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.

Wednesday, March 16, 2016

How bioRxiv will make journals pay for publishing research papers

Preprint servers are the future of scientific publishing.

There's a detailed article on biological research and the controversies surrounding the bioRxiv preprint server up at The National Post:
After several dozen biologists vowed to rally around preprints at an “ASAPbio’’ meeting last month, [bioRxiv] has had a small surge, and not just from scientists whose august stature protects them from risk. On Twitter, preprint insurgents are celebrating one another’s postings and jockeying for revolutionary credibility.

For most of the history of organized scientific research, the limitations of technology made print journals the chief means of disseminating scientific results. But some #ASAPbio advocates argue that since the rise of the Internet, biologists have been abdicating their duty to the public — which pays for most academic research — by not sharing results as quickly and openly as possible.

Unlike physicists, for whom preprints became a default method of communicating discoveries in the 1990s, biomedical researchers typically wait more than six months to disseminate their work while they submit it — on an exclusive basis — to the most prestigious journal they think might accept it for publication. If, as is often the case, it is rejected, they try another journal. As a result, it can sometimes take years to publish a paper ... and because science is in many ways a relay, with one scientist building on the published work of another, the communication delays almost certainly slow scientific progress.
Yes, paper reviews are slow and definitely consume resources, but they are usually helpful. Later on in the article, there's a bit of fearmongering that preprints will be 'detrimental to science' and that the world will end, etc. but that's coming from editors that are incentivized to keep scientists paying for the review process.

What I'd really like to see in the near future is a model where scientists post their work to bioRxiv to stake claim to something new in their field, and where it's incumbent on journals to bid for the right to accept good papers into the review process. Why shouldn't labs be compensated after the fact for doing high quality research, in addition to being funded in advance as in the current system?

Several factors work for in favor of this model:

  1. Scientists will still preprint research that's of good quality in an effort to receive journal bids. In fact, they'll still have an incentive to produce work that's as high quality as possible.
  2. Journals will still be in a position to offer a proper peer-review for preprints, and in some (most?) cases this means that the version of the paper published by the journal will be of better quality than the pre-print.
  3. Journals won't need staff to deal with inquiries from every researcher thinking that their paper is good enough to review. Instead, scouts will contact labs since they know what's out there.
  4. Excessive resources won't be spent on polishing little papers so that they're 'good enough' for submission to a journal. If someone has one or two interesting figures they can still publish it, get a DOI, and get on with their career.
  5. The corollary of #3 is that the need for a 'Journal of Negative Results' is eliminated. Just preprint the damn results and get a bit of credit for it.

I don't think preprints are the threat that some folks are imagining; on the contrary, they should improve the system at a time when the model of 20th century publishing seems to be broken or at best dysfunctional.

So if you have any other ideas reach out on @CheckmateSci.

Monday, March 14, 2016

How to name your biotech startup properly

From STAT:
Alnylam Pharmaceuticals, named after a star in Orion’s belt. “It marks the strength of our vision, and gives our effort a clear association with something that’s up in the sky,” said Chief Executive John Maraganore.

However, the Cambridge company did what many in the industry do: they tweaked the spelling, from Alnilam (the star) to Alnylam, to help it stand out to investors, in Google searches, and in trademark filings.

The word Alnylam derives from Arabic — it means “string of pearls” — and in this, too, the company’s name is illustrative of a larger industry trend: Names drawn from words in Latin, Greek, or other foreign languages.

Avak Kahvejian, who helps build life science startups at Flagship Ventures, said “one of the tricks” he uses is to run English words associated with his companies’ technologies through an online translator. That’s how he named his most recent startup, Cambridge-based Rubius Therapeutics, which launched in December to engineer red blood cell-based drugs. (Rubius means “red” in Latin.)
The article also touches on a company working in the CD47 receptor space that decided to go a much less romantic naming route: Forty Seven Inc.

Thursday, March 10, 2016

Those fighting over Editas are in it for the long haul

When I first started following the promising CRISPR/Cas9 technology after the chance that shRNA/RNAi technology becoming biotech's Holy Grail seemed to fizzle, I thought that having two or more research groups reporting CRISPR technology wasn't surprising; it was just another example of the well known multiple discovery effect operating in science.

However, the CRISPR story sounds much more like a tale of politics and competition (money necessarily follows) instead of that of independent people fighting over first rights to the same bright idea.

Via TechCrunch:
Two of Editas founders, UC Berkeley’s Jennifer Doudna and the Broad Institute’s (BI) Feng Zheng, are credited with pioneering CRISPR/Cas9, a gene-editing technology that has radically advanced the biotech industry. Editas uses this technology to develop therapies to treat humans at a genetic level.

Those with a genetically induced cancer would be able to receive treatment to snip out parts of the faulty gene sequencing using this technology, for example.

Though Doudna is listed as one of the founders of the company, she left Editas two years ago to create the competing Caribou Biosciences in Berkeley, California. However, BI filed for the CRISPR patents for Zheng and was originally awarded the rights to them.
It'll be interesting to see how this unravels.