The Inner Life of a Cell

Ok, I’m gonna crank the nerdliness up to 11…

This video shows what I love about biology: there’s all this really amazing, incredible stuff going on inside your body all the time. The most basic business of life itself is a miracle. I find it all fascinating. In fact, I’m such a nerd that this video almost brought a tear to my eye. There’s also a full-length version available.

Metabolomics and Personalized Medicine

An organism’s metabolome is all of its metabolites and metabolic processes—in other words, all of the chemicals that come out of it (like urea, carbon dioxide, and progesterone) and all of the biochemical reactions that produce those compounds. It’s one of those words that scientists concocted out of thin air because they fancy themselves clever lexicographers. But it’s a powerful concept and one of the keys to the future of personalized medicine.

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How many genes does one human need?

Recently I was watching the ST:TNG episode “Genesis“. The science in this episode is all on the level of the Heisenberg compensator, which is to say, laughably bad. (Someone did point out once that a Heisenberg compensator doesn’t necessarily mean one can determine both a particle’s speed and position, it just compensates for the fact that you can’t.) But Dr. Crusher’s estimation of the number of genes in the human genome was pretty accurate, at least for 1994.

Estimations of the number of genes make for an amusing measure of scientific progress. I’ve heard that in the 60’s, the number was estimated in the millions. According to Star Trek, it was down to 100,000 by the mid-nineties. (It’s also interesting to note that at that time, the Human Genome Project would have been considered to be only a third of the way into it’s fifteen year lifespan, but it actually finished in 2001, four years ahead of schedule, because the technology improved so drastically during the project.) I noticed recently that my genetics textbook, which was probably written in 2001, estimates the genome to be between 40,000 and 60,000. The current estimate is much more like 27,000.

For comparison’s sake, the fruit fly Drosophila melanogaster has about 12,000 genes. The bacterium E. coli, which is famous for killing people at Jack in the Box but also thrives in your intestines, has about 3000 genes.

We’re far more than twice as complex as a fruit fly, or nine times as complex as a lowly bacterium. Clearly there are other mechanisms that contribute to complexity, so that it doesn’t scale linearly with gene number. We already know about several, but we’re also finding new ones.

The picture is somewhat more complicated because the idea of a gene has changed over time, and, in my opinion, is fairly nebulous. The word “gene” actually has two different meanings, even in the halls of science. In one sense, it means “allele.” Alleles are different types (or flavors) of one gene. So when someone says, “he has the gene for sickle cell anemia,” they really mean he has the allele for it. The average person has the non-sickle cell allele.

The other meaning is “locus,” which is the physical position of the gene in the genome. You might hear, for example, that the gene for color blindness is on the X-chromosome, which really means that the locus is there.

When we talk about how many genes there are in the genome, we’re really talking about loci and not alleles. Some of the recent discoveries about gene regulation—the mechanisms that make us so much more complex than fruit flies even though we only have about twice as many genes—turn traditional notions about these mechanisms on their ear. They may even require another revision to the number of genes in the human genome.

Researcher Fakes Cloning Results

Nature reports:

The university committee looking into scientific misconduct in the laboratory of South Korean cloner Woo Suk Hwang announced on 10 January that his 2004 claim to have cloned a human embryo was fake. But his Afghan hound Snuppy is a real clone.

I’ve written about this research before, and now it all turns out to be fake. The greatest damage done by this scandal is the way it will affect the general’s public’s perception of science and of therapeutic cloning in particular. I still think this is an avenue that needs to be fully explored, in spite of temporary set backs.

The Nature article also discusses the number of human ova that Hwang went through in the course of his research and the ways he obtained them. Apparently, he coerced female lab members to donate. That’s bad. American standards require that egg donors receive no compensation.

The problem is that donating eggs involves surgery and the injection of large amounts of hormones, so that the woman “superovulates” and produces multiple eggs rather than the single one that she would normally produce. In fact, donating eggs (at least for money, I don’t know about research purposes) is legally in many European countries because it is considered to be quite dangerous.

