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NanoGagliato 2015

NANOGAGLIATO 2015 – Nanoexpansion: Interfaces that Drive Innovation

CHALLENGE SESSION 1 -Nano & Surgery
Moderator: Barbara Bass, MD

Only recently have we started applying nanoscience to the clinical domain. The dissemination of what we do here at Nanogagliato has an influence beyond this venue. Quoting from Being Mortal by Atul Gawande, how do we live the end of our lives and die? How can we move the pendulum of how we deal with the end of life?  What are the fixable priorities in health care? Eg. Ethical maldistribution of medicine.

Surgery first strikes you as a simple mechanical process – tools to deal with tissue. But fundamental to this process is relying on the ability of our bodies to heal. Whether we remove, repair, or replace a structure, it is infinitely better to couple technologies with biology that allows effective healing. Nanoscience applies to all of this, with most progress in cancer. Imaging is enhanced by nano, more effective resections. In the repair world, regenerative approaches with delivery of factors to enhance healing. With replacements, to deliver biologic agents to prevent rejection, to allow tolerating organs safely. There are many potential applications of how nanoscience can be used in the surgical world: R’s: Removal, Repair, Replacement.

Speakers: Brian Dunkin, John Breinholt

Brian Dunkin, MD

We are on the cutting edge of new technologies, eg. learning and advancing minimally invasive surgery to avoid complications of an open surgical wound we create (infection, weakness). There are significantly increased chances of surgical failure rate with infection. Repairs are reinforced with mesh but the problem with mesh is that the material has biomechanics different from a normal wall, it may cause pain, encapsulated in scar, people react in different ways, can be prone to infection, this is a serious problem, can entail more operations, including a temporary repair, do the surgery again within a hopefully clean environment.  Nanoscience can impact mesh characteristics (in a way that hasn’t been done before) with ability to resist infection, an anti-bacterial profile. Various ideas regarding imbuing mesh with qualities to resist bacterial load and to reduce adhesion were discussed. There is a team approach to working on these ideas at Houston Methodist Research Institute, ie. scientists and clinicians, residents in clinician- scientist pathway.

John Breinholt, MD

An interventional pediatric cardiologist…Dr. Breinholt discussed his work including using blood vessels of the body to perform interventions for heart problems children are born with. Some problems however do not allow fixing, and patient is committed to a life of multiple surgeries or interventions. We try to palliate, and make things survivable. He spoke of the problems once a valve degenerates, where working through adhesions/scar tissue with subsequent surgeries can be more work than the actual surgery.  Recent advances allow us to get to those targets through the blood vessels and avoid those obstacles.  While it can be gratifying with feeling like “curing” someone with implant devices to close holes in the heart, some of these devices require monitoring for erosion over the long-term. A stent in a young child doesn’t grow but the child grows and thus there is a need to go back in and expand the stent. A stent is needed that can be further expanded until  it reaches adult size as one never wants to create a surgical intervention, and you do not want to implant something that needs to be removed. Biodegradable stent? What happens when it biodegrades? Unfortunately, currently none are made that can be applied to children. Economic issues: Getting anything to practice requires working with industry and interest not there – deals with a small population -1% born with congenital heart disease and a fraction would use this. Is it possible to develop technologies for the healing process to differ?  If we did get to the point of a biodegradable stent, how would this affect the way the blood vessel would grow?

Comment - Mauro Ferrari, PhD

Emphasized the notion of using nanoscience across biological areas, cutting across different diseases. In addition to surgery, TB (Gates Foundation), cancer, which finds a way to protect itself - a sanctuary – need a powerful set of tools to transport across pathological areas. Within the immune system, there is an ability for multiple knowledges to interact – Nano is not enough, need to get cells involved signaling, kindling, with multiple players; nano scale features of stents. The broad concept is tech changes the boundaries of professional medicine. Interventional cardiologist and a surgeon overlap in different areas, we look at nano products in a more dynamic fashion.   Think of the challenge of a stent that doesn’t grow. Why not? Should be able to develop a growth pattern.

Comment - Ennio Tasciotti, PhD

What is done in the lab is inspired by nature. A new challenge for nano is development of polymers using a mix of materials that can be recognized by the body as self and which get integrated and remodeled and grow with you, maintain homeostasis.

Comment – Lorenzo Pradella, PhD

There is improvement of robotics and the use of nano – magnification with tools. Augmented imaging will transform robotics. Robotics are crucial for minimally invasive surgery so need the technology.

