MaRS tenant identifies the danger-marker for cancer

Researchers at the University of Toronto and Mount Sinai Hospital have identified a biomarker that appears to identify aggressive thyroid cancers.

The team, led by Dr. Paul Walfish, has shown that thyroid cancer biopsies from patients with a reduced overall survival had increased cleavage of the EpCAM molecule compared to those taken from patients with with longer survival. The cytoplasmic tail of the cleaved molecule (Ep-ICD) accumulates in the nucleus and is hypothesized to play a role in the increased proliferation of these cells.

The study showed an enormous difference in survival duration between the two groups:

• Five months average survival in patients where Ep-ICD accumulated in the cell nucleus and cytoplasm
• 16 years average survival in patients without intracellular Ep-ICD build-up

Further research is required to clarify if this is indeed a “chicken” or “egg” phenomenon. In other words, does the cleavage of EpCAM result from another (as yet unknown) event that drives the increase in tumour aggressiveness or can the cleavage cause the rush to full-blown tumour growth in its own right?

Kalgene Pharmaceuticals, based in the MaRS Incubator, has an exclusive license to the technology which detects the severity of thyroid cancer and hopes to expand its use to diagnostics — and ultimately therapeutics — for a variety of epithelial cancers.

As reported earlier, Toronto researchers have also helped create safer, radiation-sparing treatments for thyroid cancer.

Andy Grove sounds the alarm about innovation

By dropping the social in innovation, is North America breaking the innovation chain?

Andy Grove, a co-founder of Intel and a Silicon Valley icon, is sounding two alarms about innovation’s future. Both flow from his disagreement with the accepted article of faith that the US tech sector necessarily should focus high-end jobs in the US and export manufacturing jobs.

One alarm is that US innovation is dropping the ball in job creation. By exporting manufacturing offshore to Asia, the United States is focusing on start-ups.  “Start-ups are a wonderful thing,” says Grove in a recent essay in Bloomberg Businessweek, “But they cannot by themselves increase tech employment.”

Grove challenges that notion that “shipping jobs overseas is no big deal because the high-value work — and much of the profits — remain in the US. But what kind of society are we going to have if it consists of highly paid people doing high-value-added work — and masses of unemployed?”

Grove’s second alarm is that, by not having hi-tech manufacturing at close hand, the US innovation chain becomes broken by not participating in scale-up.  Equally important as start-up is the point when “technology goes from prototype to mass production. This is the phase where companies scale up. They work out design details, figure out how to make things affordably, build factories and hire people by the thousands. Scaling is hard work but necessary to make innovation matter.”

With hi-tech firms like Apple, Seagate and Dell, for every US worker they employ, their suppliers have 10 people working overseas on their behalf.

Besides losing US jobs, Grove says the US “broke the chain of experience that is so important to technology’s evolution.” He cites the example of batteries.  “What microprocessors are to computing, batteries are to electric vehicles. Unlike with microprocessors, the US share of the lithium-ion battery production is tiny… As happened with batteries, abandoning today’s ‘commodity’ manufacturing can lock you out of tomorrow’s emerging industry.”

Grove argues that when individual businesses make decisions to transfer manufacturing and a great deal of engineering out of the US, they have “hindered our ability to bring innovations to scale at home. Without scaling… we lose our hold on new technologies. Losing the ability to scale will ultimately damage our capacity to innovate.”

Grove recognizes that the remarkable growth of Asian manufacturing was the direct outcome of Asian states’ economic policies that said that the number-one objective was job creation.

Learning from their success, Grove calls for “job-centric economic theory — and job-centric political leadership — to guide our plans and actions.” Making a suggestion that will be seen as heretical by many, Grove is advocating for a tax on the product of offshore labour. He says the resulting money should be segregated and used to fund a Scaling Bank of the US. SBUS would make the capital available to companies scaling their US operations.  All this, says Grove, would be in aid of rebuilding of America’s “industrial commons”.

Grove’s understanding of the value of an integrated innovation chain seems highly consistent with Ontario’s recent large-scale commitment to renewable energy and its market-making deal with Samsung.

But Grove’s analysis and recommendations will also be sober reading for Canadians interested in our innovation future for two reasons:

1. His views are an acute critique of how incremental decisions (like outsourcing) might erode a country’s innovation prowess over time
2. The implications of these views are dangerous for Canada if the US goes protectionist

Andy Grove’s views are always worth reading. In his recent Bloomberg Businessweek essay, he places the social implications of innovation policy front and centre — and underscores the fact that all innovation is fundamentally social.

The future of genetics looks bright

What’s the future of genetic diagnostics? Where do the commercialization opportunities exist? Now we know.

