Why Silicon Valley Keeps Getting Biotech Wrong

Last week, an article about Why Silicon Valley keeps getting biotech ‘wrong’ made the rounds, and concluded (boldface mine):

But the “move fast and break things” mantra that has helped Silicon Valley disrupt countless industries over the last two decades is more dangerous when applied to medical science. The roadblocks that health tech companies run into are not qualitatively different from the ones that all tech companies run into. But when Uber or Airbnb run afoul of their respective laws, the result is abstracted lost money out of someone’s pocket — the government, independent contractors, independent businesses, other segments of the market. When Airbnb keeps viable apartments off the market so they can be rented short-term to its users, the money can theoretically be remanded if someone determines that Airbnb is doing something wrong. The “things” being broken by the current generation of unicorns are regulatory regimes. (Valuable, useful regulatory regimes, to be sure.) The “things” being broken by health start-ups are laws of science and ironclad guidelines for research. When a health start-up “moves fast and breaks things,” it can directly result in the death, dismemberment, and injury of real people. You can’t un-kill someone who died thanks to a bad diagnosis (at least, there’s no start-up hawking that yet).

While I don’t think this is wrong, I think it’s very incomplete. There are two significant differences between biotech and tech. The first is that much of tech does is “abstracted” (to use the author’s phrase). It is a virtualization or a simulation of the real world. In the case of Facebook or Twitter, it’s a construction out of whole cloth of a virtual reality (one that obviously draws on actual reality). As such, the rules can be rewritten. Unless one collides with regulators or some physical reality (Pets.com learned the hard way that shipping heavy bags of dog food to different locations one at a time is really expensive), it’s a ‘Green Lantern economy’: your magic slide deck or elevator pitch can be translated into (virtual) reality with enough smart programmers.

But biology, like Honey Badger, doesn’t give a shit. A cancerous cell will keep on metastasizing, aging will still happen, and so on. It’s analogous to what I once had to tell someone coming to terms with a new diagnosis of Crohn’s disease: you can fool your family and friends, you can fool the doctor, but you can’t fool your intestine.

That brings me to the second difference: natural history matters. In the day job, I work closely with computer scientists, who, on the whole, are very, very smart people. But there have been multiple occasions where either what appears to be an obvious solution will be hung up on those stupid fucking natural history facts, or what appears to be a difficult problem can be greatly simplified due to the biology. To be successful at biology, you have to know things (or listen to the people who do). That is, biological expertise matters–and it often has grey hair as well, something Silicon Valley disdains.

Just two more reasons why I think Silicon Valley has had biotech problems.

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Links 4/25/17

Trump_startofdisastermovie
Links for you. Science:

This tech was meant to explore space. Can it also solve the mysteries of breast cancer?
Federal biomedical science policy under Donald Trump, nearly 100 days in
Why slashing the NIH budget is indefensible
A Cautionary Tale About Antibiotics
The war on science is war on America’s future

Other:

United Airlines Exposes Our Twisted Idea of Dignity (excellent)
The Russians are Hacking Us Again
The American Dream Is Killing Us
As D.C. families get richer, staggering disparities persist, report finds
Metro says it will activate free WiFi at 30 stations by year’s end (but have they fixed the air conditioning?)
Trump’s D.C. Economy Plans for Life Beyond Millennials
Neighbors
California senator gets called a sellout at town hall for saying she ‘isn’t there’ for single payer
The Violent Clashes In Berkeley Weren’t ‘Pro-Trump’ Versus ‘Anti-Trump’
They’re Coming for Elizabeth Warren
Road To Single-Payer: Understanding Different Universal Health Care Systems
Don’t lose sight of what really matters about Ivanka Trump
Americans are having less sex than they once did
Europe could have the secret to saving America’s unions (card check would help too. Got EFCA?)
Math Professor: Why Our Freshmen Need Remediation
Your Broadband is About to Get Much More Expensive

Posted in Lotsa Links | 1 Comment

The Waffling On Abortion Isn’t Sanders, It’s Coming From The Democratic Party

And that’s troubling to say the least. Put another way, what is good for the gander is also apparently good for the goose (boldface mine):

Top Democratic leaders said Sunday that their party welcomes people who are pro-life, despite the party being strongly defined by its support for abortion rights.

“Of course,” House Minority Leader Nancy Pelosi (D-Calif.) said on NBC’s “Meet the Press.”

