Education Matters

It’s fair to say that there were few surprises when the Nobel prizes in Medicine and Chemistry were announced. Chemists might again quibble, since the prize again went to biophysicists/biochemists for their work on a biological problem, but other than that, the prizes deservedly recognize magnificent work in two areas of basic biology that reveal very important ways by which life, literally, goes on.

Also, for the first time, there are three women scientists winning the prize in the sciences. While the prizes themselves are “gender neutral”, it remains a fact that (at least until recently), women have been massively underrepresented in the sciences, and only a handful of women have won Nobel prizes (a reflection of that underrepresentation). If not anything else, these prizes will at least inspire many more women scientists (and the winners have all been great role models, not just for women but all scientists).

Now to the prizes themselves.

The medicine prize went for discovering how one of biology’s most important processes is enabled by a quirky unit called a telomere. People realized early that DNA, which encodes all our genetic information, was packaged into chromosomes inside cells. Later, proteins called DNA polymerases were discovered, and these proteins were responsible for making copies of DNA, which would allow the DNA to replicate and be propagated. Scientists observed very early that there would be trouble with this copying process, cine the polymerase would leave tails of DNA at the ends, and that chromosomes would slowly shorten. But if that happened, how could all the genetic information be passed on correctly over generations? And then, was there a relationship between this chromosome shortening and the lifespan of the organism? Over the years, the winners of the medicine prize, Elizabeth Blackburn, Jack Szostak and Carol Greider went on to show how all of this was made possible by telomeres, the capped ends of chromosomes. Telomeres were shown to stabilize the ends of chromosomes, and proteins called telomerases synthesize chromosome ends inside the cell. The Nobel website has an excellent short summary on the discoveries.

Here are two general comments. The first is that all these discoveries were made in two organisms that seem as different from humans as possible; the humble yeast, and a common fresh water microscopic protozoa called tetrahymena. Though some people often question the purpose or use of studying these organisms, basic biological processes (like chromosome maintenance and telomere function) are perfectly conserved across evolution, from these simple bugs through humans. So the findings that came out of these organisms were directly relevant to human and mammalian cell function. Model organisms have taught us a tremendous amount of biology that has been directly applicable to humans.

The second general comment is that when Blackburn, Szostak or Greider started working on these organisms, there was no “application” for their research. At the time, telomeres weren’t known to cause any disease, nor could any “product” be made from studying them. The work was done in tetrahymena and yeast, and there was no “utility” in studying them. But the researchers followed their noses, pursuing questions in basic biology. Now their discoveries might play key roles in developing new therapeutics for cancer, ageing or hereditary diseases. When chromosomes shorten too much (and the telomeres shorten beyond a point), the cell stops dividing and goes into senescence. Normal cells don’t divide too much, so don’t need too much telomerase activity. Yet cancer cells divide incessantly. But they still preserve their telomeres, and don’t go into senescence. It has now been observed that cancer cells have high telomerase activity, and people now believe cancer can be treated by removing telomerases from cancer cells (and thus forcing the cells to go into senescence). There is a ton of work being done now to develop therapeutics against cancer targeting telomerases. Yet when this process was being studied, none of this was apparent.

The chemistry Nobels have gone to Venki Ramakrishnan, Tom Steitz and Ada Yonath for their pioneering work revealing the structures of yet another of the fundamental enabling units of life, the ribosome. This prize also recognizes the third act by which the process of how DNA encodes the units of life is completed. All three discoveries were seen at the level of the chemical atom using the same technique, called X-ray crystallography. Something that can only be described as an atomic photographic snapshot of biological molecules can be obtained using this technique. In the first Nobel Prize awarded way back when to Watson and Crick, X-ray crystallography revealed the famous double helical structure of DNA, which showed how DNA could be easily copied and replicated. Crick was later able to devise the triplet code, which allowed us to understand how DNA, with just combinations of four nucleic acids, could encode all the information for proteins, the building blocks of all life. This DNA was faithfully copied out to another form of nucleic acid, called (messenger) RNA. mRNA is made by a complex of proteins which form the RNA polymerase units, and the precise molecular details of this process were also largely revealed by X-ray crystallography. This work was recognized in the 2006 Nobel to Roger Kornberg. But there remains the third step, the extremely complex process by which this RNA is made into the actual functional units, the proteins of the cell. This work is done by the massive RNA-protein complex within the cell, called the ribosome. Primarily using X-ray crystallography (with other structural and biophysical methods) Ramakrishnan, Steitz and Yonath revealed the structures of the ribosome, first with different sub-units of the complex, and later with the structures of the entire complex itself. The Nobel website has a good, simple summary of the process here. It is a pity that only three Nobel prizes are awarded at a time for a discovery, because Harry Noller has made just as many pioneering contributions to ribosome structure and function. It is too bad that he missed out (and it must have been a close call between Ramakrishnan and Noller).

