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Posts Tagged ‘Aviva Lev-Ari’

War on Cancer Needs to Refocus to Stay Ahead of Disease Says Cancer Expert


War on Cancer Needs to Refocus to Stay Ahead of Disease Says Cancer Expert

Writer, Curator: Stephen J. Williams, Ph.D.

Is one of the world’s most prominent cancer researchers throwing in the towel on the War On Cancer? Not throwing in the towel, just reminding us that cancer is more complex than just a genetic disease, and in the process, giving kudos to those researchers who focus on non-genetic aspects of the disease (see Dr. Larry Bernstein’s article Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?).

 

National Public Radio (NPR) has been conducting an interview series with MIT cancer biology pioneer, founding member of the Whitehead Institute for Biomedical Research, and National Academy of Science member and National Medal of Science awardee Robert A. Weinberg, Ph.D., who co-discovered one of the first human oncogenes (Ras)[1], isolation of first tumor suppressor (Rb)[2], and first (with Dr. Bill Hahn) proved that cells could become tumorigenic after discrete genetic lesions[3].   In the latest NPR piece, Why The War On Cancer Hasn’t Been Won (seen on NPR’s blog by Richard Harris), Dr. Weinberg discusses a comment in an essay he wrote in the journal Cell[4], basically that, in recent years, cancer research may have focused too much on the genetic basis of cancer at the expense of multifaceted etiology of cancer, including the roles of metabolism, immunity, and physiology. Cancer is the second most cause of medically related deaths in the developed world. However, concerted efforts among most developed nations to eradicate the disease, such as increased government funding for cancer research and a mandated ‘war on cancer’ in the mid 70’s has translated into remarkable improvements in diagnosis, early detection, and cancer survival rates for many individual cancer. For example, survival rate for breast and colon cancer have improved dramatically over the last 40 years. In the UK, overall median survival times have improved from one year in 1972 to 5.8 years for patients diagnosed in 2007. In the US, the overall 5 year survival improved from 50% for all adult cancers and 62% for childhood cancer in 1972 to 68% and childhood cancer rate improved to 82% in 2007. However, for some cancers, including lung, brain, pancreatic and ovarian cancer, there has been little improvement in survival rates since the “war on cancer” has started.

(Other NPR interviews with Dr. Weinberg include How Does Cancer Spread Through The Body?)

As Weinberg said, in the 1950s, medical researchers saw cancer as “an extremely complicated process that needed to be described in hundreds, if not thousands of different ways,”. Then scientists tried to find a unifying principle, first focusing on viruses as the cause of cancer (for example rous sarcoma virus and read Dr. Gallo’s book on his early research on cancer, virology, and HIV in Virus Hunting: AIDS, Cancer & the Human Retrovirus: A Story of Scientific Discovery).

However (as the blog article goes on) “that idea was replaced by the notion that cancer is all about wayward genes.”

“The thought, at least in the early 1980s, was that were a small number of these mutant, cancer-causing oncogenes, and therefore that one could understand a whole disparate group of cancers simply by studying these mutant genes that seemed to be present in many of them,” Weinberg says. “And this gave the notion, the illusion over the ensuing years, that we would be able to understand the laws of cancer formation the way we understand, with some simplicity, the laws of physics, for example.”

According to Weinberg, this gene-directed unifying theory has given way as recent evidences point back once again to a multi-faceted view of cancer etiology.

But this is not a revolutionary or conflicting idea for Dr. Weinberg, being a recipient of the 2007 Otto Warburg Medal and focusing his latest research on complex systems such as angiogenesis, cell migration, and epithelial-stromal interactions.

In fact, it was both Dr. Weinberg and Dr. Bill Hanahan who formulated eight governing principles or Hallmarks of cancer:

  1. Maintaining Proliferative Signals
  2. Avoiding Immune Destruction
  3. Evading Growth Suppressors
  4. Resisting Cell Death
  5. Becoming Immortal
  6. Angiogenesis
  7. Deregulating Cellular Energy
  8. Activating Invasion and Metastasis

Taken together, these hallmarks represent the common features that tumors have, and may involve genetic or non-genetic (epigenetic) lesions … a multi-modal view of cancer that spans over time and across disciplines. As reviewed by both Dr. Larry Bernstein and me in the e-book Volume One: Cancer Biology and Genomics for Disease Diagnosis, each scientific discipline, whether the pharmacologist, toxicologist, virologist, molecular biologist, physiologist, or cell biologist has contributed greatly to our total understanding of this disease, each from their own unique perspective based on their discipline. This leads to a “multi-modal” view on cancer etiology and diagnosis, treatment. Many of the improvements in survival rates are a direct result of the massive increase in the knowledge of tumor biology obtained through ardent basic research. Breakthrough discoveries regarding oncogenes, cancer cell signaling, survival, and regulated death mechanisms, tumor immunology, genetics and molecular biology, biomarker research, and now nanotechnology and imaging, have directly led to the advances we now we in early detection, chemotherapy, personalized medicine, as well as new therapeutic modalities such as cancer vaccines and immunotherapies and combination chemotherapies. Molecular and personalized therapies such as trastuzumab and aromatase inhibitors for breast cancer, imatnib for CML and GIST related tumors, bevacizumab for advanced colorectal cancer have been a direct result of molecular discoveries into the nature of cancer. This then leads to an interesting question (one to be tackled in another post):

Would shifting focus less on cancer genome and back to cancer biology limit the progress we’ve made in personalized medicine?

 

In a 2012 post Genomics And Targets For The Treatment Of Cancer: Is Our New World Turning Into “Pharmageddon” Or Are We On The Threshold Of Great Discoveries? Dr. Leonard Lichtenfield, MD, Deputy Chief Medical Officer for the ACS, comments on issues regarding the changes which genomics and personalized strategy has on oncology drug development. As he notes, in the past, chemotherapy development was sort of ‘hit or miss’ and the dream and promise of genomics suggested an era of targeted therapy, where drug development was more ‘rational’ and targets were easily identifiable.

To quote his post

That was the dream, and there have been some successes–even apparent cures or long term control–with the used of targeted medicines with biologic drugs such as Gleevec®, Herceptin® and Avastin®. But I think it is fair to say that the progress and the impact hasn’t been quite what we thought it would be. Cancer has proven a wily foe, and every time we get answers to questions what we usually get are more questions that need more answers. The complexity of the cancer cell is enormous, and its adaptability and the genetic heterogeneity of even primary cancers (as recently reported in a research paper in the New England Journal of Medicine) has been surprising, if not (realistically) unexpected.

                                                                               ”

Indeed the complexity of a given patient’s cancer (especially solid tumors) with regard to its genetic and mutation landscape (heterogeneity) [please see post with interview with Dr. Swanton on tumor heterogeneity] has been at the forefront of many clinicians minds [see comments within the related post as well as notes from recent personalized medicine conferences which were covered live on this site including the PMWC15 and Harvard Personalized Medicine conference this past fall].

In addition, Dr. Lichtenfeld makes some interesting observations including:

  • A “pharmageddon” where drug development risks/costs exceed the reward so drug developers keep their ‘wallets shut’. For example even for targeted therapies it takes $12 billion US to develop a drug versus $2 billion years ago
  • Drugs are still drugs and failure in clinical trials is still a huge risk
  • “Eroom’s Law” (like “Moore’s Law” but opposite effect) – increasing costs with decreasing success
  • Limited market for drugs targeted to a select mutant; what he called “slice and dice”

The pros and cons of focusing solely on targeted therapeutic drug development versus using a systems biology approach was discussed at the 2013 Institute of Medicine’s national Cancer Policy Summit.

