IMS Magazine Spring 2019

IMS MAGAZINE

THINK. LEARN. DISCOVER.

SPRING 2019

EMERGING

MEDICAL

TECHNOLOGIES

DEEP BRAIN STIMULATION

At the cutting edge of mental health treatments

HIGH-THROUGHPUT DRUG SCREENING

Learning to commercialize scientific discoveries

CRISPR-CAS9 GENE EDITING

The ethics & consequences of fetal genome editing

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2 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

IN THIS ISSUE Letter fom the Editors................................ 4 Director’s Message.................................... 5 Raw Talk Podcast....................................... 6 Commentary............................................... 7 Infographic................................................. 8 Feature..................................................... 10 BMC......................................................... 22 Viewpoint................................................. 24 Student Spotlight..................................... 36 Travel Bites............................................... 38 Past Events............................................... 40 Book Review............................................ 42 IMSSA...................................................... 43

INFOGRAPHIC

INFOGRAPHIC

EMERGING MEDICAL & SURGICAL TECHNOLOGY DEEP BRAIN STIMULATION

500+ COMPANIES CREATED AND

NON-INVASIVE BRAIN STIMULATION

Deep brain stimulation (DBS) involves implanting electrodes within the brain that generate specific electrical impulses designed to regulate abnormal brain activity.

Another brain stimulation technique, transcranial magnetic stimulation (TMS) is a lessinvasive option for modulating brain activity via magnetic fields.

Stimulating brain areas near the scalp may boost or reduce activity in these regions, and could even strengthen (or weaken) their functional connections with other, deeper brain structures.2 Go to page 15 to learn how IMS researchers are using non-invasive brain stimulation techniques for treatment resistant psychiatric disorders.

DBS is most commonly used to treat movement disorders (eg.

Parkinson’s, essential tremor, dystonia) and some psychiatric disorders (eg. obsessive compulsive disorder) but is also being investigated as a potential treatment for; major depression, chronic pain, addiction, dementia, Huntington’s disease, multiple sclerosis, Tourette syndrome, stroke, & traumatic brain injury.1 Read about IMS researchers using DBS to treat anorexia and alcohol use disorder on page 13.

8

INNOVATION AT UOFT

3D BIO-PRINTING

3D printing refers to the process where a material is added successively layer by layer to build a 3-dimensional product, guided by a digital design model. It’s currently being used in many industries, from food & fashion to weapons & automotive parts.

Transcranial direct current stimulation (tDCS) applies tiny electrical currents to the scalp (eg. one to two milliamps) that some researchers believe can enhance neuroplasticity.

Companies have started selling at-home tDCS devices (ranging from $40 to $700) claiming to improve motor abilities or enhance concentration – although their effectiveness has not been proven.3

MAGNETIC RESONANCE ANGIOGRAPHY

Magnetic Resonance Angiography (MRA) is a type of medical imaging that uses magnetic fields to map out the body’s blood vessels. Less invasive (and less painful) than a traditional angiogram, MRA provides detailed images of the immense network of blood vessels in the body, including

those which have been hardened or clogged with plaque (eg. atherosclerosis).5 See page 17 to read how vascular surgeons in the IMS are refining MRA to help patients with peripheral arterial disease.

IN INVESTMENT SINCE 2008.

400+

PATENTS FILED SINCE 2010.

See page 11 to read how IMS researchers are using 3D printing in facial reconstructive surgery.

Digitization and 3D modelling technology is also being used to study the intricacies of human anatomy.

MADE A DISCOVERY, DESIGNED A DEVICE, OR DEVELOPED A METHOD THAT CAN REVOLUTIONIZE MEDICINE?

Go to page 19 to see how these high-rez models can be used to advance our understanding of anatomy and even help guide surgeries.

References 1. Deep Brain Stimulation. Mayo Clinic. Retrieved from https://www. mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac20384562.

2. Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology. 2014 Nov 1;125(11):2150-206.

3. Landhuis, E. Do D.I.Y. Brain-Booster Devices Work? Scientific American. Jan 10, 2017. Retrieved from https://www.scientificamerican. com/article/do-diy-brain-booster-devices-work/

14

STOREYS OF INNOVATION COMING IN 2021.

Innovative research at the UofT has led to the creation of over 500 companies which have produced over one billion in investment since 2008. Between 2010 and 2018, over 400 patents were filed for technologies developed by UofT researchers. The UofT is building a 14 storey innovation tower across from the MaRS Discovery District, set to open in 2021.6

DIGITIZATION & 3D MODELLING

4. Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM, Toro E, Chen AA, Galie PA, Yu X, Chaturvedi R. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nature materials. 2012 Sep;11(9):768.

5. Magnetic Resonance Angiography (MRA). John Hopkins Medicine.

Retrieved from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/magnetic-resonance-angiography-mra 6. Sorenson, C. U of T innovation centre to help form ‘new cornerstone’ of the Canadian economy. July 23, 2018. UofT News.

Retrieved from https://www.utoronto.ca/news/u-t-innovation-centre-help-form-new-cornerstone-canadian-economy

| IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

8

$1,000,000,000+

3D bio-printing technology is being explored to engineer organs and body parts using inkjet printing techniques, where layers of live cells are printed onto a gel medium or sugar matrix to form complex structures, such as blood vessels.4

The Impact Centre at the UofT was designed to bring academics & industry together to accelerate development of emerging tech & services in the natural sciences and engineering fields.

Read how an IMS entrepreneurial scientist helped found the Impact Centre to use science to improve society on page 21.

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 9

FEATURE INFOGRAPHIC

By Mona Li MScBMC Candidate

MAGAZINE STAFF EDITORS-IN-CHIEF Chantel Kowalchuk Priscilla Chan

OF PHOTOGRAPHY)

EXECUTIVE EDITORS Beatrice Ballarin Colin Faulkner Jonathon Chio Krystal Jacques Natalie Osborne DESIGN EDITORS Alexander Young Colleen Tang Poy Julia Devorak Mona Li Shirley Long JOURNALISTS & EDITORS Aadil Ali Alaa Yousef Alexa Desimone Ana Stosic Ayesha Noman Bowen Zhang Corrine Doroszkiewicz Cricia Rinchon Darby Lowe Diana Hamdan Duncan Green Erika Opingari Frank Pang Jason Lau Jason Lo Kenya Costa-Dookhan

COVER ART

By Shirley Long MScBMC Candidate

Copyright © 2019 by Institute of Medical Science, University of Toronto. All rights reserved. Reproduction without permission is prohibited.

The IMS Magazine is a student-run initiative. Any opinions expressed by the author(s) are in no way affiliated with the Institute of Medical Science or the University of Toronto.

PHOTOGRAPHERS Dorsa Derakhshan Krystal Jacques (DIRECTOR Mikaeel Valli

SOCIAL MEDIA TEAM Beatrice Ballarin (EXECUTIVE EDITOR) Darby Lowe Jason Lo Louise Pei (DIRECTOR OF SOCIAL MEDIA) Maryam Bagherzadeh Riddhita De Sandy Che-Eun Serena Lee SPONSORSHIP TEAM Carina Freitas

Mathura Thiyaga Mikaeel Valli Nadia Boachie Noeline Subramaniam Parita Shah Rachel Clark Samia Tasmim Shahrzad Firouzian Sharon Yoon Sonja Elsaid Sunny Lee Valera Castanov Yekta Dowlati Yousef Manialawy Yvonne Bach

IMS MAGAZINE

THINK. LEARN. DISCOVER.

SPRING 2019

[PLACEHOLDER]

EMERGING

MEDICAL

TECHNOLOGIES

DEEP BRAIN STIMULATION

At the cutting edge of mental health treatments

HIGH-THROUGHPUT DRUG SCREENING

Learning to commercialize scientific discoveries

CRISPR-CAS9 GENE EDITING

The ethics & consequences of fetal genome editing

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 3

LETTER FROM THE EDITORS

Photo Credit: Priscilla Chan

LETTER FROM THE

H

EDITORS

ow do you make the impossible possible?

It starts with a spark of imagination, a dash of funding, and a whole lot of hard work.

Throughout every graduate student’s journey, there comes a time we face obstacles that are seemingly too great to overcome. We hope that someone out there comes up with a new technique or technology that would solve all our problems. But if we look back even within the past few years, there have already been a surge of new medical advancements to help researchers and clinicians achieve what they couldn’t before. The only question that stands in our way becomes: How can we use it?

Luckily for us, we are surrounded by supervisors, faculty members, and fellow peers who lead by example, showing us exactly how to capitalize on these new methods. In our Spring 2019 issue, the IMS Magazine provides you just a glimpse into the possible applications of Emerging Medical Techniques & Technologies.

We’ve heard about deep brain stimulation for Parkinson’s disease, but what about other neurological disorders? To answer this, Drs. Nir Lipsman and Daniel Blumberger tell us how they have used various forms of brain stimulation as experimental treatments for anorexia and depression, respectively. We’ve also seen the decorative figurines people can design and print with 3D printers, but do they have any scientific value? Dr. Anne Agur teaches us how they are generating 3D anatomical models of intricate musculoskeletal systems and Dr. Forrest shows us how he uses 3D-printed models to plan complex surgeries. With so many new discoveries, how does a scientist get into business? Dr. Cynthia Goh shares her experience in navigating this path. And what about revisiting old techniques? Dr. Andrew Dueck explains how MRI and automated imaging processing is the new way to plan vascular surgeries.

We are equally excited to share student perspectives on automation in healthcare, the use of animals in research, and the controversial CRISPR baby. Other Viewpoint articles include the rise of predatory publishing, the looming threat of superbugs, and the dissolution of Ontario’s integrated health network. We also fill you in on several recent events, including the start of a new student-run podcast, Medicine in Motion, the International Stroke Conference in Hawaii, the TRP event on medical device regulation, and IMSSA’s Bell Let’s Talk Day campaign. Last but not least, we find time to review a book about psychedelic drugs, psychiatric conditions, and society.

As always, we hope there’s something for everyone in this issue and we’d love to hear your thoughts! Feel free to email us at theimsmagazine@ gmail.com and visit out website at imsmagazine.com.

Priscilla Chan

Chantel Kowalchuk

Priscilla is currently an MSc student engineering stem cells for traumatic spinal cord injury under the supervision of Dr. Michael Fehlings at the Krembil Research Institute

Chantel is currently a PhD student investigating the metabolic side-effects of drugs used to treat schizophrenia at the Centre for Addiction and Mental Health under the supervision of Drs. Margaret Hahn and Gary Remington.

4 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

DIRECTOR’S MESSAGE

DIRECTOR’S

MESSAGE

W Photo Credit: Iris Xu

Dr. Mingyao Liu

Director, Institute of Medical Science Senior Scientist, Toronto General Research Institute, University Health Network

ith the entrance of the new season comes the publication of the Spring 2019 IMS Magazine. Spring is a time of development, emergence, and growth; this coincides nicely with the theme for this issue: Emerging Medical Technologies. Medicine is in the midst of any exciting time, where new technologies are taking the field to unknown places. Our scientists in the IMS are at the forefront of discovery, using these medical technologies to treat disease, discover more about our physiology, and perform surgeries, amongst other things.

A select few scientists are profiled in this issue, who are using medical technologies and techniques in exciting new ways. 3D printing is infiltrating all disciplines, including medicine, and Dr. Anne Agur and Dr. Christopher Forrest share how they each use 3D printing: one to discover new details about the musculoskeletal system, and another for craniofacial surgery planning and training. Another medical technique being repurposed by IMS scientists is deep brain stimulation (DBS), is a fairly new technique that is gaining traction in the field of mental health. Dr Nir Lipsman shares how he uses DBS for the treatment of anorexia, while Dr. Blumberger uses a new type of stimulation called theta burst stimulation for depression. MRI is also being used in ways, one of which is by Dr. Andrew Dueck, who uses MRI in a novel way to select the appropriate vascular surgery technique. Finally, Dr. Cynthia Goh shares how she commercialized her discovery of diffraction based sensing, created a company, and started an entrepreneurship course to educate future scientists.

The IMS magazine has also written a number of Viewpoint articles, covering the latest automations in healthcare, debating the use of animals in research, and informing us on the CRISPR baby. There are also Viewpoints on a number of subjects beyond medical technology, including the emergence of ominous predatory publishers, the recent dissolution of the Ontario health network by our government, and the threat of antibiotic resistant superbugs.

Finally, the issue gives an overview on some of the exciting events happening around the IMS, such as a new student-run podcast, IMSSA’s Bell Let’s Talk Day campaign, and the translational research program (TRP) event on medical device regulation.

As always, I would like to commend the IMS editors, journalists, photographers, and design team for the excellent production they have put together this semester. This Spring issue truly highlights the novel innovations and research being performed in the IMS, and I encourage you to read and learn something new!

Sincerely, Dr. Mingyao Liu, MD, MSc Director, Institute of Medical Science

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 5

RAW TALK PODCAST

6 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

COMMENTARY

Pursuit of a Holistic Model of Addiction Refers to Models Of Addiction: Integrating Approaches By Duncan Green

By: Nadia Boachie

C

anada is still amidst a national opioid addiction crisis.1 There is a need to take an integrated approach to model addiction and better support those suffering, but the feasibility of creating such a model is unclear. Empirical evidence has given rise to multiple models of addiction. Many of these models are not holistic in their portrayal of addiction and this has started a debate about their validity.

As Duncan Green points out in his recent article, Models Of Addiction: Integrating Approaches, development of a unified, comprehensive model is due. Establishing a model of addiction that allows us to better understand its complexity will help improve treatment and in turn reduce social and financial burdens related to the chronic condition.

Different models of addiction place varying degrees of blame on the addict. At one end of this spectrum, blame or responsibility rest completely on the addict: the moral failure model. This model implies that addicts should be blamed or punished for the bad decisions they make. The brain-disease model of addiction (BDMA) places majority of the blame on the malfunctioning brain. Many scholars believed BDMA it would combat public stigmatization of addicts.2 The National Institute on Drug Abuse (NIDA) is known for its hand in promoting addiction as a disease. Researchers and public policy makers debate the evi-

dence suggesting that framing addiction solely as a disease helps reduce public stigma.3 Nick Heather, clinical psychologist, backed by a growing number of researchers, believe that relying on the disease model is not necessary for gaining public sympathy for addicts. Perhaps, scientists should give some autonomy back to the addict.

In Models Of Addiction: Integrating Approaches, Green talks about the positives and negatives of the incentive salience model. This model describes drug addiction as an excessive amplification of psychological “wanting.”⁴ The incentive salience model describes changes in reward, motivation, and executive control circuits in the brain, ultimately leading to increased sensitivity to drugs and drug cues. This model incorporates aspects of sociological and environmental factors and compensates for the shortcomings of BDMA model. Unfortunately, the problem with the incentive salience model and many others like it is that it focuses on drugs and drug-associated cues at the expense of other aspects of addiction, such as physiological dependence to drugs.