On June 22, the Ontario Genomics Institute and MaRS Future of Medicine^TM jointly held “Dx2010: Markers to Markets” – a workshop focused on best practices and regulatory considerations for developing gene-based diagnostic and prognostic tests.

The invitation-only event drew over 70 representatives from developing biotech firms, multinationals, legal firms, investment groups and government.

If you missed this event, we now have content from the workshop available to the public.

Video:

Presentations:

We hope you will enjoy these insights from the leading edge of gene-based diagnostic development!

Stay tuned for more OGI/MaRS Future of Medicine^TM joint events on additional commercialization topics going forward.

Diabetes - it's the real thing!

We’ve had several blogs on the topic of prevention of type two diabetes (T2D) over the past few years (see Want to live longer,  Want to live (even) longer and How to avoid diabetes).  The reason for our interest is that T2D looks set to be the fastest growing health issue in North America in the next couple of decades.

Diabetes affects over 150 million people worldwide and this number is expected to double by 2025.  In North America, over 90% of all cases of diabetes are T2D.

Short of radical lifestyle changes (strict exercise regimen and substantial weight loss) is there anything we can do to prevent the development of this insidious, life-threatening disease?

A group of Toronto researchers and their colleagues in Hamilton and London have recently shown that combination of two diabetes medications at lowered doses can significantly delay the onset of T2D.

The 207-patient CANOE study, recently published in The Lancet (read here), allocated subjects with at least one risk factor for the development of T2D to treatment with low-dose metformin+rosiglitazone (MR) or placebo and followed various disease parameters over a four-year period.

The results showed that the MR-regimen patients had a significantly lower incidence of development of T2D (14% vs 39%) and had a greater relative risk reduction (66% vs 26%) than patients in the placebo group.  In terms of safety, the MR group had a higher incidence of diarrhea compared to the placebo group (16% vs 6%) but there were no clinically significant adverse events.  More work will likely have to be conducted to look at the long term cardiovascular safety of this treatment plan.

The authors concluded that the MR regimen seems safe and effective for preventing development of T2D in at risk patients.

The study was supported by GlaxoSmithKline.

And third place goes to...

The second annual Scientific American worldVIEW survey results have been published.

The take-home message is that Canada ranked third in the world for innovative capacity – a composite score based on ratings of intellectual property, intensity, education/workforce, enterprise support and foundations.

Here are the Top 5:

1. USA = 37 points

2. Singapore = 31 points

3. Canada = 29 points

4. Sweden = 28 points

5. Denmark = 27 points

Canada scored highly on intellectual property and enterprise support but could improve its overall standing by improvements in the education/workforce and intensity categories.

The “intensity” category includes the number of public companies per capita and portion of overall R&D spending used for biotech-related activities.

Read the full details here.

Did Craig Venter create life?

There has been a huge amount of media attention and a torrent of breathless commentary concerning Craig Venter’s recent publication, “Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome”.

Much of the fuss stems from the assertion that the Venter group has created synthetic life – created a new living organism from inert materials.  Is this really true?

What actually happened here was a complete reprogramming of an existing organism via the introduction of a “synthetic” genome.  Please note that “synthetic” refers to the code’s method of manufacture (via a DNA synthesizer) and not that the code itself was generated de novo. The sequence was edited from the known genome of an existing species (M. mycoides).

Furthermore, achieving the end result of a “new” organism was not possible without substantial help from other living systems. Specifically, the conjugation of the synthesized DNA strands into a genome-length construct required input from physiologic processes in yeast cells and E. coli. Plus, the newly formed genome had to be inserted into a living organism (M. capricolum) to allow the “new creation” to develop (M. mycoides JCVI-syn1.0).  The host cell cytoplasm and the epigenetic machinery which supported replication of the synthetic genome was, obviously, not of synthetic origin.

Hence, this “synthetic” lifeform required a lot of help from a variety of living cells to get off the ground.

When asked about his breakthrough at a Congressional Hearing on May 27, 2010, Venter commented “We do not consider this to be ‘creating life from scratch’; rather, we are creating new life [emphasis added] out of already existing life using synthetic DNA to reprogram the cells to form new cells with functions that are specified by the synthetic DNA.”

Once again the yeast, E.coli and M. capricolum were definitely not synthetic. Also “creating new life?”  Probably more accurate (but less attention grabbing) to say “we transformed an existing cell with a genome built from components based on another related organism that we manufactured with a DNA synthesizer and assembled in yeast and E. coli .”

The great technical achievement here is that it was possible to modify a self-replicating living organism with a different genome built from machine-derived DNA and have the new organism replicate successfully based on the new DNA.  In terms of applications, this work could allow alterations to simple organisms, such as the influenza virus, in order to quickly make improved vaccines as epidemics appear.

But artificial life?  Not at all.  As Venter and colleagues have demonstrated, life still comes from life.

