"No, thank you." "No." "No, no." "No." "Venga." "¿Quieren un poquito de agua?" "Me..." "Me llamo Charles Darwin y él Captain FitzRoy." "Me soy naturalista." "¿Hay hueso?" "¿Hueso?" "Bones." "Sí, hueso, hueso." "¿Sí?" "¿Hueso gigante?" "¿Aquí?" "Here?" "Aquí estan los huesos." "FitzRoy!" "A flood washed down part of a bank of earth." "Mi hijo le pegó con una piedra y le sacó los dientes." "Por eso que se caí tan afuera." "It was perfect, but the boys knocked out some of the teeth throwing stones at it." "How much?" "¿Cuánto cuesta?" "I wonder why these creatures no longer exist." "Perhaps the ark was too small to allow them entry and they perished in the flood." "What is there to laugh at?" "Nothing, nothing." "Do you mock me, or the Bible?" "Neither." "What sort of clergyman will you be, Mr. Darwin?" "Dreadful." "Dreadful." ""And God said, 'Let the waters bring forth abundantly" ""'the moving creature that hath life" ""'and fowl that may fly above the earth" ""in the open firmament of heaven.'" ""And God created great whales and every living creature that moveth..."" "Hello." ""...which the waters brought forth..."" "What are you doing here?" "Why such beauty where no one can see?" "You can't have been blown here." ""And God saw that it was good."" "If I were to give a prize for the single best idea anybody ever had" "I'd give it to Darwin for the idea of natural selection... ahead of Newton, ahead of Einstein because his idea unites the two most disparate features of our universe:" "the world of purposeless, meaningless matter and motion on the one side and the world of meaning and purpose and design on the other." "He understood that what he was proposing was a truly revolutionary idea." "The Darwinian revolution is about who we are, it's what we're made of, it's what our life means insofar as science can answer that question." "So it, in many ways, was the singularly deepest and most discombobulating of all discoveries that science has ever made." "In Darwin's day, the idea of evolution was regarded as highly unorthodox because it went against all of natural history in Great Britain." "It jeopardized the standing of science;" "it did jeopardize the standing of a stable society, the Bible and the church as well." "Darwin kept his thoughts to himself for many years and agonized over the problem." "If it ever got out that he was doing something that ran slap counter to established science it would ruin his career, ruin his reputation." "He was a respectable man with a dangerous theory." "Did you never get your sea legs?" "Not once in five years." "Whenever the sea was up so was the contents of my stomach." "What a delightful thought." "We should be able to squeeze 400 a year out of the governor." "Why?" "What has he said?" "He hasn't said anything, but I've seen it in his eyes, the way he pored over your letters." "A very proud father." "I told him you were going to publish a journal of your travels." "There was a definite flicker of interest." "Publish?" "Yes, of course." "No country parsonage for you, my boy." "You're under my wing now." "I'll take charge of your affairs;" "introduce you to all my clever, witty friends." "Trade on your..." "your celebrity." "Celebrity?" "Certainly!" "Everyone wants to meet you, hear stories of naked Tahitian women and giant sloths or whatever." "Captain FitzRoy!" "This is my brother, Erasmus." "Mr. Darwin." "Captain." "Good God!" "A man can collect a lot of rubbish in five years." "It's a wonder you didn't sink the ship, Charles." "Named, I take it, after your grandfather?" "Yes, and an uncle... who drowned himself in the River Derwent." "And are you a free thinker like him?" "I'm more of a free drinker, really." "And how was the voyage for you, Captain?" "That's not for me to say." "No?" "40 views of the coast as seen from the sea 80 plans of harbors and 82 coastal maps, all for the Hydrographic Department of the Admiralty." "Bravo." "Dinner at sea must have been a jolly affair." "Here... from the Galapagos Islands." "Puma roasted over an open fire... rather like veal." "Armadillo, roasted in its shell... a lot like duck." "Tortoise, of course." "Of course." "Some of them weigh as much as 500 pounds." "One I measured was 96 inches around the waist." "If one of them ever needs a suit of clothes we must send it to father's tailor." "What else?" "Llama, ostrich..." "People wonder how it is some animals come to be extinct." "Now we have the answer:" "eaten by Charlie Darwin." "You look as though you're going to the scaffold!" "Dignity!" "Poise!" "Smile!" "Remember, all eyes are on you." "The judging has begun." "Mr. President... my lords, ladies and gentlemen..." "No, no, no!" "Start with a bang." "Men of Athens!" "What?" "Friends, Romans, countrymen!" "That sort of thing." "Right." "I can't do this." "Yes, you can." "You