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“Let There Be Life” Focus: Brave New World “We have reason to believe that the disease is created by a man-made super pathogen...” AND MAN SAID, “LETa short story THERE BE LIFE” By Lawrence Valverde e have reason to believe the nearly 200 scientists simmered with “Wdisease is caused by a man- mumbled comments. The researcher made super-pathogen. The construc- whose speech had been interrupted tion seems to be loosely based on the straightened himself and raised his smallpox virus, but with significant voice in response. modifications, including genes encod- “I hear your concern, Dr. Boots, ing immune system antagonists. It but we have not confirmed whether or also seems to have been specifically not this is, in fact, a terrorist act…” engineered to resist known antivi- “Who else would do such a thing, ral…” Dr. Cervantes?” Dr. Boots demanded. “What do you mean specifically “It wasn’t necessarily done on engineered!” boomed an overweight purpose…” said Dr. Cervantes—the man as he hauled himself out of speaker—but he was interrupted by his chair. “Are you proposing that the clamor that erupted as scientists terrorists may have the technology jump up from their seats. Dr. Cervantes to synthetically create their own vi- frowned. Trying to speak over the ruses?” The surrounding panel of crowd was clearly a lost cause. When credit: Clipart courtesy FCIT. http://etc.usf.edu/clipart credit: Clipart courtesy FCIT. fall 2008 • Harvard Science Review 9 valverde.indd 9 2/9/2009 11:24:54 PM Focus: Brave New World did this whole business with artificially Dr. Boots sputtered. Dr. Cervantes, created viruses and organisms start? It interrupted from his musings, realized must’ve been the J. Craig Venter Science belatedly that the words were addressed Foundation, which created a synthetic at him. “Does it not concern you that if Mycoplasm genitalium genome barely ten the technology for synthetic production years ago. Actually, it probably started of viruses or bacteria has now become much earlier than that, when Gobind generally available, why even pathogens Khorana [2] and the rest of his team we have eradicated may be revived!” He assembled a complete gene from yeast was raising his voice with every word, in the 1970s. That allowed Dr. Venter not stopping to take a breath. By the to come up with the minimal genome end of the sentence his face had turned project and address the question of a worrisome shade of purple. how small a genome an organism can “Well, yes, but—” Dr. Cervantes have and still be alive. That was why began, but was cut short by a woman they chose M. genitalium, the bacterium with the smallest genome known. The next big step must have been when Venter, Smith and Hutchison syn- thetically assembled the five thousand- some base pair bacteriophage phiX174. They used short, single strands of com- mercial synthetic DNA, a process that took only two weeks. Four years later, Lartigue announced that her team had transplanted a complete genome and changed one species of bacteria into another! An M. capricolum became an M. mycoides—just like that! Despite the magnitude of this accomplish- ment, they saw their success as only step two in a three part plan. The last part, which was tackled back in 2008, was the question of how to insert the synthetic chromosome into a cell and booting it up, creating the first synthetic organism… A research protocol without synthetic genomics that took three years. (2) And these scientists. Dr. Cer- vantes glanced at the crowd in front him. They’re speculating about terror- in a sharp pant suit. ists, which is actually a very unlikely “Didn’t Eckard Wimmer and his “Dr. Venter came explanation for this fiasco. They don’t team assemble a neurovirulent polio- up with the seem to realize that what they should be virus in 2002? And that was only with minimal genome worrying about are the moral implica- nucleotides bought over the internet tions of synthetic genome technology. and through mail-order!” [3] project... What Are we playing God here? If man can “Yes, Dr. Davis, I remember,” Dr. is the smallest create life, is that a crowning brick on Cervantes replied, nodding in recogni- genome an the pillar of progress, or the corner- tion at the woman who’d so rudely cut organism can have stone of a tower of Babel? Boots has him off. “But do remember Wimmer’s and still be alive?” a point about being careful about bio- own comment that the process was so logical weapons, but perhaps greatest tedious, a bioterrorist wishing to do real threat actually comes from the most harm would take the easier route of well-meaning. [5] obtaining a virus already existing.” “Do you know what that means?” “But that was nearly two decades 10 Harvard Science Review • fall 2008 valverde.indd 