With the choices the tablet gave you, you realize just how important their discovery was. With their model, scientists could begin to understand genetics. You cannot wait to see what this scientist has to say about DNA replication.\nYou see the next scientist sitting in a lab.\n\n<html><img style="-webkit-user-select: none" src="http://www.nndb.com/people/936/000129549/arthur-kornberg.jpg"></html>\n\nYou pull up a chair next to the scientist and cannot contain your excitement. "So DNA replication. What do you know about it?" You ask.\nThe scientists seems amused by your curiosity grins while he says, "It's nice to see someone so excited about what most people think is dull. I'm Arthur Kornberg. Early in my carrier as a scientist I studied how vitamins affected rats but soon grew bored with that. I then started trying to understand the power source in the cell called ATP which led me to be interested in how DNA is built from smaller molecules. I experimented with enzymes that made up DNA at Washington University. Two years ago, in 1956, I successfully isolated the first DNA polymerizing enzyme. After I isolated this enzyme I successfully synthesized DNA in a test tube and my colleague Servo Ochoa synthesized RNA. Since then I have continued isolating and identifying many new enzymes."\n"It was great talking to you Mr. Kornberg but I'm afraid I have to run. Good luck to you in the future!" You say as you stand up, wave goodbye and pick up the [[tablet.|Tablet 12]]
The next lab you enter has two scientists working with microscopes.\n\n<html><img style="-webkit-user-select: none" src="http://www.lifesciencesfoundation.org/content/media/2011/06/18/1952_The_Hershey-Chase_blender_experiment_uic.edu.jpg"></html>\n\nThe man looks up from his microscopes with an excited look on his face. He catches sight of and beckons you closer. "This is amazing!" the man exclaims.\nAs you approach you ask, "What's so exciting?"\nThe other scientist has noticed you and comes to stand next to her partner before saying, "I'm Martha Chase this is my partner Alfred Hershey. We are working to see how bacteriophages infect bacteria. We replaced the sulfur inside the proteins of the bacteriophage with radioactive sulur-35. After the bacteriophage infected the bacteria we used a high speed blending process to knock off the phage coats and then a centrifugation process to separate the phage coats from the infected bacteria. None of the sulfur-35 was detected inside of the bacteria. We then replaced the phosphorus in the DNA of the bacteriophage with radioactive phosphorus-32. When the bacteriophage infected the bacteria we used a high speed blender to get the phage coats off and a centrifugation process to separate the bacteria from the phage coats and we noticed something astonishing. It goes against what modern biology would lead us to believe. When we look at the infected bacteria it contains radioactive phosphorus-32 which we used to label the DNA. The sulfur-35 never enters the cell but the phosphorus-32 does means our only conclusion for what hold the code for infecting the bacteria lies in the DNA and not the protein."\n\n<html><img style="-webkit-user-select: none" src="http://www.accessexcellence.org/RC/VL/GG/images/HERSHEY.gif"></html>\n\nYou can't help but be impressed with these two scientists and look around their lab to appreciate the work they've done when you notice the tablet on the floor. You say your goodbyes and [[continue on your journey.|Tablet 10]]
"Pardue and Gall's work in 1969 helped prove that DNA in the main-band of DNA differed from the satellite DNA. It also helped to prove that the satellites are short repetitive sequences. \n\nWe hope that your journey was an enjoyable and educational one." [[Everything goes black.|End 3]]
The room you land holds two scientists, a man and a woman, looking into microscopes.\n\n<html><img style="-webkit-user-select: none" src="http://www.une.edu/ia/communications/admin/images/DOlins-AOlins.jpg"></html>\n\nThe woman notices you and asks, "I'm Ada Olin and this is my husband Don. What can we do for you?"\n"I've always loved science and when I heard there was an experiment going on here I just had to check it out. What are you researching?" You ask.\n"I'm examining chromatin fiber using an electron microscope. We have observed spherical particles that compose the linear strands. It is much like beads on the string of a necklace. These units seem to repeat. We have referred to these particles as v-bodies." Says the man gesturing towards the electron microscope.\nYou approach and look into the eye piece.\n\n<html><img style="-webkit-user-select: none" src="http://www.bowdoin.edu/faculty/a/aolins/images/nu-dkfd1.jpg"></html>\n\n"It's amazing!" You say astonished at how much it looks like a beaded necklace. You have these inside of you.\n"I hope this was worth your trip here." Says the woman grinning.\n"It has been. Thank you." You take the tablet and [[leave.|Tablet 17]]
The tablet reads: "A year after you met him, 1959, Arthur Kornberg was awarded the Nobel Prize for the enzymatic synthesis of DNA. The polymerizing enzyme Kornberg isolated is known today as DNA polymerase I. Kornberg's work with DNA led to the discovery of [[how DNA is stored|DuPraw]] and exactly [[how DNA is replicated.|Meslesson and Stahl]]
"Ernest DuPraw examined chromosomes with an electron microscope in 1966. His work found that there were no ends to be found and led to the folded-fiber model to explain how chromatin condenses into chromosomes for stages of mitosis and meiosis. This leads us into [[how DNA is replicated."|Meslesson and Stahl]]
