Alex has to say something first. Someone had too much fun. It feels like it has a computer in it. Anyone knows who this is? I was going to give you a nice introducing. Dylan is finishing his PhD in computational biology. He is highly regarded in the comp-bio community in caltech, which is the basis for the television show "the big bang".
I have a movie running in the background. This is the state of DNA inside the cell. What you were watching were some double stranded DNA being compacted and folded so that it can fit into a cell. The width diameter is 6 orders of magnitude smaller than the contour length of the DNA that it contains. Biology is really organized, complicated, and we're talking about the future of augmenting ourselves with biology. Since I don't know the background of everyone at the conference and watching on the web, I thought it would be a good idea to do a few slides introducing you to biology. These visualizations really do present biological knowledge to people. A double helical looking strand of DNA, cycling through some awesome machinery, being split and being made into two different mechanisms. DNA has an orientation. This is complicated, it self-assembles, it's not magic. We can explain how it works. So, I'm not going to watch this entire movie, it's about 5 minutes long. It's on the web. It was made by Drew Berry on the 50th anniversery of the discovery of DNA, and he has a bunch of other movies. There's a movie called molecularmovies.com, where you can look at all sorts of awesome.
This is just a gallery or atlas of 3D structures of molecules that we know. The first structure that was solved was myoglobin in 1958, and since then there's been an explosion. You can download coordinates, load them into your favorite animating software. BikerDB. That's hosted by scripps. It has 3D structures of viruses. Download these. Go talk with the techshop people. Wear your virus on your ear, or something. Bacteria are a little more tricky. They are not homogeneous. They work against entropy to organize themselves with complicated machinery like a flagellar motor. They have a lipid bilayer of protection. They have a peptido-glycan sack. The concentrations of macromolecules within the cell is such that without some way of withstanding the pressure, the cell would just explode. Thinking about the minimal conditions for life, that might be nice. When we do quantum mechanisms, we don't solve the shrodinger equation for uranium. The bacterial cell is the hydrogen of biology.
These are the Gensen Lab at Caltech under the heading "Cool Movies". Transmission electron microscope images were taken at 1 degree increments along a few axises. A backpropagation algorithm is used to make a 3D reconstruction. You're looking at individual ribosomes. There are also features inside these bacterial cells. For the first 150 years of microbiology, people thought that bacteria were homogenous bags of enzyme. You could think about .. cells are organized; even the simplest cells are highly organized spatially. Eukaryotic cells are way more complicated. There are all these terms. I have another movie.
Movies help communicate information. Think about the budget of one of the hollywood blockbuster. Maybe the one on Mayan mythology to convince us to fear the future. It had a budget greater than the 10 most well funded research labs. I have about 10 times more slides than I have time for. If people are interested in more details on basic biology, I'm happy to hang out at lunch. That's Louis Pasteur. He helped prove that all life comes from life. Spontaneous generation doesn't happen. The cell is the fundamental unit of biology. That's a bacterial cell. They are not like a solution, it's more like a gel. Biology is hard.
We do have some concept of the components. We've begun to make a precise part list for the simplest cells. There's only a handful of precursors, and they're the same in every cell in all living organisms. These form the basic molecular currency of all living things. You can think about that as a pointer to a possible common origin. Is it just a coincidence that all of these living organisms have figured out how to be alive by choosing those peculiar molecules? Maybe every cell came from an origin cell?
Amphapilic property where their head property is hydrophilic. It likes water. The tails don't. When you put these in 3D space, all of the tails come together and go away from the water. In 3D, these form vesicles. The ideas of origins of life put these vesicles at the origin of life. We have molecular dynamics simulations that can make this behavior happen. We can barely predict the structure of proteins, and these lipid vesicles are not covalently linked and yet show a higher order of organization. Janet made a site called "Exploring Life's Origins". It's free.
Second great idea in biology. First idea was "all life from life". The second one was that the gene is the unit of heridtary. He published in an obscure journal. That's a problem with publications, that's true today. Firewall journals keep the rest of humanity that can't afford the crazy subscription fees, a plug for open access biology. All domestic dogs come from the wolf. We can look at this. Selective breeding leads to really crazy stuff. That's true with the flies from yesterday, the longevity flies. It will happen with us when we get more long-term about our future.
