Michael Graham Richard

Staphylococcus aureus. Credit: Erbe, Pooley: USDA, ARS, EMU. Public Domain license.

I mentioned in a recent post that the cost of sequencing DNA was falling exponentially. A good real-world example of the state of the art is this story from the Proceedings of the National Academy of Sciences of the USA (PNAS) that I found over at In the Pipeline:

A team of researchers looked at a single patient undergoing treatment with vancomycin for a serious infection. [...] They periodically isolated Staphylococcus aureus bacteria from the patient’s blood during the course of the treatment to look at how resistance to the antibiotic developed. [...] the way they watched the process was to sequence the whole genome of each bacterial isolate. What they found were a total of 35 mutations, which developed sequentially as the treatment continued (and the levels of resistance rose). Here’s natural selection, operating in real time

(bold and link are mine)

We’re now at the stage where we can sequence a bacteria’s whole genome multiple times to follow mutations in real-time. That’s amazing! It’s still an expensive experiment, but a few years ago it would have been an impossibly huge undertaking, and we can bet that a few years from now it will be routine and completely unremarkable.

Allow me to repost the log graph of the cost of sequencing base pairs of DNA:

Credit: Ray Kurzweil, The Singularity is Near, p.73.

A straight line on a log graph means exponential change. In this case, it’s an exponential fall in costs. If we extrapolate just a little, we see that sequencing DNA will almost be free very soon.

This almost assuredly means that soon enough we’ll have sequenced pretty much everything on Earth that 1) has DNA and that 2) we know about (we’re still frequently discovering species of insects, deep sea animals, bacteria, etc). Exciting times!

Sources:

• Tracking the in vivo evolution of multidrug resistance in Staphylococcus aureus by whole-genome sequencing
• Evolution In Action at Corante

Disclaimer: I’m not a biologist. I’ll explain things to the best of my knowledge, but errors are very possible. If you find some, please let me know in the comments and I’ll fix them. Thank you.

Proteins are the building blocks of life.

According to a recent Nature article (which I’ve also cited here), “the human genome contains some 25,000 protein-encoding genes, [but because genes can code for more than one protein, and the products described in genes can be modified after being translated into protein,] a given person’s various cells might use up to a million different proteins to do different things at different times in the course of a life.” So there are lots of proteins that we need to study to better understand life.

There are two general ways used to study the structure of proteins (the structure gives us important information about how the protein performs its function):

The Experimental Way

The experimental way is itself sub-divided in at least two techniques (there might be more).

Image: A diffractometer. GFDL license.

First is X-ray crystallography. It is a long and expensive process, and unfortunately not all proteins will crystallize (which is why nuclear magnetic resonance (NMR) spectroscopy is important):

The technique of X-ray crystallography has three basic steps. The first and generally most difficult step is to produce an adequate crystal of the molecule(s) under study. The crystal must be sufficiently large, pure in composition and regular in structure, with no large internal imperfections such as cracks. In the second step, the crystal is placed in an intense beam of X-rays of a single wavelength, producing a series of spots called reflections. As the crystal is gradually rotated, previous reflections disappear and new ones appear; the intensity of every spot is recorded meticulously at every orientation of the crystal. Multiple data sets may have to be collected, with each covering a full rotation of the crystal and containing tens of thousands of reflection intensities. In the third step, these data are combined computationally with prior chemical information about the molecular structure to produce the atomic resolution model.

The second is Protein nuclear magnetic resonance spectroscopy, which is what has recently been improved by MIT researchers. First, lets look at the “old model”:

Image: Pacific Northwest National Laboratory 800 MHz NMR Spectrometer. Public Domain license.

Traditional NMR uses coils to detect the radio-frequency signals produced by some atoms, including hydrogen and carbon, when they are exposed to a magnetic field. [...] Because the radio-frequency signals that NMR spectroscopy relies on are very weak, large samples are needed to perform experiments. The instruments also require large, powerful magnets, which contribute to their size and expense. Hence, biochemists have had limited access to the machines.

So NMR spectrometers are big, expensive and their access is limited. This could change:

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Update: After thinking some more about this, I’ve changed my mind. I’m keeping the original post below because there’s nothing wrong with changing your mind.

In short: The space tourism comparison in the Nature article might have thrown me off in the wrong direction. That comparison is flawed because with space tourism, it’s not such a big deal if it’s available to the rich first — most technologies are like that — but a technology that has big public health implications is different, and any time lost doing things that are not optimal from a scientific merit point of view are only delaying important cures and breakthroughs and thus increasing human suffering. Those delays include sequencing celebrity genomes, but also other inefficiencies and speed bumps in the research system such as ineffective bureaucracy, grants that too rarely go out to young scientists working on high risk/benefit projects (they’re too often looking for proven track records and sure things, sometimes to the point of lacking vision), etc. Anything under human control that delays results.

Credit: Richard Wheeler, 2007. GFDL license.

