At its height back in 2000, the U.S. cash equities trading desk at Goldman Sachs’s New York headquarters employed 600 traders, buying and selling stock on the orders of the investment bank’s large clients. Today there are just two equity traders left.
Automated trading programs have taken over the rest of the work, supported by 200 computer engineers. Marty Chavez, the company’s deputy chief financial officer and former chief information officer, explained all this to attendees at a symposium on computing’s impact on economic activity held by Harvard’s Institute for Applied Computational Science last month.
Web users searching for photos and cops looking for suspects in video already benefit from software that understands the content of images. Chris Gibson says it can also make it easier to find treatments for diseases not targeted by existing drugs.
“By combining robotics and machine vision, we can work at large scale on hundreds of diseases simultaneously, using a small number of people,” says Gibson, who is CEO and cofounder of the 40-person startup Recursion Pharmaceuticals.
Recursion uses software to read out the results of high-throughput screening, which automates drug testing in cells. That isn’t a new idea, but Recursion uses algorithms that inspect cells at an unusual level of detail. The software measures a thousand features of a cell, such as the size and shape of its nucleus or the distance between different internal compartments.
Americans seem to be forever undergoing a “crisis” of civility. Year after year, we’re told that the norms dictating decent behavior are eroding; that we’ve lost sight of the basic regard we owe our fellow participants in public life; that the contentiousness of our culture threatens to undermine our democracy. Worrisome stuff, of course — but a little vague. If, as any historian will tell you, people in all times and places have been alarmed by this development (the ancient Romans called it pugna verborum, or “the battle of words”), you might wonder how urgent, or even actual, the trouble really is. Then there’s the problem of definition. One man’s civility is another man’s repression. Were the Act Up protesters in the 1980s so indecorous as to disqualify themselves from political conversation, as their critics charged? Or were they the ones demanding civility, in the form of simple recognition of the lives of people with AIDS? Is Donald Trump dangerously boorish? Or is he, too, resisting an ersatz decorum, one he and his supporters call “political correctness,” which they claim honors the feelings of everyone but the beleaguered white working-class male?
One response to these complexities is to abandon the quest for civility, deeming it a historically fanciful, hopelessly imprecise ideal. Another response, exemplified by the political scientist Keith J. Bybee’s slim and artful treatise HOW CIVILITY WORKS (Stanford Briefs/Stanford University, paper, $12.99), is to suggest we continue to fight for civility but learn to think of it less romantically. Given how nasty and intractable the conflicts in our society can be, Bybee argues, it is naïve to imagine we can somehow transcend our clashing sets of values and miraculously agree on what counts as acceptable behavior and tolerable opinion. After all, if we could find common ground on something as fundamental as that, we wouldn’t have the sort of nasty and intractable conflicts we call on civility to manage in the first place. For better or worse, we must accept that civility “does not exist outside of politics as an independent force,” Bybee writes, but rather is just as much the “subject of political struggle” as everything else.
The biological advantages of something like CRISPR–Cas are clear. Prokaryotes — bacteria and less-well-known single-celled organisms called archaea, many of which live in extreme environments — face a constant onslaught of genetic invaders. Viruses outnumber prokaryotes by ten to one and are said to kill half of the world’s bacteria every two days. Prokaryotes also swap scraps of DNA called plasmids, which can be parasitic — draining resources from their host and forcing it to self-destruct if it tries to expel its molecular hitch-hiker. It seems as if nowhere is safe: from soil to sea to the most inhospitable places on the planet, genetic invaders are present.
Prokaryotes have evolved a slew of weapons to cope with these threats. Restriction enzymes, for example, are proteins that cut DNA at or near a specific sequence. But these defences are blunt. Each enzyme is programmed to recognize certain sequences, and a microbe is protected only if it has a copy of the right gene. CRISPR–Cas is more dynamic. It adapts to and remembers specific genetic invaders in a similar way to how human antibodies provide long-term immunity after an infection. “When we first heard about this hypothesis, we thought that would be way too sophisticated for simple prokaryotes,” says microbiologist John van der Oost of Wageningen University in the Netherlands.
