Is your business idea unscalable?

Jon Westenberg:

There’s a lot of pressure put on young entrepreneurs. It’s the pressure to only build scalable startups, rather than focusing their efforts on any other type of business. You can see this almost everywhere. If you’re not building high growth software or platforms, you’re seen as wasting your time.

It’s snobbish. And it’s dangerous. It relies on the idea that there are businesses that are inherently better than others. And they’re only the businesses that have room to become $100,000,000 companies.

Lots of business ideas aren't scalable, but they can still make a ton of money for the founders.

On Transgenic Zika-Proof Mosquitoes

Reinaldo Jose Lopes:

Even if [Oxitec's] transgenic mosquitoes can be proven to reduce dengue or Zika infections, it is possible that natural selection could reduce their effectiveness. Females could develop a preference for wild-type A. aegypti males — stopping the company's currently furthest-developed lineage of GM insects (called OX513A) from spreading in the wild.

At best this means a lot of money for Oxitec and little value for the payors. At worst, Zika virus adapts and the mosquitoes become useless.

Someone once said that "Life... finds a way".

Really, PubMed?:"Diverse biological effects of electromagnetic-treated water"

Really? Oh yes, if it's published it must be true:

The effects of water treated with an electromagnetic field (EMF) were investigated on two biological systems, humans and plants. Purified de-ionised water was treated by (1) boiling, (2) exposure to microwave radiation, and (3) low frequency electromagnetic oscillation molecular resonance effect technology (MRET), before being used to prepare media for culturing human peripheral blood mononuclear cells (PBMC) from three healthy females. Our results indicated that PBMC culture in MRET-activated medium showed significantly less oxidative metabolism when compared to media prepared from other types of water. As for the effects on soybean, our results indicated that both MRET- and microwave-treated water greatly enhanced the length of the root. These results suggested that electromagnetic-treated water can have diverse biological effects on both animal and plant cells. Since these effects are related to the ‘Memory of Water’, hypothesis which has been suggested as an explanation of the action of high homeopathic dilutions, our finding warrant a further investigation on the mechanisms of various types of physically conditioned water on specific cellular activities.

Issues with this paper:

1. No controls.
2. Apparently no ethics review for using healthy human volunteers.
3. A paywall. An Elsevier paywall.
4. Because of the paywall, there's no idea what the n of soy plants is.
5. Homeopathy.
6. The "Memory of Water" hypothesis is based on two PubMed citations. Hey, at least it's more than one.

Gene editing in human embryos gains traction

Nature has a short update on where human gene editing research is going:

China's lead

Fan’s team began its experiments in early 2014 and originally submitted the paper to Cell Stem Cell, Fan says. By the time the manuscript ended up on the desk of David Albertini, editor-in-chief of the Journal of Assisted Reproduction and Genetics, a different Guanghzou-based team had become the first to report human-embryo-editing experiments. That paper, which tried to correct a mutation that causes a blood disease, fed into a firestorm over the ethics of modifying human reproductive cells (or ‘germline’ modification). Some researchers called for a moratorium even on proof-of-principle research in non-viable embryos. ...

Fan’s paper should help to reassure international observers about the legitimacy of human-embryo-editing research in China, says Robin Lovell-Badge, a developmental biologist at the Crick. More such embryo-editing papers are likely to be published, he adds. “I know that there are papers floating around in review,” he says.“I’d much rather everything was out in the open.” 

The public issue, in my mind, is that many opposing human cells see the next logical step as a full blown program to produce genetically engineered human. I'm very skeptical that the science is going to go that far, that fast.  To start, through CRISPR-Cas9 gene editing is pretty specific, it's known to have off-targets, and those off-target regions depend on the site being edited.

Until all the consequences of editing a specific site (including unintentional targets) are determined to be 'safe', human CRISPR experiments in embryos should remain very basic.  First things first.

