Screaming without a Sound: Sex Trafficking in Ontario

Human-trafficking is essentially a form of slavery. It entails the movement of individuals against their will, and exploitation of their rights for profit through various services such as labour, or in this particular case: sexual services.


Victoria sobbed in fear as she felt exhaustion overtake her once again. When her eyes closed: they would come again. Sounds. Smells. Tastes. Touches. This dark room had no place to hide. Even in sleep she could not find rest. Where could she run? They would find her again.

There was no escape.

Victoria was a victim of domestic abuse when she was but a child. Her drunken father beat and killed her mother leaving her alone. What followed next was a whirlwind of neighbours, police, and social workers. Having gone through child protective services, she was placed into a new family. And that was where her story should have ended. Instead, her foster father pimped her out to his friends, and eventually other men who would put down money. She was ten.


Jacob clutched the few dollars he had, and ran back to his boyfriend. He was always running. Running at school. Running on the track team. Running away from his family… But with his new boyfriend, he didn’t have to run anymore. He could trust him.

The money wasn’t enough? Black eye. A couple dollars? Broken rib. How many people did he service? Coughing up blood. It was finally enough. A smile, all that Jacob wanted.

Restart again.

Jacob ran away from home when he came out to his family. His parents being very traditional refused to have a son who was LGBT, and he ended up wandering the streets of a large Ontario city. Very soon he fell into a group of fellow street teens who showed him how to survive. One of them took a liking to him, sharing food, advice, a bed. Then the drugs happened. Jacob couldn’t pay up, and his boyfriend beat him. Jacob loved him. He wanted it to go back to the way it was before. So he started selling himself out to pay his debts. He was 19.


 Jasmine clutched the edge of the sink and looked at herself in the mirror. She was beautiful once. Her father loved her and called her his princess. Her mother found the best clothes for her and dressed her up like a doll. But then the war happened.

The handsome man that met her in town came from Canada he said. She was very kind and gentle he said. He had children at home and would love to have her come and take care of them. She accepted. She was trapped.

The door opened. Another client. Smile he said. The men like it better when she is happy he said. You belong to me. He said.

Jasmine came from a war torn country. In that instability, a trafficker promised her legitimate work in Canada with promises of citizenship. Upon entering the country, her passport was stolen and she was sold to the next bidder. She was told that she needed to pay back her handler for fees, and that if she went to police she would be deported. She was 24.


Disclaimer: All the vignettes you just read are not real individuals. Rather, they are a culmination of many real people who have been in these situations or are currently in these situations. They have names. They have stories. They could have been you.


Human trafficking is one of the most underreported crimes in Canada. The latest report from Stats Canada (2009-2016), states that there were 1220 confirmed reports of human trafficking. Over 723 (65.8%) of these cases were in Ontario, of which 48 were in Windsor, 46 in London, and 272 in Toronto. As of September 2018, We Fight, an anti-human trafficking project in Windsor stated they have 80 open cases. Keep in mind, that this is a gross underestimate of the problem since these are the cases that were confirmed by law enforcement. Due to the nature of all illegal activity, it is extremely hard to have proper estimates of the extent of this problem. In 2013, the US Department of State released their annual report on human trafficking stating that for the 40,000 worldwide confirmed victims the previous year, it was estimated that there were still 27 million people being trafficked worldwide which were unreported. According to the Canadian Department of Justice, net revenues for trafficking on a worldwide basis account for about 32 billion dollars: an exceptionally lucrative business for organized crime and gangs.

There is no one profile of trafficked victims. Like the above stories, they come from all backgrounds and histories. However, statistically, most victims are young girls and women, starting from an age as early as 12, if not younger. In a 2013 report from the Canadian Women’s Foundation, many victims of sex-trafficking came from low socioeconomic backgrounds, homelessness, discrimination and/or childhood trauma. It should also be noted that nearly 50% of women who are trafficked in Canada belong to indigenous populations, which is absolutely horrific considering the fact that indigenous women only make up 4% of the population of women in Canada. The RCMP reports that many of these people are sold, bought, and moved against their will and forced to perform sexual acts in: “hotels/private residences and in adult entertainment establishments”.

So now comes the inevitable question? What can I do about it? As future or current physicians, we are among the frontline personnel to have contact with victims of trafficking. Studies suggest that almost 28% of victims of trafficking will eventually get into contact with healthcare workers during their imprisonment. This is a very large window of opportunity on a healthcare standpoint for early recognition and intervention. The more knowledge we have on this topic, the better our chances at identifying high-risk situations and responding to them effectively. If we, as physicians are aware to the extent of the problem and the signs of this issue, people like Victoria, Jacob, and Jasmine might stand a chance.

Below are pertinent signs of trafficking. For more information on who to contact, the end of the report from the Ontario Ministry of Children, Community and Social Services has a map in which you can enter your city and have agencies listed.

What to Look For (from the London Anti-Human Trafficking Committee):

People who are being trafficked may:
- Speak neither English nor French, or may not speak on their own behalf
- May be accompanied by someone who is controlling them
- Originate from foreign countries or from another city/province within Canada
- Be unaware of local surroundings although they have been in the area for a while;
- Show evidence of control, intimidation or abnormal psychological fear;
- Not be able to move or leave job;
- Have bruises or show other signs of abuse;
- Show signs of malnourishment;
- Be frequently accompanied or moved by their trafficker.

Map of Resources from the ON Ministry of Children, Community, & Social Services


Author: Phong Nguyen

Phong Nguyen completed his BSc.[H] in Biology at the University of Windsor. Following graduation, he worked in the US with social work non-profits providing assistance to vulnerable populations: in particular, youth experiencing homelessness and in crisis. Now at Schulich, he hopes to pursue work related to advocacy, social inequities, and field medicine.



Picture Credits: Englin Akyurt

Lies and Lyme

My first exposure to ticks was 3 years ago. In the summer of 2015, I returned home from my studies at UBC to work as a tree planter with my local conservation authority. While the job was enjoyable, I will never forget the 3 days of shear torture I spent planting trees at one particular site near Sarnia, Ontario. Why was it torture, you ask? Ticks. Dozens upon dozens of ticks. Now, I’m usually the kind of person to not be bothered by bugs. Bees, spiders, even cockroaches—bring it on. But ticks? No chance in hell. Not only do they quite literally burrow into your skin to fed, they’re tiny, vampiric-looking creatures with the remarkable ability to hide in your clothes, hair, and just about everywhere else. Simply put, if you know anything about The Office (U.S.), ticks are the Toby to my Michael Scott. My absolute fear of these little summer vampires aside, there is something even more terrifying than ticks themselves: Lyme disease.