Knowing which elements of addiction to piece together to form a new holistic model has proven challenging. First, psychoactive drugs have varying degrees of addictive features. Differences in addictive features means that drugs vary in abuse liabilities.

Second, animal models of addiction and

study designs often restricts what clinicians can study. For example, self-administration of psychoactive drugs like cannabis is very hard to teach lab animals. Third, researchers studying addiction are often in niche scientific fields. For example, scientists that study dopaminergic systems are more likely to develop a model that solely describes malfunction of the dopamine system in addiction. They are less likely to develop a model that includes contributing social factors such as childhood adversity. There are multiple models and theories of addiction, but they focus on different aspects of addictive behavior, and therefore it is difficult to compare or integrate these models. Ideally, an addiction model should incorporate all addiction aspects: its biological basis as well as the social and psychological components.

References 1. Shum D. Toronto facing mental health and addiction crisis amid spike in overdose deaths: mayor [Internet]. Global News. 2018.

Available from: https://globalnews.ca/news/4388740/toronto-mental-health-addiction-overdose-crisis/ 2. Leshner AI. Addiction is a brain disease, and it matters. Science.

1997 Oct 3;278(5335):45-7.

3.

Heather, Nick. “Q: Is Addiction a Brain Disease or a Moral Failing?

A: Neither” Neuroethics vol. 10,1 (2017): 115-124.

4. Robinson TE, Berridge KC. The incentive sensitization theory of addiction: some current issues. Philosophical Transactions of the Royal Society B: Biological Sciences. 2008 Jul 18;363(1507):313746.

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 7

INFOGRAPHIC

EMERGING MEDICAL & SURGICAL TECHNOLOGY DEEP BRAIN STIMULATION

NON-INVASIVE BRAIN STIMULATION

Deep brain stimulation (DBS) involves implanting electrodes within the brain that generate specific electrical impulses designed to regulate abnormal brain activity.

Another brain stimulation technique, transcranial magnetic stimulation (TMS) is a lessinvasive option for modulating brain activity via magnetic fields.

Stimulating brain areas near the scalp may boost or reduce activity in these regions, and could even strengthen (or weaken) their functional connections with other, deeper brain structures.2 Go to page 15 to learn how IMS researchers are using non-invasive brain stimulation techniques for treatment resistant psychiatric disorders.

DBS is most commonly used to treat movement disorders (eg.

Parkinson’s, essential tremor, dystonia) and some psychiatric disorders (eg. obsessive compulsive disorder) but is also being investigated as a potential treatment for; major depression, chronic pain, addiction, dementia, Huntington’s disease, multiple sclerosis, Tourette syndrome, stroke, & traumatic brain injury.1 Read about IMS researchers using DBS to treat anorexia and alcohol use disorder on page 13.

8

Transcranial direct current stimulation (tDCS) applies tiny electrical currents to the scalp (eg. one to two milliamps) that some researchers believe can enhance neuroplasticity.

Companies have started selling at-home tDCS devices (ranging from $40 to $700) claiming to improve motor abilities or enhance concentration – although their effectiveness has not been proven.3

MAGNETIC RESONANCE ANGIOGRAPHY

Magnetic Resonance Angiography (MRA) is a type of medical imaging that uses magnetic fields to map out the body’s blood vessels. Less invasive (and less painful) than a traditional angiogram, MRA provides detailed images of the immense network of blood vessels in the body, including

| IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

those which have been hardened or clogged with plaque (eg. atherosclerosis).5 See page 17 to read how vascular surgeons in the IMS are refining MRA to help patients with peripheral arterial disease.

INFOGRAPHIC

INNOVATION AT UOFT

3D BIO-PRINTING

500+ COMPANIES CREATED AND 3D printing refers to the process where a material is added successively layer by layer to build a 3-dimensional product, guided by a digital design model. It’s currently being used in many industries, from food & fashion to weapons & automotive parts.

$1,000,000,000+

IN INVESTMENT SINCE 2008.

3D bio-printing technology is being explored to engineer organs and body parts using inkjet printing techniques, where layers of live cells are printed onto a gel medium or sugar matrix to form complex structures, such as blood vessels.4

400+

PATENTS FILED SINCE 2010.

See page 11 to read how IMS researchers are using 3D printing in facial reconstructive surgery.

STOREYS OF INNOVATION COMING IN 2021.

Innovative research at the UofT has led to the creation of over 500 companies which have produced over one billion in investment since 2008. Between 2010 and 2018, over 400 patents were filed for technologies developed by UofT researchers. The UofT is building a 14 storey innovation tower across from the MaRS Discovery District, set to open in 2021.6

DIGITIZATION & 3D MODELLING Digitization and 3D modelling technology is also being used to study the intricacies of human anatomy.

MADE A DISCOVERY, DESIGNED A DEVICE, OR DEVELOPED A METHOD THAT CAN REVOLUTIONIZE MEDICINE?

Go to page 19 to see how these high-rez models can be used to advance our understanding of anatomy and even help guide surgeries.

References 1. Deep Brain Stimulation. Mayo Clinic. Retrieved from https://www. mayoclinic.org/tests-procedures/deep-brain-stimulation/about/pac20384562.

2. Lefaucheur JP, André-Obadia N, Antal A, Ayache SS, Baeken C, Benninger DH, Cantello RM, Cincotta M, de Carvalho M, De Ridder D, Devanne H. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clinical Neurophysiology. 2014 Nov 1;125(11):2150-206.

3. Landhuis, E. Do D.I.Y. Brain-Booster Devices Work? Scientific American. Jan 10, 2017. Retrieved from https://www.scientificamerican. com/article/do-diy-brain-booster-devices-work/

14

4. Miller JS, Stevens KR, Yang MT, Baker BM, Nguyen DH, Cohen DM, Toro E, Chen AA, Galie PA, Yu X, Chaturvedi R. Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues. Nature materials. 2012 Sep;11(9):768.

5. Magnetic Resonance Angiography (MRA). John Hopkins Medicine.

Retrieved from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/magnetic-resonance-angiography-mra 6. Sorenson, C. U of T innovation centre to help form ‘new cornerstone’ of the Canadian economy. July 23, 2018. UofT News.

Retrieved from https://www.utoronto.ca/news/u-t-innovation-centre-help-form-new-cornerstone-canadian-economy

The Impact Centre at the UofT was designed to bring academics & industry together to accelerate development of emerging tech & services in the natural sciences and engineering fields.

Read how an IMS entrepreneurial scientist helped found the Impact Centre to use science to improve society on page 21.

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 9

FEATURE Photo couresy of Dr. Christopher Forrest

Head First into the Future: By: Yousef Manialawy

M

Exploring innovation in craniofacial surgery with Dr. Christopher R. Forrest

any an artist has dedicated themselves to the pursuit of capturing the sheer complexity of the human body–from the subtle veins snaking through the hands to the quivering tendons underlying every contraction of muscle–nature has crafted a work that defies simple imitation. Of the body’s many facets, the face undeniably poses one of its greatest challenges.

Integral to human identity, its every twitch and twinge guides communication and subconscious perception. To capture its intricacies in a brushstroke is impressive, and even more so in marble and stone; but the stakes are much higher when the face you’re designing is that of a living, breathing person. As a pediatric craniofacial plastic surgeon at SickKids Hospital, Dr. Christopher R. Forrest is challenged with head and facial reconstruction of children on a daily basis.

He offers insight into how technological innovation, such as 3D-printing, is pushing the limits of craniofacial surgery.

After receiving his medical degree at UofT, Dr. Forrest pursued a residency in Plastic and Reconstructive Surgery in 1983.

Having also developed a strong interest in research, he concurrently investigated the effects of nicotine in microcirculation on post-surgical wound healing with IMS, ultimately receiving both an M.Sc. from IMS and completing his residency in 1990.

Following multiple fellowships in both Toronto and the United States, he was recruited to Sunnybrook Hospital in 1993 with a part-time appointment at SickKids.

By 1999 he was appointed Medical Director of the SickKids Centre for Craniofacial Care and Research and has been the Chair of the Division of Plastic and Reconstructive Surgery at UofT since 2003. As of 2009, he manages the largest division of full-time surgeons dedicated to paediatric plastic and reconstructive surgery in North America.

10 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

With such a wealth of experience, Dr. Forrest has emerged as a leader at the cutting edge of his field. He has long maintained an interest in pushing the boundaries of surgical technology. “There’s a saying that biology beats surgery every day,” he says. “But as surgeons doing this kind of work, we always want to beat that idea”. In a profession already riddled with complexity, operating on children adds yet another factor to the equation: “The world of pediatric craniofacial surgery is very, very challenging…but it’s also very rewarding,” explains Dr. Forrest.

“And to me, the fact is that we’re not just treating the child but we’re treating the family.” Offering some further insight, he explains how he measures the success of his operations. “I have this thing I call the supermarket test” he begins. “If you’re in the supermarket and you see this child run by, would you look twice and think to

FEATURE yourself ‘there’s something wrong with that child’…or would you not pay attention?”

Outside of the operating room, Dr. Forrest and his team are also busy developing new technologies for surgical applications, most notably through the application of 3D-printing. “We use it in creating scale models [of the skull]” he explains.

“These are really essential for planning out complex surgeries–the advantage is that we don’t have overlying soft tissue sitting on the bones, so we can see the anatomy”.

This has become standard practice for Dr. Forrest, who has used the information garnered from these 3D models to better operate on his young patients, such as in the case of 6-year old Mumtaz who was born with a cleft skull, facial disfigurement, and missing her upper right eyelid. After a CT scan was taken of her head, a model of her skull was 3D-printed and used to develop and implement a successful operation. 3D-printing has even gone a step further for direct application within the surgery. “So, I have a child who for example may be missing bone from an accident” explains Dr. Forrest. “And using CAD-CAM technology [i.e. computeraided design and manufacturing] we can actually use 3D printing to make implants to fit the patient very specifically”.

Dr. Forrest has also employed 3D-printing

for the purpose of training aspiring surgeons. As with most professions, proficiency is gained through hands-on experience, but the room for error is significantly smaller for surgeons in training. “In my world, teaching somebody how to repair a cleft lip or even nasal surgery is technically very demanding” explains Dr. Forrest. “And as a surgeon, allowing somebody to train and learn on a patient is always a little anxietyprovoking.” To address this, he teamed up with surgery resident and biomedical engineer Dr. Dale Podolsky to develop a life-sized, 3D-printed simulator model of a cleft palate (i.e. when a baby’s lip/ mouth does not properly form during pregnancy). This is a major advancement for the field, considering that cleft lip repair is a notoriously difficult and delicate procedure, not least of all because it is typically carried out in young infants.

The simulator consists of a composite silicone plastic frame with a disposable cartridge that slides in. It was designed to simulate a high-fidelity, anatomically accurate representation of the various muscles that require surgical reconstruction during the operation.

Notably, the model has offered a more accurate and objective metric by which to evaluate surgical proficiency in trainees.

“We’re moving away from an apprentice

Dr. Christopher R. Forrest, M.D., M.Sc., FRCS(C), FACS Chair, Division of Plastic and Reconstructive Surgery Medical Director, SickKids Centre for Craniofacial Care and Research Professor, Department of Surgery

model which is what I went through, where I would basically stand and watch… and when the professor felt that I was good enough to do the operation he would allow me to do it” he explains. “Now what we’ve done is break down every single technical aspect of that operation into competencies… and we have objective data that you’re able to demonstrate.”

For operations that involve reshaping the bones of the skull, Dr. Forrest and his team have also developed steel templates based on normal skull contours to help guide surgeons during reconstruction.

The difference between the reconstruction and the template is measured as the mathematical area under the curve, which serves as a proxy of how close the surgery was to achieving a healthy shape. “Based on CT scans collected from healthy patients, we’ve created standard norms for certain shapes—for example, the forehead,” explains Dr. Forrest. “The results are better, and what we’ve also found is that the time for surgery is decreased… also, we can actually rate according to where the skull fits on the scale and get objective data to show ‘that’s a five or seven out of ten’ as opposed to how funky it looks.”

In light of his many pursuits, Dr. Forrest is well on his way to making a lasting impact in his field. When asked what’s next, he shares his exciting vision for the future: “An area of interest of mine is developing a robotic approach to surgery… but we realized that we couldn’t take a robot and use it on a baby because it’s never really been done before.” To address this, Dr. Forrest is looking to use his cleft lip simulator to train the robot, which he describes as “the next huge advancement in terms of the specialty.”

With his efforts fuelling so many avenues of innovation, one could not be faulted for wondering where exactly Dr. Forrest finds his drive. To this, he offers some powerful insight: “It sounds cliché, but if you’re passionate about something, that passion will take you to whole new worlds and take you down roads that you never expected to go on. I always think when a door opens you should take advantage and walk through it because that door may close and you may never have that opportunity again.”

Photo couresy of Dr. Christopher Forrest

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 11

FEATURE

Stimulating progress Using deep brain stimulation to treat refractory

W

By: Mathura Thiyagarajah

hen conventional methods of intervention for psychiatric conditions fail, patients and physicians alike turn to novel approaches for relief. Deep brain stimulation (DBS) is gaining traction as an emerging intervention for treatment-resistant psychiatric and neurologic disorders, due in part to the work by Dr. Nir Lipsman and colleagues.

DBS is a minimally invasive form of neurosurgery where electrodes are implanted in the brain to modulate neural circuitry. While DBS has primarily been employed for the treatment of movement disorders such as Parkinson’s disease since the 1980s, Dr. Lipsman’s research has fostered its novel application in the psychiatric conditions of anorexia nervosa, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and alcohol use disorder.

“My interest has always been in the interface between brain disease and technology,” Dr. Lipsman explains. More specifically, he is interested in “how we can harness the power of technology to treat the most challenging and treatmentresistant neurologic and psychiatric disorders.” This passion led him to become a neurosurgeon and Director of the Harquail Centre for Neuromodulation at Sunnybrook Health Sciences Centre, in which his clinical and research practice focuses on ways to interact with the brain through the neuromodulation methods of DBS and focused-ultrasound (FUS) therapy.

Dr. Lipsman first helped break scientific ground in DBS research in 2013, with the publication of the world-first clinical trial of DBS in anorexia nervosa during

his PhD at IMS under the supervision of neurosurgeon Dr. Andres Lozano, together with their collaborator Dr. Blake Woodside.1 Anorexia nervosa is an eating disorder marked by an intense fear of weight gain, persistent behaviours to prevent weight gain, and disturbances in the way weight or body shape is experienced. It has the highest mortality rate of psychiatric disorders and many patients are unresponsive to treatment.2 The Phase 1 pilot trial followed six patients with chronic and severe anorexia nervosa who had suffered from years of unsuccessful treatments and numerous hospitalizations.1 In 2017, a follow-up paper was published with 16 additional patients who underwent DBS treatment.3 While starvation and malnourishment are the most visible physical manifestations of anorexia nervosa, the researchers did not target brain areas related to appetite regulation and feeding behaviour. Rather, stimulation was directed at the subcallosal cingulate, an area associated with mood and anxiety, which are the recognized driving factors underlying the illness.