Nature reports some controversy over the sequencing of the genome of some famous scientists:

Michael Egholm [described] his company’s effort [Update: his company is private and using its own funds, as far as I can tell] to sequence the genome of genetics pioneer James Watson. The company claims this is the first sequence of an individual human genome, and that it took three months and cost about $1 million. “So, is this the next space tourism?” joked a scientist inspecting the poster. [...]

“If all the sequences obtained over the next year or two are done on scientists with strong financial positions, that will send a message quite contrary to what the genome project aimed to achieve,” says Francis Collins, head of the US National Human Genome Research Institute (NHGRI) in Bethesda, Maryland. [...]

“I’d hate the availability of single-genome sequencing to be based purely on money and fame,” says Michael Ashburner, a geneticist at the University of Cambridge, UK. “Just doing famous or very rich people is bloody tacky, actually.”

Why don’t I think this is that big a problem? Because things are moving so fast.

Credit: Ray Kurzweil, The Singularity is Near, p.73.

As this logarithmic graph from The Singularity is Near (follow the link to sample it at Google Books) shows, the cost of sequencing DNA is going down exponentially (a straight line on a log graph means exponential change), from $10 per base pair in 1990 to a few pennies in 2004 and even less than that now. The rate calculated in 2004 was a halving of the cost every 1.9 years, but that too is accelerating according to Kurzweil.

A good concrete example of how fast things can move and how un-intuitive exponential progress can be is the Human Genome Project itself: It started in 1990 as a 15-year project. After one year, they had done 1/10,000th of the work. If they had progressed linearly, it would have taken about 10,000 years. Around the halfway point of the project, they had about 2% of it done. Yet, they finished 2 years earlier than planned, because from 2%, if you double each year you get to 100% in less than 7 years. Another example: It took us 15 years to sequence the HIV virus, but 31 days to sequence SARS, and so on.

So I say let these scientists work on their genomes first. They worked hard to move the science forward, let that be part of their reward. It’s not as if their genetic material is somehow without scientific value, even if not the optimal starting point for various reasons. By the time they are through with themselves and before there is time for any real public outrage, the time and cost required to sequence a complete human genome will be so small that the whole point will be moot anyway.

Besides, someone who gets his/her genome sequenced a few years from now will get a lot more useful information out of it - better bang for the buck - since we’re far from knowing everything about how to interpret all that genetic information (but that’s moving along fast too). Exciting times we live in.

While making a point about intelligence in his post titled What Smartness Means, Michael Anissomov mentions Mesosomes:

Credit: Public Domain.

The story goes: Mesosomes were discovered in the 1960s and biologists thought that they “play[ed] a role in cell wall formation during cell division and/or chromosome replication and distribution and/or electron transfer systems of respiration. [...] They act as an anchor to bind and pull apart daughter chromosomes during cell division.”

Problem is, further research showed that mesosomes were actually artifacts caused by the process used with electron microscopy — humans were inadvertently creating them. So much for the original research.

This reminded me of something I’ve read about a few years ago - possibly in Isaac Asimov’s autobiography - about the “canals” on Mars.

For a time in the late 19th and early 20th centuries, it was believed that there were canals on Mars. These were a network of long straight lines that appeared in drawings of the planet Mars in the equatorial regions from 60° N. to 60° S. Lat., first observed by the Italian astronomer Giovanni Schiaparelli during the opposition of 1877, and confirmed by later observers. Schiaparelli called these canali, which was translated into English as “canals” [though "channels" would have been more accurate]. The Irish astronomer Charles E. Burton made some of the earliest drawings of straight-line features on Mars, although his drawings did not match Schiaparelli’s.

Many astronomers couldn’t even see these lines, and most of them didn’t jump to the conclusion that they were a sign of an alien intelligence. But some, including amateur astronomer Percival Lowell, were convinced that they were a sign of an intelligence civilization, and many in the general public jumped to those conclusions too.

Here are some drawings of the “canals”:

Map of Mars by Giovanni Schiaparelli.

Here are striking drawings by Percival Lowell (the first kind of looks like giant spiders):

Martian channels depicted by Percival Lowell.

I can only imagine what it must have been to see these at the time (late 19th century, early 20th). Nowadays we’re used to knowing that we’re alone in our corner of space (and possibly in more than our corner, read these: one, two), but back then it must have made the imagination run wild. Imagine thinking that we’ve discovered signs of an advanced civilization on a nearby planet. Seriously, take a second to sit back and think about it. Must’ve been the ultimate curiosity-high!

But what did these “canals” turn out to be?

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I’ve recently found an interesting article over at MIT’s Technology Review about the James Webb Space Telescope and it inspired me to read up on the differences between the planned next generation telescope and the venerable Hubble.

The image above shows first the Hubble Ultra Deep Field (”It is the deepest image of the universe ever taken in visible light, looking back in time more than 13 billion years. The HUDF contains an estimated 10,000 galaxies.” — See here for a high-resolution picture) and in second a simulation of the performance of the James Webb Space Telescope. There’s a clear difference even to the untrained eye.

Hubble Space Telescope

First lets look at the Hubble Space Telescope.

