A, B, O and We

I had an interesting discussion with Ganaraj, that ended up in some unanswered questions on Blood Group Antigens and Antibodies. He was so interested in the Immunophysiology of the Blood Group antigens that he really dragged me to the basics. By the way, I love it when something goes to its basic. Before I throw up those questions, let me give you some background story under which he came up with those questions.

We were discussing on the issues of importance of blood groups in determining the possible consanguinity in a marriage. I told him, it's hard to estimate the genetic resemblance of the partners by blood group alone. Blood Group antigens obey a certain inheritance pattern and represent one or a few specific genes but there are million others to be considered! He then raised his question of the child getting affected by the mother's immune system if the child belongs to a blood group other than that of the mother. He was concerned about the Hemolytic Disease of the New Born. To explain that, I had go back to the basics. By the way, Ganaraj is a techie and he is no way "academically" concerned with the life sciences. Here's what I explained him.

What is an Antigen? Before jumping on the properties of an Antigen and all that stuff, Antigen is basically a Protein. And so, it has all the basic characteristics of a protein, plus some other special qualities. Further dissecting, Proteins are complex molecules, with amino acids as their building blocks. There are 20 different amino acids which all the living beings on Earth use to synthesise a protein. The "number" of amino acids and the "sequence" of the amino acids in a protein is determined by the Master Code, "DNA." So, that makes it clear - One "set of DNA (or a Gene)" codes for one 'set of amino acids' (i.e., a Protein)! So far so good? "Yes," he said, "Continue."

Alright, Antigen is a protein, mostly a protein. There are some Polysaccharide Antigens and many others, but to keep it simple, I am not considering them. Once again, antigen is a protein, made up of amino acids, the number and sequence of which are determined by a Gene. That is common to any protein. Apart from that, Antigen is special in that it is found on the surface of a cell. In other words, Antigens are found in the membranes of the cell and that makes Antigen a cell-membrane-protein! At the molecular level, these antigens are the "identity marks" of a cell which are very important in "communicating" with other cells. It is like an "Username" and "Domain" for you email address - using the same alphanumeric code (A-Z, 0-9) multiple email addresses can be created which are "unique" to an user. Similarly, the amino acids can be arranged (as dictated by their DNA sequence) and used as "username" by the cells while they communicate. "I am with you," Ganaraj allowed me to continue.

Let's go back to the time when we slept comfortably in our mothers' wombs. Ahh.. How comfortable it was! Anyways, while we slept carefree, there were million things happening at the molecular level because of which we are able to now breathe comfortably. We began our journey as a single cell with its DNA containing every single information needed to build this heavy functional machinery. That cell underwent divisions and multiplications to form a big bunch of cells. All of them had the same DNA but somehow, one group of cells decided to become Liver, some went on to become Heart, some became Brain and so on. How did this happen? Though they contained information about everything, they chose to express only what they wanted. They sort of "specialised" in their expression of the Genetic code. So, each of those cells chose an "username" for themselves. The Immune System was also developing at this time; to keep it simple, Immune system means White Blood Cells (WBCs), and it was quietly building its "Contacts List." As blood circulated to almost all the cells, these White Blood Cells went on communicating with them. Every time it got a "friend request," it identified the "Antigens" on the cell membranes and added those "Usernames" to its "contacts list." By 5th to 6th month of our life in the womb, its "Address Book" becomes complete and it would no longer accept any friend requests. The Spam Guard is now turned on, so to say!

So, from now onwards, any emails from persons NOT in the address book will be reported spam and dealt seriously; I mean, after this maturation of Immune system, if any protein other than the "Self Protein" enters the blood stream, it will be recognised as "Foreign" and an antibody response will be triggered. I have explained in my previous blog "Molecular Battlefield," how an antibody generation is triggered. Antibodies are produced by "specialised" White Blood Cells when the body is exposed to a "Foreign" Antigen. Antibodies are complimentary in structure to that of the Antigen and they fit exactly into their respective antigens like a "lock and its key." Oh, by the way, even antibodies are proteins and these are "dissolved" in the "fluid" of the blood, unlike antigens which are found on the membranes of the cells.

"Wait a minute," Ganaraj interrupted me at this time. "What about all those proteins we eat daily? Do they generate an antibody response?" Great question, you see. Perfectly logical. Yes, they would trigger an antibody response, IF ONLY they were to directly enter our blood stream. But our digestive tract is very efficient in digesting the proteins. The Hydrochloric Acid in the stomach and other digestive juices and enzymes in the intestines break down the proteins to their basic building blocks. No matter what protein you ingest, ultimately, it gets broken down into those 20 amino acids which will be absorbed by the intestines and sent into the blood stream. Amino acids are too "light" in terms of Molecular weight and hence, they do not trigger an Antibody response.