Researchers found that the DBS treatment significantly increased body mass index (BMI), decreased depressive symptoms, and improved mood regulation in patients.3 The neurosurgical procedure of DBS in these trials is completed in two stages within the same day. The first stage involves stereotactic implantation of the electrodes into specific bilateral positions of the brain while the patient is awake under local anaesthetic. Dr. Lipsman explains that this allows for the “study of the brain in real-time as you are intervening”, since patients can answer questions about how they feel when the electrodes are turned on and identify

12 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

any possible side effects. Once the team is satisfied with the positions of the electrodes, the patient is put under general anaesthetic for the second stage, in which batteries connected to the electrodes are placed in the chest under the collarbone.

Next, the patient is seen by a psychiatrist to activate the device and adjust stimulation settings over time, which is analogous to establishing an effective dosing regimen of a pharmaceutical to maximize benefits while minimizing side effects. The device is similar to a pacemaker for the heart in that it is always on, except it is constantly stimulating the brain. The stimulation can modulate dysfunctional brain circuits associated with a disorder that are hyperactive or hypoactive, though they may appear visibly normal on a computerized tomography (CT) or magnetic resonance imaging (MRI) scan.

Currently, Dr. Lipsman is targeting brain areas specific to other disorders as well.

He is the principal investigator in Phase 1 clinical trials investigating the safety, tolerability, and efficacy of DBS treatment in refractory alcohol use disorder, OCD, and PTSD. The trial in treatment-resistant chronic alcoholism, currently the project of IMS PhD student Dr. Ben Davidson, is among the first systematic prospective trials using DBS to stimulate the nucleus accumbens, an area involved in the brain’s reward pathway that is significantly associated with addictive behaviours.

The next step would be larger, multicenter trials that are sham-controlled. He explains that one of the advantages of DBS is that electrodes can be inserted without activation. As such, patients and raters can be blinded to whether the stimulation is turned on in a scientifically objective and ethical manner. This allows researchers

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in the brain: psychiatric disorders to distinguish between the effects of the patient’s expectations of stimulation compared to actual active stimulation on treatment success.

Ethical implications of DBS are of great interest to Dr. Lipsman, particularly in light of the historical era of lobotomy that still tarnishes conceptions of the field of psychiatric surgery today. “Given those transgressions, it is important that we do things in a systematic, scientifically rigorous, and safe way,” Dr. Lipsman warns.

Respecting patient autonomy is paramount in his clinical and research work, as are patient education and managing participant expectations. Though DBS is minimally invasive compared to other neurosurgeries, explaining the risks of surgery is integral to the intervention process. He stresses the importance of scientists not taking advantage of patient desperation, as the patients involved in these trials have a higher severity of sickness with poorer prospective outcomes. However, this is also why Dr. Lipsman believes “there is a lot at stake in not treating some of those patients.”

Dr. Lipsman is especially enthusiastic about the multidisciplinary and collaborative nature of this work. On an average week, he works closely with neuropsychologists, psychiatrists, and neurologists to develop a treatment strategy and must consider the pharmacology, neuroimaging, and surgery

involved. Developments in the design of devices and treatment strategy are made in parallel with advancements in the understanding of brain circuitry of these challenging illnesses.

“All of these fields are developing at the same time, so I think that is what the hope is: that all of these multidisciplinary advancements will come together to develop new therapies,” says Dr. Lipsman.

References 1. Lipsman N, Woodside DB, Giacobbe P, et al. Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet. 2013;381(9875):1361-70.

2. Arcelus J, Mitchell AJ, Wales J, et al. Mortality rates in patients with anorexia nervosa and other eating disorders: a meta-analysis of 36 studies. Arch Gen Psychiatry. 2011;68(7):724-31.

3. Lipsman N, Lam E, Volpini M, et al. Deep brain stimulation of the subcallosal cingulate for treatment-refractory anorexia nervosa: 1 year follow-up of an open-label trial. Lancet Psychiatry.

2017;4(4):285-94.

Photo by: Dorsa Derakshan

In terms of the technology involved, the concept of implanting electrodes in the brain to influence brain circuitry in psychiatric disorders is still fairly new.

Dr. Lipsman notes improvements in the physical electrodes and leads involved.

Directional lead models allow surgeons to steer stimulation current in a precise direction, thus permitting the stimulation of certain fibres in pathways that may be more important than others. This can be especially important as Dr. Lipsman explains, “We know that no two brains are truly alike and so where we put the electrodes matter a lot.”

Overall, he views DBS as an adjunctive therapy in which brain stimulation can perturb the neural circuits in a way that facilitates the actions of additional interventions, including medical, pharmacological, radiation, and other surgical treatments: “By harnessing all the tools at our disposal, we can try to achieve additive and cumulative therapeutic effects for these disorders.”

Dr. Nir Lipsman Scientist, Physical Sciences, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute Neurosurgeon, Sunnybrook Health Sciences Centre Assistant Professor, Department of Surgery, University of Toronto Director, Harquail Centre for Neuromodulation, Sunnybrook Health Sciences Centre IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 13

FEATURE Photo by: Mikaeel Valli

Dr. Daniel Blumberger Associate Professor, Department of Psychiatry, University of Toronto Clinician Scientist, Campbell Family Mental Health Research Institute, CAMH Medical Head and Co-Director, Temerty Centre for Therapeutic Brain Intervention, CAMH 14 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

Innovation through Stimulation: By: Darby Lowe

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The Cutting Edge of Mental Health Treatment

D

epression is currently the leading cause of disability around the world, affecting over 300 million people. Common treatments for depression include both psychological (e.g. cognitive behavioral therapy) and pharmacological (e.g. selective serotonin reuptake inhibitors) approaches. Despite advances in these treatment modalities over the past decade, more than one third of patients with depression do not respond to these “first-line” treatments. Moreover, some antidepressant medications can induce intolerable and systemic side effects. So, what are the alternatives for patients who do not respond to or tolerate these therapies?

Dr. Daniel Blumberger, a clinician scientist at CAMH, has spent his career advocating for clinical research, with a passion for redefining treatment. Acting as the Medical Head and Co-Director at the Temerty Center for Therapeutic Brain Intervention, Dr. Blumberger is spearheading innovation as he investigates the benefits of brain stimulation as a therapeutic option for refractory psychiatric disorders.

In the early stages of his training, Dr. Blumberger treated patients with severe, treatment-resistant depression and was able to see the benefits of electroconvulsive therapy, or ECT, first-hand.

ECT is a therapy often used as a last-resort for patients unresponsive to any other treatment and involves the application of an electric current throughout the brain of an anaesthetized patient. Dr. Blumberger described how the treatment had the ability to “transform someone within a matter of weeks,” acting as a “type of awakening” for acutely ill and catatonic patients.

In completing his training, Dr. Blumberger gained experience using ECT as well as other forms of brain stimulation, including transcranial direct current stimulation (tDCS), transcranial magnetic stimulation (TMS), and magnetic seizure therapy (MST). Dr. Blumberger has since been part of numerous clinical investigations

examining brain stimulation as a therapeutic intervention for a variety of psychiatric disorders.

Currently, Dr. Blumberger and his team are investigating a novel type of TMS called theta burst stimulation (TBS) in young adults with treatment-resistant depression.

TBS stimulates the brain with theta frequencies (4 to 7 Hz) similar to naturally occurring neural oscillations found in the brain, and can be performed in sessions as short as three minutes. This is compared to TMS, which involves magnetic stimulation of the brain with a frequency of 10Hz over multiple sessions roughly half an hour in length. Almost half of the participants in each brain stimulation modality group showed marked improvement of at least a 50% reduction in depressive symptoms, as well as increased energy and concentration and decreased suicidal ideation.

“The improvement in the patient’ overall quality of life, such as regaining their ability to function and go back to work, is particularly important,” says Dr. Blumberger. “We were also able to demonstrate that both TMS and TBS have similar clinical efficacy, and a major clinical implication of this finding is that TBS provides a shortened therapeutic session (three minutes compared to 30).”

Therefore, TBS could facilitate a larger clinical impact by increasing the number of patients that can be treated each day.

Another area of Dr. Blumberger’s research aims to improve accessibility to brain stimulation treatment by investigating the application of tDCS as a relapseprevention intervention in individuals who have previously responded to TMS. tDCS provides a much lighter form of stimulation to the brain and can be used by the patient in their own home. The theory, according to Dr. Blumberger, is that tDCS, which is a “plasticity-enhancing treatment,” will maintain the therapeutic changes that were imparted by TMS and therefore prevent relapse. If this is the case, the at-home treatment would minimize the travel burden for patients, therefore

making therapeutic brain stimulation more accessible to all populations.

When asked why brain stimulation is an important area of research, Dr. Blumberger emphasizes its minimal side effects. Compared to pharmacological interventions that can produce serious systemic side effects, such as weight gain and bleeding disorders, brain stimulation techniques produce only minor side effects (e.g. headache, scalp discomfort).

Moreover, Dr. Blumberger describes a future collaborative study in which functional magnetic brain imaging will be used concurrently with brain stimulation to biologically phenotype and potentially personalize treatment to one’s underlying dysfunction. He describes how, because of the high prevalence of depression and associated disability, as well as the high rates of treatment resistance in many patients, more options need to be available. “That’s why TMS is a very important treatment,” he explains, “it has demonstrated efficacy, it has the potential to be a personalized treatment, and it targets the brain without systemic side-effects.”

Dr. Blumberger’s work is aiming to transform brain stimulation into a safe, personalized and accessible form of medicine that may eventually be offered earlier in the care pathway of patients with depression. Dr. Blumberger’s motivation for his work researching and clinically practicing brain stimulation speaks for itself: “We are trying to advocate for these treatments because they are effective, have good tolerability and offer a new option for debilitating illness.”

References 1. Depression [Internet]. World Health Organization. World Health Organization; 2018 [cited 2019Mar15]. Available from https://www. who.int/news-room/fact-sheets/detail/depression 2. Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR* D report.

American Journal of Psychiatry. 2006 Nov;163(11):1905-17.

3. Blumberger DM, Vila-Rodriguez F, Thorpe KE, Feffer K, Noda Y, Giacobbe P, Knyahnytska Y, Kennedy SH, Lam RW, Daskalakis ZJ, Downar J. Effectiveness of theta burst versus high-frequency repetitive transcranial magnetic stimulation in patients with depression (THREE-D): a randomised non-inferiority trial. The Lancet. 2018 May 4;391(10131):1683-92.

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 15

FEATURE

Selecting the Right Vascular Treatment

for Patients with Peripheral Arterial Disease By: Mikaeel Valli

P

eripheral arterial disease (PAD) is a common circulatory problem in which plaque build-up in the arteries leads to narrowing of the vessels, commonly in the legs. This arterial narrowing process, also known as atherosclerosis, hinders sustainable blood supply to the limbs and impedes their function. In severe cases, patients’ legs could face amputation as the last treatment resort. PAD affects 800,000 Canadians, with the most common symptom being claudication—that is, leg pain when engaging in simple physical activities (such as walking) which improves with rest. However, 50% of patients are asymptomatic, known as ‘silent’ PAD, that leaves tens of thousands of Canadians at greater risk for preventable cardiovascular disease including heart attacks and strokes.

Fortunately, PAD treatments are available which greatly improve patients’ quality of life and significantly preserves and protects their legs from amputation.

When conservative measures including medication and supervised exercise are unable to improve the circulation to the limbs, revascularization becomes necessary.

Bypass surgery is an approach that involves attaching a graft that bypasses the blocked artery. Conversely, the endovascular technique is a commonly used approach that opens the arterial blockage using a catheter or a thin guidewire. This method is preferred over bypass surgery because it is minimally invasive, making it less risky with fewer treatment complications.

However, vascular surgeons are faced with a dilemma: which PAD patients are an appropriate candidate for endovascular treatment?

The IMS Magazine had the pleasure

of interviewing Dr. Andrew Dueck, a vascular surgeon and associate scientist at Sunnybrook Health Sciences Centre in Toronto. He recalled the many incidences of variability in the amount of time it takes to insert catheters into his patients, as well as multiple occasions where insertion was not possible at all. He explained, “20% technical failure rate occurs for endovascular treatment, and most immediate failure is due to the inability of the guidewire to cross the plaque build-up.”

Dr. Dueck emphasized that this variation depends on the plaque being hard or soft, where hard plaque that is especially calcified greatly impacts the guidewires ability to penetrate and thereby affecting the efficacy of the treatment.

Currently, the planning of revascularization is determined through several imaging modalities. However, these imaging techniques lack the accuracy and detail required to provide surgeons with a representative picture of the lesions in the vessels, especially relating to their level of calcification. As a result, Dr. Dueck explained that surgeons cannot make fully informed decisions about revascularization strategies. The gold-standard is X-ray with digital subtraction angiography, which can detect only heavily calcified vessel walls with 60-80% sensitivity. “The drawback is that it cannot differentiate the morphology of the calcification, which is a crucial component that impacts endovascular outcome,” Dr. Dueck explained.

Computed tomography (CT) angiography is another method that can characterize the calcification in medium-sized vessels.

The downside, Dr. Dueck explained, “is that it cannot accurately evaluate the tibial vessels of the legs because of the calcium blooming, which is an imaging artefact

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that shows the calcification to appear larger and therefore makes the occlusion appear bigger than it actually is.” In addition to this being misleading, Dr. Dueck elaborated that “the angiogram does not show the full extent of the lesions in especially distal vessels.” Duplex ultrasound is the third imaging modality that can provide a view of the vessel wall and provide physiological flow information. However, the calcification makes it challenging as it causes acoustic shadowing, creating image artefacts and obscuring the view of the vessels. “There needs to be a better way,” Dr. Dueck declared, “to plan and predict whether endovascular surgery is the right treatment for patients with PAD.” Therefore, Dr. Dueck has teamed up with Dr. Trisha Roy, a vascular surgery resident, and Dr. Grahm Wright, a scientist in cardiovascular imaging at Sunnybrook, to find a suitable solution.

Through funding from CIHR as well as the Heart & Stroke Lewer Centre of Excellence/ Toronto Academic Cardiac Vascular Collaborative, the team is exploring whether magnetic resonance imaging (MRI) could be an effective alternative tool for vascular surgeons. Dr. Roy, the main lead of this project, experimented with two MRI techniques with specific sequences: flow independent MR angiogram using 3D steady-state free precession sequence (SSFP), and 3D ultrashort echo time (UTE) using a prototype 3D cones sequence.

“SSFP angiograms allow the visualization of the lesion and blood vessel anatomy while the UTE advantageously allows the view of calcium and dense collagen,” Dr. Roy explained. Unlike X-ray angiogram, Dr. Roy described that these MRI techniques provide “a very good soft-tissue contrast and permit a detailed picture of blocked vessels, especially downstream.”