mustn't let the fact that every leading geologist in the land will be there put you off." "Oh, God!" "Now, let me hear an interesting bit." "There aren't any." "The earthquake." "Oh, stand still." "And don't wave your arms around like that." "Leave your tie alone." "Don't squint." "And speak up!" "The earthquake ran for 400 miles along the coast accompanied by the simultaneous eruption of a line of volcanoes." "We found fresh mussel beds lying above high tide the shellfish all dead." "The land had risen eight feet." "Mountains must be the product of thousands and thousands of such rises occurring again and again throughout history." "Even at the very crest of the Andes we found marine remains..." "The fossilized shells of creatures that once crawled about at the bottom of the sea elevated nearly 14,000 feet above its level." "Time... unimaginable tracts of time... is the key." "Bravo!" "Bravo!" "Well done!" "Mr. Darwin, splendid." "Thank you, thank you very much." "Congratulations." "Interesting paper." "Thank you." "Where have you placed your fossil specimens?" "I was thinking of the British Museum." "Ah... you're happy to have them languish in some dusty Bloomsbury cellar?" "No, not at all." "You'd better let me look over them for you then." "We'll let you know." "Thank you." "Pompous oaf." "Who does he think he is?" "He thinks he's Richard Owen the most brilliant anatomist in Europe." "And you're Erasmus Darwin's little brother." "Darwin of the Beagle Darwin!" "Lord it while you can." "I don't want to lord it." "Liar." "What a brilliant red!" "Brighter than the actual plumage." "I try to allow for the loss of color that comes with death." "Can you do this with my Galapagos birds?" "I haven't finished identifying them yet, Mr. Darwin." "I do know that your "wren" is a finch." "Your "grosbeak" is a finch." "Even your blackbird is a finch." "And they're unique, all new, never described before." "There's even evidence that there are separate species for each Galapagos island." "But I didn't label mine by island." "You didn't label them by island?" "Why do you want them?" "Why, I told you." "I failed to label mine by island." "No, I mean, why are the birds I collected suddenly of such interest to you?" "The vice governor of the Galapagos told me he could identify which island a tortoise came from by its markings." "Yes, yes... small variations are possible from island to island." "Adaptations to climates and so on." "Yes, but the islands all have the same climate." "My expert, John Gould, tells me he's found different species of finches." "What if these finches were blown to the Galapagos from South America and then began to change, adapt, if you will... become more and more different from their ancestors generation after generation?" "First into varieties, then into new species each new species marooned on its own island." "What are you talking about?" ""What if the finches were blown to the Galapagos"!" "God put those creatures there." "That makes no sense." "Why would God put different birds on almost identical islands?" "I have no idea." "It's not a question that requires an answer." "Species were commanded into existence by God." "They are perfect forms and they've been perfect since the day of Creation." "It's divine law, God's will." "I'll see to it that your expert receives my birds." "Thank you." "It's God you should give thanks to." "Come on!" "Tonight, and for one night only, ladies and gentlemen a guided tour of Charles Darwin's Boneyard." "Shh!" "And for goodness' sake, hurry up!" "Yes." "This is a large, extinct llamalike creature... and this is a giant ground sloth discovered by Mr. Darwin at Punta Alta." "Lastly..." "The remains of Mr. Darwin's breakfast." "This skull belongs to a huge rodent... a relative of the South American capybara." "If that's the size of a rat imagine how big the cats must have been." "I have named it Toxodon." "Thank you, thank you, Professor Owen for identifying and describing the extraordinary array of fossils discovered by Mr. Darwin on his voyage to South America." "We allow the planets and the Sun to be governed by natural laws but the smallest insect we wish to be created by a special act of God." "Surely the creation of life has to be explained in the same way as geology using natural, ordinary, everyday causes." "Well, in theory, yes." "But in practice there can be no question about the prime cause:" "divine will." "Shouldn't men of science be free to investigate each and every means by which new species come into being?" "If by that you mean wild accusations about man's ancestry the answer is no." "To destroy man's unique status is to open the floodgates to anarchy." "You might just as well throw muskets to the rabble." "People like Owen think that if there was no Church of England cucumbers wouldn't