Now let's consider the Antibodies to these Antigens. According to Landsteiner's Law (after Karl Landsteiner, an Austrian Pathologist), if an Antigen is present on the membranes of the RBCs, it's corresponding Antibody will be absent in the blood; if an Antigen is 'absent' on the membranes of the RBCs, then it's corresponding Antibody 'must be present in the blood.' Computing this law for the ABO system of the blood groups, we can tabulate certain conclusions as depicted in the following diagram:

"Sounds logical," said Ganaraj and allowed me to continue. I then, described the other medically important system, Rh. The "Rh Positive" individuals have an "Rh" antigen on their RBCs and hence, do NOT contain Anti-Rh Antibodies in their blood. The "Rh Negative" individuals do NOT contain "Rh" Antigen on their RBCs... "I got it," Ganaraj interrupted. "And therefore, they contain Anti-Rh Antibodies in their blood!"

"No. That's wrong," I continued. "An Rh-Negative individual does NOT contain Anti-Rh Antibodies in his blood! This is an exception to Landsteiner's Law." "Oh! OK," he allowed me to continue, but he was not satisfied with the explanation. I continued, "But when an "Rh Negative" individual gets exposed to "Rh" Antigen, he would then start producing Anti-Rh Antibodies." This one was logical, and he accepted this.

So, let's consider a woman who is "Rh Negative." If she gets pregnant with an "Rh Positive" baby, what would happen? "Nothing. Why should something happen?" Ganaraj was clear but I wanted him to know something more. Yes, nothing would happen until the delivery but during the delivery, some amount of baby's blood would enter the mother's blood due to rupture of Placenta. Now, the baby's RBCs carrying "Rh" Antigen would be treated as "intruders" by the mother's immune system and she would start producing Anti-Rh Antibodies in about 72 hrs. "By this time," Ganaraj added correctly, "the baby would be out and safe!" Yes. He was right. By the time she produces Anti-Rh Antibodies (3 days after delivery), the baby is no longer dependant on the mother's blood for nutrition! But the problem is, the next time she gets pregnant with an "Rh Positive" baby, she would have already had Anti-Rh Antibodies circulating in her blood and that would cross the placenta and attack the second baby's RBCs. That is what is medically termed "Hemolytic Disease of the New Born."

"Can we NOT prevent this blood-mixing at the time of delivery?" he questioned again. It's practically impossible, as the mixing occurs at microscopic levels. But there's hope. After the delivery, we have 3 days at our disposal to prevent the mother's immune system from producing Anti-Rh Antibodies. What we can do is, inject some "Neutralising Antibodies" which would mask the baby's RBCs carrying "Rh" Antigen from being recognised by the mother's immune system and that's exactly what is done routinely.

"But, I have another question," he continued. His earlier suppressed doubt now surfaced up. "Well, going back to the basics, Antigen is something that is present since birth. Antibodies are produced when the immune system is exposed to "Foreign" antigens. How can a O+ve individual produce Anti-A and Anti-B antibodies without being exposed to the "A" and "B" Antigens? I mean, what's the basis of Landsteiner's Law?" His question was perfectly logical. Even I had this question in my mind when I was in my med school. With all due "respects" to my Alma Mater, my physiology professors were so lousy that I dared not to ask them questions, that made sense! Fortunately, now I am associated with someone who is at the other end of the spectrum and he doesn't mind even if I ask him the silliest of the questions. So, I paused the discussion with Ganaraj until I discussed it with my professor.

Meanwhile, I opened this discussion on Facebook and some of you contributed to that. Anirudh came up with an idea of exposure to "A" and "B" antigens through gut (digestive tract). I was apprehensive about two issues at that time - how would an "A Positive" blood enter the digestive tract of a O+ve individual, unless that O+ve individual "drinks" it (as a contaminant)? OK, even if it enters, it should be broken down into amino acids by the digestive juices. Even if it "somehow" enters the blood stream triggering Antibody response, why doesn't the same phenomenon occur to Rh system? Then, Anirudh came up with another interesting approach. Exposure of "A" and "B" Antigens through the placenta during our "womb-days." I had two more issues at this time - what if the mother is also O+ve? How can she expose her baby to the "A" and "B" Antigens? And also, if it is exposed during the "womb-days," the immune system should recognise those antigens as "Self-Antigens" and should NOT mount an Antibody response!

