Living in the future
Posted by ycpmicro
I had an interesting thought while writing up the Black Death posting from the other day, and that was how incredible it seemed to me to be able to recover the DNA of an organism, an ancient isolate of Yersinia pestis, from a mix of DNA fragments. The first sequence determination of a living organism was that of the bacterium Haemophilus influenzae, and was published in the journal Science in 1995 while I was in graduate school. That work was a Big Deal then, and that publication initiated the modern field of genomics. Currently, Genbank holds the sequence data of about 1700 completed prokaryotic genomes, and around 500 eukaryotic genomes, including the human genome (completed in 2003). In 16 years, we have accumulated many billions of nucleotides of genetic information, which has transformed modern medicine. Today’s students may have a hard time believing that it wasn’t always this way.
When I was in graduate school, DNA sequencing was typically accomplished in labs using a set of tedious manually-assembled reactions, and could successfully generate two hundred or so nucleotides of usable sequence data. I vividly recall the excitement of reading off my first sequence gel, and being able to identify a short segment of DNA of biological interest. Still, it was a technique that any researcher could accomplish easily, and it allowed me personally to move quickly forward with my thesis project. And even though I was present when this was becoming widely available, it was hard for me to realize that this technique was new.
I recall two conversations I had about then that altered my perception of how quickly technology changes modern biology. The first was with a scientist named Ira Herskowitz, who was studying how yeast cells mate. His 1988 manuscript with Susan Michaelis described a protein from the yeast Saccharomyces cerevisiae that enabled cells to secrete hormones that initiated the mating process. The key insight from this paper came from the analysis of the sequence of the STE6 gene, which turned out to be highly conserved evolutionarily with the gene in humans that is defective in the disease Cystic Fibrosis. The yeast finding actually shed light on the molecular mechanism behind Cystic Fibrosis pathology. I asked Dr. Herskowitz about the time frame for getting this key insight; after all they had identified the gene quite a few years previous to this paper, yet had no clue. His response? Sequencing, even a tiny bit to get that insight, was hard work even in the late 1980’s.
The other conversation was with my father, who for his graduate work in 1966 to 1968 was studying the stability and structure of proteins from thermophilic bacteria. He and his research mentor were studying a glycoprotein that they had purified, and one step in that characterization was determining the molecular mass of the protein, which was a significant technical hurdle. They accomplished it with a technically demanding procedure called analytic ultracentrifugation. I think I said something like “Duh Dad, why didn’t you just run a polyacrylamide gel and get the answer in an afternoon?” He looked at me strangely, and reminded me that this was in the late 1960’s, and the technique of PAGE analysis mass determination of proteins wasn’t published until 1970.
We spend a lot of time in classes at York College of Pennsylvania teaching students about how science is done today, and if we want our students to be competitive, we need to give them the tools used today. Still, with no appreciation for the tremendous work that went into developing those tools, students lose in the process. First, there is little to fall back on when the brand new, cutting-edge machine is out for repairs and we either need to troubleshoot or improvise. Second, I think that without a basic understanding of how things used to be done, we may lose the ability to create tomorrow’s innovations. And that worries me just a bit.