  • Andrea Califano, PhD – Precision Medicine predictions based on statistical associations where systems biology predictions based on a physical regulatory model
  • Spyro Mousses, PhD – open biomedical knowledge and private patient data should be combined to form systems oncology clearinghouse to form evolving network, linking drugs, genomic data, and evolving multiscalar models
  • Razelle Kurzrock, MD – What if every patient with metastatic disease is genomically unique? Problem with model of smaller trials (so-called N=1 studies) of genetically similar disease: drugs may not be easily acquired or re-purposed, and greater regulatory burdens

So, discoveries of oncogenes, tumor suppressors, mutant variants, high-end sequencing, and the genomics and bioinformatic era may have led to advent of targeted chemotherapies with genetically well-defined patient populations, a different focus in chemotherapy development

… but as long as we have the conversation open I have no fear of myopia within the field, and multiple viewpoints on origins and therapeutic strategies will continue to develop for years to come.

References

  1. Parada LF, Tabin CJ, Shih C, Weinberg RA: Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 1982, 297(5866):474-478.
  2. Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP: A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986, 323(6089):643-646.
  3. Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA: Creation of human tumour cells with defined genetic elements. Nature 1999, 400(6743):464-468.
  4. Weinberg RA: Coming full circle-from endless complexity to simplicity and back again. Cell 2014, 157(1):267-271.

 

Other posts on this site on The War on Cancer and Origins of Cancer include:

 

2013 Perspective on “War on Cancer” on December 23, 1971

Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

World facing cancer ‘tidal wave’, warns WHO

2013 American Cancer Research Association Award for Outstanding Achievement in Chemistry in Cancer Research: Professor Alexander Levitzki

Genomics and Metabolomics Advances in Cancer

The Changing Economics of Cancer Medicine: Causes for the Vanishing of Independent Oncology Groups in the US

Cancer Research Pioneer, after 71 years of Immunology Lab Research, Herman Eisen, MD, MIT Professor Emeritus of Biology, dies at 96

My Cancer Genome from Vanderbilt University: Matching Tumor Mutations to Therapies & Clinical Trials

Articles on Cancer-Related Topic in http://pharmaceuticalintelligence.com Scientific Journal

Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

Issues in Personalized Medicine: Discussions of Intratumor Heterogeneity from the Oncology Pharma forum on LinkedIn

Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

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Podcast Review: Quiet Innovation Podcast on Obtaining $ for Your Startup

Reporter: Stephen J. Williams, Ph.D.

I wanted to highlight an interesting interview (What it Really Takes to Get Money for Your Startup) with David S. Rose, serial entrepreneur and Founder and CEO of Gust.com, which is a global collaboration platform for early stage angel investing, connecting hundreds of thousands of entrepreneurs and investors in over 75 countries. The interview with David and CFA John P. Gavin was broadcast on the podcast Quiet Innovation (from PodCast Addict @Podcast_Addict) from. I had tweeted it out on my Twitter account below (see the http link)

 

… but will include some notes from the podcast here. In addition you can link to the podcast directly using the links below:

QI-013 David Rose Interview_01.mp3

Or download the mp3

http://t.co/XPjLrJQG7O

This post is a followup from yesterday’s post Protecting Your Biotech IP and Market Strategy: Notes from Life Sciences Collaborative 2015 Meeting.

Some highlights from the podcast

  • IDEAS DON’T GET FUNDED

David Rose discusses how there are hundreds of thousands of new ideas, some which are great some which are not… having an idea may be an initial step but for an investor to even consider your idea it is more important to have

  • EXECUTION

This is what David feels is critical to investors, such as himself, to decide whether your idea is investable. A startup needs to show they can accomplish their goal and show at least a rudimentary example of this, whether it is putting up a website or writing up a design blueprint for a new widget. He says starting a business today (either tech or manufacturing) requires a lot less capital than years ago (unless you are starting a biotech). He gives an example of internet startups he had founded in the 90’s versus today… in the 90’s you needed $2 million… today you can do it for $2,000. But the ability to show that you can EXECUTE this plan is CRITICAL.

David sites three aspects which are important to investors:

  1. Integrity – Be humble about yourself. He says there are way too many people who claim ‘our idea is the best’ or ‘we do it better than anyone’ or ‘we are the first to have this idea’. As he says Jeff Bezos of Amazon was not the first to have the idea of selling books over the internet, he just EXECUTED the plan extremely well.
  2. Passion- Investors need to see that you are ‘all in’ and committed. A specific example is angels asking how much money have you put into your idea (skin in the game)
  3. Experience- David says there are TWO important types of experience in developing startups and both valid. The first is how many startups have you done and succeeded and the second is how many startups have failed. He says investors actually like if you have failed because they are learning experiences, just as valuable if not more than having startups always succeed. Investors need to know how you can deal with adversity. All three points goes back to execution.

David Rose gave some reading suggestions as well including

Lucky or Smart? Secrets to an Entrepreneurial Life by Bo Peabody – He highlights this book to help people understand that a startup entrepreneur should always hire someone smarter than themselves.

Derek Sivers post Ideas Are Just a Multiplier of Execution  – where a great idea is worth $20 but a great idea plus execution is worth $20 million.

Eris Reese’s post The Lean Startup in his blog StartUpLessonsLearned – being frugal (gets back to what he said about not needed as much capital as you would think i.e. Don’t Burn Through the Cash) and also get metrics on your startup or idea (as long as you have the IP). He suggests taking out an ad to see what the interest is out there. You can measure the clicks from the ad and use that as a marketing tool to potential investors i.e. Getting Feedback

Some other posts on this site about Investing and Startups include:

Protecting Your Biotech IP and Market Strategy: Notes from Life Sciences Collaborative 2015 Meeting

THE BLOOMBERG INNOVATION INDEX: Country Rankings by Six Measures of the Capacity to Innovate as a Nation

Updated: Investing and Inventing: Is the Tango of Mars and Venus Still on

Sand Hill Angels

The Bioscience Crowdfunding Environment: The Bigger Better VC?

Technion-Cornell Innovation Institute in NYC: Postdocs keep exclusive license to their IP and take a fixed dollar amount of Equity if the researchers create a Spinoff company

Tycho Brahe, where art thou? Today’s Renaissance of the Self-Funded Scientist!

 

 

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Protecting Your Biotech IP and Market Strategy: Notes from Life Sciences Collaborative 2015 Meeting


 

Protecting Your Biotech IP and Market Strategy: Notes from Life Sciences Collaborative 2015 Meeting

Achievement Beyond Regulatory Approval – Design for Commercial Success

philly2nightStephen J. Williams, Ph.D.: Reporter

The Mid-Atlantic group Life Sciences Collaborative, a select group of industry veterans and executives from the pharmaceutical, biotechnology, and medical device sectors whose mission is to increase the success of emerging life sciences businesses in the Mid-Atlantic region through networking, education, training and mentorship, met Tuesday March 3, 2015 at the University of the Sciences in Philadelphia (USP) to discuss post-approval regulatory issues and concerns such as designing strong patent protection, developing strategies for insurance reimbursement, and securing financing for any stage of a business.

The meeting was divided into three panel discussions and keynote speech:

  1. Panel 1: Design for Market Protection– Intellectual Property Strategy Planning
  2. Panel 2: Design for Market Success– Commercial Strategy Planning
  3. Panel 3: Design for Investment– Financing Each Stage
  4. Keynote Speaker: Robert Radie, President & CEO Egalet Corporation

Below are Notes from each PANEL Discussion:

For more information about the Life Sciences Collaborative SEE

Website: http://www.lifesciencescollaborative.org/

Or On Facebook

Or On Twitter @LSCollaborative

Panel 1: Design for Market Protection; Intellectual Property Strategy Planning

Take-home Message: Developing a very strong Intellectual Property (IP) portfolio and strategy for a startup is CRITICALLY IMPORTANT for its long-term success. Potential investors, partners, and acquirers will focus on the strength of a startup’s IP so important to take advantage of the legal services available. Do your DUE DIGILENCE.