Comment –Brian Dunkin, MD

Need to move away from light visualization, need real time radiologic imaging, to augment my reality.

Wrap-up: Dr. Mauro Ferrari

Scientists, Clinicians, and Industry are integrated with different perspectives. Multiple level of interactions (including the ethics of…), not solely level of scientific sophistication makes the conference “thinktank.” How to optimize development?

Introduced the Salvatore Venuta memorial scholarship awardees (5 PhD students) attending and participating in the conference.

CHALLENGE SESSION 2 –Nano & Bioethics and Community

Moderator: Joseph Fins, MD, MACP

The future of nanotechnology presents challenges for the scientists, patients, and families within grappling with the potential and the reality nano might entail. Beyond the science, politics/economy/ ethics can craft the future and determine if scientists can do this work. Cited NY Review of Books article by Flannery (which describes how we consist of “tiny machines”, ribosomes as “nanomachines”) to emphasize how the boundary line between life and nonlife is at a nano level.  Some challenges (granular issues): 1) are nano devices regulated as drugs or devices?; devices as tools of discovery. Diagnostic tools not just therapeutic tools. 2) Intellectual property issues – ideas from bench to bedside. Commodifying ideas, conflict of interest? 3) Clinical challenges – how temper expectations, “therapeutic misconceptions,” potential to be misunderstood as being in the experimental stage when in pre-experimental stage. Important to temper expectations as we make the current transition from research in the short-term. Being realistic, don’t want to get ahead of ourselves, tempering hype in the media, being careful advocates for knowledge.

Speakers: Rahul Mehta, Hedy Wald

Rahul Mehta

Rahul Mehta highlighted the patient component and the patient’s family component in this work. He described his experience as an Alzheimer’s dementia caregiver (4 years) and some of the difficult challenges, some of them ethical challenges, within behavioral management treatment decisions. How do we manage patient needs, caregiver needs? What is the right balance with medicating a patient with Alzheimer’s dementia (patient perspective, caregiver perspective)? Concerns were expressed about 80% without access to basic health care – how do we determine funding support priorities?

Hedy Wald, PhD

Dr. Wald spoke on: “Reflecting on Hype, Hope, and Reality: 12 ‘Tips’ (Reflection Inviting Questions) for Crafting the Nano Research Story.” Reflective awareness within tempering the “nano” research narrative as one crafts such a narrative in understandable format for the public, being prudent was emphasized…The need for cultivating and maintaining emotional and ethical resilience within these endeavors was discussed, resonating with participants’ interest in and concern about “biomedical burnout” and in line with one of the conference’s suggested readings. The growing need to communicate research beyond the confines of scholarly circles was emphasized (no longer an option) given increased presence and expanding role of patient and research advocates (“partnering”) on grant peer review committees (including their scores on overall ratings of grant applications), editorial boards and informed consent/IRB committees as well as increased political activism.

Dr. Wald highlighted the power of narrative about the process of scientific study and discovery for patient/public engagement and informed the discussion with sharing her “backstory,” professional and personal. She discussed her work with using reflective writing to foster reflective capacity supporting professional identity formation (including resiliency) in health care professions education as foundational. She then shared her personal narrative as a cancer caregiver, having had a “story” of a recommended clinical trial explained to her and her husband, a physician and brain cancer patient, and their trusting the medical team - which included researchers- to balance hype, hope, reality within the crafting and communicating of that story.

Discussion: Dr. Mauro Ferrari

Dr. Ferrari discussed the explosion of nano, with an example that less than 1% of cancer drugs were nano-related 5 years ago while currently 10% of all cancer-related drugs are nano-related. The current regulatory framework for approving drugs and devices is tragic with an average of 17 years to get these to a patient, creating an ethical dilemma. Clinical trials are done in the most stringent respect within regulatory framework but can new pathways streamline the process?

Discussion: The “humanitarian exception” for new drugs was mentioned as “all we have.” Allocation of scarce resources is also problematic within regulatory burden. Dr. Cooke – an ethical issue can be “paralysis by analysis.” Dr. Breinholt highlighted that not a single stent has been approved for children.

Other discussants mentioned scientists within the nano research community reaching out and engaging society and referred to the personal stories presented (R. Mehta and H. Wald) as grounding and informing the discussion as this is about people and “sometimes you treat the family.” Dr. Breinholt marveled at the families he works with. Dr. Bass highlighted inherent themes of tension in the work including innovation and barriers to clinical translation, patients’ access to innovative technology, devices, and drugs, everything we learn coming with risk so who sets the bar for risk?, and tension that may arise between caring for the patient and caring for the family.  R. Mehta discussed needing to bring humility to the space of giving advice – how you work with patients and with families.  

