P.C. Shannon

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.

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?

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.

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?

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.

I was reading an article in the New York Times the other day about the damage to offshore drilling platforms caused by hurricane Katrina. The platforms are built to survive a hundred-year storm. Hurricane Ivan, a couple years ago, was classified as a 2500-year storm, and Katrina rates as at least a 100-year storm. When one engineer remarked that these powerful storms were becoming more common, I couldn’t help but think to myself that since hurricanes are powered by warm water, the increase clearly indictes a rise in global temps, if not proof outright of global warming.

So it was no shock today when I found another article in the Times that says, “Storms with the power of Hurricane Katrina are becoming more common, in part because of global warming, according to a report from a team of researchers that will be published Friday.”

Then there’s this really encouraging piece from the UK’s Independent:

A record loss of sea ice in the Arctic this summer has convinced scientists that the northern hemisphere may have crossed a critical threshold beyond which the climate may never recover. Scientists fear that the Arctic has now entered an irreversible phase of warming which will accelerate the loss of the polar sea ice that has helped to keep the climate stable for thousands of years.

Here’s the think about global warming: This increase in global temperature may just be part of the planet’s natural cycle of minor climate shifts. Or it may be very very bad. And by the time we have enough evidence to make a convincing argument one way or another, it will be too late. So doesn’t it seem like we should do all we can now to minimize our impact on the environment (notice I didn’t say, reverse the climate shift), just to be safe? I know it’s important for everyone to drive a bigass fucking truck, but wouldn’t it be nice for your great-grandchildren to be able to play in the ocean?

I�m been thinking, on and off for some time, about what constitutes intelligence. A recent Wired article points out that IQ test scores have been increasing since World War II, in spite of the supposed “dumbing down” of America. Researchers attribute this increase in intelligence to environmental factors, but can�t pin down the exact cause. One hypothesizes that the prevalence of iconographic interfaces in our society, such as those found on cellular phones or in videogames, has boosted the reasoning skills that IQ tests measure.

I personally buy into this, to a certain degree. IQ tests typically require you to pick out the next in a series of changing shapes. They do this in order to minimize or eliminate language or cultural bias. But on the other hand, they�re also only testing this sort of visual reasoning skill.

On the one hand, I’m inclined to say that any intelligence test for which you can study and improve your score is not a very good measure of intelligence. On the other hand, I certainly feel like I’ve gotten smarter as I’ve gotten older, but perhaps this is just a corollary of my education. It has gotten easier for me to learn as I�ve gotten older, which again may just be a function of motivation rather than any real increase.

This leads us back to my central question of what constitutes intelligence. Think about how you typically gauge someone�s intelligence, especially when you first meet someone new. You base your judgment on the way that person talks. Big words and complex sentences equals smart; monosyllabic speech filled with “like” and “uh” equals not so smart.

Language provides a handy metaphor for analyzing intelligence. A smart person can readily understand words with complex and nuanced meanings, and she can put them together in complicated, sometimes novel patterns. Similarly, she can see the relationships between complex concepts and sometimes see connections where no one has seen one before.

There are two components to this model. One is the ability to reason, to see connections and relationships. In a visual sense, this is what gets commonly tested by intelligence tests and what is taught by videogames. Unfortunately, visual intelligence doesn�t get you very far in the real world. The second component is knowledge. Really, this is the first component, because in order to see connections between concepts, you first must understand those concepts.

The author of the article, Steven Johnson, also wrote a book called Everything Bad Is Good for You: How Today's Popular Culture Is Actually Making Us Smarter. In this article, he goes so far as to postulate a dramatic jump in IQ scores is right around the corner, when kids who grew up on videogames, the Internet, and Pokemon start taking intelligence tests. Their visual reasoning skills have been honed since before they can remember to excel in the areas that IQ tests measure.

Dr. Flynn, the researcher who hypothesizes that videogames are driving up test scores, gets a little closer to reality. He notes that we�re not seeing improvements in other areas, such as math tests. He reasons �that society has priorities. Let's say we're too cheap to hire good high school math teachers. So while we may want to improve arithmetical reasoning skills, we just don't.�

Videogames improve visual reasoning skills, and IQ tests measure visual reasoning skills. So playing more videogames will give you a better IQ score, but it does not make you smarter. Make sure that this is clear. IQ scores do not necessarily reflect intelligence. There’s a correlation, probably, just like there’s a correlation between someone�s spoken language and their intelligence. But I’ve known people who sound like blathering idiots yet turn out to actually be very intelligent. Beating up hookers in Grand Theft Auto may not make you dumber, but it’s not going to make you a math whiz either. That requires, as Dr. Flynn says, good math teachers.

I have a lot of anxiety over what I’m going to do after I finish grad school. Even though I’m only starting my second year, I’ve still spent some time browsing job listings online at sites like Nature Jobs. This is not necessarily representative because in my field, I think a lot of recruiting is done at conferences and via word-of-mouth. In fact, I think it’s only fueled my anxiety because most of the bioinformatics lobs listed are for coders and technicians — people with Bachelors and Masters degrees — which is not what I want to do.

Strangely, it took me a while to figure out that rather than being paranoid about limited opportunities available to me (as listed online), I need to position myself as a bioinformatics researcher as opposed to a mere technician. This is similar to the difference in the software industry between a coder and an engineer. What I need to be doing, I realized, is not just taking one bioinformatics course and farting around on my computer. I need to be developing my toolbox so that I have a variety of ways of solving new problems rather than just getting headaches while trying to reinvent the computer science wheel. (Much of the foundation of computer science was set out years ago by people who are much smarter than me, so I couldn’t possibly recapitulate it all.)