Most of the work on ribosomes was also done on the most obscure of organisms, mostly microbes that live in harsh environments, like Geobacillus stearothermophilus or Haloarcula marismortui (which lives in the Dead Sea) or Thermus thermophilus. Much of the basic mechanisms of ribosome function are conserved right from bacteria through eukaryotes (of which humans are also a part of). Yet, there are also many differences between bacteria and eukaryotes (and the microbial yeast, a eukaryote, has ribosomes more similar to humans than to bacteria, a fellow microbe). Yonath, Steitz and Ramakrishnan soon had structures of ribosomes with various antibiotics bound to them, showing how these antibiotics could block the ribosome and hence kill bacteria. Their work now gives us a fantastic snapshot to ribosome function, and provides a platform for chemists to come in and make new antibiotics against harmful bacteria.

All in all, the prizes have gone to recipients without any major surprises, and their work has tremendous impact, and is a celebration of research in basic, fundamental biology.

I’ll leave you with this video of the ribosome from Tom Steitz’s lab. I never thought the ribosome looked like a death star, but with the music playing I see it in a different light.

On Friday, November 13, I drove back home to San Jose from Las Vegas. The drive is a long one, and requires a lot of energy. In the last year, I have made it several times. It takes me just about nine hours and 20 gallons of gasoline to supply the motive force that compels my Jeep to travel the 515 miles from the middle of the Las Vegas strip to my house. The drive takes me through about 300 miles of the Mojave Desert and 140 miles of California’s Central Valley. See Figure 1.

Figure 1 Las Vegas to San Jose

In the last few months I have had a few problems (about 8K bucks worth) with my Jeep, so when I drive it now, I keep my ears open for sounds that might indicate approaching danger and my eyes on the Jeep’s instrument panel gauges for indications of imminent vehicle
failure and/or the end of the universe. See Figure 2.

Figure 2 Jeep gauge panel

Just this last August, 2009, I left the Flamingo Hotel in Las Vegas at 2:30 AM to make the drive back to San Jose. About 50 miles out and in the desert, I started getting a clanking sound at about 70 mph. I slowed down to 65 mph and the clanking stopped. But then it started again at 65 mph. I slowed to 60 and it stopped. Then it started again at 60 mph. This was not good, I thought. I am in the middle of desert at night and my car is going to break down and strand me. I will die a horrible death, my bones being picked clean by buzzards near Zyzzx Road. I don’t know much about scavenger type birds, but this is what I imagined. See Figure 3.

Figure 3 Zzyzx Road near Baker, CA

I get chills just thinking about it even now.

My Jeep did not break down and I was able to limp home without incident. It turns out the problem was in my transmission. I forget now what the part was called, but I do remember it cost me 22-hundred bucks to get it and install it.

Staring just this last July, 2009, the “check engine” light on my Jeep’s instrument panel began illuminating. It first illuminated when I was in Los Angeles putting gas in my car to start the 265 mile drive to Las Vegas. Just what anyone would want to see, the check engine light. What light could be worse? Of course the check engine light must be Jeep’s way of politely saying, “impending and inescapable engine explosion.” See Figure 4.

Figure 4 Denny’s Jeep exploding

I drove to Vegas anyway. I was nervous the entire trip, but I still went. Then, with the light still on, I drove around Vegas for a few day, then drove the 520 mile back to San Jose.

My mechanic checked for the cause of the light. His diagnostic machine announced the cause of the problem as, let’s just call it Mistaken Cause 1. He fixed it. Three hundred miles later, the check engine light pops back on. The diagnostic machine states the cause of the problem as, let’s call it Mistaken Cause 2. To make a long story shorter, the cause was not found until after $1200 worth of Jeep parts. The Jeep dealer finally correctly determine the cause to be an 80¢ fuse.