grow." "If the globe has undergone such profound changes in its history, geologically then surely all living creatures must have changed with it to adapt to their new conditions." "Otherwise they would have perished." "Some did perish, it seems." "Yes, but the continued existence of life on Earth can only be explained by the assumption that a creature like this was replaced by the modern-day armadillo." "There must be a law which causes new species to appear in place of the extinct ones." "Oh, that, my boy, is the mystery of mysteries." "The person who can solve that riddle will take all of the scientific prizes." "It's the variety of their beaks that's so amazing." "They graduate perfectly in size." "From this large parrot-like beak similar to a hawfinch perfectly designed for cracking nuts to this tiny warbler finch fine as a chaffinch to feed on insects." "And they're all descended from this one:" "the common ground finch." "I've started to prepare some color plates." "They'll put my words to shame." "Ras?" "Ras!" "Oh." "Ras." "Wake up!" "What time is it?" "Lunch time." "Well, then go away and come back at tea time." "The Galapagos Islands are almost identical, the same geology, the same climate." "I'm glad to hear it." "Now go away." "So why should different finches inhabit identical islands?" "Ras?" "Small changes over ages and ages can throw up mountain ranges and sink continents." "If mountains can move and rivers can move then why can't animals?" "Finches." "Tortoises." "Iguanas." "If you trace animals across the surface of the earth or dig down and trace them back through time you come face to face with the same truth." "Which is?" "New beings can appear on the earth." "Perhaps everything is part of one ancestral chain." "Man... mouse..." "armadillo." "No." "It's nonsense to think of animals or man as climbing some ladder... to talk of one animal being higher than another." "No." "No." "I think... it's more like a tree." "A tree of life." "Each new species springs from the parent tree like a shoot." "These shoots branch and divide in their turn and so on and so on." "Some branches die out;" "others keep developing." "The trunk, the ancient common ancestor." "The stock... the stock from which all animals and plants sprang." ""Nurs'd by warm sun-beams in primeval caves" ""Organic life began beneath the waves" ""Hence, without parent by spontaneous birth" "Rise the first steps of animated Earth."" "Grandfather's Zoonomia." ""Would it be too bold to imagine" ""that all warm-blooded animals have arisen from one living filament?"" "It's in our blood, Charles." "And grandfather was vilified for it." "It's in our blood." "What Charles Darwin glimpsed over 150 years ago is now the bedrock of biology:" "All forms of life on Earth have evolved on a single, branching tree of life." "One of the most important ideas that Darwin had was that all living things on Earth were related." "How can you realize that you are part of this single tree of life and not be fundamentally moved by that?" "It's... it's something that stirs the soul." "Following in Darwin's path biologist Chris Schneider and his colleagues have come to South America to a remote region of Ecuador near the base of the Andes Mountains." "The rain forest may be home to more species of animals than anywhere else on Earth." "Darwin had been awestruck by its endless variety of life." "He wrote that he felt like a blind man being given sight and that the sounds of the rain forest were like a great cathedral at Evensong." "For biologists today the lowland rain forest and the nearby Andes Mountains are laboratories for exploring Darwin's ideas." "Did he bite you?" "Over the next several days" "Schneider's team will track down rats and frogs bats, birds and lizards through day and night both here in the rain forest and high up in the mountains." "By comparing the two groups of animals they hope to better understand how changing environments might trigger the evolution of new species." "You just can't help but be awestruck by the fact that there are so many different kinds of things here." "There are 12 species of primates." "There are 550 species of birds that have been identified here." "There are 100 species of frogs right here in this little area." "Why is there such diversity here?" "We got some good stuff." "We got a mindblower or two." "Did you?" "I'll show you this one." "Ornithologist Tom Smith wants to compare the size of birds' beaks from the rain forest with those he hopes to find in the mountains." "Even subtle differences may offer clues about how and why new species arise just as it was the beaks of finches from the nearby Galapagos Islands that spurred Darwin's thinking in the 1830s." "Darwin saw that the finches he brought back had uniquely shaped beaks adapted to the different foods on