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Cell Biology - Lecture 1 - Video 1 - Notes

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Boston University
CAS BI 203
Martin Steffen

Lesson 1 – Video 1 [00:00:00.00] 3 [00:00:01.11] SPEAKER: Hi. In this first video, I thought I'd offer a personal perspective about 4 the place of biology and biomedical engineering in modern society. I'll start by giving a 5 historical perspective. There have been certain times and places when human history reaches a 6 turning point, and the trajectory of civilizations are altered. I believe we live in such a time right 7 now with respect to the biomedical sciences. 8 [00:00:28.39] With the deciphering of the human genome, the emergence of stem cell 9 technologies, and the tools of genetic and genomic engineering, we have the potential to 10 significantly increase health, longevity, and human capabilities, while decreasing disease. And 11 indeed, we'll even have the ability to transform what it means to be human. Will these 12 developments turn out to be a good thing for humanity? History will be the judge of that. 13 [00:00:54.17] Speaking of history, and since we're at a liberal arts university, do you know what 14 the revolutions or epochal events that the dates and places here refer to? Spend a few minutes 15 looking those up, and we'll spend a few minutes in class checking your knowledge. Now in 16 contrast to these previous events, which should have a fair degree of geographical localization-- 17 Athens, Rome, Florence-- the current movement transforming biology is truly international. 18 [00:01:23.72] And I only put Boston there because of the concentration of universities, research 19 headquarters of Big Pharma, and all the biotechnology firms in this area. It's really true that for 20 any existing biomedical problem, it's likely that one of the top three of the world's experts in that 21 area is just a cab right away, in Boston. No other areas have that kind of concentration of skill 22 and expertise. 23 [00:01:48.70] And that's another thing you should be taking advantage of while you're here. 24 Many advances in human society, or great leaps forward for civilizations, are the result of 25 technological advances. I've drawn up my highly unofficial list of seminal inventions and 26 discoveries that I thought were the most important for shaping society as it is today. 27 [00:02:13.41] I invite you to look at a recent compilation of the top 50 inventions, compiled by 28 Atlantic magazine. We might discuss a few these briefly in class. Spend a few minutes thinking 29 about two of the biggies-- fire and the printing press. Do you know why fire was such an 30 important technological advance for the progress of the human species? I'll give you a hint. It's 31 not for warmth in colder climates. It's something much more fundamental. Bring your best ideas 32 about fire to class. I'd like to hear them. 33 [00:02:46.58] I'd also like to hear what you think are the important inventions and discoveries 34 that I've left off. Make your case for the important things that I have left out, and we'll discuss 35 them in class. The point of this slide is to motivate the next one. Which is, once again, my highly 36 unofficial list of the top 10 biological developments of the last half century that has helped to 37 establish modern biology as it is today, in 2014, and will shape it going forward. These are in 38 chronological order. 2 [00:03:19.89] The discovery of the structure of DNA, the 39 double helix, reveals a tremendous 40 amount of biology. It made clear the way information was stored in the hereditary material. It 41 suggested how DNA was replicated to make copies of itself. And it led, in short order, to the 42 elucidation of steps needed to make RNA and then protein. 43 [00:03:41.11] The next major development I have listed is recombinant DNA engineering. This 44 is the ability to take a piece of DNA, digest it, cut it with a restriction enzyme, so that you can 45 have a molecularly defined piece of DNA. You could then clone it into a plasmid and grow it in 46 bacteria and have millions of identical copies of that piece of DNA to study. Prior to 47 recombinant DNA, it was impossible to work on the same piece twice. 48 [00:04:09.92] Long pieces of DNA were sheared, and they would be fragmented randomly. And 49 now with recombinant DNA, we can start to engineer and manipulate DNA in ways that will 50 help us study the DNA and produce desired effects. DNA sequencing, which was first developed 51 by Frederick Sanger, Walter Gilbert, and Allan Maxim, let us decode the information stored in 52 DNA, the sequence that held the information. 