Among the dozens of diseases around the world that ticks have been shown to carry, Lyme disease is the one that poses a unique and rapidly worsening threat in North America. Lyme disease is an inflammatory infection in humans caused by Borrelia bacteria, which is found in a variety of animals including birds, mice, and deer. Ticks are the main transmission vector of Borrelia, and pick up the bacteria by biting other animals. When humans are bitten by bacteria-ridden ticks, infection occurs.

‘Bulls-eye’ rash at site of tick bite – characteristic for Lyme disease.

What makes Lyme disease particularly challenging for physicians is the difficulty of early diagnosis, with Stage 1 infection often presenting with non-specific symptoms such as fever, pain, headaches, and muscle aches. Some cases also present with a “bull’s eye” rash near the site of the tick bite (pictured on right). As Lyme disease progresses, the symptoms worsen dramatically—affecting mental health status, causing chronic fatigue, neurological symptoms like tremors and numbness, as well as even causing chest pain, heart palpitations, and shortness of breath.


The worst part? We had a vaccine for Lyme disease; LYMErix, an effective, albeit relatively expensive vaccine (at $50 USD per dose), was sold from 1998 to 2001. While shown to be over 90% effective at preventing Lyme, LYMErix was withdrawn due to a multitude of factors, most notably due to public pressure on behalf of anti-vaxxers. Their argument? The LYMErix vaccine caused widespread adverse effects, namely musculoskeletal issues like arthritis. This argument, despite little evidence in support of it, still made LYMErix one of the earliest casualties of the still-growing anti-vaccine movement.

Fast forward to today, and I had more or less forgotten about ticks and Lyme disease. That is, until I listened to a particularly interesting episode of Canadaland, a podcast tackling issues in Canadian media and politics (which I highly recommend you listen to, by the way). In this episode, a controversy about a Lyme disease cover-up was mentioned, whereby this originally-removed story in the Halifax Chronicle Herald was replaced in favour of this piece by the province’s chief medical Officer of Health, Dr. Robert Strang. While the first article argued for the existence of significant deficiencies in the Nova Scotia healthcare system in addressing Lyme, Dr. Strang argued the opposite: Lyme disease is under control and not worth worrying about.

Well, Dr. Strang, I respectfully disagree.

While we have come a long way in diagnosing Lyme disease, currently available diagnostic testing is complicated and only available at a handful of centres across the country. And despite my forgetting (or conscious repression) of my nightmare-inducing tick experience, ticks—and Lyme disease—are spreading fast. In Canada, cases of Lyme disease have risen sharply from just 144 reported cases nationwide in 2009 to nearly 1000 cases in Ontario alone in 2017. And just like so many other things, we have climate change to thank for it. Rising temperatures have not only increased the range that ticks occupy, but they have also increased the developmental rate of ticks—meaning more and more adult ticks ready and able to spread Lyme disease each and every year. And while provincial and federal governments are finally waking up to the growing problem of Lyme disease, as well as with climate change, such action may be too little, too late. With the catastrophic effects of climate change predicted to start in as little as 22 years, Lyme disease has the potential to become a huge public health crisis in the years to come.

So, where does that leave us? Nowhere good. Lyme disease is a big problem that is only going to get worse, plain and simple. Tackling Lyme disease means tackling climate change—an effort yet to be seen on the scale that’s necessary. And if Nova Scotia and other jurisdictions are telling us they’ve got a handle on Lyme, not only are they lying to us, they’re lying to themselves.


Author: Zachary Weiss

Zach Weiss completed his B.Sc. in Microbiology & Immunology at UBC in Vancouver. Over the years, Zach has become increasingly fascinated with the world of politics and policy, and has spent way more hours listening to political podcasts than he’s willing to admit. As a first-year medical student at Schulich, He’s particularly interested in merging his interest in politics and policy with his growing medical knowledge to advocate for and bring awareness to issues that are often overlooked.

Photo Credits: Pixabay


How Medical Students Actually Feel About the Med Backpacks

Here’s a truth they don’t tell you when you get into medical school: you’ll be congratulated for it at least a hundred times. Your first congratulations will come from your official acceptance. Then you’ll be congratulated by your family, your friends, your doctor, your hairdresser, that chatty lady on the bus, professors during the first week of class, speakers from organizations vying for your money. But the Canadian Medical Association (CMA) will take it just one step further and give you their congratulations in the form of a brand new, brightly coloured, High Sierra backpack.

The backpacks aren’t subtle either; for those who know what they are, it’s an identifier. With every Canadian medical student in the same year having the same backpack, the wearer is visually inducted into a new group: medical student, class of ____.

There’s a sense of unity that comes from sharing an identifier with your class, and a sense of familiarity when you spot someone with the same backpack. In a way, the backpack is also a tribute to the hard work the wearer has put in to get into medical school. “Congratulations from us at CMA. You worked hard to get here, here’s a little something to let everyone else know that too.”

However, the backpack comes with responsibility. New expectations of professionalism and integrity are placed on medical students, even though we have yet to achieve ‘MD’ at the end of our names. The backpacks hold us accountable to the expectations of those who see us wearing it.

Or I could be wrong and it could just be a backpack. I asked some of my peers if they wore their CMA backpacks and how it might tie into their identities as medical students.

Mobolaji Adeolu, Class of 2021

I wear the CMA backpack because I find it valuable to be recognizable as a medical student. It allows me to identify and strike up conversations with other medical students at Schulich and throughout Canada. Moreover, I think it’s important for students from backgrounds that are underrepresented in medicine to be recognizable members of the medical community; both to show people striving for medical school that systematic barriers to admission can be overcome and to act as an approachable source of mentorship for students who want advice that can speak to their unique challenges.

Sarah Cassidy Howard, Class of 2022

I wear the backpack sometimes. I wear it when I have longer days because I have more stuff and it’s a really nice big bag that can carry a lot of stuff. On other days, it’s just nice to wear the backpack that I’ve always worn because it’s really nice, I’ve sewn patches in it, and it shows a little bit of my personality. So I feel like that’s nice to have as well—kind of a mix of both.

Bojana Radan, Class of 2021

I actually don’t wear my backpack. The first reason I always tell people is because my current backpack fits really well on my back, and I need to work on my posture. But secondly, I don’t like wearing it because I feel like I’m around medicine and medical school all the time in London, so it’s nice not being identified as solely a medical student outside of this space. Sometimes it’s nice to just walk around the city or go downtown where I don’t have to associate with that. I can just be that learner, be that person as a med student, but without actually showing it to the whole world.