The tablet reads: "Hershey and Chase proved once and for all in 1952 that DNA held the genetic material which had been debated for decades. Now that this was proven, the genetics world was prepared for the [[structure of DNA to be explained.|Watson and Crick]]
The tablet reads: "After publishing their paper in 1953, Watson and Crick won the Nobel Prize in 1962 for their work on the structure of DNA. Their work opened up even more doors for future scientists interested in DNA. For example, scientists began to learn [[What causes DNA to replicate|A Kornberg]] and [[how it replicates.|Meslesson and Stahl]]
The tablet reads: "Put in simpler terms, in 1965 Jerome Vinograd found that identical DNA molecules have different densities based upon whether the molecule is linear, circular or supercoiled. Supercoiling occurs during replication. For more information about the replication process we now head to Japan where two scientists are discovering [[exactly how DNA replicates.|Okazaki]]
The stone building surrounds a courtyard where you see hundreds of plants in orderly rows. Among the rows you see a man in monk's clothing walking slowly, studying the plants and furiously writing notes in a moleskin journal. The man is too engrossed in the plants to notice you. [[You approach the man slowly, not knowing who he is or where you are.|Mendel]]
The tablet reads: "In 1958 Meselson and Stahl carried out what is sometimes referred to as "The most beautiful experiment in biology" for how simple and logical an answer it provided. This answer was an important step on the track to discovering how DNA replication works. We are nearing the end of our journey. You understand how the process works now and can choose to either [[continue with the overview of the history of DNA|Britten and Kohne]], [[learn more on the discoveries revolving around replication|Vinograd]] or [[discover more about later DNA research on the function of DNA.|Olins]]
The tablet reads: "Britten and Kohne's work in 1968 helped us understand the function of DNA. Some of our DNA is repetitive and without their research we wouldn't know about it to try to understand why. \n\nWe hope that your journey was an enjoyable and educational one." [[Everything goes black.|End 2]]
"Since the dawn of man, the mystery of genetics had eluded those curious enough to question it. Why do siblings look alike? Why do kids have different eye color from their parents? Questions like these are what led the curious to discover the basic components of life. One of the first steps in the journey of discovering what makes life possible was Robert Hooke's discovery of the [[cell....."|Book]]
<html><iframe class="vine-embed" src="https://vine.co/v/h5F9jX0xpMW/embed/simple" width="600" height="600" frameborder="0"></iframe><script async src="//platform.vine.co/static/scripts/embed.js" charset="utf-8"></script></html>\n(click to play video)\n\nYou think to yourself, 'When does this get interesting? Learning from college textbooks is so boring! I wish I could go back and talk to the scientists instead. Too bad I don't have a [[time machine.|TIME MACHINE]]"
The lab you land in accommodates two scientists one of which is carrying a bottle of Giemsa stain.\n\n<html><img style="-webkit-user-select: none" src="http://www.infocusmagazine.org/1.2/images/opinion.gif"></html> <html><img style="-webkit-user-select: none" src="http://emb.carnegiescience.edu/sites/emb.carnegiescience.edu/files/pictures/picture-36.jpg"></html>\n\n"What's the stain for?" You ask.\nThe woman holding the stain replies, "To stain chromosomes so that we can see them better. We developed the C-banding method. We denature DNA and treat it with this stain. Only the centromeric regions will take up the stain. We also developed in situ molecular hybridization. We use it to study satellite DNA. We label a section of DNA or RNA probes. From there we can use autoradiography to locate the complements to the sections of DNA and RNA. Look at this under the microscope...\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.well.ox.ac.uk/_asset/image/giemsa-stain-text.jpeg" width="600" height="426"></html>\n\n... Pretty cool right?"\n"Yes thank you so much!" You reply, "I really have to get going but I can't wait to see what else you discover!"\nYou pick up the tablet and walk out of the room. On the door to the lab you see the names Mary Lou Pardue and Joe Gall. You make a mental note to look them up later. \nYou look down at the tablet and [[read:|Tablet 19]]
When you open your eyes you see a man sitting at a desk pouring over notes made in a journal.\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.fmi.ch/members/marilyn.vaccaro/ewww/fm-6.jpg" width="243" height="333"></html>\n\nYou approach the man and tap his shoulder, startling him out of his intense study. \n"I didn't hear you come in, what brings you here?" The man asks running a hand though his beard.\n"I had heard about your work and was wondering if you could tell me a little more about it because..." You trail off because there is no way this man will believe how you got there. You'll just have to get information out of him without blowing your cover.\n"How did you hear about my work? It hasn't been published yet." He inqires with a look of distrust on his face.\n"Well actually I had just heard that someone here was working on something new in the science world and I was curious so I came to find you."\nWith a smile the man replies, "It's good to see young people taking an interest in science. My name is Friedrich Miescher and I work here at the University of Tubingen. Follow me to my lab and I'll show you my lastest [[discovery|Miescher Lab]]."
