Venter’s synthetic cell

Last Thursday, the creation of a `synthetic cell’ by Craig Venter’s institute was announced in the journal Science to much media fanfare.  What they actually did was to synthesize an entire genome  of a known bacterium and transplant it into another bacterium. This achievement was not unexpected although Venter’s team had to overcome two  significant technological hurdles to make this happen now rather than later.  The first was the ability to transplant an entirely new genome into a bacterial cell and have the new cell actually function.  This was achieved last year by Venter’s team and published in Science.  The second was to synthesize a continuous ring of  DNA consisting of a million base pairs, which was over a factor of 20 more than what had been done before.

It is still mysterious as to how the feat of transplantation actually works.    They first incubate the recipient cells in a soup that essentially consists of beef broth and sugar at 37 degrees Celsius, which makes the soup more acidic.  This causes the bacterial cells to change shape and become more elongated and branched.  They then carefully add the synthesized DNA, which are cushioned in specially prepared gel plugs.  They  gentle rock the tube, incubate it some more and in a few day cultures of the new cells, which they have been manipulated to be blue, appear.  It is not clear how generalizable this procedure will be for other types of cells but amazingly it works at all.

The task of synthesizing the DNA was less about inspiration and more about perspiration.  They divided the sequence of the donor genome into a little over a thousand  1080 base pair long segments or cassettes and had the company Blue Heron synthesize these cassettes from scratch.  Venter’s group  then combined these cassettes into a hundred nine 10,000 base pair long assemblies,  combined these  into eleven 100,000 base pair assemblies, which were then joined into the circular genome that was transplanted.  The whole procedure was only possible because of half a century of molecular biology know how.

I don’t think that this achievement represents a major transitional moment for society or even science.  The hype is that this now allows us to design synthetic bacteria that secretes gasoline or can clean up oil spills.  However, in reality this just provides another means to achieve those ends.  Prior to this work,  people would insert and delete genes in existing organisms to attain some end.  For instance, human insulin has been produced by bacterial cells for three decades by genetically manipulating genes.  Now, instead of swapping genes in and out, they can synthesize the entire genome.  The difference is the same as that between building a new house versus renovating an old house.  If you only want a bigger kitchen or bathroom, then its best to renovate.  If you want an entirely new floor plan then it might be better to build from scratch.   However, just as new houses don’t look that much different from existing houses, I think this will be true of synthetic cells as well.  We simply do not understand enough (and perhaps never can from a computational complexity point of view) to be able to design ab initio life forms that are completely independent of what already exists.  Hence, our forays into synthetic biology will likely always involve some form of modification to existing life forms. It then becomes a question of expediency and cost whether you build from scratch or renovate.

Objectivity in art

About five years ago, there was a big story in the news about a child artist named Marla Olmstead.  She started painting at two and by the time she was four  she was selling large abstract oil paintings for tens of thousands of dollars. The paintings were bold and colourful and were quite impressive.  They wouldn’t look out of place in any modern art exhibit.

Her story was  documented in the 2007 film My Kid Could Paint That.  Her parents had always maintained that she painted the works herself but a 60 Minutes special in 2005 suggested that her father either helped her or painted the works himself.  Immediately after the episode aired there was a huge uproar.  Many of the patrons that bought her art became quite angry and the gallery where her art was shown stopped showing her work for awhile.  The documentary was mostly neutral on whether or not she actually painted the paintings.  She was filmed painting two of the paintings but the results seemed different from the other paintings.

One of the messages of the film was that perhaps modern art was somewhat of a hoax.  The gallery owner that first put on her shows, painted detailed realistic pictures that took months to complete and he had quite a bit of bitterness towards abstract artists who throw a bucket of paint against a canvas and sell the work for hundreds of thousands of dollars. Promoting Marla was partly his way of making a statement to the art establishment.

I took away two messages from the film.  The first is that abstract random patterns are often pleasing to our eyes.  I thought many of Marla’s paintings were quite beautiful but I also think some of the art my four year old daughter brings home from school also looks quite nice.  We basically see what we want when we look at a mass of colours and patterns.  It is why a dried river bed, a forest scene or swirling clouds can be so awe inspiring.  We find beauty in randomness.