I think it’s a great marketing advertisement for those that created it because it’s a backpack and its essential to students. I definitely think it [represents] that identity of the med school because it’s so hard to get in, so once you do get in—especially if it’s been your number one goal from the start—it’s kind of like wearing a badge of honour. So, I can definitely see that it plays into it, because other students know, and once … someone tells you it’s a med school backpack, you see it everywhere.

Jane Ding, Class of 2022


Initially, I wore my backpack to fit in, and I relied on the bright red backpacks to identify my classmates and find my way around a new school. I think that because of this, my world was narrowed down to Schulich and its students. It took time to realize that I was part of a greater community at Western. I think that as time goes on, I’m a little less comfortable wearing the bright red backpack that may set me apart. As medical students, we are part of the Western community. As doctors, identifying as part of the community we serve will be even more important.

Dan Li, Class of 2021

The first [reason I don’t wear my backpack] is that it’s really conspicuous. The moment you have that on campus, everyone knows who you are. And not just who you are, but roughly how old you are as well, because it shows your year (each year is different). The second reason is that it’s a little impractical. I’m not sure if you’ve weighed the backpack or not; it’s actually five or six pounds. I only usually take my notebook and my laptop with me, pens, my umbrella, and those things added together is like four pounds. So if the bag is heavier than what I carry around, it’s kind of pointless. And other than that, I just don’t like the look.

Katie Marriott, Class of 2021


I do wear the backpack, but I didn’t always. In undergrad I went to UBC and no other program had an identifier, only the meds. I wanted to be a medical student so badly and whenever I saw the backpack, it made me feel jealous and kind of angry. I felt like the students were flaunting it in my face—very negative things, looking back—which was totally on me. I shouldn’t have let it get to me that way. But nevertheless that’s how I felt. So at that time I vowed that if I were to get into medical school I would never wear the backpack. It’s actually quite dramatic I suppose, because of all the negative emotions that I thought that the backpack had given me. So for the first two months of first year, I did not wear it. I also started to notice some things that were a little bit unsettling to me, like when I would introduce myself to someone. They would ask me what I studied, and sometimes I wouldn’t say medicine. Sometimes I would say physiology or sciences, or just beat around the bush. I would sometimes have a bit of a stutter when I did say medicine, and there would be this horrible, awkward pause, “I study…medicine…”, which just made the whole thing quite awkward.” So from talking with some mentors, some [doctors] who had gone through it too, I came to see that the problem wasn’t the backpack, the problem was me now identifying (or not identifying) as a medical student. I had put so many stereotypes on that backpack and on medical school, a lot of them not good ones, and so I’d thought that by rejecting the backpack I could reject those stereotypes. I’ve since started wearing the backpack because I need to accept that this is who I am. This is what I want to study and I’m going to be a doctor. I can’t (and don’t want to) escape it, and I shouldn’t try to hide it anymore.

Wendy Wang, Class of 2022


I do wear my CMA backpack! Entering a new school with new goals in mind, it only makes sense to pair it with a brand new backpack. Functionally, it is large and sturdy, perfectly tailored to carry everything I need throughout the day. More importantly, the backpack symbolizes identity of medical students. The bright red backpacks of the class of 2022 fosters a sense of community, and with that, a sense of belonging. It is a comforting feeling to see a group of red backpacks on campus, knowing that they are my friends and my colleagues. Whereas it creates unity within medicine, the bright red colour of the backpack significantly stand out amongst a crowd. Wearing the backpack, therefore, holds me accountable to professional values, and serves as a visual reminder of the power and privilege I possess as a medical student.

Michele D’Agnillo, Class of 2022


Don’t wear the backpack, primarily because I like this backpack better. It’s smaller, and I like to separate my things, like have a lunch bag and a gym bag. And I like to scatter, like the lunch in the lounge or in the locker room. It’s kind of an aesthetic thing too. The backpack they give you is a little bit of a cheap one – I’m not a big fan of that. It may be subconscious, but it could have something to do with the fact that I may be a bit of a contrarian, I see myself as a black sheep, but I don’t think it consciously factors into the decision. Maybe a little bit.


Author: Nicole Lam

Nicole Lam graduated from Western University with a BMSc in Interdiscplinary Medical Sciences. She likes writing about science, pop culture, and student life. Nicole might be spotted on campus with a black, teal, or red backpack.


Photo Credits: CMA 

A Prescription for Income: The Ontario UBI Pilot Cancellation and the Impact of Poverty on Health

Case Study 101 

Imagine you’re a cancer patient. You’ve been undergoing treatment for almost a year now—a combination of radiation and chemotherapy. Finally, after months of fighting, these treatments have nearly eliminated all of the cancer from your body. With only a few more treatments, your doctors are confident you’ll be able to be declared cancer-free. Now, imagine one day you turn on the news to find that the government will no longer be paying for your cancer treatment. The government’s argument? That this kind of service is “clearly not benefitting all citizens”. Your treatments are to be suspended and you’re left with no other options.

This is ludicrous, isn’t it? Of course, no government in their right mind would halt treatment for a disease with readily accessible treatment options, right?

Enter Universal Basic Income.


What is Universal Basic Income?

Universal Basic Income (UBI), has a history that dates back to Thomas More’s Utopia in 1551, where, among other things, More argues that every person should receive guaranteed income.

The premise of UBI is simple: instead of providing citizens supplemental income and social security through an array of programs like welfare, old age security, and unemployment insurance, the government instead gives a lump sum payment every month. While various trials around the world have mostly offered UBI to citizens in lower income brackets, a nationalized UBI would, in theory, provide a basic income to all citizens regardless of their income, education, or profession. In Canada or the United States, a theoretical UBI system would provide each adult approximately $1000 monthly; not enough to fully support an unemployed individual, but enough to ensure that those with low incomes don’t struggle just to make ends meet.

Of course, UBI is not without controversy. Providing “no-strings-attached” money to all members of a society (include the wealthy) seems challenging, if not a little crazy. After all, who is going to pay for this? Won’t this just encourage laziness? Put simply, supporters of UBI argue that such a system would increase worker productivity and economic output, eliminate the administrative costs of running multiple welfare agencies, reduce healthcare spending, and reduce the stigma of receiving government support. Supporters also argue that all of these benefits, in addition to raising corporate tax rates and closing tax loopholes, would result in more than enough money to finance a full-fledged program—estimated to cost $43-billion annually in Canada.

Over the years, the idea of UBI has been tested around the world in several capacities, including ongoing projects in Scotland, Finland, and Kenya. Contrary to the belief of many skeptics, in each of these studies, researchers found the money doesn’t cause poor people to give up work. Instead, people invested in improving their own lives and the lives of their families. Things that were just out of reach—like sufficient food, quality healthcare, and education—suddenly became accessible. Although the merits of UBI continue to be debated, when coupled with other policy solutions such as a federal jobs guarantee, UBI has the potential to dramatically change the way nations address poverty.