DNA Part II, courtesy of Toronto

One surprising finding from the Human Genome Project was that our genome is of a relatively modest size compared to some lowly organisms (e.g. the marbled lungfish and the amoeba Polychaos dubium have genomes 40-200 times the size of ours).  How is it that we can make do with a fraction of the genes of these more simple species?  We are important after all!

Driven by gene envy, scientists the world over have tried to figure out just how we can generate sufficient complexity from such a (ahem) puny genome.

Canada to the rescue!  The results of a pivotal research study that sheds light on this puzzle has recently been published in Nature.  The work was conducted at the University of Toronto by a team led by Ben Blencowe and Brendan Frey.

The research shows the presence of a second genetic code – the splicing code – that governs in a tissue-specific manner how genes are processed to generate the complexity the organism requires.  By combining coding sequences in different ways the human genome is able to generate a much larger array of proteins than our ~23,000 genes would indicate.

All biologists know the mantra “Phenotype = Genotype + Environment” but few would have guessed the degree of interplay between our gene expression profiles and environmental cues.  The U of T study underlines the active dialog between our genes and the tissues they reside in.  Change the environment for a cell and you’ll see different gene splicing patterns and, ultimately, altered cellular behavior.

The implications of this work are profound.  For one, it makes you wonder how truly informative in vitro studies are since those cells are residing in a highly artificial environment lacking many of the tissue-specific cues they would encounter in the body.  Are in vitro gene expression patterns a faithful representation of what happens in the body?

In addition, alternative spicing patterns vary greatly between species (e.g. only 20% conserved between humans and mice) which casts doubt upon how much we can extrapolate from gene expression studies in rodent models.

One thing is for sure, the U of T study has changed the way we look at the function of the genome.  There is sure to be a torrent of research activity developing from this pioneering work which should shed further light on how our body talks to our genes.

3D for the masses

How would you like to play a 3D video game with your family as the main characters? Or how about walking around a 3D virtual city of Toronto that shows all the details of the city as you know it?

Sound like technology that you’d expect in the next 15 to 20 years? Thanks to award-winning Toronto start-up Verold, we may have to only wait a few years to get there.

Verold’s software reduces the time to create ready-to-animate 3D content for games, web content, augmented and virtual reality as well as films.

It’s been proven consistently that 3D content is more engaging and immersive, allowing for a better user experience, but why is 3D content not yet widely adopted? A huge portion of the costs for 3D content is the labour — it’s expensive because it takes so long and is quite complicated. It’s a key factor in the limited 3D content we see right now. Verold’s technology has the potential to make 3D content creation so cheap and easy that the average person can create their own 3D images for their own personal use, whether it be for videos or games. I for one am anxious to see the day when 3D is everywhere. Just imagine the massive influx of 3D videos that will flood YouTube!

So how can I place such high hopes on a small start-up? Verold is no ordinary start-up.

1. They are the 2010 winners of TieQuest’s Business Venture Competition (a network of highly affluent and influential entrepreneurs supporting start-ups), receiving over $81,000 in prizes.

2. They have been selected for the competitive “48 hours in the valley program” by the C100 (a collection of high-powered Canadian executives supporting Canadian start-ups).

3. And just yesterday, Verold won the $7500 elevator pitch prize at OCE Discovery 2010.

Then add MaRS to the list of groups supporting Verold – they’re our client and we’ve been helping them along the way. That’s one heck of a group that can provide a lot of leverage to a start-up.

Now, winning competitions is certainly not enough. They also have significant traction with lead customers and even in such a tough VC market, already have investors of all types knocking on their door. It also doesn’t hurt that they’ve got a superstar CEO and CTO (Jad and Matthew) running the company. I might be a bit biased since I know them and have seen Verold grow from the very start, however, I truly believe that Verold is on an exponential path to success.

So if you’re wishing you could tour the world but can’t afford to do it, Verold might just bring the whole world to your doorstep in an immersive 3D form. You and your friends might not need to leave your home!

Got a computer? Help map space

“Contribute to real science by helping classify galaxies with the Sloan Digital Sky Survey’s Galaxy Zoo.”

In March, a world record was set for the most explosive man-made collision between two particles (3.5 TeV for all you physicists). Such experiments, conducted at the Large Hadron Collider (LHC) near Geneva, are expected to yield valuable insights into the early moments of our Universe.

The LHC has heralded some other firsts, namely the first paper authored by over 1000 people. The paper represents a new way of conducting science that allows for unprecedented, rapid collaboration.

The practice of allowing crowds of people to perform a task, instead of one highly qualified individual, is well-documented in such books as The Wisdom of Crowds and Wikinomics. The Firefox browser, the Linux operating system, Wikipedia and the Apache web server are examples of open-source products created for free by a pool of eager contributors.

