MOOOOO HA HA HA!!!



Although I felt like giving this post a funny title, killer diseases like Ebola or Mad Cow Disease are anything but funny, and I am dead serious (pun intended) about their existence.

The best book on infectious diseases I had read until now was Richard Preston's chilling portrait of Ebola, 'The Hot Zone'. It kept me awake through a few nights because of morbid fascination alone. The concept of a new, incurable epidemic which kills almost instantly and in a hideous way is a sobering thought for us humans, with the potential to turn to dust all that we have achieved since the dawn of our existence, and our existence itself.

Richard Rhodes, in his book 'Deadly Feasts: Tracking the Secrets of a Terrifying New Plague', has woven another riveting and ominous but completely matter-of-fact portrait of BSE (Bovine Spongiform Encephelopathy). We know it by the more common, ironic name of Mad Cow Disease, a name originally concocted by British reporters to describe the tipsy behaviour of cows affected by it. Up close and personal, it is one of the most pernicious and terrifying, not to mention fascinating diseases, to ever confront humanity. One reason is simple. It's incurable and one hundred percent fatal, and a fast killer. Within months of getting affected, victims start the relatively slow but inexorable march toward becoming a vegetable, losing their sanity, and finally and mercifully dying at a time when one would have wished them dead much earlier. The agent which causes the disease is a completely novel and enigmatic entity that is beyond definition, surviving on the border between living and dead. Dubbed the 'Prion', it has a fascinating scientific history of it's own. Yet, after hundreds of research papers on it and two Nobel Prizes, what makes it tick, and how to stop it's rampage, remains a mystery.

Rhodes's book opens with a gory but all too real scenario, a cannibalistic feast among the natives of Papua New Guinea in the 1950s-the so called 'Fore' people. Rhodes reminds us that for all the myths surrounding it, cannibalism was a common ritual among many tribes, and sporadic incidents of it crop up even today. Interestingly, among the Fore, it was a symbol of gender power. It seems that only the women practised cannibalism upon other women's dead bodies. Secretly eating the meat of the dead woman in the shadows, away from the men, gave them a vicarious sense of thrill and supremacy. But unbeknownst to them, this is where the first footprints of the fearsome disease arose, the terrifying malady called 'Kuru', which in Fore lingo, literally means 'The Shivers'. Victims of this disease slowly lose their sanity, develop extreme shivers as in Parkinson's disease. Within just a few months, they lose sense of space and time, and sometimes they become unable to swallow. Death is a welcome event, mostly and painfully caused by starvation, or more mercifully simply caused by the brain becoming dead. For the fore, it was a curse which no witch doctor could cure.

To study this strange disease came one of the most remarkable scientists about whom I have read- D. Carleton Gujdusek. An American Doctor with a penchant for travelling deep and wide in the world in search of exotic diseases, he arrived in New Guinea just when the epidemic was starting in the late 1950s. He finally came to love this wild place and its people so much, that returning back to civilization was almost painful for him. After doing exhaustive investigation, he realised that he was dealing with a new disease caused by a new agent, something never seen before, that was causing the brains of the victims to be literally riddled with holes; hence the name 'spongiform encephelopathy'. It was probably caused by consumption of dead people's brains. But what a disease this was! Its most outstanding characteristic was the absolute lack of inflammation in the victims' bodies. Medically, this is an astounding enigma. As we know, the body fights against any foreign organism invading it, be it bacteria or virus, and inflammation is an obvious telltale sign of this. But this strange new disease was infectious, yet produced no inflammation at all. Even now, this is a most enduring puzzle.

After studying this disease, scientists began to find remarkable parallels for it in medical history- a similar disease called 'scrapie' in sheep, and a human counterpart with the hard to pronounce name Creutzfeld-Jakob disease (thankfully abbreviated as CJD), first documented in the early twentieth century in Germany. This disease ominously arises in a spontaneous way, affecting one in a million people in the world. The symptoms of all these maladies were similar: tremors, loss of sanity, a loss of a sense of hygiene, and finally and inevitably, death. It was, and still is, a certainty. Within a year at most. However, the incubation period of all these is substantially long, somtimes as much as ten to fifteen years. All through the 60s and 70s, Rhodes recounts the tales of these remarkable scientists' work, the linking together of the disparate threads of evidence, the failure to ascertain the identity of the notorious agent. Carleton Gujdusek received the Nobel Prize for his work in identifying a new form of infection in 1976, and more importantly, for demonstrating that it could be transmitted to chimpanzees-an ominous observation. Another brilliant scientist, Stanley Prusiner would do detailed genetic and biochemical studies on the agent and receive his prize in 1994. He would coin the title 'prions', short for 'proteinaceous particles', for them. These prions are fabulously resistant. Boil them in water for a week, and they won't disintegrate. Neither UV light, nor other forms of radiation, both of which incapacitate Ebola, kill them. In fact, one of the cases was distressingy spread through the use of infected silver electrodes which were used on an unfortunate patient, as a part of therapy. Before they were used, they had been autoclaved under the harshest condition.

The most startling and logic defying conclusion of all this work was that whatever the causative agent was, it contained no nucleic acid such as DNA or RNA, a component fundamental to life, which is possessed even by those most primitive forms of life, the viruses. Whatever it was, it was just protein, the other fundamental component of life. We are still grappling with this puzzle today because the most basic tenets of biology say that proteins alone cannot reproduce (However, ther has been some evidence now that proteins can participate in a primitive form of 'self-assembly'). As if this shock was not enough, another discovery was made that the genes for producing the protein in CJD are present even in normal human beings. There is something which goes terribly wrong with a few individuals, that causes this usually benign protein to become malignant. In fact, we don't even accurately know the function that the 'normal' protein performs in our body.

