MANN-KEY “Cracking the Code of Life: The race to decode human DNA” Video Questions (A video on the Human Genome Project) NOVA – © 2001 “When you look at the mirror, you don’t see DNA or RNA. You see proteins and the action of proteins. We are the product of our proteins and their activity.” Craig Venter, “Cracking the Code of Life” Video 1) How much of a banana’s DNA is similar to ours? ___50%_OF THE GENES_ 2) 4 and some billion years ago – 1st speck of life on warm surface of a BUBBLE 3) Raw DNA looks like what in raw form? Eric Lander – geneticist found that it looks like LONG STRANDS OF MOLECULES: these double helices of DNA ARE LIKE LITTLE THREADS OF COTTON WHEN PUT ALL TOGETHER._ 4) Human beings only have __TWICE___ as many genes as the fruit fly. 5) DNA is organized similar to steps in a __ladder____ 6) Each step is made of base pairs: cytosine-guanine and adenine-thymine. 7) DNA is 3 billion steps long in form of a double helix. 8) Size of DNA – 10 angstroms = ____1 billionth______ of a meter. 9) Each step in the ladder can give information about what will be passed to your children. 10) Every human baby born is ___99.9___% identical to every other human baby in the world. 11) Since 1990, scientists have been involved in the Human Genome Project to understand the tiniest differences in our genes that makes us healthy or sick. 12) Only about 1% of the _GENES___ are active and this is why scientists needed a map to find these genes. 13) Revolutionized technology – ___10,000___ letters every second. 14) Boeing 777 – _about 100,000___ parts. 15) Genome project, is similar to getting a parts list, but that’s all you have. It’s important to have, but that doesn’t mean you know how to put it together. 16) Allison and Tim had a son Hayden – something was not right – something clearly wrong by time he was 1 year old. Laughed all the time. Never crawled or ate with his hands. Started regressing. Started missing developmental milestones. Slowly getting worse – Tay Sachs Disease. 17) Tay Sachs begins with just 1error in a letter/base of the DNA molecule. 18) Genes create proteins, and the protein that is supposed to dissolve fat in brain, which when it is not produced, the fat builds up in the brain and begins to destroy the baby’s brain. 19) Hayden has gone blind, can’t eat solid food, has seizures as much as __10__ times a day. Only one outcome. Most die by age _5-7 years__. 20) Tim’s identical twin brother, Charlie, and wife Blythe, who have 2 girls, including little ___Cameron_____, who startled easily just like Hayden always did. Cameron had Tay Sachs also. 21) Tay Sachs is a very rare condition and it usually occurs in specific groups, like Ashkenazi Jews. And even then, the baby must inherit the bad gene from both parents. 22) Hayden Lord died a few months before his_3rd__ birthday. 23) The promise of the human genome project – an ____early warning system__ for parents, doctors, etc. about genetic diseases. Geneticists can spot these catastrophes while they’re still insignificant dots on the gene. 24) Craig Venter, a government scientist thought that he could find the human genome much faster than the other science team in 1990. 25) Craig Venter wanted to use the new machine that could identify Cs and Ts and As and Gs. 26) This machine worked as a robot chopped human genes_ into tiny pieces. A laser bounces __light__________ off of each tiny bit of DNA and the color that it sees represents individual letters in the genetic code 1 27) Venter’s dream was to have several of these machines going at once, so he quit his government job and started a company called __Celera Genomics________, (Celera) means speed. 28) Served time in navy and was drafted to ___Navy_____, where he saw many people die. Returned in __1968___ and wanted to make use of this gift. 29) He didn’t like the attitude of the government team – planned to take 15 years. 30) Venter said his team would finish in _2__ years! 31) Craig Venter's announcement that his team would finish the entire genome in just two years galvanized everybody working on the public project. Now they were scrambling to keep up 32) Skip to 33:45 to 38:15 33) Bullet point notes: *We invested in a national highway system in the 1950s. We got tremendous return for building roads for free and letting everybody drive up and down them for whatever purpose they wanted. We're building a road up and down the chromosomes for free. People can drive up and down those chromosomes for anything they want to. They can make discoveries. They can learn about medicine. They can learn about history. Whatever they want. It is worth the public investment to make those roads available. *The laboratory was a laboratory in Buffalo. And so they put an ad in Buffalo newspapers and they got random volunteers from Buffalo. They got about 20 of them, and chose at random this sample and that sample and that sample *Celera: They also got a bunch of volunteers, around 20, and picked five lucky winners. * I mean, could that guy from Buffalo, could he really be a stand-in for all human kind? * Hasn't it been drummed into us since birth that we are all different, each and every one of us completely unique? We certainly look different. People come in so many shapes and colors and sizes the DNA of these humans has got to be significantly different from the DNA of this human. right? *The genetic difference between any two people: one tenth of a percent. Those two, and any two people on this planet are 99.9 percent identical at the DNA level. It's only one letter in a thousand differences. *So people are incredibly similar to each other.. It turns out we also share many genes, with everything. Fifty percent of the genes in a banana are in us? *Look, you've got cells, you've got to make those cells divide. All the machinery for replicating your DNA, all the machinery for controlling the cell cycle, the cell surface, for making nutrients—all that's the same in you and a banana. *Deep down, the fundamental mechanisms of life were worked out only once on this planet, and they've gotten reused in every organism. The closer and closer you get to a cell the more you see a bag with stuff in it and a nucleus, and most of those basic functions are the same. Evolution doesn't go reinvent something when it doesn't have to. Take baker's yeast. Baker's yeast we're related to one and a half billion years ago. But even after one and a half billion years of evolutionary separation, the parts are still interchangeable for lots of these genes. ROBERT KRULWICH: Now, does that mean—I just want to make sure if I understand this right. Does that mean when you look through those things that all the Cs and the As and the Ts and the Ts and the Gs...are you seeing the exact same letter sequences in the exact same alignment? When you look at the yeast and you look at the person, is it C-C-A-T-T-T? ERIC LANDER: Sometimes. It's eerie. The gene sequence is almost identical. There are some genes, like ubiquitin, that's 97percent identical between humans and yeast, even after a billion years of evolution. 