I have served many years in Congress with members who have not shared my very positive, my family would say ‘aggressive’, position on promoting a woman’s right to choose,” she said. “But what you asked… was about what unifies Democrats. Our values unify us. We are unified with our commitment to America’s working families about job creation, about budget policies that invest in the future, good-paying jobs.”

Senate Minority Whip Dick Durbin (D-Ill.) said it’s fine if an elected Democratic official personally opposes abortion, but from a policy standpoint, he or she must support a woman’s right to choose.

“When it comes to the policy position, I think we need to be clear and unequivocal,” Durbin said on CNN’s “State of the Union.” “As long as they are prepared to back the law, Roe vs. Wade, prepared to back women’s rights as we have defined them under the law, then I think they can be part of the party.”

…Sen. Bernie Sanders (I-Vt.) went to Omaha last week to rally for Heath Mello, who is trying to unseat the city’s current GOP mayor. He said Sunday that he didn’t think the intraparty scuffle was that big of a deal.

“I have a 100 percent lifetime pro-choice voting record,” Sanders said on CBS’ “Face The Nation.”

“But if we are going to become a 50-state party, if you’re going to go to Omaha, Nebraska, which has a Republican governor, two Republican senators, all Republican Congress people, Republican legislature, you know what?” he continued. “If you have a rally in which you have the labor movement, and the environmentalists, and Native Americans, and the African American community, and the Latino community coming together, saying, ‘We want this guy to become our next mayor,’ should I reject going there to Omaha? I don’t think so.”

Sanders pointed out that Mello’s opponent is also anti-choice.

This isn’t Sanders, it’s coming from the Democratic Party (and one should note Democratic National Committee chairman Perez didn’t jump in and critique or disagree with Sanders*).

Before I continue, I want to make clear that what follows is an explanation, not a justification or an excuse. Personally, I think this is another doomed attempt by Democrats to play eleven-dimensional chess–or for that matter, two dimensional checkers–and it will blow up in their faces like Wiley E. Coyote with some Acme dynamite. But it’s essential to try to figure out why the Democratic establishment thinks this is the smart, despite anger from a significant rank-and-file (including yours truly).

Every so often, Something Happens that forces us that requires us to have another National Conversation About Race (that we typically don’t behave less racist as a result is an entirely different topic). But one would be led to believe that the Great Dividing Line is racism. Yet that’s not the case: as I’ve noted multiple times, Democrats get about a third of the white racist vote.

Re-read that last sentence and mull it over.

If you look at where the Democratic and Republican Parties are in 2017, that one out of three white racists would vote for the party that would, however imperfectly, attempt to weaken the effects of racism, is kind of amazing. While racism is important to many whites, opposition to racism is not a deal-breaker for many racists.

So how does this relate to the politics of abortion? I think the Democratic establishment believes that the red line for many voters isn’t racism, but abortion. Does anyone really think that one-third of voters who are strongly anti-abortion would support a pro-choice candidate? I would be surprised if ten percent of these voters would abandon their anti-abortion beliefs. What I’m guessing is that the Democratic establishment thinks there’s an advantage in downplaying abortion in order to entice some anti-abortion voters to switch to voting Democratic. At the national level, this might backfire, but, as Sanders noted, if the local Democratic-aligned groups like an anti-abortion candidate, should the national party interfere? How else do you win in white, conservative areas, when, at the state and local levels, the demographic advantage that Democrats might enjoy nationally simply doesn’t exist?

Like I said, I don’t agree with this. I think it’s bad political strategy and bad policy, but this is why I think the Democratic establishment is adopting this line.

*That Clinton’s vice-presidential running mate Senator Tim Kaine of Virginia went out of his way to support the Hyde amendment has been studiously ignored by Sanders’ critics. One might conclude that something else is going on with the Sanders-specific criticism.

