans of online information in search of clues to how genes work.
Better meat through science
Paul Elias of the AP reports on how geneticists are trying to make tastier hogs:
Even before the pig genome is completed sometime next year, top commercial producers such as Pig Improvement Co. and Monsanto Inc. are using preliminary results from genetic screens to see if they can determine which pigs are the tastiest before they are butchered. The screens will also be used to manage herds and make breeding decisions, among other improvements.
"They can now look inside the pig," Rothschild said. "They are both building better pigs with this technology."
Cattle, too:
Minnesota-based Cargill Inc., which supplies about 20 percent of the nation's beef, is working on a genetic screen to sort its cattle by the quality of their meat, something that can't be done now until the animal is slaughtered.
Cargill is testing the screen on 30,000 of its cattle. If it works, the company can reserve the best feed and care for its prime beef producers, or ensure that the best animals mate with each other.
The idea is that you eliminate a lot of guesswork by having direct genetic assays for alleles that correlate with meat quality -- instead of selecting indirectly through the observed qualities of genetic relatives.
Most people aren't aware of how much math goes into breeding science -- and this article isn't all that helpful, calling it an "art". It's probability theory, not an art!
In any event, genotyping is a way to raise certain probabilities, and in so doing cuts out a lot of math. It's just ironic that it takes computer screening to help us make meat taste better!
Breastfeeding via rice
On the topic of biotechnology, this AP article describes Ventria Bioscience's field tests of rice altered with a human gene:
Ventria, with 16 employees, practices "biopharming," the most contentious segment of agricultural biotechnology because its adherents essentially operate open-air drug factories by splicing human genes into crops to produce proteins that can be turned into medicines.
Ventria's rice produces two human proteins found in mother's milk, saliva and tears, which help people hydrate and lessen the severity and duration of diarrhea attacks, a top killer of children in developing countries.
Critics say that the practice of farming these genetically modified plants in the open air may "contaminate" conventional crops; the company argues that rice is self-pollinating and the spread of the gene is virtually impossible.
The potential payoff is interesting. The idea is that the protein, expressed in human breast milk and saliva, will help to fight diarrhea, particularly in infants and children. From a PR standpoint, of course that brings in the concept of helping children in developing countries, which has been such an effective argument in favor of the so-called "golden" rice enriched with vitamin A.
But from the article it appears that the company has a bigger market in mind:
Ventria hopes to add its protein powder to existing infant products. There is no requirement to label any food products in the United States as containing genetically engineered ingredients.
The company also has ambitious plans to add its product to infant formula, a $10 billion-a-year market, even though the major food manufacturers have so far shown little interest in using genetically engineered ingredients. But Deeter says Ventria can win over the manufacturers and consumers by showing the company's products are beneficial.
"For children who are weaning, for instance, these two proteins have enormous potential to help their development," Deeter said. "Breast-fed babies are healthier and these two proteins are a big reason why."
I think parents will buy it, and it might well be an improvement on regular infant formula -- which lately has been getting various kinds of protein additives to make it "more similar" to breast milk.
So, it's dog corn next.
Amy Harmon explains some dog genetics in the NY Times today, in an article focused on whippets. The problem is that undesirable characteristics of some breeds are homozygote recessives for alleles that the breeders have been strongly selecting:
FORT MOTT STATE PARK, N.J. — When mutant, muscle-bound puppies started showing up in litters of champion racing whippets, the breeders of the normally sleek dogs invited scientists to take DNA samples at race meets here and across the country. They hoped to find a genetic cause for the condition and a way to purge it from the breed.
It worked. "Bully whippets," as the heavyset dogs are known, turn out to have a genetic mutation that enhances muscle development. And breeders may not want to eliminate the "bully" gene after all. The scientists found that the same mutation that pumps up some whippets makes others among the fastest dogs on the track.
They're going to apply genetic screening to eliminate the "bully" whippets, although the article doesn't explain just how. I suppose, they will use DNA screening results to decide to breed only heterozygotes with homozygote dominants, yielding a 50-50 chance of fast-running heterozygote offspring. But it seems to me, the breeders are just as likely to mate a bully with a slow homozygote dominant, getting 100 percent heterozygotes as a result.
It's like hybrid corn, except with dogs!
In fact, if they could make purebred lines for three or four alleles at a time, they would really vastly improve their ability to breed for fast dogs by hybridizing.
It's interesting how people find it much more disturbing to have a categorical difference between to individuals (like an allele) instead of a continuous difference. I mean, speed is a continuous variable, and we all know that different people vary in how fast they can run. This has been an unremarkable fact since the beginning of time. But somehow when genes get involved, people get all funny about it:
"It would be extremely interesting to do tests on the track finalists at the Olympics," said Elaine Ostrander, the scientist at the National Institutes of Health who discovered that the fastest whippets had a single defective copy of the myostatin gene, while "bullies" had two.
