OopsCriticality

I decided when I heard about the maple water fad that if I ever Break Bad, I'm going to sell snake oil patent medicines to the Whole Foods crowd. Walking down their alternative medicine section was… inspirational. I especially liked the colloidal silver[1].

[1] https://en.wikipedia.org/wiki/Argyria

I did my PhD work on colloidal semiconductor quantum dots right at the peak of the nano fad. I would say that popular buzz doesn't help or hurt, it's mostly noise. Academically, we're expected to spend some time on outreach, so if your field is in the public eye at the moment it does make outreach easier.

Believe it or not, the hype among scientists was even worse than among the public, to the point of (in my opinion) hurting good science. Everyone was shoehorning "nano" into their proposals, regardless if their work was legitimately nano[1], and that really hurt the SNR for manuscripts and grant proposals.

[1] I define nanotechnology as dealing with something sufficiently small to access properties not seen in bulk materials. For many materials, restricting one or more dimensions below 100nm will lead to side-dependent properties. There was a lot of stuff during the Great Nano Hype that was claimed to be nano, but was say 500nm—that would be "submicron".

By that logic, physics is merely an ersatz subsidiary of mathematics, therefore technological progress mostly relies on discoveries made in mathematics.

Obligatory xkcd: https://xkcd.com/435/

> Technological progress mostly relies on discoveries made in physics.

I couldn't disagree more. Take the Haber process as a counterexample from chemistry, or vaccinations as a counterexample from medicine.

The charging cables do lock on many electric cars: some models unlock when charging is done, others only when the doors are unlocked.

Of note, this paper is based on data from only two volunteers (a third was used to exclude THCA-A as a cofound).

Track record of results, corporate memory, facilities, and the collective wisdom and experience of the fellows.

YCR could be the same, one day. Nevertheless, it's a very long and perilous road from YCR the proposal, to Bell Labs 2.0.

Publication means peer-reviewed and scholarly. Yes, a publication in Nature, Cell, Science, NEJM, etc. opens doors, but so do publications in discipline specific journals (like JACS). What matters is that one's papers be read and cited.

The system is far from perfect, but I don't think you'll find anyone in academia saying otherwise. I think of it being like Churchill's quote about democracy being the worst form of government, except for all the others that were tried.

Publications and grants are the currency of academia: if one doesn't have a recent publication record, a hiring committee doesn't have a way to gauge one's performance and capabilities as an academic; if one doesn't have a history of getting grants, a hiring committee will be (rightfully) skeptical of one's ability to bring in money. Excepting teaching schools, one is hired for one's abilities as an academic researcher to bring prestige (through publications and PR) and secure grants (along with that sweet, sweet F&A money). To get grants, one needs publications and preliminary data. One also needs grantsmanship skills, and one only gets those from direct experience.

A YCR "fellow" (or whatever it'd be called) would probably not be a competitive candidate for an academic position. It's not because they weren't in academia, it's because they will likely not have the work product used to measure performance in a academic setting. A hiring committee is not going to risk department funds on someone with a non-existent track record when there's a line out the door of other candidates.

I think OP is correct in perceiving that selecting YCR would probably close the door to a future in academia. I will also predict that YCR will have difficulty hiring top academic talent.

That's hardly a portable solution considering that California has 4 National Labs when most states are lucky if they have even one.

The model year 2005 Camry in question from the trial would have been made available in 2004, and the electronic throttle control system was designed prior to 2004 (IIRC, the ETC design was carried forward from the previous model). How does it makes sense to apply MISRA-C:2004 in this case, especially when the Toyota ETC in question was admittedly not designed under MISRA-C:2004 nor prior MISRA-C revisions?

It is inaccurate to claim Michael Barr determined the cause of Toyota's unintended acceleration: he proposed a possible failure mode that was persuasive to a lay jury. His proposed failure mode didn't leave a DTC, so there's no way to actually know if his proposed failure mode actually happened in this case (or in any other).

I didn't realize that that Peter Seibel (author of Practical Common Lisp) worked at Twitter. Neat.

The article is pretty hand wavey, although the point made feels to be along the right lines; I'm left wondering what data supports the claims.

In Top Gear's tribute to Saab, Clarkson said that a senior designer friend at "another Sweedish car company" told him that no one could figure out why Saabs cost as much as they did, until they crash tested them.

The regulatory approval pathway for a combination drug/device platform, with a automatic clinical decision component, is a nightmare.

Assume one did create the device, and got it to work across a wide patient population with varying diets, disease severity, treatment responsivity, etc., and then (somehow) got approval for it. Existing insulin pumps are already challenging to get reimbursed under insurance, and they have a more straightforward regulatory approval path with lower R&D costs. The super pump would need to be reimbursed for quite a bit more money to justify the increased R&D costs. That is going to be a very hard sell under quality of life improvement alone—clinical data showing an improved patient outcome or decreased long-term healthcare costs is what is needed. You're benchmarking against existing pumps with separate monitors, which sets a high bar.

I sure hope not.

This is an interesting personal project, but it is far from how medical devices should be (and are) developed. Where is the risk analysis, for example? Or the FMEA? Was the software developed under ISO 62304? Etc.

There's a lot of activity that happens in a regulated industry that is completely missing here, which is why I see this as a poor example.

Because there is no clinical evidence for the survival benefit of total pancreatectomy over a Whipple.

There's absolutely nothing simple about surgery when the pancreas is involved.

