I was asked earlier whether the goal is to dissect what Schrödinger had spoken and written, or to present the new summary, and I always like to be forward-looking, so I won't give you a history lesson except for very briefly. I will present our findings on first on reading the genetic code, and then learning to synthesize and write the genetic code, and as many of you know, we synthesized an entire genome, booted it up to create an entirely new synthetic cell where every protein in the cell was based on the synthetic DNA code.
As you all know, Schrödinger's book was published in 1944 and it was based on a series of three lectures here, starting in February of 1943. And he had to repeat the lectures, I read, on the following Monday because the room on the other side of campus was too small, and I understand people were turned away tonight, but we're grateful for Internet streaming, so I don't have to do this twice.
Also, due clearly to his historical role, and it's interesting to be sharing this event with Jim Watson, who I've known and had multiple interactions with over the last 25 years, including most recently sharing the Double Helix Prize for Human Genome Sequencing with him from Cold Spring Harbor Laboratory a few years ago.
Schrödinger started his lecture with a key question and an interesting insight on it. The question was "How can the events in space and time, which take place within the boundaries of a living organism be accounted for by physics and chemistry?" It's a pretty straightforward, simple question. Then he answered what he could at the time, "The obvious inability of present-day physics and chemistry to account for such events is no reason at all for doubting that they will be accounted for by those sciences." While I only have around 40 minutes, not three lectures, I hope to convince you that there has been substantial progress in the last nearly 70 years since Schrödinger initially asked that question, to the point where the answer is at least nearly at hand, if not in hand.
I view that we're now in what I'm calling "The Digital Age of Biology". My teams work on synthesizing genomes based on digital code in the computer, and four bottles of chemicals illustrates the ultimate link between the computer code and the digital code.
Life is code, as you heard in the introduction, was very clearly articulated by Schrodinger as code script. Perhaps even more importantly, and something I missed on the first few readings of his book earlier in my career, was as far as I could tell, it's the first mention that this code could be as simple as a binary code. And he used the example of how the Morse code with just dots and dashes, could be sufficient to give 34 different specifications. I've searched and I have not found any earlier references to the Morse code, although an historian that I know wrote Crick a letter asking about that, and Crick's response was, "It was a metaphor that was obvious to everybody." I don't know if it was obvious to everybody after Schrodinger's book, or some time before.
One of the things, though, Schrodinger was right about a lot of things, which is why, in fact, we celebrate what he talked about and what he wrote about, but some things he was clearly wrong about, like most scientists in his time, he relied on the biologist of the day. They thought that protein, not DNA was the genetic information. It's really quite extraordinary because just in 1944 in the same year that he published his book is when the famous experiment by Oswald Avery, who was 65 and about ready to retire, along with this colleagues, Colin MacLeod and Maclyn McCarty, published their key paper demonstrating that DNA was the substance that causes bacterial transformation, and therefore was the genetic material.
This experiment was remarkably simple, and I wonder why it wasn't done 50 years earlier with all the wonderful genetics work going on with drosophila, and chromosomes. Avery simply used proteolytic enzymes to destroy all the proteins associated with the DNA, and showed that the DNA, the naked DNA was, in fact, a transforming factor. The impact of this paper was far from instantaneous, as has happened in this field, in part because there was so much bias against DNA and for its proteins that it took a long time for them to sink in.
Continue reading (Long Read) - What Is Life? A 21st Century Perspective
The Biological-Digital Converter —Or— Biology At The Speed Of Light
These are exciting and challenging times for science and society. If you look at the practical side of things, in the next 11 years we're going to add a billion people to the planet, so basically the equivalent of China being added in 11 years, and 12 years after that we're going to add another billion people. Last October we just passed the 7 billion mark, and that took 12 years to happen from 6 billion. In the 1800s it took well over 100 years to go from 1 to 2 billion people. We're in a unique time in history where there are more people alive than have ever existed in human history, and we keep expanding tremendously, and exhausting the resources of the planet.
There are a number of things that come into play here. We've been doing everything from trying to understand the human genome, and human genetic inheritance, and we have teams that are doing some of the first genomes of early populations in Africa and have traced down actually the oldest populations in Southern Africa that we all have evolved from, from groups that migrated out of Africa. It turns out I have a Northern European ancestry primarily, and so we probably all share this. My ancestors, and probably most of yours found Neanderthals attractive and mated with them. And so what was thought to not be any coexistence, we now ... 3 to 4 percent of my genome is Neanderthal-derived. My friend, Bill Clinton, when we shared an honor a couple of years ago, told me he learned that he was 3 percent Neanderthal, and that explained all his problems while in office.
We're learning about our own history, our own migrations, but we have to do something different for the future. A major producer once argued that we have two hopes for humanity, one is to be able to populate distant planets, and the other is to alter our genetic code so we can survive in a very deteriorated environment here on the planet.
We're working on both, and there are some exciting changes. Science is changing things very quickly. Think about how the Internet has changed all of our lives in the last decade or so. I assume most people here have an iPad, and that's three years old, barely? And it's hard to imagine life without an iPad in our culture. But very soon we're going to be able to send something else across the Internet. We can now send biology at the speed of light, and this is one of the implications of our work, which we recorded two years ago making the first synthetic life form. We completely synthesized the genetic code of a cell starting with a digital code in the computer—it's the ultimate interface between computers and biology. The digital code and the genetic code have a lot in common; something Schrodinger pointed out in 1943, saying it could be something as simple as the Morse code.
Digital code, as you know, is a binary code, and ones and zeroes, and your genetic code is literally four-base code with ACGs and Ts. We can now readily convert in between the two, and we can define life at its most basic level. Things that were a mystery fifty, sixty, seventy years ago, we now understand completely.
We know what a cell is, know that all the components, all the proteins in the cell are miniature robots. They don't have a brain, they don't have a soul, they have a structure that defines their function, and their structure is determined by the genetic code, which defines the linear code of the protein, which determines how it folds, how it functions, and how stable it is. You don't feel it sitting there, but every one of your 100 trillion cells is rapidly metabolizing proteins. Your proteins have a half-life between a few seconds and ten or twenty hours. You don't know that you're sloughing 500 billion skin cells a day. All that dust you find around your houses, in your apartments? That's you, little bits of you. You turn over your entire skin every two to three weeks. Biology is a constant state of renewal, and it's a software-driven state of renewal. Take the DNA out of the cell, and the cell dies. In fact, that's why radiation kills people. It disrupts the genetic code, breaks it up, and people die because all the proteins degrade very quickly.
But imagine if you could e-mail yourself to Mars or some distant planet. We can actually do that now, because with our synthetic cell, we start with the digital code in the computer, and there's no difference between digital code and genetic code. Because digital code can move as an electromagnetic wave, basically close to the speed of light, we can now move biology at the speed of light. This has some practical applications.
The recent movie Contagion portrayed how everybody died from flu pandemic, while awaiting the vaccine. Real life is much better than science fiction. We can now make a new flu vaccine in less than twelve hours using synthetic DNA. Instead of having to deal with a major pandemic where you can't travel out of your home or your city, imagine that you had a little box next to your computer, and you got an e-mail, and that gave you a chance to actually make a vaccine instantly, sort of like 3D printers. What we do with information now, we will be doing with information and biology together.
Obviously the downside is you could instead of giving your partner a genetic disease or an infection, you can e-mail it. So people could use this to do harm, as we see with computer viruses all the time. You would, of course, want good computer and biological virus protection on your DNA decoder.
Continue reading (Long Read) - The Biological-Digital Converter —Or— Biology At The Speed Of Light
'What is Life? A 21st Century Perspective' by Dr Craig Venter
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