You arrive in a well-lit lab where a man in a white lab coat is working. \n\n<html><img style="-webkit-user-select: none" src="http://www.g2conline.info/content/c16/16349/16349_14.jpg"></html>\n\n"Are you here with my papers? The papers for Phoebus Levene?" The man asks, glancing up at you.\n"I'm actually here to learn about your work," you reply, "What are the papers about?"\n"My papers on some biochemical structures how the components of DNA are linked together. After I identified the four bases used in DNA I figured out that the structure linked phosphate to sugar to base. These nucleotide units make up a string with phosphate groups as the backbone with only four nucleotides per molecule. These four nucleotides are guanine, cytosine, adenine and thymine. I believe that the four nucleotides are arranged to form a tetranucleotide."\n\n<html><img style="-webkit-user-select: none" src="http://upload.wikimedia.org/wikipedia/commons/thumb/f/f0/Tetranucleotide_.png/220px-Tetranucleotide_.png"></html>\n\n"I really have to find those papers. Sorry I can't tell you more." Levene apologizes as he rushes out the door. \nYou look around his lab until your gaze lands on the tablet. It must be time to go. You pick up the tablet and [[read.|Tablet 7]]
Either the transitions are getting less violent or you're becoming used to them. You see three men working at three different work stations.\n\n<html><img style="-webkit-user-select: none" src="http://www.xtimeline.com/__UserPic_Large/170191/evt120221194300189.jpg"></html>\n\nThe three men are discussing something about genetic material when they look up and notice you.\n"What do you want?" The bald one with glasses asks.\n"Umm. I was lost and heard voices so I followed them here," you lie, "But now that I heard you talking I'm intrigued. What are you studying?"\nLuckily, they believe you and the bald one without glasses says, "Well since you asked, we are discussing our paper over our past 10 years of research starting in 1934 and ending with our paper being published in 1944. I'm Colin Macleod by the way. You see, up to this point many scientists have believed protein to hold the key to genetics. There are enough proteins that it would make sense that it could hold the code for life."\nThe balding man with glasses interrupts him, "I'm Oswald Avery. We started by taking heat-killed S strain pneumococcus and removed the proteins, lipids and carbohydrates. When we combined it with R strain bacteria, transformation still occurred so whatever held the information that caused the transformation had to be left. We then repeated the process and transformation still occurred."\nThe third man continues, "My name is Macyln McCarty. Then comes the important part. We repeated those steps again but treated the heat-killed S strain with deoxyribonuclease as well to eliminate the DNA. When it came in contact with the living R strain bacteria transformation did not occur. DNA had to have been the transforming factor that instigated transformation. DNA holds genetic material. The work we are doing is very important so we don't have time to go any more into detail." McCarty pushes you to the door and opens it for you. \nYou pick up the tablet and walk out with the door slamming behind you. [[The tablet reads|Tablet 6]]:\n
"You have begun the journey following the development of modern genetics. Gregor Mendel is only the beginning. He is still considered today as the father of genetics because he realized the importance of heredity long before others began to study it. Before you chose which path to follow, there is another key chapter relevant to all paths. You now will travel to 1869 where a Swiss scientist has made an important discovery." The ground spins and everything turns to [[black|Meischer]].
You find yourself in a room with chalk boards covered in equations. Across the room you see two men standing and staring at a graph drawn in front of them. You approach them and the graph looks more complex the closer you get. \n\n<html><img style="-webkit-user-select: none" src="http://bio3400.nicerweb.com/doc/class/bio3400/Locked/media/ch10/10_26-reassociation.jpg"></html>\n\n"What are you doing?" You ask them, rocking back and forth on your feet.\n"Are you our new assistant? We are comparing the graphs for reassociation of E. coli DNA and Calf thymus DNA." Says one of the men still examining the graphs.\n"Umm no. What do you mean reassociation of DNA?" You ask trying to understand the graphs.\n"When we heat up DNA so the strands separate and then measure the rate they find their complimentary strands as we cool them back down. I'm Roy Britten by the way." He said walking to a different chalk board.\n"I'm David Kohne. The interesting thing is we took E. coli DNA and denatured the DNA to break the hydrogen bonds and then let it cool and recorded the time it took to reassociate. When we did the same thing to the DNA from a calf thymus we expected the reassociation to go much slower because there is more DNA. Instead of a singular curve we had two. Part of the DNA reassociated slower and the other reassociated faster. Something had to make it so some of the DNA could find a complimentary strand. The reasoning we discovered is that the longer DNA of the calf had repetitive portions of DNA that allowed it to reassociate more rapidly than the E. coli. It also has non repetitive segments that take longer to reassociate than the E. coli which only has one copy of the DNA that it needs to survive. This is a tedious process and we really can't afford distractions so I must ask you to leave." Kohne finishes, turning back to the chalkboard in front of him.\nYou say thank you, pick up the tablet and [[continue on your way.|Tablet 15]]
Your eyes pop open to the sound of the school bell ringing. Around you, the other 6 students pack up their materials and head for the door.\n"Have a good weekend!" Your teacher, Mr. Fetter, calls to the retreating class, "And don't forget your Biology 2 project is due next week!"\nYou quickly pack up your materials and leave the room.\nYou finally have an idea of what to do for your project.\n\n\n\nThe End.
Your eyes pop open to the sound of your alarm clock. Whatever you had been sleeping on was terribly uncomfortable. When your eyes come into focus you realize that your makeshift pillow was actually your Biology 2 textbook. You reach next to you to grab your phone but instead you feel a foreign object lying there. You run your fingers over the object because you're too lazy to lift your head off the makeshift pillow.\n'Where have I felt this before?' You think.\nYou snap your head up and glance at the object. \nThe tablet from your dream is sitting right next to your textbook. \nWhen you pick it up to make sure it's real, a line of writing flashes across the tablet.\n"Hope that helps on your Biology 2 project!"\nThe tablet vanishes and you stare at your empty hands in disbelief.\n\n\nThe End.
"How did you come up with your postulates?" You ask Mendel after your flashback.\n"How do you know about my postulates?" Mendel says as he looks up from his writing.\n"I uh..." You stammer "no reason?" but the monk has already pressed on with his explanation, obviously pleased that someone is interested in his work.\n"After some time studying the pea plants, I noticed that there are 7 different traits that appear to be independent of each other. I then crossbred and cultivated the 7 traits with each other and observed the resulting generations.\n\n<html><img style="-webkit-user-select: none" src="http://upload.wikimedia.org/wikipedia/commons/thumb/e/ea/Mendel_seven_characters.svg/592px-Mendel_seven_characters.svg.png"></html>\n\nI then performed monohybrid crosses with the traits and observed the filial generation. After I established the monohybrid probabilities of genotypes and phenotypes, I started dihybrid crosses which led me to discover recessive and dominant traits. I've almost completed my work after 12 years. I've been working with these plants since 1856!"\nYou think anyone who spends 12 years from 1856-1868 working with pea plants has a lot of dedication so you ask, [["Why have you spent so much time working with these plants?"|Mendel why]]
The next lab you enter holds a man doing calculations with complicated looking drawings around him.\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.nature.com/emboj/journal/v31/n7/images/emboj201266f1.jpg" width="214" height="426"></html>\n\nYou quietly walk up to the man. \n"Wow. That looks complicated." You say as your head starts to hurt from the perplexing notes.\nThe man turns around, startled, and says, "I suppose it can be. During interphase we can't see chromosomes. The DNA exists as chromatin and is dispersed throughout the nucleus. When a cell is in other stages of mitosis and meiosis the DNA becomes visible as chromosomes. Using an electron microscope I could study how this process of coiling into chromosomes works. Two sister chromatids join at a centromeric region. I have concluded that each arm extending from the centromeric region is a single strand of DNA wound around protein and folded thousands of times. It is an amazingly precise process. Sorry to ramble on. I'm Ernest DuPraw by the way. Who did you say you were?"\n"I didn't." You say, noticing the tablet on the ground. You bend down to pick it up. "I just forgot something. I'll just get out of your way. Sorry to bother you." You make your way out of the [[lab|Tablet 13]].