"But we wouldn't know what to do with the information," Ms. Ostrander said. "Are we going to segregate the athletes who have the mutation to run separately?" For the moment, it is whippet owners who find themselves on the edge of that particular bioethical frontier.
It was not exactly news to breeders that speed is an inherited trait: whippets were developed in the late 1800s specifically for racing. But knowing that one of her dogs was sired by a carrier of the gene, said Jen Jensen, a whippet owner in Fair Oaks, Calif., makes its championships seem "less earned." Ms. Jensen's suggestion that a DNA test be required for all dogs and that the fastest ones without the mutation be judged and raced separately, however, has not gone over well.
I suppose the disquieting part is that genetics somehow reduces everything to simple mathematics. Keeping two strains of loser dogs for crossbreeding really fast ones will take away from the stuff about "spirit" and "magic":
Even those who want to exert more direct control over dog DNA, however, agree that no genetic test can predict the intangible qualities that make a dog great.
If a dog does not have the spirit to run a race, it is not going to win, said Betsy Browder, a whippet owner in College Station, Tex.
"'Keenness' is what we call it," she said. "Just like you can have a human athlete who's really lazy, and all the genes in the world aren't going to help."
Yeah, until they find the gene for that, too.
This stuff about separating out the human athletes by genotype is nonsense. There will always be this problem -- is it an athlete's training or gene X? Or as-yet-unknown-effect gene Y? Or gene Z in combination with her genetic background? Is it fair? I suppose that depends on the other consequences of genes X, Y and Z, and the entire genetic background. Which is the same question as, "Is life fair?"
At the moment, training discrepancies are quite a bit greater than most (though not all) genetic differences between athletes. But that won't remain true forever -- eventually, all credible competitors will have the same training -- or at least training that they believe to be the same. The training may even be specialized for their genotype. All they're doing is substituting one kind of variance (environmental) for another (genetic).
The only thing fairer is flipping a coin at the start of each race. Maybe some of them will want to trade, but I doubt it.
Frankencotton on the roll
Now, I hadn't considered this:
How would the world feel, how do you feel, knowing that at the moment you are reading this you may be wearing transgenic underpants?
Happily, the New York Times has me covered. No, not that way!
Yes, it's that kind of story.
Despite some opposition to genetically modified crops, even ones not grown for food, Frankencotton has been so successful that it is now grown all over the world, including the United States. It is particularly popular in Asia.
According to a recent report in The Proceedings of the National Academy of Sciences by researchers at the University of Arizona, farmers who grew Bt cotton reduced their use of pesticides and increased the diversity of their insect populations, while protecting crops against the dread pink bollworm.
A similar genetic modification in corn has caused an uproar. Many countries have rules about labeling food that contains genetically modified organisms, or G.M.O. Zambia, for instance, has refused to import transgenic corn. But cotton has faced no such trade barriers.
The obvious reason is that people tend not to eat their shirts.
Plant drug introgression
This is a nice little article in the times by "collaborative problem solving" director Denise Caruso
A NEW generation of genetically engineered crops that produce drugs and chemicals is fast approaching the market -- bringing with it a new wave of concerns about the safety of the global food and feed supply.
The plants produce medicinal substances like insulin, anticoagulants and blood substitutes. They produce vaccine proteins for diseases like cholera, as well as antibodies against tooth decay and non-Hodgkin's lymphoma. Enzymes and other chemicals from the plants can be used for a range of industrial processes.
As in past debates over genetically modified crops, biotech developers say that the benefits outweigh the risks, and that the risks are manageable. Critics question the benefits, and say the risk of a contaminated and potentially toxic food supply is untenable.
Ellstrand was a good expert to interview -- I included several of his articles in my introgression bibliography -- and his points seem like the most relevant ones:
"I don't think that engineering plants for pharma is a bad idea, with two caveats," Professor Ellstrand said. One, he says he thinks that planting should be done in greenhouses rather than in open fields. "The other issue is food," he said. "Why do we have to do this in food crops? It doesn't matter what you're squeezing the compound out of. It could be a carnation, a corn plant or a castor bean."
That last seems like a good point: why not switchgrass or something? I suppose that the real answer to this question is that there is lots of farm equipment that is designed to deal with the seeds of existing agricultural crops, making the economics of these plants much more appealing than non-food plants. But there probably is some compromise crop that would suit this concern.