Panelists:

John F. Ritter, J.D.., MBA; Director Office Tech. Licensing Princeton University

Cozette McAvoy; Senior Attorney Novartis Oncology Pharma Patents

Ryan O’Donnell; Partner Volpe & Koenig

Panel Moderator: Dipanjan “DJ” Nag, PhD, MBA, CLP, RTTP; President CEO IP Shaktl, LLC

Notes:

Dr. Nag:

  • Sometimes IP can be a double edged sword; e.g. Herbert Boyer with Paul Berg and Stanley Cohen credited with developing recombinant technology but they did not keep the IP strict and opened the door for a biotech revolution (see nice review from Chemical Heritage Foundation).
  • Naked patent licenses are most profitable when try to sell IP

John Ritter: Mr. Ritter gave Princeton University’s perspective on developing and promoting a university-based IP portfolio.

  • 30-40% of Princeton’s IP portfolio is related to life sciences
  • Universities will prefer to seek provisional patent status as a quicker process and allows for publication
  • Princeton will work closely with investigators to walk them through process – Very Important to have support system in place INCLUDING helping investigators and early startups establish a STRONG startup MANAGEMENT TEAM, and making important introductions to and DEVELOPING RELATIONSHIOPS with investors, angels
  • Good to cast a wide net when looking at early development partners like pharma
  • Good example of university which takes active role in developing startups is University of Pennsylvania’s Penn UPstart program.
  • Last 2 years many universities filing patents for startups as a micro-entity

Comment from attendee: Universities are not using enough of their endowments for purpose of startups. Princeton only using $500,00 for accelerator program.

Cozette McAvoy: Mrs. McAvoy talked about monetizing your IP from an industry perspective

  • Industry now is looking at “indirect monetization” of their and others IP portfolio. Indirect monetization refers to unlocking the “indirect value” of intellectual property; for example research tools, processes, which may or may not be related to a tangible product.
  • Good to make a contractual bundle of IP – “days of the $million check is gone”
  • Big companies like big pharma looks to PR (press relation) buzz surrounding new technology, products SO IMPORTANT FOR STARTUP TO FOCUS ON YOUR PR

Ryan O’Donnell: talked about how life science IP has changed especially due to America Invests Act

  • Need to develop a GLOBAL IP strategy so whether drug or device can market in multiple countries
  • Diagnostics and genes not patentable now – Major shift in patent strategy
  • Companies like Unified Patents can protect you against the patent trolls – if patent threatened by patent troll (patent assertion entity) will file a petition with the USPTO (US Patent Office) requesting institution of inter partes review (IPR); this may cost $40,000 BUT WELL WORTH the money – BE PROACTIVE about your patents and IP

Panel 2: Design for Market Success; Commercial Strategy Planning

Take-home Message: Commercial strategy development is defined market facing data, reimbursement strategies and commercial planning that inform labeling requirements, clinical study designs, healthcare economic outcomes and pricing targets. Clarity from payers is extremely important to develop any market strategy. Develop this strategy early and seek advice from payers.

Panelists:

David Blaszczak; Founder, Precipio Health Strategies

Terri Bernacchi, PharmD, MBA; Founder & President Cambria Health Advisory Professionals

Paul Firuta; President US Commercial Operations, NPS Pharma

 

Panel Moderator: Matt Cabrey; Executive Director, Select Greater Philadelphia

 

Notes:

David Blaszczak:

  • Commercial payers are bundling payment: most important to get clarity from these payers
  • Payers are using clinical trials to alter marketing (labeling) so IMPORTANT to BUILD LABEL in early clinical trial phases (phase I or II)
  • When in early phases of small company best now to team or partner with a Medicare or PBM (pharmacy benefit manager) and payers to help develop and spot tier1 and tier 2 companies in their area

Terri Bernacchi:

  • Building relationship with the payer is very important but firms like hers will also look to patients and advocacy groups to see how they respond to a given therapy and decrease the price risk by bundling
  • Value-based contracting with manufacturers can save patient and payer $$
  • As most PBMs formularies are 80% generics goal is how to make money off of generics
  • Patent extension would have greatest impact on price, value

Paul Firuta:

  • NPS Pharma developing a pharmacy benefit program for orphan diseases
  • How you pay depends on mix of Medicare, private payers now
  • Most important change which could affect price is change in compliance regulations

Panel 3: Design for Investment; Financing Each Stage

Take-home Message: VC is a personal relationship so spend time making those relationships. Do your preparation on your value and your market. Look to non-VC avenues: they are out there.

Panelists:

Ting Pau Oei; Managing Director, Easton Capital (NYC)

Manya Deehr; CEO & Founder, Pediva Therapeutics

Sanjoy Dutta, PhD; Assistant VP, Translational Devel. & Intl. Res., Juvenile Diabetes Research Foundation

 

Panel Moderator: Shahram Hejazi, PhD; Venture Partner, BioAdvance

  • In 2000 his experience finding 1st capital was what are your assets; now has changed to value

Notes:

Ting Pau Oei:

  • Your very 1st capital is all about VALUE– so plan where you add value
  • Venture Capital is a PERSONAL RELATIONSHIP
  • 1) you need the management team, 2) be able to communicate effectively                  (Powerpoint, elevator pitch, business plan) and #1 and #2 will get you important 2nd Venture Capital meeting; VC’s don’t decide anything in 1st meeting
  • VC’s don’t normally do a good job of premarket valuation or premarket due diligence but know post market valuation well
  • Best advice: show some phase 2 milestones and VC will knock on your door

Manya Deehr:

  • Investment is more niche oriented so find your niche investors
  • Define your product first and then match the investors
  • Biggest failure she has experienced: companies that go out too early looking for capital

Dr. Dutta: funding from a non-profit patient advocacy group perspective

  • Your First Capital: find alliances which can help you get out of “valley of death
  • Develop a targeted product and patient treatment profile
  • Non-profit groups ask three questions:

1) what is the value to patients (non-profits want to partner)

2) what is your timeline (we can wait longer than VC; for example Cystic Fibrosis Foundation waited long time but got great returns for their patients with Kalydeco™)

3) when can we see return

  • Long-term market projections are the knowledge gaps that startups have (the landscape) and startups don’t have all the competitive intelligence
  • Have a plan B every step of the way

Other posts on this site related to Philadelphia Biotech, Startup Funding, Payer Issues, and Intellectual Property Issues include:

PCCI’s 7th Annual Roundtable “Crowdfunding for Life Sciences: A Bridge Over Troubled Waters?” May 12 2014 Embassy Suites Hotel, Chesterbrook PA 6:00-9:30 PM
The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy
The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC
The Vibrant Philly Biotech Scene: Focus on Vaccines and Philimmune, LLC
The Bioscience Crowdfunding Environment: The Bigger Better VC?
Foundations as a Funding Source
Venture Capital Funding in the Life Sciences: Phase4 Ventures – A Case Study
10 heart-focused apps & devices are crowdfunding for American Heart Association’s open innovation challenge
Funding, Deals & Partnerships
Medicare Panel Punts on Best Tx for Carotid Plaque
9:15AM–2:00PM, January 27, 2015 – Regulatory & Reimbursement Frameworks for Molecular Testing, LIVE @Silicon Valley 2015 Personalized Medicine World Conference, Mountain View, CA
FDA Commissioner, Dr. Margaret A. Hamburg on HealthCare for 310Million Americans and the Role of Personalized Medicine
Biosimilars: Intellectual Property Creation and Protection by Pioneer and by Biosimilar Manufacturers
Litigation on the Way: Broad Institute Gets Patent on Revolutionary Gene-Editing Method
The Patents for CRISPR, the DNA editing technology as the Biggest Biotech Discovery of the Century

 

 

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Artificial Intelligence Versus the Scientist: Who Will Win?

Will DARPA Replace the Human Scientist: Not So Fast, My Friend!

Writer, Curator: Stephen J. Williams, Ph.D.

scientistboxingwithcomputer

Last month’s issue of Science article by Jia You “DARPA Sets Out to Automate Research”[1] gave a glimpse of how science could be conducted in the future: without scientists. The article focused on the U.S. Defense Advanced Research Projects Agency (DARPA) program called ‘Big Mechanism”, a $45 million effort to develop computer algorithms which read scientific journal papers with ultimate goal of extracting enough information to design hypotheses and the next set of experiments,

all without human input.