<html><img style="-webkit-user-select: none" src="http://1.bp.blogspot.com/-SxLoS7JMtMI/T6PwxuEtNJI/AAAAAAAACac/gDWCfLIndRc/s200/Mendel.jpg"></html>\nThe man notices you as you approach and brushes some stray dirt from his sleeve. "Excuse me sir," you ask, "where am I?"\n"The Abbey of Saint Thomas." The man replies as he turns back to his plants. \nYou watch him take measurements of two different plants and can't stifle your curiosity so you ask, "What are you doing?"\nWithout looking up from his work the man replies "I'm observing how pea plant's characteristics differ between generations based upon the characteristics of the two parent plants."\nSomething about his reply triggers a memory of yours. "Wait. What did you say your name was?"\n"I didn't. But if you must know my name is Gregor Mendel." he replies.\n"Oh I've heard of you!" You say as a memory of your boring 9th grade biology teacher droning about [[Mendel's Postulates|Mendel 2]] comes to mind.
The next lab you enter holds a man standing by one of the centrifugation machines you saw earlier.\n\n<html><img style="-webkit-user-select: none" src="http://archives.caltech.edu/pictures/10.28-116.tn.jpg"></html>\n\nThe man's nametag reads Jerome Vinograd.\nYou interrupt the man's work by saying, "Excuse me Mr. Vinograd, I have a few questions about the centrifugation you're working on. What exactly are you trying to figure out?"\n"Well I was inspired by the results of the centrifugation of the polyomavirus. The DNA separated out into three separate levels of density. They all had identical molecular weight. I have a theory that there is linear and two types of circular DNA that are more compact and sediment easier. Then there is the two circular DNA levels of density. I believe that the more dense has helices that are wound less tightly so in other sections of the strand the double helix is stabilized by supercoiling. This would cause the DNA to be packed tighter and sediment at a much faster velocity." Vinograd explains to you.\nMost of that goes over your head so you thank the scientist and hope the [[tablet can explain it better.|Tablet 16]]
Your eyes pop open to the sound of your alarm clock. Whatever you had been sleeping on was terribly uncomfortable. When your eyes come into focus you realize that your makeshift pillow was actually your Biology 2 textbook. You check your phone to see what time it is. A text is waiting for you from the Bio 2 Wiggio group. The text reads:\n"Reminder: Bio 2 projects due today at 1:15."\nYou check the time. 7:45. \n'Oh crap' you think as you rush through your morning routine, dreading 4th hour.\n\n\n\n\nThe End.
The next lab you enter has something different from all the other places you've been to before now: there was a woman working at a lab table. A man then enters from the other side of the room and makes his way over to you.\n\n<html><img style="-webkit-user-select: none" src="http://www.ontrack-media.net/biology/bm2l1image11.jpg"></html>\n\nThe man reaches out his hand for you to shake and says, "You must be Watson. I'm Maurice Wilkins. We discussed your research and I invited you here."\nTo cover up your confusion you say, "No. I am here for the lecture though and I do have some questions. What exactly did you two do?"\nThe woman walks over and introduces herself, "I'm Rosalind Franklin and my associate Maurice Wilkins doesn't have to do with the research done for this lecture. We do both work with x-ray crystallography but this is on the photographs I took with the help of Raymond Gosling who is a student here. We have improved our x-ray crystallography methods and managed to take high resolution x-ray crystallographs of DNA. The set of photographs were at two different hydration levels." She said as she picked up a file and took out a photograph.\n\n<html><img style="-webkit-user-select: none" src="http://www.howdoweknowit.com/wp-content/uploads/2013/04/X-ray-DNA-Diffraction.jpg"></html>\n\n"This is our most important photograph we were able to obtain. It may not look like much but by using Bragg's law we are able to deduce that the shape of DNA is some sort of a helix. It also confirms Astbury's spacing of 3.4 angstroms." She continues.\n\n<html><img style="-webkit-user-select: none" src="http://2.bp.blogspot.com/_7ycFHfdh3bk/TLg-MGSy6jI/AAAAAAAAAHo/h3e2HivNxfQ/s640/photo+51+explanation.jpg"></html>\n\nAt this point Wilkins chimes in, "Well if you aren't Watson I really must be going to find him." He shakes you hand and leaves without a word to Franklin.\n\nShe pauses for a second to recollect her thoughts and continues, "I suppose you'll hear more of this at my lecture. It is almost time so I should go however if you want to hear more on the processes and implications of our results please do attend." \n\nShe shakes your hand and returns to her work. You [[pick up the tablet.|Tablet 9]]
The lab you land in houses two scientists, a man and a woman, looking at microscopes.\n\n<html><img style="-webkit-user-select: none" src="http://mujeresdeciencias.blogia.com/upload/20070828205659-tuneko-okazaki.jpg"></html> <html><img style="-webkit-user-select: none" src="http://ap-biology-lab.wikispaces.com/file/view/192px-Okazaki_Reiji.jpg/176168959/192px-Okazaki_Reiji.jpg"></html>\n\nYou approach them and ask, "What are you looking at?"\nThe man replies, "We're figuring out how DNA replicates. A lot of people just assume that it replicates continuously from both 3' to 5' and 5' to 3'. This doesn't make sense because that would mean that one of the strands would be replicating backwards. We pulse labeled the DNA of E. coli and then denatured the DNA we extracted after replication. There were many short radioactively labeled segments of DNA that would mean that instead of having two strands continuously replicating one of them had to be broken down into segments to replicate the proper direction rather than backwards. We've also discovered an enzyme that links short DNA strands together such as those produced when replication occurs and the strand breaks into shorter segments." \n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.stmary.ws/highschool/science/APBIO/Heredity/DNA_replication_fork.png" width="673" height="327"></html>\n\n"These fragments are longer in E. coli than in eukaryotes. They use RNA primers on the ends until the enzyme ligase removed the RNA primers and connects the segments. This is just on the lagging strand of DNA. The leading strand is replicated continuously because it is already 3' to 5'. I'm Tsuneko Okazaki and this is my husband Reiji Okasaki." She says still too concentrated on her work to wonder who you are.\nYou see the tablet and [[make your way out of their view.|Tablet 20]]