I'm fairly certain editing sperm or eggs is going to be even more challenging than an embryo---think of the effects of meiosis alone.

Contrast your prediction of elective eugenics for offspring with my own for autologous bone marrow transplants for sickle cell anemia: sickle cell is a single point mutation, there's a lot of tissue that we can sequence and work with, you don't need to transform anywhere near 100% of the tissue to get a good therapeutic effect, and we already do cure sickle cell anemia with bone marrow transplants given the right circumstances. All of that is in part why I think you are completely wrong with your prediction.

Have you tried Cabelas, Duluth Trading, or Filsons? They do a good job for me, and it sounds like we have similar pants sizes. I bet you also have the same problem as I have with non-tall shirts: they're always too short in the torso and sleeves when they're the "right size" instead of baggy.

It's not just you.

If you skim through the comments on what they're calling "Cars Technica" articles, you'll find heavy criticism (especially on the earlier articles), some of which is along the lines of native advertising or sponsored content allegations---not helped by Porsche and Audi being advertising partners. The Ars writers and editors are however on record saying that they are absolutely not using native advertising or sponsored content (except when there is a clear banner declaring so).

Personally, I find that the further Ars gets from it's traditional domain of computers and consumer tech, the worse the quality of the article. In the case of the automotive articles, I don't think the editors or writers have sufficient subject matter expertise to write the well-informed articles that are common for Ars' computer and consumer tech coverage.

> My layman's understanding of the situation is that the most likely first use of this in humans will be for personal eugenics of one's offspring. Meaning, removing deleterious genes from, or adding beneficial ones to, your sperm or egg cells in a lab and then implanting an embryo.

My non-layman's prediction is that you are quite incorrect. As others are pointing out, successfully using CRISPER/Cas is hardly as trivial or as easy as the media's hype machine (or university PR offices) would like us to believe. Blatantly obvious ethical issues aside, embryos are hard to tamper with, and the odds of successfully achieving multiple edits to the genome are miniscule.

I think the most likely first application of the CRISPER/Cas system in human medicine will be in an autologous bone marrow transplant to correct a genetic disorder of the blood, likely sickle-cell anemia.

In the more familiar unit of "swimming pools", it looks like it might be around 10.

> that still leaves 24 million pounds of lead each year from car batteries that don't get recycled

Is that actually a lot? Similar statements are made with respect to nuclear waste, but frankly, I've regarded these statements in units of mass as deliberately misleading due to nuclear waste (or lead in this case) to be uniquely dense relative to what we are accustomed to dealing with on a daily basis.

Siri, via Wolfram Alpha, says that 24 million pounds of lead is about 33,900-ft3, or a cube of 32-ft a side. If correct, that doesn't feel like a lot considering this is framed as a the global lead acid car battery recycling waste.

This has been a great series: clearly written, solid examples, and obvious utility. Thanks for doing it!

What about RTP?

Honestly? The pattern of biotech groups that YC has invested in, signals that YC is in over its head. They're the sort of selections that smart people would make, but not the sort of selections that smart people with domain experience would make.

You reference Gingko, but that company is (in my opinion) uniquely viable in terms of YC biotech investments.

Of course, my perspective is based on media reports (famously unreliable), by public information, and by my own experience in biotech. I would love to be completely wrong, and I could easily be completely wrong since I don't have access to the information that you do. Also, maybe an outside perspective is what is needed in biotech—good things happen when smart people from other disciplines cross-pollenate. Also, my own startup is not yet successful, so I criticize from within a lovely glass house surrounded by stones. That said, based on what is public, I don't have confidence in YC's biotech investments. I am hesitant to even consider applying, given with what is publicly available.

I don't think this is an appropriate forum to be specific with criticisms, nor do I wish to be a "negative Nancy" with YC's new push—if YC could do a fraction of what it did in software in the biotech area, it'd be amazing. I would however like to offer one particular outsider's perspective.

That's an interesting thought, SBIR then YC. How would you recommend dealing with the SF relocation issue? I ask from the prospective of a biomedical startup not in CA.

With respect, there is a large gap between the letter of the law and the spirit of the law. Yours is a good example: using a gene gun may not be regulated in the US at present, but as was pointed out in a Nature piece covering the controversy around your company [0], that may not hold for the future [1]. My experiences with the FDA, and I have reason to believe they hold true at the USDA, lead me to conclude that regulators are fickle. What is the plan for when Monsanto, seeing your early success, copies your business plan and regulators respond to their terrified constituents in order to "fix the glitch"?

Trying to move fast and break things in a regulated industry strikes me as producing fragile business plans, at best.

[0] http://www.nature.com/news/glowing-plants-spark-debate-1.131...

[1] http://www.nature.com/nature/journal/v475/n7356/full/475265b...

G. I. Taylor did it better!

See around the 13 minute mark: https://www.youtube.com/watch?v=51-6QCJTAjU

So you're looking for a class of problems that you can better address than the existing system? Something for which SBIR/STTR takes too long to fund, needs more money/support than self bootstrapping, doesn't need exotic equipment, etc.

Sure, but I was thinking more along the lines of the SBIR/STTR-based incubator ecosystems at major research universities. They too have good advice and a strong community, and also have more domain experience, rentable high-end lab equipment, proper wet lab space, clean rooms, contract personnel, regulatory consultants, industrial hygiene assistance, etc. I don't understand (but would like to) what the value proposition of YC is over a good university incubator---superior general business advice? (I could easily see that!)

Apologies, my original post was incompletely expressed.