A Take Progress in Science and Technology

I’m putting this blog up together with a BDN blog I did on evolution and synthetic biology in 2010, I could have sworn it was 2015 or later that I did that post, but it was a year after the 150th anniversary of Darwin’s publication of ‘On the Origin of Species, so times goes by! A gist of that post is my imagining my future science lab where I could create synthetic microbes at my lab bench by building an entire bacterial chromosome with whatever modifications I wanted to make, then using a kit to turn my synthetic chromosome into a living cell that could be experimented with. I wrote it at the time that the first ‘synthetic microbe’ had been described. I use quotation marks because that cell had a ‘man-made’ chromosome, but was far from my imaginary synthetic microbe, nonetheless, it stimulated the imagination to think about what was possible with synthetic microbes.

Since it really is 15 years hence, it gets me to pondering about the pace of scientific discovery and technology development, and the realities thereof. At the time I wrote that BDN blog I might have said in 15 – 20 years, the experiment I had envisioned might be possible, and here I am 15 years later thinking maybe in another 15- 20 years a limited type of this experiment could be possible, but probably only in a very well-funded laboratory. That’s not to say that aspects of this experiment couldn’t be done now, especially with viruses that have small genomes and are easy to manipulate. Indeed, there is continuing debate as to whether Covid-19 was a lab construct that escaped.

Now, for a short ethical aside (my previous blog had a much longer ethical aside). Would this really be a good idea? As a scientist interested in the fundamentals of understanding how life works, absolutely! As a techno-geek interested in pushing the boundaries of human knowledge, capacity, and getting a leg up on my rivals, absolutely! As a human born into a  complex world full of amazing natural beauty and wonder, maybe not. As a responsible citizen of my town, my state, my country, my planet, who believes in progress and inalienable rights for all humans, and is concerned about technological abuse of fellow citizens and the environment, that’s a tough one.  Therein lies the dilemma of a scientist.

At any rate, in terms of development of synthetic microbes, none of this is very close to my thought experiment. Cheaply synthesizing entire assembled chromosomes of even modest bacterial genomes is not possible, and there are no kits for using these synthetically produced genomes to generate fully functioning bacterial cells with widely divergent physiologies. There are lots of papers on ‘synthetic bacteria’, but these are based on genetically engineering existing microbes to have some function that the ‘nonsynthetic’ cell did not. Not to say, that the current work on developing synthetic bacteria isn’t complex and challenging, it is, and that’s exactly the point.

It’s hard to predict how hard complex problems are to solve. The challenge of synthesizing and assembling even small bacterial genomes and then creating a functioning cell is turning out to be very complex indeed. Even in the most well-studied cell/genome on the planet, E. coli, we still don’t understand the function of nearly a quarter of its genes. This really should not come as a surprise to me. Whenever I look through my microscope at a water sample, I am still amazed at the diversity of small ‘animicules’ (to quote Antonie Van Leeuvenhoek) zipping around. We don’t even know who the majority of them are, what functions they can carry out, and have almost zero understanding of their behavior. And those are just the basics: the molecular machinery used for replication, gene regulation, translation and expression, epigenetics, and cellular defense likely have a mind-boggling number of nuances and variations on the central dogma’s we have developed by studying a handful of model organisms in the lab.

To give another illustration, I remember assuming in the year 2000, that I would have a DNA sequencer sitting on a bench in my lab within a decade, or 12-15 years at the outside. This machine would be well within the budget of a modestly funded microbiology lab. It would allow my lab to do all its own DNA sequencing, maybe waiting 24h to get a result, as opposed to sending DNA samples out to a sequencing service and waiting days, weeks, and sometimes months to get results back (the waiting time often inversely commensurate to the cost). Twenty-five years later, I still don’t have a DNA sequencer in my lab.

It’s worth a bit of a ponder on how I could be so far off in my projections of technological development. The bottom line is that lots of technologies are hard, there is also a corporate business aspect. DNA sequencing is a good example where the field is dominated by one company, Illumina, that produces the bulk of the world’s DNA sequencers. Ilumina machines are good, the company continues to improve its instruments, and make some of them more affordable, but it’s all been along a corporate proscribed path with aggressive protection of intellectual property (IP) with deep corporate pockets and a strong legal bench. Technical prowess is not the only factor at play in technological advance.

On the other hand, ‘old hat’ technologies like mass spectrometry that simply put, weigh individual molecules, and can make all kinds of interpretations and identifications based on the infitesimally small weight differences between them, continue to develop with amazing new innovations, like being able to characterize all the proteins in an individual cell. I played around with MS for bacterial identification a number of years ago. I was impressed how well it worked and also how limited it was, and wouldn’t have predicted then, that in 20 years it would be possible to characterize all the proteins in a single cell and compare them to another cell that was maybe experiencing different environmental conditions, and that all this could be cheaper than genomic methods. Maybe I should have seen this coming, but didn’t.

The main point about technological complexity is simple, it’s hard to predict how the development and applicability of complex technologies will play out.  I would say it’s especially true for biological ones, but these are what I know best, so I suspect it also applies to electronics, including computers, and transportation systems. Heed an expert, but also recognize an expert is likely to be blinded, not by ignorance, but by their own hopes and ambitions in predicting what’s going to happen next.