Sunday, March 24, 2013

The revolution is inside you


She was a dignified beast.  Stuffed full of coils of wire and disk drives and mysterious metal-laced innards, she occasionally emitted whirring sounds or high pitched beeps from within her thick plastic carapace.  Her husk was beige and somewhat rough, because those were the textures of that day, kind of like black and white photographs.  We had to feed her a floppy disk to get her to boot.  She only had about a thousandth of the storage space of a modern thumb drive, and the same computing power as a modern throwaway flip-phone, but we didn’t care -- she crunched our numbers for us and had a word processor.  What else could we ask of one?  My brother was one of the few, the elite, who understood how to even use her.  He was fluent in DOS.  He even taught himself back then a few of the mystical languages of programming.  Yes, my family’s first computer was a Brontosaur.  But she was a Brontosaur with some megs, and it made all the difference.  

All that wasn’t so long ago.  Who would have thought we would have smartphones and tablets with apps for every bit of our lives in our hands by the year 2013?  Computers have exploded in speed, functionality, and ubiquity since those early days.  While this explosion involved billions of programmer-hours, its most convenient metric is Moore’s law, which states that computers tend to double in computing power approximately every two years.  The trend has held since the mid 1960’s.  Bootstrapping off of those advances, we have reached an era of computerization that a generation ago, few could have possibly predicted.  

But this blog post isn’t about computers.  You see, there’s another technological explosion happening right in front of our faces, an explosion every bit as far reaching and powerful as the computer one, but one about which tremendously fewer people are aware.  I mentioned it in my last blog, but I didn’t get too deeply into it.  What I’m talking about is the explosion in Genomics.   

What is most striking is that over the last decade, genomics has been advancing at a rate even faster than Moore’s law.  How much faster?  Well, if we measure the progress of genomics by the cost at which we can determine the sequence of DNA in an organism, then nearly four times faster.  This means that while sequencing the length of DNA in a bacterium in 2001 would have cost around $20,000, today it would cost something less than a dollar.  The cost to sequence is not the whole story -- to actually assemble the genome of a whole bacterium you need to do quite a bit more sequencing and other processing, and interpreting genomes is one of the biggest challenges we face in science today -- but you can imagine what this reduction in cost has enabled.  What this all means is that what took ~3 billion dollars, 13 years, and millions of man-hours to achieve in 2001 at the pinnacle of the Human Genome Project -- sequencing a human’s genome -- is now possible in a few weeks for several thousand dollars, and will be possible for less than a $1000 price-tag within only a few years.  

The $1000-genome milestone matters, because around that price, genome sequencing starts to become relevant on an individualized basis in medicine.  To put this more clearly, this means that when you go to the doctor not too long from now, she will be able to send off a drop of your blood or skin and have your genome sequenced as a routine procedure.  In fact, even now, companies like 23andme will sequence parts of your DNA that indicate susceptibility to a plethora of diseases for just a few hundred bucks.  

Just as with the computer revolution, by the time that the genomics revolution is done, we may barely even recognize the world that we live in.    

If you were to ask a person on the street what genomics will do for them in their lifetime, they probably wouldn’t even know what you’re talking about.  They might respond like a 1950’s housewife may have responded to a question about computers, or a pre-industrial farmer to a question about gasoline.  Or perhaps they’ll think about embryonic stem cell research or human cloning and have a gut negative reaction.  Most wouldn’t think of designer bacteria that emit wonderful perfumes, genetically modified algae that may solve the majority of our energy needs, cures for pretty much any genetic disorder, or totally personalized medicine (like a more advanced version of this).  But these things are precisely what scientists think, talk, and dream about.  The field is so rife with potential and is expanding so rapidly that how it will reshape us in the future is extremely hard to predict.  But just as computers have changed our lives in ways we couldn’t have fathomed, so may genomics.  And just as with computers, although there are certainly negative consequences, the potential of genomics for our lives is one of vast improvement in quality of life and happiness.

