A disclaimer: This post is partly a test of my ability to embed Youtube videos. 

A couple of posts back, I listed a few books I thought were worth their salt*. Now I'm moving on to a few videos that are a little more contemplative (it may be arrogant, but one of the refrains that's evolved from this blog is a provocation of thought and direct discussion on disparate topics). 

First up is John Oliver's treatise on retirement plans. I have previously written in detail about the evils of investment advisors. Oliver covers the same basic points with far more humor than I was able to bring to the topic. If you couldn't parse through my post, consider watching this video. 

Next up is a video from Prager University. From the estimable Mike Rose of Dirty Jobs fame, the topic tackled is why you shouldn't pursue your dreams. Those of you who know me would (correctly) assume that I would vehemently reject almost everything the ultraconservative Prager University has ever put out. Thus, it was somewhat surprising when I found myself strongly agreeing with the premise of this video: find something you're good at, then figure out how to make money doing it.

Lastly, I couldn't go ten seconds without a science video. This is an oldie-but-a-goodie - the high def animation of cellular processes are reasonably accurate insofar as I can tell. It's enough to make a jaded old science monkey like me shut up for a few minutes and enjoy the ride. This originally came from the biovisions group at Harvard, if you're interested in attribution (I've linked a sketchy Russian account version here that cheats by telling you what's happening in some of the processes). The score for this pretty amazing as well. 

OK, that's what's in my virtual bag of treats at the moment. 

*If you're interested in another good book, try Boss Life. Nonfiction, written by a guy who spent the last 20+ years running a company that makes custom conference room tables. The book is the day-to-day operations for one calendar year. Sounds boring, right? That's what I assumed, but nothing could be further from the truth. The guy's business nearly collapses three times during the year (once due to a tiny glitch with Google Ads!) and the vacilations between feast and famine are amazing to watch. As a british soccer announcer once said, "it's like living on the edge of a lightning bolt." I'd highly recommend reading this, especially for someone who's one day thinking of starting their own business. 

Time to write a post for people considering working for a start-up. I did this once upon a time. It wasn't a great experience, but that's a story for another day. 

Unlike a bigger companies, there's often very little information on start-ups. The average applicant has little idea what to expect and - if they're new to the sector - what questions to ask. 

Knowing what to ask is critically important for a start-up employee. You will be working at a discounted rate (i.e., lower salary/benefits) in exchange for stock options. Generally (and I'm oversimplifying a bit) your options will be granted at the current valuation (see note). If the company goes public and/or is acquired, your options will be worth the difference between the strike price (the price the options were granted at) and the sales price or current value. For example, if you get 1,000 shares at an 11 dollar/share valuation and the company does an IPO where the shares settle at 25/share, you can sell your shares for a profit of $14,000. If the company goes out of business or the share price is lower/equal to the strike price, you get nothing. Essentially, you are gambling on the small chances of a big payoff against the certainty of lower compensation in the near-term.  

The only other advantage of start-ups is the fact that you will be, to some degree, an early employee. If a company rapidly expands, a literal pyramid of employment will likely be built below you. Thus, rapid advancement is possible, but only if you're in the right place at the right time. 

Side note: I'm not saying not to work at a start-up. Just understand the risks and rewards before jumping into the pool. To help with this, I wrote some questions and pointers I wish I'd had a decade ago. 

Who is funding you?

Ideally, you want a reputable venture capital firm (or more than one) along for the ride. For what it's worth, VC's are pros who have some skill at identifying what will work (or at least have a fighting chance). 

How many rounds of fundraising have you gone through? 

Companies raise money in multiple rounds. Ideally, the value of the company goes up each round. Employees shares are often diluted (lose value) with subsequent rounds). Also, a "down round" (where the company's value diminishes) is a serious warning sign that things are not rosy.

Am I a new hire or am I replacing someone who's left?

In effect: Is the company growing actively? I asked this one, but ignored the fact that I was replacing a guy who'd quit and fled to greener pastures. 