34) Skip from 46:54 to 58:16 35) Cystic fibrosis discussion: - Riley Demose – 13 days old – Cathy got the call that Riley had tested positive for cystic fibrosis. CF, Cystic Fibrosis, attacks several organs of the body, especially the lungs. Its victims suffer from chronic respiratory infections. - Half of all patients die before age _30___ 2 - - - - When you look at yourself in the mirror, you don't see DNA. You don't see RNA. You see proteins and the result of protein action. So that's what we are physically composed of. Proteins are 3-dimensional because _we_ are 3-d. Every protein is given a shape, which defines them and their function. In the protein world, “your shape is your __destiny_______”. Riley is missing __3_ letters out of __3 billion_____, but the consequences are huge. But because of that error, he has a faulty gene. And that faulty gene creates a faulty, or misshapen protein. And just the slightest little changes may just have consequences that are huge. The protein is misshapen, and lung cells can’t do their job. His lung cells will not let salt out of the cell, causing it to be trapped in the cell. The lung cell becomes sticky and covered in mucus. If doctors could just get the shape of the protein right, then it would be recognized and allowed in the cell to do its job. Just finding the letters in the Genome project was one dimensional . Fixing the proteins from the letters is _three__-dimensional. Toni also has CF, but she developed it later. Didn’t fit the profile. She was told she might not survive beyond her 21st birthday, and now she’s in her mid-40s. She still has to go to hospital to get lungs cleaned out. She still has the mistake in the genes, but she has something that most patients don’t have. Craig Gerard, Toni’s doctor, says that “no gene acts in isolation”. Could she have some good genes that are helping her? Dr. Gerard is looking for special ingridient in Toni that might be helping her. Maybe they could bottle it and give to Riley and other CF patients. 36) The first building blocks are the DNA letters. From them we can infer the genes. 37) From the genes, you get to the protein products and then you have to understand what each of the proteins does, wht its shape is, how they interact with each other and how they make connections with each other.. 38) A human being only has 30,000 or so genes, only about twice as many as a fruit fly. That’s bothersome. But the difference is that our genes seem to do more. 39) One gene in fruit fly might only make 1-2 proteins, while one in human might make 1-4 proteins, causing different functions. 40) Male pattern baldness search – look at the gene’s letters for hair for bald guys. Compare the letters with those of men with hairs. Look at brothers’ genes so that the only differences may be the genetic difference. If you use related people, it’s easier. Why? Comb through the DNA of lots of people who are related, and I find some of them are sick and some of them are healthy, I might have a much better chance of figuring out which genes are involved. 41) Iceland – little island with tiny population of 280,000 people, mostly all descended from Vikings 1000 years ago. They have a fantastic written history, almost everyone’s family tree, and it’s on a database. - Lady with osteoarthritis - Got sick at 12 and 11 of her 17 siblings had to have hip replacements b/c it was so bad. This is the family that the decoding people were looking for . - They started combining family trees, medical records, and DNA to learn what’s going on. 42) What’s the problem with everyone seeing your medical records? They do know everything about you, not only about your medical history, about your medical past, but they now do have your gene, the DNA. They know about your future, something about your children, about your relatives. 43) Movie clip “Gattaca” – everyone’s DNA (future diary) is available and most babies are genetically produced. The main character in the movie was conceived the “old fashioned” way. 3 44) Making gene chips – came from babies. A single chip will allow you to test _10,000 or so babies for certain diseases. 45) Knowing is great; knowing early is preventitive– as long as there is something that you can do something about it. 46) What if it took 20-50 years to find a cure for a disease you were going to get? Would you still want to know? 47) What if the test just tells you that you may get the disease? May and will are different. There may be a chance of disease vs. you will get a disease. 48) Alyssa and Lori and Melanie (younger sister who died of ovarian cancer). Died in 1983. - Alyssa then got breast cancer at age 34. She did well, but then found another lump in 1996. - There are links b/t breast and ovarian cancer – brca1 and brca2 are perfectly healthy normal genes that we all have. Sometimes there is a mutation on them – 2 letters missing and genes are reconfigured. This mutation causes a very high cancer risk – 80% - Lori went to be tested – she was fine. However, Alyssa does carry the mutated gene, so she’s wondering what day she’ll get sick. - Alyssa’s son and daughter could also be carrying the gene – 50% chance - Alana found lump in her own breast in senior year of high school (17 years old). Lump was benign or not cancerous but Alana decided not to have the test that year. 49) Do we want to know? And, can we live with the answer of maybe or not? ____________ 50) In “Gattaca”, they could choose the baby that they wanted, one without baldness, obesity, etc. We have the beginnings of the ability to do this today. -If we can do this, can we also add in the eyesight of a hawk? Not right now. -It’s a very complex machine, and going in with a monkey wrench could break the machine. -But, we do it with plants and some animals. Does that make is okay though…. 51) What about with humans? How do you feel about this topic? Please support your answer. ANSWERS WILL VARY 53) Who won the race of finding the Human Genome first? IT WAS A TIE!!! Notebook Questions –BE SURE TO ANSWER THESE AS WELL! 1. What is the significance of knowing the human genome? 2. Do you think we have to be careful with the power that knowing it gives us? Explain. 3. What can we do with this knowledge? 4