Thursday, March 7, 2013

The New Science & FuturICT


The New Science & FuturICT

The new comprehensive research on LiFE,

for the Human Condition,

recently launched by  

FuturICT at Zürich,

which looks promising like the "LHC" at CERN;

may help us to come closer to "Our Truth".

Notes on the new movement of science

"... Science is getting very advanced with regard our understanding life. We know what it is, and we now know how to reproduce it. We produce life by writing new software.



"Many of us know the space, electric car, and solar energy inventor and entrepreneur Elon Musk, whose rockets are doing extremely well. Based on this success, within a decade we're likely going to see attempts to colonize the moon. Elon wants to colonize Mars. Depending on how close moon and Mars are to each other, it takes between four minutes and twenty-one minutes for an electromagnetic wave, for light, to go from Earth to Mars.  


But imagine you're on a colony on Mars, and you want a new cell that produces food, or fuel, or some medicine, or a vaccine, you can just e-mail that and convert it back into biology.

The idea that you're basically a DNA-driven software device is not the view that people necessarily have of themselves. But every cell on this planet works that way in a biological-to-mechanical kind of fashion. No brain controlling what happens with DNA reading and protein synthesis in your cells. The combination of one hundred trillion cells gives different people different abilities to make wonderful music, to make science advances, to think, but every one of those cells operates in the same fashion.


And that means we will be able to decode how the brain functions by understanding these same mechanisms. There's no need to evoke mysticism or a higher being.


That's what Schrodinger did seventy years ago. He couldn't explain things, so he did what people do when they can't explain something. He evokes mysticism. But science is getting very advanced with regard our understanding life. We know what it is, and we now know how to reproduce it. We produce life by writing new software.

Our announcement made eighteen months ago, was one of the few science announcements that received an immediate response from the President and the Pope. The President asked his Bioethics Commission to start looking at this development as their number one issue, and the Vatican released a statement that all we did was change one of the engines of life. They said it could lead to some important advances, but it wasn't creating life itself.

But DNA is not the engine of life, it's the software of life; the proteins are the engines, they're driven directly by that code in a very understandable, predictable fashion now. This has implications in many different areas." (my emphasis)


My perception and synthesis: 


In sociology we are well beyond the legacy perception.... The "magic" conception is understanding the working parameters of  complexity and emergence through billion aspects of social and natural interactions.

The Logo: A H-uge -  H decoded as (S-C & M-C)
H ( I <--> I)consists of two'I' s combined with hyphen '-' in the middle...The first I has on the top S for the Social, and on the bottom C for the Cultural. The second I has on top M for the Material, and on the bottom S for Spiritual. The Hyphen in the middle combining the two I s is vectored by the moments of Intelligence on the left side and Energy on the right side exactly similar to the Left and right hemisphere of the humans mind.

And H means in its totality not more or not less than Harmony or Human as Harmony carrier of the omega and alpha of creativity (not alpha and omega, it is the reverse process); transforming itself into an energy charged body. Now or today we are just on the way and we are still matter or mass charged and just biological! This Idea - The Idea of the transformation of the prevailing  matter/mass charged nature ( E = M* c*c (c squared; c the speed of Light) into an Energy/light charged nature ( E= m*c*c) or m = E/c*c occurred to me eight years ago,  during moments and stances of deep meditation with special "Dasein" experiences, which prompted me to come up with the harmony Model as the bridge towards that Energy charged nature, (which I believe is the nature of that BEYOND our reach at the moment but that which we, once in a while through special experience, could touch and what perhaps in the far-fetched future may be a day-to-day experience under the status-quo of the  dual modus of life and nature; the biological and non-biological-life, approximating that of that Beyond, which we don't know yet except in some sense of intuition and special experiences).

 "H"- with the intrinsic  meaning  of Harmony 

H <==> I= h*q*q  ^ E=m*c*c  

( q, quality of music or aesthetics;" ^ " meaning AND combined and related)

I feel the following research and the above is indicating in this direction. The 22nd century will indeed be an exciting phase of  A HUMAN Development! 




Those properties as social capital, like trust, they result from social network interactions. We've seen that one of the biggest problems of the financial crisis was this evaporation of trust. It has burned tens of thousands of billion dollars. If we would learn how to stabilize trust, or build trust, that would be worth a lot of money, really. Today, however, we're not considering the value of social capital.


FuturICT logo

FuturICT for Economics


The FuturICT at Zürich

Is that going to be the social wing of The LHC at Cern?


A Conversation with Nicholas A. Christakis [8.21.12]


This new frontier in the social sciences is being abetted and even accelerated by three things that are happening. The first is that a biological hurricane is approaching the social sciences. Discoveries in biology are calling into question all kinds of ideas, historically important ideas, in the social sciences—everything from the origin of free will, to collective expression and collective behavior, to the deep origins of basic human behaviors. All of these things are being challenged and elevated by discoveries in biology.

The second thing that is going to change, or challenge the social sciences, is the era of computational social science, or "big data." If you had asked social scientists even 20 years ago what powers they dreamed of having, they would have said, "It would be unbelievable if we could have this little tiny Black Hawk helicopter that could be microscopic, fly on top of you, and monitor where you are and who you're talking to, what you're buying, what you're thinking, and if it could do this in real time, all the time, for millions of people, all at the same time. If we could collect all these data, that would be amazing."

Of course, that's exactly what we have now. We have, in everyone's pocket, a little device that functionally does all of the foregoing. We can pool these data, and we can understand human behavior. For me, one of the most interesting aspects of human behavior is collective expression. Not just individual-level behavior, but how do humans aggregate to form collective entities, whether they are thought of as a super-organism, or thought of as communities or groups or networks or nation-states? How do human beings find a collective expression? And we can use all these data to begin to understand human behavior and collective human behavior in a completely new way.