The head of the project, artificial intelligence expert Paul Cohen, says the overall goal is to help scientists cope with the complexity with massive amounts of information. As Paul Cohen stated for the article:

“‘

Just when we need to understand highly connected systems as systems,

our research methods force us to focus on little parts.

                                                                                                                                                                                                               ”

The Big Mechanisms project aims to design computer algorithms to critically read journal articles, much as scientists will, to determine what and how the information contributes to the knowledge base.

As a proof of concept DARPA is attempting to model Ras-mutation driven cancers using previously published literature in three main steps:

  1. Natural Language Processing: Machines read literature on cancer pathways and convert information to computational semantics and meaning

One team is focused on extracting details on experimental procedures, using the mining of certain phraseology to determine the paper’s worth (for example using phrases like ‘we suggest’ or ‘suggests a role in’ might be considered weak versus ‘we prove’ or ‘provide evidence’ might be identified by the program as worthwhile articles to curate). Another team led by a computational linguistics expert will design systems to map the meanings of sentences.

  1. Integrate each piece of knowledge into a computational model to represent the Ras pathway on oncogenesis.
  2. Produce hypotheses and propose experiments based on knowledge base which can be experimentally verified in the laboratory.

The Human no Longer Needed?: Not So Fast, my Friend!

The problems the DARPA research teams are encountering namely:

  • Need for data verification
  • Text mining and curation strategies
  • Incomplete knowledge base (past, current and future)
  • Molecular biology not necessarily “requires casual inference” as other fields do

Verification

Notice this verification step (step 3) requires physical lab work as does all other ‘omics strategies and other computational biology projects. As with high-throughput microarray screens, a verification is needed usually in the form of conducting qPCR or interesting genes are validated in a phenotypical (expression) system. In addition, there has been an ongoing issue surrounding the validity and reproducibility of some research studies and data.

See Importance of Funding Replication Studies: NIH on Credibility of Basic Biomedical Studies

Therefore as DARPA attempts to recreate the Ras pathway from published literature and suggest new pathways/interactions, it will be necessary to experimentally validate certain points (protein interactions or modification events, signaling events) in order to validate their computer model.

Text-Mining and Curation Strategies

The Big Mechanism Project is starting very small; this reflects some of the challenges in scale of this project. Researchers were only given six paragraph long passages and a rudimentary model of the Ras pathway in cancer and then asked to automate a text mining strategy to extract as much useful information. Unfortunately this strategy could be fraught with issues frequently occurred in the biocuration community namely:

Manual or automated curation of scientific literature?

Biocurators, the scientists who painstakingly sort through the voluminous scientific journal to extract and then organize relevant data into accessible databases, have debated whether manual, automated, or a combination of both curation methods [2] achieves the highest accuracy for extracting the information needed to enter in a database. Abigail Cabunoc, a lead developer for Ontario Institute for Cancer Research’s WormBase (a database of nematode genetics and biology) and Lead Developer at Mozilla Science Lab, noted, on her blog, on the lively debate on biocuration methodology at the Seventh International Biocuration Conference (#ISB2014) that the massive amounts of information will require a Herculaneum effort regardless of the methodology.

Although I will have a future post on the advantages/disadvantages and tools/methodologies of manual vs. automated curation, there is a great article on researchinformation.infoExtracting More Information from Scientific Literature” and also see “The Methodology of Curation for Scientific Research Findings” and “Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison” for manual curation methodologies and A MOD(ern) perspective on literature curation for a nice workflow paper on the International Society for Biocuration site.

The Big Mechanism team decided on a full automated approach to text-mine their limited literature set for relevant information however was able to extract only 40% of relevant information from these six paragraphs to the given model. Although the investigators were happy with this percentage most biocurators, whether using a manual or automated method to extract information, would consider 40% a low success rate. Biocurators, regardless of method, have reported ability to extract 70-90% of relevant information from the whole literature (for example for Comparative Toxicogenomics Database)[3-5].

Incomplete Knowledge Base

In an earlier posting (actually was a press release for our first e-book) I had discussed the problem with the “data deluge” we are experiencing in scientific literature as well as the plethora of ‘omics experimental data which needs to be curated.

Tackling the problem of scientific and medical information overload

pubmedpapersoveryears

Figure. The number of papers listed in PubMed (disregarding reviews) during ten year periods have steadily increased from 1970.

Analyzing and sharing the vast amounts of scientific knowledge has never been so crucial to innovation in the medical field. The publication rate has steadily increased from the 70’s, with a 50% increase in the number of original research articles published from the 1990’s to the previous decade. This massive amount of biomedical and scientific information has presented the unique problem of an information overload, and the critical need for methodology and expertise to organize, curate, and disseminate this diverse information for scientists and clinicians. Dr. Larry Bernstein, President of Triplex Consulting and previously chief of pathology at New York’s Methodist Hospital, concurs that “the academic pressures to publish, and the breakdown of knowledge into “silos”, has contributed to this knowledge explosion and although the literature is now online and edited, much of this information is out of reach to the very brightest clinicians.”

Traditionally, organization of biomedical information has been the realm of the literature review, but most reviews are performed years after discoveries are made and, given the rapid pace of new discoveries, this is appearing to be an outdated model. In addition, most medical searches are dependent on keywords, hence adding more complexity to the investigator in finding the material they require. Third, medical researchers and professionals are recognizing the need to converse with each other, in real-time, on the impact new discoveries may have on their research and clinical practice.

These issues require a people-based strategy, having expertise in a diverse and cross-integrative number of medical topics to provide the in-depth understanding of the current research and challenges in each field as well as providing a more conceptual-based search platform. To address this need, human intermediaries, known as scientific curators, are needed to narrow down the information and provide critical context and analysis of medical and scientific information in an interactive manner powered by web 2.0 with curators referred to as the “researcher 2.0”. This curation offers better organization and visibility to the critical information useful for the next innovations in academic, clinical, and industrial research by providing these hybrid networks.

Yaneer Bar-Yam of the New England Complex Systems Institute was not confident that using details from past knowledge could produce adequate roadmaps for future experimentation and noted for the article, “ “The expectation that the accumulation of details will tell us what we want to know is not well justified.”

In a recent post I had curated findings from four lung cancer omics studies and presented some graphic on bioinformatic analysis of the novel genetic mutations resulting from these studies (see link below)

Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for

Non-Small Cell Lung Cancer

which showed, that while multiple genetic mutations and related pathway ontologies were well documented in the lung cancer literature there existed many significant genetic mutations and pathways identified in the genomic studies but little literature attributed to these lung cancer-relevant mutations.

KEGGinliteroanalysislungcancer

  This ‘literomics’ analysis reveals a large gap between our knowledge base and the data resulting from large translational ‘omic’ studies.

Different Literature Analyses Approach Yeilding

A ‘literomics’ approach focuses on what we don NOT know about genes, proteins, and their associated pathways while a text-mining machine learning algorithm focuses on building a knowledge base to determine the next line of research or what needs to be measured. Using each approach can give us different perspectives on ‘omics data.

Deriving Casual Inference

Ras is one of the best studied and characterized oncogenes and the mechanisms behind Ras-driven oncogenenis is highly understood.   This, according to computational biologist Larry Hunt of Smart Information Flow Technologies makes Ras a great starting point for the Big Mechanism project. As he states,” Molecular biology is a good place to try (developing a machine learning algorithm) because it’s an area in which common sense plays a minor role”.

Even though some may think the project wouldn’t be able to tackle on other mechanisms which involve epigenetic factors UCLA’s expert in causality Judea Pearl, Ph.D. (head of UCLA Cognitive Systems Lab) feels it is possible for machine learning to bridge this gap. As summarized from his lecture at Microsoft:

“The development of graphical models and the logic of counterfactuals have had a marked effect on the way scientists treat problems involving cause-effect relationships. Practical problems requiring causal information, which long were regarded as either metaphysical or unmanageable can now be solved using elementary mathematics. Moreover, problems that were thought to be purely statistical, are beginning to benefit from analyzing their causal roots.”