CHALLENGE SESSION 3 - Nano & Science

Don Tullio Proserpio gave a blessing to start the session.

Moderator -John Cooke, MD, PhD

Opened the session with discussing the RNA therapeutic in cells and looking to nanoscientists to develop the technology to deliver these particles. 

Speakers: David Katzmann, Steve Conlan, Ennio Tasciotti

David Katzmann, PhD

Dr. Katzmann discussed issue of risk assessment within discoveries, need for rigor yet issue if takes too long to be revealed, inherent issue of pressure within current scientific recession when monetizaton, consideration of underdeveloped results. Provided overview of exosome work: mechanisms of extracellular vesicles, role in cancer prevention? Cellular nanoparticles generating physiologic response – what is the basic mechanism of how these particles do what they are supposed to do? How program them for diagnostic and therapeutics?

Steven Conlan, PhD   

Discussed work in artificial and native nano particles, biomimicry, synthetic biology. He discussed his work in developing scanning tools for measuring cell hardness. Wants to understand how elasticity affects cancer cell production. Hard and soft particles can react differently with the body. Is there an elasticity receptor in cells?  Biophysical properties of nanoparticles? Use exosomes to reprogram cells?

Ennio Tasciotti, PhD

Science is a beautiful story. Provided various metaphors to convey the nano story. Predator and prey in nature. “Good guys” (nano) and “bad guys.” Predator (macrophages) trying to catch the prey (particles). Can particles be camouflaged to get beyond the “enemy”? In the process of setting one goal, other things were discovered. Particles communicating with other molecules – relates to various disease states – cancer, sepsis, cardiovascular disease, brain injury, inflammatory bowel disease. Particles as therapeutic per se, inflammation goes down even if drug not delivered. Learned there is much more to delivery of a drug, “artificial exosome”. Interested in fighting disease through triggering innate mechanisms of the healing. What are the signaling pathways being activated?

M. Ferrari – discussant. Highlighted the value of serendipity and having a prepared mind to make that observation. Discussed proof of concept paper – therapeutic application of exosomes. These are early days of exosomal therapeutics –can we use them as disease indicators? Track progression of disease?  Are they bionano tools? Can we synthesize them? Reinfuse your own material to heal? Use our own body as bionano tools?

CHALLENGE SESSION 4 -Nano & Business

Moderator -Chris Anzalone, PhD

Discussed challenges of translating nanoscience into business, regulation of intellectual property, nanoscience communication and the broader business community.

Speakers: Doug Given, Rahul Mehta, Neil Bush, Lorenzo Pradella

Doug Given, MD, PhD, MBA

Just increasing utilization of what we have and using it effectively with compliance could reduce health care costs by 30%. Need incentives. Discussed spending for the health care economy and relatively minor amount spent on science. Discussed the “Wild Wild West” of venture capital for digital health and other innovations. Significantly increased investment more recently in digital health. Emphasized time it takes for development (needing patience) and needing leadership to recruit public interest. Discussed potential of Health 2047, AMA innovation with interdisciplinary design teams. Discussed innovation for value, moving from research to product, dreamers and pragmatism.

Rahul Mehta

Shared his personal story of multiple businesses development, themes of being focused, having a vision, building good teams and partnerships, ecosystem, work ethic.

Neil Bush

Discussed the difficulty of taking an idea from the lab to commercial productivity.  Trying to empower the body to solve health issues. An early stage start-up venture can sound better than it is, 1 out of 10 start-up ventures survive. Artificial barriers between the lab and manufacturing, ideas stymied due to bureaucratic process of getting approvals – need to consider this in order to stay competitive (other countries not as encumbered).        

Lorenzo Pradella, PhD

Dr. Pradella discussed nano as a frontier, creating possible new landscapes for solutions. Highlighted how behavior of physicians and patients is different around the world – attitudes, culture, behaviors including relationship between physicians and patients.  Discussed business as having to do with products, not technology. Venture capitalists as looking for solutions, levels of revenue that can be generated.