Photo by: Mikaeel Valli

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Dr. Andrew Dueck, MD, MSc, FRCSC, FACS, RPVI Associate Scientist, Physical Sciences, Schulich Heart Research Program, Sunnybrook Research Institute Vascular Surgeon, Head of Vascular Surgery, Sunnybrook Health Sciences Centre Assistant Professor, Division of Vascular Surgery, University of Toronto The trio ran a pilot study in collaboration with Dr. Hou-Jen Chen at Sunnybrook, using the two MRI techniques to see if they can effectively identify which lesions will be more difficult to cross with a guidewire.

Dr. Roy enthusiastically stated that “lesions identified as hard by MRI correlated with longer guidewire travel time, an average of 14 minutes. In contrast, lesions defined as soft by the MRI took about 2 minutes to cross.” She continued to explain that the images were able to detect hidden passages within the arteries that were not entirely blocked (called ‘occult patencies’) and noncalcified hard lesions that were not visible on X-ray angiography. “This pilot study showed that MRI poses to be a potentially useful and effective tool in the planning of peripheral endovascular interventions, or to decide if conventional surgery is a better option, as we now have the prior knowledge of where the lesion is and what kind of lesion is deposited in the arteries,” Dr. Roy said.

The tricky part of using these two MRI techniques is that they are complicated for clinicians to interpret compared to conventional CT scans. Dr. Dueck cautioned that if the generated images are not simplified or easy to read and use, translating the use of MRI to clinical practice will be hindered, and MRI will remain a research tool. Therefore, the team collaborated with Dr. Michael Schumaker, who developed software equipped with segmentation algorithms and is capable of automated image processing. Dr. Roy explained, “this automated software colour codes the MRI to make it easier to read; for instance, purple represents dense collagen while blue is for calcium.” The team has filed a patent for this software and are looking forward to optimizing its function as a user-friendly clinical tool for guiding all vascular surgeons in selecting the appropriate patients for endovascular treatment.

“The next step going forward is to validate the use of these MRI techniques and software on a larger patient scale at St. Michael’s and Toronto General Hospital,” Dr. Dueck explained. However, before doing that, he clarified, “we are looking to hire an MRI software engineer that can make the specific MR sequences compatible with other brands of MRI machines as currently, it is only compatible with the G.E. brand.”

In conclusion, Dr. Dueck and Dr. Roy believe that the use of MRI will permit better revascularization planning and patient selection, allowing for a higher success rate of endovascular treatment.

The MRI based tools have the potential to reduce treatment complications and ultimately, improve the overall quality of life for PAD patients.

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 17

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Digitization and A Revolutionary Technology

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By: Valera Castanov

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ne of Canada’s largest musculoskeletal laboratories is located in the basement of the Medical Sciences Building at the University of Toronto. This lab focuses on cutting edge research dealing with digitization and three-dimensional (3D) modelling of human anatomical structures. The goal is to construct volumetric models of blood vessels, nerves, connective tissues, and particularly, muscular and skeletal elements. These volumetric models can then be digitally constructed/deconstructed and analyzed in 3D space to elucidate important tissue properties and functional characteristics.

This novel technology was pioneered in the musculoskeletal laboratory and has since been employed in numerous labs across North America. Digitization and 3D modelling are actively being used to improve medical and surgical diagnostic, treatment, and rehabilitation techniques.

At the heart of the laboratory driving this research and innovation is the worldrenowned anatomist, Dr. Anne Agur.

She is the author of Grant’s Atlas of Anatomy, a textbook that is used not only across Canadian and American medical schools, but also around the globe. Dr. Agur is a leader in anatomical research and education, and she has agreed to discuss the ground-breaking work that her laboratory is currently focusing on and shed some light on the novel digitization and 3D modelling technology that her team has developed.

“Until recently, there was no reliable way to accurately capture the 3D architecture of fiber bundles of muscles, connective tissues, or nerve branching patterns at a sub-millimetre resolution,” Dr. Agur began. “However, our research team was able to overcome this challenge with the development of the digitization and 3D modelling methodology, which enabled the capture of the architecture of anatomical structures as in situ and the construction of volumetric anatomical models at a detail not previously possible.”

Dr. Agur continued: “To date, the majority of anatomical studies were observational in nature, and once the dissection was complete, there was no way to reassemble the anatomical structure to further investigate its architecture. Moreover, as previous studies involved two-dimensional (2D) observations, it was difficult to visualize and analyze the complex volumetric architecture of structures—for example, the intricate 3D nerve branching pattern within a muscle’s volume.”

The development of digitization and 3D modelling technology changed the paradigm of approaching human anatomy from a purely observational perspective, and provided a way to not only capture the architecture of anatomical structures as in situ, but also to analyze them through construction and deconstruction of individual anatomical elements postdissection. The models allow researchers to observe anatomical structures from different angles and perspectives to

18 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

understand their spatial organization, as well as volumetric computation of various structural and functional characteristics.

This novel methodology involves capturing Cartesian plane (X, Y, Z) coordinates along the full extent of muscle fiber bundles, nerves, blood vessels, connective tissues and skeletal elements. The stylus end of a digitizer is used to trace each anatomical element from start to finish, and Cartesian coordinates are stored along the full extent of the tracing. These data points are then imported into a modelling computer software and reconstructed into comprehensive 3D models. These models can then be joined with other elements to form complete structures. For example, in order to construct a model of a whole muscle, all of its fiber bundles and tendons have to be digitized, reconstructed in 3D, and digitally assembled. Models of nerves and blood vessels can be used to study their branching patterns and determine the anatomical regions that they supply.

Models of fiber bundles and intramuscular connective tissue elements can be used to study muscle architecture as related to function.

“Importantly, our research group is a part of a multi-disciplinary and a multilaboratory international collaboration with the goal of constructing the first dynamic 3D model of a human being at a fiber bundle level, which digitization and 3D modelling technology has made possible. It is a very exciting and ambitious task” Dr. Agur remarked. Last year, one of

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3D Modelling: 92 53 4

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Dr. Agur’s PhD graduates completed the digitization and 3D modelling of all of the musculoaponeurotic and skeletal elements of the lower limb, generating close to 60,000 digital anatomical elements and over 500,000 data points. This is the most in-depth and highest-resolution analysis of the human lower limb musculature to date.

“Digitization and 3D modelling methodology is being used to gain a detailed understanding of the human anatomy and physiology, which can then be translated to the fields of medicine and surgery,” Dr. Agur explained. For instance, detailed knowledge of a muscle’s volumetric architecture, neurovascular supply, and functional characteristics can be used to plan surgeries, such as muscle flaps and tendon transfers, guide intramuscular botulin toxin injections to treat post-stroke spasticity, and develop rehabilitation protocols to target a specific anatomical area to reverse pathology and regain normal function of that region.

Furthermore, muscle’s 3D architecture, including that of its intramuscular partitions, can help inform probe/ electrode placement in ultrasound and electromyography studies and diagnostic procedures. Digitization and 3D modelling are actively utilized in research studies by anesthesiologists studying the branching patterns of nerves that supply joint capsules. Knowing detailed branching patterns of sensory nerves can help guide denervation procedures to help patients with chronic joint pain.

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Dr. Agur is currently collaborating with anesthesiologists, orthopedic surgeons, physiatrists, physiotherapists, occupational therapists, and biomechanical engineers, along with other professionals and researchers in a multitude of fields. They share a common goal to further understand the anatomy, physiology, and biomechanics of the human body through digitization and 3D modelling, and to translate these findings to their clinical practice.

One of the lab’s endeavours is optimizing the incorporation of volumetric musculoaponeurotic architecture (obtained using digitization and 3D modelling) into patient-specific magnetic resonance imaging (MRI) muscle volume shells. This will help construct dynamic finite element musculoskeletal models capable of higher-fidelity simulation of in-vivo muscle dynamics. Presently available models primarily use idealized muscle fiber bundle templates to fill

muscle volumes, which have been shown to lead to differences of 10-20% in the predicted muscle force and contracted geometries when compared to models that were based on in situ 3D architectural data. In the near future, Dr. Agur and her team hope to develop an efficient method of registering 3D architectural data to MRI-obtained surface scans to construct patient-specific models that could facilitate diagnosis, treatment and rehabilitation.

“Overall, digitization and 3D modelling is a truly novel and innovative technology, that will continue to further contribute to our understanding of human anatomy and the development of improved medical and surgical approaches,” Dr. Agur concluded.

Dr. Anne Agur, BSc(OT), MSc, PhD Division of Physical Medicine and Rehabilitation, Department of Medicine, Faculty of Medicine, University of Toronto Department of Occupational Science & Occupational Therapy, Faculty of Medicine, University of Toronto Department of Physical Therapy, Faculty of Medicine, University of Toronto Division of Biomedical Communications, Institute of Communications and Culture, University of Toronto at Mississauga IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 19

FEATURE

Becoming a scientist-entrepreneur: An interview with Dr. Cynthia Goh

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By: Alexa Desimone

rowing up on a remote island in the Philippines, Dr. Cynthia Goh found her passion in the simplest of places—a chemistry textbook. At a young age, Dr. Goh became interested in understanding how atoms and molecules worked together in order to control the properties of matter. This interest led her on a linear path to becoming a scientist.

She received her PhD from the University of California, Los Angeles, after which she went on to pursue postdoctoral fellowships at Columbia University and the University of California, Berkeley, prior to accepting

a faculty position at the University of Toronto in 2001. Currently, Dr. Goh is a Professor in the Department of Chemistry, the Institute of Medical Science, the Munk School of Global Affairs, and Director of the Impact Centre.

As a physical chemist, Dr. Goh’s research investigates a fundamental aspect of chemistry: structure-property relationships. Understanding the chemical, physical, and structural properties of a molecule can provide extraordinary insight into its specific mechanical and thermal behaviours under certain

Photo by: Krystal Jacques

Dr. Cynthia Goh Professor, Department of Chemistry, University of Toronto Professor, Institute of Medical Science, University of Toronto Professor, Munk School of Global Affairs, University of Toronto Director, Impact Centre, University of Toronto 20 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

conditions. Dr. Goh is particularly interested in the mechanical interactions of monomers—molecules that can react to form very large molecules or polymers—in creating various assemblies that can aid the building or designing of structures where cells or matter can thrive. However, there was no way of measuring these specific interactions, until Dr. Goh invented the technique of diffraction-based sensing.1 Here’s how it works. The simple concept of diffraction—the bending of light as it passes around an object—is manipulated to gain insight into a particular binding event for a protein or molecule of interest.

For instance, a protein immobilized on a solid support will produce a biological diffraction grating when illuminated. This diffraction grating translates to a specific diffraction image. When combined with a solution containing the target molecule of interest, the immobilized protein will bind with the free-flowing molecule creating a change in the diffraction image.

This binding event can be recorded, and the change in height and/or refractive index measured. With this knowledge, Dr. Goh was able to develop a method of measuring the strength, kinetics, and thermodynamics of multiple proteinprotein (or protein-molecule) interactions.

It was with this discovery that she began the process of commercialization and the development of her first company, Axela Biosensors Inc. Dr. Goh was new to entrepreneurship, but she wanted to make a difference. Commercializing her technology allowed other researchers to benefit from its utilization and in turn add even further value to society.

This is when she realized her second passion—translating scientific discovery to technology and products.

As a successful scientist, Dr. Goh felt that there was something more she could be doing. She wondered how her work in

FEATURE the lab could make a greater impact on society. Dr. Goh decided to expand her basic science knowledge into tangible applications. Though many scientists would like to translate their research findings into these meaningful outcomes, often they are at a loss due to a lack of knowledge on how to develop products and companies to bring discoveries to the market. To address this training gap, Dr. Goh developed a seminar series entitled “An Introduction to Scientific Entrepreneurship.” The goal of the seminar series was to train students at the start of their careers, when they have the necessary drive and ideas to become successful scientist-entrepreneurs.

One of the many success stories that came from the non-credit seminar series was a company called Vive Crop Protection. Dr. Goh and a few of her students discovered a way to synthesize nanoparticles in an inexpensive and efficient way. Although Dr. Goh and her students were not experts in the agricultural field, they were able to manipulate the nanoparticles to deliver pesticides to crops in an eco-friendly process. This new product enabled farmers to enhance crop performance while reducing the exposure of soil to harmful chemicals. By translating and applying their research findings into a solution for an important problem, they were able to add value to their technology and positively impact agricultural practice.

Stemming from its great success, Dr. Goh’s seminar series partnered with the MaRS Discovery Tower and became “Entrepreneurship 101”, a program designed to help nearly 20,000 yearly registrants gain the knowledge of how to become an entrepreneur.

As the Director of the Impact Centre, Dr. Goh strives to bring science to society. The Impact Centre is an independent institute at the University of Toronto that is tailored towards researchers and companies within the natural sciences and engineering fields.

It is here that the academic and industrial worlds collide in order to accelerate the development of emerging products or services that will benefit society.

In 2010, Dr. Goh introduced Techno, a one-month intensive workshop for academic scientists interested in building a technology-based business. Techno is the Impact Centre’s flagship entrepreneur training program. The program emphasizes the importance of hands-on experience and provides an opportunity for mentorship, whether it be financial advice or website development. If Techno trainees choose to continue and found their own company, they become Techno Fellows where they are provided further mentorship, year-round training, and access to fundraising tools. Techno has helped grow numerous start-ups since its inception, making an impact in a variety of different fields. Strikingly, many of the start-ups founded through Techno are interdisciplinary crossing multiple scientific fields. As evidenced by Dr. Goh’s basic chemistry research developing into an agricultural company, it is possible for even the most basic science discoveries to have applications in other fields.

For students interested in developing a technology-based business, Techno can provide the skills, knowledge, and support necessary to produce a scalable business.

Since the beginning of her career, Dr. Goh has wanted to give back to underprivileged communities. “One of my passions is

to actually bring technology to the low resource communities of the world… one of our companies that came out of the Impact Centre, called ‘Pueblo Science’ is focussed on bringing science literacy to the remote villages of the world, starting with the Philippines,” Dr. Goh explained. Pueblo Science is a non-profit company that aims to promote science literacy in low-resource communities in countries such as Jamaica, Guyana, Thailand, and Philippines. Volunteers are tasked to design experiments to teach children basic scientific concepts using only local resources. The program challenges volunteers to be creative with limited resources and helps them learn how to effectively communicate science in lay terms. Pueblo Science allows a new generation of scientists to be inspired, while allowing its volunteers to develop critical skills in scientific communication.

Dr. Goh has committed much of her career to bringing scientific discoveries out of the laboratory. She feels that as academics, we have a responsibility to the public to bring innovative discoveries into the marketplace. “Anybody can innovate in their backyard…but at the university we have additional knowledge that is not easily access[ible],” stresses Dr. Goh. Through her seminar series, the Impact Centre, and Techno, Dr. Goh has helped make scientific entrepreneurship more accessible than ever. The lesson that Dr. Goh left me with is that a deep understanding of science is essential to building solutions to society’s problems.