Now I am always nervous about the ability of this car to operate in a way that will not leave me stranded in the middle of the Mojave Desert in the 150 degree summer heat or the biting winter cold.

When I drive my Jeep now, I am constantly aware of noises and smells and clunks and jerks. I keep a close eye on my instrument panel gauges.

So Friday on my drive back to San Jose from Las Vegas, I am on Highway 58 passing the Desert Sage apartments near Edward’s Air Force Base and the town of Mojave, and I check my water temperature gauge. I expect to see the needle in the standard operating zone just slightly to the left of 210. But its not! Oh no, it is just slightly to the right of 210. It is never there, it is always just to the left of 210. I am sure my engine is overheating and ready to explode. See Figures 5 and 6.

Figure 5 The bad zone and the good zone

Figure 6 The Desert Sage Apartments near Mojave

To delay engine explosion, I back off on my speed from 65 to 60. Ahh, the temperature gauge needle moves to the left back into the standard operating zone. All is well. I speed back up to 65. The needle moves back to the right in the engine explosion zone. Oh no, I am 300 miles from home and my car is about to ignite into flames.

But now I have another problem. I am having trouble reading and making sense out of the water temperature gauge. Check out the increments on both the fuel and oil gauges. See Figure 7.

Figure 7 Fuel and Oil and Water temp gauges

I think they read as one would expect. Each increment is the same. That is, the scale is linear. In the case of the fuel gauge, each increment is 1/8 of a tank of gas. In the case of the oil gauge, each increment in 10 psi. Count them. The oil pressure starts at 0, then with markings at every 10 units, goes to 40 psi then to 80 psi. Forty psi is right in the middle between 0 and 80 psi, right where we would expect it to be. These scales are linear as they indicate constant change.

But look at the increments on the water temperature gauge. What the? The increment lines are evenly spaced, visually giving us the idea that the gauge is set up linearly. But look closely at the numbers. Visually 210 is halfway between 100 and 260.

If the scale is linear between 100 and 210, then each increment represents an increase of 27.5 degrees.

(210 – 100)/4 = 27.5

If the scale is linear between 210 and 260, then each increment represents an increase of 12.5 degrees.

(260 – 210)/4 = 12.5

So not each tick mark represent an integer value water temperature. The tick marks represent:

100
100 + 27.5 = 127.5
127.5 + 27.5 = 155
155 + 27.5 = 182.5
182.5 + 27.5 = 210
210 + 12.5 = 222.5
222.5 + 12.5 = 235
235 + 12.5 = 247.5
247.5 + 12.5 = 260

This looks like a crazy way to design a gauge to me. There must be some logic to this as I want to believe that Mr Jeep would not be joking around with me while I am in the middle of the desert.

Now I worried about high water temperatures and crazy gauges. I am in the middle of the desert and I am about to drive uphill into the Tehachapi mountains. I am sure my water temperature indicator needle will move even farther to the right, my car will overheat and my engine will explode, taking me out as well as all the cars around me.

It didn’t happen. I eased the Jeep up the mountain, the needle bounced back and forth between OK and Explode and I made it to the summit. Once there, I could drive without putting much of a load on the engine, keeping the water temperature in the safe zone. That went well.

When I got down the mountain and into Bakersfield, the needle stayed in the standard zone and all was well.

Driving north on Hwy 5, I tried to figure out why the needle moved to the right when I was in the desert. The outside air was cool and I was at a high elevation. Both these features I thought would keep the water temperature low. But if the Jeep really is running well and is not experiencing mechanical problems, there is something else going on. I am thinking about the gas laws and I will explore that this week.

Its almost the end of 2009, and I read on Planet Debian today a entry on writing man pages.

So man pages… where do we start? We have HTML / CSS / XML / RST which are all generally globally accepted formats of communication. Unfortunately, man pages do not use those.

And quite frankly, I am a fairly busy person, and have quite enough things to accomplish in a day. Why would I learn yet another formatting language? What justifies these files being in their own little world, when the whole world as a courtesy is supposed to provide them with their packages?

There really needs to be a movement to kill man pages in their current form, and bring them up to speed. A dialect for the sake of having a dialect really isn’t worth it when we have abundant alternatives.