Posted in Blastocyst Liberation, Democrats, Racism | Leave a comment

Links 4/24/17

Trump_callmybluff
Links for you. Science:

Unravelling why shoelace knots fail
The Knull Legacy
The Medical Uses of Maggots
Why the US science and engineering workforce is aging rapidly
Dingo Wins Competition for World’s Most Interesting Genome

Other:

Living by the Girl Scout Law, Even Without a Home
Are alley dwellings the solution to D.C.’s lack of space?
Push to expand free Metro rides in DC
A homeless family needed shelter. D.C. gave them bus tickets to North Carolina.
How not to create traffic jams, pollution and urban sprawl
Metro isn’t hopeless: Here are four realistic reforms the region could agree on.
When commuting in the D.C. region, distance doesn’t tell the whole story
Donald Trump’s Multi-Pronged Attack on the Internet
How Liberals Fell In Love With The West Wing (good, but I will restate my common complaint that liberal has become an utterly meaningless word)
Asian Poverty and the “Model Minority”
Carter Page Went to Moscow With a Tape of Donald Trump Offering Treason For Hacking (dunno, but I love publicly funded entertainment!)
Appalachia Needs Big Government
Bernie Sanders doesn’t need to pay for his socialist utopia
When Rising Seas Transform Risk Into Certainty
Why America should stop taxing corporations — and start seizing their stock
You’re Too Busy. You Need a ‘Shultz Hour.’
Merkin Patriot checks in

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Cherries, Close Up

Observed on 19th Street NW, between Q and Corcoran, Dupont Circle, D.C.:

Closeup cherries

Posted in Uncategorized | Leave a comment

What We Mean By ‘Antibiotic Resistance’: The Ciprofloxacin-Shigella Alert Edition

While the problem of antibiotic resistance is a common topic (and not just on this blog!), there is little discussion of how we actually measure it–and those details do matter. So before we get to a recent CDC alert–one all doctors, and not just infectious disease specialists, should be aware of–let’s review some stuff.

A common method to figure out if a bacterial isolate is resistant to a given antibiotic is to determine its minimal inhibitory concentration breakpoint, or ‘MIC.’ The bacterium is grown in a liquid broth, and then a small amount of this bacteria-laden broth is added to different sterile liquid broths, each of which contains a certain concentration of the antibiotic. The MIC is the lowest concentration that inhibits growth and is usually expressed in units of micrograms/milliliter (or grams/liter*). Obviously, I’m glossing over many technical details, but this is the basic idea.

So how do we know what MIC breakpoint to use? Well, we do TEH SCIENTISMZ! We correlate outcomes of infections with various strains’ MICs as well as use animal models and do a whole lot of pharmacokinetics. And MIC breakpoints are changed if we see treatment failures**.

Finally, one other thing before we get to the CDC alert, which is some bacterial taxonomy. As we’ve mentioned before, Shigella are really just a subset of E. coli***, which cause a lot of urinary tract infections.

So onto the CDC alert (I’ll translate into English; boldface mine):

This Health Advisory describes the identification of emerging Shigella strains with elevated minimum inhibitory concentration values for ciprofloxacin and outlines new recommendations for clinical diagnosis, management, and reporting, as well as new recommendations for laboratories and public health officials. Current interpretive criteria provided by the Clinical and Laboratory Standards Institute (CLSI) categorize these strains as susceptible to ciprofloxacin, which is a fluoroquinolone antibiotic and a key agent in the management of Shigella infections.

However, recent data from the Centers for Disease Control and Prevention (CDC) and state and local public health partners show that these strains often have a quinolone resistance gene that may lead to clinically significant reduced susceptibility to fluoroquinolone antibiotics. Clinicians treating patients with multidrug-resistant shigellosis for whom antibiotic treatment is indicated should avoid prescribing fluoroquinolones if the ciprofloxacin MIC is 0.12 μg/mL or higher even if the laboratory report identifies the isolate as susceptible, and should work closely with their clinical microbiology laboratory and infectious disease specialists to determine appropriate antimicrobial therapy….

CDC has identified an increase in Shigella isolates in the United States with minimum inhibitory concentration (MIC) values of 0.12–1 μg/mL for the fluoroquinolone antibiotic ciprofloxacin. Preliminary data suggest that all Shigella isolates with ciprofloxacin MICs in this range for which results are available harbor at least one quinolone resistance gene known to confer reduced susceptibility in enteric bacteria. Shigella isolates without a quinolone resistance gene typically have a ciprofloxacin MIC of ≤0.015 μg/mL. Current CLSI criteria categorize Shigella isolates with a ciprofloxacin MIC of ≤1 μg/mL as susceptible to ciprofloxacin.

CDC does not yet know whether fluoroquinolone treatment of a Shigella infection with a ciprofloxacin MIC of 0.12–1 μg/mL is associated with a worse clinical outcome for the patient or if such treatment increases the risk of transmission to other individuals. In Salmonella isolates, ciprofloxacin MICs of 0.12–1 μg/mL have been associated with reduced susceptibility, prolonged clinical illness, and treatment failures and are now categorized by CLSI as intermediate or resistant to ciprofloxacin in Salmonella species.