In a sense, the process of scientific research has always been open-source, with results published for peer-review by the community. Colleagues test and refine theories and give them back up to the crowd. But new technologies are allowing science to proceed in a much more collaborative way. The LHC hosts scientists from 111 different countries.

The Human Genome Project is another oft-cited example of massive collaboration, with thousands of scientists working towards the same goal. In astronomy, the Sloan Digital Sky Survey employs hundreds of astronomers with the goal of mapping 25% of the known sky.

But true “crowd-sourcing” taps into the energy of non-specialists too and their deep-seated motivation to contribute to the sum of human knowledge. Galaxy Zoo is a website where anyone can sift through data from the Sloan Digital Sky Survey and help out with the classification of galaxies.

The Search for Extra-Terrestrial Intelligence (SETI) project is another example from astronomy, tapping into the unused computing power of idle desktop computers. Contributors download a program that runs as a screen-saver, looking for patterns in radio telescope data from distant stars.

If biology is your bag, consider FoldIt, a simple program that lets users test the millions of iterations of a folded protein by working through a puzzle much like a Rubik’s cube. Researchers have also harnessed the ubiquity of cell phones and laptops, using them to track everything from noise pollution and earthquakes to bird populations.

The philosophy of engaging such “citizen scientists” is spreading, recasting the process of science as profoundly collaborative and democratic. The Creative Commons organization has recently released the Science Commons designation as a platform for presenting research to the public.

The Public Library of Science, OpenSourceScience, and OpenScience are all popular web platforms designed to foster such open-sourced collaboration amongst scientists and the crowds that are interested in their work.

Most private research companies, however, are understandably nervous about opening up their research results to the commons for fear of revealing valuable proprietary information. Innovative companies such as Proctor and Gamble provide a model of how to harness the power of the crowd without revealing trade secrets.

InnoCentive is a so-called “marketplace for ideas,” where inventive freelance scientists can be paired up with problems posed by the research community. P&G have reaped enormous benefits by posting problems on the site, using the collective power of the community to brainstorm solutions. Some 35 Fortune500 countries now use InnoCentive to outsource their research.

Newer models of transparency and crowd-sourcing are poised to become the dominant model for scientific research. They tap into people’s motivation to feel a sense of purpose and to contribute to something bigger than themselves.

Expect more 1000-author papers in the future.

BIO: A close-up on the biotech industry

Just got back from the 2010 BIO International Convention in Chicago – the Superbowl of the biotech industry.

Last year’s BIO was a decidedly gloomy affair as investment dropped to levels not seen since the mid-90s, but this year there was a cautiously optimistic tone as the industry adapts to the “new normal” of capital constraints.

Here are some take home messages from the event.1. Finance

According to Steve Burrill, 2009 was the best ever year for biopharma financing.  However, the bulk of that was accounted for by massive mergers (Merck/Schering Plough, Pfizer/Wyeth, Roche/Genentech and Dainippon/Sepracor).  Subtract those whoppers and the amounts are much more modest.

The IPO window creaked open slightly which allowed some of the more mature companies in the waiting room to get out.  In all cases the pricing was significantly reduced versus expectations and it seems that the beleaguered VCs were the ones who bore the brunt.

Nowadays it is necessary to be much more advanced to attract VC or pharma interest (i.e. Phase II clinical data at least) which does not auger well for the vast majority of emerging life sciences companies (95%).

2. Future Trends

Straining health-care systems will require the optimized use of drugs which may indicate that bioinformatics and pharmacogenomics plays are set to flourish.  I eagerly attended several biomarker/prognostic sessions at BIO looking for future champions, but came away with the impression that there is still a big gap between where we are now and what the market will require.  The companies who can get this right should do very nicely indeed.

There is only so much money that pharma, insurers and government can extract from one individual life and we’re close to that limit now.

3.  Tech Transfer

A session on novel approaches in tech transfer featuring our very own MaRS Innovation (“tech transfer on steroids”) attracted a lot of attention.  If the traditional model is broken, we need new ideas, right?

Here are some of them:

• Karolinska Institute: No angel or VC interest locally so they raised their own $200 million commercialization fund

• Imperial College: placed their emerging companies into a pool and listed it on the London Stock Exchange

• Harvard and Partners Healthcare have created their own proof-of-concept funds to assist in-house innovations.

Great to see such proactive approaches moving technologies closer to market in the absence of early stage investors.

4. Leading Economic Indicators

Mood: cautiously positive

Attendance: rather low (17,000) compared to the 25,000 levels seen a few years ago

Quality of swag in exhibition hall: low-to-medium

Most active nations: US, Canada, EU, China, Australia

MIA award: Japan

Most down-to-earth luncheon presenter: Former President George W. Bush