There ain't no rules around here! We're trying to accomplish something!

Archive for the ‘Biology’ Category

Google on H1N1 swine flu

In Biology, Delights on April 30, 2009 at 3:38 am

For your datahead enjoyment, a user has added a layer to Google Maps that lets you track cases of swine flu as they are reported.  We are still very much at the point of discovering preexisting cases of swine flu, so this will be a lagging indicator, but it’s still fun (and a little unsettling) to see how many cases of the disease have been spotted in the vicinity of Princeton.

swinemap

A more utilitarian Google widget is Flu Trends, which tracks common search terms that, according to a Nature paper published by the company correlate well with actual disease levels.  (These terms include searches for symptoms that are related to flu; as Google points out, you get more allergy searches during allergy season and more sunburn searches during the summer.)  This can actually predict disease loads two weeks before health authorities announce new outbreaks.

Considering the hubbub about H1N1, it may surprise you that Flu Trends shows that influenza levels in the US are low and steady.  In the media blitz as new cases are discovered, it’s important to keep in mind that the normal seasonal flu causes 36,000 deaths a year.  While swine flu is newsworthy because of its potential to mushroom into a full-blown pandemic, in absolute numbers it is still a minor player in the disease world.

While the disease cannot be acquired by eating pork, pig farmers are naturally concerned that calling H1N1 “swine flu” will hurt sales.  However, the disease did originate in pigs, recombining with avian and human flu viruses, so it is unlikely that the industry’s calls for it to be redubbed will be heeded.  (“Mexican flu” was one suggestion, and I can think of at least one group that would be riled up over the name.)

Update: A remarkable new website allows you to tell whether or not you are suffering from swine flu.  This represents a significant step forward for online diagnostics.  Get yourself checked out here!

Flu intervention: then and now

In Biology, Policy on April 27, 2009 at 8:18 pm
Policemen in masks, San Francisco, 1918
Policemen in masks, San Francisco, 1918

In our earlier swine-flu related post, we mentioned that early intervention may well make the difference between an isolated outbreak and a deadly repeat of the 1918 Spanish flu.  Just how important is starting countermeasures early, and what kind of interventions work?  The tragedy of the Spanish flu provides a natural laboratory for public health measures, as cities throughout the US differed both in scale and timing of their interventions.

Medical science in 1918 was still getting on its feet.  The majority of older physicians of the time were not educated under the scientific regimen of the Flexnerian revolution.  The leading bacteriologists of the day mistakenly believed that influenza was a bacterial disease, and it was not until 1943 when it was recognized that a virus was responsible. As a result, medical intervention in the pandemic was of questionable value, not least because most of the best doctors had been drafted to serve in the military for WWI.

However, nonmedical interventions were also employed.  These included quarantines, isolation of the sick in makeshift wards, closure of public gathering places such as churches and schools.  A recent study examined the effects of timing and duration of these measures, with the major findings summarized in two graphs:

C: Mortality vs. time to intervention.  D: Mortality vs. length of intervention

C: Mortality vs. time to intervention. D: Mortality vs. length of intervention

The study examined the experience of 23 cities in implementing various public health measures, and measured the impact of response time and duration of intervention.  They found that quick action (as measured by when flu cases rose to double the baseline number of cases) had a strong correlation with reduced mortality, and that maintaining the measures was important to keep the disease from spreading.

St. Louis, for example, closed schools and canceled public gatherings early, and maintained quarantines for over ten weeks, leading to a significantly lower mortality rate.  However, not all cities were as proactive; the median duration of these interventions was only four weeks, insufficient to protect the population.  Some cities were even counterproductive: Philadelphia hosted a military parade to promote war bonds, over the objections of numerous doctors and public health officials.  Soon afterwards, it became one of the hardest-hit cities in the US.  (Here is more, from the New York Times.)

In a sense, we are both better and worse off than those who experienced the Spanish flu.  On one hand, our medical science is more advanced; we can now produce vaccines against new influenza strains, albeit at a delay of several months.  (Because the flu virus mutates rapidly, older vaccines, including the one prescribed this past winter, are ineffective against emergent strains such as this one.)  We have also learned the importance of quick and sustained public health measures: witness the recent warning against traveling to Mexico as a result of the disease.