References

1. Goh, J.B., Loo, R.W., McAloney, R.A., & Goh, M.C. (2002).

Diffraction-based assay for detecting multiple analytes. Analytical and Bioanalytical Chemistry, 374, 54-56.

of my passions is to actually “ One bring technology to the low-resource

“

communities of the world

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BMC FEATURE

Master of Science in

Biomedical Communications

Contessa Giontsis, 1T9

I believe that visual communication has the power to bridge knowledge gaps in scientific disciplines. Thus, I aim to create visuals that are educational, impactful and inspiring to all types of audiences. For my Master’s Research Project, I am developing an animation for Mount Sinai Hospital to help educate fertility patients on what happens in the Fertility Lab between Egg Retrieval and Embryo Transfer. I aim to continuously improve my skills in design, to achieve effective knowledge translation and foster meaningful communication, for current and future projects.

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BMC FEATURE

Taeah Kim, 2T0 I attended University of Toronto for my undergraduate to study Genetics in the Human Biology program. While I was passionate about science and pursued it even after a two-year hiatus after my first year of university, I never let go of my love for art. My study notes would always include drawings, and I would create art whenever I had time from school work.

When I came across the Biomedical Communications program, I still doubted that science and art could be combined and turned into amazing educational tools for everyone. Yet I thought about how perfect the field was for me all throughout my undergraduate studies and found myself volunteering for things related to putting art and science together. Now that I am in the BMC program, I’m falling in love with the field more every day and I am so excited to keep learning the skills to become a great medical illustrator.

Su Min Suh, 2T0

My curiosity for the arts and sciences was present at a very young age, when I had an urge to document the world around me through pencil crayons and coloured markers. However, it was my internship at Credit Valley hospital that solidified my vision to become a Biomedical Communicator. During my internship, a mother was diagnosed with breast cancer. The hospital room was filled with confusion and fear as the illness and possible treatments were addressed to the patient. I wondered, is there any way to make this process more comforting and clearer to the patient? I knew that the answer existed in Biomedical Communication and that I can resolve these issues by creating visualizations that are accurate/clear while demonstrating a gentler approach to reach patients about diagnosis and treatments. To pursue this goal, I earned a HBSc in Biology for Health Science and Art and Art History from the UofT along with an Honours diploma in Art from Sheridan College. As a candidate of the BMC program, I am honoured to learn from the BMC faculty and my amazing classmates who inspire me every day!

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VIEWPOINT

My first paper

The Looming Black-Market

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he other day, I received an email:

Dr. Doctor, Heartily Welcome! Endocrinology & Diabetes Case Reports are launching to publish special editions on “Insulin Resistance”. It would be a great honour for us if we get a chance to publish your manuscript which can reach millions for sure. Our journal and group needs active authors/ members like you. If you are current research work not related to any special issue kindly write an editorial or short communication within scope of Endocrinology & Diabetes Case Reports.

Thanks & Regards, James Samuel Editorial Manager: Austin Endocrinology & Diabetes Case Reports, USA

At first glance, this could seem like an exciting invitation for a junior researcher like myself. However, upon a second read through, I notice the poor grammar, and I am a bit confused because journals do not usually solicit articles. I decide this must be another predatory journal trying to scam me.

For those of you unfamiliar to the topic, the term ‘predatory journals/publishers’ is a phrase used to describe a thriving publishing scam where these “journals” solicit articles in return for a publishing

fee, without providing the standard peer review and editorial process. The article may or may not actually be published.

The term ‘predatory publisher’ was coined in 2008 by Jeffery Beall, a librarian at the University of Colorado Denver. Beall put together a list of all journals and publishers he deemed predatory, colloquially known as “Beall’s List”. The original list cited 18 publishers but has since been shut down; now, a similar list has grown to include 1335 journals and 1176 publishers.1 The industry is so lucrative that it has spurred fake conferences and fake metrics as well.

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Now, based on the email I first presented, you may assume this scam would fail.

However, an estimated 420 000 articles were reportedly published in predatory journals in 2015.2 How are these companies successfully scamming so many of the world’s researchers? Multiple factors intersect to put these predatory journals in an optimal position to take advantage of academics.

First, not all communications sent by predatory journals have the same level of poor grammar and excessive adjectives as the example I presented. Many emails come from journals with titles only slightly different from the familiar high impact journals in your field. For example, there is the reputable Journal of Economics and Finance, and then there is the imposter, Journal of Finance and Economics.3 Many of these journals also cite well-known scientists as part of their editorial team, unbeknownst to the scientists.4 Some journals and publishers go so far as to create counterfeit websites of authentic journals, accepting submissions as though they are the legitimate scholarly publishing house and then pocket the submission fees. Predatory publishers have also been buying out reputable journals, eliminating quality standards like peer review and aggressively pursuing new submissions under the established name, adding further difficulty in distinguishing the real from the fake.4 Second, there are several social factors, beyond blatant deception, that feed into the success of the predatory publisher.”Publish or perish” is a common phrase used to describe the constant pressure in academia to publish journal articles or else perish professionally.

VIEWPOINT

Industry of Predatory Publishing By: Chantel Kowalchuk

ACADEMIC SUCCESS

PUBL ICATION

Your number of publications contributes immensely to your academic success, influencing job advancement, conferences, and grant funding. This constant looming pressure could make one vulnerable to being duped by these predators. However, not all authors are tricked into publication, but rather use these journals to their advantage. Those who are aware of the minimal-to-no peer review used by these journals see this as an easy way to increase their number of publications.5 Either way, Dr. Katarzyna Pisanski, a psychologist interviewed in a recent New York Times article, sums up the issue well: “If you were tricked by spam email you might not want to admit it, and if you did it wittingly to increase your publication counts you might also not want to admit it.”5 Another factor contributing to the success of predatory journals is the high cost of publishing in authentic journals.

The average cost of publishing in a predatory journal is approximately 178 USD,2 whereas the cost of publishing in reputable journals start, on average, in the thousands. Cost is a concern for most researchers, as the challenge for funding is eternal and universal. In particular, publishing costs impact developing countries, where funding can be limited.

Of the thousands of articles published in predatory journals every year, nearly three quarters are from researchers based in Africa or Asia, with the largest group, 35%, from India. 2 The consequences of these scams extend beyond tricking thousands of academics out of money. Without the peer review process, we cannot be certain that what is being published is scientifically valid.

This raises concerns about the spread of

false information and the loss of reputable scientific discoveries. Ultimately, this undervalues our work as scientists, and halts scientific discoveries. As Dr. Dewayne Fox, an associate professor of fisheries at Delaware State University, said in a recent New York Times article: “Think about human medicine and how much is on the line. When people publish something that is not replicable, it can have health impacts.”

Ultimately, the negative impacts of predatory journals can also jeopardize the public opinion of science. A recent survey found that only 35% of respondents have “a lot” of trust in science.6 Publishing potentially false information will not improve the public’s perception of science.

With the current public distrust, the possibility of bad science being brought into public knowledge is a serious issue that could have permanent, lifethreatening consequences—we only have to look at the current vaccine “debate” to see the results of bad science entering the public sphere.

So, what is the solution? Scientists and policymakers are trying to hold these predatory publishers accountable.

A winning ruling for Federal Trade Commission (FTC) in November 2017 ruled that OMICS, a major predatory publisher, misrepresented their journal practices. “The defendants in this case used false promises to convince researchers to submit articles presenting work that may have taken months or years to complete, and then held that work hostage over undisclosed publication fees ranging into the thousands of dollars,” said Jessica Rich, Director of the FTC’s Bureau of Consumer Protection in a press release7. However,

according to the Toronto Star, this resulted in simply removing misleading terminology on their website. OMICS is currently still a large publisher of hundreds of journals8.

At the individual level, perhaps the most effective solution is increasing education and awareness of these predatory publishers. Academics maintain an online list of these publishers, but it is difficult to keep the list up to date as new journals arise, and the names of these journals frequently change. A new website, https:// thinkchecksubmit.org/, has tools and resources to identify reputable journals.

However, in the end, all you have is your good judgement. As such, it is integral to stay educated, stay ethical, and stay vigilant. If it seems too good to be true, it probably is.

References 1. List of Predatory Journals | Stop Predatory Journals [Internet]. [cited 2019 Mar 26]. Available from: https://predatoryjournals.com/ journals/ 2. Shen C, Björk B-C. ‘Predatory’ open access: a longitudinal study of article volumes and market characteristics. BMC Med [Internet].

2015 Dec 1 [cited 2019 Mar 26];13(1):230. Available from: http:// bmcmedicine.biomedcentral.com/articles/10.1186/s12916-0150469-2 3. Beall J. Hijacked Journals [Internet]. Scholarly Open Access. 2016.

Available from: https://archive.fo/Hr8tk 4. Chown Oved M, Favaro A, St. Philip E. Canadian medical journals hijacked for junk science. The Toronto Star [Internet]. 2016 Sep 29; Available from: https://www.thestar.com/news/world/2016/09/29/ canadian-medical-journals-hijacked-for-junk-science.html 5. Kolata G. Many Authors Are Eager to Publish in Worthless Journals. The New York Timess [Internet]. 2017 Oct 30; Available from: https://www.nytimes.com/2017/10/30/science/predatoryjournals-academics.html 6. Tsipursky G. (Dis)trust in Science. Scientific American [Internet].

2018 Jul 5; Available from: https://blogs.scientificamerican.com/ observations/dis-trust-in-science/ 7. FTC Charges Academic Journal Publisher OMICS Group Deceived Researchers | [Internet]. Federal Trade Commission; 2016 [cited 2019 Mar 26]. Available from: https://www.ftc.gov/news-events/ press-releases/2016/08/ftc-charges-academic-journal-publisheromics-group-deceived 8. Chown Oved M. Junk science publisher ordered to stop ‘deceptive practices.’ The Toronto Star [Internet]. 2017 Nov 23; Available from: https://www.thestar.com/news/world/2017/11/23/junk-sciencepublisher-ordered-to-stop-deceptive-practices.html

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VIEWPOINT

The apocalypse is coming Your next infection could be your last

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By: Bowen Zhang

T

here are many impending crises to worry about in life, from climate change to the threat of a global nuclear conflict. Yet one developing crisis receives little, if any, media coverage. A silent killer - antimicrobial resistance (AMR) - that wages an ongoing war between humanity and microorganisms.

In 1928, the British scientist Dr. Alexander Fleming found a mold, Penicillium notatum, on his Petri dishes that was able to kill his bacteria samples. It was this discovery that sparked the first invention of an antimicrobial drug, Penicillin, that altered our world forever.

Antimicrobial drugs are used against microorganisms, such as bacteria, viruses, parasites, or fungi, that cause disease. Antimicrobial drugs quickly became the “magic bullet� in medicine for treating diseases and infections.

Before its discovery, infections were a major cause of death worldwide.

However, the overall mortality rate due to infection has drastically plummeted after implementation of the use of antimicrobial medications, saving countless lives1.

For the first time in our battle with microorganisms, the humans seemed to be gaining the upper hand.

Our victory was short-lived. The

marvelous invention of antimicrobial drugs had also hastened the evolution of new, antimicrobial-resistant microorganisms. AMR occurs when microorganisms become immune to the drugs that are commonly used to kill them. To the microbes, AMR is a natural biological process. One chance experience by a genetic mutation gave some microbes the ability to survive exposures to drugs which should have otherwise killed them.

The survivors now can pass on their resistance encoding genes, making other microorganisms resistant as well. With the use of antimicrobial medications, we are hastening microorganisms’ evolutionary clock - inadvertently selecting resistant ones by killing off the susceptible ones.

On August 18, 2016, a 70-year-old female patient from Nevada, U.S., was admitted to acute ambulatory care with a primary diagnosis of systemic inflammatory response syndrome, a likely result of an infected right hip seroma. None of the administered antimicrobial medications had worked. She developed septic shocka bacterial infection that spread to the blood -and unfortunately, died in early September. This incident was reported to the U.S. Centers for Disease Control and Prevention (CDC) where an autopsy revealed that the patient was infected with carbapenem-resistant Enterobacteriaceae

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(CRE), specifically the Klebsiella pneumoniae. This bacterium was resistant to a staggering 26 types of antibiotics, equating to all of the antibiotics drugs available at that time2. Her AMR-related death not only shocked the entire medical community but shook the foundations of modern medicine. Humanity was once again reminded of the dark ages before the invention of antimicrobial medications.

Similar incidences to the case in Nevada are occurring all over the world, and the numbers are increasing. In 2013, the CDC estimated that in the U.S. alone, more than two million people were impacted by antibiotic-resistant infections, responsible for at least 23,000 deaths per year3. In 2016, the Review on AMR reported that 700,000 human fatalities worldwide resulted from antibiotic-resistant bacteria, while projecting an additional 10 million annual fatalities expected by 20504.

Although these estimates have been disputed, a lack of a global surveillance system and inadequate monitoring in lowincome countries make finding the true figure near impossible.

Just recently, a news article published by the CBC on March 15, 20195, reported shrimp products contained antibioticresistant bacteria in Canadian grocery stores. Among the 51 shrimp samples

VIEWPOINT

tested at the Rubin Lab at the University of Saskatchewan, scientists discovered that nine samples contained bacteria, such as E. coli and Staph aureus, that were resistant to at least one antibiotic, and two samples had multidrug-resistant Staph Aureus (MRSA). The Public Health Agency of Canada commented that these findings were “deeply concerning”5.

These reports of AMR microorganisms are a serious wake-up call, as AMR is not a hypothetical or a future threat, but a real one. Although these facts are worrying, there are ways for us to mitigate the problem. The CDC suggests the best ways to prevent fatalities due to AMR is through prevention of infection, responsible usage of AMR medications, developing new medications and diagnostic tests, and tracking existing resistances.

Secondly, physicians and patients need to work together to combat AMR. The problem of AMR has been exacerbated by the overuse and misuse of antimicrobial medications. Physicians and other health professionals should prescribe antimicrobial medications responsibly, using the right medications only when necessary. Patients should take their medications as prescribed, not skipping doses, and completing their course of treatment even if they start feeling better.

Fourthly, centralized institutions that gather and share data on AMR infections should be implemented. With accurate and comprehensive information, experts and scientists can track and develop specific strategies to target and prevent infections that could spread resistant microorganisms.

AMR is a serious global health issue that is rapidly growing and outpacing the development of previously effective

antimicrobials. Combating AMR requires international attention and collaboration.

Only through a holistic and comprehensive set of actions can we keep this problem from becoming an epidemic.

References 1. Gaynes R (2017) The Discovery of Penicillin—New Insights After More Than 75 Years of Clinical Use, Emerg Infect Dis. 2017 May; 23(5): 849–853. DOI: 10.3201/eid2305.161556 2. Chen L, Todd R, Kiehlbauch J, Walters M, Kallen (2016) A. Notes from the Field: Pan-Resistant New Delhi Metallo-Beta-LactamaseProducing Klebsiella pneumoniae — Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep 2017;66:33. DOI: http:// dx.doi.org/10.15585/mmwr.mm6601a7 3. Li B and Webster TJ (2017) Bacteria Antibiotic Resistance: New Challenges and Opportunities for Implant-Associated Orthopaedic Infections, J Orthop Res. 2018 Jan; 36(1): 22–32.