The third thing that's happening that is going to radically reshape the social sciences—and it intersects with the foregoing two ideas, the biological hurricane and big data, or computational social science—is a newfound appreciation for experimentation in the social sciences. There was always a tradition of doing bona fide experiments in the social sciences, going back well over 100 years, where people would be randomly assigned to different treatments. Psychologists have always been doing this, of course, but other branches of the social sciences are increasingly rediscovering, and more broadly applying, experiments in all kinds of settings: workplaces, schools, hospitals, the developing world, online. People are doing experiments all the time right now, and these experiments offer a robustness of causal inference that is phenomenal.

These three things: the biological hurricane, computational social science, and the rediscovery of experimentation, are going to change the social sciences in the 21st century. With that change will come, in my judgment, a variety of discoveries and opportunities that offer tremendous prospect for improving the human condition.


When you do science, you need data, you need analytic ability, you need ideas. All of these things are required. I don't think it's appropriate to somehow say that data is just a commodity and it should just be given away. Part of the intellectual contribution and the step forward is figuring out how to get the data. So long as you describe what you did, and you describe how you got the data and what kind of data you have, in principle, other scientists could do the same thing.

In my particular lab, generally speaking, we widely share data. For instance, our Framingham Heart Study social network dataset was posted online; it's subject to certain restrictions that NIH imposed, but people can get that data. We've made publicly available many, many data sets, and we've also benefited from the kindness of others. We've gotten access to data from commercial firms, from other labs. There's a kind of widespread—actually cooperative, collaborative—system in place. At least in my judgment, so far, it's working.

In the series of the new science, worth reading!


BOOKS & IDEAS: Connected



The Edge Bookstore

Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives
By Nicholas A. Christakis, James H. Fowler

Product Description

Your colleague's husband's sister can make you fat, even if you don't know her. A happy neighbor has more impact on your happiness than a happy spouse. These startling revelations of how much we truly influence one another are revealed in the studies of Drs. Christakis and Fowler, which have repeatedly made front-page news nationwide.

In CONNECTED, the authors explain why emotions are contagious, how health behaviors spread, why the rich get richer, even how we find and choose our partners. Intriguing and entertaining, CONNECTED overturns the notion of the individual and provides a revolutionary paradigm-that social networks influence our ideas, emotions, health, relationships, behavior, politics, and much more. It will change the way we think about every aspect of our lives.



James Watson congratulates Craig Venter at conclusion of the lecture


J. CRAIG VENTER: 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.


In 1949, was the first sequencing of a protein by Fred Sanger, and the protein was insulin. This work showed, in fact, that proteins consisted of linear amino acid codes. Sanger won the Nobel Prize in 1958 for his achievement. The sequence of insulin was very key in terms of leading to understanding the link between DNA and proteins. But as you heard in the introduction, obviously the discovery that changed the whole field and started us down the DNA route was the 1953 work by Watson and Crick with help from Maurice Wilkins and Rosalind Franklin showing that DNA was, in fact, a double helix which provided a clear explanation of how DNA could be self-replicated. Again, this was not, as I understand, instantly perceived as a breakthrough because of the bias of biochemists who were still hanging on to proteins as the genetic material. But soon with a few more experiments from others, the world began to change pretty dramatically.

The next big thing came from the work of Gobind Khorana and Marshall Nirenberg in 1961 where they worked out the triplet genetic code. It's three letters of genetic code, coding for each amino acid. With this breakthrough it became clear how the linear DNA code had coded for the linear protein code. This was followed a few years later by Robert Holley's discovery of the structure of tRNA, and tRNA is the key link between the messenger RNA and bringing in the amino acids in for  protein synthesis. Holley, Nirenberg and Khorana shared the Nobel Prize in 1968 for their work.


[Enlarge] [Englarge]

The next decade brought us restriction enzymes from my friend and colleague, Ham Smith, who is at the Venter Institute now; in 1970 discovered the first restriction enzymes. These are the molecular scissors that cut DNA very precisely, and enabled the entire field of molecular engineering and molecular biology. Ham Smith, and Warner Arber, and Dan Nathans shared the Nobel prize in 1978 for their work. The '70s brought not only some interesting dress codes and characters, (Laughter) but the beginning of the molecular splicing revolution, using restriction enzymes, Cohen and Boyer, and Paul Berg all published the first papers on recombinant DNA, and Cohen and Boyer at Stanford filed a patent on their work, and this was used by Genentech and Eli Lilly to produce a human insulin as the first recombinant drug.

DNA sequencing and reading the genetic code progressed much more slowly. In 1973 Maxam and Gilbert published a paper on only 24 base pairs, 24 letters of genetic code. RNA sequencing progressed a little bit faster, so the first actual genome, a viral genome, an RNA viral genome was sequenced in 1976 by Walter Fiers from Belgium. This was followed by Fred Sanger's sequencing the first DNA virus, Phi X 174. This became the first viral DNA genome, and it was also accompanied by a new DNA sequencing technique of dideoxy DNA sequencing, now referred to as "Sanger sequencing" that Sanger introduced.

This is a picture of Sanger's team that sequenced Phi X 174. The second guy from the left on the bottom is Clyde Hutchison, who is also a member of the Venter Institute, and joined us after retiring from the University of North Carolina, and played a key role in some of the synthetic genome work.

In 1975 I was just getting my PhD as the first genes were being sequenced. Twenty years later I led the team to sequence the first genome of living species, and Ham Smith was part of that team. This was Haemophilus influenzae. Instead of 5,000 letters of genetic code, this was 1.8 million letters of genetic code. Or about 300 times the size of the Phi X genome. Five years later, we upped the ante another 1,600 times with the first draft of the human genome using our whole genome shotgun technique.

I view DNA as an analogue coding molecule, and when we sequence the DNA, we are converting that analogue code into digital code; the 1s and 0s in the computer are very similar to the dots and dashes of Schrodinger's metaphor. I call this process "digitizing biology".

The human genome is about a half a million times larger the Phi X genome, so it shows how fast things were developing. Reading genomes has now progressed extremely rapidly from requiring years or decades, it now takes about two hours to sequence a human genome. Instead of genomes per day or genomes per hour, or hours per genome, we can now and have recently done a demonstration sequencing 2,000 complete microbial genomes in one machine run. The pace is changing quite substantially.