However, modern transportation makes it easier for civilians to pass the flu from country to country, making it harder to isolate the disease to a single region.  In 1918 the flow of soldiers throughout the US and between the US and Europe are credited with helping to spreada disease that originated in the Midwest to every corner of the globe.  This time it may be passenger jets, not steamships, that spread this emerging pandemic.

New swine flu outbreak

In Biology, Policy on April 26, 2009 at 7:42 pm

For years we’ve been worried about a bird influenza strain (H5N1) mutating to infect humans and permit human-to-human transmission.  Now it appears that a pig flu (H1N1) has in fact adapted to humans, infecting almost a thousand in Mexico and several in the US, and causing nearly 100 deaths.

The United States government declared a public health emergency Sunday as the number of identified cases of swine flu in the nation rose to 20.

The declaration is part of a “standard operating procedure” that will make available additional government resources to combat the virus, Homeland Security Secretary Janet Napolitano said at the White House.

Additional cases of swine flu are expected to be reported in the coming days, added Dr. Richard Besser, acting director of the Centers for Disease Control and Prevention.

Past flu pandemics have caused up to a million casualties, and the epic 1918 “Spanish” flu pandemic is estimated to have killed up 10% of young adults worldwide.  However, there have been false alarms as well; a few cases in 1976 prompted massive immunizations in the US for an epidemic that never materialied, and the vaccine caused a number of adverse reactions.

Unlike earlier epidemics, however, it appears that public health services are being more proactive, both in monitoring the disease and in responding, in Mexico, with closure of gathering places such as schools.  It’s thus very possible that we will avoid repeating the mistakes of past pandemics that led to mass casualties.  However, this is a story to keep an eye on.

Here’s a presentation that two classmates and I did for an infectious disease class.  It talks about the experience of the 1918 flu pandemic, the biology of the influenza virus, and the precautions necessary to prevent a new pandemic (bird flu in this case, but relevant to today).

Masks in Mexico City subway

Masks in Mexico City subway

Just the science?

In Biology, Policy on March 17, 2009 at 6:51 pm

Last week, the Obama administration rolled back restrictions on federal funding for embryonic stem cell research on newly created embryos.  When he was in the Senate, Obama said the following:

…the promise that stem cells hold does not come from any particular ideology; it is the judgment of science, and we deserve a president who will put that judgment first.

A recurrent theme of this blog is that science policy is more than just science.  Like all policy decisions, it is informed by facts but fundamentally comes down to a question of priorities.  What is the value of a human embryo, and is it worth trading off X of these to develop Y therapies?  What is the cost of climate change, and how much are we willing to pay economically to mitigate the effects?  The “judgment of science” can tell us the characteristics of a blastocyst and vaguely sketch out possible benefits from stem cell research.  But the decision whether to have the government fund it is a political and ideological one, and to point to one side of the argument as “science trumping ideology” is disingenuous.

The Economist article goes on to point out that Obama opposes human cloning.  In his remarks on embryonic stem cell research he called human cloning “dangerous, profoundly wrong, and has no place in our society, or any society,” and promised that “we will ensure that our government never opens the door to the use of cloning for human reproduction.”  Now there are good reasons for this opposition: even on animals there is a very low success rate, and even for successful clones there are often lingering medical issues.  But notice how the reasoning has suddenly changed – he is morally opposed to human cloning based on these known risks, thus justifying at least defunding of the research and possibly (the wording is unclear) banning it altogether.  From science trumping ideology we now have ideology directing science.

Not that this makes these decisions necesarily wrong.  There are strong arguments for embryonic stem cell research, which become stronger or weaker depending on the value you place on a human blastocyst.  Likewise many (but not all) believe that the suffering attendant upon human cloning efforts is too great to justify scientific advance in that field.  But we need to be clear that these decisions are informed by science but ultimately based on personal beliefs and priorities, not solely on “the judgment of science.”

