Chad Vader: Full time loser

Heh...

Do not underestimate the power of the dark side. It also spawns the iconic Chad Vader, brother of the slightly better known Darth Vader.

Here's the first episode of the series:


You can view all four episodes of Matt Sloan and Aaron Yonda's hillarious creation here.

Have fun, and may the force be with you.

Using bacteria to deliver anti-cancer drugs

Cancer patients and their friends and families know that cancer chemotherapy is notoriously difficult and toxic to patients for a wide variety of reasons, and the big problem is to kill cancer cells while leaving the rest of the normal cells in the body alone. There are a few strategies to go around this problem. One popular strategy tries to create drugs that target something unique in cancer cells, and so affect tumor cells more than normal cells. Another strategy uses a “zoning agent”, like an antibody that binds to something specific on a cancer cell, to which the drug itself is attached, so that the drug reaches the cancer cell alone. A third strategy often uses agents such as liposomes (which are sacs made of fatty substances), which can penetrate the pores present in tumors (but also a few other organs). The drug is delivered within the liposome sac. Once they get in, they stick around, and the drug within is released, so can act on the tumor alone. However, all of these methods have some limitations.

But can biology provide tools and answers that will allow the combination of two or more of these different systems, to make the cancer drug even more specific and effective? There are numerous different efforts going on across various research groups, but this rather nifty way to answer this question, where some researchers have found their solution in a bacteria really caught my attention.

There is a large genus of bacteria called Clostridium, which includes some toxic ones that cause botulism (common in food poisoning) or tetanus or colitis (from diarrhea to death), while other species of this genus are harmless and non-toxic. Now, these bacteria are anaerobic, living in low oxygen areas. Most cancerous tumors have a “hypoxic” core (where oxygen levels are very low, due to excessive growth of cells, and a cutting off of blood supply). So, strains of clostridium would selectively infect this cancerous area. A strain of clostridium called C. novyi-NT (NT is non-toxic) also has a second property, in that it secretes something that disrupts lipid bilayers (which constitute the liposome). The researchers figured that this second property could also be used to improve drug release from liposomes.

So, combining this strategy, they infected mice with tumors with this bacteria, C. novyi-NT, AND liposomes containing an anti-cancer drug. If they injected the bacteria alone, or the liposome with drug alone, they only found limited therapeutic effects. But when they injected the bacteria as well as the liposome+drug, they saw dramatic therapeutic effects. All the infected mice showed reductions in tumor size, and 65% of them showed prolonged survival. Basically, C. novyi-NT dramatically improved the anti-tumor activity of the drug in cancerous mice. The bacterial treatment appeared to improve the distribution of the drug in cancerous tissues six fold, compared to just the liposome with the drug, while showing almost no effect on normal tissue.

The results are pretty striking, and actually do suggest the possibility of using such strategies (with this bacteria) in delivering anti-cancer drugs. The researchers also went one step further. They identified and characterized the specific protein in the bacteria that cause the liposomes to break. This actually provides even more strategies, where infection with the bacteria itself may not be required (you could for example attach this protein to a tumor targeting drug, and improve that drug’s efficacy).

A wonderful bit of research. You can read all about it in Science, 24 Nov 2006: Vol. 314. no. 5803, pp. 1308 – 1311

The fear of a timeout

There was a time when I used to think a timeout was only something basketball players took during a game. But that was a long time ago. I came to observe the full power of a timeout only after I came to America some years ago. And I found out that it was the most powerful weapon parents had in the fight against their kids. Whenever their kids did something they weren’t supposed to, a simple timeout would suffice to put the fear of gods, hell, pink unicorns or worse, parents, in to the kids.

The concept remains simple. Kid goofs up/throws a tantrum/kicks up a fuss/does badly in school/is just plain stupid. Parent(s) get hold of aforementioned kid, and put the smack down on him/her, by the use of a timeout. The order will be given (“you have a timeout for 20 minutes”), and all it means is that the kid needs to sit in a corner without doing anything for 20 minutes. And magically, the kid would start pleading for forgiveness, even as I imagine this to be perfect nap time. The more powerful version of a timeout, being grounded, amazed me even more. Being grounded just meant that the kid would have to sit in a room (complete with all the modern comforts of a TV, playstation, a computer, a comfy bed, and books) for a day, a week or a month. That, to me, seems like the definition of heaven.