UBI and Health 

Poverty, like cancer, is a chronic disease. The effects of poverty and cancer don’t last for months, but instead impact the lives of those affected for years, decades, and maybe even their entire lives. These diseases often don’t have one discernible trigger, and remit and relapse throughout one’s life for no apparent reason. In medicine, things like income and poverty belong to a collection of factors known as the social determinants of health (SDH). In the case of inadequate income, the stress associated with this can cause a negative ripple effect to all elements of one’s life. Poverty has been implicated as a contributing factor to poor childhood development, mental and physical health problems, and an inability to access to healthcare services. Furthermore, treatments for the health-related impacts of poverty remain elusive. UBI represents one potential solution.

Particularly when it comes to healthcare, past and present UBI trials have shown that UBI has the potential to dramatically reduce the health inequities that remain pervasive in our society. Alaska, home of the Alaska Permanent Fund, reports 14% decreased likelihood of low birth weight compared to other US states. In Kenya, youth experienced 24% less depressive symptoms alongside reports of feeling healthier and more hopeful. In Manitoba, an 8.5% decline in healthcare utilization and decreased hospital visits for psychiatric reasons were reported.


The Ontario UBI Pilot

Given the immense potential of UBI to address a slew of issues, in 2016 the Ontario Government under the leadership of Premier Kathleen Wynne developed a UBI pilot program. This $150-million, three-year program, which took place in a mix of urban and rural locations in the Hamilton, Thunder Bay, and Lindsay areas, enrolled 4,000 low income participants to receive a combined yearly UBI stipend of $17,000 for a single person or $24,000 for a couple, minus 50% of any yearly earned income from those actively working. This group was then compared to a control group 2,000 participants not receiving any monthly UBI payments. Overseen by researchers from St. Michael’s Hospital and McMaster University, the study was meant to investigate the impacts of UBI on those living on lower incomes with regard to food security, stress, anxiety, mental health, housing stability, and a slew of other health-related factors.


Pilot Cancellation

After less than a year of formal operations, and despite the remarkable amount of promise UBI holds, the Ford government formally announced its intentions to “wind-down” the basic income pilot project in August 2018. Asked about the cancellation of the UBI pilot, Children, Community and Social Services Minister Lisa Macleod said that the project was expensive and that “it really is a disincentive to get people back on track”.

Wait, what?

Saying that providing extra income to citizens encourages dependence on the government is akin to saying that needing treatment for cancer encourages dependence on the healthcare system. Nobody seeks cancer treatment because they wish to be there forever. People seek cancer treatment because it is their only option to becoming healthy again. Likewise, nobody relies on programs like UBI because they want to be dependent on government support. People rely on programs like UBI because it is a path to financial independence. To further counter the government’s narrative, the PC government chose to cancel this project before any meaningful data was able to be collected. Meanwhile, as previously mentioned, past UBI trials have shown that UBI empowers its recipients to find work — hardly the disincentive the Ontario government says it is.

Ultimately, this decision by the Ford government, much like their decision to once again “review” the merits of safe injection sites, (see James Payne post on SSIs) is the wrong one. The cancellation of the UBI pilot will rob the entire world of important data needed to assess the merits and implementation of UBI on a broader scale. Furthermore, this decision will further disadvantage our most vulnerable citizens. It will result in worse healthcare outcomes and it may very well cost lives. And for a government that prides itself on being “for the people”, these kinds of decisions are anything but.


Author: Zachary Weiss

Zach Weiss completed his B.Sc. in Microbiology & Immunology at UBC in Vancouver. Over the years, Zach has become increasingly fascinated with the world of politics and policy, and has spent way more hours listening to political podcasts than he’s willing to admit. As a first-year medical student at Schulich, He’s particularly interested in merging his interest in politics and policy with his growing medical knowledge to advocate for and bring awareness to issues that are often overlooked.

Photo Credits: Pexels 

Natural Discovery of AAV Serotypes, Directed Evolution of AAV Serotypes, and their Importance to Gene Therapy

As we reach the end of the first month back from break, I think it’s a nice time to continue on our journey into the world of gene therapy. My last blog entry focused on why the adeno-associated virus (AAV) capsid is such an important part of gene therapy, and this time, we’ll focus on how different types of AAV capsid affect therapy efficacy and what researchers are doing to find new types of AAV capsids.

AAV was first discovered in the 1960s by groups of scientists when they found small particles riding along with adenovirus cultures. In 1982, the first AAV serotype, AAV2, was cloned. (For a more in-depth review of AAV history, click here: Birth of a New Therapeutic Platform: 47 Years of Adeno-associated Virus Biology From Virus Discovery to Licensed Gene Therapy). However, it was soon discovered that AAV2 displays natural tropism towards certain tissues. What this means is that once injected into the blood stream, AAV2 automatically moves toward specific areas of the body; in this case, the CNS and kidneys. (For more information on serotype tissue specificity, click here: Adeno-associated Virus (AAV) Guide). This specificity would prove to be a double-edged sword. On the one hand, tissue specificity reduces risks of systemically expressing genes and reduces immunogenicity; on the other hand, this means that unless new capsid types are found to target an organ system, diseases of that system would be impenetrable to gene therapy.

Fortunately, soon after the isolation of AAV2, several other natural AAV serotypes were discovered (such as the, ‘Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy’). These new serotypes were found to have drastically different tropisms from AAV2, which opened up new doors towards creating novel therapies that were more specific, and less immunogenic. However, as hard-working scientists go, you knew that they weren’t just going to let a couple new dozen natural serotypes be discovered. Researchers began to tinker with mixing capsids together to generate new hybrid AAVs, in the hopes of creating new capsids that combined properties that would make them even more efficient. Soon, hybrid capsids like AAV2/5 were created, combining their organ specificities and AAV2’s already well-established production efficiency.

The idea of discovering new AAVs in nature and combining them with other natural AAVs to create hybrids sounds all fun and exciting, but we must take a moment to think. What if we can create an environment that drives AAV evolution towards specific tropisms and/or improved production efficiency? What if we force AAV to adapt to certain set conditions in the lab and create new AAV serotypes that are better than those that evolved in nature? Within the past two decades, the idea of using directed evolution to create new serotypes of AAV has exploded in the field of gene therapy, and multiple methods have been described in literature to achieve this goal (here is a rather well known one: Directed evolution of adeno-associated virus yields enhanced gene delivery vectors). The basic idea of directed evolution is simple: subject AAV to a hostile environment, collect the survivors, let them grow, and repeat until the hardiest one is left. Thus, it became possible to not just find AAV in nature and hybridize them, but it became possible to speed up nature to make our own AAV serotypes.