the islands." "He envisioned that these different species of finch had all descended from a common ancestral population that had flown over from the mainland." "Darwin's bold insight was to apply this vision to all of life to see that the great variety of life on Earth, leopards and lichens, minnows and whales flowering plants and flatworms, apes and human beings," "all descended from one root, one common ancestor." "It was indeed another one of his radical proposals not only to say that evolution happened but that there was a root of common ancestry to everything that lived on this planet, including us." "You could construe it in other ways that, as I like to say, are more user-friendly." "You could have thought well, God had several independent lineages and they were all moving in certain preordained directions which pleased His sense of how a uniform and harmonious world ought to be put together." "And Darwin says, "No, it's just history all coming with descent, with modification, from a single common ancestry."" "The key to Darwin's thought in every realm is that given enough time and innumerable small events anything can take place by the laws of nature." "So whether it's the raising of mountains or the evolution of new species all of these things happen through time and change." "The rain forest holds striking examples." "Take a look at this mantis here." "This thing is almost perfectly disguised as a leaf but you can see, if you look at the underside that it's a praying mantis just like you'd find in a garden in North America." "But this one is highly modified." "Its thorax is flattened out to look like a leaf and its wings are modified to look like leaves." "You can even see the veins." "If you imagined a population of mantises and some looked more like leaves than others those ones that look like leaves may tend to survive and reproduce more than others." "And so a series of modifications could build up over time to result in an almost perfectly leaflike mantis." "But if you put it on a background on which it doesn't belong" "I mean, it just sticks out like a sore thumb." "It would almost certainly..." "hey, where you going there, pal?" "It would almost certainly get eaten by something." "Before heading into the mountains" "Smith collects more birds to add to what he's learned in the rain forest." "Bill length..." "How different will the highland birds prove to be?" "...is 9.2." "Common is 10." "Different enough to be considered new species branching off in a new direction on the tree of life?" "When the Andes were uplifted it created a whole variety of new habitats." "The animals that were in the lowland rain forest had an enormous opportunity to colonize these new habitats and they did so." "The real question is whether adaptation to these new environments can lead to the formation of new species." "Flying less than one hour" "Schneider and Smith move from the steamy lowlands to the windswept Andean peaks." "Animal populations made the same journey but gradually, over many generations." "And as the environment changed from rain forest to the high, cool grasslands animal populations were forced to adapt." "These grasslands lie nearly two miles above sea level." "Seasons never change here, so close to the equator but it is said that winter visits every night." "Temperatures often drop below freezing." "Animals not well adapted will not survive." "Hummingbirds are amazing." "It turns out that they can drop their body temperature 50 degrees and go into a state of hibernation to withstand the frigid nights here." "You can imagine a small-billed hummingbird living in cloud forest some thousand meters down slope from us." "And if those individuals were to expand their range up into this habitat where perhaps flowers are much longer you could expect that individuals with slightly longer bills might survive better." "And in fact, there are many examples in hummingbirds where we know that small changes in bill length can make important differences in how that bird extracts nectar and how well it survives." "We're seeing that changes in the environment can be very important in changing the characteristics of those animals as they move between environments." "And we believe very strongly that, in many cases, anyway that this can be very important in the progression to new species." "From one species of bird, the common ancestor hummingbirds with beaks of different lengths evolve over many generations." "And if these populations change so much that they can no longer reproduce with one another they are considered separate species on the tree of life." "Smith and Schneider want to see how closely related the highland birds are to the birds they examined in the lowland rain forest." "They compare color, beak length, wingspan... just as Darwin would have