Kim Robinson - Sixty Days and Counting

Then it was less than a mile’s walk back up the road (though he was the only person walking it), and he was north of the university, at the old Torrey Pines Generique facility, now the National Science Foundation’s Regional Research Center in Climate and Earth Sciences, RRCCES, which of course they were pronouncing “recess,” with appropriate comparisons to Google’s giant employee utopia in Mountain View—“They’ve got the playground, but we’ve got recess.”

Inside, the reception room was much the same. The labs themselves were still under construction. His first meeting was in one of these, with Yann Pierzinski.

Frank had always liked Yann, and that was easier than ever now that he knew Yann and Marta were just friends and not a couple. His earlier notion that they were a couple had not really made sense to him, not that any couple made sense, but his new understanding of Yann, as Marta’s housemate and some kind of gay genius, like Da Vinci or Wittgenstein, did make sense, maybe only because Yann was odd. Creative people were different—unless of course they weren’t. Yann was, and in a strangely attractive way; it was as if Frank, or anybody, could see the appeal Yann would have to his partner.

So, now they discussed the latest concerning the new institute, comparing it to the Max Planck Institutes that had been its model. It was an intriguing array of sciences and technologies being asked to collaborate here; the scientists ranged from the most theoretical of theorists to the most lab-bound of experimentalists. In this gathering, as one of the only first-rank mathematicians working on the algorithms of gene expression, and one with actual field experience in designing and releasing an engineered organism into the wild, Yann was going to be a central figure. The full application of modern biotechnology to climate mitigation; it got interesting to think about.

Yann’s specialty was Frank’s too, and to the extent Frank had been on Yann’s doctoral committee, and had employed him for a while, he knew what Yann was up to. But during the two years Frank had been away Yann had been hard at work, and he was now far off into new developments, to the point where he was certainly one of the field’s current leaders, and as such, getting pretty hard to understand. It took some explaining from him to bring Frank up to speed, and speed was the operative word here: Yann had a tendency to revert to a childhood speech defect called speed-talking, which emerged whenever he got excited or lost his sense of himself. So it was a very rapid and tumbling tutorial that Yann now gave him, and Frank struggled just to follow him, leaping out there on the horizon of his mind’s eye.

Great fun, in fact: a huge pleasure to be able to follow him at all, to immerse himself in this mode of thinking which used to be his normal medium. And extremely interesting too, in what it seemed might follow from it, in real-world applications. For there was a point at which the proteins Yann had been studying had their own kind of decision tree; in Yann’s algorithm it looked like a choice, like a protein’s free will, unless it was random. Frank pointed this out to Yann, wondering what Yann had been thinking when he wrote that part of the equation. “If you could force or influence the protein to always make the same choice,” he suggested, “or even simply predict it…” They might get the specific protein they ultimately wanted. They would have called for a particular protein to come out from the vasty deep of a particular gene, and it would have come when they called for it.

“Yes,” Yann agreed, “I guess maybe. I hadn’t thought about it that way.” This kind of obliviousness had always been characteristic of Yann. “But maybe so. You’d have to try some trials. Take the palindrome codons and repeat them maybe, see if they make the same choice in the operation if that’s the only codon you have there?”

Frank made a note of it. It sounded like some pretty good lab work would be needed. “You’ve got Leo Mulhouse back here, right?”

Yann brightened. “Yeah, we do.”

“Why don’t we go ask him what he thinks?”

So they went to see Leo, which was also a kind of flashback for Frank, in that it was so like the last time he had seen him. Same people, same building—had all that out in D.C. really happened? Were they only dreaming of a different world here, in which promising human health projects were properly funded?

But after a while he saw it wasn’t the same Leo. As with the lab, Leo looked outwardly the same, but had changed inside. He was less optimistic, more guarded. Less naive, Frank thought. Almost certainly he had gone through a very stressed job hunt, in a tight job market. That could change you all right. Mark you for life sometimes.

Now Leo looked at Yann’s protein diagrams, which illustrated his model for how the palindromic codons at the start of the KLD gene expressed, and nodded uncertainly. “So, basically you’re saying repeat the codons and see if that forces the expression?”

Frank intervened. “Also, maybe focus on this group here, because if it works like Yann thinks, then you should get palindromes of that too…”

“Yeah, that would be a nice result.” The prospect of such a clearly delineated experiment brought back an echo of Leo’s old enthusiasm. “That would be very clean,” he said. “If that would work—man. I mean, there would still be the insertion problem, but, you know, NIH is really interested in solving that one…”

Getting any of their engineered genes into living human bodies, where they could supersede damaged or defective DNA, had proven to be one of the serious stoppers to a really powerful gene therapy. Attaching the altered genes to viruses that infected the subject was still the best method they had, but it had so many downsides that in many cases it couldn’t be used. So literally scores or even hundreds of potential therapies, or call them outright cures, remained ideas only, because of this particular stumbling block. It vexed the entire field; it was, ultimately, the reason that venture capital had mostly gone away, in search of quicker and more certain returns. And if it wasn’t solved, it could mean that gene therapy would never be achieved at all.

To Frank’s surprise, it was Yann who now said, “There’s some cool new stuff about insertion at Johns Hopkins. They’ve been working on metallic nanorods. The rods are a couple hundred nanometers long, half nickel and half gold. You attach your altered DNA to the nickel side, and some transfer-rin protein to the gold, and when they touch cell walls they bind to receptors in pits, and get gooed into vesicles, and those migrate inside the cell. Then the DNA detaches and goes into the nucleus, and there it is. Your altered gene is delivered and expressing in there. Doing its function.”

“Really?” Leo said. He and his Torrey Pines Generique lab had been forced to look at a lot of options on this front, and none had worked. “What about the metals?”

“They just stay in the cell. They’re too small to matter. They’re trying out platinum and silver and other metals too, and they can do a three-metal nanorod that includes a molecule that helps get the thing out of the vesicles faster. They want a fourth one to attach a molecule that wants into the nucleus. And the nickel ones are magnetic, so they’ve tried using magnetic fields to direct the nanorods to particular areas of the body.”

“Wow. Now that would be cool.”

And on it went. Leo was clearly very interested. He seemed to be suggesting in his manner that insertion was the last remaining problem. If this were true, Frank thought…for a while he was lost in a consideration of the possibilities.

Leo followed Yann better than Frank had. Frank was used to thinking of Leo as a lab man, but then again, lab work was applying theory to experiments, so Leo was in his element. He wasn’t just a tech. Although he was obviously confident of his ability to work the lab as such, to design experiments expressly for his machinery and schedule. Sometimes he stopped and looked around at all the new machinery as if he were in the dream of a boy on Christmas—everything he ever wanted, enough to make him suspicious, afraid he might wake up any second. Cautious enthusiasm, if there could be such a thing. Frank felt a pang of envy: the tangible work that a scientist could do in a lab was a very different thing from the amorphous, not to say entirely illusory, work that was consuming him in D.C. Was he even doing science at all, compared to these guys? Had he not somehow fallen off the wagon? And once you fell off, the wagon rolled on; again and again as the minutes passed he could barely follow what they were saying!