I mean, it’s like they’re donating a kidney not to save some sick kid, but for research purposes. Doesn’t it seem like they should get some compensation for that?

Evolution and You

I was just thinking the other day about how human civilization has effectively halted our evolution. Then I read this in Nature today (full article):

Icelandic scientists reported earlier this year, for instance, that 20% of Europeans carry a large genetic inversion that is spreading throughout the population. Women who carry the inversion have more children than those who don’t — a classic sign that it confers some sort of selective advantage.

It turns out that not only are we still evolving, but evolution may be more about large-scale rearrangements in the genome than changes in single base-pairs.

This reminds me of a presentation I saw a year or two ago about transposons in the rice genome. Transposons are these weird little pieces of DNA that exist in the genome. They are capable of jumping around the genome from place to place to place. Typically, they’re thought of as parasitic, although clearly they’re not organisms in their own right. They do nicely embody the idea of the “selfish gene” quite nicely.

The point of the presentation was the researcher’s assertation that transposons become active—that is, they jump around the genome a lot more—during periods of stress, and this increased activity promotoes evolution. The idea is that by stimulating evolution, the transposons make the host better able to deal with the stress, such as relocating to a colder climate.

It’s an interesting idea, although I’m not sure how many scientists buy into. But the notion from Nature that evolution involves reorganization of genome is certainly widespread, even though it upturns many long-held ideas about evolution and the very nature of biology. But this century has seen many such revolutionary ideas come to light. It’s an exciting time.

The Avian Flu is Going to Kill Me First

Listen people, the avian flu is coming. Hopefully later rather than sooner, but there will be a pandemic. And it’s gonna be bad. I’m not going to scare you with apocalyptic predictions, but please, get a flu shot.

As far as anyone can remember, I personally have only ever had the flu once. Never had it as a kid, never got it in college, even when my roommate in the dorm did. I finally caught it in New York City at the end of 2003. Caroline got it too, which was surprising because she’d had her flu shot that year. The injection only protects you against the three most common strains from the previous year, and that year, a strain of influenza called Fujian was very common. Still, the shot provides some generalized protection against all types of flu, so Caroline had a slightly better time of it than I did.

As a microbiology student in college, I realized that one possible reason that I never got in flu in spite of obvious exposure was that I had a mutation that made me immune. In a large enough population, there are always individuals with a natural immunity to a given disease; there are some people in the world who are immune to HIV, for example.

I also knew the particulars of influenza mutation and evolution. I won’t go into the specifics, but suffice it to say that influenza mutates and evolves rapidly, so that different strains appear every year and every few decades theres a pandemic. This means that if I had a natural immunity (and not just good luck), it wouldn’t protect me forever. The fear in the back of my mind is that when the next pandemic came, my mutation would make me hypersensitive to the virus, sealing my fate.

Now, my theory of natural immunity turns out to be true. A recent article in the journal PLoS Biology (technical article and general audience synopsis; I love PLoS, but that’s a subject for a different time) examined the genes of a number of flu viruses collected in New York State, including the so-called Fujian strain. Fujian just so happens to have certain mutations that make it different from the more common types of influenza, hence the epidemic of the 2003-2004 flu season.

These mutations also, apparently, allow it to overcome my natural immunity. The mutations obviously contribute to the strains increased pathogenicity. The bug that causes the coming pandemic is likely to have similar mutations as well as being ferociously virulent. Clearly, it has my name on it.

Really, its an emotional reaction to think that my mutation, which has so far granted me immunity, would work to my detriment when the avian flu strikes. Logically, I would be no more or less susceptible than anyone else. On the other hand, my body has only ever had to fight off one influenza virus, and that lack of general flu antibodies might work against me.

Hmm… When do flu shots start?