done." "But they have another tool that Darwin never even dreamed of..." "DNA." "Darwin was convinced that traits were passed on from generation to generation, but he didn't understand how." "We now know that the sequence of the four chemical building blocks of DNA determines the traits of all living things." "Each generation passes on this text of As, Ts, Cs and Gs to its offspring." "But occasional mistakes in copying (mutations) can result in new traits." "By comparing DNA we can determine who is most closely related to whom we can determine when they had a common ancestor and when they diverged from that common ancestor." "Laboratory analysis reveals that DNA from the rain forest hummingbirds differs only very slightly from that of the highland hummingbirds." "They must have diverged from a common ancestor relatively recently in the history of life on Earth, about three million years ago." "We're examining the genetic material that makes organisms what they are." "And written in that DNA is the history of their evolution." "The fact that the blueprints for all living things are in the same language, the genetic code of DNA, is powerful evidence that they all evolved on a single tree of life." "How is it that organisms that are so different can be related?" "That we are related to a flatworm or a bacteria?" "Darwin emphasized that small changes would accrue every generation and these changes could build up to amount to enormous changes." "It's not really hard to understand how major transitions could come about given that life has been around for 3½ billion years." "Darwin really had it right." "Come here, Squib." "There." "There we are." "Well, Emma, you're a remarkably good shot!" "(both chuckle)" "Hello, Parker." "Miss Wedgwood." "You've met my cousin, Mr. Darwin, before?" "Sir." "He's fast, eh?" "The fastest in the county." "Did you breed him yourself?" "I mated him with a bitch who was pretty swift." "And how would you breed a fellow like Squib here?" "From the runts, I suppose." "(men laugh)" "How dare you!" "Squib is quite as nice as any of your rotten dogs." "It's true." "It's from the runts and monsters that breeders can produce tailless cats or pygmies like Squib." "I'm not listening to any more of this." "Take me back to the house at once and stop saying horrid things." "From wolves to greyhounds from bulldogs to fellows like Squib in what, a matter of a few hundred years." "I take it you don't find talk of dogs all that interesting?" "I can think of more interesting topics of conversation." "Such as?" "The novels of Miss Austen." "And what does she have to say about selective breeding?" "Nothing, as I recall." "Well, that's a great pity." "Why shouldn't nature produce such differences these different breeds of dog?" "Why should it?" "What would be the point?" "Survival." "In nature, a little poppet like Squib who was the smallest in her litter, would die." "You nearly did die, didn't you?" "Yes, that's true." "But what about the one with a little more vigor or a head start because of some peculiarity?" "Such as?" "A puppy born with an extra-thick coat in a hot climate would be a monstrosity but in a cold climate that would be a good adaptation." "That puppy would have an advantage." "Got you." "Charles." "Emma." "Let me go." "Not until you've paid the toll." "Which is?" "A kiss, for me rather than the dog." "You can make a big dog or a small dog but you can't produce feathers on a dog nor can you create organs as miraculous as the heart and the eyes." "That can only be the work of God." "Hurry up." "It's these blasted ties!" ""Marry." "Not marry." ""Marry." "Children, if it please God..."" "Give me that!" "It's private." "I'm your brother;" "you've no secrets from me." "Yes, I do;" "I have secrets from everybody." "Give it to me." "Thank you, Garmon." ""Constant companion and friend in old age."" "Ras!" ""Object to be loved and played with better than a dog anyhow."" "You old romantic!" "Well, it's intolerable to think of oneself spending one's life like a neuter bee working, working, working." "And all this is a response to your trip to Cousin Emma's?" "Not necessarily." "You don't know anyone else." "No, it's true, your collection won't be complete without that most interesting specimen in the whole series of vertebrate mammals." "And why haven't you married if it's such an enviable state?" "Oh, I'm too lazy to take on anything requiring as much effort as a wife and family." "But you're the marrying kind." "Good Lord, what was that?" "We're being mobbed!" "They probably think we're Poor Law Commissioners." "Why would they think that?" "It's enough that we're top- hatted toffs in a smart carriage and they're scavenging on rubbish heaps, starving to death." "Too many people, not enough food!" "Thank God we'll always have food on our