In summary, with the discovery of new natural AAV serotypes, the hybridisation of these natural serotypes, and by incorporating the directed evolution of AAV; we have created an entire host of AAV agents that are specific to organ systems (and sometimes even to specific cells!). At the same time, it also became possible to develop new techniques that made AAV production costs much cheaper as multiple new serotypes grew much faster in culture. Next time, we will take a look at the beginning of the era of human gene therapy trials.


Author: Danning Li

Danning Li completed his BSc. majoring in Physiology at McGill University. Afterwards, he worked for two years on developing a gene replacement therapy for Canavan Disease, a rare inherited leukodystrophy, at the Horae Gene Therapy Center at the University of Massachusetts Medical School. Now a medical student at Schulich, he wants to bring attention to the interesting genetic therapies that will become available in the not so distant future.


Photo Credits: Mehmet Pinari, Creative Commons

Safe Injection Sites: Sometimes it Pays to Do the Right Thing

In this country, we too often take for granted that most sacred and coveted of human rights: the freedom to choose our own destiny.  But when we are allowed to elect our own leaders, there is an implicit responsibility invested in each of us to hold them accountable for their actions; especially when those actions are fundamentally wrong. The Ford Government’s recent decision to reconsider the “merit” of safe injection sites is the worst kind of partisan politics.  It is a move designed solely to appeal to a minority of base voters, regardless of the cost in both dollars and lives.  It is so rare that a policy is both morally just and cost effective, and yet at a time when the opioid crisis is spiraling out of control, Ontario is on the verge of reversing the few gains we have made.  If this action is allowed to continue then those dollars, and those lives we could have saved, will be on each of us.

Canadians hear a lot about this “Opioid Crisis”, yet many of us have likely never see its direct effects.  You may be asking, what is this so-called “crisis”?  Or perhaps more importantly, why should I care?  Essentially, the Opioid Crisis refers to the North America-wide (and global) problem of rapidly increasing opioid drug use and related fatalities.  The figures are staggering. Ontario alone suffers two or more overdose deaths (ODs) each day, quadruple the rate from just 25 years ago, and the numbers are continuing to climb.  On the other side of the country, BC’s rates are twice as high as those in Ontario.  Moreover, deaths due to opioid overdose are just the most visible consequence of a much larger systemic issue at play.

Our Local Context

Here in London, a public health emergency was declared in 2016 in an attempt to combat outbreaks of HIV and hepatitis C related to IV drug use. Cutaneous infections, endocarditis, and a wide range of other potentially dangerous health conditions are all linked to the use of needle drugs.  The roots of this issue are systemic, and while the rise of illicit fentanyl and heroin are certainly major contributors, prescription painkillers are the source of addiction for many.  The role of physicians in creating this situation cannot be overlooked, nor can the actions of pharmaceutical companies like Purdue, which made false claims to doctors and patients denying the addictive nature of oxycodone, a synthetic opioid marketed by the company.

Ok, so we can all agree now that the Opioid Crisis is a big deal, and as future physicians, our profession is at least partly at fault.  So what can we do about it?  A number of measures have been proposed and implemented in the hope of lowering mortality and reducing infectious diseases related to IV drug use.  Naloxone, for example, is a drug that can temporarily reverse the respiratory-depressive effects of an opioid drug overdose; essentially, it restores life to someone who has OD’d and stopped breathing, buying more time for them to receive proper medical attention. Health care workers have begun to carry naloxone kits with increasing frequency, and these have also started to be placed in public spaces more regularly.  For example, our own Schulich Political Advocacy group recently met with London’s local municipal government officials to discuss the inclusion of a Naloxone kit at every public AED machine in the city; and in May 2018, the measure was approved and taken into effect over the summer. This represents a huge success for harm reduction in Ontario, and early data has shown that the expanded availability of naloxone has reduced mortality while sparing potential medical expenses.

Perhaps the most valuable initiative, however, has been the development of supervised injection sites (SISs).  These are facilities where IV drug users can go to use drugs under direct medical supervision.  Such sites often involve a needle exchange program in parallel, where used needles can be traded in for fresh ones.  This is designed to reduce the transmission of infection diseases, most notably HIV and hepatitis C.  These sites also act as first points of contact for providing healthcare to people who use drugs, often offering them referrals for rehabilitation, counseling, and education on infectious disease control and safe drug use.  As a relatively new concept, the effectiveness of SISs is still being evaluated, but the early data have proven very positive.

Safe-Injection Site Efficacy

A study done in Vancouver showed that with the opening of a single injection site, a 33% drop in mortality was seen from pre-SIS levels. Furthermore, there was a reduction of 40% in cutaneous infections, average length of stay in hospital fell by 67%, and ambulance calls for suspected ODs were also reduced by two thirds.  A further study of this site published in the CMAJ, found that not only was there a significant drop in mortality, but that this was done at a significant cost reduction for the healthcare system as well.  Most relevant for this effect was the decrease in HIV transmission resulting from the needle exchange program.  The cost of preventing one case of HIV was calculated to be around $20 100; which is only one tenth of the lifetime cost of an HIV patient.  When we add up all of these benefits – the reduced hospital stays, the drop in infectious disease, the prevention of overdoses – the overall result is clear: not only are we saving lives, but we are saving money while we do it!

The Ford Government now wants to evaluate the “merit” of these safe injection sites, and while they do so, they will be pausing the development of further sites.  This will cost money.  It will cost lives.  The Premier made his position on this issue quite clear during his campaign, and his actions should not be surprising. Yet his actions are nonetheless wrong. The role of the medical professional in the coming discussion will be important, and as community turns to us for answers, we must ensure that our actions and responses are measured with facts and compassion.  It is rare to find an issue with such a clear answer, and for safe injection sites, one thing at least is clear: sometimes it pays to do the right thing.


Author: James Payne

With a last name tailor-made for a future doctor, James really couldn’t have wound up anywhere but Schulich!  A London native, he did his undergrad at Queen’s, where he majored in Chemistry and Economics; the latter of which was the focus of his work for the UWOMJ journal.  James loves sports (he can catch a football better than Tom Brady), music, and, as you may come to find out, semi-colons.

Photo Credits: Marco Verch, Creative Commons 

How can we understand disease? In search of “best evidence”. Triangles, Diseases, and Illness in the History of Medicine.

Is it real? In the busy family medicine clinic, I am talking to a middle aged woman with a new diagnosis of diabetes. Even though she is reasonable and intelligent, she doesn’t really buy into it. I’d rather not be on medication. I feel fine. She’s right, but I know what could happen to her if she’s untreated.