Maybe they could find a way to make drugs in plants destined for ethanol -- two birds with one stone.
Global biopharming
Planting time has arrived in most of the country -- even here in zone 4 -- so you may be reading those seed packets carefully. This paragraph may catch your attention:
One anti-biotech group even managed to bamboozle some seed companies that cater to home gardeners into signing on to something called the Safe Seed Pledge: "We pledge that we do not knowingly buy or sell genetically engineered seeds or plants." This is fascinating because, with the sole exception of wild berries and wild mushrooms, all the fruits, vegetables and grains in North American and European diets have been genetically modified or engineered by one technique or another. This even includes 'heirloom' varieties of fruits and vegetables. Often, this genetic modification has involved radical changes at the level of DNA, including the movement of genes or even entire chromosomes across natural breeding barriers.
That's from a TCS Daily column by biotechnology analyst Henry Miller. This is a point that constantly amazes me -- do people not realize that it is unnatural to have purple potatoes and zebra-striped tomatoes, and all other manner of garden mutants? That, for the most part, it is unnatural for vegetables (i.e., non-fruit and non-seed plant parts) to be tasty and delicious? Plants don't want you to eat them!
Most of the column is devoted to reviewing some of the misleading parts of a recent report on international biotechnology trends by the Organization for Economic Cooperation and Development. It's a fair critique, but a little dry for light reading. Certainly it's valuable to have critics go through definitions in these international reports, because so much of the conclusions are essentially determined by the assumptions that go into compiling lists. Some countries look different than others, just because their regulatory agencies define things in different ways.
I approach this issue from the perspective of teaching the debate in my genetics course, and also as a way to examine how the debate around human genetic engineering may be framed in the future. After all, franken-people are bound to be a lot more interesting than franken-food.
Not to mention the possibility of Neander-people -- or, dare I suggest, NEANDER-FOOD!
I find the trend toward GMO production of pharmaceuticals to be a very interesting angle in the current biotechnology scene, because of the clear resonance of the issues with human genetic alteration. Both the opposition and promotion of GMOs have both involved heterogeneous groups of interests. Much of the muscle behind both positions has come from agriculture industry groups -- So far, the critics of GMO deployment have been successful when they frame their opposition in terms of risk of introgression into non-GMO crops or wild plants. They have also had success with the "natural food" frame.
A month or so ago, I referred to an article that discussed the potential of introgression by plants genetically engineered to produce pharmaceutical compounds. Quoted in the article, Norman Ellstrand asked, why not modify non-food plants, and thereby eliminate all risk of consumption?
In his article, Miller gives an answer to this question:
Although there is substantial and growing acreage of gene-spliced crops cultivated worldwide each year - 252 million acres in 2006 - more than 90 per cent of it is four large-scale commodity crops; largely because of the huge costs of meeting regulatory requirements, the application of the technology to fruits, vegetables and subsistence crops has been minimal, and disappointing.
In short, it is easier to get approval for altering one of the four major food crops, because they have a research history and are already grown on a immensely large scale. Introducing genetic modification on another kind of plant requires much more work to conform to regulations.
There is also the issue of a less-recognized mode of genetic modification; namely, Simpsons-style:
Currently, dozens of genetically improved varieties that are produced through hybridization, irradiation and other traditional methods of genetic improvement enter the marketplace and food supply each year without any governmental review or special labeling. A technique in use since the 1950s, induced-mutation breeding, involves exposing crop plants to ionizing radiation or toxic chemicals to induce random genetic mutations. These treatments most often kill the plants (or seeds) or cause detrimental genetic changes, but on rare occasions the result is a desirable mutation. For example, a mutation might produce a new trait in the plant that is agronomically useful, such as altered height, more seeds, larger fruit or enhanced resistance to pests.
On a large scale, these random mutations pose more potential of introgressing into wild plants, because they don't carry the baggage of a plasmid, and they might have unknown beneficial side effects on plant fitness. Plus, a strain bearing many random mutations might have some unintended ones along with the one that is strongly selected by subsequent breeding. This kind of induced-mutation breeding is really nothing more than ordinary breeding sped-up a little faster, but then, the only thing making trans-species gene transfer different is that you know in advance that the inserted gene works in some other organism.
In a previous column, Miller argued against legislation being considered to regulate the farming of gene-spliced plants in California. At the same time, he points out the harmful consequences that sometimes result from conventional breeding:
This measure is pointless. In the production of new plant varieties using conventional - that is, pre-gene-splicing - techniques, breeders, farmers and food producers lack knowledge of the exact genetic changes that produced the useful traits. More important, they have no idea what other changes have occurred concomitantly in the plant -- including those that could alter the ability to cause allergic reactions.