Coming soon: Desktop genome sequencing

The sequencing of the human genome project took ten years and cost millions and millions of dollars. It was coordinated effort of researchers around the world. But the technology used to sequence DNA developed so quickly during the project that it finished five years ahead of schedule. And the technology continues to improve.

In fact, it generally follows Moore’s Law, which states that computer processor power will double every 18-months but has been applied to many areas of technology. As price comes down and speed and accuracy increase, some in the field have projected that in ten years, a single individual will be able to have her own genome sequenced for $1000.

That day is getting closer. A recent paper in Nature (PubMed; subscription required for summary and article) demonstrates a new sequencing technology that allows a single technician to sequence 25 million bases in just four hours. By comparison, the sequencers that I used when I worked on the Human Genome Project could each produce about 10,000 bases in the same time frame. The authors of the paper assembled an entire bacterial genome in a single run.

The advent of individualized genomic medicine will be a boon to health care, provided that safeguards are put in place to protect patients’ privacy. Otherwise, it may just further corrupt our already-crippled health insurance system.

Technology like this and the Internet always remind me of my 8th grade history teacher (who was also a football coach) who told us that, unlike every previous generation of Americans, our standard of living would not increase dramatically from what our parents experienced. It makes me chuckle.

More on Monsanto

I happened across this randomly today. Unsurprisingly, Mansanto is pulling research and all kinds of business from the EU, where there is adamant consumer and farmer opposition to GM foods. Not the like U.S. where we don’t really care about anything except how much it costs to fill the gas tank on the Suburban.

Superorganics

Wired’s current coverstory is about so-called “superorganic” foods, which the article sells as the next generation of genetically modified (GM) foods, frequently referred to as “frankenfoods.” The current crop of GM foods has genes inserted from other species to give them improved functions, such as drought resistance or added nutrients. Superorganics do this one better and activate dormant genes or insert genes from different strains of the same species.

First off, let’s not mince words the way Wired does. Superorganics are still genetically modified. But so are dogs and wheat. Dogs and wheat are the product of controlled breeding whereas “frankenfoods” come out of a lab and, more importantly, contain genes from other species, usually bacteria or some equally foreign donor. Superorganics get sold in the article as being equivalent to the breeding process, just one that has been accelerated by lab techniques. The fact of the matter is that superorganics probably spend more time in the lab than GM foods and achieve results that no breeder in a thousand years could do.

That’s not to knock them at all. Much to the contrary, I think these “superorganic” foods are the way to go. They solve two of the biggest problems of GM foods. The scariest is the idea of “genetic pollution,” which can be thought of as artificially changing the wild gene pool. If a gene that produces beta-carotene is transferred from a GM crop to some native species, who knows what the effect of that would be. Or if a crop contains a bacterial gene that makes it naturally resistant to insects, we run the risk of breeding hardier insects the same way that antibiotics have resulted in many strains of antibiotic-resistant bacteria. By using only genes native to a species, superorganics avoid this problem. Indeed, many strains currently under development simply reactivate genes that have been shut off by generations of controlled breeding.

The second problem is intellectual property rights. Most of the GM strains were developed by Monsanto, and they have patents on not only the crops but the techniques used to create them. This makes it difficult to feed hungry people in developing countries. Superorganics instead rely on public domain techniques that are free from intellectual property issues.

Superorganics also overcome a number of other issues associated with both modern and traditional techniques of genetic modification. Inbreeding, for example, is a big problem for dog breeders but not superorganics. I’ve long thought that the solution to humanity’s current food crisis — malnutrition is responsible for something like 30 million cases of blindness annually — lies in modifying our crops to better accommodate our needs. As the population grows over the coming century, the food crisis will only worsen. Superorganic foods are part of the solution.

New Jersey gets it

This stem cell silliness has produced the most unlikely victors. First Korea, and now New Jersey. Looks like California may not be far behind either. There may be some hope for this country after all.