4. O’Neill J (2016) Tackling Drug-Resistant Infections Globally: Final Report and Recommendations, The Review on Antimicrobial Resistance, https://amr-review.org/sites/default/files/160525_ Final%20paper_with%20cover.pdf 5. Grundig T, Osborne R, Denne L. (2019) Shrimp containing antibiotic-resistant bacteria found in Canadian grocery stores, CBC News, https://www.cbc.ca/news/canada/shrimp-antibioticsresistance-amr-marketplace-1.5055101

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Thirdly, we should encourage the development of new antimicrobial medications and new technologies to combat them. Since AMR occurs as

a part of a natural process by which microorganisms evolve, it can be slowed but not stopped. Therefore, there will always be the need for new ways to keep up with resistant microorganism. Effective and efficient detection of infections can reduce the chances of wrongly prescribed medications, improve treatment outcomes, and decrease the chances of AMR development.

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Firstly, avoiding infections reduces the amount of antimicrobial required in treatments and reduces the likelihood that resistance will develop during therapy.

There are easy steps that we can take to prevent infection, such as comprehensive and frequent sanitation (e.g. handwashing), vaccination, safer food-handling and preparation, taking travel precautions, practicing safe sex, and avoiding bugborne and air-borne pathogens. With greater prevention, we can reduce the spread of resistant microbes.

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VIEWPOINT

The Chinese

CRISPR Babies

Are We Ready for Fetal Genome Editing?

By: Jason Lo

T

he idea of editing human embryos makes a lot of people queasy, and it should,” said Dr. Mercola from the Stanford Cardiovascular Institute on the risks of fetal genome editing. Genome editing treatments have been used for decades and have largely positive public support, partly due to the interventions being done in adult cells where altering their DNA will not affect their offspring.1 However, in November 2018, scientist Dr. He Jiankui announced the birth of the world’s first babies immune to HIV infection through fetal genome editing using CRISPR technology. While this may appear as pioneering research with noble intentions, a deeper look into the situation reveals a flagrant disregard for international regulations in favour of personal scientific glory. This news was met with massive controversy in the scientific community and sparked debate about whether we are, or will ever be, ready for fetal genome editing.

Labelled as the scientific discovery of the decade, CRISPR along with an accompanying protein called Cas9 work together to defend bacteria from viral infection. It acts as a heritable genetic record of past infections which is used by the Cas9 protein to identify repeat infections, which it then promptly destroys.2 Scientists discovered

that this precise CRISPR/Cas9 mechanism can target DNA of their choosing at a lower cost and in a more efficient manner than any previously developed techniques, thereby opening a world of possibilities for genome altering research. Historically, somatic cells have been the most common cell type used in genetic research as modifications to these cells cannot be passed down to offspring. Scientists have been wary of the possible implications of altering germ cells that will impact future progeny. Hence, international regulations have been put in place to control the use of any genetic modification to germline cells in an effort to prevent irreversible changes to the human gene pool. Consequently, when the birth of twins with CRISPR edited fetal genomes was announced by Dr. Jiankui, it provoked an international outcry in the scientific community.

Dr. Jiankui was a scientist at the Southern University of Science and Technology of China, specializing in genome-editing research. While giving a talk at a summit, Dr. Jiankui unveiled the birth of Chinese girl twins whose genome had been edited using the CRISPR/Cas9 system in an attempt to make them resistant to HIV. He did this by disabling a gene called CCR5 which encodes a protein that allows HIV to infect a cell, theoretically making these girls immune to infection by preventing it

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from ever entering their cells. The CCR5 gene was targeted due to extensive literature implicating its involvement in HIV and performed as a preventive measure, with the father of the girls being HIV positive. According to Dr. Jiankui, there was sufficient medical reasoning to attempt this treatment, implicating that this technique could be employed for a multitude of genetic diseases.3 While a paper has yet to be published on this matter, these results may serve as the pioneering study that leads to a change in the way disease treatment and prevention is approached.

However, the scientific merit of the study has been called into question as it appears that Dr. Jiankui had violated a slew of legal and ethical regulations.

In 1998 the UK Gene Therapy Advisory Committee (GTAC) published a report on gene therapy in utero which established that: (1) fetal treatments must have a clear advantage over other treatments, and (2) must be used for life-threatening diseases with no suitable treatment.4 Herein lies the biggest problem with the genetic intervention of these twin girls. HIV is a disease with well established, effective treatments and in the absence of any real reason to employ an experimental treatment with vastly unknown consequences, and therefore Dr. Jiankui’s intervention cannot be justified. Additionally, the CCR5

VIEWPOINT

Cas9

“

The idea of editing human embryos makes a lot of people queasy, and it should

modifications has not yet been confirmed to be successful and even in the case of successful modification, this would not translate to complete HIV resistance, as some HIV strains exploit a different receptor called CXCR4 to gain cell entry.5 While CCR5 deficiency may reduce the risk of HIV infection, it has been shown to increase susceptibility to other diseases such as the West Nile virus, various tickborne diseases, and influenza, a disease especially prone to outbreaks in China.6,7 Moreover, due to the stage at which the CRISPR mechanism makes its changes, the resulting “mosaic” of edited and unedited cells has been identified as one of the biggest barriers to this application, with one of the two Chinese twins exhibiting this problematic mosaic pattern.8 Lastly, as only the father was known to be HIV positive, there would have been a minuscule chance that their offspring would have been infected in the first place. After further investigation, Dr. Jiankui has since been fired by his university for breaking national regulations and the police have now begun their own inquiry. Among the scientific community, there is a well-established pathway for developing new treatments, beginning with animal models that inform highly controlled clinical trials before a treatment ever reaches the general population and Dr. Jiankui has shown a complete disregard for this quality control process.

The fact that the genetic intervention was unnecessary, potentially exposing the babies to other major complications shows that this work was highly unethical and consequently should not have been performed.

In response to this use of the CRISPR/Cas9 system to edit the human genome, the World Health Organization has convened an expert panel to examine challenges with human genome editing and come to a consensus on appropriate oversight and governance mechanisms. The agreement was to focus on promoting transparency and trust, ensuring proper use of genetic techniques at the national and international level.9 These discussions aim to ensure that CRISPR technology is applied appropriately in the research setting, mediating the medical, ethical, and social problems associated with genetic modification. The basic principles of the original GTAC guidelines on gene therapy should be reinforced, in that it should be utilized only when absolutely necessary—only in case of no other suitable alternatives.

Dr. Jiankui’s team has shown flagrant disregard of these regulations in an attempt to gain personal glory at the expense of the study participants, their potential children, and for their future generations. This has raised the question of whether we are, or ever will be, ready to edit the fetal genome.

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The answer is that it doesn’t really matter because fetal genome editing is coming whether we like it or not. There are already other projects underway studying gene editing in human embryos, and the findings while promising, also illustrate the difficulty of editing embryos.8 One good thing that came from this event is that it brought attention to the importance of reinforcing ethical experimentation to ensure the proper use and application of such a powerful technology, in the hopes that it will one day be used the right way.

References 1. Schwartz M. Target, Delete, Repair: CRISPR is a revolutionary gene-editing tool, but it’s not without risk. Stanford Medicine.

Winter 2018.

2. Sontheimer EJ and Barrangou R. The Bacterial Origins of the CRISPR Genome-Editing Revolution. Human Gene Therapy. 2015;26(7).

3. Cyranoski D and Ledford H. Genome-edited baby claim provokes international outcry. Nature. 2018;563:607-608.

4. Health Departments of the United Kingdom. Gene Therapy Advisory Committee: Report on the Potential Use of Gene Therapy in Utero. Human Gene Therapy. 1998;10:689-692.

5. Woodham AW, Skeate JG, Sanna AM, et al. Human Immunodeficiency Virus Immune Cell Receptors, Coreceptors, and Cofactors: Implications for Prevention and Treatment. AIDS Patient Care and STDs. 2016;30(7):291-306.

6. Glass WG, McDermott DH, Lim JK, et al. CCR5 deficiency increases risk of symptomatic West Nile virus infection. The Journal of Experimental Medicine. 2006;203(1):35-40.

7. Falcon A, Cuevas MT, Rodriguez-Frandsen A, et al. CCR5 deficiency predisposes to fatal outcome in influenza virus infection. Journal of General Virology. 2015;96(8):2074–8.

8. Le Page M. Mosaic Problem Stands in the Way of Gene Editing Embryos. NewScientist. 2017;3117.

9. World Health Organization. Human Genome Editing [Internet].

World Health Organization; 2018 [cited 2019 Mar 11]. Available from : www.who.int/ethics/topics/human-genome-editing/en/

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VIEWPOINT

Automated

Healthcare Are We Ready?

By: Frank Pang and Duncan Green

F

or many blue- or white-collar workers the word “automation” commonly invokes thoughts of several large production line machines performing simple, narrow range, yet accurate functions; for example, they may think of machines placing potato chips in bags with precision, or cutting lumber to specific dimensions. Although this type of automation was prevalent in the 1950’s, automation has since surpassed what most employed adults think of it. One example of such great change in automation is purchasing stocks at the New York Stock Exchange. This stock exchange—which used to be a bustling area filled with stockbrokers—is now empty save for the computers. Another example lies in the food industry, where some restaurants are highly automated. From taking orders,

to preparing dishes, to tabulating and collecting bills—all of these tasks are now performed by machines. These restaurants may have one or two employees, but their job really centers around maintenance for their machines. Finally, a notable example that we may all be aware of is the ongoing development of completely autonomous, self-driving cars. These self-driving cars reveal some interesting insights on how people view automation.

Individuals driven by a self-driving car may attest that the experience was initially nerve-wracking, and close to 50% of all drivers would not feel safe with self-driving cars.1 This is not a surprise as we have been accustomed to having control behind the wheel all our lives. Therefore, a large limitation of automation is not a limitation of the machines themselves,

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but peoples’ mentalities towards them.

Waymo, a self-driving car project within Alphabet (Google’s parent company), has had self-driving cars clock in over a million miles on Californian roads in 2018 alone2. It is still too early to reliably compare driving safety between human and machine-driven vehicles. However, when considering the safer option, it is important to consider that machines do not necessarily have to be perfect-they simply have to be better than their human counterparts. The reality is that lines of computer code have the capability of instructing a car to operate and respond to real-time changes in our surroundings.

It is clear that a big mental hurdle must be overcome if self-driving cars are to be in wide-spread use, as many people do not feel comfortable relinquishing autonomy to automation.

VIEWPOINT The worries that people have towards automated cars and other machines may also apply to automation of healthcare. For example, if you were ill, would you choose to be seen by a computer or a physician at the clinic? Patients may not trust a robot performing surgery on them, or they may not want to lose the physician-patient interaction they are accustomed to. Based on these concerns, it is conceivable that you responded with “physician”. However, Google Brain published a paper which showed their artificial intelligence was able to more accurately predict the onset of diabetic retinopathy (the global leading cause of blindness) compared to a panel of eight ophthalmologists.3 Does your answer to the aforementioned question change now that you know that computers can provide a more accurate diagnosis than a physician? Despite the slow advancement of automation, more advanced tools are continually being built so that professionals can deliver more accurate and precise diagnoses and treatments. One of the most recent advancements is in the surgical field, where the Da Vinci surgical system, received a fair bit of media attention. It was recently the subject of a meme, “they did surgery on a grape,” which demonstrated that the system was precise enough to remove the skin off a grape and stitch it back on.

The development of such surgical techniques provides interesting issues as well as life saving opportunities. On one hand, it provides a potential remedy for one of the most pressing issues in surgery overall: overwork. It is not uncommon for surgeons to work nearly 16 hour shifts, which could lead to fatigue and costly mistakes.

Surgeons also frequently have a difficult time maintaining a healthy work-life balance. Canadian surgeons frequently work 60 hours per week not including on-call hours.4 A 2014 study found burnout from overwork in surgeons had a total cost of $213 million.5 Using these machines in surgery would decrease the hours surgeons need to work by replacing them in the surgery room. On the other hand, it presents a variety of issues inherent to robotics and automation; for example, a robot does not have the same judgement, experience, or ability to reason as a human. A set of metal arms and a few software packages do not, and most likely will not, be able to replace the experiences and knowledge obtained by physicians with years of medical education and practice.

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If you were ill, would you choose to be seen by a computer or a physician at the clinic?

Despite this shortcoming, avoiding the use of robotic surgery altogether is not for the best. Instead of avoiding surgical automation, physicians can take a more nuanced approach to the use of robotics.

In lower risk surgeries, such as superficial procedures (i.e. cosmetic surgeries, skin cancer removal) and appendectomies, the use of robots in the surgery room will be a welcome addition as stand-ins for overworked surgeons. In higher risk surgeries, however, such as complex neurosurgery and cardiovascular surgery, robots would be better left to simple support roles. Such roles would include clamping, holding, or lighting, but nothing more complex would be involved. The margin for error is too thin, and the potential risks are too great, for a fully automated system to completely perform complex surgeries. In a support role, these robotic instruments may provide significant assistance. Surgical support is undertaken by surgical support staff, who may tire during an extended surgery. Conversely, a robot would never tire or lose grip while holding an incision open. As well, these instruments can be set in stable, secure positions that may be difficult for a human assistant to achieve.

”

In summary, automation provides interesting opportunities for surgery, which, by its nature, does not require physician to patient interaction. These machines would be especially suitable for support roles during high risk surgery, or as a stand-in during superficial procedures. However, technology must advance before robotic surgery can fully replace surgeons, and society’s perception must change before we will fully accept automated healthcare.

References 1. Richter F. Consumer Concerns About Self-Driving Cars. Statista.

[Internet]. 2018 Mar. 20. Available from: https://www.statista.com/ chart/5950/concerns-about-self-driving-cars/ 2. Madrigal A. Waymo’s Robots Drove More Miles Than Everyone Else Combined. The Atlantic. [Internet]. 2019 Feb 14. Available from: https://www.theatlantic.com/technology/archive/2019/02/the-latest-self-driving-car-statistics-from-california/582763/ 3. Ting, D., Cheung, C. Y., Lim, G., Tan, G., Quang, N. D., Gan, A., … Wong, T. Y. (2017). Development and Validation of a Deep Learning System for Diabetic Retinopathy and Related Eye Diseases Using Retinal Images From Multiethnic Populations With Diabetes.