...
Only the molecular, gene-splicing methods allow breeders to identify and fully describe the changes that have been made in the progeny, so perhaps it isn't surprising that only the imprecise, trial-and-error techniques of conventional plant-breeding methods have led to food safety problems. Two conventionally bred varieties each of squash and potato and one of celery were found to contain dangerous levels of endogenous toxins and had to be barred from commercialization. Such mishaps are far less likely when genetic changes are wrought with the more precise and predictable gene-splicing techniques.
The difference is not mainly that the trans-species genes are predictable in effect, but that they are introduced only a few at a time. This is less likely to cause incidental side effects than altering the frequencies of many genes by conventional breeding. The point is that anything that we change may generate bad side effects, and we want to find ways to minimize these. One approach is not to change anything. But since nature changes things for us anyway, maybe best to change with science...
The future of genetics is corny
Elizabeth Pennisi's story about maize genomics is a good reminder for why biology will continue to grow in importance toward our understanding of human history:
With $9.1 million from the Mexican government, Jean-Philippe Vielle-Calzada of the National Laboratory of Genomics for Biodiversity in Irapuato and his colleagues have decoded a native "popcorn" strain grown at elevations above 2000 meters. Although still in more than 100,000 pieces, the sequence has revealed many new genes, he reported. This variety's genome "will be of tremendous value in terms of understanding the evolution of [maize] domestication," he says.
Oh, and if you're interested in biology, consider the potential experiments from this:
Another resource introduced at the meeting will help ... sort out how genes interact. The agribusiness giant Syngenta announced it was making available 7500 lines of corn, each representing a B73 genome with a single piece of DNA bred into it from one of the 25 strains of the Maize Diversity Project. Taken together, the lines incorporate all the genetic diversity of those strains but make it easier to understand the activity of particular genes. The community has long awaited these tools, says Brutnell: "They are really going to revolutionize the way we do genetics."
I'd say. Imagine 7500 twins, all identical except for a unique piece of DNA spliced in from some other person. Except with corn, it's not 7500 twins, its 7500 experimental plots full of twins. Now, see what they all do!
References:
Pennisi E 2008. Corn genomics pop wide open. Science 319:1333. doi:10.1126/science.319.5868.1333
Grass on the run
Genetically engineered creeping bentgrass has been found growing miles from a test plot where it was planted two years ago, according to a NY Times story:
Two years ago, scientists at the E.P.A. laboratory in Corvallis, Ore., published a paper showing that pollen from a test plot of the grass had spread as far as 13 miles downwind, much farther than many had expected. That made it likely that genetically engineered grass would be found in the wild, though the scientists did not look for that.
In the new study, scientists sampled 20,400 plants up to three miles from the edge of an 11,000-acre zone surrounding the test plots. They found 9, or 0.04 percent, that were genetically engineered, the farthest being 2.4 miles from the control zone border.
The scientists said some of the plants had been created by seeds that had blown off the test plot and others by hybridization of wild grass with pollen from the genetically engineered grass. All were of the same species of grass being developed by Scotts and Monsanto.
I generally think genetic engineering of crops is a good idea, although I would prefer it not be used in the service of easier monoculture -- which these golf course grasses certainly are.
But articles like this always miss the point about the escape of plants or genes into wild populations. They tend to make it sound like the rate of escape is the limiting factor -- as if a low or "negligible" rate of escape will prevent gene flow to wild populations.
However, in reality it is the advantage or disadvantage an an introduced allele that determines whether it will spread or not. Wild populations are pretty well adapted, so in almost all cases an introduced allele (or gene) is likely to fail. But once in a while they may succeed -- especially if the gene is very different from alleles that might have arisen naturally (like moving genes from rice to corn), and if the trait is related to biotic resistance or drought tolerance or other ecological problems shared with wild plants.
And if an escaping gene begins with a few copies, it will take a long time to reach an appreciable frequency in the wild. In other words, the effects are long-delayed.
Unhappily, natural selection has no test plots for us to figure out in advance which genes will be adaptive in wild populations, and logic only takes us so far. So we're left with uncertain consequences, that may take a long time to manifest themselves.
I think in most cases, the risks of transgenic organisms are pretty minor compared to their economic benefits (which include feeding people who would otherwise be hungry). But it would be nice if other -- nonpatentable -- approaches to increasing production were getting some of the resources going into trangenic organisms.
