Thursday, November 13, 2008

Find The MIssing Experiment

Prof. Santa Singh, a world class scientist from Chandigarh, was also interested in locating the Ultimate Sensor, just like us. He, however, was focusing on the sense of Sound. He decided to use the fruitflies - Drosophila melanogaster - for his research for two important reasons - a) firstly, the fruitflies are very genetically amenable and b) secondly, the female flies respond to the male courtship song by spreading their wings, a visual signal for males (and Santa Singh) to indicate their readiness to mate (Not with Santa Singh! but with male flies).


Prof. Santa Singh was delighted with his idea and the possibilities that it represented. He wanted to conduct full time research on it. He decided to apply for NIH Research Grant R01 that would supply him with a crucial fund of 1 million dollars over the course of four years to conduct his research without any distractions. There is a lot of competition for these grants, so some preliminary experimental data is also supplied by the applicants in addition to their proposal to demonstrate the strength of their proposal.


Thus motivated to do some real experimental work before submitting the proposal, Prof. Santa Singh arrived at his lab on one fine Monday morning. He downloaded the courtship songs from the internet, borrowed a few wildtype virgin flies from the neighboring lab, put them on a Petri Dish containing aphrodisiac food and .... played the music!


For the first one minute, nothing happpenned - the female flies behaved as if nothing was happenning. Then one female fly spread her wings for two seconds and retracted them. Then, nothing remarkable happenned for the next 5 minutes. Then, another female fly spread her wings for five seconds. And then, nothing remarkable happenned for the next half an hour. By then, Prof. Santa Singh was frustrated.


He had imagined that the flies would be always ready to mate - they were like machines - Supply the Stimulus, Elicit the Response - but alas, his brilliant idea was trumped a well known universal truth - that the females are very moody and not always ready to mate! He went home frustrated and discussed the matter with his wife, a psychologist who ran a successful marital counselling business. She explained to Prof. Santa Singh that only two types of females are always ready to mate - 1) those who have been abused as children and are suffering from low self esteem, and 2) those that have a higher hormonal level than the normal people due to genetic alteration. "Ah Ha!", said Prof. Santa Singh. He just had had a "Eureka" moment. He thanked his wife profusely for her expert counselling and excused himself to go to the study to write up his proposal.


Prof. Santa Singh's idea was simplicity itself - he wanted to propose an isolation of "horny" mutation in fruit flies, whose behavior would be an immediate spreading of wings in response to the courtship song recording. By way of preliminary experiments, he wanted to isolate such a mutant fly. He knew it would be done very quickly, because his neighboring lab was screening 2000 mutant lines for behavior at the very moment. He just had to borrow their flies, put them on a dish, play the music and watch for the wing-spread. It was a very quick assay! He was very pleased with himself.


The next day, it was a beautiful Tuesday morning, he arrived at his lab, armed with the twenty trays of 100 vials containing 2000 mutant flies. He started doing his assay - anaesthatize the flies by giving them a puff of Carbon Di Oxide, put them on the petridish, play the music and score for wing spread action. He was very efficient ... he was workig with 20 vials at a time ... In four hours, he had screened all 2000 lines. He was no more so ecstatic as he had been when he started out. Not a single vial contained flies that would spread their wings within 10 seconds of playing the courtship song. How disappointing! Yet ... there was that one vial .. vial number 297 ... which had some weird behavior ... he remembered them being particularly "jumpy".


He went back to vial 297, poured some more flies out, anaesthetized them, laid them on a petridish, and waited for them to become active. They were behaving normally. They looked normal. The eyes were red, the wings were straight, the body was normal, the bristles long ... in fact, as far as looks were concerned, they looked completely normal! Yet, when he turned the music ON, a few of the flies JUMPED and hit the ceiling of the Petri Dish. The kept JUMPING. They stopped when the music was turned off.


Prof. Santa Singh felt another Eureka experience building up in him. So, he did not have "horny" mutant but a "jumpy" mutant. He needed the "horny" mutant because he wanted a visual response of spreading wings to the stimulus of playing courtship song. But "jumpy" mutants also had a visual response - that of jumping to the ceiling of the Petri Dish - in response to the very same stimulus - namely the courtship song. All he had to do was substitute "jumpy" for "horny" and "jumps to celing" for "spreads her wings" in his proposal that he had drafted yesterday, and the proposal would essentially still be good!