What are the metrics for successful stage-up?

In biotech, there will be milestones in place to demonstrate you are progressively marching towards a successful tech/product/whatever. This is a schedule that closely matches when a company runs out of money. If you learn what you need to do and when you need to do it by, your expertise should give you 

What are the long-term plans for the company?

You're asking if they are aiming for an IPO or planning to be acquired. Being acquired is, surprisingly, often the goal, especially for single-product companies. 

Other pointers:

Is the person interviewing you letting you interact freely with the other employees, or are they trying to keep you away from them? Any place that won't let you meet potential co-workers (especially those you interact directly with) is showing you a danger sign. 

Do you like the boss? At a small company, the boss is essentially the office god. He has ultimate power and there's nowhere to go to escape him. If you get a bad vibe, time to go. 

Look at the equipment and space. Is it decent (not luxury stuff, necessarily, but sufficient to do the job) or is it a mismash of other people's junk? The latter can suggest acute money problems. 

Are there experienced people working there who - in your opinion - could be making more somewhere else? Yes = good sign. Obviously, if it appears you're surrounded by the D-team, you might want to ask yourself why. 

Most of all: If there's even the slightest blank look or hesitation in answering any of the questions I listed, get the fuck out of there and never look back. ​

Note: How are companies valued? If the company raises $1 million from investors for 10% equity, the company's valuation is $10 million. Note that this is not necessarily what the company is worth. 

I love to read. I don't have the time or energy to do really elaborate book reviews (book reports, anyone?), but I wanted t share a few books I've recently gone through that aren't written by really famous authors. Take 'em or leave 'em.

A Higher Call
Nonfiction

On its first mission over Nazi Germany, a damaged American bomber is trying to limp home, engines failing and half its crew dead or wounded. As it approaches the coast, a German fighter appears on its tale. Instead of shooting down the helpless airmen, the fighter's pilot escorts them to safety. Years later, both sides of the story are told in an amazing story of the air war in World War Two. After reading the book, I'm surprised any German airman survived the war. 

The Art of Racing in the Rain
Fiction

A bittersweet story written from the exclusive perspective of the family pet. I am not a racing fan, but the author combines a significant amount of moral philosophy with autosports in a wholly unique way. I heard this was getting made into a movie. I cried at the end the first time I read it and the second. Susan one-upped me by crying at the end of the first chapter. Seriously, if you can get ten pages into the book, you'll know whether you want to read the rest. A note: after Reading TAORITR I checked out some other stories by the author. So far, he's a one-hit wonder. 

The House of God
Nonfiction (mostly, I think)

Written by a classmate of Michael Crichton's when they were both in medical school in Boston, the book tracks the intern year of a new doctor in the late 70s. The book is to modern medicine what One Flew Over the Cuckoo's Nest was for modern psychiatry, and was of significant impact on reforming how the medical system delivers care and views patients.

It appears I've stolen the image from the German edition here. 

Ready Player One
Fiction

This is being made into a movie by Stephen Spielberg. Read it before everyone else does. It's a near-future SciFi that's a combination of Charlie and the Chocolate Factory and The Matrix. Sort of a scavenger hunt in a virtual world, with a little real-world intrigue thrown in as well. Interestingly, there's also a tremendous amount of 80s and 90s nostalgia for geek culture, which is a topic you don't see too much about these days. Another possible one-hit wonder author. 

Shadow Divers
Nonfiction.

Hat tip to my good friend friend (and Bloomberg Reporter) Andrew Harris (his blog here) for turning me on to this one. A group of deep water diving enthusiasts discover a previously undiscovered German U-boat sunk off the coast of New Jersey. Book focuses on the quest to identify the boat. Very cool real-world adventure story.

Disrupted
Nonfiction. 
​
Written by one of the writers of the HBO show Silicon Valley. The former tech editor of Newsweek is laid off and finds himself, in his early 50s, working at one of the tech start-ups he used to report on. Interesting look into the tech bubble that's been forming in Silicon Valley for some time now. 

