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Lab Notebook Software, Bypassed By Biologists, Poses Tough Challenge For Software Developers

By Steve Dickman, CBT Advisors

More than ten years ago, I stopped using paper notebooks for my writing and consulting work. As someone who writes and thinks for a living, this was a big transition. But what a payoff I received in return! I no longer had to refer to handwritten notes or to type them later. My typed notes suddenly became searchable and editable. Since they are easy to access, they push me to new conclusions and new beginnings.

Just imagine how useful such a shift would be for biologists. Unlike the typical solitary writer or consultant, biologists work both on their own and collaboratively. Keeping their thoughts locked in paper notebooks has got slow down the free flow of ideas both between biologists as well as inside each one’s head. Indeed, putting biological data – in handwriting! – into a notebook that can only be read by one person seems almost criminal. “Cloud” software platforms have already enabled faster, more efficient collaboration in many industries and on many levels. Think Salesforce, Dropbox and Slack. Why not free the data and biologists’ early thoughts about it? Why not let the “hive mind” of the community go to work earlier and more efficiently? Over the internet, such sharing could break geographic boundaries and supercharge the thinking of biologists all over the world.

Especially in the areas of biology research that have a natural affinity for digital data and analysis – think genomics – biologists are already using online tools to record and share data. The same is true for chemistry, where protocols and starting materials (such as chemical precursors) are much more standardized. But in the less digitally aligned areas of biology, the shift from paper to electronic laboratory notebooks and similar online tools has been slow, sometimes glacially so. When it comes to their personal lives, the same biologists are emailing, texting and Slacking with the rest of us. But for many if not most biologists, when it comes to recording or sharing data, unless the lab procedure is performed by robots, the front end of the data collection process still looks like it did decades ago. Fresh data is recorded on paper or locked up within individual pieces of laboratory equipment. Then, later, perhaps, it gets transcribed into a sanitized version of biological reality.

The push for widespread electronic lab notebook (ELN) use is just beginning in biology. (The fact that these software tools are still even called “electronic lab notebooks” points to the fact that adoption has been repeatedly attempted – and has repeatedly failed – ever since “electronic” was the term for what we now call “online.”) One company I know performed an analysis that showed that electronic data recording and workflow management tools has only penetrated 8% of biology labs. Even if the actual number is larger – several industry-based biologists I asked said that 8% sounded low – the opportunity is undoubtedly huge. Consequently, a number of small and big software providers have plunged into this messy world, each hoping to convert biologists to a new paradigm or, better yet, to capture a mass movement that they believe is already underway. Some investors, including the Silicon Valley heavyweight firm Andreessen Horowitz, have announced a bold and public stake in the “clouding” of biology, as they call it, and promising big productivity and ease-of-use gains from that. The way that role model companies such as Salesforce and Dropbox have taken over other verticals, would certainly point to possible or even dramatic improvements. Seen in this light, the progress of the early entrants into ELN field would seem to be the leading indicators for when biology will shift more of its daily practice to the cloud and how completely and efficiently that can happen.

This piece aims to answer these key questions: Why has change been so slow? How is that starting to shift? And for what I believe to be at least a $10 billion question: will this transition happen quickly and powerfully enough to reward the companies, including those in the portfolios of investors like Andreessen Horowitz, currently hoping to capitalize on it?

Adoption is a tough slog

The challenges in converting biologists to cloud tools fall into a number of categories. To me, they break down like this:

Inertia and lack of immediate value: What has made Salesforce work in customer relations management, for example, is the obvious utility of the platform at local scale but especially globally. By contrast, at this early point in the ELN adoption curve, there is a lot of inertia retarding adoption and little history of productivity gains. One entrepreneurial molecular geneticist I know, currently working as a product development lead at a Bay Area molecular diagnostics company, said that he had thought about starting an ELN company back in 2012 but then abandoned it. Adoption of ELNs in biotech and academic biology labs “is very likely inevitable,” he wrote, “but the platform has to be heavily customized to each company’s unique needs, so it’ll likely be very complicated, need a LOT of effort to initiate, need extensive training for users to get it, require separate audits and so on.”