And then I see the inimitable Carlos Mencia a few weeks ago on Comedy central, talking about the same thing. Of course, here he’s making fun of kids doing badly in school (with his typically “inappropriate” racial stereotypes). White kids who are troublesome or do badly in school get time outs. Hispanic kids screw up; they go home and get thrashed. Asian kids………get the shit beaten out of them even before they screw up, so that they will never dream of screwing up!

Which reminded me of what an African researcher here (I think he’s Ugandan or Kenyan) said. If he did something mischievous in school, his teacher would beat the crap out of him. He’d go home and tell his mom, and she’d go “you stupid kid, why did you have to annoy your teacher?” and proceed to then beat the crap out of him for annoying his teacher. So, the sorry kid would go and tell his uncle about his beating. His uncle, furious, would grab him, say “why the hell did you have to piss off your mother by pissing off your teacher”, and then beat the crap out of him. So that stupid bastard would finally go to his last hope, his dad, who’d hear the story, turn blue in rage, and then proceed to give him a sound beating for annoying his uncle by annoying his mother who got annoyed because he pissed off his teacher first.

Heh.

Now that story may well fit in India. I’ve seen some teachers soundly thrash their students. Canings (or that tight rap on the knuckles with a wooden ruler) at least used to be rather common when I was a kid. And I got off lightly, since the teachers in my school were a rather good lot, who rarely dished out a beating. I’ve heard some pretty good stories of teachers beating the shit out of a student for something as trivial as forgetting to bring the homework notebook, or writing English notes on a Hindi notebook, or not bringing a compass and protractor to the geometry class, or not wearing a uniform to school.

Sound familiar to some of you?

Somehow, it all seems to come down to the old colonial saying, “spare the rod, and spoil the child”. The concept of beating kids to discipline them has long been abandoned in the west, and if that happens in the States or the UK, that poor teacher is going to prison or will face some rather hefty lawsuits. Much of this holds for parents as well. But in most of the old British colonies (in South Asia, or Africa) the rule of the wooden ruler holds sway to this day.

Now, the question that always remains in my mind (which remains amazed at the power of a timeout) is this. How does one get parents or teachers in Asia (India in particular, since I’m most familiar with the environment there) to stop beating the crap out of the kids?

Bad boy..

Look at that bad boy.

Zero to sixty in FOUR seconds. Can cruise at 130 mph. To quote the manufacterers "How powerful is the acceleration? A quick story to illustrate. A favorite trick here at Tesla Motors is to invite a passenger along and ask him to turn on the radio. At the precise moment we ask, we accelerate. Our passenger simply can’t sit forward enough to reach the dials."

So what's cool about that? Any Lamborghini can do that.

Aha! But this puppy is fully electric.

Yup. With an equivalent efficiency of 125 mpg, AND a max range of 250 miles (don't need to worry about this stopping in the middle of a ride).

This is the future of electric cars. And it's not a prototype. You can buy it.

Their website, Time magazine best inventions 2006

You don’t need to be a rocket scientist.....

.......to be the president of India.

(Apologies for a rare “political” post on this blog).

As is often the case, conversations with friends (particularly Indian friends) tend to drift towards some discussion of politics. And it is quite common to end up discussing the present president of India, Dr. Abdul Kalam. Now, many of my friends think it’s wonderful that a prominent scientist is the head of the nation. They’re taken in by his grand visions of the nation, and his optimistic books on India’s future. But most also are disappointed with his stint as president. They say he’s too naïve and trusting to be president, or conclude that the president of India has no real power, is just a rubber seal of approval, and all the power lies with the elected prime minister and his/her cabinet.