The tablet reads: "The "v-bodies" that the Olins observed were later named nucleosomes. Their research in 1973 was very important to understanding how DNA formed chromosomes. To learn more about the function of DNA we will [[visit the son of the 1959 Nobel Prize winner."|Roger Kornberg]]
"Erwin Chargaff may have been on his way to a meeting with James Watson and Francis Crick. Chargaff's findings were used to set science back on the right path to discovering the secrets of genetics. Two other scientists, whose research was used later to aid in discovering the structure of DNA, were working in 1952 as well as Chargaff at King's College. These two scientists were [[Rosalind Franklin and Maurice Wilkins.|Franklin and Wilkins]]
The tablet reads: "Franklin and Wilkins knew what they had discovered in 1952 would be a key factor in hypothesizing the structure of DNA. All they needed was a few connecting pieces to reach the goal of discovering DNA's structure. To learn more about the structure of DNA you'll want to [[visit two men who finally put all the pieces together|Watson and Crick]] or to learn more about DNA being the genetic material you can [[visit a man and a woman at Washington University."|Hershey and Chase]]
<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://origin-ars.els-cdn.com/content/image/1-s2.0-S0012160604008231-gr4.jpg" width="326" height="333"></html>\n\nYou enter Miescher's lab and he leads you to a workstation filled with equipment.\n"This is where much of my research was conducted. First I was trying to find the composition of white blood cells so I took used bandages from the hospital and used the pus that contained the white blood cells needed for study. I tried using different salt solutions and settled on sodium sulfate. When I had filtered the cells I separted the nuclei. Then I used alkaline extraction and acidification. I couldn't beleive what I was left with. The substance that was left did not contain sulfur but instead phosphorus and nitrogen! I repeated my experiment before submitting it to others last year in 1869 because it still astounded me. I named this substance nuclein. I am still unsure what its function is but I'm trying to find out." Miescher passionately explains.\nIntrigued you reply, "What are you going to try to do to find out what this nuclein's function is?" \n"I am trying to find a new way to obtain the white blood cells needed without resorting to using pus. There has to be a way to isolate the nuclein in other cells. I will keep working until I uncover its secrets. I've truly enjoyed our coversation. Your interest in my work has motivated me so I really must go." He responds as he quickly returns to his work.\nYou follow Miescher back to his desk and notice the tablet laying on the ground where you first appeared in the room. You reach the tablet, pick it up and read what it [[says|Tablet 2]].
<html><iframe class="vine-embed" src="https://vine.co/v/h5UqEBnXgYA/embed/simple" width="600" height="600" frameborder="0"></iframe><script async src="//platform.vine.co/static/scripts/embed.js" charset="utf-8"></script></html>\n(Click to play video)\n\nYou open your eyes and see a [[large building made of stone looming above you|Monastary]]
<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.benchfly.com/blog/wp-content/uploads/2010/01/Morgan2.jpg" width="263" height="333"></html>\n\nWhen the spinning stops you open your eyes to find yourself in a dark room with a less than pleasant smell. There's a man sitting at a table surrounded by hundreds of jars. He is inspecting the one in his hands and you notice flies buzzing around inside.\n"What's with all the flies?" You ask bending over to inspect the jars.\n"I'm working to see how traits are passed from one generation to the next. The name's Thomas Morgan." The man says glancing up at you, "And put that jar back where you found it. I've been working on this for 8 years!"\n"You've spent 8 years in this dank room studying flies? What have you been doing?" You ask, both impressed and repulsed at the same time.\n"Some things take dedication. We crossbred Drosophila melanogaster fruit flies and in 1909 the first genetic mutations were identified. Some of them agreed with Mendel's studies. I was initially against the theory of heredity but in the years since we started this fly room my results have changed my mind. We've found sex linked traits and other traits that are recessive. The short life of the fruit flies makes them perfect subjects once you are able to see the different traits." He explains as he takes a fly out of a jar and places it on a slide. He then carries the slide over towards a microscope but halfway there the slide slips out of his hand and crashes onto floor. Morgan throws his hands up in frustration.\n"Do you need help cleaning that up?" You offer.\n"No," Morgan says, shaking his head, "I'll just get my student Alfred Strutevant to help." Morgan storms out of the room.\nYou take this as your cue to leave and look to where you landed for the now familiar [[tablet|Tablet 3]].