A couple more snapshots. Francis Crick and Watson. Matt Puruts. He solved the first structure (hemoglobin and myoglobin) of a protein. He probably would roll over in his grave he knew we were using giant synchtorons to solve protein structures. It took him 7 or 8 years, working full time in a lab with lots of people. You're all familiar with the general notion, the "central dogma of molecular biology". When someone says this is a dogma, please step back. There's all kinds of feedback, and complicated interactions at various levels. There's a really exciting new result out of MIT this fall, where they used DNA sequencing to figure out the 3D organization of human chromosomes inside cells. It's not randomly organized polymers. The differently colored domains are colored by the distance on the linear polymer. The structure of the chromosome is a fractal globule in the sense that the individual components form clusters, so it's self-similar. That has ramifications in understanding which genes are expressed. There's hetero-chromatin, u-chromatin. The spatial location of genes in the chromosome indicate how you can express them. Lots of variables, lots of scales, it operates at least in 9 orders of magnitude. From the nanometer scale to the human meter scale, and how you can abstract the laws of physics that work on atoms and molecules, to the laws of mechanics. I'm trying to get you excited that biology has a lot of potential and there's a lot to do.
The genome, that's all the DNA. All the RNA. All the proteins. We have machines that can tell us all of it. So in the past biology was really an observational science. And now it's a data-rich science. The data comes to you, and it demands that you analyze it. We need computer scientists come into biology and make sense of this huge influx of information. That's interesting to look at. That's all the ways that life makes a living on earth. Inorganic processes, along the top is a scale of the redox potential of different reactions. You can take any single piece of this and look at it globally. How are these pieces recycled in the biosphere? We can show the flux of matter and energy through living organisms. You can do that for the whole planet, a single cell. That's a mess. Biology needs software. We need some user accessibility analysis on this, and figure out if you can make sense on it. You need a lot of metabolic reactions to make a living. In that diversity is unity, because all living things share the same basic metabolism. Exciting evidence for a common origin. Despite the common origin, all of them use a common biochemistry. Among the organisms is my favorite, Stella. She is a bacterium that forms a star-shape. Why? How does it form a star-shape? Alright. So, it's a picture, it forms a 6-pointed star. It was found in the dead sea.
The fact that life comes in different forms was apparent people to even before Darwin. Darwin's grandfather. Organic life beneath the shoreless waves was nursed in ocean's pearly caves, first moves minute unseen by spirit glass, move on the mud or pierce the watery mass. This, in successive generations, new powers acquire and larger limbs assume, whence countless groups of vegetation assume, and blah and blah and blah and wings. So if you're wondering who was sitting on his knee when he was reading that, you can guess it was Charles. That book is not on the Origins of Species. He didn't write "on origins" first. He sat on his results for a very long time. Why? Because his results scared him. It's like confessing to a murder, to explain a common origin for all living things in 1859. That's the only figure in the origin of species, where he's trying to figure out extinction. He denotes an entire chapter to what's wrong with his own theory. If you're not confronting the probelms in your theory, you're probably not being a good distinction. Thermal vents in the sea. Avoiding the sun when there was no sun to have. We can thank them for all kinds of stuff. Plants and fungi and people all fit in that box. You've seen slide like that. Sequences are coming, and they are coming faster. We can't do a talk at hplus without showing something that looks exponential. As those sequences come, we, computer science and quantitative bents, we have to parse them. I can talk at lunch. There's variation in the human genome, you hear about mutations. A bunch of different kinds. There are SNPs. The rest are more complicated and harder to find. As of June, there are 439 published genome-wide association studies that have identified one of those SNPs associated with a disease. At a p-value, that's pretty good. They're probably involved. They're involvement isn't so full that we actually understand the cause of the disease. They only explain a very small percentage of the disease, and as we do whole genome sequencing, we're going to do a lot more. Human genome sequencing is going to happen and it is happening now. Different diseases. Same gene. All kinds of promiscuity in biology.
People are diverse, it's true. They die from diverse reasons. This is a great figure. Different ethnicities, different age groups, top 3 causes of death. Up in youth, there's only one group that seems to not take their own lives, and no idea why, but it's pretty fascinating. Then there's some sad stats about the state of evolution in America. We're down here with Turkey with disbelief. Iceland is up at the top, but that's because Geneco decided to sequence everyone. America, we have problems. And, uh, you know, it's odd but true. Right. Anyway. I'm going to end here with a quote from Erasmus' grandson, Charles Darwin.
"There is grandeur in this view of life, with its several powers, having been originally breathed into a few forms or into one. And whilst this planet has been cycling on according to the fixed law of gravity, from so simple of a beginning, beautiful forms most simple and most wonderful have been and are being evolved."