According to him first

1) articulate assumptions

2) define research question in counter-inference terms

Then it is possible to design an inference system using calculus that tells the investigator what they need to measure.

To watch a video of Dr. Judea Pearl’s April 2013 lecture at Microsoft Research Machine Learning Summit 2013 (“The Mathematics of Causal Inference: with Reflections on Machine Learning”), click here.

The key for the Big Mechansism Project may me be in correcting for the variables among studies, in essence building a models system which may not rely on fully controlled conditions. Dr. Peter Spirtes from Carnegie Mellon University in Pittsburgh, PA is developing a project called the TETRAD project with two goals: 1) to specify and prove under what conditions it is possible to reliably infer causal relationships from background knowledge and statistical data not obtained under fully controlled conditions 2) develop, analyze, implement, test and apply practical, provably correct computer programs for inferring causal structure under conditions where this is possible.

In summary such projects and algorithms will provide investigators the what, and possibly the how should be measured.

So for now it seems we are still needed.

References

  1. You J: Artificial intelligence. DARPA sets out to automate research. Science 2015, 347(6221):465.
  2. Biocuration 2014: Battle of the New Curation Methods [http://blog.abigailcabunoc.com/biocuration-2014-battle-of-the-new-curation-methods]
  3. Davis AP, Johnson RJ, Lennon-Hopkins K, Sciaky D, Rosenstein MC, Wiegers TC, Mattingly CJ: Targeted journal curation as a method to improve data currency at the Comparative Toxicogenomics Database. Database : the journal of biological databases and curation 2012, 2012:bas051.
  4. Wu CH, Arighi CN, Cohen KB, Hirschman L, Krallinger M, Lu Z, Mattingly C, Valencia A, Wiegers TC, John Wilbur W: BioCreative-2012 virtual issue. Database : the journal of biological databases and curation 2012, 2012:bas049.
  5. Wiegers TC, Davis AP, Mattingly CJ: Collaborative biocuration–text-mining development task for document prioritization for curation. Database : the journal of biological databases and curation 2012, 2012:bas037.

Other posts on this site on include: Artificial Intelligence, Curation Methodology, Philosophy of Science

Inevitability of Curation: Scientific Publishing moves to embrace Open Data, Libraries and Researchers are trying to keep up

A Brief Curation of Proteomics, Metabolomics, and Metabolism

The Methodology of Curation for Scientific Research Findings

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

The growing importance of content curation

Data Curation is for Big Data what Data Integration is for Small Data

Cardiovascular Original Research: Cases in Methodology Design for Content Co-Curation The Art of Scientific & Medical Curation

Exploring the Impact of Content Curation on Business Goals in 2013

Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison

conceived: NEW Definition for Co-Curation in Medical Research

Reconstructed Science Communication for Open Access Online Scientific Curation

Search Results for ‘artificial intelligence’

 The Simple Pictures Artificial Intelligence Still Can’t Recognize

Data Scientist on a Quest to Turn Computers Into Doctors

Vinod Khosla: “20% doctor included”: speculations & musings of a technology optimist or “Technology will replace 80% of what doctors do”

Where has reason gone?

Read Full Post »


  • Oracle Industry Connect Presents Their 2015 Life Sciences and Healthcare Program

 

Reporter: Stephen J. Williams, Ph.D. and Aviva Lev-Ari, Ph.D., R.N.

oraclehealthcare

Copyright photo Oracle Inc. (TM)

 

Transforming Clinical Research and Clinical Care with Data-Driven Intelligence

March 25-26 Washington, DC

For more information click on the following LINK:

https://www.oracle.com/oracleindustryconnect/life-sciences-healthcare.html

oracle-healthcare-solutions-br-1526409

https://www.oracle.com/industries/health-sciences/index.html  

Oracle Health Sciences: Life Sciences & HealthCare — the Solutions for Big Data

Healthcare and life sciences organizations are facing unprecedented challenges to improve drug development and efficacy while driving toward more targeted and personalized drugs, devices, therapies, and care. Organizations are facing an urgent need to meet the unique demands of patients, regulators, and payers, necessitating a move toward a more patient-centric, value-driven, and personalized healthcare ecosystem.

Meeting these challenges requires redesigning clinical R&D processes, drug therapies, and care delivery through innovative software solutions, IT systems, data analysis, and bench-to-bedside knowledge. The core mission is to improve the health, well-being, and lives of people globally by:

  • Optimizing clinical research and development, speeding time to market, reducing costs, and mitigating risk
  • Accelerating efficiency by using business analytics, costing, and performance management technologies

 

  • Establishing a global infrastructure for collaborative clinical discovery and care delivery models
  • Scaling innovations with world-class, transformative technology solutions
  • Harnessing the power of big data to improve patient experience and outcomes

The Oracle Industry Connect health sciences program features 15 sessions showcasing innovation and transformation of clinical R&D, value-based healthcare, and personalized medicine.

The health sciences program is an invitation-only event for senior-level life sciences and healthcare business and IT executives.

Complete your registration and book your hotel reservation prior to February 27, 2015 in order to secure the Oracle discounted hotel rate.

Learn more about Oracle Healthcare.

General Welcome and Joint Program Agenda

Wednesday, March 25

10:30 a.m.–12:00 p.m.

Oracle Industry Connect Opening Keynote

Mark Hurd, Chief Executive Officer, Oracle

Bob Weiler, Executive Vice President, Global Business Units, Oracle

Warren Berger, Author of “A More Beautiful Question: The Power of Inquiry to Spark Breakthrough Ideas.”

12:00 p.m.–1:45 p.m.

Networking Lunch

1:45 p.m.–2:45 p.m.

Oracle Industry Connect Keynote

Bob Weiler, Executive Vice President, Global Business Units, Oracle

2:45 p.m.–3:45 p.m.

Networking Break

3:45 p.m.–5:45 p.m.

Life Sciences and Healthcare General Session

Robert Robbins, President, Chief Executive Officer, Texas Medical Center

Steve Rosenberg, Senior Vice President and General Manager Health Sciences Global Business Unit, Oracle

7:00 p.m.–10:00 p.m.

Life Sciences and Healthcare Networking Reception

National Museum of American History
14th Street and Constitution Avenue, NW
Washington DC 20001

Life Sciences Agenda

Thursday, March 26

7:00 a.m.–8:00 a.m.

Networking Breakfast

8:00 a.m.–9:15 a.m.

Digital Trials and Research Models of the Future 

Markus Christen, Senior Vice President and Head of Global Development, Proteus

Praveen Raja, Senior Director of Medical Affairs, Proteus Digital Health

Michael Stapleton, Vice President and Chief Information Officer, R&D IT, Merck

9:15 a.m.–10:30 a.m.

Driving Patient Engagement and the Internet of Things 

Howard Golub, Vice President of Clinical Research, Walgreens

Jean-Remy Behaeghel, Senior Director, Client Account Management, Product Development Solutions, Vertex Pharmaceuticals

10:30 a.m.–10:45 a.m.

Break

10:45 a.m.–12:00 p.m.

Leveraging Data and Advanced Analytics to Enable True Pharmacovigilance and Risk Management 

Leonard Reyno, Senior Vice President, Chief Medical Officer, Agensys

 

Accelerating Therapeutic Development Through New Technologies 

Andrew Rut, Chief Executive Officer, Co-Founder and Director, MyMeds&Me

12:45 a.m.–1:45 p.m.

Networking Lunch

1:45 p.m.–2:30 p.m.

Oracle Industry Connect Keynote

2:30 p.m.–2:45 p.m.

Break

2:45 p.m.–3:15 p.m.

Harnessing Big Data to Increase R&D Innovation, Efficiency, and Collaboration 

Sandy Tremps, Executive Director, Global Clinical Development IT, Merck

3:15 p.m.–3:30 p.m.