Politicians ought to appoint scientific advisors on a nonideological basis and listen to what they have to say, but it is ultimately their job to issue a judgment based on their value system.  However rhetorically convenient it may be, it is disingenuous for them to claim to follow science’s lead when approving of research, only to voice moral disapproval when they wish to hit the ideological brakes.

Mammalian ancestor genome sequenced

In Biology on March 2, 2009 at 3:07 am

They’ve reconstructed the genomes for the woolly mammoth and the Neanderthal — now paleogeneticists led by Ian Holmes at UC Berkeley have sequenced the earliest mammal genome. How do you do that without a primitive mammal handy? It’s a statistics hack; they extrapolate from the genomes of living animals. Writes Holmes,

The cool thing is that you can get a lot of information about ancestral genomes just by crunching probabilities — even if you don’t have any fossils, or mosquitos-trapped-in-amber, or time machines, or whatever.

The even cooler thing (to my bioinformatics-geek mind) is that the algorithms used for this are almost exactly the same ones that linguists use to reconstruct ancient languages, like “Indo-European” or “Gondwanese”.

The problem here is to construct a phylogenetic tree (an evolutionary family tree), then deduce the amino acid sequences of the common ancestral proteins at the branches. So by looking at the DNA of present-day mammals, we can infer the shared genome of a common ancestor. This is reminiscent of the divergence of words from their original Indo-European ancestors: for example, the Proto-Indo-European word for snow (*sneigwh-) can be reconstructed from the descendant words for snow in the descendant Indoeuropean languages (German schnee, French neige, Irish sneachta, Russian sneg, Sanskrit snihyati, and so on).

The first scientists who proposed to reconstruct the genetic past from the present were Linus Pauling and Emile Zuckerkandl, who, in 1963, resurrected an ancient form of hemoglobin. They actually reconstructed the molecule in the lab. Which leads us to wonder, now that we have entire genomes of ancient organisms, whether some kind of Crightonesque resurrections might be possible. Would you want to meet a Neanderthal?
A velociraptor?

Much more here, in a book on ancestral sequence reconstruction.

Fish with transparent head

In Biology, Delights on February 25, 2009 at 5:55 pm

barreleye2-350

The barreleye fish Macropinna microstoma lives at the bottom of the ocean off the coast of central California — and Monterey Bay Aquarium researchers have discovered that its head is transparent. Its eyes are surrounded by a transparent, fluid-filled shield that covers the top of the fish’s head, and they are free to rotate in any direction. Normally the shield is destroyed when the fish is dredged up to the surface — this is the first time it has been seen intact.

Darwin zen

In Biology, Delights, History on February 15, 2009 at 3:33 am

In honor of Charles Darwin’s 200th anniversary: the best and oddest of the web.
evolve
Darwin’s complete published and unpublished works.

Convergent evolution could reflect molecular constraints: “Things don’t just happen in chemistry.”

Adam Gopnik talks Darwin and Lincoln.

Swimbladders and humble-bees.

Darwinian animation.

Chuck’s daily routine.

Darwin has a posse.

Read aloud from the Origin of Species.

Darwin’s London.

Darwin and Adam Smith.

Darwin’s grant proposal is turned down.
darwin_by_boneface

Was Darwin overrated?

In Biology on February 15, 2009 at 2:06 am

Watch John Horgan and Carl Zimmer, preeminent science journalists, gab about Darwin (his birthday was Thursday.) Darwin as Hollywood star, horizontal evolution, rethinking the tree of life, group selection — it’s all good.

As for whether Darwin is overrated, there are a couple ways of looking at it. You can focus on his contemporaries and predecessors, and note that he wasn’t alone in thinking about evolution: there was traveling naturalist Alfred Russel Wallace, whose observations about the geographic distribution of species led him to theorize about the divergence of species, and whose correspondence heavily influenced Darwin’s Origin of Species. The idea that species change over time was advanced by Robert Grant, who saw a progression in fossil animals; Robert Chambers, author of the popular-science bestseller Vestiges of the Natural History of Creation; and Charles’ grandfather Erasmus Darwin, who hypothesized that all life had a common origin. You could argue that Darwin worked in a ferment of ideas about life’s origins and variation, that he was not alone. It’s a useful perspective. Scientists are rarely lone geniuses, even if they are geniuses — they collaborate, borrow, and bicker like everybody else.