Genetics versus energy costs
Either this continues today's Kansas theme, or this week's genetics theme. In either case, it's nice to see some attention to agricultural genetics and its growing connection to energy economics, in this Times article:
Like his father and grandfather before him, Mr. Kepley grows wheat. But energy costs that have quadrupled in three years, along with one of the worst droughts to grip the region in a century, have made it too expensive for him to irrigate. So today Mr. Kepley grows wheat under dry-land conditions, capturing rainfall for two years to make one year's crop.
"These are called semi-dwarfs," he said while surveying his burnt-looking wheat stalks one recent afternoon. âOur geneticist started developing this. Generally our wheat will be about knee-high when it is harvested. It doesnât use much energy in developing the stalks.â
The theme is that pumping water has become more and more expensive with increasing energy costs, and farmers are looking for improved draught-tolerant breeds to help compensate. It's not a cure, since productivity and diversification both are improved with irrigation, but it can be a more economical solution as irrigation becomes more expensive.
Ancient hair preserves DNA better?
That's the strand of this LiveScience article:
Contamination from bacteria DNA generally make up 50 to more than 90 percent of the raw DNA extracted from the bone and muscles of ancient specimens, [University of Copenhagen reseracher Tom] Gilbert said. In contrast, more than 90 percent of the DNA extracted from hairs taken from woolly mammoth specimens in the new study belonged to the extinct mega-mammals themselves.
It sounds like this might make a difference to forensic work:
The new study overturns previous assumptions about where in hair DNA could be harvested. "When people thought of sequencing DNA from hair, the usual assumption was that the material must come from the hair root, which contains recognizable cells, because the hair shaft appears to be dead," said study team member Webb Miller of Pennsylvania State University.
That reminds me, CSI starts its fall season tonight. As if I needed reminding...
No Neanderhair, unfortunately. Of course, if we had real live Neanderthals, like that show that starts next week, I'd be after them like the OSI guys after Jaime Sommers. Or we could just send Hiro back in time to get a sample...
If you want to clone a baby mammoth, for goodness' sake keep it frozen!
Nicholas Wade writes to answer the mammoth cloning question. I know, nobody cares about anything else. It's always, "Clone, clone, clone!"
Well, keep this in mind:
The reconstructed sequence of DNA units would then need to be turned into an actual mammoth genome. Mammalian genomes are made up of chromosomes of about 100 million DNA units in length and are beyond the capacity of current synthesis. Still, researchers at the Venter Institute in Rockville, Md., say they are close to synthesizing the genome of a bacterium that is 500,000 units long.
There's a lot of doing between a bacterium genome and a chromosome. Don't hold your breath.
And then, there's the picture:
Inspecting the baby mammoth carcass. Photo credit: Sergei Cherkashin/Reuters
Here's a piece of advice: If the room is warm enough for tank tops, it's too warm to preserve permafrost mammoth sperm.
No, that's not Henry Harpending. At least, I don't think it is...
The cloning of the bulls
Here's an AP story about cloning bullfighting bulls. Yes, I know, "bullfighting bulls" is redundant, but what else are you supposed to call them? I suppose corrida bulls.
The story adds to last year's discussion about horse cloning (horserace horse cloning?). But here the main theme is the affection that owners have for their bulls:
"I am extremely fond of this bull," del Rio said at his ranch in this town outside Madrid, watching 16-year-old Alcalde graze with some of his latest offspring -- mere toys next to their prolific, half-ton father. "He has given us tremendous satisfaction."
This has become quite the going concern:
ViaGen spokesman Ben Carlson confirmed the orders from del Rio and Fernandez, but would not comment on pregnancies or expected birth dates. Carlson said the breeders would pay standard cattle cloning prices: $17,500 for the first calf, $15,000 for the second, $12,500 for the third and $10,000 for the fourth and beyond.
ViaGen has cloned about 300 mammals, including show pigs, rodeo horses and bucking broncos, since its founding in 2002. But this is the world's first go at cloning the breed that takes on matadors in the deadly minuet of bullfighting.
The common strain between the bulls and the horses is the time you have to wait to see if your careful breeding made any difference:
Even in its traditional mode, bull breeding is a slow, hit-or-miss business. Studs are crossed with cows carefully selected for feistiness through simulated fights in the ring, albeit without bloodshed. Then the rancher has to wait a few years for the resulting bull to grow up, and see if it has the right stuff.
They're worried that the clones won't have the same qualities as the originals; calling it all an experiment.
Shining glowing people
Sarah-Kate Templeton of the London Times has reported that a Cornell University group created a genetically-modified human embryo:
The Cornell team, led by Nikica Zaninovic, used a virus to add a gene, a green fluorescent protein, to an embryo left over from in vitro fertilisation.
The research was presented at a meeting of the American Society of Reproductive Medicine last year but details have emerged only after the HFEA highlighted the work in a review of the technology.