I view DNA as an analogue coding molecule, and when we sequence the DNA, we are converting that analogue code into digital code; the 1s and 0s in the computer are very similar to the dots and dashes of Schrodinger's metaphor. I call this process "digitizing biology".


Numerous scientists have drawn the analogy between computers and biology. I take these even further. I describe DNA as the software of life and when we activate a synthetic genome in a recipient cell I describe it as booting up a genome, the same way we talk about booting up a software in a computer.

June 23rd of this year would have been Alan Turing's 100th birthday. Turing described what has become to be known as Turing Machines. The machine described a set of instructions written on a tape. He also described the Universal Turing Machine, which was a machine that could take that set of instructions and rewrite them, and this was the original version of the digital computer. His ideas were carried further in the 1940s by John von Neumann, and as many people know he conceived of the self-replicating machine. Von Neumann's machine consisted of a series of cells that uncovered a sequence of actions to be performed by the machine, and using the writing head, the machine can print out a new pattern of cells, allowing it to make a complete copy of itself on the tape. Many scientists have made the obvious analogy between Turing machines and biology. The latest was most recently in nature by Sydney Brenner who played a role in almost all the early stages of molecular biology. Brenner wrote an article about Turing and biology, and in this he argued that the best examples of Turing and von Neumann machines are from biology with the self-replicating code, the internal description of itself, and how this is the key kernel of biological theory.

While software was pouring out of sequencing machines around the world, substantial progress was going on describing the hardware of life, or proteins. In biochemistry the first two decades of the 20th century was dominated by what was called "The colloid theory". Life itself was explained in terms of the aggregate properties of all the colloidal substances in an organism. We now know that the substances are a collection of three-dimensional protein machines. Each evolved to carry out a very specific task.

Now, these proteins have been described as nature's robots. If you think about it for every single task in the cell, every imaginable task as described by Tanford and Reynolds, "there is a unique protein to carry out that task. It's programmed when to go on, when to go off. It does this based on its structure. It doesn't have consciousness; it doesn't have a control from the mind or higher center. Everything a protein does is built into its linear code, derived from the DNA code".


There are multiple protein types, everything you know about your own life, and most of it is protein-derived. About a quarter of your body is collagen, it's a matrix protein just built up of multiple layers. We have rubber-like proteins that form blood vessels as well as the lung tissue, and we have transporters that move things in and out of cells, and enzymes that copy DNA, metabolize sugars, et cetera.


The most important breakthroughs, outside of the genetic code, was in determining the process of protein synthesis.  To show you how recent all of this is, this is the three-dimensional structure of the bacterial ribosome determined in 2005, and the three-angstrom structure of the eukaryotic chromosome, which was just determined and published in December of last year. These ribosomes are extraordinary molecules. They are the most complex machinery we have in the cell, as you can see there are numerous components to it. I try to think of this as maybe the Ferrari engine of the cell. If the engine can't convert the messenger RNA tape into proteins, there is no life. If you interfere with that process, you kill life. It's the major antibiotics that we all know about, the amino glycosides, tetracycline, chloramphenicol, erythromycin, et cetera, all kill bacterial cells by interfering with the function of the ribosome.

The ribosome is clearly the most unique and special structure in the cell. It has seven major RNA chains, including three tRNA chains and one messenger RNA. It has 47 different proteins going into the structure and one newly synthesized protein chain, and a size of several million Daltons. This is the heart of all biology. We would not have cells, we would not have life without this machine that converts the linear DNA code into proteins working.

The process of converting the DNA code into protein starts with the synthesis of mRNA from DNA, called "transcription", and protein synthesis from the mRNA is called "translation". If these processes were highly reliable, life would be very different, and perhaps we would not need the same kind of information-driven system. If you were building a factory to build automobiles that worked the way the ribosome did, you would be out of business very quickly. A significant fraction of all the proteins synthesized, are degraded shortly after synthesis, because they formed the wrong confirmations and they aggregate in the cell, or cause some other problem.

Transfer RNA brings in the final amino acid to a growing peptide chain coming out of the ribosome. The next step is truly one of the most remarkable in nature, and that's the self-folding of the proteins. The number of potential protein confirmations is enormous: if you have 100 amino acids in a protein then there are on the order of 2 to the 100th power different conformations, and it would take about ten to the tenth years to try each conformation. But built into the linear protein code with each amino acid are the folding instructions in turn determined by the linear genetic code. As a result these processes happen very quickly.


Here's a movie that spreads out 6 microseconds of protein folding over several seconds, to show you folding of a small protein. This is the end folded structure that starts with a linear protein, and over 6 microseconds it goes through all the different confirmations to try and get to the final fold.

Somehow the linear amino acid code limits the number of possible folds it can take, but each protein tries a large number of different ones, and if it gets them wrong in the end, the protein has to be degraded very quickly or it will cause problems. Imagine all the evolutionary selection that went into these processes, because the protein structure determines its rate of folding, as well as the final structure and hence its function. In fact, the end terminal amino acid determines how fast a protein is degraded. This is now called "The "N" rule pathway for protein degradation". For example, if you had the amino acid, lysine, or arginine or tryptophan as the N terminal on a protein beta-galactosidase, it results in a protein with a half-life of 120 seconds in E. coli, or 180 seconds in a eukaryotic cell, yeast. Whereas you have three different amino acids, serine, valine or methionine, you get a half-life of over ten hours of in bacteria, over 30 hours in yeast.

Because of the instability, aggregation and turnover of proteins in a cell one of the most important pathways in any cell is the proteolytic pathway.  Degradation of proteins and protein fragments is of vital importance as they can be highly toxic to the cell by forming intracellular aggregates.