Does that make Darwin overrated? I don’t think so. He did, after all, put forward the theory of natural selection as we now know it. Vestiges was a vast, mystical treatment of the origins of the universe (complete with some racial theorizing unsavory to contemporary eyes); Origin was a cautious work, anticipating every counterargument, bolstered with pages of evidence about pigeon breeding. Darwin made evolution a subject of scientific study.

He’s also a profoundly appealing figure. Unlike, say, Newton (combative, paranoid, devoted to his alchemy), Darwin the man was genuinely likeable. He had something of the attitude of the humble, persistent noodler. He measured armadillo fossils in the Galapagos, and thought it was odd that they resembled (but were not identical to) the armadillos his expedition was roasting for dinner over the campfire. He was a rigorous observer, but he also had a useful aimless curiosity. He was an abolitionist and a loving husband and father. We can sympathize with the loss of his daughter and his doubts about the theory of evolution. If we want to put a human face on science, we could do worse than Darwin.

Facebook, evolution, and mathematical modeling

In Biology, Delights, Math on February 12, 2009 at 6:09 pm

Slate has a neat article about Facebook’s new “25 things about me” craze. (For those who have remained blissfully ignorant: thousands of users wrote notes about random personal habits or goals, and tagged their friends in an expanding web of navel-gazing.) Turns out it can be modeled like an epidemic. A user is “contagious” for about one day — the day he tags a bunch of his friends in the note. After being tagged, most users respond within one day. Then response frequency drops off exponentially.

Here’s a nice Nature Review about the mathematics of modeling infectious disease.

biological infectiousness of influenza, HIV, and malaria

biological infectiousness of influenza, HIV, and malaria


The number of individuals that an infected person infects is given by a probability distribution. The probability that an infected person will infect another person within a small interval is

b(t) s dt

b is infectiousness, dt is an arbitrarily small amount of time, and s is the probability that the other person is infected.
If a group of individuals all have the same infectiousness, then the number of secondary infections that are caused by each infectious individual is a random number drawn from the Poisson distribution with mean R, where R is the expected number of new infected victims.

The interesting thing here is that the whole field of mathematical modeling of disease transmission isn’t going to be just a biological subject forever. It’s also going to be a behavioral subject. The idea that cultural ideas propagate and evolve like organisms isn’t new — it’s as old as Dawkins and his notion of “memes.” But back in the sixties he couldn’t have predicted just how concrete the similarities would be — that we could see the exact same differential equations governing Facebook crazes as malaria outbreaks. Watch as epidemiologists get drafted as marketing consultants in the next few years.

Better labs

In Biology, Delights on February 10, 2009 at 2:43 am

xwpn0s3l4h6uu7t10ezprxceo1_500
DIYBio, “an organization that aims to help make biology a worthwhile pursuit for citizen scientists, amateur biologists, and DIY biological engineers” has a lot of wonderful, decentralized ideas for making biology work better. One project is the SmartLab, a benchtop that can

1. identify tools (microscopes, pipettes, gel electrophoresis boxes, etc.) by barcodes or RFID tags, and display contextual information for them; how much you’ve pipetted, what you just put in the tube, and so on.

2. guide you through a protocol.

3. keep a virtual lab notebook of everything you do. Video, audio, measurements. Your electrophoresis box is “smart” and records data in realtime.

It’s a radical idea: human error isn’t inevitable. “Forgetting” a step in your protocol isn’t inevitable. You can work around your own fallibility.

Incidentally, this reminds me of something from my high school days as a Kid Intern in a genetics lab. The lowliest job was racking pipette tips by hand, and it was a running joke that someday someone would invent a machine that could rack tips automatically and make a fortune. Well, I found it. It was invented by a couple of guys in a kibbutz, the year I graduated.
il2006000660_14122006_gz_enx4-b