Zaninovic pointed out that in order to be sure that the new gene had been inserted and the embryo had been genetically modified, scientists would ideally need to grow the embryo and carry out further tests.
The Cornell team did not have permission to allow the embryo to progress, however.
Another article about the work appears in the New York Times by writer Andrew Pollack:
But the researchers, at Cornell University, say they used an abnormal embryo that could never have turned into a baby.
"This particular piece of work was done on an embryo that was never going to be viable," said Dr. Zev Rosenwaks, director of the Center for Reproductive Medicine and Infertility at NewYork-Presbyterian/Weill Cornell hospital. He said the purpose of the work was stem cell research.
That did not stop some from criticizing the work, saying that the techniques being developed could be used by others to create babies with genes modified to make them smarter, taller, more athletic or better looking. They also said there should have been more public discussion.
"It's an important ethical boundary that scientists have been observing," said Marcy Darnovsky, associate director of the Center for Genetics and Society, a watchdog group in Oakland, Calif. "These scientists, on their own, decided to step over that boundary with no public discussion."
I don't really have any comments, but I wanted to point to these stories because I've been teaching a class that addresses these issues. Also, it strikes me that the opposition is poorly stated -- expressing an aversion to "smarter, taller, more athletic or better looking" children doesn't make much sense on its face.
One possible interpretation, that people may be forced to use such technologies if they want their children to remain competitive (the "private school" problem) won't carry much weight with most people, who don't feel such pressure now despite the many ways that people may invest in their children. Another, that such technologies may have "unforeseen side effects" (that is, the Frankenstein problem) doesn't argue against the technologies in general, it merely suggests an appropriate amount of caution.
Anyway, this discussion demands a longer post, and I just wanted to point to these articles.
They clone horses, don't they?
"Horse racing editor" Mike Brunker checks in with an excellent MSNBC article on cloning in the horse racing world. Racing officials are, so far, against it, but cloning solves a number of problems for owners and breeders.
Not least, what do you do when a gelding becomes a champion?
Among the cloned horses is Clayton, the 14-month-old son of the legendary quarter horse Scamper, a gelding. Scamper won a record 10 consecutive barrel racing world championships from 1984 to 1993 in events sponsored by the Professional Rodeo Cowboys Association, and is the only barrel-racing horse to be inducted into the Pro Rodeo Hall of Fame. He also helped make his rider, Charmayne James, the first million-dollar cowgirl and the all-time leading money winner in barrel racing.
...
[Co-owner Tony] Garritano said he and James paid $150,000 to ViaGen, an Austin, Texas, firm that is a leader in the commercial applications of cloning, to restore the otherwise extinct bloodlines of Scamper. Scamper, while still in good health at 30, can't be bred because he was gelded at an early age.
I suppose that's a sinking feeling -- you've got a 10-time world champion quarter horse, and you can't breed him. And of course, castration may not be merely incidental -- it may have affected the performance -- so you can't just say never geld the horse. Particularly with utility horses, you may never have the idea you are going to breed one, but then he turns out to be a champion.
"Carrying on bloodlines" seems to be one of the main appeals of cloning. The article describes how owners stop racing their champion thoroughbreds at 3 years old, just to put them out to stud, because that's where the money is. Perversely, they are breeding for a particular kind of early performance, which has effects on training and life histories of the animals.
Critics have silly arguments. For example, "How much fun would it be to watch a basketball game with 10 Michael Jordans?" Well, if you didn't want to at least maintain the fiction that every team is nearly equally competitive, you wouldn't have an NBA draft! For horses, since the point of racing is to get to the finish line fastest, you're not really promoting phenotypic diversity now, are you?
What I didn't know is that there are cloned mules in competition:
An estimated 1,000 people turned out on June 5, 2006, to watch two cloned mules compete in the Humboldt Futurity in Winnemucca, Nev., a contest that was billed as the first race between cloned animals. One of the clones -- Idaho Gem -- finished third while his identical twin, Idaho Star, finished seventh in the field of eight.Â
Heck, I didn't even know there was mule racing!
[T]he third mule, Utah Pioneer, never kicked it in.
"He went into race training, but the feeling was that he just wasn't going to cut it as a racing mule," Vanderwall said. "He has returned to the university campus and is just hanging out."
Uhhh...ummm... Oh, never mind.
Meanwhile, the thoroughbreeders are dead-set against (it seems they profit too much on the current system, where your horse has 2 years to make good, and if not, you come back for more sperm), and the quarter-horse breeders are trying to find ways around the current ban (they run their horses for many years, have more of a feeder system in the utility horse market, and have non-regulated events of various kinds where they might run a cloned horse).