With all these doubts, I went to my professor. Before he answered, he first took time to appreciate the questions! That made me comfortable and curious as well. He explained, "There are certain strains of E. coli (an harmless bacteria in our digestive tract) and some of their antigens resemble the Human "A" and "B" Antigens in their molecular structure. This is a sort of 'Antigenic Mimicry'!! Blood group "AB" individuals recognise these antigens as "Self Antigens" and they do NOT mount any response; the "A" individuals mount response only to "B-resembling" Antigen; the "B" individuals mount response only to "A-resembling" Antigen; and the "O" group individuals mount response to both "A-resembling" and "B-resembling" Antigens.

"Wow," I exclaimed, "that's interesting!" "That's not all," he continued. "Mounting these antibodies is believed to help the individual in fighting off the E. coli, if it 'misbehaved' and so, blood group "O" individuals are able to better tolerate the infection than "AB" individuals. That's one of the explanations as to why there are more "O" group individuals in the world than are the "AB" group individuals!"

"So, this can be explained by Darwin's theory of Natural Selection?" I became even more curious. He explained me that I was right in guessing. "If you look at the DNA sequence of the Gene coding for "A" Antigen, it very closely resembles the DNA sequence of the related Gene in "O" group individuals. So, it means, the "A" Gene must have mutated and got silent, without expressing any Antigen (that's what is "O" group) and this mutation must have given a "survival benefit" to the individuals in fighting off the bacterial infection and hence must have been Naturally Selected and propagated!"

"Ahhh..." I took a nice long audible breath. That was absolutely a brilliant explanation. But my professor, had got something more to add to the believed theory. "This observation of 'there are more O group individuals than A' holds good only in the tropical countries. If you see the Scandinavian countries, there are equal or more "A" group individuals than "O." My experience on the study of Malaria parasite tells me that there are certain "Malarial Antigens" which resemble "A" and "B." So, I believe, this "O" group must have added benefit against Malarial infection also!"

"That gives us a whole new dimension to look at Malaria and the blood groups!" I was thrilled. "But what about the Rh system?" I asked him again. "Oh, Chethan, that's another interesting story," he continued. "Karl Landsteiner and Alexander Wiener were working on the blood groups when they were unable to explain an adverse reaction. Some "A" group individuals developed adverse reactions even if they were given another Group "A" blood. This made them think, there must be another system of blood group and they went in search of that. Wiener observed that humans and monkeys (a Rhesus monkey) shared a common antigen. He took the blood of the monkey, injected into Guinea pigs to get trigger antibodies against that antigen and used those antibodies to classify the human blood. Blood of some individuals "reacted" with those antibodies while blood of other individuals did NOT "react" to them. Those that reacted, were believed to be having a "Rhesus" Antigen and they were termed "Rh Positive" (Rh stands for Rhesus) and others were "Rh Negative." Including this system in the blood grouping reduced the no. of 'adverse reactions' and this came to be known as the "Rh System."

"But there was some confusion about the claim. An obstetrician, during those times, had observed the babies getting affected by mother's immune system. He used the serum (fluid part of the blood) of those mothers to classify the human blood. Some blood samples reacted positive and some reacted negative. This classification very closely resembled Wiener's Rh System. And hence, there was dissatisfaction regarding the claim of "Rh" Antigen. Careful studies have now shown that, what Landsteiner and Wiener had discovered is NOT "Rh" Antigen but something else. It is now named "LW" Antigen, LW standing for Landsteiner-Wiener. What the obstetrician had discovered was the actual "Rh" Antigen. Therefore, although Rh stands for Rhesus, Rh antigen is not found in monkeys. It's unique to human blood. "LW" antigen is what humans share with monkeys!"

His explanation was not at all esoteric. It was an easy listening to me, as if I was listening to a piece of instrumental music - a soothingly joyful experience. In simple words, he had explained me a whole chapter of physiology. It was as if teaching me, "If you want to convey something effectively, keep it simple!"

A Tale of The Champions

Men's Tennis has been both a kingdom ruled by the legends as well as fierce battleground for the Kingship. Much of it is spoken about the open era in tennis when professionals were once again welcomed into playing the championships but I started following the tour only in the early 90's and for me, the tale began in the summer of 1993.

McEnroe, Becker and Edberg were in the last days of their professional life and there were gossips about who could be the next emperor. I was particularly fascinated by a young American tennis player who never cared for the critics commenting on his two-finger-wipe of the sweat off his forehead before he served or his tongue that hung loose beyond his lower lip during most of the time he spent on-court. Pete Sampras was clearly my favourite and my best pick - a dedicated professional, strict serve-and-volleyer and a slam-dunker!

