Wednesday, February 22, 2017

Do European Research Council applications foreshadow what may happen with the NIH?

It looks like Brexit is having repercussions on UK science funding from the European Research Council, according to David Lomas:
Applications to EU funds are usually made by consortiums of researchers from a variety of EU countries. Britain has a strong track record of taking the lead in these groupings. 

Britain also has a leading position in applications for individual research grants made under the European Research Council, the ERC. 

“Previously having a British member would help you in your application to get funding … Now you are less than an asset, so we have had academics removed from grant applications,” Lomas said.
One has to wonder whether US funded research organisations, like the NIH, will be forced to "Buy American" in the future and prevent spending on research activities in foreign countries.

I get the whole populist sentiment around trade deficits and job losses, etc., but the fact of the matter is that the US can't just cut out part of international trade and partnerships without impacting the productivity of US-based initiatives. For example, groups in Toronto can offer US scientists many different kinds of scientific services on a fee-for-service or collaborative basis on very competitive terms, mostly due to the favourable USD/CAD exchange rate.

So why cut out that part of the value chain?

Monday, December 26, 2016

What's really up with Roche and PacBio?

You're probably aware that Roche recently severed its 2013 partnership with PacBio and decided to go it alone without access to long read SMRT technology. Neil Gunn, Roche's head of sequencing R&D explains that Roche will now 'focus more intently on its internal R&D efforts to "drive our long term strategy, which is to be a leader in clinical diagnostic sequencing."'. This wouldn't have anything to do with the 2014 acquisition of Genia, would it?

Keith Robison at Omics! Omics! has already speculated about various reasons for Roche's break up, but I think that the developments around Genia are the primary reason for this parting of way. As Robison explains:
The obvious culprit would be Genia, the nanopore sequencing technology which Roche purchased. ... Genia has twice reported this year technical success, first with their nucleotide chemistry and then their protein engineering.

But good publications do not a commercial instrument make, and there has been no signal that a launch is imminent.  Perhaps we will hear a lot more at JP Morgan or AGBT, but Genia has burned a lot of credibility in the past with premature announcements.
This may be true, but consumers in the genomics space have been pretty forgiving:
Many of complained that ONT announced vaporware at 2012, but they've delivered devices to customers since mid-2014.  
And as of now there are a lot of working ONT devices in the field.

But back to Roche/Genia. It's tempting to speculate that Roche is building a competing platform to Oxford Nanopore's technology, which on the surface may look like what it is. However, the technologies and the way sequence is read from them is different.  On one hand, ONT's nanopores detect electrical signals generated by DNA kmers traveling through the pore, and in comparison Genia's technology reads DNA by having a polymerase send engineered tags through their pore.

How will Oxford Nanopore's MinION compare with Roche's Genia?

At this point, they look like competing technologies in the nanopore sequencing space, but without more information on the Genia it's hard to make a call. However, since the Genia relies on proprietary modified bases called NanoTags read by a nanopore, I'm going to speculate and assume that the Genia will have a higher consumable cost as result; potentially a big drawback for the Roche platform. Nevertheless, here's how they compare across a two key value drivers.

Read accuracy is a big deal. At the moment, it looks like Genia might have a hand up due to their NanoTag read system. I suspect that it easier to calling bases directly using engineered NanoTags that it is to infer bases from electrical signals generated by DNA going through a pore, as is the case with ONT. If Roche can make up the additional cost of NanoTag reagents by offering a higher read accuracy, the Genia might be worth it, particularly if the flow cell cost is kept below that of ONT's.

Cost. There are two major categories of cost sequencing teams are concerned with; operating costs and capital costs. The nice innovation that ONT has brought to the genomics field is the idea of zero (or nearly zero) upfront capital costs. You buy a flow cell for <$1000 and start sequencing.  The capital cost of a Genia is an unknown, but if it's anywhere near that of PacBio or Illumina equipment it'll be an obstacle to adoption in the field. Unfortunately, without a target purchase price (and other assumptions about the Genia's longevity) it's impossible to come up with a cost model and estimated $/gigabase.

Some guidance from Roche is needed here both in terms of cost and accuracy. I haven't even touched read length as a dimension of performance, but given ONT's extreme read lengths (up to 200kb, more commonly ~50kb), Genia needs to easily hit >30-50kb even to be considered as competition.

Saturday, October 22, 2016

Why you should be wary of companies hiding everything for 'intellectual property reasons'

Think of Theranos. I remember reading this article when it came out, thinking 'what can they possibly be protecting?':
The technical details about Theranos' seemingly revolutionary tests are hard to come by, and the company is known for its secrecy about its founder's invention.

There's one fundamental question, one that in some ways is unanswerable without revealing information that Theranos wants to keep confidential: How, exactly, does what Holmes invented work? ... [The company] hasn't published peer-reviewed studies comparing its tests to traditional ones, and the company hasn't allowed independent experts to publicly assess its labs, citing the need to protect its intellectual property.
IP comes in many flavours: patents, designs, trade secrets, and business processes, to name a few. Not all intellectual property can be protected like a patent, but some of it can, and that means that not all intellectual property needs to stay secret.