DNA Through the Ages
"You have just encountered Friedrich Miescher who isolated the contents inside of the nucleus that we now know as DNA in 1896. From here on out you will be able to choose the path you wish to take as continue to expand upon your knowledge. You may choose from three paths. You may [[continue|Morgan]] with the overview of DNA, focus more closely on [[how DNA was discovered and how it replicates|Braggs]] or follow along the discovery of DNA with an [[emphasis on its function|AMM]]
The tablet reads "The legacy of the work Thomas Morgan and his students did from 1911-1928 in the fly room led to several ground breaking discoveries. Morgan received a Nobel Prize for his work in 1933. The work done there helped support the theory of inheritance and the behavior of chromosomes. Today the fly rooms still exist and are used in research. \n\nThe fly room provided groundwork for many advances made in the field of genetics. Our next stop on this journey provided the essential tools for the advances in discovering what housed the genetic code. We now travel a different part of the world where two scientists are working with salt crystals to create a method of photographing [[microscopic objects|Braggs]].
"William Henry Bragg and William Lawrence Bragg won the 1915 Nobel Prize in Physics for their work on X-ray crystallography in 1912 and are credited with discovering "Bragg's Law" which explains x-ray diffraction. It may not seem so now, but their discoveries were critical in the discovery of the DNA structure. At age 25, William Lawrence Bragg became the youngest Nobel Prize winner in history. Now that's something to Bragg about.\nAgain you must choose which path you wish to take. You may choose to [[learn about bacteria strains|Griffith]] or [[learn about genetic material|AMM]]
The tablet reads: "Griffith's discovery of the transformative abilities of the heat killed S strain bacteria led others to discover that something inside the cell caused the characteristics to change. For example, the pneumococcus created the protective membrane so the bacteria was unaffected by the body's immune system. Many other researchers continued his studies further including a group of scientists at Rockefeller Institute who [[expanded upon Griffith's work|AMM]].
"Avery, Macleod and McCarty helped prove that DNA contained the genetic material for cells. They disproved the previous belief that protein held the genetic code. Establishing this fact allowed for the genetics field to advance further. From here there are multiple paths you can take. You can take the path to learn about the [[components of DNA|Levene]] or learn about the [[composition of DNA|Chargaff]]
"You visited Levene after his hypothesis of the tetranucleotide in 1910 when he was studying the linkage and components of DNA. He hypothesized correctly about the components and linkage of DNA but the tetranucleotide hypothesis was proven wrong by scientists after Levene had died. After Levene's discoveries, a man at Columbia University expanded upon them and fixed his mistakes. We travel there [[now.|Chargaff]]
The tablet reads: "In 1974 Roger Kornberg worked to discover how DNA formed chromosomes. His work was very important and led to him winning the Nobel Prize in 2006. The nucleosome theory he came up with has led to many other discoveries to help us understand chromosomes and DNA. The last stop on our journey is to [[visit two scientists who worked to find a way to stain chromosomes."|Pardue and Gall]]
"Well I wanted to work with mice but the bishop here didn't want one of his monks to be studying animal sex so closely so I switched to pea plants." Mendel said. "As much as I enjoyed talking to you I really must get back to my peas. Farewell."\nThe monk returns to his work and you begin walking away. You turn over your shoulder and shout back at him "PEAS OUT YO!"\nMendel glances up from his work, clearly confused. \nYou continue walking away with a grin dancing across your face as a result of your own wittiness. The grin slips off your face as you remember that you're stuck in the 1860's. You sprint back to the spot you landed to see if there are any clues. On the ground you spot a tablet which [[reads|tablet]]:
You land in an office filled with books and notice a man scrawling calculations in a journal. \n\n<html><img style="-webkit-user-select: none" src="http://www.macroevolution.net/images/erwin-chargaff-200x297-0.jpg"></html>\n\nYou're starting to get a hang of how to handle barging in on people's lives unannounced so you clear your throat to get the man's attention. "Excuse me sir," you say, "I'm here from the local school and am interested in what you are studying here at Columbia. Could you tell me a little bit about what you're working on Mr...." You look at the nameplate on his desk, "...Erwin Chargaff?"\nHe sets down his pen and begins speaking. "Well, I don't usually have visitors. I suppose I could explain what I'm working on. Your body is composed of little cells. Inside that cell there is a nucleus. There are these chains inside of those called DNA. They have four components that make up the links of the chains. Previously it was believed that these bases existed in equal amounts. Using a process called chromatography it is possible to separate these chains and measure the amounts of each component. A man by the name of Phoebus Levene discovered these nucleotides and assumed they were all in one molecule called a tetranucleotide. But what I found in 1952 is that inside the cell the ratios are not 1:1:1:1 like he assumed. There are equal amounts of the adenine and thymine and equal amounts of the guanine and the cytosine. That would disprove his theory. In the DNA of different organisms there are different percentages for the amounts of each. Others have previously assumed that the variation was due to experimental error but that is not the case. I hope that was what you needed. I'm a busy man and I have meetings soon so I must go. Goodbye and good luck." Chargaff gathers his things and heads out the door.\nYou reach for the tablet and [[read what it says.|Tablet 8]]\n
Mendel's Postulates, you remember, are:\n\nGenetic characters are controlled by unit factors that exist in pairs in individual organisms.\n\nWhen two unit factors responsible for a single character are present in a single individual, one unit factor is dominant to the other, which is said to be recessive.\n\nDuring the formation of gametes, the paired unit factors separate, or segregate, randomly so that each gamete receives one or the other with equal likelihood.\n\nDuring gamete formation, segregation pairs of unit factors assort independently of each other.\n\nYour 9th grade biology teacher was great at teaching the facts of biology but was too lazy to teach the more important and more interesting aspects of biology; the why and the how. \n\nWith the father of genetics himself right beside you, it would be a shame if you didn't ask him [[how|Mendel How]] he discovered his postulates.