Even amidst tough competitors like Goran Ivanisevic on grass; Andre Agassi on fast courts and hard courts, by 1995, Sampras entrenched his rule in the kingdom of men's tennis. His matches against Ivanisevic were particularly interesting. The big serving Croat offered tremendous resistance to take a point in his service game. Sampras too played an almost perfect game on his service games and most of the times the set would end up in a tie-break. The guys were so perfect with their service games that, all they needed was ONE BREAK on the opponent's serve - and they would definitely close the set! I haven't seen such games after their era, I doubt if I ever would!!



Another notable rivalry was Sampras - the perfect server Vs Agassi - the all-time best returner of serves. It was simply a connoisseur's delight! It was Sampras who lead the head-to-head but in the end, it little mattered who won. In the summer of 2000, Sampras won his 7th Wimbledon title, his 13th Grandslam trophy and went into the history books. Sampras wasn't satisfied, may be he didn't want to stop at the unlucky "13."

It indeed proved unlucky because he went into a title-draught for the next 24 months. His signature-serve no longer worked and the giant who topped the ATP men's ranking for 286 consecutive weeks succumbed to every Tom, Dick and Harry on tour. By this time, the technology had improved and young players with powerful light-weight titanium racquets stood fearlessly against his thunderbolt - a heavy Wilson Prostaff 6.1 graphite racquet. Little did he care for the critics who strongly felt he should consider retirement and entered the US Open of 2002 with a ranking as low as 17! The 4 time champion in New York was no longer among the favourites for the betting. It was then that he put all his experience and hard work into play. Two weeks later, Sampras ended the event with his 14th Grandslam win and celebrated by kissing his heavily pregnant wife in the stands of the Arthur Ashe Stadium.



His absence from the tour for most of the 2003 had clearly sent his unspoken words of retirement into air. That summer, Sampras bid a tearful farewell to the crowd at the Arthur Ashe Stadium as he walked out of the court with his son and wife. The kingdom, by this time, was without a ruler and every American teenage kid with a tennis racquet in hand felt he could be the next king! Between 2002 and 2003 there were 8 different Grandslam champions.

The grasses at the All England Lawn Tennis and Croquet Club changed their direction and their blades would now face the net instead of the baseline. This prevented the balls from sliding and slowed the pace of the game. The tennis balls were being opened three weeks before the start of the tournament and this would help them absorb some moisture. The heavy balls started bouncing high and favoured the hard-hitting base-liners. Serve-and-volley was a thing of the past and top-spin was the new Mantra at the spiritual home of tennis - the Championships Wimbledon. It was then that the Swiss express rushed to the barren land and ended the speculation of Andy Roddick being the hope of continuing the American reign on the kingdom. Although not a strict serve-and-volleyer, Roger Federer mixed his baseline shots to rush to the net and finish-off the rallies with crisp volleys.

I was not happy with Federer's arrival just because of one silly reason - he seemed like breaking every other record set by my all-time favourite, Pete Sampras. Except that, it was always a pleasure to watch his intelligent construction of the rallies and he almost flawlessly finished the weak returns off his opponents' racquets. Although Federer looked docile on the French clay [even Sampras was!], his game spared a room for improvement and gave a hope to his fans that he would one day complete his career-slam, something that Sampras failed to achieve! During the latter half of the 2004 tour, Federer occupied the throne left vacant by Sampras. Ranked no. 1 in the world, he seemed mighty as the 2005 season opened. Though he lost a 5-set-thriller at the semifinals of the Australian Open to the eventual Champion Marat Safin, he looked confident of winning the other three and finishing his career-slam that year.

When every other player stood nervous across the net against Federer, an 18-yr old boy from Majorca dared to carry the Spanish torch at the Roland Garros. Playing his first French Open, Rafael Nadal was seeded fourth in the tournament. Dressed in a green sleeveless shirt, white knee-length shorts and a white head-band to keep his shoulder length hair out of sight, Nadal entered the Philippe-Chatrier court to take on the top-seed Roger Federer in the semifinals. He counted on his stamina and stretched Federer's patience beyond limits and earned a match point in the fourth set. Unable to face the heavy top-spin off the Nadal-backhand, Federer sent the ball long and Nadal celebrated his 19th birthday rolling joyously over the French clay! Later that week, Nadal pocketed his first Grandslam trophy and posed a real threat to Federer's dream of a career slam.



Nevertheless, Federer confidently walked around the AELTC and Flushing Meadows through rest of the summer and finished the season with Wimbledon and US Open titles. Like most French open winners, Nadal fared lousy on other surfaces and there's was no one to pose even a slight threat to the Fedex. The American hope, Andy Roddick started failing consistantly against the Swiss ace and even Jimmy Connors could not tame the big server to control his erratic ground-strokes.