It was launched April 24, 1990, and NASA celebrated its 17th birthday recently with the following stats: “800,000 observations, 500,000 images and 100,000 trips around the Earth.” The main benefits of putting a telescope in orbit are that it’s images are not distorted by the Earth’s atmosphere, it is not affected by light pollution and it can observe frequencies of light that cannot be observed well on the Earth’s surface (f.ex. Ultra-violet light, because it is absorbed by the ozone layer).

Credit: NASA and the European Space Agency, Public Domain image.

Hubble’s mirror has a collecting area of 4.2 square meters (46 square feet) and a diameter of 2.4 meters (94 inches). It can observe on the following wavelength: Optical, ultraviolet, near-infrared.

Improvement in Hubble images after the first service mission. Credit: NASA/ESA.

The Hubble Space Telescope was designed to be regularly serviced. The first service mission December 1993 allowed the Space Shuttle Endeavour crew to upgrade Hubble as well as boost its orbit. As you can see from the picture above, the upgrade was worth it: The result was much sharper images.

There was at least 3 other servicing missions (see here) but they had less dramatic results than the first one.

The impact of the Hubble Space Telescope on astronomy, physics and science in general is immense: Over 4,000 scientific papers based on Hubble data were published in peer reviewed journals.

Hubble has helped to resolve some long-standing problems in astronomy, as well as turning up results that have required whole new theories to explain them. Among its primary mission targets was to measure [...] the rate at which the universe is expanding, which is also related to its age. Before the launch of Hubble, estimates of the Hubble constant typically had errors of up to 50% [...]

While Hubble helped to refine estimates of the age of the universe, it also cast doubt on theories about its future. [It] uncovered evidence that, far from decelerating under the influence of gravity, the expansion of the universe may in fact be accelerating. [...]

The high-resolution spectra and images provided by the Hubble have been especially well suited to establishing the prevalence of black holes in the nuclei of nearby galaxies. [...]

Other major discoveries made using Hubble data include proto-planetary disks (proplyds) in the Orion Nebula; evidence for the presence of extrasolar planets around sun-like stars; and the optical counterparts of the still-mysterious gamma-ray bursts.

One interesting fact about Hubble: “Anyone can apply for time on the telescope; there are no restrictions on nationality or academic affiliation.” But of course, competition for time on the space telescope is extremely intense.

James Webb Space Telescope

Now on to the James Webb Space Telescope, which is named after NASA’s second administrator, James E. Webb:

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The research centre being built in Copenhagen will offer the computing power needed to resolve complex protein interactions. Credit: H. JEONG, UNIV. NOTRE DAME/SPL

Kudos to the Novo Nordisk Foundation (”The objective of the Foundation is to provide a stable basis for the commercial and research activities of Novo Nordisk and support scientific, humanitarian and social purposes.”) for the biggest donation to research ever in Denmark: 600 million kroner (US$110 million) to fund a protein research project at the University of Copenhagen.

A core component of the new centre will be a high-throughput facility to express and purify proteins, determine their structure and investigate their properties. The centre will focus on human disease, and will seek to formulate proteins for preclinical tests if they look promising as therapeutics. The university will keep the project’s intellectual property, says vice-dean Birgitte Nauntofte.

They shouldn’t be out of work soon:

genes can code for more than one protein, and the products described in genes can be modified after being translated into protein. This means that although the human genome contains some 25,000 protein-encoding genes, a given person’s various cells might use up to a million different proteins to do different things at different times in the course of a life. To crank up the complexity further, the proteins work in coordinated teams, requiring their relevant members to be in the right place at the right time if they are to generate the right response.

If you care about protein research and want to help, I suggest distributed computing projects, in particular Rosetta@Home and BOINCSimap.

This is the kind of philanthropic donation that I wish Craigslist would do, but unfortunately, it doesn’t look like it’s going to happen.

Source: Denmark launches big push for protein power

Artist’s impression of the planetary system around the red dwarf Gliese 581. Credit: ESO

In the May 3rd issue of Nature there is an article about the potentially habitable planet I wrote about.

They describe an experiment that would allow us to measure the density of the planet, the best way to find out if it’s a larger Earth (rocky planet) or a smaller version of Neptune.

Public domain image by NASA.

The problem is that for the experiment to work, the Canadian space telescope MOST (Microvariability and Oscillations of Stars) has to observe the planet, Gliese 581 c, when it crosses in front of its star, Gliese 581; the planes of its orbit would need to be aligned with the star from our position. The chances of that happening were about 2% on May 7th. I haven’t seen a report on whether or not the experiment was successful yet, but I’ll keep an eye out for it.

A rendering and a photo during testing of MOST, the Canadian telescope.

Before anyone asks, my interest in that planet and other astronomical objects is more based on increasing our understanding of the universe, not on some pipe dreams about moving there soon or replacing the Earth. We have so much to do here in the short and mid term to improve the human condition and the state of the biosphere, lets not kid ourselves about planets that are 20 light years away. They are interesting to study, but not on the agenda for now.