When you land you see two men who look familiar. You think you may have studied them in 9th grade biology.\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www.nobelweekdialogue.org/wp-content/uploads/2012/06/H4000039-Watson-and-Crick_cropped-by-CM-v1-1440x866.jpg" width="867" height="522"></html>\n\nThe two men are working on building a metal structure. You recognize the structure of DNA in a double helix. These two must be James Watson and Francis Crick.\nYou don't want to interrupt but your curiosity gets the best of you. You ask, "Excuse me, are you two willing to tell me a little about what you're building? It looks fascinating!"\nCrick glances at you and replies, "We are building a model of what we believe DNA looks like. We believe that two strands of phosphate-sugar-base run anti-parallel in opposite directions forming a double helix. The sugars and phosphates act as the backbone of the helix with bases in pairs on the inside. The bases are in pairs. Adenine and thymine fit together with two hydrogen bonds and so do cytosine and guanine with three hydrogen bonds. They coiled around a central axis in a double helix. As the helix twists the flat structures of the bases are 3.4 angstroms apart. One complete turn of a helix is 34 angstroms apart making each turn the result of 10 rungs of the ladder turning slightly. We are building this model to see if the angles and bonds make sense the way we believe that they do."\n"How did you come up with such an odd but brilliant design for DNA? What evidence have you found for it?\n\n<html><img style="-webkit-user-select: none" src="http://www.pinkmonkey.com/studyguides/subjects/biology-edited/chap8/fig_4.gif"></html>\n\n"A man by the name of Chargaff found that adenine and thymine exist in the same abundance in a cell and so does cytosine and guanine. This led us to believe that they existed in pairs. We found how they could fit together and be held together by hydrogen bonds. A photograph we received from Wilkins using x-ray diffraction that suggested that the DNA forms a helix led us to try a double helix as opposed to the triple helix others were trying. We need to publish our work before our competition figures it out too. It's not really something we should be telling to strangers when we have so much at stake...who are you again?"\n"Oh no one of importance." You see the tablet and nonchalantly pick it up. "I'll just be on my way. Best of luck though." You leave the [[room|Tablet 11]].
You land in a room and see two men working with a strange contraption.\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://www1.sulekha.com/mstore/laraphds/albums/default/Sir%20William%20Henry%20Bragg%20and%20William%20Lawrence%20Bragg.jpg" width="421" height="333"></html>\n\nOne has a hideous moustache that wouldn't have worked in any time period. You don't want to break their concentration but you advance towards them and clear your throat to get their attention.\n"What is that thing?" You ask when you get their attention.\n"It's an X-ray spectrometer. We are using it on a salt crystal to look at the diffraction patterns it creates to calculate the position of the atoms as well as the angles between them." The older one says as the younger one continues working.\n\n<html><img style="-webkit-user-select: none" src="http://images.tutorvista.com/content/solid-state/x-ray-diffraction.jpeg"></html>\n\n"What? How does that work?" You ask having no idea what any of that means or how it relates to DNA.\nThe younger one looks up from his work and smiles while saying, "We shoot x-rays at the crystal and from how the rays bounce off we can deduce the structure using physics and the rules we established."\nYou still have no idea how these x-rays have anything to do with DNA so you respond, "Oh. That's cool. Do you guys study genetics at all?"\n"We're physicists," The elder replies, "I'm William Henry Bragg and this is my son William Lawrence Bragg."\n\n<html><img style="-webkit-user-select: none; cursor: -webkit-zoom-in;" src="http://images.bridgemanart.com/cgi-bin/bridgemanImage.cgi/400wm.UIG.1983450.7055475/540712.jpg" width="255" height="333"></html>\n\nYou wonder why the mysterious tablet would have brought you here. These two scientists aren't studying the type of science you want to learn about. There must be a reason you were brought here so you decide to ask more questions.\n"How did you develop this spectrometer?" You inquire.\n"The atoms of the crystal are too small to see but with this even if we can't see them we can figure out their structure. It's like seeing a shadow of a cat when you can't actually see the cat itself. You can see the tail and shape of it and figure out what it is," the younger, William Lawrence explains.\nYou nod your head as the men return to their work. You look around trying to think of how the Braggs relate to DNA when you notice the tablet laying on the ground.\nYou pick the tablet up thinking that for it to have appeared you must have learned what was needed to complete the task. [[The tablet reads|Tablet 4]]:
The next lab you enter seems far more modern that then ones you have visited before. You must be nearing the end of your journey. There is a man sitting in lab coat by a work station.\n\n<html><img style="-webkit-user-select: none" src="http://med.stanford.edu/featured_topics/nobel/kornberg/slideshow/kornberg-lab.jpg"></html>\n\nFeeling more at ease closer to your own time you look at the nameplate outside of the room and knock on the door of Roger Kornberg's lab to get the man's attention. "Excuse me sir." You say when he turns to the doorway, "Can I ask you a few questions?"\n"Ask away!" The man says.\n"I was just wondering what you were working on here."\n"I've been working with chromatin using x-ray crystallography. What I've found and theorized is that a length of about 200 base pairs of DNA wrap around eight histones. This structure is known as a nucleosome core."\nYou notice the tablet on the ground and say, "Thank you Mr. Kornberg." [[You pick up the tablet and walk out the door.|Tablet 18]]
Austin Sack and Ellen Kane