Towards the beginning of 2006, Australian open witnessed a young Cypriot Marcos Bhagdatis (don't ask me where he is now!!) who dismantled Andy Roddick and David Nalbandian on his way to the finals. It was too much to hope for a magical run to continue past the Swiss master and Bhagdatis finally woke up from his dreams when Federer won his second Australian Open. As if dormant through the winter, Nadal sprung back to life with the beginning of that summer. Federer faced Nadal in the finals of the French Open and Federer's fans were on a high when he won the first set 6-0 against the young Spaniard. Nadal shrugged off his languid attitude and bounced back in the second set and continued it till he won the match. Grandslam no. 2 for Nadal and another disappointment for Federer.

But what surprised everyone was, they both met again in the finals of the Wimbledon. Traditionally, those who won in Paris never stayed in London beyond the first week of the tournament. Whatever, it was time for Roger Federer to take revenge against Nadal and he just did that, although in four sets. Federer carried the momentum from London to New York and won his third successive US Open title.

Australian Open 2007 had another surprise finalist, Chilean Fernando Gonzalez, who ousted Nadal in the semifinals. Like Bhagdatis, he could not run past Federer in the finals and Federer won his third Australian Open trophy. Nadal's fortune bloomed with the onset of summer and he continued his clay court reign. Again, Federer was tested when he faced Nadal in the finals. Nadal consistantly hit those heavy top-spin forehands to Federer's single-handed backhand. Federer could not swallow the bounce as he either committed unforced errors or returned them weakly. Nadal would simply punish him for his weak returns. Grandslam no. 3 for Nadal and another disappointment for the Swiss' fans.

Federer looked forward to Wimbledon to take his revenge. And they met again on the second Sunday of the tournament. Surprisingly, Nadal levelled the match at two-sets all. Federer used his experience and played a brilliant fifth set. In the eighth game of the deciding set, at match-point, Federer was handed a high ball at the net which he smashed effortlessly before rolling over the broken grasses!



With a fifth straight title at the AELTC, Federer went to New York with greater confidence in his sports kit. By this time, a young Serb was doing well on the hard courts. Although he managed to reach the finals of US Open, Novak Djokovic was too inexperienced for a big challenge and handed a fourth consecutive trophy to the Swiss entrepreneur.

Australian Open 2008 maintained its tradition of unfurling another surprise finalist, this time a 6'2", 93 Kg heavy-weight Jo-Wilfried Tsonga who proved too much for Nadal in the semifinals. Unlike before, the other semifinal also saw an upset when Novak Djokovic derailed the Fedex train in three straight sets! Djokovic's victory over the surprise finalist won him his first grandslam but it was not at all a clear threat to Federer, as he was still recovering from Infectious Mononucleosis (don't ask me who he got it from!).

Nadal continued his tradition of clay court dominance as the summer blossomed. This time, he got even better and hardly put out any sweat. Roger Federer was handed was completely dominated and Nadal, even after winning his fourth consecutive title in the French capital, controlled his urge to roll on the clay, as a mark of respect to the reigning emperor. But he maintained his tradition of biting his trophy as he posed in front of the photographers!

Federer flew to Germany to warm up for Wimbledon. Nadal chose to warm up at the Queen's club and he sent a clear warning to Federer by winning the tournament. Federer, little affected by that, continued to religiously sacrifice all those who fell into the top half of the draw. The crowd at the South West London witnessed one of the finest matches in the history of Wimbledon as Federer and Nadal contested in a four hour 48 minutes battle in the finals. With rain interuppting twice in the match, the contest went on till quarter past 9 in the evening, when the five-time defending champion netted a forehand at the match point. As if it was a lightening, cameras around the stadium flashed and lighted the 22 year old Spaniard, as he fell to the ground in ecstasy.



The emperor's reign was further challenged when Nadal went on to Beijing, to win a Gold for Spain in the Olympics. That summer, Nadal ended the Swiss's four-and-a-half year reign at the ATP rankings. With no major victory throughout the season, Roger Federer came to New York to seek solace. Top-seed Rafael Nadal failed again to pass his semifinal examination. The playing conditions were tough, given the rain interruption and heavy winds at the Louis Armstrong stadium, but it should not have theoritically bothered the then World No. 1, as he fell in four sets to the British hope Andy Murray. Murray was another easy opponent and Federer ended his title draught of the season - a fifth straight title at the Flushing Meadows for Federer!