Discussion points post-panel about need for stretching boundaries and needing a new manifesto regarding academics working with industry (not the dark side!) vis a vis difficulty proceeding with important work only with government funding. Also discussed cultivating personal responsibility within health care for our wellness and wellbeing with this being embedded in the ethical role of a physician, “affordable, delightful, accessible.” Need to include yoga? Health coach?  Risk aversion within federal funding and problem for innovation. Discussed concern about shrinking pool of funding and having more clinician-scientists. Is there a market for the science of prevention? Can we alter the way we train health care professional with technology to create long-term chronic disease management/coordinated care? How patient behavior change? Movement toward integrative medicine. Accountabiity (patient health behavior change) as preventive medicine. How to cultivate patient responsibility? How to empower patient? ?Move funding resources out of the medical care with prevention and shift the resources to research? Re: education of physicians, discussed science informing humanities and humanities as instrumental to giving value and meaning to the science, encouraging creativity and synthesis of two cultures. Need for science education and literacy for all citizens, making the picture accessible to people. How align incentives and priorities?

CHALLENGE SESSION 5 -Nano & Healthcare

Moderator -Susan Miller, MD, MPH

This session provided an overview of differences between research and health care delivery. Within the fields of medicine, science, and religion – the exploration of human suffering is integral to the care provided by these professions. Discussed the challenges of moral distress – the psychological disequilibrium when a health care professional realizes judgment about the right thing to do but is unable to do it. A lesson provided by a colleague summarized the scope of this concept – “we meet people for a moment, for a reason, for a season, for a lifetime.”

Speakers: Ed Jones, Don Tullio Proserpio, Fabiano Quaglia

Ed Jones, MBA

Highlighted the need for different perspectives in work and how organizational theory can be helpful – how people relate to each other and within their respective programs. He shared his personal story of his education with science and business background and a passion for ethics related to biomedical research. Work mission of protecting the institution but not in such a stifled way that can’t move it forward. Considering external regulatory frameworks, where pendulum swings with Safety (FDA) depending on comfort level of the public and needing to do a better job of educating the public about this. Think about interface of FDA and nano? Discussed decision making within clinical trials. Discussed issue of being risk-adverse leading to developing more regulations…pathways to providing patient access eg., Right to Participate (RTP) but considering issues of therapeutic misconception, premise of research, false premise of hope? Need for new paradigm, working with FDA and companies, scientists developing novel platforms, informing public about meaning of RTP, having more based on computational models (there is a lot of data), partnership with companies with ethical responsibility. Nano as an emerging platform.

Don Tullio Proserpio

Provided his personal story as a Catholic priest in a parish and asked by the Archbishop to go to the National Cancer Institute. Recently published in a medical journal because he wishes to use the same language as that used by physicians and scientists, showing results with the scientific method.  Working together with health care professionals to help sick people in their particular situation.  Devised a questionnaire about hope – giving trust to physicians within therapeutic relationships gave sick people great hope. “I’m not only a number, I’m a person” gives patients more hope. Discussed spirituality within this and his role within palliative care.

Fabiana Quaglia

Pharmaceutical technologist. Discussed the bridge between new drugs and delivery within the body, sometimes active in vitro, not in vivo, need reliable proof of principle for our concepts in the scientific community. Sometimes there is no real benefit even after it’s ok in the research; need to remember toxicity. Regulation blocks needed for safety, need ethical perspective as a researcher for an honest contribution to the scientific community.

Discussion post –panel – Book “Moral Entanglements,” how do we manage risk vs.risk-adverse? Importance of the consent process, bioethicists embedded in the ICU.

CLOSING CHALLENGE SESSION (6)--Nano & Regeneration

Moderator: Tim Boone, MD, PhD

Discussed merges of nanotechnology with electrophysiology, nano improving regeneration, nanoscale implementation. Can we connect man to machine? Compassion for patients.

Speakers: Phil Horner, Anita Kadala

Phil Horner, PhD

Discussed new bridge material for damaged processes. Bran chemicals and activity can change progress of disease – discussed brain components of various diseases, how nerves influence the end organ. Discussed opportunity for nano within scarring due to injury of brain/spinal cord, change elasticity of scar, way to think about nerve repair. Need nanomaterials to target axons for nerve repair, neurodegenerative disease, develop something to be delivered directly to the axon.

Anita Kadala, JD

Great innovation occurs at the exchange of different disciplines.  Discussed commercialization and getting things out of the lab and into the clinic. It’s all about relationships and connections. 

Discussion points post-panel – how discussion of tissue regeneration, evolution of tissue engineering, bone regeneration is inspirational, discussed ethical components. Also discussed the challenge of keeping the flame of innovation alive while maintaining focus and rigor to get task done, get product out there. Things happen along the way – the genius of science and creativity…Interdisciplinary collaboration, breaking boundaries…But need infrastructure in the institution to get the product delivered. Doing discovery with abandon but with the backbone of translation. Translational research initiative – how to pay for great ideas to move down the highway.  Identifying financial resources to do these things so self-sustainable, with greatest likelihood of getting it into the clinic. Recession in the sciences. Generous communities can make an impact, give meaning, helping the world.  