A bacterial cell in an hour or less will have to remake of all its proteins. Our cells make proteins at a similar rate, but because of protein instability and the random folding and misfolding of proteins, protein aggregation is a key problem. We have to constantly synthesize new proteins, and if they fold wrong, you have to get rid of them or they clog up the cell, the same way as if you stop taking out the trash in a city everything comes to a halt. Cells work the same way. You have to degrade the proteins; you have to pump the trash out of the cell. Miss folded proteins can become toxic very quickly. There are a number of diseases known to most of you that are due to misfolding or aggregation, Alzheimer's and mad cow disease are examples of diseases caused by the accumulation of toxic protein aggregates.

Life is a process of dynamic renewal. We're all shedding about 500 million skin cells every day. That is the dust that accumulates in your home; that's you.  You shed your entire outer layer of skin every two to four weeks. You have five times ten to the 11th blood cells that die every day. If you're not constantly synthesizing new cells, you die.

Several human diseases arise from protein misfolding leaving too little of the normal protein to do its job properly. The most common hereditary disease of this type is cystic fibrosis. Recent research has clearly shown that the many, previously mysterious symptoms of this disorder all derive from lack of a protein that regulates the transport of the chloride ion across the cell membrane. More recently scientists have shown that by far the most common mutation underlying cystic fibrosis hinders the dissociation of the transport regulator protein from one of its chaperones. Thus, the final steps in normal folding cannot occur, and normal amounts of active protein are not produced.

I'm trying to leave you with a notion that life is a process of dynamic renewal. We're all shedding about 500 million skin cells every day. That is the dust that accumulates in your home; that's you.  You shed your entire outer layer of skin every two to four weeks. You have five times ten to the 11th blood cells that die every day. If you're not constantly synthesizing new cells, you die.  During normal organ development about half of all of our cells die. Everything in life is constantly turning over and being renewed by rereading the DNA software and making new proteins.

Life is a process of dynamic renewal. Without our DNA, without the software of life cells die very rapidly.  Rapid protein turnover is not just an issue for bacterial cells; our 100 trillion human cells are constantly reading the genetic code and producing proteins.  A recent study assaying 100 proteins in living human cancer cells showed half-lives that ranged between 45 minutes and 22.5 hours.


Now, as you know, all life is cellular, and the cellular theory of life is that you can only get life from preexisting cells, and all kinds of special vitalistic parameters have been attributed to cells over time. This slide shows what an artist's view of what a cell cytoplasm might look like. It's quite a crowded place, it's relatively viscous, it's not this empty bag with a few proteins floating around in it, and it's a very unique environment. About one quarter of the proteins are in solid phase.

A key tenant of chemistry is the notion of "synthesis as proof". This perhaps dates back to 1828 when Friedrich Wöhler synthesized urea. The Wöhler synthesis is of great historical significance because for the first time an organic compound was produced from inorganic reactants.  Wöhler synthesis of urea was heralded as the end of vitalism because vitalists thought that you could only get organic molecules from living entities. Today there are tens of thousands of scientific papers published that either have "proof by synthesis" as the starting point or as a key part of the title.

We decided to take the approach of proof by synthesis that DNA codes for everything a cell produces and does. Back in 1995 when we sequenced the first genome, we sequenced a second genome that year.  For comparative purposes we were looking for the cell with the smallest genome, and we chose mycoplasma genitalium. It has 482 protein-coding genes, and 43 RNA genes. We asked simple questions, how many of these genes are essential for life?; what's the smallest number of cells needed for a cellular machinery? After extensive experimentation we ultimately decided that the only way to answer these questions would be to design and construct a minimal DNA genome of the cell.  As soon as we started down that route, we had new questions. Would chemistry even allow us to synthesize a bacterial chromosome? And if we could, would we just have a large piece of DNA, or could we  boot it up in the cell like a new chemical piece of software?

We decided to start where DNA history started, with Phi X 174. We chose it as a test synthesis because you can make very few changes in the genetic code of Phi X without destroying viral particles. Clyde Hutchison, who helped sequence Phi X in Sanger's lab, Ham Smith and I developed a new series of techniques to correct the errors that take place when you synthesize DNA. The machines that synthesize DNA are not particularly accurate; the longer the piece of DNA you make, the more spelling errors. We had to find ways to correct errors.


Starting with the digital code we synthesized DNA fragments and assembled the genome. We corrected the errors and in the end had a 5,386-basepair piece of DNA that we inserted into E. coli, and this is the actual photo of what happened. The E. coli recognized the synthetic piece of DNA as normal DNA, and the proteins, being robots, just started reading the synthetic genetic code, because that's what they're programmed to do. They made what the DNA code told them to do, to make the viral proteins. The virus proteins self-assembled and formed a functional virus. The virus showed its gratitude by killing the cells, which is how we effectively get these clear plaques in a lawn of bacterial cells. I call this a situation where the "software is building its own hardware". All we did was put a piece of DNA software in the cell, and we got out a protein virus with a DNA core.

Now, our goal is not to make viruses, we wanted to make something substantially larger. We wanted to make an entire chromosome of a living cell. But we thought if we could make viral-sized chromosomes accurately, maybe we could make 100 or so of those and find a way to put them together.  That's what we did.

The teams starting with synthetic segments the size of Phi-X, we sequentially assembled larger and larger segments.  At each stage we  sequenced  verified them before going on to the next assembly stage. We put four pieces together creating segments that were 24,000 letters long. We would clone the segments in E. coli, sequence them, and assemble three together, to get pieces that were 72,000 base pairs. This was a very laborious process that took about a year and a half to do.

We put two of the 72,000bp segments together to obtain new segments representing one quarter of the genome each at 144,000 letters in length. This was way beyond the largest piece that had ever been synthesized by other of only 30,000 base pairs. E. coli didn't like these large pieces of synthetic DNA in them, so we switched to yeast. I found out last night this is a city that loves beer that is produced from the same brewer's yeast.  Aside from fermentation, this little cell has remarkable properties of assembling DNA.


All we had to do was put the four synthetic quarter molecules into yeast with a small synthetic yeast centromere, and yeast automatically assembled these pieces together. That gave us the first synthetic bacterial chromosome, and this is what we published in 2008. This was the largest chemical of a defined structure ever synthesized.