plates!" "Speaking of which, I think I'll have the turbot in the white sauce." "Cabbage, sprout, cauliflower, all bred from the same ancestor." "Cabbage, the leaves;" "sprouts, the side buds;" "cauliflower, the flower head." "All monstrously enlarged." "Sitting opposite me is that strange creature, Homo thesis:" "half man, half theory." "A word of advice." "In my entire life" "I have known only three women who were skeptics and two of them were not permitted in polite society." "Keep your theory from Emma." "It's too late." "I told her... sort of..." "not a theory." "I don't have a theory, just thoughts." "How did she take it?" "She asked me to read her favorite part of the New Testament... our Savior's farewell to his disciples." "You see what I mean?" ""I am the vine, and ye are the branches." "If man abide not in me..."" "Wilberforce's ears have pricked up!" ""If man abide not in me, he is cast forth as a branch" ""and is withered;" "and men shall gather them and they shall be cast into the fire, and they are burned."" "And how is your sole?" "What?" "Your fish?" "Oh... delicious." "I understand your carriage was stoned tonight." "Well..." "We're meeting the threat on the streets head-on." "We're drilling with the Honorable Artillery Company." "Gentleman volunteers." "In the event of riots we will back the police." "Every man, as long as he obeys the law of the land should be free to pursue his own interest in his own way." "Yes, of course." "Charge what he likes for bread or anything else for that matter." "Laissez-faire." "Let individuals compete and struggle for their advantages." "Good night." "Good night." "Good night." "Whenever I can't sleep" "I reach for Malthus." "Or, as I prefer to think of him the Reverend T.R. Morpheus." "Still warm." "Two brandies, hmm?" "Yes, sir." ""The natural tendency of mankind is to reproduce." ""Humans can double their numbers every 25 years."" "But they don't." "A struggle for resources slows growth and death and disease, war and famine check the population." "I know the argument." "Yes, but don't you see exactly the same struggle takes place throughout nature?" "I don't know why I didn't make the connection before." "Why are we not overrun with insects and frogs given the rate at which they reproduce, the number of eggs produced by each and every female?" "Nature's broom sweeps away the ugly ducklings, the runts." "Yes, but it's not that simple." "It's not that simple." "Sometimes it's the ugly ducklings that are better adapted to the situations of life." "They have longer legs and can run faster." "They have bigger beaks that can crack harder nuts and seeds in harsh winters." "They survive, have more offspring." "Nature selects them to pass on their traits to future generations." "And where do we fit in?" "Hmm..." "Well, the sun does not revolve around the earth." "Nature does not revolve around man." "Man must fall into nature's cauldron." "He's no deity, no exception." "Once you accept that species can pass into one another the whole fabric totters and falls." "They'll burn you at the stake for this." "Yes." "But now you have a theory." "So I said, "Don't come down the ladder, Mother;" "I've taken it away."" "Good evening." "Darwin's work began with the observation that individuals differ from each other." "And these minute differences, Darwin believed might be advantageous." "It might give each individual an edge when it came to getting food or finding a place to survive in nature." "Darwin realized that in nature individual organisms compete for limited resources." "Those with some kind of advantage in coloration, for example... or in speed... or in vision... are more likely to survive and reproduce and pass on these advantages to their offspring." "Those who are less fit will not succeed." "Darwin called it "natural selection"" "because the forces of nature select which organisms will survive." "The survivors will be those whose variation fortuitously adapts them better to changing local environments." "And then because they pass on those traits to their offspring the population changes." "That's natural selection;" "that's all it is." "It's not a principle of progress." "It's just a principle of local adaptation." "You don't make better creatures in any cosmic sense;" "you make creatures that are better suited to the changing climates of their local habitats." "That's it." "Darwin couldn't actually see natural selection acting in real time but today, scientists can, by observing the evolution of HIV, the virus that causes AIDS." "Jeff Gustavson has been infected with HIV for over a decade." "He takes a host of medications, but to little avail:" "the virus keeps adapting evolving into new strains that evade the drugs." "There's a pervasive feeling that all you have to do is take your medicine and you'll be