Fluoroquinolone resistance is of particular concern given that data from the National Antimicrobial Resistance Monitoring System indicate that many Shigella isolates with a quinolone resistance gene also are resistant to many other commonly used treatment agents, such as azithromycin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanic acid, and ampicillin. This susceptibility profile may encourage clinicians to prescribe fluoroquinolone antibiotics to patients who require treatment.

Several points:

  1. A strain can be called susceptible (sensitive), yet still have a resistance gene. This can either be a misunderstanding of what sensitivity is (i.e., the strain isn’t sensitive), or a potential problem in that the strain is one step closer to clinical resistance.
  2. We don’t know if Shigella isolates with reduced susceptibility to ciprofloxacin (i.e., the presence of a quinolone resistance gene and an MIC of 0.12–1 μg/mL) will respond differently than highly susceptible Shigella isolates (MIC =< 0.1 μg/mL). But in Salmonella, a relative of Shigella/E. coli this reduced susceptibility did lead to treatment failure (the patient was still sick after treatment). It’s worth noting that EUCAST, which determines breakpoints used in Europe, doesn’t bother to distinguish between E. coli/Shigella and Salmonella; they use the same breakpoints.
  3. Shigella that are resistant to ciprofloxacin are often resistant to other first-line antibiotics.

The CDC recommends that when confronted with Shigella infections, doctors should “not routinely prescribe antibiotic therapy for Shigella infection. Instead, reserve antibiotic therapy for patients for whom it is clinically indicated or when public health officials advise treatment in an outbreak setting.”

The CDC also advises that “[w]hen antibiotic treatment is indicated, tailor antibiotic choice to antimicrobial susceptibility results as soon as possible with special attention given to the MIC for fluoroquinolone antibiotics.”

You can read the full CDC report here.

By the way, maybe we should reconsider Il Trumpe’s proposal to cut CDC funding by twelve percent? Just saying.

*The use of grams/liter, “g/L”, is becoming more common place, as many ‘smart’ word processors and the like will autocorrect the mu symbol to “u.” Progress, or something.

**Oddly, though, it’s easier to get breakpoints changed for something not on patent.

***For the biologists, Shigella is both polyphyletic and paraphyletic. Because it’s an asshole.

Posted in Antibiotics, CDC, E. coli | Leave a comment

Links 4/23/17

Trump_Igraspscience
Links for you. Science:

Banning trans fats in New York prevented thousands of heart attacks, study finds
Tackling genomic data corruption with a new tool
Strategy of “inconvenience” may be the best way to boost vaccination rates
With this new system, scientists never have to write a grant application again (seems really easy to game, also the amounts are rather small)
Scientists Unearth Ancient DNA Depicting a Battle Between Viruses and Our Ancestors

Other:

Everything Is An Enormous Pain in the Ass (excellent)
The Elements of Bureaucratic Style: The bureaucratic voice presents governments and corporations as placid, apologetic, and unmovable. It also makes their victims as active as possible.
Video Evidence of False Claims Made in the White House Intelligence Report of April 11, 2017 by Ted Postol (Postol got the Star Wars chicanery right)
Donald Trump Is Making the United States an Anti-Corruption Laughingstock
Why You Can’t Have a Shorter Workweek
Why libraries could soon need a national endowment (or just real federal funding)
The Easter Sunday massacre in Colfax, Louisiana, and the awful Supreme Court decision that followed
“I’m Back in the USSR / You Don’t Know How Lucky You Are”
Pittsburgh Post-Gazette: “Medication Errors in Hospitals Don’t Disappear with New Technology.” Government: “It’s the Doctors’ Fault.”
ELEGANCE, WITH PAINSTAKING ATTENTION TO DETAIL (NO, NOT REALLY)
‘Journalism is becoming powerless’: Inside a nervous Turkish newsroom as the government closes in
Airlines Treat People Like Dirt Because the Republicans in Congress Let Them
The public only thinks it likes low inflation
Bowser Budgeted $1 Million For Statehood. Here’s How She Wants To Spend It
Towards Democratic Regulation of the Airline Industry
After hyping itself as antidote to fake news, New York Times hires extreme climate denier
A Feminist Case Against Kosher Wine

Posted in Lotsa Links | 4 Comments