The second was that I found it odd that no one questioned why it would matter who the artist was.  Why would a painting be less beautiful if it was painted by the father instead of a four year old?  It made me think that perhaps art should be presented anonymously.  It is interesting that the value of a painting by a famous artist vanishes the moment it is discovered to be a forgery. What exactly changed in the painting to cause it suddenly to be worth so much less?  Why is it so important that a Vermeer or a Cezanne be painted by Vermeer or Cezanne?  If someone had the skill to forge a piece of art so perfectly that it could fool anyone, how is that different from the original?  The fact that we put value on things because of their history says a lot about how our brains work and how our priors strongly determine value.

The scale invariant life

The most recent episode of WNYC’s Radiolab was about human limits.  The first two stories were on the limits of the human body and mind and had people telling stories of surviving extreme endurance events and participating in memory competitions.  The last story was about the limits of science.  I was expecting the usual take on Godel’s Incompleteness Theorems but they touched on something different.  Instead they talked about how this algorithm called Eureqa written by two Cornell computer scientists could deduce the dynamics of unknown systems.  They used it to deduce the equations of a double pendulum based on the time series of the angles and angular velocities.  They then applied it to a biological system and produced some dynamical equations.  However, they then claimed that they had trouble publishing the results because they couldn’t explain what those equations described or meant.  Steve Strogatz then came on and started to lament on the fact that as we begin to explore more and more complex systems, our brains may not be able to ever understand it.  He basically said that once we reached that limit we may need to hand over science to computers.

I think that Steve is confounding the limits of a single human being with the limits of humans in general.  To me, understanding is all about data compression.  One says they understand something when they can give a simpler description of it or relate it to something they know already.  Understanding is not a binary process.   I understand some things better than other things and I attain a greater and sometimes lesser understanding of things the more I think about them.  However, I do agree that there may be limits to the number of different things I personally can understand.  This applies to things that other humans already understand like for example Turkish.  Now, perhaps if I studied hard enough I could learn to speak Turkish but the time it took for me to do that would preclude me from learning something else like say Category Theory.

What Steve was specifically referring to I believe was that it may be difficult or impossible to understand certain complex systems by trying to relate them to what we know now. I think this is probably true but that doesn’t mean we won’t have intuitive understanding of such systems in the future.  For example,  it would be very difficult for an adult 500 years ago, who should be genetically indistinguishable to a person alive today, to understand Andrew Wile’s proof of Fermat’s last theorem.  Most of them would first have to learn how to read and then learn 500 years of mathematics.  Wiles basically used everything humans know about math up to this point to prove the theorem.  The average mathematician alive today that doesn’t specialize in arithmetic algebraic geometry has trouble understanding the proof.  They simply don’t have the background to follow all the arguments.

Now, I do believe that there are things that we can never understand  because we are bound by the rules of computation.  Turing showed us that there are undecidable problems that cannot be solved in general like if a computation will halt.  However, I do think that humans have the capability to understand individual things that arise out of computations and that includes physical objects like biological systems. We may not know whether a given computation will halt but we could understand what has already been computed.   For complex systems that Steve was alluding to, we just don’t yet know what the form of that understanding will be.  Consider Brownian motion, which is the modern paradigm of an unpredictable process.  Until  Einstein pointed out that the process should be understood probabilistically and calculated  the time dependence of the mean square deviation of a Brownian particle people didn’t even know how to think about the phenomenon.  I think most physicists would claim that they have a good understanding of Brownian motion even though they have no idea what a single trajectory of a Brownian particle will do.  From a neuroscience perspective, Brownian motion has become a primitive concept and we can understand more complex things in terms of it.  I think this will hold true for even more complex phenomenon.  We can always reform what we consider to be intuitive and build from that.

Addendum:  I forgot to relate everything back to the title of the post.  I called this the scale invariant life because I think everyone will go through similar stages where they learn what is known, make some new discoveries and then reach a crisis where they can’t understand something new in terms of what they already  know.  Thus there are no absolute thresholds of discovery or knowledge.  We just make excursions from where we start and then the next generation takes over.