And I'm spent.

Science post, folks. Just stop now if that's not your groove.

Yesterday Forbes re-listed the net worth of one member of their richest women in the world. Well, formerly one of the richest women in the world. Elizabeth Holmes, the founder of the embattled biotech Theranos, had a net worth estimated at 4.5 BILLION dollars last year, based in large part on her controlling interest in her company which carried a 9 billion dollar valuation. Forbes has trimmed back that net worth estimate to... well, zero. This reflects the new valuation of the company at 800 million (the 750-ish million raised plus a modest amount of intellectual property - whatever that says for the people valuing companies, it ain't good). With the investors preferentially getting back their seed money, that leaves just enough for a cup of coffee for the person who was recently one of the richest self-made women in the world.

What's striking is how drastically public perception has shifted towards the once-darling company. Here is an article about Theranos from a couple years ago. You can almost wipe the admiring drool of the author off of it. Here is an article from last week. One of many, actually. 

Those of you who follow my Facebook posting know that I've been a critic of Holmes and her company for some time. I first learned of her existence through one of those stupid "A Mighty Girl" posts that get forwarded around Facebook. I thought it dubious that a college dropout with no scientific training could invent a revolutionary blood testing machine and create a company worth billions by the age of 32. 

So I dug into it. Theranos, for those not familiar, is a blood testing company whose technology is based on combining two ideas: miniaturization and multiplexing (running multiple tests on the same amount of blood). The idea was that the patient should go to a drugstore or health center and provide little more than a drop of blood. The company claimed they'd invented a machine (which they had the gall to call 'The Edison') that could run something like 250 tests on a single droplet. Makes for a nice-sounding headline, yes? 

To outsiders, the idea was apparently revolutionary - venture capital poured in and valuation soared. As a scientist, my reaction was no shit. Scientists already do this all. the. time. in routine research techniques. Miniaturization isn't particularly special either. I regularly work with fluid volumes in the single microliter range (there are about half a million microliters in a can of coke). 

What would make or break the company wasn't the idea but the technology. How would the company accomplish this in a way that eclipsed existing methods? Interestingly, this was the part Theranos was most secretive about. You'd think with patents filed the company would be eager to show off their fancy, cutting-edge technology. But the company remained mute, even when they were sitting on a giold mine in the form of a multi-billion dollar valuation.

Always be wary of a biotech company that won't let you look up their skirt after signing a nondisclosure agreement. 

But back to the narrative: Even though I wasn't privy to proprietary information, it didn't mean it that didn't exist - surely venture capital firms had seen the technology up close before forking over hundreds of millions of dollars. Surely Walgreens had performed due diligence before entering into a partnership to use the Edison to analyze samples in their stores. 

Turns out... not so much. Once the first infusion of venture capital was made, other investors apparently thought the technology was sufficiently de-risked to invest. Maybe they forgot that the first VC to give Holmes money was a close family friend. Elizabeth Holmes was just 19(!) when the first million rolled in. Years later, Walgreens rushed into a partnership in part to prevent CVS or another chain from snatching away the deal. Oops. 

Turns out I wasn't alone in my suspicions. The WSJ reported the story as well, though they arrived there through an entirely different route - one of the principal scientists of the company committed suicide; the man's widow tipped a reporter that there were big problems with the company. From there things unraveled famously - the Edison machine, to make a long story short, didn't work as intended. Theranos was using machines from other companies to run most of their tests. When they did use the Edison, the results were often substantially off (a consequence of poor design or the forced dilution of the samples). They faked results, covered things up, yada yada yada. Under harsh external scrutiny triggered by the WSJ article(s), the company has rapidly crumbled into dust. Currently, several members of the executive board are facing the specter of criminal charges.

Theranos lasted more than a decade before it hit the skids. I'm shocked it lasted as long as it did - the whole affair was a lie that just got bigger and bigger. 