All this would have been just a fascinating academic curiousity. Then, in 1985, the disease hit the British cattle industry. It was identified as another type of 'spongiform encephelopathy', bovine in this case. Scientists studying the cases realised that the disease had spread through hundreds of thousands of cows through our own version of what Rhodes calls 'high tech neo-industrial cannibalism'. That is to say, the disease spread through the high protein cow feed which is made out of leftover pieces of cows and other animals after they have been slaughtered-cannibalism among cows. This was a common practice. In studying the new phenomenon, and never having thought that a variant would be found in cattle, the scientists made what would be turn out to be a crucial, misleading, and woefully wrong assumption: that the disease entered the cattle industry through the remnants of sheep meat in the cow feed. The form of the disease in sheep called 'scrapie' was well known for years and was known not to affect human beings, ergo eating the infected cows would not affect human beings as well. This conclusion would have distressingly serious repurcussions. In fact, the British agricultural minister John Gummer even caused a public stir when he photographed himself and his teenage daughter eating a hamburger. Prime Minister John major himself endorsed beef. Nonetheless, beef sales dropped, and the industry suffered a massive setback.

All was peaceful until 1993, when cases of CJD like cases began erupting all over England. Pathologists who performed autopsies on the vicitms realised that they were looking at a new type of CJD, much like the disease in cows. That was when hell broke loose, and the world at large heard about Mad Cow Disease. The British Ministry for Agriculture, Food and Fisheries (MAFF) tried at first to downplay the impact of the event, but the bare facts soon became painfully clear: the disease had spread to human beings through infected beef, something that had been thought to be almost impossible. After a lot of political deliberations, the Government finally broke the news to a stunned nation. Within days, the cattle industry lost billions of dollars, boards with warnings were hung on British McDonald'ss and hundreds of thousands of cows were buthered. Europe stopped imports of British beef after cases in France and Belgium. Since the incubation period of the disease was so long, no one could say for sure how many cases would emerge (We may still be looking at a few of them). Since then, there have been isolated cases, but the picture at large has fortunately not been as nightmarish as imagined. However, I think we can never know how much information the Government has suppressed from us, given the immense importance of the problem.

Rhodes's book was published in 1997. The first case of BSE in the US appeared in a Seattle cow in December, 2003. In the US, soybean protein largely substitutes for the cannibalistic cow feed fed to cows in Europe. Yet, it seems a painfully obvious conclusion that the counterpart of spontaneous CJD in humans, is spontaneous BSE in cows. Similar diseases have been implicated in many other species including everything from cats to minks. At the heart of the global question is a fundamental scientific one: What is the exact identity of this enigmatic proteinacious agent and how does it replicate? Rhodes says that the most alluring and fascinating theory comes from the master Gajdusek himself. To put things in perspective, Gujdusek draws upon Kurt Vonnegut's novel 'The Cat's Cradle'. In it, a wild scientist comes up with a theory, in which the ice that we see is only one of many crystalline forms. Crystallization is something with which we are all familiar. It is a well-known phenomenon in Physics and Chemistry that the conditions under which something crystallizes can have a striking effect on its final state. The most pronounced example is Carbon. One way, it gives Graphite, the other way it gives Diamond. Both could not be more different. In Vonnegut's novel, the protagonist discovers a new form of ice called 'Ice-9' which, when dumped into the oceans, cause all the water to freeze. The folding of proteins is a well known similar process, upon which life itself depends. Change the conditions and a protein misfolds, for example causing Alzheimer's disease- whose symptoms are similar to those of the spongiform diseases. What if, suggests Gujdusek, conditions in the body cause a part of the protein which is normal, to misfold and give rise to to a deadly agent. This agent then would act as a center of nucleation and would ceaselessly 'hijack' similar molecules and make copies of itself, just the way a crystal of ice can cause accelerated growth around it. It's a very interesting theory, but unfortunately one that has been very hard to validate. One reason is because these prions are almost impossible to 'grow' in test-tubes. Secondly, this theory just reduced the problem to another one: what causes the protein to misfold in the first place? Until we know this fundamental process of formation of prions, we are far far away from finding a cure. The most abstract part of the problem is that we cannot even call prions 'living' and yet they can reproduce and cause havoc in an organism just like any other infection. The problem of treating a deadly disease comes down to defining life itself.

In the end, of course, it's the facts that matter. The most insidious and fastest killing disease imaginable, a possible 'slate-wiper' as Preston calls it, would admittedly be one that infects a major component of our diet. I cannot even begin to contemplate the effects of a fatal, resistant disease that infected wheat or rice. Beef is admittedly the most popular meat in America. Steak is not only a food item but part of American culture. The Atkins diet spurred the sales of beef in the US as never before. It's a 175 billion dollar industry. Even after the December scare, nobody takes it very seriously. For now, things are calm. But it can very well be the eye of the storm. Until we know the exact cause and mode of operation of the disease, we will be playing a game of hit and miss for finding the cure. And until there's a cure, we have a responsibility to watch out. After all, who can predict the future?

Reading Rhodes's book alerted me to the tenuous existence that we live, without even noticing it. Let's hope that past wisdom serves us in the future too.