But really, that is only partially true. Actually, the president does have substantial power, and I’ve always held that you don’t need to be a great scholar (or, in this case, a rocket scientist) to be president. All you need are three attributes: a strong, independent, non-partisan mind, a good understanding of constitutional law and the powers of the president, and the courage to see things through. Unfortunately, the Dr. Kalam hasn’t demonstrated any of these qualities. He’s undoubtedly learned, honest, dedicated, has a vision and loves his country, but that alone isn’t enough.

There are (in my mind) three or four occasions when the president of India does have a lot of power. The first (and perhaps greatest) power is his executive power, during the swearing in of a government. At this time, the president is all powerful, and he/she administers the oath of office for the prime minister and cabinet. Here, let us say there is some one who’s a known criminal, who is trying to become a minister (these hypothetical examples might reflect reality, but that is purely coincidental). If the president want’s to, he/she can actually refuse to administer the oath of office to that person. There is absolutely nothing anyone can do about it. The second (somewhat related) occasion is when a governor of a state is appointed. That person too is appointed by the president (based on the recommendation by the government). At this time, the president can refuse to appoint strongly partisan governors, or governors known to be docile or easily satisfied. He can insist on the appointment of a governor with the same qualities of non-partisanship and understanding of constitutional law. This then has a direct and tremendous impact on the appointment of state legislatures, and we might avoid seeing some of the circuses during the process of state legislatures being elected.

The third occasion where a president has a lot of power is in his legislative role, in the passing of a bill. A bill becomes a law only when the president has given his approval. The parliament sends a bill to the president, and if the president does not approve of the bill, it can be sent back. However, the rule states that if the parliament does send the bill back to the president a second time, the president has to sign it, and the bill becomes a law. Now, with weak, populist governments (as is usually the case in India), sometimes bills that should never be passed reach the president. The president sometimes does disapprove of the bill (if I remember correctly, Kalam did do so for some bill, which I can’t remember), but it is often sent back to him a second time, and he has to sign it.

But the rule does not say how quickly the president has to sign it. If the president strongly feels that a bill is against the greater interest of the nation, but is in a situation where he has to sign it (because it has been returned to him a second time), he can just sit on it for as long as he wants, making life rather uncomfortable for the politicians pushing for it. In this time, the president can make his views clearer to the national public through the media, and particularly through his speeches during independence or republic day (which is televised live, and is printed in every single newspaper in the country).

To do this, however, the president needs to have the courage to not succumb to the pressure that is bound to follow him if he does not sign the bill. But this is one quality that a good president needs to have.

Of course, there is the fourth occasion where the president becomes all powerful, during a national emergency. But that is a situation I never wish to see, since it is invariably accompanied by the suspension of most fundamental rights and the right to freedom. It is particularly important to have a strong president during these times (or else there might be other incidents like what Indira Gandhi did to keep herself in power).

So, the president of India is not really all that powerless. His/her power is different, that’s all. You don't have to be a rocket scientist to be a good president. In fact, you probably shouldn’t be one.

A world of wonder

Recently Selva put together a fantastic science fiction short story contest, for which I was one of the panelists. I thoroughly enjoyed reading the 29 stories that were sent in, and the results are out with the top nine for every one to read. The authors were all enthusiastic, though some stories needed more work. But the best stories made me think about why I loved sci-fi so much.

My own love for science fiction started early, even before I really knew what science fiction was. I was probably some 8 or 9 years old (and already an avid reader) when some one gifted me an abridged version of Twenty thousand leagues under the sea and the enigmatic Captain Nemo had me hooked. A submarine the shape of a whale seemed too fantastic to believe. I didn’t wait long before I started reading the complete, unabridged versions of Jules Verne’s stories, which remain fascinating to this day. Verne was one of the earliest visionary sci-fi writers, writing about underwater travel or space travel a century before it happened. Dang, he wrote about space travel before the Wright brothers invented the airplane. And his stories were of intrepid adventurers, and non-stop action, something I could hardly resist in my early teens (and still can’t ignore). His twenty thousand leagues as well as From the earth to the moon remain amongst my all time favorites. The other grandmaster of sci-fi who caught my early attention was H.G. Wells. But it wasn’t his more popular Time machine or War of the worlds that fascinated me. It was his darker The island of doctor Moreau, with the man-creatures and the law that captivated me.