okay, and that really isn't the case, you know." "HIV has the capacity to evolve no matter what you give it." "There are 19 HIV drugs on the market today, and of those 19" "I've already been through 14 of them." "Clarence Johnson, too, is locked in a daily struggle against the rapidly evolving virus." "Sometimes I feel like I'm fighting a losing battle." "I haven't given up yet but there have been times that I just want to lay down and give up, but, um..." "I can't leave my family behind." "Clarence Johnson's doctor, Michael Saag has seen HIV evolve into new varieties over the last dozen years." "The virus is constantly changing subject to the forces of natural selection in the environment of a patient's body." "Imagine we didn't have the concept of evolution and we started giving drugs to a patient that in the test tube looked great and all of a sudden the virus starts coming back and it's not susceptible to the drugs anymore." "What a mystery!" "How in the world did that happen?" "There's only one way that it happened: through evolution." "Once inside a patient's white blood cells" "HIV replicates at an alarming rate." "Billions of new viruses are spawned every day and each time it reproduces random genetic copying mistakes" "(mutations) result in slightly different varieties of the virus bursting forth into the bloodstream." "Some of these new varieties, just by chance will have traits that make them resistant to certain drugs." "So when drugs enter the bloodstream natural selection favors the drug-resistant forms:" "they survive and reproduce." "Before long, drug-resistant viruses dominate in the patient's body." "Evolution seems pretty easy to understand when we look at big animals." "We can kind of see it, in a sense." "But that's evolution that took centuries to develop." "When you're talking about something like a virus that you can't see in everyday life its hard to image how it changes." "In the case of HIV, we're talking about minutes to hours to move from one species to another." "It's mind-boggling in terms of the speed with which HIV can replicate." "Clarence?" "How are you feeling overall?" "I'm doing okay." "Great." "Every time I see a patient in the back of my mind I'm thinking" ""What is the virus doing in the environment of that patient?"" "The virus is producing itself on the order of billions of copies a day." "Those few that happen to be able to work in the presence of drug say, "Hey, this is my chance," and they emerge." "So it creates the appearance that the virus has thought this through but in fact it's just a matter of chance." "It's a matter of a virus being there that's not susceptible to the drugs." "It emerges, and the virus begins to win the war." "That's just what happened to Jeff Gustavson." "Each time he tried a new drug, the virus evolved to resist it." "Even a cocktail of multiple drugs made little difference." "Here's this puny little virus that doesn't have a brain and yet it can outwit some of the top scientists in the world." "All the virus has going for it is it can't copy itself too well." "I mean, that's pretty awe-inspiring and scary." "All that happens in evolution, at least under Darwinian natural selection, is that organisms are struggling in some metaphorical and unconscious sense for reproductive success, however it happens." "The process of natural selection feeds on randomness." "It feeds on accident and contingency and it gradually improves the fit between whatever organisms there are and the environment in which they're being selected." "But there's no predictability about what particular accidents are going to be exploited in this process." "For millions of HIV patients, evolution is the enemy." "If only there were a way to take advantage of natural selection to make it work in a patient's favor." "In 1997, at Goethe University in Frankfurt, Germany a researcher may have discovered such a way... quite accidentally." "We had a patient and even though he was being treated with five drugs his virus replication could not be controlled and, at the same time, he was suffering from a lot of side effects of the medications." "So at that point he asked his physician if it wouldn't make sense to just stop taking the drugs for a while since he was really having nothing much from them other than the toxicities he was experiencing." "After three months off drugs the patient's virus population was tested for drug resistance." "Dr. Miller could not believe the results." "At first I thought a mistake had happened because the lab that did the resistance test was not able to detect any resistance whatsoever in this virus population." "We sent a second sample and this result was confirmed." "Within a matter of three months his virus population had changed completely from being resistant to every single drug to appearing