This indeed was very good luck! He already had the "jumpy" mutant fly. In fact, he even knew which possible genes were mutated in it, because the flies had come from the Bloomington Stock Center, a centralized stock center in the world, on which the whole world was working!


Prof. Santa Singh quickly revised his proposal, and rushed it by FedEx to NIH. The grant was reviewed and voted on. It was a fantastic proposal - it ranked in the top 90 percentile of all the proposals. A few months after the submission of the grant, Prof. Santa Singh received a letter congratulating him on being awarded the R01 grant from NIH and the details of how he would be receiving the $1,000,000.
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In the meantime, Mr. Banta Singh, an aspiring graduate student, had expressed his desire to join Prof. Santa Singh's lab and conduct research on the anatomical location of Sound Sensors in "jumpy" flies. Just the day before receiving the letter from NIH, he had concluded the most fascinating research in his entire life - he had made a breakthrough! He had identified THE ANATOMICAL location of Sound Sensor. When he mentioned this to his mentor, Prof. Santa Singh smiled at Mr. Banta Singh and advised him to write up a thesis proposal and take his qualifying exam. When Mr. Banta Singh submitted his thesis proposal the very next day, all the members of his thesis committee were surprised by the industry of Mr. Banta Singh. Three weeks later, everyone was looking forward to the presentation.


Mr. Banta Singh started his presentation by narrating the story of how the "jumpy" mutant had been isolated in just a day and what a brilliant tool it had turned out to be in the research of anatomical location of the Sound Sensor. He then outline the four approaches he had initially undertaken - a) to genetically ablate a few neurons in the brain, b) to anatomically ablate a few body parts at a time c) to use laser to ablate different patches of neurons in the brain and d) to combine these approaches and ablate Multiple body parts simultaneuosly.


Genetic ablations of neurons by induction of the apoptotic genes in the adult head in different tissues resulted in dead flies, normal flies or severly retarded flies. Anatomical ablation of single body parts such as a leg, a wing, an eye etc. did not lead to any difference in the "jumpy" behavior. Laser ablation of different patch of neurons in the brain yielded the same results as the first one. However, the final approach had yielded some really great positive results!


He then showed a video he had made of the final crucial experiment. The video showed a single "jumpy" fly in a Petri Dish. The courtship music was turned on. Within a second of starting the music, the "jumpy" fly jumped. Then one leg was removed from the "jumpy" fly and released back into the Petri Dish. The courtship music was turned back on again, and now the "jumpy" fly jumped again! Mr. Banta Singh proceeded to remove one leg at a time with a pair of tweezers, release the fly into the Petri Dish, play the courtship song and write a comment in his notebook until the "jumpy" fly had only one leg left. Mr. Banta Singh placed the "jumpy" fly with just one leg back into the Petri Dish and played the courtship song one more time. The "jumpy" fly made its best effort to jump, which he recorded in his notebook. After he pulled off its last leg, he placed the legless "jumpy" fly back into the Petri dish for one last time and played the courstship song. After repeating the song many times without the "jumpy" fly responding, he stopped the video, and exclaimed to his audience, " After the fly loses all of its legs it becomes completely deaf!"


The audience laughed. They thought that either Prof. Santa Singh or Mr. Banta Singh had played a joke on them. They were surprised by the solemn expression on the faces of both Prof. Santa Singh and Mr. Banta Singh. They were in earnest! They both really believed that the site of auditory sensation resided in the legs of the fruitflies. Mr. Banta Singh proceeded, "I did one last experiment to confirm the results, and here is the video". After his demonstration of the video, his entire audience was dumbfounded. They burst into applause. Everyone thought that Mr. Banta Singh and Prof. Santa Singh had made a Nobel Prize winning breakthrough. Indeed, ten years later, they both went to Sweden to accept the accolade.


The question to you, my gentle reader, is: "What was the last experiment performed by Mr. Banta Singh that was documented in the final video"? Hint: The last experiment was performed on wild-type flies ... the clues / information are already available in this article .... And YEAH! THIS IS A SERIOUS SCIENCE QUESTION DESPITE ALL APPEARENCES!

2 comments:

Vidhi Patel said...

the wild type female flies, when exposed to the courtship music, spread out their wings..
if the legs of these were removed anatomically, and then the music played, and if the flies do not respond by spreading the wings, it shud conclude that site of sound sensation was in legs...???

Srikanth said...

Well done! That's the idea!