Break

3:30 p.m.–4:45 p.m.

Transforming Clinical Research from Planning to Postmarketing 

Kenneth Getz, Director of Sponsored Research Programs and Research Associate Professor, Tufts University

Jason Raines, Head, Global Data Operations, Alcon Laboratories

4:45 p.m.–6:00 p.m.

Increasing Efficiency and Pipeline Performance Through Sponsor/CRO Data Transparency and Cloud Collaboration 

Thomas Grundstrom, Vice President, ICONIK, Cross Functional IT Strategies and Innovation, ICON

Margaret Keegan, Senior Vice President, Global Head Data Sciences and Strategy, Quintiles

6:00 p.m.–9:00 p.m.

Oracle Customer Networking Event

Healthcare Agenda

Thursday, March 26

7:00 a.m.–8:15 a.m.

Networking Breakfast

8:30 a.m.–9:15 a.m.

Population Health: A Core Competency for Providers in a Post Fee-for-Service Model 

Margaret Anderson, Executive Director, FasterCures

Balaji Apparsamy, Director, Business Intellegence, Baycare

Leslie Kelly Hall, Senior Vice President, Policy, Healthwise

Peter Pronovost, Senior Vice President, Patient Safety & Quality, Johns Hopkins

Sanjay Udoshi, Healthcare Product Strategy, Oracle

9:15 a.m.–9:30 a.m.

Break

9:30 a.m.–10:15 a.m.

Population Health: A Core Competency for Providers in a Post Fee-for-Service Model (Continued)

10:15 a.m.–10:45 a.m.

Networking Break

10:45 a.m.–11:30 a.m.

Managing Cost of Care in the Era of Healthcare Reform 

Chris Bruerton, Director, Budgeting, Intermountain Healthcare

Tony Byram, Vice President Business Integration, Ascension

Kerri-Lynn Morris, Executive Director, Finance Operations and Strategic Projects, Kaiser Permanente

Kavita Patel, Managing Director, Clinical Transformation, Brookings Institute

Christine Santos, Chief of Strategic Business Analytics, Providence Health & Services

Prashanth Kini, Senior Director, Healthcare Product Strategy, Oracle

11:30 a.m.–11:45 a.m.

Break

11:45 a.m.–12:45 p.m.

Managing Cost of Care in the Era of Healthcare Reform (Continued)

12:45 p.m.–1:45 p.m.

Networking Lunch

1:45 p.m.–2:30 p.m.

Oracle Industry Connect Keynote

2:30 p.m.–2:45 p.m.

Break

2:45 p.m.–3:30 p.m.

Precision Medicine 

Annerose Berndt, Vice President, Analytics and Information, UPMC

James Buntrock, Vice Chair, Information Management and Analytics, Mayo Clinic

Dan Ford, Vice Dean for Clinical Investigation, Johns Hopkins Medicine

Jan Hazelzet, Chief Medical Information Officer, Erasmus MC

Stan Huff, Chief Medical Information Officer, Intermountain Healthcare

Vineesh Khanna, Director, Biomedical Informatics, SIDRA

Brian Wells, Vice President, Health Technology, Penn Medicine

Wanmei Ou, Senior Product Strategist, Healthcare, Oracle

3:30 p.m.–3:45 p.m.

Networking Break

3:45 p.m.–4:30 p.m.

Precision Medicine (Continued)

4:30 p.m.–4:45 p.m.

Break

6:00 p.m.–9:00 p.m.

Oracle Customer Networking Event

Additional Links to Oracle Pharma, Life Sciences and HealthCare

 
Life Sciences | Industry | Oracle <http://www.oracle.com/us/industries/life-sciences/overview/>

http://www.oracle.com/us/industries/life-sciences/overview/

 
Oracle Corporation

 
Oracle Applications for Life Sciences deliver a powerful combination of technology and preintegrated applications.

  • Clinical

<http://www.oracle.com/us/industries/life-sciences/clinical/overview/index.html>

  • Medical Devices

<http://www.oracle.com/us/industries/life-sciences/medical/overview/index.html>

  • Pharmaceuticals

<http://www.oracle.com/us/industries/life-sciences/pharmaceuticals/overview/index.html>

 
Life Sciences Solutions | Pharmaceuticals and … – Oracle <http://www.oracle.com/us/industries/life-sciences/solutions/index.html>

http://www.oracle.com  Industries  Life Sciences

 
Oracle Corporation

 
Life Sciences Pharmaceuticals and Biotechnology.

 
Oracle Life Sciences Data Hub – Overview | Oracle <http://www.oracle.com/us/products/applications/health-sciences/e-clinical/data-hub/index.html>

http://www.oracle.com  …  E-Clinical Solutions

 
Oracle Corporation

 
Oracle Life Sciences Data Hub. Better Insights, More Informed Decision-Making. Provides an integrated environment for clinical data, improving regulatory …

 
Pharmaceuticals and Biotechnology | Oracle Life Sciences <http://www.oracle.com/us/industries/life-sciences/pharmaceuticals/overview/index.html>

http://www.oracle.com/us/…/life-sciences/…/index.html

 
Oracle Corporation

 
Oracle Applications for Pharmaceuticals and Biotechnology deliver a powerful combination of technology and preintegrated applications.

 
Oracle Health Sciences – Healthcare and Life Sciences … <https://www.oracle.com/industries/health-sciences/>

https://www.oracle.com/industries/health-sciences/

 
Oracle Corporation

 
Oracle Health Sciences leverages industry-shaping technologies that optimize clinical R&D, mitigate risk, advance healthcare, and improve patient outcomes.

 
Clinical | Oracle Life Sciences | Oracle <http://www.oracle.com/us/industries/life-sciences/clinical/overview/index.html>

http://www.oracle.com  Industries  Life Sciences  Clinical

 
Oracle Corporation

 
Oracle for Clinical Applications provides an integrated remote data collection facility for site-based entry.

 
Oracle Life Sciences | Knowledge Zone | Oracle … <http://www.oracle.com/partners/en/products/industries/life-sciences/get-started/index.html>

http://www.oracle.com/partners/…/life-sciences/…/index.ht…;

 
Oracle Corporation

 
This Knowledge Zone was specifically developed for partners interested in reselling or specializing in Oracle Life Sciences solutions. To become a specialized …

 
[PDF]Brochure: Oracle Health Sciences Suite of Life Sciences … <http://www.oracle.com/us/industries/life-sciences/oracle-life-sciences-solutions-br-414127.pdf>

http://www.oracle.com/…/life-sciences/oracle-life-sciences-s…;

 
Oracle Corporation

 
Oracle Health Sciences Suite of. Life Sciences Solutions. Integrated Solutions for Global Clinical Trials. Oracle Health Sciences provides the world’s broadest set …

 

 

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The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

Curator and Interviewer: Stephen J. Williams, Ph.D.

 

 

philly philly2night

 

 

 

 

 

 

 

This post is the second in a series of posts highlighting interviews with Philadelphia area biotech startup CEO’s and show how a vibrant biotech startup scene is evolving in the city as well as the Delaware Valley area. Philadelphia has been home to some of the nation’s oldest biotechs including Cephalon, Centocor, hundreds of spinouts from a multitude of universities as well as home of the first cloned animal (a frog), the first transgenic mouse, and Nobel laureates in the field of molecular biology and genetics. Although some recent disheartening news about the fall in rankings of Philadelphia as a biotech hub and recent remarks by CEO’s of former area companies has dominated the news, biotech incubators like the University City Science Center and Bucks County Biotechnology Center as well as a reinvigorated investment community (like PCCI and MABA) are bringing Philadelphia back. And although much work is needed to bring the Philadelphia area back to its former glory days (including political will at the state level) there are many bright spots such as the innovative young companies as outlined in these posts.

efavirenz_med-2In today’s post, I had the opportunity to talk with molecular modeler Charles H. Reynolds, Ph.D., founder and CEO of Gfree Bio LLC, a computational structure-based design and modeling company based in the Pennsylvania Biotech Center of Bucks County. Gfree is actually one of a few molecular modeling companies at the Bucks County Biotech Center (I highlighted another company RabD Biotech which structural computational methods to design antibody therapeutics).