Even after biologists get over the initial activation energy barrier, the “aha” may not arrive immediately, if it does at all. One academic biologist I interviewed, Kristen DeAngelis, a junior faculty member at the University of Massachusetts in Amherst, put it like this: “When I was a postdoc at one of the government labs in 2007, there was a big push for electronic lab notebooks. They didn’t catch on. The software was clunky and slow, so it was not possible to capture observations as quickly as with writing; it was difficult to make sketches and record observations like numbers; and there is a big cost to switching, since lab notebooks have to stay in the lab for safety, so purchase of special tablets just for this was required and not many labs could make it work.” Set against these practical challenges, the promise of “big-data-like” returns on the initial ELN investment might be perceived as pie in the sky.

Secrecy and competition: Competition in academic biology, let alone in biotech, can sometimes be brutal. Every vendor makes it possible to limit outsiders’ access to online data but how many biologists will feel like they can trust this promise in light of the security breaches that have run rampant in, say, the financial sector? Especially because so many person-hours are invested in each hard-won experiment needed to win publication in a top journal, some academic biologists will likely prefer to go slow on uploading to any online platform including ELNs. 

Degree of difficulty of biology: Some biological problems require inordinate amounts of faith and hard work, sometimes over years. In identifying new classes of receptor proteins (think about the netrins, for example, discovered by Marc Tessier-Lavigne, now president of Stanford University after three years of NOT discovering them) or puzzling out the intricacies of complex biological pathways, working solo or in a small, tight-knit group will be seen as an advantage. Easy connection with other biologists, not so much.

Lack of a common standardized computable biology language: This is a big one. Unlike, say, chemistry, in which most terms are unambiguous and new ones are rare, biology is a rapidly evolving field with little or no standardization of terms. Machine learning algorithms have been challenged by biology for a long time. As I wrote for the journal PLOS Biology in a different context fourteen years ago, ‘whereas extraction of person and place names from news text routinely reaches 93%, results in biology remain mired in the 75%–80% range.’ I quoted a brilliant structural linguist, Lynette Hirschman of the MITRE Corporation: ‘ “It’s a little depressing. Even something as simple as a slash may imply two different entities or a single compound.” Programmers eager to codify the rules of biology,’ my piece went on, ‘have been stymied by what one bioinformaticist calls “a sea of exceptions.”’ Even now, the lack of standard terms and the constant addition of new ones is a major hurdle for improving the utility of ELNs.

Both the software itself and the software-biologist interface is not doing the job: Working biologists from all parts of the spectrum – academia, the biotech industry and the pharmaceutical industry – reported major or minor difficulties with existing software packages. From pharma, where ELN use is typically mandatory, one senior neuroscientist I know reported that “The [ELN] software is actually a little slow. I believe the server is in France so it takes a few minutes to open the program and it is sluggish. That definitely aggravates people and makes them less inclined to adopt but honestly people don’t have a choice. It’s actually part of everyone in R&D’s performance review to adopt ELN best practices.” Adopt ELNs kicking and screaming! What a great marketing angle!

A very accomplished bioinformaticist responded to my email query about ELNs by saying that, barely one year into their transition to ELNs, his company had already split into two sets of users, one of which was continuing to use one platform while the other abandoned it and embarked on another. He wrote that the platform that part of the company abandoned – I won’t name it here – “…was advertised with the promise it can do anything — and that was the argument for buying it and [the accompanying] initial optimism.  But that ‘do anything’ meant a lot of customization. Underneath it is an Oracle database that tries to be very, very generic. So you end up paying for [the vendor] to do that customization. So there was one [vendor representative] nearly living with us and still progress was very slow. That led to dissatisfaction.”