10 2/9/2009 11:24:54 PM Focus: Brave New World ago!” she responded, flabbergasted. account! Who’s to say—” “How many procedures that were “Although this is a serious issue,” tedious ten years ago are now com- Dr. Cervantes said, cutting him short monplace? Imagine if a terrorist were even quicker in an attempt to regain “Are you proposing to assemble the 1918 influenza virus. control, “it’s for another time. What terrorists may have the Or worse! Imagine them getting a hold we are dealing with here is clearly not technology to synthetically of the nucleotide sequence of variola a clone of some previously subdued create their own viruses... virus! [2] They wouldn’t even need an virus. We still don’t know whether this [or] a designer virus, actual specimen to create an epidemic, even is a terrorist attack. It could just or a pandemic!” be an accident.” constructed specifically for A lanky man with thick spec- “That’s true,” Dr. Schmidt said. mass destruction?” tacles rose and began answering before “About a year before Wimmer’s poliovi- Dr. Cervantes could open his mouth. rus experiment, I remember some Aus- “Remember, Dr. Davis, that while it is tralians accidentally made an especially virulent mousepox. They were trying to improve a mouse contraceptive vaccine and instead created a virus that even killed mice that had been immunized or were treated with an antiviral drug. [3] True, mousepox doesn’t effect humans, but imagine a smallpox mutant!” Dr. Cervantes paused. Dr. Schmidt did have a point: What could happen “accidentally” if scientists started mak- ing whole new organisms from scratch? Even microorganisms—especially microorganisms—could have an un- foreseeable impact on the environment. Who’s to say tomorrow’s miracle bug won’t be an ecological plague next week? Is it irresponsible to carry this to the end, designing and creating syn- thetic organisms? [5] “Exactly!” Dr. Boots boomed. “What if we’re being presented, here, An equivalent research protocol may take six weeks from order to deliver with a designer virus, constructed spe- with synthetic genomics. (2) cifically for mass destruction?” easier than before to synthetically cre- “While that may be the case,” ate pathogens, it’s still perhaps easier Dr. Cervantes answered, “the relative to track down already existing virus complexity of synthesizing the virus strains, such as the 2003 SARS epidemic from scratch, paired with our still lim- virus, nearly eight thousand patient ited knowledge of how viruses work samples of which, by the way, may be and how the immune system responds, stored in hospitals around the world. leads me to think that that we don’t [2] Furthermore, viruses kept in labo- need to be concerned about the level of ratories tend to accumulate mutations sophistication you are suggesting. [2] to the point that they may not even be “Please recall how the researchers virulent any more by the time they are at the J. Crag Venter Institute synthe- released.”[2] sized M. genitalium back in January 2008. “But, Dr. Schmidt,” another It was the largest man-made DNA panelist interject quickly, “who’s to say structure at the time, with 582,970 base a terrorist would even take that into pairs, I believe. First they needed to se- fall 2008 • Harvard Science Review 11 valverde.indd 11 2/9/2009 11:24:55 PM Focus: Brave New World The five-stage process in M. genitalium production. (4) quence the correct native genome into tor to synthesize twenty-five groups of one hundred chemically synthesized four adjacent cassettes. These groups DNA cassettes of five thousand to were then assembled the same way “Synthetic genes seven thousand base pairs each.” [4] three at a time. These larger groups have been a boon to “It wasn’t even as simple as that,” were likewise taken and combined two interrupted a middle-aged Indian scien- at a time to get four assemblies, each white biotechnology, tist from the back of the room. “The approximately one fourth the size of facilitating research cassettes overlapped their adjacent the entire genome.” [4] in engineering plants neighbors. There was also a watermark “Yes,” said the speaker. “I think and microbes to inserted in cassettes 14, 29, 39, 55, and I have some notes on that as well… produce materials for 61 to distinguish the synthetic genome. Ah, yes. The process specifically in- To do this they inserted noncoding volved digesting the overlapping DNA which we now rely on sequences at intergenic sites because it molecules to expose complimentary petroleum, especially was unclear what biological effects may overlaps, which were then annealed. fuels.” result by synonymous codon changes in The joints were then repaired, and the coding regions.” 4 samples were subjected to field inver- “Yes, Dr.
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