Below is the interview with Dr. Reynolds of Gfree Bio LLC and Leaders in Pharmaceutical Business Intelligence (LPBI):

LPBI: Could you briefly explain, for non-molecular modelers, your business and the advantages you offer over other molecular modeling programs (either academic programs or other biotech companies)? As big pharma outsources more are you finding that your company is filling a needed niche market?

GfreeBio: Gfree develops and deploys innovative computational solutions to accelerate drug discovery. We can offer academic labs a proven partner for developing SBIR/STTR proposals that include a computational or structure-based design component. This can be very helpful in developing a successful proposal. We also provide the same modeling and structure-based design input for small biotechs that do not have these capabilities internally. Working with Gfree is much more cost-effective than trying to develop these capabilities internally. We have helped several small biotechs in the Philadelphia region assess their modeling needs and apply computational tools to advance their discovery programs. (see publication and collaboration list here).

LPBI: Could you offer more information on the nature of your 2014 STTR award?

GfreeBio: Gfree has been involved in three successful SBIR/STTR awards in 2014.   I am the PI for an STTR with Professor Burgess of Texas A&M that is focused on new computational and synthetic approaches to designing inhibitors for protein-protein interactions. Gfree is also collaborating with the Wistar Institute and Phelix Therapeutics on two other Phase II proposals in the areas of oncology and infectious disease.

LPBI: Why did you choose the Bucks County Pennsylvania Biotechnology Center?

GfreeBio: I chose to locate my company at the Biotech Center because it is a regional hub for small biotech companies and it provides a range of shared resources that are very useful to the company. Many of my most valuable collaborations have resulted from contacts at the center.

LPBI: The Blumberg Institute and Natural Products Discovery Institute has acquired a massive phytochemical library. How does this resource benefit the present and future plans for GfreeBio?

GfreeBio: To date Gfree Bio has not been an active collaborator with the Natural Products Insititute, but I have a good relationship with the Director and that could change at any time.

LPBI: Was the state of Pennsylvania and local industry groups support GfreeBio’s move into the Doylestown incubator? Has the partnership with Ben Franklin Partners and the Center provided you with investment and partnership opportunities?

GfreeBio: Gfree Bio has not been actively seeking outside investors, at least to date. We have been focused on growing the company through collaborations and consulting relationships. However, we have benefitted from being part of the Keystone Innovation Zone, a state program that provides incentives for small technology-based businesses in Pennsylvania.

LPBI: You will be speaking at a conference in the UK on reinventing the drug discovery process through tighter collaborations between biotech, academia, and non-profit organizations.  How do you feel the Philadelphia area can increase this type of collaboration to enhance not only the goals and missions of nonprofits, invigorate the Pennsylvania biotech industry, but add much needed funding to the local academic organizations?

GfreeBio: I think this type of collaboration across sectors appears to be one of the most important emerging models for drug discovery.   The Philadelphia region has been in many ways hard hit by the shift of drug discovery from large vertically integrated pharmaceutical companies to smaller biotechs, since this area was at the very center of “Big Pharma.” But I think the region is bouncing back as it shifts more to being a center for biotech. The three ingredients for success in the new pharma model are great universities, a sizeable talent pool, and access to capital. The last item may be the biggest challenge locally. The KIZ program (Keystone Innovation Zone) is a good start, but the region and state could do more to help promote innovation and company creation. Some other states are being much more aggressive.

LPBI: In addition, the Pennsylvania Biotechnology Center in Bucks County appears to have this ecosystem: nonprofit organizations, biotechs, and academic researchers. Does this diversity of researchers/companies under one roof foster the type of collaboration needed, as will be discussed at the UK conference? Do you feel collaborations which are in close physical proximity are more effective and productive than a “virtual-style” (online) collaboration model? Could you comment on some of the collaborations GfreeBio is doing with other area biotechs and academics?

GfreeBio: I do think the “ecosystem” at the Pennsylvania Biotechnology Center is important in fostering new innovative companies. It promotes collaborations that might not happen otherwise, and I think close proximity is always a big plus. As I mentioned before, many of the current efforts of Gfree have come from contacts at the center.   This includes SBIR/STTR collaborations and contract work for local small biotech companies.

LPBI: Thompson Reuters just reported that China’s IQ (Innovation Quotient) has risen dramatically with the greatest patents for pharmaceuticals and compounds from natural products. Have you or your colleagues noticed more competition or business from Chinese pharmaceutical companies?

GfreeBio: The rise of Asia, particularly China, has been one of the most significant recent trends in the pharmaceutical industry. Initially, this was almost exclusively in the CRO space, but now China is aggressively building a fully integrated domestic pharmaceutical industry.

LPBI: How can the Philadelphia ecosystem work closer together to support greater innovation?

GfreeBio: A lot has happened in recent years to promote innovation and company creation in the region. There could always be more opportunities for networking and collaboration within the Philadelphia community. Of course the biggest obstacle in this business is often financing. Philadelphia needs more public and private sources for investment in startups.

LPBI: Thank you Dr. Reynolds.

Please look for future posts in this series on the Philly Biotech Scene on this site

Also, if you would like your Philadelphia biotech startup to be highlighted in this series please contact me: sjwilliamspa@comcast.net or @StephenJWillia2.
Our site is read by ~ 570,000 readers, among them thousand international readers daily and followed by thousands of Twitter followers.

 

Other posts on this site in this VIBRANT PHILLY BIOTECH SCENE SERIES OR referring to PHILADELPHIA BIOTECH include:

RAbD Biotech Presents at 1st Pitch Life Sciences-Philadelphia

The Vibrant Philly Biotech Scene: Focus on Vaccines and Philimmune, LLC

What VCs Think about Your Pitch? Panel Summary of 1st Pitch Life Science Philly

1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

LytPhage Presents at 1st Pitch Life Sciences-Philadelphia

Hastke Inc. Presents at 1st Pitch Life Sciences-Philadelphia

PCCI’s 7th Annual Roundtable “Crowdfunding for Life Sciences: A Bridge Over Troubled Waters?” May 12 2014 Embassy Suites Hotel, Chesterbrook PA 6:00-9:30 PM

Pfizer Cambridge Collaborative Innovation Events: ‘The Role of Innovation Districts in Metropolitan Areas to Drive the Global an | Basecamp Business

Mapping the Universe of Pharmaceutical Business Intelligence: The Model developed by LPBI and the Model of Best Practices LLC

Read Full Post »


Twitter is Becoming a Powerful Tool in Science and Medicine

 Curator: Stephen J. Williams, Ph.D.

Life-cycle of Science 2

A recent Science article (Who are the science stars of Twitter?; Sept. 19, 2014) reported the top 50 scientists followed on Twitter. However, the article tended to focus on the use of Twitter as a means to develop popularity, a sort of “Science Kardashian” as they coined it. So the writers at Science developed a “Kardashian Index (K-Index) to determine scientists following and popularity on Twitter.