Mojica and others deduced the function of CRISPR–Cas when they saw that DNA in the spaces between CRISPR’s palindromic repeats sometimes matches sequences in viral genomes. Since then, researchers have worked out that certain CRISPR-associated (Cas) proteins add these spacer sequences to the genome after bacteria and archaea are exposed to specific viruses or plasmids. RNA made from those spacers directs other Cas proteins to chew up any invading DNA or RNA that matches the sequence (see ‘Lasting protection’).
How did bacteria and archaea come to possess such sophisticated immune systems? That question has yet to be answered, but the leading theory is that the systems are derived from transposons — ‘jumping genes’ that can hop from one position to another in the genome. Evolutionary biologist Eugene Koonin of the US National Institutes of Health in Bethesda, Maryland, and his colleagues have found1 a class of these mobile genetic elements that encodes the protein Cas1, which is involved in inserting spacers into the genome. These ‘casposons’, he reasons, could have been the origin of CRISPR–Cas immunity. Researchers are now working to understand how these bits of DNA hop from one place to another — and then to track how that mechanism may have led to the sophistication of CRISPR–Cas.
The first results of a high-profile effort to replicate influential papers in cancer biology are roiling the biomedical community. Of the five studies the project has tackled so far, some involving experimental treatments already in clinical trials, only two could be repeated; one could not, and technical problems stymied the remaining two replication efforts.
Some scientists say these early findings from the Reproducibility Project: Cancer Biology, which appear tomorrow in eLife, bolster concerns that too many basic biomedical studies don’t hold up in other labs. “The composite picture is, there is a reproducibility problem,” says epidemiologist John Ioannidis of Stanford University in Palo Alto, California, an adviser to the project whose attention-getting analyses have argued that biomedical research suffers from systemic flaws.
But others say the results simply show that good studies can be difficult to precisely reproduce, because biological systems are so variable. “People make these flippant comments that science is not reproducible. These first five papers show there are layers of complexity here that make it hard to say that,” says Charles Sawyers, an eLife editor and cancer biologist at Memorial Sloan Kettering Cancer Center in New York City.
The ability of custom-made microbes to sense the environment and make biological molecules would be particularly valuable for devices that work inside the body, says William Bentley at the University of Maryland.
“If you want to discover what’s going on in the gastrointestinal tract or the oral cavity, if you can connect to electronics you have a way of interpreting what’s going on and you may be able to manipulate it,” he says.
For example, a device could use an organism to sense chemicals produced by harmful bacteria in the body and secrete an antibiotic when it detects them.
To get specific genes in bacteria to respond to electrical stimulation, Bentley’s team took advantage of what are called redox molecules. These biological molecules are found in all cells and can pick up and pass on electrons. They are said to have a reduced state when they gain electrons, and an oxidised state when they lose electrons.
The team also made use of naturally occurring genetic components in E. coli that respond to oxidative stress, which occurs when too many molecules in the cell are o apply electrical input, the researchers submerged an electrode in a liquid containing the bacteria. When the electrode supplies a positive charge, certain redox molecules get oxidised and trigger the genetic mechanisms that respond to oxidative stress.
Most organizations would be happy to last for centuries, as the Venetian Republic did. From 697 to 1797 AD, Venice’s technological acumen, geographic position, and unconventionality were interlocking advantages that allowed the Most Serene Republic to flourish. But when change comes suddenly, it can turn strengths into weaknesses and sweep away even thousand-year success stories.
Venice’s military technology and the city’s pivotal location on the main trade routes of the time gave Venice several strong, mutually reinforcing advantages.
The Arsenal, an advanced naval munitions factory that anticipated by several centuries the production-line method of manufacture, was the beating heart of the Venetian naval industry. From the thirteenth century on, the Arsenal nurtured creativity and spurred innovation and entrepreneurship in the construction of its galleys.
The city’s geographic location helped it to defend itself from both land- and sea-based invaders. This location, consisting of a series of islands in a marshy lagoon, also pushed it to develop a (then unusual) trading and moneylending economy, since there was little land to support agriculture. And its position at the top of the Adriatic Sea allowed it to become a vital trading hub, connecting the East with the West via the Mediterranean.
If, as Michael Porter wrote, competitive advantage stems from how “activities fit and reinforce one another….creating a chain that is as strong as its strongest link,” then strategic fit is something that the Venetian Republic had in spades.
But, like a lot of successful entities, Venice reached a point where it focused more on exploitation than exploration: Venetian traders followed existing paths to success.