What interesting politics!
Rolling and the health care challenges of the disabled
The New England Journal of Medicine is carrying an article by researcher Gretchen Berland, which describes her work documenting the health access needs of the wheelchair-bound:
By the time Galen Buckwalter's physician knocked on the exam-room door, Buckwalter's video camera had been recording for nearly 40 minutes. He had booked the appointment because his shoulders were hurting, and the camera recorded his view of the examination table, the comments he made while waiting and, eventually, a largely transactional and superficial exchange with his physician. Two weeks later, in his home, the camera would record a strikingly different take on his shoulder pain -- a growing problem that, Buckwalter worried aloud, might cost him even more of his cherished independence.
As an internist, I was disturbed by the contrast between those two scenes, the second revealing the depth of Buckwalter's concerns and fears, none of which were apparent during the conversation with his doctor. In the later tape, Buckwalter's struggle is palpable. If such stark contrasts are common, how much do I really know about my own patients? Probably far less than I care to admit.
She doesn't call it medical anthropology, but it is a nice example of the use of new ethnographic methods (in this case, video observation) to document social interactions. I think it would be a great article for introductory courses; it provokes a range of reactions. Berland describes the film that she made from some of the video, titled Rolling, and the reactions to the problems faced by one of the covered subjects, an MS patient named Vicki Elman:
Rolling has been shown in many venues, perhaps most memorably One World Berlin, a human-rights film festival. After one screening there, several audience members -- some from the German disability community, others Berlin health care providers -- approached Elman. Having seen her experiences in the United States, they had some advice: Stay here.
It was tempting to contemplate that a move might alleviate some of her problems, but Elman had built her life in Los Angeles, not Berlin. Still, I savored that moment, because other viewers were less sympathetic, convinced that the responsibility for change lay with Elman, Buckwalter, and Wallengren. At a meeting of a state medical society, a physician asked whether the participants were taking antidepressants: it might make things feel less difficult, he advised. At one screening, a medical student even inquired whether the participants had considered having their legs amputated, in order to make transfers from their wheelchairs easier.
I know I have a lot of readers interested in the medical aspects of human variation who might not notice an article in NEJM. This one helps to illustrate the ways that cultural anthropological methods can be valuable.
Drugging brains, young and old
I read two interesting articles today on brain performance-enhancing of one kind or another. Denise Grady of the New York Times contributes a long article about the quest for an Alzheimer's cure:
Answers are urgently needed. Alzheimer's was first recognized 100 years ago, and in all that time science has been completely unable to change the course of the disease. Desperate families spend more than $1 billion a year on drugs approved for Alzheimer's that generally have only small effects, if any, on symptoms. Patients' agitation and hallucinations often drive relatives and nursing homes to resort to additional, powerful drugs approved for other diseases like schizophrenia, drugs that can deepen the oblivion and cause severe side effects like diabetes, stroke and movement disorders.
It's a good article with lots of history about the disease and its social and economic toll. But I found this passage the most significant:
The potential market for prevention and treatment is enormous, and drug companies are eager to exploit it. If a drug could prevent Alzheimer's or just reduce the risk, as statins like Lipitor do for heart disease, half the population over 55 would probably need to take it, Dr. Thies said.
If new drugs do emerge, they will come from studies in patients who already have symptoms, Dr. Thies said. But he said the emphasis would quickly shift to treating people at risk, before symptoms set in. Many researchers doubt that even the best preventive drugs will be able to heal the brains of people who are already demented.
Treating preventively, Dr. Thies said, "will be more satisfying to patients and physicians, and there will be an economic incentive because you'll wind up treating more people."
The only thing that could slow the drive for early treatment, he said, would be serious side effects -- and Dr. Morris, at Washington University, said drugs powerful enough to treat Alzheimer's would probably have strong side effects.
It's interesting to me because of the recent genetic stuff I've been working on. But also in light of this other story in today's LA Times, by writers Karen Kaplan and Denise Gellene:
Drugs to build up that mental muscle
Academics, musicians, even poker champs use pills to sharpen their minds, legally. Labs race to develop even more.
People are already using various psychoactive drugs to get a leg up in whatever mental competitions they pursue. Some of this is no more sophisticated than late-night coffee drinking for the Ritalin generation. But some is more surprising:
"There isn't any question about it -- they made me a much better player," said Paul Phillips, 35, who credited the attention deficit drug Adderall and the narcolepsy pill Provigil with helping him earn more than $2.3 million as a poker player.
...
The growth of the brain drugs bears a striking resemblance to the post-World War I evolution of plastic surgery -- developed to rehabilitate badly disfigured soldiers but later embraced by healthy people who wanted larger breasts and fewer wrinkles.