We continued to work on DNA synthesis, and somebody who started out as a young post-doc, Dan Gibson, came up with a substantial breakthrough. Instead of the hours, to days, to years, he found out that by putting three enzymes together with all the DNA fragments in one tube at 50 degrees centigrade for a little while, they would automatically assemble these pieces. DNA assembly went from days down to an hour. This was a breakthrough for a number of reasons. Most importantly, it allows us now to automate genome synthesis. Having a simple one-step method allows us to go from the digital code in the computer to the analogue code of DNA in a robotic fashion. This means scaleing up substantially. We proved this initially by just one step synthesizing the mouse mitochondrial genome.

I had two teams working, one on the chemistry and one on the biology. It turns out the biology ended up being more difficult than the chemistry. How do you boot up a synthetic chromosome in a cell? This took substantial time to work out, and this paper that we published in 2007 is one of the most important for understanding how cells work and what the future of this field brings.

This paper is where we describe genome transplantation, and how by simply changing the genetic code, the chromosome, in one cell, swapping it out for another, we converted one species into another. Because this is so important to the theme of what we're doing, I'm going to walk you through this a little bit.  And by the way, these are two of the scientists pictured here that led this effort, Carole Lartigue and John Glass, and the team working with them.


[Enlarge] [Enlarge]

We started by isolating the chromosome from a cell called M. mycoides. Chromosomes are enshrouded with proteins, which is why there was confusion for so many years over whether the proteins or the DNA was the genetic material. We simply did what Avery did, we treated the DNA with proteolytic enzymes, removing all the proteins because if we're making a synthetic chromosome, we need to know can naked DNA work on its own, or are there going to be some special proteins needed for transplantation? We added a couple of gene cassettes to the chromosome, one so we could select for it, and another so it turns cells bright blue if it gets activated. After considerable effort we found a way to transplant this genome into a recipient cell, a cell M. capricolum, which is about the same distance apart genetically from M. mycoides as we are from mice. So relatively close, on the order of 10 percent or more different.

Life is based on DNA software. We're a DNA software system, you change the DNA software, and you change the species. It's a remarkably simple concept, remarkably complex in its execution.


Let me show you what happened with this very sophisticated movie. We inserted the M. mycoides chromosome into the recipient cell. Just as with the Phi X, as soon as we put this DNA into this cell, the protein robots started producing mRNA, started producing proteins. Some of the early proteins produced were the restriction enzymes that Ham Smith discovered in 1970, we think that they recognized the initial chromosome in the cell as foreign DNA and chewed it up.  Now we have the body and all the proteins of one species, and the genetic software of another. What happened?


In a very short period of time we have these bright blue cells. When we interrogated the cells, they had only the transplanted genome, but more importantly, when we sequenced the proteins in these cells, there wasn't a single protein or other molecule from the original species. Every protein in the cell came from the new DNA that we inserted into the cell. Life is based on DNA software. We're a DNA software system, you change the DNA software, and you change the species. It's a remarkably simple concept, remarkably complex in its execution.

Now, we had a problem, that some of you may have picked up on or have read about. We were assembling the bacterial chromosome in a eukaryotic cell. If we're going to take the synthetic genome and do the transplantations, we had to find a way to get the genome out of yeast to transplant it back into the bacterial cell. We developed a whole new way to grow bacteria chromosomes in yeast as eukaryotic chromosomes. It was remarkably simple in the end. All we do is add a very small synthetic centromere from  yeast to the bacterial chromosome, and all of a sudden it turns into a stable eukaryotic chromosome.


[Enlarge] [Enlarge]

Now we can stabley grow bacterial chromosomes in yeast. We had the situation where we had the M. mycoides chromosome in the eukaryotic cell, we could try isolating it and doing a transplantation. The trouble is, it didn't work. This little problem took us two and a half years to solve of why it didn't work. It turns out when we initially did the transplantations taking the chromosome out of the M. mycoides cell, that DNA had been methylated, and that's how cells protect their own DNA from interloping species. We proved this by isolating the six methylases, and methylating the DNA when we took it out of yeast. If we methylated the DNA, we could then do the transplantation. We proved this ultimately by in the recipient cell removing the restriction enzyme system, and in that case we can just transplant the naked unmethylated DNA because there's nothing to destroy the DNA in the cell.


We were now at the point where we thought we had solved all the problems. We could create the new bacterial strains from the bacterial genomes cloned in yeast. We had this new cycle, we could work our way around the circle, we could add a centromere to the bacterial chromosome and turn it into a eukaryotic chromosome. The advantages, for those of you who work with bacteria, most bacteria do not have genetic systems, which is why most scientists don't work with them. As soon as you put that bacterial genome in yeast, we have the complete repertoire of genetic tools available in yeast such as homologous recombination. We can make rapid changes in the genome, isolate the chromosome, methylate it if necessary, and do a transplantation to create a highly modified cell.

With all the new techniques and success we decided to synthesize the much larger M. mycoides genome. Dan Gibson led the effort that started with pieces that were 1,000 letters long. We put ten of those together to make these over 10,000 letters long. We put ten of those together to make pieces now that are 100,000 letters long, and we had eleven 100,000 base pair pieces. We put them in yeast, which assembled the genome. We knew how to transplant it out of yeast and we did the transplantation and it didn't work.

Those of you who are software engineers know that software engineers have debugging software to tell them where the problems are in their code. So we had to develop the biological version of debugging software, which was basically substituting natural pieces of DNA for the synthetic ones so we could find out what was wrong. We found out we could have 10 of the 11 synthetic pieces, and the last piece had to be the native genome DNA to get a living cell. We re-sequenced our synthetic segment and found one letter wrong in an essential gene that made the difference between life and no life. The deletion was in the DNAa gene, which is an essential gene for life. We corrected that error, the one error out of 1.1 million, and we got the first actual synthetic cell from the genome transplants.