The important thing to remember about sci-fi is that it may be easy to get carried away with gadgets or innovations, but sci-fi is always about human problems and weaknesses, and is driven by its science content. And the masters of sci-fi always remembered that.

I only moderately enjoyed Arthur C. Clarke (though the 2001:A Space Odyssey movie did perfect justice to the exceptional book), but remain a committed reader of the man Arthur C. Clarke described as the best science fiction writer in the world (in the famous Asimov-Clarke Treaty of Park Avenue), Isaac Asimov, with the Elijah Baley series being my favorite, particularly as the blurring between android and human become greater . His popular science books remain amongst the easiest to read for a lay-reader.

There also remains the cross-over genre of Science fantasy, from Ray Bradbury through Frank Herbert and his messianic Dune series, and sci-fi pulp with Star Wars (“A long time ago, in a galaxy far away”) where science meets religion, politics, power and the survival of humanity. Where did science stop and fantasy begin? Then there is the often depressing but brilliant work of Philip Dick, who’s The man in the high castle played fantastically between worlds of alternate history, in the book as well as the book within the book.

Some of my friends think all this reading of science fiction and fantasy has ruined my mind. But they forget that I was saved thanks to the irreplaceable wit and ever reliable satire that Douglas Adams wrote, and Terry Pratchett continues to write. Reading Dirk Gently’s mostly harmless escapades has made life (almost) worth living, so I’ll thank my small gods for that.

This brings us around to the beginning of this post, the Scian science fiction short story contest. Some of the stories were dark, often futuristic, and sometimes with a view that science in the future could lead to doom. Sure, it is a paranoid world today. Sure, some people think we’ll have cloned humans rampaging around destroying humanity. Sure, some day some nut-job might want to rule the world by moving continents or aliens might invade the earth. But to me that’s not what science fiction, or science itself, is only about. There will always remain a universe of knowledge that we’ll never know. Science will always be about that quest of discovery and the frustration during the quest and is always overcome by the thrill of discovery. The only way to find out what is out there is to adopt the trekkie philosophy, and go boldly where no man (or woman) has gone before. It doesn't matter if it is dark or bright out there. The fun is in the ride. It's magic.

(Here are Falstaff’s thoughts about the contest).

Self recognition, and science in the Islamic world

From the beeb’s always excellent Science page comes a fascinating story.

Elephants don’t just remember, they also show self awareness.

Yup, elephants can recognize their own reflections in the mirror. To quote the article:
“Many animals will respond to a mirror but very few show any evidence that they recognise themselves in the reflection. Canines, for example, will react to the "other dog" and will even look behind the mirror to try to find it."

This puts elephants in the group of animals with the highest degrees of self awareness; humans, the great apes, and dolphins. Read all about it here.

---------------

And for some more interesting reading, Nature has an extensive feature on Science in the Islamic world.

To quote some nuggets:

“Low investment and a low profile combine to keep the scientific community small, marginalized and unproductive. This is not simply a matter of underdevelopment; the oil-rich Gulf states invest pitifully in R&D…”

Or “The conditions in which knowledge flowered a millennium ago are hardly those that today's Islamists say they favour. Back then, support for scientific enquiry was matched by an openness to other cultures and sources of knowledge.”

The articles range from the present seemingly hopeless state of science in Islamic countries, to a beautiful timeline of historical scientific achievement in the Islamic world, to poor support for science oil rich gulf states, with a few bright spots in Turkey, Malaysia or (surprisingly) Iran, and many, many more excellent articles.

Surprisingly (for Nature), many of these articles are free to access.

The articles are well worth your time. Here.

Be cool, live long

I had earlier written about Calorific restriction (eating less) and living longer. This wasn’t about starvation, but just by eating less in terms of calories (but still getting enough essential nutrients) led to substantially longer and healthier life spans (in everything from the humble yeast to mammals, and likely, us). Now, the New York Times has an article chronicling the same story, but perhaps written in a more entertaining style.

But that is not what this post is about. That’s old news. This one is cool.

Literally.