Traditionally, the 2009 tour began with Australian Open and this time, Nadal was fighting another potential surprise-finalist, Fernando Verdasco. The Nadal-Verdasco semifinal was one of the finest matches of the tournament and Nadal lighted up the center court with a stunning running forehand down-the-line - the ball went past the sideline but once it crossed the net, it curved inwards and landed within the court! The crowd rose to their feet and Verdasco stood wondering what else he could do.



Playing his first finals at the Flinder's park, Nadal fought Federer in another five-set thriller that lasted four hour 23 minutes and Nadal became the first Spaniard to win the trophy in Melbourne. As he received his runner-up trophy, Federer broke out in tears, "God, it's killing me." Nadal collected his trophy and went straight to Federer, put his arm around his shoulders and comforted him. Once the match was over, they were good friends again!

Three months later, things changed. Federer changed his game strategy as his took on Nadal in the Madrid clay. Federer mixed his game with surprise rush to the net and forced Nadal to give short balls on the return. Federer convincingly beat the clay court king in the Roland Garros warm up event. Federer was sure to give a shock to Nadal if they were to meet again in Paris but Nadal was given a shock before that. In the fourth round, Nadal faced a 6'4" Swede, Robin Soderling who was little affected by the top spin Nadal manufactured. He took advantage of his height and started attacking the balls staying closer to the baseline. Nadal was forced to step back and this created ample room for Soderling to close out the rally. After a four-set loss, the Spanaiard revealed his knee-injury that further disappointed his fans. Soderling eventually reached the finals. Federer, though struggled to reach the finals, played confidently against the Swede. He wasn't playing Nadal in the finals, so he made sure he won it! Equalling Sampras' record of 14 Grandslams, Federer also completed his career-slam and joined the elite club of four others to have won all the four major events on the tour.

Nadal's injury made it clear that there would not be a Federer-Nadal finals at the Wimbledon. Federer breathed the comfort air in London as he sailed to the finals to face the fastest server in the world, Andy Roddick. Though he won the first set, Roddick made the biggest mistake of his life in the tie breaker of the second set. Leading 6-2 in the tie break, he wasted 3 of the 4 set points. At 6-5, Roddick had a set point on his serve, hit a hard serve, got a weak return, pushed it to the Federer's forehand corner, Federer handed him a easy backhand volley at the net, Federer's backhand-court wide open, Roddick had all the time and space in the court but he chose to send it 3 feet wide!! If I were Roddick, I would have quit playing tennis at that moment itself. Anyways, Federer won his 15th Grandslam with a 16-14 victory in the fifth set of that match.





Also that summer, Federer regained his World No.1 spot. Meanwhile, Nadal announced his recovery from the knee injury and fared well at the hard court warm up tournaments for the US Open. At the start of the open, we were hoping for another Federer-Nadal thriller in New York, but destiny had its own choice. Nadal was handed a tough draw and he had to work out his way through the rain interrupted second week of the tournament. Nadal faced another tall guy, 6'6" Juan Martin Del Potro in the semifinals. Though an abdomenal injury bothered him in the earlier matches, it was clearly not the reason why he lost the tall Argentine. Once again, his top-spin proved inefficient against the tall guy. As if the Argentine had thoroughly revised the book chapter, "How Soderling defeated Nadal," Del Potro exactly did the same - took advantage of his height, attacked the top-spin early and sent the injured Spaniard running for balls! Federer continued his tradition of making it to the finals of US Open and Del Potro seemed an easy opponent.

Del Potro, who lacked experience at 20 years of age, surely had the energy to mount a fight-till-death attack. In the first set, Federer was comfortable with his strategy of pushing the tall guy away from the baseline. In the second set, he had a couple of chances of taking a 2-0 lead but Federer relaxed. May be, he thought he would have a couple more opportunities but Del Potro held on to his momentum. During the later half of the match, I don't why Federer chose to drag him side-to-side, it was blessing in disguise for the tall Argentine. He ran effortlessly chasing the balls and experimented with new angles on the court. Federer was completely dominated in the fifth and Juan Martin Del Potro announced the arrival of a new contender to the emperor's throne!

Where does Nadal go from here? Troublesome injuries, worst defeats at the Grandslam, once again failed his semifinal exam at the US Open and what's worse, a new opponent has emerged. His 3200 rpm top-spin is not working anymore. It's time to do some homework, Nadal, you have to change your strategy. Where does Federer go? Straight into the history books, with bold and big-font prints! He's already achieved so much, whatever he wins will be icing the cake. My guess is, he could win another 3 Wimbledons before he bids adieu to the kingdom! The American tennis has no hopes as of now. The Spaniard needs to recover from his injuries and change his strategy, Del Potro has to gain some more experience, Andy Roddick needs to improve his return of serves, and Andy Murray and Novak Djokovic are yet to find out a strategy and stick on to it, rather than playing impulsively. The Quest for Perfection continues - who's next??