One of the ways that we knew that what we had was a synthetic cell was by watermarking the DNA so we could always tell our synthetic species from any naturally occurring one.  Now about the watermarks, when we watermarked the first genome we just used the single letter amino acid code to write the authors names in the DNA. We were accused of not having much of an imagination. For this new genome we went a little bit farther by adding three quotations from the literature. But first the team developed a whole new code where by we could write the English language complete with numbers and punctuation in DNA code. It was quite interesting. We sent the paper to Science for a review, and one of the reviewers sent back their review written in DNA code, much to the frustration of the Science editor, who could not decipher it. (Laughter) But the reviewer's DNA code was based on the ASCII code, and with biology that creates a problem because you can get long stretches of new without a stop codon. We developed this new code that puts in very frequent stop codons, because the last thing you want to do is put in a quote from James Joyce and have it turn into a new toxin that kills the cell or kills you. You didn't know poetry could do that, I guess.

We built in the names of the 46 scientists that contributed to the effort, and also there was a message with an URL. So being the first species to have the computer as a parent, we thought it was appropriate it should have its own Web addressed built into the genome. As people solved this code, they would send an e-mail to the Web address written in the genome. Once numerous people solved it, we made this available.

The three quotes are the first one, and the probably most important one to this country is James Joyce, "To live, to err, to fall, to triumph, to recreate life out of life." Somehow that seemed highly appropriate. The second is from Oppenheimer's biography, "American Prometheus". "See things not as they are, but as they might be." In the third, from Richard Feynman, "What I cannot build, I cannot understand."

Everybody thought this was very cool until a few months after this appeared, we got a letter from James Joyce's estate attorney saying, "Did you seek permission to use this quotation?" In the US, at least, there are fair use laws that allow you to quote up to a paragraph without seeking permission. We sort of dismissed that one, and James Joyce was dead, and we didn't know how to ask him anyway.

Then we started getting an e-mail trail from a Caltech scientist saying we misquoted Richard Feynman. But if you look on the Internet, this is the quotation that you find everywhere. We argued back this is what we found, and this is what was in his biography. So to prove his point, he sent a picture of Feynman's blackboard with the original quotation, and it was, "What I cannot create, I do not understand." I think it's a much better quotation, and we've gone back to correct the DNA code so that Feynman can rest much more peacefully.


All living cells that we know of on this planet are DNA software driven biological machines comprised of hundreds to thousands of protein robots coded for by the DNA software.  The protein robots carry out precise biochemical functions developed by billions of years of evolutionary software changes.

Science can go much further now, and there is an exciting paper out of Stanford with a team led by Markus Covert and that included John Glass from my institute using the work on the mycoplasma cell to do the first complete mathematical modeling of a cell. But this is coming out in Cell next week. It's going to be an exciting paper. We can go from the digital code to the genetic code, and now modeling the entire function of the cell in a computer, going the complete digital circle. We are going even further now, by using computer software to design new DNA software to create a new synthetic life.

I hope it is becoming clear that all living cells that we know of on this planet are DNA software driven biological machines comprised of hundreds to thousands of protein robots coded for by the DNA software.  The protein robots carry out precise biochemical functions developed by billions of years of evolutionary software changes.  The software codes for the linear protein sequence, which in turn determines the rate of folding as well as the final 3-dimensional structure and function of the protein robot.  The primary sequence determines the stability of the protein and therefore its dynamic regulation in the cell.  By making a copy of the DNA software, cells have the ability to self-replicate.  All these processes require energy.  From all the genomes we have sequenced we have seen that there is a range of mechanisms for the generation of cellular energy molecules through a process we call metabolism.  Some cells are able to transport sugars across the membrane into the cell and by some now well defined enzymatic processes capture the chemical energy in the sugar molecule and to supply it to the required cellular processes.  Other cells such as the autotroph Methanococcus jannaschii use only inorganic chemicals to make every molecule in the cell while providing the cellular energy.  These cells do this by a series of proteins that convert carbon dioxide into methane to generate cellular energy molecules and to provide the carbon to make proteins. These processes are all coded for in the genetic code.

Schrödinger citing the second law of thermodynamics (entropy principal)-the natural tendency of things to go over into disorder, described his notion of "order based on order". We have now shown using synthetic DNA genomes that when you put new DNA software into the cell the protein robots coded for are produced, changing the cellular phenotype.  When you change the DNA software you change the species. This is consistent with Schrodinger's Code-script and "An organism's astonishing gift of concentrating a 'stream of order' on itself …"

We can digitize life, and we generate life from the digital world. Just as the ribosome can convert the analogue message in mRNA into a protein robot, it's becoming standard now in the world of science to convert digital code into protein viruses and cells. Scientists send digital code to each other instead of sending genes or proteins. There are several companies around the world that make their living by synthesizing genes for scientific labs. It's faster and cheaper to synthesize a gene than it is to clone it, or even get it by Federal Express.

As an example BARDA in the US government sends us as a part of our synthetic genomic flu virus program with Novartis, an email with a test pandemic flu virus sequence. We convert the digital sequence into a flu virus genome in less than 12 hours. We are in the process of building a simple smaller faster converter device, "a digital to biological converter", that in a fashion similar to the telephone where digital information is converted to sound; we can send digital DNA code at the close to the speed of light and convert the digital information into proteins, viruses and living cells. With a new flu pandemic we could digitally distribute a new vaccine in seconds around the world, perhaps even to each home in the future. 

Currently all life is derived from other cellular life including our synthetic cell.  This will change in the near future with the discovery of the right cocktail of enzymes, ribosomes, and chemicals including lipids together with the synthetic genome to create new cells and life forms without a prior cellular history. Look at the tremendous progress in the 70 years since Schrodinger's lecture on this campus.  Try to imagine 70 years from now in the year 2082 what will be happening.  With the success of private space flight, the moon and Mars will be clearly colonized.  New life forms for food or energy production or for new medicines will be sent as digital information to be converted back into life forms in the 4.3 to 21 minutes that it takes for a digital wave to go from earth to Mars. 