But I'm not writing this to say ""I told you so. There's more to Theranos than a cautionary tale. Like the mortgage bubble, it's easy to lay this on a few unscrupulous individuals and forget that millions of other people bought into a fundamentally flawed concept. In this case, there were loads of VCs, media, and even scientists who signed off blindly on unsubstantiated, shit technology. Particularly members of the media, whose job it is to scrutinize the facts. Much of the steam that Theranos gathered came by dint of favorable reviews of a wunderkind who dressed like Steve Jobs. I increasingly find that reporters - even science reporters - are drawn into credibly reporting terrible, terrible stuff all the time (remember when the Raelian cult cloned a human?). Often, it's innocuous, easily-forgetten mistakes; a report on a press release from a shitty academic group that oversells a fairly mundane finding (these are the sources of many of those optimistic 'we're two years from curing every kind of cancer articles' you see about in the paper). But other times, they buy into a start-up that's trying to use publicity to raise money like Theranos. I've taken to calling this Biohype. 

I've been waiting to publish this article until I had a good current example in the news. That happened recently when I  saw this classic biohype story today on Youtube. The narrative is a classic nonstory. A company received permission from an Institutional Review Board to inject a mishmash of stem cells and trophic factors into the brains of brain-dead patients, ostensibly in an attempt to reanimate them. 

Scientists Aim to Reverse Death!!!

Makes for a catchy headline, no? Problem is, this is a probably (and I only qualify this for legal reasons) bullshit company that at best has no idea what it's doing and at worst is an active scam. Check out their website. The group's raison d'etre seems to be, well, a lizard can regrow a limb; let's just blast the same shit into a human's brain and see what happens. It's a different, vastly more complicated organ in organ in a distantly-related species, but fuck it. I'll say this in plain english: There is no basis whatsoever that this approach will work. 

Time for a hard truth: maybe in 50 or 100 years we'll be able to help brain-dead people, but not anytime soon. Protect your head. Bioquark, if they're able to get the money to do this, will torture 20 families who will furtively believe this non-treatment will bring their Grandpappy back after a major stroke.

Maybe you think I'm too skeptical. Maybe you think that I'm not in a position to judge other scientists. Maybe they - gasp - just know a little more than me. Maybe I'm harping on them because I'm jealous. 

So let's take a look at the crew attempting to reanimate the near-dead. Their CEO, Ira Pastor, last engaged in scientific training in 1991, when he got an BS in pharmacy from Rutgers. Their CSO, Sergei Paylian doesn't even have a PhD and has a degree from Armenia, which, last I checked, was not a hotbed or research on anything. His last recognizable job before Bioquark was a visiting scientist at the University of South Florida. I strongly recommend checking out their executives page for an example of the kind of people this enterprise has drawn. You can see their "executives" are a mishmash of ill-qualified misfits who either don't know that they're the D-team or don't care (though I will say that their VP of aesthetic medicine looks like Angelina Jolie). 

Yet, amazingly, reporters take them seriously. Even this non-story (the press release is that the company got approval to inject their crap into almost dead people). There are no results, no real scientific information. Just stupid ideas and paperwork. 

Here's another thought: This could be done in animals, mice or nonhuman primates. We could aggressively determine what, if anything, worked by immediately sacrificing the animals and analyzing their brains. Why is Bioquark rushing this into humans? Biohype. And money. The fact that I struggled to find even a single scientific article on the company's website suggests this is nascent tech at best. Perhaps no one has ponied up to do this experiment in mice. However, if you announce you're swinging for the fances by jumping straight into humans, it only takes one rich guys with a vegetable relative to put them in business. All for waving their hands and promising the world to desperate people. 

The really scary thing is that this thing could scale, if the media really sinks their teeth into it. If a few angel investors read the story and throw a few bucks Bioquark's way, the whole sketchy crew might get rich quick before the whole thing implodes. The ride can last for years - just ask Lizzy Holmes. All because of Biohype.