 

anzalone

Chris Anzalone, Ph.D.
Director, President and Chief Executive Officer
Arrowhead Research Corporation
Pasadena, CA
USA

 

bass


Barbara L. Bass, M.D
John F. and Carolyn Bookout Distinguished Endowed Chair of Surgery 
Professor of Surgery, Institute for Academic Medicine
Director, Methodist Institute for Technology, Innovation and Education 
Houston Methodist
Houston, TX
USA

boone

 

Tim B. Boone, M.D., Ph.D. 
Chair, Department of Urology
Professsor of Urology, Institute for Academic Medicine
Houston Methodist
Houston, TX
USA
 

breinholt

 

John P. Breinholt, M.D.
Director, Division of Pediatric Oncology, Department of Pediatrics
Memorial Hermann
Houston, TX
USA



bush


Maria Bush
Owner, Real Estate Investments 
Houston, TX
USA



NBush

 

Neil Bush
Chair, Points of Light
Houston, TX
USA

 


conlan


Steve Conlan, Ph.D
Director, Centre for NanoHealth 
Institute of Life Science College
Swansea University, Wales
UK


cooke

John P. Cooke, M.D., Ph.D. 
Chair, Department of Cardiovascular Sciences 
Professor of Cardiovascular Sciences, Institute for Academic Medicine
Director, Center for Cardiovascular Regeneration
Houston Methodist
Houston, TX
USA

dunkin


Brian J. Dunkin, M.D.

John F., Jr. and Carolyn Bookout Chair in Surgical Innovation and Technology, Department of Surgery Professor of Surgery, Institute for Academic Medicine
Medical Director, Methodist Institute forTechnology, Innovation and Education
Houston Methodist
Houston, TX
USA

ferrari


Mauro Ferrari, Ph.D.
Ernest Cockrell Jr. Distinguished Endowed Chair
President and CEO, Houston Methodist Research Institute  
Professor of Nanomedicine and Director, Institute for Academic Medicine 
Executive Vice President 
Houston Methodist
Houston, TX
USA

fins

 


Joseph J. Fins, M.D.
E. William Davis, Jr., MD Professor of Medical Ethics
Weill Cornell Medical College
New York, NY
USA


given

 

Douglass Given, M.D., Ph.D., M.B.A.
Partner 
Bay City Capital
San Francisco, CA
USA


horner


Phil Horner, Ph.D. 

Professor of Neuroregeneration, Institute for Academic Medicine
Houston Methodist
Houston, TX
USA

 

jones

 

Ed Jones, M.B.A.
COO, Research Institute
Senior Vice President, Institute for Academic Medicine
Houston Methodist
Houston, TX
USA

kadala

 

Anita Kadala, JD
CEO & Legal Counsel
Ingeneron
Houston, TX
USA


katzmann

 
David J. Katzmann, Ph.D.

Associate Professor of Biochemistry/Molecular Biology
Mayo Clinic
Rochester, MN
USA


metha

 

Rahul Mehta
Mehta Family Foundation




miller

Susan Miller, M.D., MPH
John S. Dunn Research Chair in General Internal Medicine, Department of Medicine
Professor of Clinical Family Medicine, Institute for Academic Medicine
Houston Methodist
Houston, TX
USA



pradella

Lorenzo Pradella, Ph.D.
Co-Founder, CEO & COO of GreenBone Ortho srl. 
Member of ETPN Executive Board
Honorary President of Business Development Academy
Italy




tasciotti


Ennio Tasciotti, Ph.D.
Associate Professor of Nanomedicine, Institute for Academic Medicine
Co-Chair, Department of Nanomedicine
Houston Methodist
Houston, TX
USA

 

proserpio

 

Don Tullio Proserpio
Chief of Spiritual Care
European Cancer Institute
Milan,
Italy



wald

 

Hedy S. Wald, Ph.D.
Clinical Associate Professor of Family Medicine 
Warren Alpert Medical School of Brown University
Providence, RI
USA


weiner 

Bradley K. Weiner, M.D.
Professor of Clinical Orthopedic Surgery, Institute for Academic Medicine
Chief of Spinal Surgery, Houston Methodist Hospitaly 
Houston Methodist
Houston, TX
USA