What is a disease? Who is a patient?

These are fundamental questions to medicine. Studying the history of medicine allows you a deeper understanding of diseases. This is important because it has implications on what we are actually doing as medical students / future health professionals.

Maybe surprisingly, we don’t ask the question “what is a disease” very often in the medical school curriculum. It’s obvious most of the time; a problem in anatomy or physiology is a disease. Tuberculosis, diabetes, and thyroid cancer are all obviously diseases.

The closest the pre-clerkship curriculum comes to asking “what is a disease” directly is through psychiatry course in pre-clerkship. According to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (the “DSM”), the definition of a disease depends on symptoms, but requires also a “functional deficit”. This means the symptoms must interfere with your life. According to this model, if a person had persistent low mood, changes in appetite, and visual hallucinations, (all symptoms of major depression), but was still able to function (ie. go to work or school), he would not have the mental disease we call depression.

Answering the question “what is a disease” is out of the scope of this blog post, and there is more nuance to the DSM in that functional deficit can include emotional distress, which I will also put aside. What about my patient who was unconcerned with her high blood sugar over the past year? If she is able to go to work, and is not bothered by it, does she avoid having the disease called diabetes? Before you say “no, obviously” In order to understand the diseases we treat today, it is helpful to know that disease is a changing entity.

The pyramid of evidence based medicine

At some point in every medical school, this triangle is studied.

The “triangle of evidence” describes modern biomedical science in a single figure.

The picture describes a hierarchy of scientific studies. There are many variations on it, but the essentials are as follows: individual patient experiences (case series), and expert opinions are nearest to the bottom, while randomized large sample trials are nearer to the top. Even higher are “reviews” which average out multiple RCTs. The point is to average out as many patients as possible to average out the noise and arrive to an answer.

Nearly every one of these graphs has an arrow pointing upwards, reminding us which way to move. Strictly, the higher we go on the chart the more strength there are for causal claims. Most graphs drop the nuance and just say “increasing strength” or “increasing quality”.

The triangle is powerful, and this process provides medicine with practical answers to questions about causality. It has been applied to every area of medicine.

I argue that, while a powerful approach, EBM has a great weakness.

III. Duffin’s Hippocratic Triangle

The triangle of evidence is so commonplace it’s difficult to imagine what medicine looks like without it.

There were many scientific advances which dramatically revolutionized medicine – around 1900 germ theory is developed and doctors began to think about pathology at the level of cells. New ways are developed to look into the body and these become .the gold standard.

Before all this, diseases were primarily defined by symptoms, and the model for disease was based upon a balance of four humors – theoretical fluids filled in the body. For example, jaundice was caused by an excess of yellow bile.

The core of medicine was not in cells, but instead the ability to care for patients (from Latin patientem meaning “one who suffers”).

Dr. Jacalyn Duffin, a hematologist and historian, develops a different triangle in order to teach what a disease is which is rooted in history. By Hippocratic teaching, a disease is made up on a combination of the observer (the physician), the patient, and the illness. Two patients, being different people, have different experiences even with the same illness being treated by the same doctor – this means they have different diseases! Crucially, the observer (doctor or medical student) also makes up a part of the disease.

This triangle also lacks a hierarchy. There is no clear way “up” – the doctor, the illness, and the patient are equally important in defining a disease. In contrast, the “case report”, is always on the bottom rung of the EBM.

How does this help?

It’s good to know that metformin works to reduce blood sugars in diabetes. Even though the evidence is backed by RCTs, some diabetic patients do not take their prescribed medications. The medical term for this behaviour is noncompliance or denial. Often medical trainees and doctors can find this frustrating.

Being aware of Duffin’s triangle (and the history of medicine) makes you understand that the patient’s experience with an illness will actually produce a different disease every time. The triangle also reminds us that the physician matters. Diabetes, then, is not simply just abnormal blood values. Validating the “noncompliant” patient’s experience changes the disease.

Further reading

  1. Duffin ‘s book Livers and Lovers uses explores changing disease concepts over time
  2. Podcast lecture on the history of the stethoscope. This is related to the transition in medicine,

About the Author: Ariel Gershon

Ariel Gershon (Meds 2019) completed a BSc at the University of Toronto in pathobiology before starting at Schulich. He was a president of Schulich’s Osler Society from 2016-2017, a group of medical students who meet to talk about the history of medicine over lunch. He‘s interested broadly in the medical sciences, medical humanities, and indoor gardening. Tweet at me @GershonMD2019


Photo Credits: Featured Image; Internet Archive Book, Creative Commons
Header Image; Ryan Adams, Creative Commons

Rogue One: A Drug Wars Story. What Can History Tell Us About Pharmacy?

How should we regulate pharmaceutical innovation?

This blog will have a series of posts which seek to explain why a medical student ought to care about the history of medicine.

In the distant past, James Payne, MD candidate 2021, wrote a compelling article arguing that the current pipeline for producing new medications may be overregulated. Contemporary drug development is loaded with checks for safety, efficacy, even just plain bureaucracy. James raises the possibility that regulation results in worse medicines.

In particular, the FDA has legal authority to approve or deny new medications on the basis of safety and efficacy. If clinical trials are unavailable or unconvincing, the drug cannot make it to market. Presumably, this is to protect the public health– how could it possibly be to anybody else’s benefit?

The world of pharmaceuticals is a complex swirl of economics, policy, organic chemistry, and medicine. What could a historian add to our understanding?

I argue that there are unique insights that the study of the history of medicine can contribute to this medical problem.

HIV medications, ACT UP.

In the early 1980s there was an unprecedented health crisis brewing in the US. In 1981, it was noticed that a population of homosexual men were suffering from diseases previously only associated with severely immunocompromised patients: Pneumocystis jirovecii pneumonia, esophageal candidiasis, Kaposi sarcoma. By the end of 1981, 270 of such cases were documented by the Centre for Disease Control. In 1992 alone, 33,590 were estimated to die of HIV related illnesses.

Amongst the outbreak, organizations advocating for faster drug development materialized.

Anti-retroviral were being developed but had not yet found use in the clinic. ACT UP was an activist organization whose goal was to take down the FDA. The main argument was that medications were a health care commodity, and that patients then had a right to access to those medications, even if through a research study. The specific research methodology of double-blind placebo was called into question as unethical. The slogan was simply “drugs in people”.

It was effective. HIV is, of course, still with us today. It has been tamed from a devastating epidemic into a chronic condition. In large part, this was due to the activists which called for the dismantling of FDA bureaucracy in a time of crisis.