You're actually somewhat prepared for the spinning and are barely disoriented when you land in a new room. You see a man in a lab coat inspecting a dead mouse. \n\n<html><img style="-webkit-user-select: none" src="http://upload.wikimedia.org/wikipedia/en/thumb/f/f4/Griffithm.jpg/140px-Griffithm.jpg">\n</html>\n\nThe man is mumbling under his breath about pneumococcus bacteria as you approach him. You see cages of mice surrounding the room. \n"What'd you do, forget to feed it?" You say to the man.\nHe doesn't look amused as he replies, "No this mouse died from pneumonia. You see I noticed there are different types of pneumococcus, the bacteria that causes pneumonia. Strain S has a protective coating on it that will protect it from the body's immune system and it appears smooth. The R strain appears rough and cannot protect itself from the body's immune system. When I inject a mouse with the avirulent R strain it doesn't get pneumonia. When a mouse is injected with the virulent S strain they get pneumonia and die. I can use a heating technique to kill the S strain and when it is injected into a mouse it doesn't die. If I inject a mouse with both heat-killed S strain and living R strain the mouse will get pneumonia and die."\n"But if you injected the mouse with two things that don't cause pneumonia on their own how can they kill the mouse together when one of them is dead?" You ask baffled by the subject.\nThe man sighs and takes a deep breath and continues, "When the heat-killed S strain comes in contact with the living R strain it must cause a change in the bacteria cells. When I inspected the blood of this mouse, I found living S strain bacteria even though all the S strain I injected it with was heat-killed. I call this process transformation although I'm still not sure what in the heat-killed S strain cells causes it."\n\n<html><img style="-webkit-user-select: none" src="http://education-portal.com/cimages/multimages/16/Griffith_1928a.png"></html>\n\n"That's amazing. How long have you been working on this?" You ask wondering just how many mice this man has killed.\n"Just the two years starting in 1927. I'm hoping to publish my findings in the near future..." He trails off before continuing, "Oh I'm sorry! I never introduced myself! I'm Fredrick Griffith."\nYou notice the tablet on the ground while Griffith was talking so you quickly reply, "I will be sure to tell the people I meet of you genius Mr. Griffith!"\nYou pick up the tablet and leave the room before Griffith can see what you're holding. When you reach the hallways you see where the tablet will lead you [[next|Tablet 5]].
The tablet reads: "You just visited the Okazakis in 1968. Their discoveries explained how DNA replicates. \n\n<html><img style="-webkit-user-select: none" src="http://i.imgur.com/wHO8zek.gif"></html>\n\nAt the fork, helicase is unwinding the double helix. Binding proteins attach to the strands to keep it from reforming the double helix. Gyrase keeps the tension low as it supercoils. The leading strand is on the bottom and synthesis occurs continuously. On the lagging strand polymerase I and ligase replace the RNA primer and attach the fragments of DNA. \n\nWe hope that your journey was an enjoyable and educational one." [[Everyhting goes black.|End 1]]
You find yourself in a lab where two men standing around a small contraption.\n\n<html><img style="-webkit-user-select: none" src="http://www.nature.com/nature/journal/v417/n6885/images/417121a-i1.0.jpg"></html>\n\nOne of the men is slouching with his arms crossed. "Only five more minutes." The other man explains sympathetically.\n"What are you waiting for?" You ask, taking the two men by surprise.\nThe man with his arms crossed looks you up and down, "Who wants to know?" He asks sounding accusing.\n"I just want to learn more about your research. I mean no harm. Just a curious student." You reply trying to cover your tracks.\nThe man does not seem any less wary of you but thankfully his lab partner steps in, "What would you like to know? I'm Matthew Meselson. I apologize for Frank Stahl, my partner. The experiments we do are somewhat infuriating for impatient people."\n"What kind of experiments are you conducting?" You ask Meselson.\n"Well there are three proposed methods of replication of DNA. The one that Watson and Crick have proposed is the semiconservative method. In replication the strands separate and act as a template for the synthesis of new strands. Each of the double helix would have one new strand and one of the strands that acted as the template. There's also the conservative method. The double stranded helix acts as the template and histones expose the nucleotide bases that create a completely new double helix. The third theory is the dispersive. Rather than having the helix unwind, the backbone would break every 10 or so nucleotides and untwist the molecule and then attach to the newly synthesized strands. It would create shorter pieces that would alternate from old to newly synthesized pieces." Meselson said checking the machine again.\n"Nitrogen is a major component in DNA. We can replace the regular nitrogen in the DNA with a heavier isotope by growing E. coli for several generations in a medium of the nitrogen isotope. We centrifugated the DNA from these cells in a salt density gradient. The DNA settled out to its density in the salt solution. We centrifugated E. coli DNA with the normal nitrogen and found where it settled out to its density. From there we took E. coli with the heavier isotope nitrogen and allowed them to divide in a medium of the normal nitrogen. After one replication the DNA was found to have close to the intermediate density. This disproved the conservative method because half of the DNA would be at each density. To determine if the semiconservative and dispersive methods we needed to allow the E. coli more replications. After two replications the DNA separated into two densities during centrifugation. One corresponded with the regular nitrogen and the other corresponded with the DNA that contained one strand with normal nitrogen and one strand with the heavier isotope. After the third replication it continued to be consistent with the semiconservative method of replication. We are repeating our results before we publish our findings." said Stahl impatiently waiting to revalidate their results.\n\n<html><img style="-webkit-user-select: none" src="http://www.biology.arizona.edu/molecular_bio/problem_sets/nucleic_acids/graphics/M_SExp1.GIF"></html>\n\n"That's a brilliant process." You respond genuinely impressed by how logical a process like this is.\n"Thank you. We've enjoyed our conversation. It's helped provide us a distraction." Meselson said stopping the centrifugation process with an anxious Stahl waiting to check their results.\nYou see the tablet and wonder how long until you get home but [[continue on your way|Tablet 14]].