I suggested in place of sending living humans to distant galaxies that we can send digital information together with the means to boot it up in tiny space vessels.  More importantly and as I will speak to on Saturday evening synthetic life will enable us to understand all life on this planet and to enable new industries to produce food, energy, water and medicine as we add 1 billion new humans to earth every 12 years.

Schrodinger's "What is Life?" helped to stimulate Jim Watson and Francis Crick to help kick off this new era of DNA science.  One can only hope that the newest frontier of synthetic life will have a similar impact on the future.


JAMES WATSON: In 1963, which was 10 years after the Double Helix, I began putting together a book which became the Molecular Biology of the Gene. It was before we knew the complete code, it was after what Nirenberg had shown and so I thought we knew the general principles. I thought initially the title we would use for the book was This Is Life, but I thought that will be controversial because I hadn't explained everything, so it just became The Molecular Biology of the Gene.


I want to congratulate Craig on a very beautiful lecture.

Certainly Craig's talk is …it's much more beautiful 60 years later. And everything. I think chemistry is a good thing. I think our finding the DNA structure was unusual in that Crick or I, neither of us knew any chemistry. Luckily there was a chemist in the room, and helped. But I think we're in this era of beautiful high technology. Sentimentally, I hope there's still a role for the biologist.

Time will tell, but I want to congratulate Craig on a very beautiful lecture.


WoL&K (Wheel of Life & Knowledge )
A Conversation with Alex (sandy) Pentland [8.30.12]
With Big Data we can now begin to actually look at the details of social interaction and how those play out, and are no longer limited to averages like market indices or election results. This is an astounding change. The ability to see the details of the market, of political revolutions, and to be able to predict and control them is definitely a case of Promethean fire --- it could be used for good or for ill, and so Big data brings us to interesting times. We're going to end up reinventing what it means to have a human society
ALEX 'SANDY' PENTLAND is a pioneer in big data, computational social science, mobile and health systems, and technology for developing countries. He is one of the most-cited computer scientists in the world and was named by Forbes as one of the world's seven most powerful data scientists.
He currently directs the Sandy Pentland's Edge Bio Page
Understanding these human-machine systems is what's going to make our future social systems stable and safe. We are getting beyond complexity, data science and web science, because we are including people as a key part of these systems. That's the promise of Big Data, to really understand the systems that make our technological society. As you begin to understand them, then you can build systems that are better. The promise is for financial systems that don't melt down, governments that don't get mired in inaction, health systems that actually work, and so on, and so forth. The barriers to better societal systems are not about the size or speed of data. They're not about most of the things that people are focusing on when they talk about Big Data. Instead, the challenge is to figure out how to analyze the connections in this deluge of data and come to a new way of building systems based on understanding these connections.
Adam Smith And Karl Marx Were Wrong
These Big Data issues are important, but there are bigger things afoot. As you move into a society driven by Big Data most of the ways we think about the world change in a rather dramatic way. For instance, Adam Smith and Karl Marx were wrong, or at least had only half the answers. Why? Because they talked about markets and classes, but those are aggregates. They're averages. While it may be useful to reason about the averages, social phenomena are really made up of millions of small transactions between individuals. There are patterns in those individual transactions that are not just averages, they're the things that are responsible for the flash crash and the Arab spring. You need to get down into these new patterns, these micro-patterns, because they don't just average out to the classical way of understanding society. We're entering a new era of social physics, where it's the details of all the particles—the you and me—that actually determine the outcome. Reasoning about markets and classes may get you half of the way there, but it's this new capability of looking at the details, which is only possible through Big Data, that will give us the other 50 percent of the story. We can potentially design companies, organizations, and societies that are more fair, stable and efficient as we get to really understand human physics at this fine-grain scale. This new computational social science offers incredible possibilities.
This is the first time in human history that we have the ability to see enough about ourselves that we can hope to actually build social systems that work qualitatively better than the systems we've always had. That's a remarkable change. It's like the phase transition that happened when writing was developed or when education became ubiquitous, or perhaps when people began being tied together via the Internet. The fact that we can now begin to actually look at the dynamics of social interactions and how they play out, and are not just limited to reasoning about averages like market indices is for me simply astonishing. To be able to see the details of variations in the market and the beginnings of political revolutions, to predict them, and even control them, is definitely a case of Promethean fire. Big Data can be used for good or bad, but either way it brings us to interesting times. We're going to reinvent what it means to have a human society.
(our bold and italics)
Creating A Data-Driven Society
Who Owns The Data In A Data-Driven Society?


Wheel of Life & Knowledge (WoL&K)

MIND & Brain - A Problem of Symmetries

WoL&K (Wheel of Life & Knowledge )
A Problem of Symmetries
Iain McGilchrist

Keywords: Scheler, hemisphere, asymmetry, phenomenology,
schizophrenia, depression, Drang, Geist

John Cutting is among the most interesting
minds writing in psychiatry today. He has,
with a rare combination of erudition and
imagination, forged links between aspects of
reality as delineated by philosophy and those that
come into being through the workings of the two
hemispheres of the brain.
The phenomenological reduction......
Read MORE:

The scientific reduction is the left hemisphere Geist, still in touch with the right hemisphere’s Drang, but not allowing the products of its work a return to the right hemisphere, to be subject to the right hemisphere’s Geist and Drang: it represents the world as conceived by scientific materialism and it achieves only the lowest level of Scheler’s hierarchy of values.
The Asymmetry of the Asymmetries

Drang and Geist need to work together, and only do so in the right hemisphere, because the right hemisphere has both, where the left hemisphere has Geist only. In this, as in so much else, the hemispheres are not symmetrical. This is because the right hemisphere has a different status from the left: it is both where whatever-it-is-thatexists- apart-from-ourselves is first experienced and where it is finally understood. The left hemisphere is intermediate, where phenomena are ‘unpacked’ before a return to the right hemisphere. Geist has awareness of all the values, but none of them can be fulfilled without Drang. Geist on its own is a Faustian, Luciferian spirit. I hold that neither Drang nor Geist alone is able to achieve the higher levels of Scheler’s hierarchy—Drang because it is blind to what Geist can see, but Geist because it is essentially ‘egotistical,’ out for itself. If Geist is on its own, it is constantly brought back to the lowest level values, those of self-interest (sinnliche Werte and those of utility). In addition, Geist derives its power from Drang. However, Geist can achieve certain things that would be important for both of them only if it can be either temporarily or partially free from Drang. Thus, they need both to be separate and then to reunite. This is achieved by the bihemispheric structure of the brain, although not, I would say, by Geist being in one hemisphere and Drang in the other, but by both being in one hemisphere (right) and Geist alone in the other (left). (My bold & italics)

Read MORE:
mind-brain-assymetry.pdf Download this file
Reference on Max Scheler's Thoughts

What is IT? - The Universe!