to be susceptible to every single drug that we currently have." "Here's what had happened." "With drugs present in the patient's bloodstream only the drug-resistant strains of the virus could replicate." "But some of the nonresistant virus (the "wild type")" "still lingered in the white blood cells." "When the patient stopped taking drugs the environment changed, and the wild type came back." "It replicated extremely rapidly and soon outnumbered the drug-resistant strains." "In Darwinian terms the wild type virus was more fit in this drug-free environment." "Dr. Miller's findings have led to a new experimental treatment strategy:" "take a patient off drugs for a time and if the virus reverts to the nonresistant wild type hit it hard with a combination of drugs." "Clarence!" "How are you?" "The concept of a treatment interruption is a new strategy that we might be able to apply in Clarence's case but we've just got to make sure that we aren't putting him at too much risk if we choose that route." "So one of the options is to take all the drugs away for a while let the virus spring back into its natural state of not having any mutations and then pounce on it again with the regimen, and it might even be the same regimen that we used before." "On first blush, the evolution back to wild type would seem to be a great thing:" "the drugs all of a sudden can work again." "But it's a double-edged sword:" "as the virus goes back to wild type it becomes more dangerous for the host, it's a much more effective killer of cells." "And so we have to find a way to balance those two things out." "Jeff Gustavson is also beginning a treatment interruption, despite the risks." "I feel like I've played all the cards that I have in my hand with the medicines that are available." "I feel like it's worth the risk to try and take another card or a different strategy and just stop taking medicine altogether and hope that the next time that I do go on medicine that it will actually work." "After five weeks off drugs" "Clarence Johnson is enjoying being free, at least temporarily, from their debilitating effects." "If the wild-type virus is staging a comeback it doesn't yet appear to be affecting his immune system." "We took a bit of a gamble." "I think, so far, you know, it's paid off." "And the virus has gone from being resistant to certain drugs and now that population has shifted so that now they're susceptible again." "What I hope for Clarence is that we can find the right course... find a way to stretch his survival out even further so that he's healthy and happy until the next new approach to treatment is able to get him to a point where he can live to 80." "My greatest hope is that when I do go back on medications those drugs will bring my viral load down to an undetectable amount." "I don't know what it feels like to be undetectable so that would be a great experience." "Six weeks into his treatment interruption" "Jeff Gustavson's virus also has changed to the drug-susceptible wild type." "He's now on a new course of medication, and responding well." "From day one of this epidemic we were put into a race with HIV." "Over the last decade or so we've been catching up;" "we've learned a lot about it;" "we've scouted out the enemy;" "we've learned how it replicates;" "we've learned how it tries to survive;" "we learned how it evolves." "And we're now taking those principles that we've learned and applying them to putting the brakes on the virus in this race." "Towards me... towards me..." "There!" "The angle needs to be more acute." "More acute..." "Let's see if it works." "And... open!" "Good God!" "Ras!" "What a horrible shock." "Thought I'd surprise you." "Welcome to Down House." "When is the moat to be dug?" "When the drawbridge is in place." "Who are you trying to keep out, Charlie?" "Everyone, especially you." "Ras..." "What a wonderful surprise!" "My dear, what a journey." "It's not far." "Nature abhors a journey of 16 miles almost as much as a vacuum." "Hello, Annie." "Tea, the man needs tea." "One, and a two, and a three and off you go!" "I've thought of a new name for the village." "Oh, yes?" ""Down-in-the-Mouth."" "If you speak" "I can find you really easily." "Shh!" "How's your work progressing?" "I've sent the manuscript off to be copied." "I've no idea what I'm going to do with it when it comes back." "Everyone be quiet!" "Aren't we glad we're not blind?" "If you're blind you can't see the sky or the flowers." "Or anything else, for that matter." "I can get any of you any time I want!" "Well, go on, then!" "We feel sorry for moles, don't we?" "Moles don't need to be able to see because they live underground." "That's why their eyes have got smaller and smaller ...and owls' have got bigger and bigger." "I can't play." "Everyone's talking about eyes all the time!"