From academia, Megan Krench, who completed her neuroscience PhD in 2016 at MIT, reported that it was “astonishing” to her that academic biologists are not more avid users of ELN. She went on: “I’m not sure that we will see widespread adoption in the next ten years, since we haven’t seen it in the last ten. Everyone who has been a grad student in the last ten years was a digital native: why weren’t we all keeping ELNs?” This former student went on to say that “…of the roughly twenty labs I knew in grad school, only one had a lab-wide policy to use ELNs – and that was a young professors’ lab where he bought everyone iPads as a carrot to entice good bookkeeping. Of the roughly fifteen people in my lab, perhaps two of them kept an ELN instead a traditional paper one.”

DeAngelis, the University of Massachusetts biology professor, rounded out her comments by writing, “You didn’t ask [what my lab uses for a lab notebook]. I buy these by the case and issue them to all my lab members”:

Lab notebook _SL1500_

The lab notebook of tomorrow? © 2017 TOPS Products (www.tops-products.com)

The lab notebook of tomorrow?

Attracting entrants

Despite or perhaps because of all these challenges, it seems like the ELN market, such as it is, has attracted more new entrants than ever. If anyone can foresee the drivers of change in the laboratory market, these companies can. In digging into this topic, Benchling is the company with which I spent the most time in researching this post (see disclosure). Benchling is in the portfolio of Andreessen Horowitz, which makes it one of the most high-profile players in a very diverse group of companies.

To read the rest of this post, click through to the original post here.

 

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Can biology, even drug discovery, ever be “clouded”? It’s early but Andreesen Horowitz VC thinks so

By Steve Dickman, CEO, CBT Advisors

Can you create biological insight on a laptop? If you could, it might overturn a fundamental paradigm of drug discovery: that it takes a great scientist or team of scientists to find a clear path through the messy complexity of biology. In the conventional model, sometimes the scientist is at a university. Other times she is in a company. But always, always, there is a series of iterative interactions – scientist running experiments in lab, scientist struggling to interpret results, scientist designing new experiments, scientist analyzing new results – until biological insight arises. If it ever does.

Of course, many drug discovery advances over the past thirty years have been driven by technological innovation: combinatorial chemistry; high-throughput screening; vastly improved imaging and prediction software; and rapid and reproducible assays run in some cases by robots on groups of cells or even individual cells leading to large and hopefully meaningful datasets.

But none of these advances has replaced the “Aha” moment of insight that arises from a human being’s engagement with a biological phenomenon that is thorny or one that had not even been perceived to exist. I always expected – and still do expect – to find that kind of insight in labs, not on laptops.

But now a renowned Stanford professor-turned-Silicon Valley venture capitalist, Vijay Pande, has set his sights on this challenge. Pande, the architect of the award-winning Folding@Home project and himself an award-winner in computational biology, recently joined a top Palo-Alto-based venture fund, Andreesen Horowitz, which formed a new $200 million fund to invest in “cloud biology” and other areas of software companies in the bio space. To read the post, click here or copy-paste http://onforb.es/1Sq3Q2G.

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Health IT: Will Europe catch the wave?

By Steve Dickman, CEO, CBT Advisors

The US health IT space is white hot. Europe lags far behind both in the number of companies and in the amount of money being invested. There have been very few (no?) exits. I was wondering if Europe will ever catch up and which companies and geographies are emerging winners. So I decided to survey a half-dozen Europe-based VC partners active in healthcare investing some of whom have taken their first tentative steps into health IT investing. Here’s what I found out.

But first the impressive US benchmarks: HealthITNews reported in mid-July that VC investment into health IT surpassed $1.8 billion just in the second quarter of 2014, double the amount that had been raised in the previous quarter. Investors have cashed in on exits from companies such as Castlight Health (NASDAQ IPO in 2014); Humedica (acquired by United Health for a reported several hundred million dollars in 2013); and Healthy Circles (acquired by Qualcomm Life in 2013 for an undisclosed amount).