What is the Universe? Still an unresolved Theme! What is IT? - and what is all the more behind and beyond IT? What was IT before and whither does IT move?


Is IT just HERE and NOW; not more not less! It is just a perpetual process of fluctuation from one mode to another what ever it is or was?

A Book on the whole spectrum of the topic  kindly presented on the Internet for Discussion :


The Universe is Only Spacetime by John A. Macken

How many component parts are required to construct the universe? The standard model has so many component parts that it is difficult to state a specific number. String theory has vibrating strings, branes, exchange particles and 11 dimensions. This book makes the case that everything in the universe can be formed from the single building block of 4 dimensional spacetime. However, this is not the quiet, smoothly curving spacetime envisioned by Albert Einstein. Instead, it is the composite of Einstein's spacetime and the quantum mechanical spacetime filled with a tremendous energy density of quantum fluctuations. This book shows how all fundamental particles, forces and cosmology can be derived from this energetic 4 dimensional spacetime.

Download the book (5 MB .pdf)

Revision 6.3 – Placed online for comments – July 2012

Download a short essay on the unification of forces (150 KB pdf)

Placed online for comments – August 2012


Quantum mechanics is the most successful theory devised by man. However, this success is largely a case of the equations corresponding to experimental observation. The current physical interpretation of quantum mechanics does not lead to a conceptually understandable model of the universe. Furthermore, there is clear evidence that the current starting assumptions for some quantum mechanical calculations contain at least one error. When calculations fall apart and yield an impossible answer such as infinity, these equations are screaming that a rigorous extension of the starting assumptions gives nonsense. Renormalization might seem to fix the problem, but this is merely a case of artificially adjusted the answer so that it no longer is a logical extension of the starting assumptions. Instead the unreasonable answer should be taken as an indication that the model being analyzed contains at least one erroneous assumption. The approach taken in this book is to build a new conceptual model of the universe that is compatible with the equations of quantum mechanics and general relativity but is based on the simplest possible starting assumption: The universe is only spacetime.


Univers-OnlySpacetime.pdf Download this file

Institutions make the big difference




"Economic institutions are those that really shape the economic incentives. They create opportunities or incentives for investment and innovation. They are crucially related to how level the playing field is. You now have many societies in which only a small fraction of the population are given the opportunity to get into the action. They are the only ones who can work in the modern sector. They're the only ones that can open businesses or open factories or get into trade or get into whatever occupations that they want. So that's really important to have this level playing field, in addition to economic institutions such as property rights and contracting institutions that give incentives to people to take advantage of whatever calling they have in life."

READ More:

The Divided Brain and the Western Mind

Following is a good and extensive review of

Iain McGilchrist on The Divided Brain and the Making of the Western World

on the becoming &  "agony" of the ´Western Mind" today at the the fascinating  blog of Amira Skomorowska: a nice blog, which deserves a look on other themes too; like

"Philosophy vs science: which can answer the big questions of life?"


The telling picture's source on the two sides of the brain is from a series of Mercedes Benz ads. found at


The text reads:

Left brain: I am the left brain. I am a scientist. A mathematician. I love the familiar. I categorize. I am accurate. Linear. Analytical. Strategic. I am practical. Always in control. A master of words and language. Realistic. I calculate equations and play with numbers. I am order. I am logic. I know exactly who I am.

Right brain: I am the right brain. I am creativity. A free spirit. I am passion. Yearning. Sensuality. I am the sound of roaring laughter. I am taste. The feeling of sand beneath bare feat. I am movement. Vivid colors. I am the urge to paint on an empty canvas. I am boundless imagination. Art. Poetry. I sense. I feel. I am everything I wanted to be.


Amira Skomorowska:

Iain McGilchrist on The Divided Brain and the Making of the Western World


“Just as the human body represents a whole museum of organs, with a long evolutionary history behind them, so we should expect the mind to be organized in a similar way. (…) We receive along with our body a highly differentiated brain which brings with it its entire history, and when it becomes creative it creates out of this history – out of the history of mankind (…) that age-old natural history which has been transmitted in living form since the remotest times, namely the history of the brain structure.”

Carl Jung cited in The Master and His Emissary, Yale University Press, 2009, p.8.

Renowned psychiatrist and writer Iain McGilchrist explains how the ‘divided brain’ has profoundly altered human behaviour, culture and society. He draws on a vast body of recent experimental brain research to reveal that the differences between the brain’s two hemispheres are profound.

The left hemisphere is detail-oriented, prefers mechanisms to living things, and is inclined to self-interest. It misunderstands whatever is not explicit, lacks empathy and is unreasonably certain of itself, whereas the right hemisphere has greater breadth, flexibility and generosity, but lacks certainty.

It is vital that the two hemispheres work together, but McGilchrist argues that the left hemisphere is increasingly taking precedence in the modern world, resulting in a society where a rigid and bureaucratic obsession with structure and self-interest hold sway.



Amira Skomorowska's blog:



More on The Divided Brain from a Philosophy corner (Review of Iain McGilchrist's Book):

Arran Gare

The-Master-and-His-Emissary.pdf Download this file

Interview with Iain Mcgilchrist:

Towards ... Change