One part of history of medicine is a collection of facts. Remembering the fact that thousands of HIV positive people died of AIDS in the absence of treatment can be an important consideration when thinking about the troubles associated with studying the safety of medication. It’s not simply an academic concern, but a lesson people have had to suffer through.

Psychiatry and FDA from 1950-1970s

The FDA was first established to regulate the safety of medications. On the face of it, they act as an agency to prevent the powerful pharmaceutical companies from taking advantage of the general population by producing unsafe or ineffective medications.

As ACT UP has argued, the outcomes of FDA regulation did not serve the general public in the case of patients dying from HIV. As opposed to outcomes, exploring the intent of the FDA, however also reveals that the priority may not have been for public good.

Dr. Edward Shorter, historian of psychiatry, explored unpublished and archival internal communications of the FDA from 1950s-1970s. In this time, the FDA was gaining new legal authority (through the Kefauver-Harris amendment in 1962), and was exercising this political will not in service of the public, nor in service of pharmaceuticals, but for itself! A number of previously safe and efficacious medications for mood disorders were banned from the market, for example meprobamate. Dr. Shorter describes this as the agency going “rogue”. The FDA decided first that meprobamate was to be regulated, and actively suppressed expert testimony to the contrary, as per internal documents.

The second part of the history of medicine is the process by which new facts are discovered. These new insights into the pharmaceutical industry could only be discovered by interrogating the archive.

One of the reasons I love studying history of medicine is that it allows us to seriously reconsider our presumptions. If we start by assuming pharmaceutical regulation is a positive, history gives us examples of the contrary. It’s our duty as future physicians to learn lessons from the suffering in the past.


Author: Ariel Gershon

Ariel Gershon (Meds 2019) completed a BSc at the University of Toronto in pathobiology before starting at Schulich. He was a president of Schulich’s Osler Society from 2016-2017, a group of medical students who meet to talk about the history of medicine over lunch. He‘s interested broadly in the medical sciences, medical humanities, and indoor gardening. Tweet at me @GershonMD2019

10 Traveling Tips for Global Health Electives

By: Adriana Cappelletti (Meds 2018)

1) Read up: Find out as much as you can ahead of time about the place you’re visiting.

Learn about the country’s history, current political situation, and local customs. Find out what people wear to work and around town to make sure you pack appropriate clothing. Some countries have more conservative styles. For example, where we stayed in Uganda, women almost exclusively wear skirts (usually to the knee or lower), while men wear button-down shirts and full pants, even in the heat.

2) Medical supplies: Bring your own masks, gloves and hand sanitizer. In low resource settings, you do not want to put a dent in their supply.

Also, try to snag any surgical gloves or sterile sutures you can get your hands on. You can ask surgeons, residents or scrub nurses you have worked with about any slightly expired, unopened sutures they’d be willing to donate.

3) Little Pharma: Stock up on your own mini drug supply and plan all vaccinations well in advance.

This takes up more time than you’d expect! You’ll need prescriptions for both drugs and travel vaccinations. Useful prescription drugs can include antimalarials, HIV post-exposure prophylaxis, and ciprofloxacin (or alternatively azithromycin) in case of bacterial gastroenteritis.

Travel vaccinations you might need include yellow fever, typhoid, and hepatitis A/B. Yellow fever is in limited supply in Canada and is necessary for entry to many countries in Africa and South America, so don’t leave this to the last minute. Do not expect to get travel prescriptions filled by a walk-in clinic. You can either pay $80 for an appointment at a travel clinic, or if you have a family physician, they may provide you with these prescriptions and save you eighty bucks. Over-the-counter drugs for your mini pharmaceutical kit might include polysporin, ibuprofen, acetaminophen, bismuth salicylate, PEG, and immodium.

4) Moula: Seek out any funding opportunities for global health initiatives.

If you look for it, there’s plenty of money out there to help fund your global health elective. Check out this link  for the opportunities available to students at Schulich.

5) Safe living quarters: Don’t skimp on accommodations and compromise safety for savings.

When going somewhere unfamiliar to you, it’s best to err on the side of caution and choose trusted accommodations. We connected with a Guest House owned and operated by Massachusetts General Hospital for medical trainees and staff. For $25 USD per day, we had a private bedroom and bath, 24/7 on site security, and we were walking distance from the hospital. We felt safe and at home, and we met other Global Health aficionados.

6) Expectations: Establish mutual goals with your supervisor abroad.

Either ahead of time online or in person on your first day, try to establish a sort of contract of expectations with your supervisor. Let them know what you’re hoping to get out of your elective. Find out from them what they’re expecting of you and what is actually possible at their site. This can prevent disappointment or misunderstanding on either end.

7) Dive in: Embrace the culture, food, and local language(s).

Get to know locals, either from the hospital or through your accommodations. Ask them about their lives: how did they grow up, what is medical school or residency like for them, and what do they like to do for fun in their spare time? Immerse yourself in daily living by going to market and visiting shops. Find out if there is a nearby cultural centre. When we went to the Igongo cultural centre for the Ankole district of Uganda, we learnt about how farming, construction and traditions evolved in the area.

Try traditional foods. Avoid street meat, which can be undercooked, or raw vegetables, which may be washed with unfiltered water. Learn some basics of the local language. In Western Uganda, the academic language is English, but many people speak only Runyankole, the regional dialect. Knowing simple phrases like, “How are you?” or “How was your night?” can go a long way in building patient trust. If you show interest in the country’s culture and language, people will notice and be appreciative that you are making an effort to understand their way of life.

8) Ethical tourism: Support local businesses when buying groceries or gifts and planning weekend getaways.

As a visitor to a developing country, you have the opportunity to contribute to that nation’s economy and be a responsible traveler.  When grocery shopping, hit up local markets. At supermarkets, try to buy food items manufactured within that country. If you’re planning something tourist-y (we went on safaris), book transportation and accommodations that are operated by and employ local people.

Gifts for your friends and family back home (or, let’s be real, for yourself) are also an opportunity to contribute to the economy. In Uganda and many other developing countries, tailors can be commissioned to make custom clothing at low cost. We bought fabrics in traditional African patterns from the market and had one-of-a-kind clothing made for $30 or less per item.

9) Emotional support: Know who you can talk to about your experience.

Global Health electives can be extremely enriching, but they can also be emotionally draining. Your clinical experience in a low resource setting might raise moral and ethical dilemmas you didn’t anticipate.

Let’s use an example: a young man gets in a bota-bota (motorcycle) accident and needs an emergent head CT. The cost isn’t covered by the government, and he and his relatives cannot afford the $200 CT that is needed to save his life. Everything is stalled while he is dying. Do you pay the $200 out of your own pocket? If you do, what happens when other patients’ families find out that the international student (you) can pay for imaging or drugs?