When a company like Theranos doesn't even let independent experts in to check out the technology and say 'Yes, I've seen what they do and it works', which they could conceivably do under an NDA, it raises a red flag that something isn't right. Most medical device/diagnostic companies have at least something that can go through the patent prosecution process, which allows experts to understand how the new widget works and whether it will eventually provide value in a business model.

Sometimes the best strategy is to show everyone that at least part of your firm is not just smoke and mirrors.

Monday, July 11, 2016

Scientists' perennial problem: The Brexit Effect

I've spent the last week or so thinking about the effect a Brexit would have on U.K. science, as have many other folks on the 'net. Having lived through the Canadian War on Science (2006-2015), there are lots of parallels to draw between policies and strategies that try to cut out basic research and what scientists seem to be freaking out over with regards to the Brexit (which by the way isn't a done deal after the key leaders bailed on the movement).

In my experience, three things related to changing science policy hit a nerve with researchers: funding cuts, restricted mobility of people, and general political instability. All of these aren't unique to the kind-of-hypothetical Brexit Effect; they're just brought to top of mind by it.

Funding cuts. It's no doubt that money and resources are the lifeblood of a research group - any group, for that matter - and whenever there's less money to go around it's an uncomfortable time, by definition.

There's a wonderful post at the London School of Economics' BrexitVote blog that goes into extensive detail about how the UK science funding may change. Specifically on how whatever gains won by leaving the EU are overshadowed by the general loss of economic activity if the UK were to go through with the plan:
Importantly, even the more optimistic assessments of the UK’s economic performance following a Brexit ,.. model an immediate loss in GDP for the transition years following a Brexit. The size of that loss is substantially larger than the current net contribution of the UK to the EU budget. ...

Therefore the attempt to financially gain in the short term via a Brexit is akin to killing the goose that lays the golden egg. It is a sure-fire short term loss, wiping any free money for Research & Innovation investment until at least a decade down the line – according to the most optimistic scenarios. This strongly counters any claim that voting to leave the EU provides immediate funds for a shot in the arm of national science. The extra money simply will not be there for science as the UK economy is hit by huge transition costs. 
Other parts of the post go on to explain how Switzerland manages to get along with science just fine without being an EU member.

Now you might point out that the above scenario explains what would happen to global research funding (similar to a US-style Sequestration effect), and ask what about cuts to specific programs or areas of research? This, sadly, is sometimes needed. Just as in any other business, as the needs of the 'market' move on, science needs to adapt to ask new questions, use new technologies, and re-train people.

This process of creative destruction has been accepted by mainstream business people and spawned so many different bestsellers (including the classic ones by Eric Topol and Rotman Professor Sarah Kaplan). It really should be one of those things that's accepted as a given by grant funded researchers, not fought against.

Next post, Mobility of People.

Thursday, April 28, 2016

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".

Tuesday, April 26, 2016

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.

Friday, April 15, 2016

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.

Sunday, April 10, 2016

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. 

Tuesday, April 5, 2016

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)

Friday, April 1, 2016

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?

Tuesday, March 29, 2016

The Ontario health minister on overpaid physicians

From the National Post:
Health Minister Eric Hoskins complained Wednesday about the billing practices of some Ontario doctors, who he said were taking hundreds of millions of dollars away from home care and other services. “Unpredictable and frankly out of control billing by some doctors is a problem that creates huge income for some doctors, but it leaves less for family doctors,” said Hoskins.  

“It leaves less for our salaried doctors in community health centres, it squeezes our ability to invest more money in home care and community care, and it robs of us of the capacity to responsibly plan our health care spending each year.”
I never thought he'd have the guts to finally say that.

BC company offers free cancer tumour screening to 1,500 Canadians

From the CBC:
Free cancer tumour genetic screening? That's the unusual offer from Contextual Genomics, a private company in Vancouver.

Starting this month, the first 1,500 Canadians who get their oncologists to send in their tumour samples will have their cancer tested using the the company's trademarked Find-It Cancer Hotspot Panel at no charge. After that, the test will be offered for sale for less than $1,000.

"You could call it marketing, but it's making this test available to people who haven't had access to it before," said Contextual Genomics CEO Chris Wagner. The idea is that there might be a drug out there that can target the particular cancer mutation. But that's if a drug exists, and if it's approved for use, and if the oncologist knows what to do.
This is progress. Why attempt to make an issue of a private company providing a new test? Most of Canadian health care is delivered by private companies anyways.

That said, the Contextual Genomics is making an excellent strategic decision to offer their test for free. I'm actually surprised that they're limiting it to 1,500 people; the marginal cost of running these tests can be pretty low, especially for those testing highly specific mutations. I'm not so sure about the full cost of delivery, though.

After this phase of their National Access Program, my guess is that they'll eventually offer some kind of compassionate access program for those that can't pay ~$1,000 out of pocket.