JAMA, 318(22), 2211–2223. doi:10.1001/jama.2017.18152 4. Nousiainen, M. T., Latter, D. A., Backstein, D., Webster, F., & Harris, K. A. (2012). Surgical fellowship training in Canada: what is its current status and is improvement required?. Canadian journal of surgery. Journal canadien de chirurgie, 55(1), 58–65. doi:10.1503/ cjs.043809 5. Dewa, C. S., Jacobs, P., Thanh, N. X., & Loong, D. (2014). An estimate of the cost of burnout on early retirement and reduction in clinical hours of practicing physicians in Canada. BMC health services research, 14, 254. doi:10.1186/1472-6963-14-254

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 31

VIEWPOINT

Are animal models dispensable in research?

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VIEWPOINT By: Diana Hamdan

A

nimal testing dates back as early as the fourth and third centuries BCE, when Aristotle and Erasistratus first performed experiments on living animals, as documented in the writings of the Ancient Greeks.1 Animals make practical model organisms that enable us to better understand disease and test new drugs before using them in human clinical trials. Numerous scientific discoveries would not have been possible without the use of animals, from Louis Pasteur’s germ theory using anthrax-induced sheep in the 1880s2 and Ivan Pavlov’s classical conditioning demonstrated in dogs in the 1890s3 to the discovery of insulin by Frederick Banting and John Macleod from operating on a dog’s pancreas in the 1920s.4 Nowadays, millions of animals are used in research studies every year. The Canadian Council of Animal Care (CACC) reported that 4,415,467 animals were used in 2017.5 However, this number is an underestimate since not all institutions belong to the CACC. While scientific progress made through animal experimentation is indisputable, animal use in research presents ethical challenges and remains a subject of heated debate. Vivisection, operations performed on live animals, only first faced opposition in the nineteenth century, where the increased rate of pet domestication prompted the founding of the Society for the Protection of Animals Liable to Vivisection in 1875.6 Queen Victoria was one of the earlier opponents to animal testing in England, according to a letter written by her private secretary in 1875: "The Queen has been dreadfully shocked at the details of some of these practices, and is most anxious to put a stop to them."

Shortly after, the United Kingdom passed the first law controlling the use of animals in research, known as Great Britain's Cruelty to Animals Act of 1876.7 The most prominent criticism of animal testing is that it is cruel and inhumane. Research animals are usually subjected to pain and distress through force feeding, food or water deprivation, infliction of wounds or burns, and euthanization by carbon dioxide asphyxiation or cervical dislocation.

However, that is contested by the notion that the significant contributions animal testing provides outweigh the moral cost of

harming a portion of them. Yet, opponents of animal testing argue that the number of animals sacrificed and the amount of suffering inflicted on them outweigh the moral justifications of their use, even if the benefits are exceptionally valuable to human health and welfare.

Concerns from the general public regarding animal welfare has led to the internationally accepted concept of the three R’s, proposed by W.M.S Russell and R.L. Burch. The three R’s stand for: 1) Reducing the number of animals needed to obtain valid results; 2) Refining experimental techniques to minimize pain and distress; and 3) Replacing animal models with other methods whenever feasible.8 These principles have been implemented in most animal handling guidelines to provide a framework for performing ethical research involving animal subjects.

In pursuit of Russell and Burch’s third ‘R’, the quest for alternatives to animal models has led to the creation of a range of valuable tools, including cell and tissue cultures, computer simulations, and the more recently developed organ-on-achip models. While these techniques have opened new avenues of research, the nature of some experiments limit these methods as only complementary to animal models rather than replacing them altogether. The complexity and interconnectedness of the whole-body system make it impossible to study the course of a disease or effects of potential drugs without observing the entire living system.

Unfortunately, as with all other experiments, those involving animals are not free of flaws, which result in trading animals lives for poor research. A peer-reviewed study found that 87% of publicly funded studies failed to randomize the selection of animals, while 86% did not use blinding.9 These sub-standard practices suggest that it is vital to critically question both the methodology and the results of animal studies.

drugs as humans. Moreover, the availability of the mouse genome, its small size, and short life cycle facilitate large-scale studies making it a cost-efficient model.

Nonetheless, scientists need to approach results obtained from animal models with caution since they may not be equally valid in humans. For instance, 90 HIV vaccines that succeeded in animals failed in humans.10 Conversely, drugs that were shown to be ineffective or harmful to animals have proven to be valuable when used by humans. Aspirin and penicillin, for example, are unsafe in some animal species and would have been shelved away if we completely relied on animal test results.11, 12 All things considered, even with the advent of new technologies, animal research is indispensable to advancing knowledge and human health thus far and will continue to be an important facet of biomedical research in the years to come. However, researchers must remain mindful of the ethical and moral considerations that underpin responsible animal testing.

References 1. Cohen BJ, Loew FM. Laboratory animal medicine: historical perspectives. Laboratory animal medicine/edited by JG Fox, BJ Cohen, FM Loew. 1984.

2. Pasteur L, Chamberland C, Roux E. Compte rendu sommaire des experiences faites a Pouilly-Le-Fort, pres de Melun, sur la vaccination charbonneuse. C. R. Acad. Sci. 92, 1378–1383. 1881.

3. Pavlov IP. Conditional reflexes: an investigation of the physiological activity of the cerebral cortex.

4. Rosenfeld L. Insulin: discovery and controversy. Clinical chemistry.

2002 Dec 1;48(12):2270-88.

5. Canadian Council on Animal Care Facts & Legislation. Canada.

2018. Facts & Figures. 2018 Oct 4. Available from: https://www.ccac. ca/Documents/Publications/CCAC-Facts-and-Figures.pdf 6. Archives of the British Union for the Abolition of Vivisection, 18651996. Hull University Archives, Hull History Centre. GB 50 U DBV. Available from: https://archiveshub.jisc.ac.uk/data/gb50-udbv 7. Godlee SR. Lord Lister. Macmillan; 1918 Jan 26.

8. Russell WM, Burch RL, Hume CW. The principles of humane experimental technique. London: Methuen; 1959.

9. Kilkenny C, Parsons N, Kadyszewski E, et al.Survey of the quality of experimental design, statistical analysis and reporting of research using animals. PloS one. 2009 Nov 30;4(11):e7824.

10. Aysha A. "Want to Improve Medical Research? Cut Out the Animals!," huffingtonpost.com, July 11, 2013 11. Hartung T. Per aspirin ad astra... ATLA-Alternatives to Laboratory Animals. 2009 Dec 1;37(2):45.

12. Schneierson SS, Perlman E. Toxicity of penicillin for the Syrian hamster. Proceedings of the Society for Experimental Biology and Medicine. 1956 Feb;91(2):229-30.

Additionally, critics argue that animals commonly used in research laboratories, such as mice (31.2%), birds (27%), and fish (19.1%), greatly differ from human beings and therefore do not make reliable test subjects.5 At the same time, however, mice share more than 98% DNA with humans, and are thus likely to exhibit similar health problems and effects to IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 33

VIEWPOINT

The Dissolution of LHINs is

a Loss for Transparency with No Resolution in Sight

By: Colin Faulkner

I

n Ontario, our health care system has been one of incremental changes. There has not been any widespread structural reform since 1959, when Ontario began its involvement in the federally funded Medicare program.1 In March, the provincial Progressive Conservative government's instituted health care reform that involves the dissolution of the 14 Local Health Integration Networks (LHINs), along with six other agencies, including Cancer Care Ontario and eHealth Ontario. Instead, these agencies will be consolidated into a 'super-agency', named Ontario Health.2 Widespread reform takes time, and ambitions are often reined in by the next political party to take power. Instead, parties frequently initiate programs that address specific issues, like the changes made by the Liberal government in 2004: to address the unique health needs of various regions in Ontario, LHINs were created.3 LHINs were mandated from the start to engage the community, citing this involvement as a critical factor to success.

They sought to understand the full diversity of community needs and perspectives.

Community, by the LHINs definition, goes beyond location, and includes service providers who may have experience with ethno-cultural needs, or communities that

have been neglected by major institutions.

LHINs also developed tools for community and individual participation to engage the most marginalized and vulnerable populations. For example, a goal of LHINs was to consult with groups such as Count Us In and Street Health, to give a voice to marginalized women and homeless people (respectively). These groups work with front-line service providers and conduct community-based research. LHINs also took diversity into account—a task accomplished by ensuring representativeness in the boards and staff, delivery of competent care, and the sustainability of the program.4 Although many of the reforms to the delivery and payment of health care in Ontario may seem small, these changes have yielded one of the most successful systems in Canada. A portion of this success is attributed to the networks and programs that have emerged from LHINs. Experts have lauded Ontario’s superb cancer system, organ-transplant system, renal network, cardiac network, and critical-care network; these programs reflect the distinct needs of regions within the province.

According to Dr. Bob Bell, former deputy minister of the Ministry of Health, one of the biggest strengths of LHINs is the accountability toward the public that they bring to the system. Bell says that beyond the innovations that LHINs have brought,

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LHINs also keeps hospitals and health providers in a consistent dialogue with the community they serve. At the Champlain LHIN, recent changes have reduced wait times and expanded care with no added costs. When the community expressed concerns for wait times for hip and knee surgeries, a systematic central assessment and intake were performed, resulting in reduced wait times by three months at no increased costs. Another example is to address expensive hospital stay during stroke rehabilitation, addressed with a community program that saves $1 million a year. For rural community members, the LHIN in Champlain created a regional orthopedic program to bring surgical services to hard-to-reach patients at no increased costs. Often evidence-based, these changes are accountable to those who requested them, which provides a layer of accountability in the case that a program is unsuccessful or inefficient.5 The purported successes of LHINs were not uniform across all health regions, where some suffered from high administrative costs and a loss of control for physicians over local health care decisions. Poor oversight at certain LHINs could explain bloated administration, and compromised physician autonomy within the system signals a lack of integration between health care providers. Paul

VIEWPOINT William, from the University of Toronto’s Institute of Health Policy, Management and Evaluation, surmises that LHINs were not properly equipped to meet the demands of certain communities. He considers them “thoughtful and progressive”, but ultimately in need of change to deliver on their initial goals. This view is mirrored

by Dr. Chris Simpson, the vice-dean of Queen’s University school of medicine, who vacillates between abandoning LHINs, or giving them more authority in the delivery of health care within each LHINs region.5 The current government has begun the dissolution of LHINs, answering Simpson’s question. Following the Ontario premiere Doug Ford’s campaign promise to cut costs, the LHINs were seen as non-essential. However, the new Ontario Health

“

The details of the new health act were released mid-February, and the initial concern expressed by the New Democratic Party opposition was the initiation or funding of private, for-profit health care services. This concern reflects a reform two decades ago. After the PC provincial government was elected in 1995, with Mike Harris as premier, the Independent Health Facilities Act (IHFA) was amended in 1996 to remove priority assigned to non-profit delivery of medically necessary ‘highlevel’ diagnostic services. This change gave rise to the potential for private, for-profit services to get public funding to establish themselves in the market. However, we do not see the effect of this amendment because the for-profit organizations would be required to pay prohibitive licensing fees that are not worth the capital expenditure.3

The standard has been set

by LHINs, and ignoring the benefits of communityinvolvement casts a shadow on the early formation of the super-agency

Teams (OHT) may benefit from the LHINs organization. In recent years, many subLHINs were created and assigned care coordinators, whose role was to connect primary care, home care, and mental health care services in each region. The special expertise of the care coordinators allowed them to facilitate care plans for complex patients, which reduced medical complications and eased their experience navigating the system.8 While this model is lost with the recent reforms, it may help to inform the integration of primary and home care with the major public health institutions, a goal stated in the new OHT documents.5

”

The fear of privatization, mirrored today by the reforms in 1996, masks a greater issue. The 1996 amendment is often called a ‘counter-consensus’ reform, as the proceedings of the provincial government were not made visible to the public.

The documentary trail for the reform is nearly non-existent, as it was surrounded by larger legislative changes. This reform resulted in a lack of transparency, whether intentional or not.3 History repeats itself, and we are seeing the same relationship between fear of privatization and loss of transparency with

the new health act. With the new health reform, the knee-jerk fear of privatization envisions for-profit services making health care better for only wealthy Ontarians, with a loss of health care providers devoted to vulnerable populations. However, the real concern should be with the loss of LHINs, and the transparency they provide, without a sufficient replacement in the process of creating the super-agency.

Reported in The Star, a former LHIN board member anonymously expressed concern that the super-agency shouldn’t be holding private meetings “with no public knowledge”. The standard has been set by LHINs, and ignoring the benefits of community-involvement casts a shadow on the early formation of the super-agency. The ministry’s communications branch released a statement explaining that “the board will be required to establish mechanisms for public engagement to ensure openness and transparency”6. But with no timeline, and vague plans given by the ministry, the new super-agency could be building a foundation that again ignores the health needs of the most vulnerable populations.7 While LHINs are not perfect, largely from being ill-equipped, their dissolution is a loss for transparency and community involvement. The current reforms have promised to mitigate this loss, but decisions have already been made outside the public eye.

References 1. Dunlop M. Health Policy | The Canadian Encyclopedia [Internet].

2015 [cited 2019 Mar 18]. Available from: https://www.thecanadianencyclopedia.ca/en/article/health-policy 2. Crawley M, Feb 26 rea J·CN·P. Here’s what Ontario’s new healthcare agency will look like | CBC News [Internet]. 2019. Available from: https://www.cbc.ca/news/canada/toronto/doug-ford-ontariohealth-super-agency-lhin-cancer-care-1.5032830 3. Forest P-G, Lazar H, Lavis J, Church J, Queen’s University (Kingston O., Institute of Intergovernmental Relations, et al. Paradigm freeze: why it is so hard to reform health-care policy in Canada [Internet].

2016. Available from: http://deslibris.ca/ID/451313 4. Gardner B. Community Driven Planning, Priority Setting and Governance [Internet]. Government & Nonprofit; Wellesley Institute. Available from: https://www.slideshare.net/WellesleyInstitute/ontario-hospital-association-conference-community-engagement-in-a-lhins-environment 5. January 22 EPU, 2019. If Ontario scraps its LHINs, what’s next for health care? | Ottawa Citizen. 2019 Jan 22 [cited 2019 Mar 18]; Available from: https://ottawacitizen.com/news/local-news/if-ontario-scraps-its-lhins-whats-next-for-health-care 6. Boyle. Questions raised about transparency as board of new health super agency meets in secret | The Star. 2019. Available from: https://www.thestar.com/politics/provincial/2019/03/13/questionsraised-about-transparency-as-board-of-new-health-super-agencymeets-in-secret.html 7. Crawley M. Why privatization isn’t the biggest issue with Doug Ford’s health reforms | CBC News. 2019. Available from: https:// www.cbc.ca/news/canada/toronto/ontario-health-changes-privatization-doug-ford-1.5007957 8. Bell B. Ontario health teams are useful incremental change | The Star. 2019; Available from: https://www.thestar.com/opinion/ contributors/2019/03/06/ontario-health-teams-are-useful-incremental-change.html

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 35

STUDENT SPOTLIGHT

The Medicine in Motion Podcast By: Krystal Jacques

T

he word “podcast” is a combination of the words “iPod” and “broadcast” and was coined by The Guardian columnist and BBC journalist Ben Hammersley shortly after podcasting was first established in 2004.1 Podcasts have seen a surge in popularity recently; between 2010 to 2017, the percent of Canadians listening to podcasts had doubled.1 Its rising popularity could be due to the ever-growing variety of podcasts currently available. Different podcasts delve into niche topics of interests or humorous banter. In contrast to radio broadcasting, which contains content for a relatively broad audience, podcasts tailor content to a very specific audience who share similar interests as the content creator(s). Swapna Mylabathula, who is currently in her 5th year of her PhD in the MD/PhD program at the Institute of Medical Science (IMS), is one of many who have realized the potential of using podcasts as a platform to share her perspective with the world.