This makes sense given the obvious drivers for health IT activity in the United States: the mandated shift to electronic medical records (EMRs); consumer interest in web and especially mobile health apps; the boom in analytics in all areas including health; and especially the multi-payer system, one that heavily involves employers. Castlight would not even exist without the employer aspect. Rock Health reported in its excellent midyear funding report published in late June that startups developing payer administration tools took in more VC money (over $200 million in the first half of 2014) than any other subsector within health IT.

A Europe of borders

Meanwhile, as much as Europe has dismantled many of the internal impediments to the single market (local currencies, border crossings), there are many barriers to developing solutions to Europe-wide healthcare challenges. These include:

  • Language barriers. Start a web site for a consumer-facing business and you will see your user base fracture unless you can communicate in at least three (or four!) languages.
  • Scaling challenges. Try to remedy the challenges inherent in the healthcare system and you will soon realize that there has been virtually no harmonization yet. Single payer systems are fine as long as you stay within them. If you try to work cross-border, then look out! As Antoine Papiernik, a managing partner at Sofinnova Partners in Paris put it, “Our European system is also messed up, but in a different way than in the US. It is the fact that [EU healthcare systems] are completely state controlled and operated that makes it difficult for a Health-IT play to get to scale as well as it could in the US.”
  • Missing incentives. When it comes to reducing inefficiencies and shifting responsibility and benefit to the consumer, the US healthcare system is a target rich environment. Similar incentives are hard to find in Europe, especially across borders. Consumers are less incentivized when they get cradle to grave healthcare financed by payments much lower than those in typical US health plans. Therefore, said Anne Portwich, a partner at LSP in the Netherlands, it is hard to imagine a consumer-focused company gaining VC financing in Europe, at least before it has huge traction (some promising examples will come up later). This is because “Something the consumer has to pay for him or herself, even 1 Euro per month, that is a completely different [and more challenging] dynamic and a different business model than what we are familiar with.”
  • Big data not yet “in.” Finally, a less obvious example. The larger business environment in the States has been largely penetrated by the type of thinking that favors “big data” and “analytics” as solutions to real problems. This way of thinking is years away in Europe, said Simon Meier, investment director at Roche Venture in Basel, Switzerland. Meier went part-time for a year in 2013 to work with a startup in big data and advertising so he observed this firsthand. Even sectors ripe for analytics such as retail and advertising have not yet been overhauled in Europe, he says. Therefore, Meier said, “our data scientists are still occupied in resolving issues or setting up infrastructure in areas from which US scientists have already moved on. There are plenty of markets in the European Union that have not even started thinking about data science. Compared to the US, applying data science to healthcare in Europe is going from a simple sailor knot to a Gordian knot.”

For all of these reasons, successful early-stage European health IT companies (see inset below) seem to be primarily single-country focused for now. Sometimes that leads to companies in different countries occupying similar niches, such as helping consumers improve sleep. Consumer-focused sleep-aiders we found include sleepio in the UK and iSommeil in France. Either app could be used in any country. Sleepio, which offers online sleep therapy, even prices its services in US dollars, so perhaps these apps’ reach is very broad. However, iSommeil’s sample language is all in French so I suspect that a majority of their readers are in French-speaking countries. Its app is available in the US iPhone app store but there are no reviews.

The bulk of Euro health IT activity that we turned up is in the UK, where a couple of active VCs (SEP, Albion) and some pioneering companies are mining turf (e.g. practice management software, EMRs) that has either already proven fertile in the States (despite the vastly different healthcare system) or that, though initially local or Europe-focused, may later turn out to be interesting for expansion. Those rounds have been on the small side, in keeping with the early stage of the companies and the low initial capital needs of software businesses. We’ll see if even more international VC funds begin to follow the pioneers in later rounds. Those international VCs, some of whom we reached, are certainly paying keen attention.

Withings' connected (and stylish) blood pressure monitor

Take your BP at home – in style

Breaking the mold

One company that breaks the mold is Withings, an Apple-like consumer products company based in France that started out selling an internet-connected scale added a blood-pressure cuff and is now branching out into a stylish wristwatch that doubles as a self-tracking device. 