Don’t keep this inner turmoil to yourself. Rely on physicians with experience in Global Health. Share your thoughts with them, and have a discussion around the complexity of these situations. Back in Canada, debrief with the Office of International & Health Equity Learning (IHEL) and a physician mentor. It’s also really helpful to complete this type of elective with another medical student, for both safety reasons and to have someone who understands what you’re going through abroad and back home. For moral and ethical cases to work through in preparation for your elective, check out this link .

10) Share: Make use of the new insight you’ve gained by publishing or presenting about your elective.

You’ve had a life-changing experience! Take advantage of your unique perspective and the learning you’ve had to contribute to medical journals, blogs and conferences. You can write reflections or poems for the UWOMJ Blog or the CMAJ Humanities Blog. You can partner with your supervisor abroad to publish a case study. You can prepare a poster presentation on your experience and attend a Global Health conference in Canada or internationally.


Author: Andriana Capelletti

Adriana Cappelletti (Meds 2018) completed a Global Health elective in Obstetrics & Gynecology in Uganda in November 2017, alongside Rachel Loebach (Meds 2018). Adriana is pursuing a career in Family Medicine and intends to incorporate Women’s Health and Global Health within her practice. Adriana’s clinical experience in Uganda was cut short by an unfortunate physician strike, which left countless patients without care. Witnessing the repercussions of political turmoil on population health has only heightened her sense of social accountability and motivation to engage in international partnerships.
Twitter @cappelletti07.



Viral Vectors as Containers and Their Importance to Gene Therapy

By: Danning Li

Hello everyone and welcome back to the big wide world of gene replacement therapy and medicine! On our last blog post, we tackled the general idea of gene replacement therapy, which was namely to put a working copy of a gene into a patient’s body, so that the gene product could be produced permanently. This idea of course sounds incredibly simple, but considering the lack-luster implementation of gene replacement therapy in medicine today, why hasn’t this idea become widespread? Well, this blog post is going to tackle that exact question, and look at some of the challenges facing gene therapy today.  

To start off, the main problem in gene replacement therapy is that the human body really hates taking in undigested DNA (if anyone wants to read about extracellular DNA in the body, here’s a good paper: The Origin and Properties of Extracellular DNA: From PAMP to DAMP). So, automatically, the idea of oral gene therapy pills is difficult to implement, since stomach acid and digestive enzymes would rapidly degrade incoming DNA into individual base pairs or base pair components. At the same time, injecting DNA directly into the blood stream or local tissue would meet a different problem; the immune system, which would rapidly detect the foreign DNA and then degrade it into all of its components (click here to see how the innate immune system detects DNA). Therefore, this leaves scientists and physicians with a problem, how can we create a therapy that can sneak past the immune system to deliver our uncompromised DNA to our target tissue?

Infective Solutions: The Virus

First thought: viruses, a common solution to a scientist’s dilemma. By the 1970s, it was already known that viruses are natural agents at injecting their genetic information into host cells for viral reproduction purposes. The goal then became to find a good viral candidate that could somehow be used as a gene delivery system to the human body. To be considered a good candidate, the virus must meet several criteria: it must be able to deliver the genetic information efficiently, it must be minimally immunogenic, it must be non-replicative, and it should have a low risk of insertion into the host genome (this article is a good summary of viral vectors for gene therapy).

The process to meet these goals requires the original viral DNA to be removed, and only the viral capsid to be used. Without going into a lot of details, since the virus has been rendered non-replicative, the production of the viruses would have to be split into multiple parts; this means that the DNA plasmid of our target gene would be given alongside our packaged plasmid expressing the viral capsid protein using a co-transfection protocol (triple transfection is the newer technique and has much better yield than double transfection). However, the question remains, just what kind of virus should be used? After all, there are so many types of viruses to choose from! For now, we will focus on 3 types of viruses that are of interest: retroviruses, adenoviruses, and adeno-associated viruses.

A) Retrovirus

As medical students, we have all heard of retroviruses, with HIV being the most widely known member of the retroviral family. For gene therapy purposes, lentivirus, a subtype of retrovirus, is used instead of a standard retrovirus, since a lentivirus can infect non-dividing cells. The good and bad thing about a lentivirus is that it will insert its own genome into the host genome-this is great because once the insertion occurs, the cell will have the DNA forever (no backsies)-but on the negative side, inserting DNA into random places within the human body will disrupt normal gene function and could lead to cancer. This was unfortunately shown when children given an experimental gene therapy to cure X-linked SCID-XI syndrome developed leukemia due to random insertion inducing mutagenesis (they were cured of their SCID-XI syndrome though, so mission success with unfortunate side-effect?).

B) Adenovirus

Our second virus of interest is the adenovirus, a virus responsible for many infections in the respiratory tract, among others. This early candidate for gene therapy however, had the tendency to spread throughout the body and become immunogenic. This was shown sadly in 1999, when Jesse Gelsinger died due to an immune reaction to adenovirus in a trial to cure ornithine transcaramylase, a metabolic disease that affects ammonia elimination,.

C) Adeno-associated Virus (AAV)

Finally, we arrive at our last viral candidate, the adeno-associated virus or AAV. The name is pretty straight forward, AAV depends on adenoviruses to reproduce (it’s like a virus of a virus). In fact, when AAV was first visualized under electron microscopy, scientists weren’t quite sure what it was due to its small physical size. Since AAVs are naturally non-replicative, they are minimally immunogenic, and there are no diseases that are known to be caused by AAV. The major limit of AAV usage however is their small size, since only about 2.5kb worth of DNA can be delivered with one virus, which significant limits the amount of treatable diseases with this strategy, since human genes are quite large in base pairs. However, since safety is the major concern of viral gene delivery, much of the focus on gene replacement therapy has focused on developing good recombinant AAV (rAAV) platforms because of their high safety features.

To conclude, I hope this post provided you a brief understanding of some of the current challenges in delivering gene replacement therapy in medicine and next time, our topic will be on the different types of rAAV vectors (delivery gene mechanisms), and how the choice of this rAAV subtype (there are a lot) is important for therapy development.

Author: Danning Li

Danning Li completed his BSc. majoring in Physiology at McGill University. Afterwards, he worked for two years on developing a gene replacement therapy for Canavan Disease, a rare inherited leukodystrophy, at the Horae Gene Therapy Center at the University of Massachusetts Medical School. Now a medical student at Schulich, he wants to bring attention to the interesting genetic therapies that will become available in the not so distant future.

Photo Credits: Creative Commons, Capsid