Swapna, along with a team of seven other members–Mackenzie McLaughlin, Edward Lin, Sandhya Mylabathula, Lauren Handler, Rachel Walker, Jayden Blackwood, and Brett MacDonald– launched the Medicine in Motion Podcast (M&M) earlier this year. Swapna is an executive producer of M&M, and a

member of the Raw Talk Podcast. The founders of Raw Talk Podcast, Jabir Mohamed and Richie Jeremian, are advisors of M&M. The inspiration for launching M&M came two years ago from a desire to advocate for exercise. “A lot of people have questions about sport and exercise medicine, and podcasting is an excellent platform to share information, stories, feelings, thoughts, and history,” Swapna explained. Swapna and her twin sister, Sandhya Mylabathula, grew up loving sports of all kinds. Their love of hockey inspired their work on federal concussion policy, where they have been advocating for better awareness, prevention, and management of concussions across Canada since 2010. This interest in sports also inspired Swapna to join Exercise as Medicine on Campus at U of T (EIMC @ UofT) in 2014, an initiative which encourages interdisciplinary awareness and practice of exercise prescription by health care providers.

From brainstorming ideas, to interviewing Canadians on the street, and post-production editing, making the M&M podcast is a team effort. Not only does every M&M member make the podcast possible, but their various backgrounds provide unique perspectives about exercise and health.

The fields of industry, nursing, occupational health, exercise science, and clinical research are all represented within the

36 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

M&M team, providing the public with the most up-to date, science-based evidence about the bio-psycho-social aspects of exercise.

Aside from advocating about concussions, managing a podcast, and creating a movement for concussion policy to Canadian parliament, Swapna conducts concussion policy research, is a science communicator with multiple organizations, performs in an orchestra and plays hockey on a weekly basis. Swapna credits her ability to balance all these activities to the infectious enthusiasm of the people she works with and her passion for everything she does. She makes a conscious effort to avoid treadmilling in her work and hobbies.

Swapna and her team at M&M have inspired people around the world to improve their health. Currently, M&M has been downloaded in many countries including, Canada, the United States, the United Kingdom, Norway, Hong Kong, and India. Next time, while you’re spending hours imaging at the confocal microscope, give Medicine in Motion a listen to learn more about how to live your healthiest life.

References 1. Moore O, Moore, J. The future of podcasting: A history lesson. Medium [Internet]. 2017 July 21 [cited 2019 Mar 29]. Available from: https://medium.com/@justinemoore_85088/the-future-of-podcasting-a-history-lesson-1ec24862ac9a.

STUDENT SPOTLIGHT

Photo courtesy of Medicine in Motion

SWAPNA MYLABATHULA (LEFT) AND EDWARD LIN (RIGHT) IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 37

TRAVEL BITES

Aloh

from the Interna Stroke Confer

By: Beatrice Ballarin

I

left Toronto in the midst of an extreme cold warning that had already dragged on for a couple of weeks, wearing only my leather jacket. I recall walking on a huge pile of snow, boots soaking wet, ready to be shipped to Honolulu-yes, you read correctly, I was leaving at 4AM for Hawaii.

This story seems to be a constant for our travel bite section: leaving an extremely cold Toronto towards a warmer location–in the name of science, of course.

Although I am a senior PhD candidate in the lab (but don’t ask a lady her age), I have never attended a conference before, let alone an international conference-let’s blame it on my vast collection of negative data! Thus, when my supervisor encouraged everyone to apply to the International Stroke Conference 2019 (ISC2019), I was all in–the Honolulu destination was

probably all I read of that email. You can’t imagine my surprise when, a few months later, I heard back from the conference organizers and not only did my abstract get accepted, but it was selected for an oral presentation! I felt so proud of my research and so honoured to share it-I even bought a UofT hoodie, just to show how cool I felt to be a UofT student. It did feel like a bit of a payback after so many countless nights, weekends, and holidays spent in the lab (even as gorgeous as the Krembil Research Institute is!)

After 14 hours of flying, disoriented about the current time, I arrived in Honolulu.

A warm breeze instantly made me forget about my worries. I stayed at an Airbnb downtown, very close to the conference, which I recommend. It was cheap and I only needed a place to crash; plus, I was awoken with a fresh cup of coffee every

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morning-what more could a girl ask for?

However, I didn’t know what to expect from the conference and just the thought of having to give a talk made me very anxious. Thus, I decided to go ahead of time to check out the room where I would present and hopefully give a couple of practice talks to myself there. Becoming familiar with the room was a very helpful tip (thank you Graduate Centre for Academic Communication workshops) and I definitely recommend it! The room could host around 100 people with two big screens, and I knew my supervisor, Dr. Tymianski, would be there too. At this point I am not sure if the word intimidating really captures the moment. I decided to start focusing on my redeeming qualities (including the fact that I talk a lot) and I knew I had a good presentation with videos to entertain the audience, good data to show, and a good story to tell.

TRAVEL BITES

ha

ational rence

Photos by Beatrice Ballarin

Thus, I tried to hide my fears by speaking up and making eye contact with the public (in reality, if you could only record my heartbeat, I was probably close to a heart attack). Luckily-for my mental well-being-my talk was on the first day of the conference and all went well. I got a lot of questions and two post-doc offers out of it.

Not bad at all!

The International Stroke Conference is known to be a very clinical conference; nevertheless, my days were full of basic science talks, mini-symposiums, and posters. I attended all the talks regarding basic science research in stroke recovery (my field of work), and I have to admit that I was very excited to finally put a face to all the names that I read over and over in research papers. I attended the talks of Dr. Carmichael, Dr. Nudo and Dr. Jones (in Hollywood terms, the Brad Pitt,

George Clooney, and Kate Winslet of the stroke recovery research world)-three of my favourite stroke recovery researchers.

What I found interesting about the conference is how it demonstrated the direction of the research field, which is moving towards the role of immunology. I wouldn’t be surprised if in the next couple of years more papers will be published about that.

The aspect of the conference I enjoyed most is that people could present negative data, because this data is often a dealbreaker for getting published in scientific journals. Getting positive behavioural data after a stroke is very challenging, which is what I have been doing on a daily basis for the past 4 years. It was a huge relief seeing other people struggling with the same issues. For once I felt normal, I had the same behavioural results as other people!

This showed me that I was not doing anything wrong, and that it is just a difficult animal model (intracerebral hemorrhage) to work with. The funny thing is that I did my literature background consultation a while ago, but I couldn’t find anyone talking about it. Only the unique

environment of the conference allowed a safe space to discuss difficult results.

Although for some unknown reasons (even to myself) I was in a rush to get back to the lab, I did schedule a final day to enjoy myself and explore the Oahu’s island (the so-called #metime, according to my Instagram account!). Apparently, I was there at a time where there are major waves that attract professional surfers.

I became friends with a fellow scientist (and surfer on the side) and together we decided to rent a car and head for the North Shore. I spent an amazing day that I will forever remember, watching the surfers ride huge waves, swimming in the cool Pacific Ocean, eating fresh and delicious shrimps, and trying to get as much sun as I could. I still don’t know how I made myself take the flight back.

This was one of the best experiences I have had as a scientist, and I am eternally grateful to my supervisor for the opportunity to attend the conference. What else can I say?

Next year the conference is in Los Angeles; stay tuned for some California dreaming!

IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES | 39

PAST EVENTS

Tra n s l at i o n a l Re s e a rch Ta l ks:

Regulatory Jurisdictions in Medical Devices By: Yvonne Bach

O

n February 26, 2019, the Translational Research Program (TRP) hosted a panel discussion on the challenges that health technology innovators face in the process of accessing the markets in Canada and other countries. As a part of their TR Talks series, the panel of speakers consisted of Dr. Brian Courtney, a clinical scientist at Sunnybrook and Executive Chairman of Conavi Medical; Dr. Bradley Strauss, Chief of the Schulich Heart Program and Head of Cardiology at Sunnybrook; and Mr. Lahav Gil, CEO of Relay Medical Corp. Each speaker shared their experiences in working with Canadian and international jurisdictions to test and market their potentially life-saving innovations to the public.

The application process for a medical device license (MDL) is a financially and mentally strenuous process—a deterrent for many of our Canadian-based clinician-scientists who have minimal business knowledge or industry experience in executing their entrepreneurial vision.

Currently, Canada is importing more medical devices than they are exporting. The regulatory standards set by Health Canada and other jurisdictions in the world are variable and extensive. For instance, the US Food and Drug Administration (FDA) is the only jurisdiction that allows companies to expedite their application if their device is similar to a previously FDAapproved device. There is no fast-track application in either Canada or Europe.

For large companies, obtaining a MDL and passing extensive audits are a minor hiccup. However, changes in the application process can place a financial strain on

40 | IMS MAGAZINE SPRING 2019 EMERGING MEDICAL TECHNOLOGIES

start-ups. Thus, many small and mid-sized Canadian companies sell their intellectual property to larger international corporations or migrate south of the border.

Throughout the discussion, feelings of frustration and cynicism about the landscape of health innovation in Canada were unanimous and unyielding. The misalignment of government and industry goals were highlighted by Dr. Courtney, who said that Health Canada’s only mandate is to protect the health of the public.

Government and industry need to agree on a common set of objectives in order to successfully optimize the benefits and minimize the risks of simplifying the approval and commercialization of medical devices.

In hopes of retaining Canadian talent and being recognized as a country on the forefront of health technology and innovation, Health Canada created a Scientific Advisory Committee on Digital Health Technologies in 2018. This was also a way to perform a pre-market review of digital technologies (i.e. smart phone applications, telemedicine, and wearable devices) that are evolving at an increasingly fast rate.

The discussion led by TRP was an eyeopener to the stagnant growth of the medical device industry in one of the world’s most developed countries. The addition of a representative from Health Canada to the panel of speakers would have provided an interesting perspective and depth to this much-needed conversation. It is time that clinician-scientists, industry leaders, and government officials work together to update and streamline the process of approving and commercializing medical devices so that patients do not end up paying the price.

PAST EVENTS

Photos courtesy of the IMSSA

Bell Let's Talk By: Rachel Dadouch

O

n January 30th, Bell Let’s Talk Day, the notorious mental health campaign, was the perfect opportunity for the Institute of Medical Science Students Association (IMSSA) to open the dialogue on maintaining mental health.

IMSSA’s Community and Outreach and Health and Wellness committees collaborated to spread awareness and take action with their peers, while raising money for Bell Let’s Talk Day donations through Twitter, Facebook, and other platforms.

IMSSA designed a mural that was blown up for students and faculty to colour at a table in the Medical Sciences Building (MSB). Through initiating a mindfulness activity in the middle of a hectic day, they demonstrated the value of dedicating time to fulfill activities that are beneficial for our mental health. IMSSA students took shifts and spent the day colouring the large-scale poster while encouraging hustling and bustling MSB-goers to do the same. Visitors who could not stop and colour had the opportunity to snap a photo of the mural-in-progress and

use the Bell Let’s Talk hashtag for the five cent donation. IMSSA students also had a whiteboard where participants could write what mental health meant to them, encouraging reflection on their own mental health and their perception of others’ struggles. Throughout the day, many students did not want to leave their peaceful time colouring to attend to the next item on their Wednesday agenda!

Graduate students comprise of one of the most vulnerable populations to poor mental health, making this day one that was well spent.

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BOOK REVIEW

Taking a New Trip A Book Review of Michael Pollan’s How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence By: Kenya Costa-Dookhan It’s an annual ritual of mine to look at the New York Times’s “10 Best Books of the Year” to see which books I’ve read and browse for future reads. On the 2018 list, a book that caught my eye was: How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence by Michael Pollan.

Michael Pollan is among the best scientific writers, well known for his books The Omnivore’s Dilemma and In Defense of Food: An Eater’s Manifesto. His New York Times best book list feature is one of his recent works and lives up to his talent.

How to Change Your Mind is a historical recount, personal narrative, and mini-literature summary of psychedelic drugs in relation to human connection, mental health, and one’s self. In accord with the overarching theme prevalent in many of his books, How to Change Your Mind focuses on how humans achieve alternate states of mind and how the human condition can be reformed through exposing our body to substances. Beyond looking at the experiences of the individual, How to Change Your Mind provides a “big picture” look on the societal impact of the tabooed, tempting, and transcending use of substances psychedelic drugs.

How to Change Your Mind is divided into three sections. The first section is a historical summary of mind-altering drugs, focusing on the discovery and early implementation of psychedelics in research and recreation. Part one also speaks heavily to the work and influence of pioneers in psychedelics research, like Timothy Leary and Al Hubbard. The second section is Pollan’s recount of the personal experiences in the world of psychedelics. He shares his innate curiosity and drive, which initiated his psychedelic journey. Pollan discusses the experience of his trips and the interactions he had with his psychedelic guides; those individuals who assisted with the experiences before, during, and after being under the influence of psychedelics.

The final section of the novel emphasizes the current research surrounding psychedelics. From molecules to medicine, this section highlights the modern research in neuroscience regarding psychedelics and their application to treating depression, overcoming addiction, and confronting one’s fear of death. Psychedelic research has long been silenced, largely due to “America’s War on drugs.” Since the prohibition of psychedelics in the 1970s, a stigma has enshrouded the potential benefits of psychedelic drugs and their contribution to neuroscience.

This negativity has placed research and

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implementation of these findings on hold.

By being engaging and accessible to the non-expert, How to Change Your Mind describes how the conversation on psychedelic drugs and psychedelic drug research can be reformed.

Throughout How to Change Your Mind, Pollan clearly explains the potential devastating effects that psychedelics can have on people - especially those individuals with or predisposed to severe mental illnesses such as schizophrenia or bipolar disorder.

Equally as important to note, Pollan does not endorse the casual or recreational use of psychedelic drugs. Overall, Pollan uses lay language, personal experiences, and a vast array of scientific references to support his points and provide a summary regarding the power of psychedelics.

Michael Pollan has holistically exposed the role of psychedelics in understanding an individual’s mind, and how this can be applied to society. With the meticulous crafting that formulated this book, Pollan’s highly regarded influence in the scientific writing genre, and the need to establish new treatments to improve psychiatric health, How to Change Your Mind is one of the essential stops in a journey towards understanding the mysteries of psychoactive plants and the human mind.

IMSSA

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