Now as much buzz Kim Kardashian or a Perez Hilton get on social media, their purpose is solely for entertainment and publicity purposes, the Science sort of fell flat in that it focused mainly on the use of Twitter as a metric for either promotional or public outreach purposes. A notable scientist was mentioned in the article, using Twitter feed to gauge the receptiveness of his presentation. In addition, relying on Twitter for effective public discourse of science is problematic as:

  • Twitter feeds are rapidly updated and older feeds quickly get buried within the “Twittersphere” = LIMITED EXPOSURE TIMEFRAME
  • Short feeds may not provide the access to appropriate and understandable scientific information (The Science Communication Trap) which is explained in The Art of Communicating Science: traps, tips and tasks for the modern-day scientist. “The challenge of clearly communicating the intended scientific message to the public is not insurmountable but requires an understanding of what works and what does not work.” – from Heidi Roop, G.-Martinez-Mendez and K. Mills

However, as highlighted below, Twitter, and other social media platforms are being used in creative ways to enhance the research, medical, and bio investment collaborative, beyond a simple news-feed.  And the power of Twitter can be attributed to two simple features

  1. Ability to organize – through use of the hashtag (#) and handle (@), Twitter assists in the very important task of organizing, indexing, and ANNOTATING content and conversations. A very great article on Why the Hashtag in Probably the Most Powerful Tool on Twitter by Vanessa Doctor explains how hashtags and # search may be as popular as standard web-based browser search. Thorough annotation is crucial for any curation process, which are usually in the form of database tags or keywords. The use of # and @ allows curators to quickly find, index and relate disparate databases to link annotated information together. The discipline of scientific curation requires annotation to assist in the digital preservation, organization, indexing, and access of data and scientific & medical literature. For a description of scientific curation methodologies please see the following links:

Please read the following articles on CURATION

The Methodology of Curation for Scientific Research Findings

Power of Analogy: Curation in Music, Music Critique as a Curation and Curation of Medical Research Findings – A Comparison

Science and Curation: The New Practice of Web 2.0

  1. Information Analytics

Multiple analytic software packages have been made available to analyze information surrounding Twitter feeds, including Twitter feeds from #chat channels one can set up to cover a meeting, product launch etc.. Some of these tools include:

Twitter Analytics – measures metrics surrounding Tweets including retweets, impressions, engagement, follow rate, …

Twitter Analytics – Hashtags.org – determine most impactful # for your Tweets For example, meeting coverage of bioinvestment conferences or startup presentations using #startup generates automatic retweeting by Startup tweetbot @StartupTweetSF.

 

  1. Tweet Sentiment Analytics

Examples of Twitter Use

A. Scientific Meeting Coverage

In a paper entitled Twitter Use at a Family Medicine Conference: Analyzing #STFM13 authors Ranit Mishori, MD, Frendan Levy, MD, and Benjamin Donvan analyzed the public tweets from the 2013 Society of Teachers of Family Medicine (STFM) conference bearing the meeting-specific hashtag #STFM13. Thirteen percent of conference attendees (181 users) used the #STFM13 to share their thoughts on the meeting (1,818 total tweets) showing a desire for social media interaction at conferences but suggesting growth potential in this area. As we have also seen, the heaviest volume of conference-tweets originated from a small number of Twitter users however most tweets were related to session content.

However, as the authors note, although it is easy to measure common metrics such as number of tweets and retweets, determining quality of engagement from tweets would be important for gauging the value of Twitter-based social-media coverage of medical conferences.

Thea authors compared their results with similar analytics generated by the HealthCare Hashtag Project, a project and database of medically-related hashtag use, coordinated and maintained by the company Symplur.  Symplur’s database includes medical and scientific conference Twitter coverage but also Twitter usuage related to patient care. In this case the database was used to compare meeting tweets and hashtag use with the 2012 STFM conference.

These are some of the published journal articles that have employed Symplur (www.symplur.com) data in their research of Twitter usage in medical conferences.

B. Twitter Usage for Patient Care and Engagement

Although the desire of patients to use and interact with their physicians over social media is increasing, along with increasing health-related social media platforms and applications, there are certain obstacles to patient-health provider social media interaction, including lack of regulatory framework as well as database and security issues. Some of the successes and issues of social media and healthcare are discussed in the post Can Mobile Health Apps Improve Oral-Chemotherapy Adherence? The Benefit of Gamification.

However there is also a concern if social media truly engages the patient and improves patient education. In a study of Twitter communications by breast cancer patients Tweeting about breast cancer, authors noticed Tweeting was a singular event. The majority of tweets did not promote any specific preventive behavior. The authors concluded “Twitter is being used mostly as a one-way communication tool.” (Using Twitter for breast cancer prevention: an analysis of breast cancer awareness month. Thackeray R1, Burton SH, Giraud-Carrier C, Rollins S, Draper CR. BMC Cancer. 2013;13:508).

In addition a new poll by Harris Interactive and HealthDay shows one third of patients want some mobile interaction with their physicians.

Some papers cited in Symplur’s HealthCare Hashtag Project database on patient use of Twitter include:

C. Twitter Use in Pharmacovigilance to Monitor Adverse Events

Pharmacovigilance is the systematic detection, reporting, collecting, and monitoring of adverse events pre- and post-market of a therapeutic intervention (drug, device, modality e.g.). In a Cutting Edge Information Study, 56% of pharma companies databases are an adverse event channel and more companies are turning to social media to track adverse events (in Pharmacovigilance Teams Turn to Technology for Adverse Event Reporting Needs). In addition there have been many reports (see Digital Drug Safety Surveillance: Monitoring Pharmaceutical Products in Twitter) that show patients are frequently tweeting about their adverse events.

There have been concerns with using Twitter and social media to monitor for adverse events. For example FDA funded a study where a team of researchers from Harvard Medical School and other academic centers examined more than 60,000 tweets, of which 4,401 were manually categorized as resembling adverse events and compared with the FDA pharmacovigilance databases. Problems associated with such social media strategy were inability to obtain extra, needed information from patients and difficulty in separating the relevant Tweets from irrelevant chatter.  The UK has launched a similar program called WEB-RADR to determine if monitoring #drug_reaction could be useful for monitoring adverse events. Many researchers have found the adverse-event related tweets “noisy” due to varied language but had noticed many people do understand some principles of causation including when adverse event subsides after discontinuing the drug.

However Dr. Clark Freifeld, Ph.D., from Boston University and founder of the startup Epidemico, feels his company has the algorithms that can separate out the true adverse events from the junk. According to their web site, their algorithm has high accuracy when compared to the FDA database. Dr. Freifeld admits that Twitter use for pharmacovigilance purposes is probably a starting point for further follow-up, as each patient needs to fill out the four-page forms required for data entry into the FDA database.

Other posts on this site on USE OF SOCIAL MEDIA AND TWITTER IN HEALTHCARE and Conference Coverage include:

Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA

Strategy for Event Joint Promotion: 14th ANNUAL BIOTECH IN EUROPE FORUM For Global Partnering & Investment 9/30 – 10/1/2014 • Congress Center Basel – SACHS Associates, London

REAL TIME Cancer Conference Coverage: A Novel Methodology for Authentic Reporting on Presentations and Discussions launched via Twitter.com @ The 2nd ANNUAL Sachs Cancer Bio Partnering & Investment Forum in Drug Development, 19th March 2014 • New York Academy of Sciences • USA

PCCI’s 7th Annual Roundtable “Crowdfunding for Life Sciences: A Bridge Over Troubled Waters?” May 12 2014 Embassy Suites Hotel, Chesterbrook PA 6:00-9:30 PM

CRISPR-Cas9 Discovery and Development of Programmable Genome Engineering – Gabbay Award Lectures in Biotechnology and Medicine – Hosted by Rosenstiel Basic Medical Sciences Research Center, 10/27/14 3:30PM Brandeis University, Gerstenzang 121

Tweeting on 14th ANNUAL BIOTECH IN EUROPE FORUM For Global Partnering & Investment 9/30 – 10/1/2014 • Congress Center Basel – SACHS Associates, London

http://pharmaceuticalintelligence.com/press-coverage/

Statistical Analysis of Tweet Feeds from the 14th ANNUAL BIOTECH IN EUROPE FORUM For Global Partnering & Investment 9/30 – 10/1/2014 • Congress Center Basel – SACHS Associates, London

1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

What VCs Think about Your Pitch? Panel Summary of 1st Pitch Life Science Philly

How Social Media, Mobile Are Playing a Bigger Part in Healthcare

Can Mobile Health Apps Improve Oral-Chemotherapy Adherence? The Benefit of Gamification.

Medical Applications and FDA regulation of Sensor-enabled Mobile Devices: Apple and the Digital Health Devices Market

E-Medical Records Get A Mobile, Open-Sourced Overhaul By White House Health Design Challenge Winners

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