P.C. Shannon

The sequencing of the human genome project took ten years and cost millions and millions of dollars. It was coordinated effort of researchers around the world. But the technology used to sequence DNA developed so quickly during the project that it finished five years ahead of schedule. And the technology continues to improve.

In fact, it generally follows Moore’s Law, which states that computer processor power will double every 18-months but has been applied to many areas of technology. As price comes down and speed and accuracy increase, some in the field have projected that in ten years, a single individual will be able to have her own genome sequenced for $1000.

That day is getting closer. A recent paper in Nature (PubMed; subscription required for summary and article) demonstrates a new sequencing technology that allows a single technician to sequence 25 million bases in just four hours. By comparison, the sequencers that I used when I worked on the Human Genome Project could each produce about 10,000 bases in the same time frame. The authors of the paper assembled an entire bacterial genome in a single run.

The advent of individualized genomic medicine will be a boon to health care, provided that safeguards are put in place to protect patients’ privacy. Otherwise, it may just further corrupt our already-crippled health insurance system.

Technology like this and the Internet always remind me of my 8th grade history teacher (who was also a football coach) who told us that, unlike every previous generation of Americans, our standard of living would not increase dramatically from what our parents experienced. It makes me chuckle.

Along with the phage idea from a few days ago, I was thinking about how you would synthesize really big pieces of DNA with a novel sequence from scratch. Obviously we can produce oligos but it’s just not practicle (nor feasible I would think) to build really long pieces this way. I can’t remember if this is an idea i had or (more likely) something someone else came up with and I just can’t recall where I’ve seen it before.

You could synthesize a lot of oligos (maybe 20-mers) for your sequence and the complementary strand. The oligo would be designed such that the breaks in one strand fall in the middle of an oligo for the other strand, crudely diagrammed thusly:

BBBBBBBBBB BBBBBBBBBB BBBBBBBBBB
BBBBB BBBBBBBBB BBBBBBBBBB BBBBB

For best results, the gaps could even span multiple bases in the antisense strand. Mix with some PolIII and ligase, repeat until sufficiently long DNA.

It’s my understanding that in his latest book, Stephen Wolfram asserts that humen beings are born with an understanding of physics. (I haven’t personally read the book.) I don’t think this is exactly the case. Rather, human beings are born with the capacity to understand physics, in much the same way we are born with the capacity to learn language. No one is brought into the world speaking English or Swahili, but we learn it over time. Some extreme cases of child abuse have demonstarted that if we don’t learn a language by the time puberty hits, then that capability is lost. Likewise, we all learn physics to some degree because we’re all exposed to it. A child born and raised in a zero-gravity environment would have a very different understanding of physics than her earthbound cousins.

Nonetheless, even if the knowledge itself isn’t encoded in our DNA, it is still humbling to realize that that molecule contains the power to enable us to learn. DNA is responsible for the structures that form in the brain, that then absorb experience and transform it into knowledge. This is where the size of the human genome comes into play. It seems farfectched to me to imagine that there’s a gene (or more specifically, an allele) for “physics brain structures” any more than there’s one for a dog’s olfactory lobes. It seems much more plausible that there are highly complicated mechanisms that control the development of these structures, especially in the embryo.

This idea of complex and intricate control mechanisms is borne out by the size of the human genome. It was once estimated to be 100,000 genes, but it is now thought to be closer to 30,000. Same number of base pairs, no matter what the count. All that extra data may not be just “wasted space.” Instead, perhaps it is highly complex and evolved control mechanisms, many of which function primarily (or exclusively) during embryonic development. And it is these control mechanisms that are really what separate human beings from nematodes.

Tyrosine kinases and signaling pathways are one example of a control mechanism that’s found only in higher animals. I imagine there are many many more.