MyTomorrows, based in the Netherlands, also offers something novel and very intriguing: an online platform that allows patients who have exhausted standard therapies to be treated with medicines not yet approved by regulatory authorities. Self- and angel-funded with $6 million, MyTomorrows already offers patients with an impressive list of diseases the opportunity to ask biotech companies directly for medications on a compassionate basis. If it gets over what are likely to be some very challenging regulatory hurdles, this one has real promise. 

But there are not many outliers like these and even fewer that have been financed by top VC firms. Furthermore, outside of the UK, VC activity in European health IT in general has been very limited. 

Will Mint be the solution? 

Thus it was with great interest that I noted the recent $6M Series A investment by two top-tier European VC firms, LSP and Seventure, in Mint Solutions, an early-stage company that originated in Iceland and has relocated to the Netherlands. 

As much a device as an IT play, Mint Solutions illustrates what is working about European health IT and at the same time why scaling will be hard. The challenge Mint addresses is errors that hospital personnel sometimes make in administering medication. Mint features a small bedside scanner (PICTURE?) that images the pills and confirms their identity before they are dosed. “The real challenge is the oral meds,” said Portwich, “not infusions. Mint has a scanner, a box with a drawer that comes out. First it does a 3D scan – shape, size, accompanying instructions. An algorithm verifies the identity of each pill. Then it gives a readout in a couple of seconds. It’s connected to the e-prescribing system. And it puts into the chart: ‘Mr. Miller got 2 ibuprofen and Lasix at 10am.’” 

Demand among Dutch hospitals – the company’s test market – is strong, said Portwich, spurring optimism that Mint’s solution, dubbed “MedEye,” can be marketed in other countries as well. A good review of MedEye and Mint Solutions appears here.

MedEye scanner

What’s next, a robot nurse? Don’t answer that…

In the “avoiding medical errors” market, though, the technology that has already taken hold in the United States is barcoding. This does not trouble Portwich. “We know that barcode scanning is widely used [in the States]. There is not yet 100% penetration but big hospitals have implemented it. But when you look at the long-term care facilities, that is a different story. Barcoding is not so well established there. So that could be our entry market.” 

Though LSP was early to discover Mint, to encourage co-founder Gauti Reynisson and his team to set up shop in the Netherlands rather than his native Iceland and to make a commitment to invest, Portwich recalled that, until Seventure came along, the search for a syndication partner was not so simple. “It felt like we are the only one” investing in health IT, she said. We spoke to IT investors and they said, ‘We only do software and this has a hardware component. They also said, ‘Oh, you are selling to hospitals – the sales cycle is too long.’ And our healthcare colleagues said, ‘Wait, but this is IT. We don’t do IT. We prefer medical devices.’” 

It helped that in 2012 LSP had set up a “health economics fund (HEF)” backed by two Dutch insurers, among other investors, in order to invest specifically in private healthcare companies with products close to market. In most cases, Portwich said, the HEF’s investments will go into traditional medical technology. 

Mint Solutions represents a type of company that Meier of Roche Venture says he is seeing increasingly often in the diagnostics space. To capture an opportunity, Meier says, “You have to number-crunch AND design a small device that does its job well. Both for the company and the investor, the small device is more the focus than the big data.” 

“Big time” IT and data plays in the healthcare space such as Foundation Medicine, in which Roche Venture invested, are still rare in Europe. “Look at Flatiron Health,” Meier said, an oncology-focused cloud-based data and analytics platform in which Google invested $100 million: “I have not seen anything similar in Europe.” 

Language barriers, fragmented markets, a pot of gold across the ocean: no wonder many European health IT entrepreneurs I know either have already moved or are thinking of moving to the States

I suppose the best that Europe can hope for besides outliers is that some of its best companies hit it big in the States and then return and offer their services in their home markets. But it will take a while before that starts to happen. 

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This post originally appeared on The Healthcare Blog.

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