The use of cognitive-enhancing drugs has been well documented among high school and college students. A 2005 survey of more than 10,000 college students found 4% to 7% of them tried ADHD drugs at least once to remain focused on exams or pull all-nighters. At some colleges, more than one-quarter of students surveyed said they had sampled the pills.
The article discusses the "blockbuster drug that labs are racing to develop," a memory pill. Which of course brings us full circle to Alzheimer's treatment.
You may be thinking there is something unnatural about this; maybe even something unfair -- like an athlete using steroids to enhance his performance. But with psychological factors, it is a little more evident that there is a continuum of uses, some of which are pretty clearly acceptable. For example, the performance artists who take a pill to calm their nerves before appearing on stage are literally enhancing their performance, but in a way that is arguably different from their skill as artists.
Likewise, there is a continuum among normal people -- how do we justify allowing Adderall for the student who has trouble taking an eight-hour exam, but denying it to the student who had trouble sleeping before the exam?
Progress on these kinds of drugs will only come with understanding the continuum of psychological and cognitive variation among living people -- along with the causes of that variation, both developmental and genetic. We might like some chemical to increase memory performance. But the brain is a complicated place with countless interactions of different structural and regulatory processes. Maybe some people already have the chemicals that enhance memory, and other people don't, or don't express them in the right places in the right amounts. If so, then Alzheimer's treatment may focus on the metabolic processes of non-Alzheimer's brains, for example.
Plus, as we've learned recently with respect to traumatic stress, it's not always good to remember things well, so there is no reason to assume that the human population has been adapting toward longer or better memory. In general, it's not obvious exactly what memory characteristics have tended to increase fitness recently or during earlier phases of human evolution. Aside from the energy and life history constraints of large brains, we don't know what evolutionary trade-offs exist with respect to memory or other aspects of cognitive function.
Athletes take performance-enhancing drugs for a relatively slight advantage. Pharmaceutical firms are pursuing brain drugs on the expectation that millions of people will take a daily pill for years on end, in order to stave off Alzheimer's. Unshackling the mind power of a large proportion of the older population will no doubt have a tremendous impact on the societies of the future.
Pretty exciting stuff, if only we could figure it out.
Coming next: virus toothpaste?
I couldn't help but wonder after reading this story:
Bacterial biofilms can form almost anywhere, even on your teeth if you don't brush for a day or two. When they accumulate in hard to reach places such as the insides of food processing machines or medical catheters, however, they become persistent sources of infection.
These bacteria excrete a variety of proteins, polysaccharides, and nucleic acids that together with other accumulating materials form an extracellular matrix, or in Lu's words, a "slimy layer," that encases the bacteria. Traditional remedies such as antibiotics are not as effective on these bacterial biofilms as they are on free-floating bacteria. In some cases, antibiotics even encourage bacterial biofilms to form.
Lu and senior author James Collins, professor of biomedical engineering at BU, aim to eradicate these biofilms using bacteriophage, tiny viruses that attack bacteria. Phage have long been used in Eastern Europe and Russia to treat infection.
The story describes research that built a sort of "phage toolkit", for those times when you don't "want to dig through sewage to find these phages."
Reviving old viruses buried in the genome
This story caught my attention:
In a controversial study, researchers have resurrected a retrovirus that infected our ancestors millions of years ago and now sits frozen in the human genome. Published online by Genome Research this week, the study may shed new light on the history of these genomic intruders, as well as their role in tumors. Although this particular virus, dubbed Phoenix, is a wimpy one, some argue that resuscitating any ancient virus is inherently risky and that the study should have undergone stricter reviews.
Basically, they took a consensus sequence of one family of human endogenous retroviruses, which have implanted their own genomes within ours over millions of years, and used the sequence to build a real virus. And it worked, creating a weakly infectious agent.
Lots of people think this is a bad idea. After all, resurrecting ancient viruses is like a box of chocolates: you never know when they'll escape from the petri dish and start eating your flesh off.
Personally, if it wasn't such a bad idea, I have to wonder why they gave the virus such an obviously military-sounding name! I mean, "Phoenix"?
DDT and the malaria wars
I'll be lecturing on hemoglobinopathies again this week, and I stumbled across this 2001 article by Malcolm Gladwell, profiling Fred Soper and the early 20th century effort to eradicate malaria.
This passage is from a longer section describing his work eliminating invasive Anopheles gambiae from Brazil in 1938:
Four thousand men were put at his disposal. He drew maps and divided up his troops. The men wore uniforms, and carried flags to mark where they were working, and they left detailed wri