It is widely believed that body temperature acts in concert with calorific restriction in increasing life span, as calorific restriction does seem to lower body temperature.

The normal body temperature is 98.6 F (or 37 degrees Centigrade). That’s what we all know. We also believe that this temperature is the optimal temperature for survival and life. This body temperature is controlled by a region of the brain, the hypothalamus, where a complex network of different types of neurons interact to maintain and control body temperature. By directing blood flow to shift to cutaneous blood vessels (that reach the skin), heat can be spent, while directing blood flow to deep blood vessels retains heat.

Researchers decided to test the cool-body temperature- long lifespan theory, and to do that they made use of this central temperature controlling system. Cells have a certain organelle, the mitochondria, which convert organic material in to energy (in the form of ATP) that the body uses. Now, mitochondria also have a protein called UCP (with two forms, 1 and 2) that uses up this energy and results in the release of heat. In this study, the researchers cleverly decided to take advantage of the central temperature controlling region of the hypothalamus to modify the core body temperature itself.

What they did was to engineer mice to over express this UCP protein (UCP-2) exclusively in the hypocretin region of the hypothalamus. This excess of UCP-2 slightly increased the heat in that small region alone. This effectively fooled the hypothalamus in to thinking that the entire body was too hot, and resulted in a lowering of the core body temperature of the mice, resulting in a lowering of temperature by 0.3-0.5 degrees centigrade.

The engineered “cool” mice were then fed the same amount of food as wild-type (normal) mice, and were monitored. Due to their lowered body temperature, these engineered mice ended up gaining more weight (compared to the normal mice), even though they ate the same amount of food. This was somewhat expected, since maintaining a lower body temperature would require less energy.

One would imagine that this weight gain (which is normally known to adversely affect lifespan) would result in a lowered life span. But surprisingly, what the researchers observed was exactly the opposite.

What they saw was that the engineered mice with slightly lower body temperature on average increased their life span by about 8% (in human terms that would be an increase in lifespan of about 8 years!). To push the question further, both the normal as well as the lower body temperature mice were fed on a fat diet. The engineered mice ate normally, and ended up surviving longer than the normal mice.

Now, what was earlier known was that calorific restriction would result in lower body temperature as well as longer lifespan. But here, the results suggested that lower body temperatures actually increase lifespan, independent of calorific restriction.

This study raises some really interesting questions. Would it be desirable to decrease body temperature slightly, and therefore live longer? Body temperatures are tightly regulated, and have evolved over millions of years to be where they are today. So, even if a slightly lower body temperature results in a longer lifespan, could there be other adverse side effects on behavior, or psychology or reproduction or something else? Calorific restriction appears to lead to healthier longer lives. Will just lowering of the body temperature do the same?

As always, more questions, each as fascinating as the other.

(You can read the complete article here (Science Vol. 314. no. 5800, pp. 825 – 828), or a short comment here)

Borat

Borat.

Go watch it. It is as outrageous, irreverant and hillariously brilliant as I had hoped it would be, and impossible to review. If you are easily offended, stay at home and watch Friends.

There was one moment, during a scene where Borat crashes an evangelical meeting, where I was nervous. After all, this is Texas, the heart of the evangelical bible belt. But then, after a few nervous, silent moments, the audience started chuckling, and then laughing.

I'll leave you with the Borat version of the Kazakh national anthem till then.



I'm eagerly waiting for Sacha Cohen's next creation.

Change in the air?

I thought things were changing when I read that people in the most unlikeliest of places, Texas, were lining up to buy hybrid cars like the Prius, and began to believe it when I started seeing them on the highways, cruising right next to your friendly neighborhood Hummer.

But you know there’s real change in the air when truck and car dealers start talking about gas mileage on TV ads.

Another two years of high gas prices, and our little stick-shift 40-mpg Honda Civic coupe may not feel as lonely on Texas roads, and Texans will be hopping in to their Civics and Toyotas and screaming down the highways.

Of course, if that really happens pigs will also have wings, and cows will start mooing “Texas, our Texas”.

(There will be some some “nice” science posts to look forward to for next week).