T h e L o v e S h e T a u g h t

It was just another busy day at work. I came home, prepared some coffee and as I began to sip, I got a call from my cousin. It seemed Bhanavi, his 5 yr old daughter, had a question for me. “Hello, why are we here on Earth? And what would have happened if we were not to be on Earth?” I kept my coffee mug down and almost instantaneously broke into laughter.

I have already told you in one of my previous blogs (Funny Bone) how smart Bhanavi (not Bhavani) is. Of late, I was into reading some Neurobiology and so I was able to better appreciate her pranks. What's more, she effortlessly puts her subjective experiences into words and hence, for someone interested in Neurobiology, Bhanavi is an open book – ready to read!

[Click here for a comprehensive outlook of the brain.]

There is a popular statement in Neurobiology regarding memory - “Neurons which fire together wire together.” Let me explain. Neurons are basically the nerve cells, the building blocks of our brain. Neurobiologists wonder how we can go on to build our memory while the no. of neurons in our brain remain fairly constant throughout our life. The accepted theory is that when two neurons are stimulated (fired) together they develop more synaptic connections between them (wire together), especially in the Hippocampal area of the brain which is concerned with learning and memory [Click here for the animation]. For example, as toddlers, when we were shown a cat and were told “cat” every time we saw the animal, the “sight of the cat” - that is, one set of neurons processing the “image of the cat” - gets wired with the word “cat” - that is, another set of neurons processing the phonemes and pronunciation of the word “cat.” So, after repeated exercise, when we hear the word “cat,” we begin to instantly recall the animal in our imagination or when we see the animal, we begin to say “cat.”

As I watched Bhanavi build her memory, I noticed something interesting. Bhanavi had seen in her books, the cow being associated with milk and the chicken with eggs. Bhanavi understood that the cow gave us milk and so, the chicken gave us the eggs. But she didn't stop there; she extended her observation and hypothesized that the monkey gave us the banana and the rabbit gave us the carrot!! Careful she was, not to associate monkey with the carrot or the rabbit with the banana. However, it was hard to convince her that monkeys actually ate the bananas and didn't give them to us. After that incident, I understood that there's something more to memory than just wiring up of the neurons. It involves complex interaction between various areas of the brain including higher order association areas of the Neocortex which were beginning to develop in Bhanavi.

There are scads of things that I observed in Bhanavi and I can't go on explaining them in detail (if you are interested, you can mail me for detailed discussions). Just to mention – if you see all her drawings till date, there is a striking improvement in the quality of her sketches and as I watched her crayon-strokes I could appreciate the orchestrated firing of the Purkinje cells in her Cerebellum which went on improving their rhythm over time.

Like Bhanavi, there are many kids among my relatives with whom I have spent some time. I have had some interesting experiences with them. The other day, I was observing my 2-yr old niece, Sharanya, who is very good at picking up nouns. With a little prompt, she used to fluently pronounce everyone's names. When it came to 'me' she would say, “I wont tell you!” I initially thought she was having some stranger-anxiety. That wasn't the case. She was consciously suppressing her impulse to speak out, “Chethan.” She was clearly demonstrating the maturity of her Orbitofrontal cortex!

Now, this Orbitofrontal cortex is an area of the brain that has got to do with our social behavior, impulse control and decision-making abilities. Often, I like to call it - The Lying Cortex! Let me illustrate. Let's say someone whom you don't want to talk to rings your doorbell. You send a kid to answer the door and ask him to tell the person that you are not at home. If the kid's Orbitofrontal cortex isn't matured, it is most likely that it will say, “Papa said, he is not at home!” When your friend invites you for a movie or a dinner, this Orbitofrontal cortex analyses the situation. If the person is your favorite or if it's a weekend, it will give a positive response. Or else, it immediately scans its database for some lame excuse and executes the best one!

This Orbitofrontal cortex is a part of the frontal lobe of our brain. Frontal lobe has many different areas and this is where many higher order functions including abstract thinking and problem solving skills happen. Bhanavi's frontal lobe was particularly interesting to me because in the process of solving problems she used to create problems as well! The other day she asked me, “How do planets fly? Why are they up in the sky?” Even as I wondered she had another question, “Why are we made up of bones?” I replied, “We are made up of bones because we can be strong!” I don't know what neurotransmitter got released in her frontal lobe, she asked me back, “Why then, the thigh bone is the strongest of all the bones?”