Genomics is the study of genomes.  A genome is the collection of all DNA in a person or organism.  DNA is a long, stringy molecule that dictates all of your genes, i.e., the traits passed on to you by your parents.  The most amazing thing about DNA is that it dictates our genes using a digital code with only four basic letters -- A, T, C, and G -- which act sort of like binary code in a computer.  This makes it extremely amenable to computerized analysis, an aspect that scientists have taken tremendous advantage of.

Every person on earth has a unique genome, and to sequence a genome means to use a combination of automated physical platforms and sophisticated computational methods (often run on a huge number of computer servers) to figure out the exact series of the A’s, T’s, C’s, and G’s that make a particular person genetically unique.  Although the genome doesn’t explain a person’s every trait, it explains a great majority of them.    In 2001 when researchers published the first draft human genome, it was actually an averaged genome of several people.  Now, our technology enables us to sequence individual genomes to near completion, which may be the key to truly personalized medicine.  

Each one of your cells has a couple copies of your own personal genome (except for a few weird cell types, like red blood cells, which contain no DNA).  The fact that there’s a copy in every cell is how, for example, scientists were able to create embryonic-like stem cells out of skin cells, a technology that may both bypass many ethical issues and allow for some amazing new therapies.  Imagine regrowing a damaged organ, and having a transplant from yourself.  As we get better at understanding and manipulating genomes, we will shine guidelights into many more areas than just that.  

This was amply demonstrated in 2010 when a team led by Craig Venter created the first ever synthetic lifeform.  To do this, they synthesized from scratch the entire genome of an organism based on a string of DNA code that had been planned on a computer (mostly following the DNA plan of a natural organism, Mycoplasma mycoides), and then implanted the synthesized genome into a cell whose DNA had been removed.  The “synthetic” cell proved to be viable, replicating billions of times.  While this synthetic cell was not so different from its natural parent, the process could be repeated for much more outlandish designed genomes.  

I saw Craig Venter speak about this in Tel Aviv last year when he accepted a science award called the Dan David Prize.  During a student Q&A session, he spoke about automated evolution: creating synthetic lifeforms and then mutating, evolving, re-sequencing, analyzing, and re-designing them, and thus closing the loop between computers and biology, enabling us to build and understand bugs that do anything.  He spoke about cells in a way I had never heard before from a biologist -- as computers running DNA software that is now, with Venter’s technology, easily exchangeable between silicon machines and biological hardware.  I asked him about Ray Kurzweil’s singularity, and whether he feels his technology is driving towards it.  He smiled like a man in the know.  

Of course, such power is not without dangers.  Who should be able to wield this technology, especially if synthesizing new genomes becomes cheap enough to be commoditized?  Because of the potential damage, it is almost inconceivable to release synthetic cell technology into lay hands.  Think atomic energy.  Good bioethicists and regulators must play a role, but even there we will face difficult dilemmas.  

And the dilemmas don’t just begin with synthetic lifeforms.  There are also basic ethical questions surrounding the mere sequencing, and not even getting into the manipulating, of genomes.  Sergey Brin, the co-founder of Google, knows this well.  When his wife founded the sequencing company 23andMe, Sergey Brin was one of the first to have parts of his genome sequenced.  It turns out he has a rare mutation putting him at high risk for Parkinson’s disease.  Brin has taken a pragmatic approach, and is now doing everything he knows of that will decrease his risk.  But the lesson is obvious.  Even if you can know about all the diseases you’re at risk for, do you really want to?  Do you want potential employers to?  Your insurance provider?   

That being said, to forsake such technology because of fear of its dangers seems foolhardy.  Last century saw the atomic age and the space age and the computer age, and I believe that when we look back, we may call nowadays the genomics age.  We should proceed with caution… but we should proceed.


See my related post:
Why a black swan named Brooke Greenberg might make you immortal -- or not