Our SiMSenSeq: Simple, Multiplexed, Sensitive, DNA Sequencing paper is out

The SiMSenSeq PCR method that I've been working on for about two years has just been published in Nucleic Acids Research.  Here's the abstract:

Detection of cell-free DNA in liquid biopsies offers great potential for use in non-invasive prenatal testing and as a cancer biomarker. Fetal and tumor DNA fractions however can be extremely low in these samples and ultra-sensitive methods are required for their detection. Here, we report an extremely simple and fast method for introduction of barcodes into DNA libraries made from 5 ng of DNA. Barcoded adapter primers are designed with an oligonucleotide hairpin structure to protect the molecular barcodes during the first rounds of polymerase chain reaction (PCR) and prevent them from participating in mis-priming events. Our approach enables high-level multiplexing and next-generation sequencing library construction with flexible library content. We show that uniform libraries of 1-, 5-, 13- and 31-plex can be generated. Utilizing the barcodes to generate consensus reads for each original DNA molecule reduces background sequencing noise and allows detection of variant alleles below 0.1% frequency in clonal cell line DNA and in cell-free plasma DNA. Thus, our approach bridges the gap between the highly sensitive but specific capabilities of digital PCR, which only allows a limited number of variants to be analyzed, with the broad target capability of next-generation sequencing which traditionally lacks the sensitivity to detect rare variants.

I'm currently packaging up the informatics pipeline used to analyze SiMSenSeq data, which will be up on GitHub pretty soon.

Working 24/7 is the cognitive equivalent of coming to work drunk

In an NPR interview about her new book, The Sleep Revolution, Arianna Huffington offered up this perfect quote on the importance of sleep and its relationship to the workplace:

We hear employees being congratulated for working 24/7, which now we know is the cognitive equivalent of coming to work drunk. But it's changing. We are now in this amazing transition period where more and more companies are beginning to realize that living like that and working like that has actually terrible consequences — not just on the health and productivity of their employees but also on their bottom line. 

Why AbbVie still has traction despite looming Humira patent expiry

Arthur Jeannerot, on Seeking Alpha:

In 2015, Humira (Adalimumab) represented 61% of AbbVie's total revenues, which could be seen as problematic since the composition of matter patent covering Humira expires in December 2016 in the U.S., and in October 2018 in the European Union. However, Humira is covered by more than 50 other patents on formulation, method of treatment, manufacturing and more. Those other patents are due to expire between 2022 and 2034, which should make it more difficult for competitors to come up with biosimilar versions of Humira.

Either way, AbbVie is going to start experiencing competition from other companies that are more than capable of producing Humira biosimilars - the technology to produce therapeutic antibodies is becoming more and more commonplace, and even large academic groups are jumping on the bandwagon. This means that, as far as technical complexity goes, making a biosimilar is within the capability of a talented PhD student.

What I think the market is over-estimating is the ability for competing biosimilars to carve out Humira market share, probably with the assumption that customers will be able to substitute one antibody for another as easily as one proprietary molecule for a generic drug in the small molecule drug space.

Unfortunately, it's not that easy. Antibodies can have a ton of idiosyncratic activities; they're bigger, and less well defined than small molecule drugs. In addition, there's going to a great deal of brand name inertia with Humira, as consumers stick with what works until a generic proves that it's as good as the original - which will take some time. This likely means that Abbvie can ride out the storm and plan a strategy to protect this drug for a little while longer.

Move over cronut burgers; the Burgerizza has arrived

In Toronto, The Ex is known for outrageous food being created for the once annual occasion.  Leave it to a baseball stadium to top Cronut Burgers, poutine balls and Krispy Kreme burgers with The Burgerizza:

Yuck. No thanks.

(Photo credit: National Post)

Is your work scalable?

Douglas Rushkoff posted this on LinkedIn:

Most of the technologies we're currently developing replace or obsolesce far more employment opportunities than they create. Those that don’t—technologies that require ongoing human maintenance or participation in order to work—are not supported by venture capital for precisely this reason. They are considered unscalable because they demand more paid human employees as the business grows.

Sometimes you need to stop and ask yourself: Is what I'm working on today scalable, or is it limited by some finite constraint, like highly skilled people or the number of hours in a day?