53 [00:04:38.93] The sequencing technology has evolved over time and is now improving faster 54 than Moore's Law for resistors and has led to the possibilities of a $1,000 genome. Monoclonal 55 antibodies is the first time that we were able to produce immortalized antibodies, essentially 56 creating an infinite supply. And this was critical for the standardization of protein studies. 57 [00:05:04.87] Now, a researcher in Boston and a researcher in California could say, I'm studying 58 the protein that reacts with this antibody, and weighs about 50 kilodaltons, and it gave a great 59 deal of certainty that you were talking about the same protein. PCR, developed by Kary Mullis in 60 the early '80s, greatly increased our ability to manipulate DNA. Basically, turbo charging 61 recombinant DNA. The ability to amplify a single DNA molecule into billions of copies that can 62 be sequenced or cloned or used for any particular purpose. 63 [00:05:42.88] We couldn't have modern biology without the development of personal computers. 64 There is so much information that no human being can store them. The data sets of grown so 65 large that, like Big Physics, single biological experiments can now include millions of data 66 points. And the only way to keep track of it is with the use of computers. Microarrays, or DNA 67 chips, developed in the mid '90s, was a major step forward in enabling the global or systems68 level study of a cell or organism where we could keep track of each gene, 69 [00:06:24.00] and think about how the parts relate to the whole. Prior to this, biology was 70 extremely reductionistic. The goal was to study and isolate a single protein and learn all about it, 71 and then trying afterwards to fit it back into a picture of the cell's operations. But microarrays 72 essentially enabled the ability to take snapshots of what every part in the cell is doing at a 73 particular time. 74 [00:06:53.04] Two events in the late '90s, the cloning of Dolly the sheep and the isolation and 75 growth of embryonic stem cells, have hinted at the immense potential of what can be achieved 76 using these very powerful biological techniques. We are still in the earliest days of these 77 technologies, and no doubt, they're scary to many people. But they have so much promise for the 3 eradication of disease and the enhancement of human health t 78 hat they will undoubtedly be the 79 biggest story 100 years from now. 80 [00:07:28.37] Then in 2003, the completion of 97% of the human genome sequence finally gave 81 us a picture of what it takes to make a human. It's been over 10 years since then, and we have 82 miles to go before we achieve that level of understanding. But I think it's probably not too long 83 until you have your genome sequenced. And then, it'll be a little longer, and we'll be able to 84 interpret what that means. 85 [00:07:56.05] But with the greatest hope of perhaps anticipating disease or treating diseases that 86 one might develop or changing lifestyles to prevent certain diseases from ever occurring. Now in 87 class, I would like you to come prepared to class having thought about some of these and 88 develop what you think the top three most important developments are. 89 [00:08:21.04] Biomedical engineering itself is undergoing a tremendous change in terms of how 90 the field is defined. It's probably safe to say that 10 or 15 years ago, the only approach to fixing a 91 failing heart that a biomedical engineer would consider is the implantation of some sort of device 92 or instrument to help assist the heart, like a ventricular assist device, a pump, or a pacemaker. 93 [00:08:57.72] Nowadays, it's equally appropriate to think about using stem cells to repair a heart, 94 to regrow healthy heart tissue, to do genetic engineering, to change the behavior of certain cells 95 in order to have improved performance. It is extremely important for you to not look at these two 96 approaches as opposed to each other. As an engineer, your goal should be to fix a broken tissue. 97 It doesn't matter what methods you use. It matters how well you fix it. 98 [00:09:32.48] If you take a narrow viewpoint and insist that only devices or instruments is truly 99 biomedical engineering, you risk defining yourself into obsolescence. The best methods will 100 prevail, and you might as well cast a wide net. I'd say the same for the delivery of a drug 101 compound from a pharmaceutical company. Don't think of that as the realm of biology, of a 102 person taking a drug. You can think of it just as well as that you're an engineer who is giving a 103 inducer molecule to perturb a system from an unhealthy state to a new, healthier state. You're 104 changing engineering and fixing a system by the delivery of a small molecule. That is biomedical 105 engineering. 106 [00:10:27.26] Now, this is sort of the bummer
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