This curriculum was driven home recently by an editorial in the journal Bioinformatics by Pavel Pevzner, a name I recognized from browsing bioinformatics books on Amazon.com. Pevzner’s argument is that undergraduates in molecular biology need to take an introductory algorithms class, but his broader point is that biologists need to understand the logic behind bioinformatics and not just “cookbook” their way thru computational biology.

The bioinformatics class that I’m currently taking does a good job of explaining the algorithms that are used. The students in there certainly understand sequence alignments better than most practicing biologists. The professor is not just giving us a recipe, he takes us through the algorithms. The problem for my educational goals is that, out of necessity and aim, he only hits a few algorithms that are currently employed. He can’t build the toolkit that I want to have. He does a good job of explaining the current state of the science, but he’s not preparing us to advance that state. It’s just beyond the scope of his course.

The class is a good starting point, a solid foundation that I have already applied to my research. But from here, I definitely want to take at least a basic algorithms class and I’d like to take something more advanced, too. But I also want to take some high level statistics and math courses, too, because a lot of bioinformatics is statistical modeling and such, so I need that background as well. The only problem is that I don’t want to have to subject myself to taking a slew of undergraduate classes if I can avoid it. So maybe I’ll just audit all of the class, we’ll see. Certainly having this plan has alleviated much of my anxiety.

The conventional wisdom is that intellectual property is generally a good thing, although it can lapse into the absurd. Shakespeare is in the public domain, but just about anything printed in the last 100 years is not, even though the vast majority of it is long out-of-print. In the present tense, IP laws are intended to protect innovation and allow inventors to profit from their ideas. This is thought to drive innovation, and innovation ultimately benefits everyone. However, I've come across two examples recently where IP laws, while perhaps protecting innovation, nonetheless are not working in the public interest.

The first example comes from everyone's favorite evil corporation: Microsoft. Gates and company had some ideas about how to stop e-mail spam. They joined forces with AOL and maybe even Yahoo, and presented their ideas to IEEE, the body that approves standards for electronics and communications. IEEE considered the idea only briefly because they learned that Microsoft intended to file for a patent on their idea. IEEE can't very well make a patented process into a standard because that would force everyone to pay a licensing fee to the patent-holder. So someday we may be free from spam, but thanks to Microsoft, that day won't come soon.

While spam is certainly annoying, the second example is much more serious. A technology called DNA microarrays allows researchers to examine how genes are turned on or off in a cell across its whole genome. It's a very powerful tool and has the potential to give us great insights into the biology of cancer. In fact, there have probably been enough microarray experiments conducted on human DNA to date to be a tremendous boon to cancer researchers. Unfortunately, it's locked away in the intellectual property of dozens of companies. Each has just a piece of the puzzle, which is useful but not nearly as powerful as the whole picture.

To be fair, microarray experiments are expensive. The companies that do this work went into it with the intention of making a buck in addition to curing disease. As more or less a believer in capitalism, I think that's their right. It's just a shame that every once in a while, we can't put aside our materialism for a greater good. On the other hand, without the lure of riches, the microarray data wouldn't exist in the first place.

Modern nanotechnology, such as it is, is concerned with producing materials on an atomic scale, such as fiber made from so-called “bucky balls.” Star trek fans and other afficionados of science fiction think of nanotechnology as it may some day exist — millions of microscopic machines (referred to as “nanites” or more accurately “assemblers”) pushing around individual atoms and molecules. Part of this scenario is that the assemblers are self-replicating, meaning they copy themselves using any available materials. This leads to the grey goo problem, wherein an out-of-control replication process reduces the Earth and everything on it to a mass of replicators (which look like nothing so much as grey goo).

K. Eric Drexler, the father of nanotechnology, recently published a paper refuting the grey goo danger. Basically, he says that even if we are someday able to make assemblers, it will be very difficult to make them self-replicating and there won’t be much need to do so. In fact, he says, the danger from military applications (i.e. nanotech weapons) is much greater. The problem with Drexler’s thesis is that he’s an engineer.

I mean no disrespect. In my experience, there are two camps of nano people, each with very different ideas of how the whole “assembler” idea will play out. On the one hand, you have the engineers, who are used to working with machines, so they expect that assemblers will be some sort of machine (a bioMEM in the jargon, which stands for biological micro-electromechanical machine, or something like that). On the other hand, there are the biologists, who work with cells all day and think that assemblers will be some sort of heavily engineered cell. After all, cells are just biological machines that have been programmed by nature to carry out specific tasks. Why couldn’t we just reprogram them?

It’s this biological notion of the assembler that Drexler ignores in his paper. It’s pretty much impossible that a bacteria, no matter how much you engineered it, could rearrange individual atoms in a molecule, so the massive, planet-wide grey goo problem isn’t a concern. However, I can easily envision a scenario where a biological assembler intended to clean your arteries of cholesterol grows out of control and quickly kills the patient. The crux of the problem is that while mechanical assemblers are manufactured, biological ones are necessarily self-replicating.

To control this problem of uncontrolled growth, we need multiple ways to permanently turn off the cell’s ability to replicate itself before it is administered to the patient. One solution is to knock out the replication genes in the genome and put them on a plasmid, then we would need a way to destroy the plasmid before setting the bugs loose on someone’s arteries. The cells should also have multiple metabolic dependencies (similar to the way the dinosaurs in Jurassic Park needed lysine in their diet) as well as susceptibility to multiple antibiotics.

The scientists in Michael Crichton’s novel thought they had their creations under control by making them dependent on a dietary amino acid. This was a single point of control and a single point of failure, which nature is often very good at overcoming. That’s why our biological assemblers need multiple points of control. The Jurassic Park scientists should have realized this, but I guess they weren’t very good scientists. Fortunately, they were also fictional.