Most of her questions are difficult to explain even though we know the answer. But this question, “Why are we here on Earth?” was a complete bouncer. We told her that we are here because God wanted us to be here. Somehow, she wasn't convinced. For once, she shifted my thinking from Neurobiology to Philosophy and I could faintly recollect a related story from the Upanishads. I told her, “We are here to enjoy, to be happy.” She showed some signs of relief and retired to bed. But I myself wasn't convinced with the answer and I had to revert back to my spiritual teacher. I had a lengthy discussion with him (mail me if you are interested in the details) and we were confused as to how to explain all that to this 5 yr old brain. The final equation was, “We are here to help others, to love and not to hurt anyone, be happy and make others happy.”

I don't know how Bhanavi analyzes me but she likes asking me questions. I too welcome her questions though I am sure I will not be able to answer. We switch-on Skype and have a video chat on the weekends. She asks me some questions, she shows me her sketches, teaches me some nursery rhymes and together we do at least one stupid thing every time we connect. Whenever she did those naughty things she seemed to release some Dopamine and endorphins in her endogenous reward system.

The endogenous reward system consists mainly of Nucleus Accumbens Septi, Ventral Tegmentum and their vast connections that form a loop. When the Ventral Tegmental area releases Dopamine (a biogenic amine molecule) in the Nucleus Accumbens Septi, it kicks up a series of circuits involving the endogenous reward system that we subjectively feel as an “elated mood” and an overall sense of well-being. Also the release of endorphins (naturally occuring molecules in our brain similar in structure and function to those of Morphine and other opioids) appears to relieve our physical pain and even the emotional stress. All these things naturally reinforce the original stimulus, so that we feel good. I wondered, how a simple rhyme like “Twinkle twinkle little star” or a simple game like Peek-a-boo which once released that dopamine in our endogenous reward system can no longer do so? Why it now requires sophisticated electronic gadgets and high-end luxury automobiles to release the same dopamine there?

I also observed a couple of other things that I could not explain with our current understanding of this wonderful organ system. Why is it that I continue to associate the feelings of love and trust with my heart even after discovering that they are the functions of my brain? Why is that, whenever I spend time with Bhanavi or any other kid, I exchange with them only love, hope, kindness, strength and humility? Why do I never get negative feelings like fear, anger, lust, greed, pride or jealousy? Perhaps thats what kids are meant for – to make our lives so very beautiful! When kids are around, unknowingly we release more and more of Oxytocin into our Limbic System.

There are particular areas in our brain which process a range of emotions, play a vital role in our behavior, learning and memory, and collectively these areas are called Limbic System. It is this wonderful limbic system that helps us engage with the world around us and associate persons with one or many emotions. Release of Oxytocin (a chemical and a neurotransmitter) in our brain activates the areas concerned with the feeling of Love and Trust. And this Oxytocin is pure and unconditional unless interrupted by other areas of the brain!

The other day Siya, my another niece asked us a question, “Why don't animals speak?” I went back to my neurology resources to analyze how she could come up with such question. It was all because Siya's right-half of the brain was simply doing its job. This right side of the brain engages us with the present world and everything in the world that is “right” - right here, right now. It sort of unifies us with the energy of the world. [Click here for a wonderful video demonstration – a must view!] But why don't we feel that? It is because we also have a left-side to our brain, that separates us from the world. To everything we see, the left-half attaches something from the past experience or probable experience in the future and separates it. When someone does you a favor, your right brain is all thankful and wants you to release some Oxytocin for that person, but then your left brain takes into account the person's appearence, caste, race, status, personal details and modifies the way you thank that person! Fortunately, Siya's left side of the brain hasn't yet matured. She feels one with everyone, including plants and animals, she's one with the energy of the nature and that's why she's so cheerful all the time!

We, the so-called grown ups, also love. But we aren't as blissful as Bhanavi or Siya because we have a so-called matured left-brain that brings in a “reason” to love. Have you noticed a child playing with a currency note? It's of no value to the child except for its attractive colors. It is we, the grown-ups, who pollute its left lobe with the idea of money. Haven't you seen people loving their parents only because they in turn would get some pocket-money or what's worse, their parents haven't written a “Will” yet? I can feel their Oxytocins being contaminated with some deadly neurotoxins. In the words of Shakespeare, “Love has no reason, if it has, it's not love.”

Though many chapters in neurobiology and philosophy are yet to be thoroughly understood, one thing is clear. Why do you think Bhanavi loves me? She has but one reason – she loves me because she loves to love me. And that is the love she taught me.