You may have heard the big news that came out this past Tuesday in Nature - a patient in London has been in HIV remission for over 18 months (since September 2017). This news comes 10 years after Timothy Brown (formally referred to as the Berlin Patient) was found to be in remission from a previous HIV infection and a related cancer, following a set of two stem cell transplantations. Mr. Brown is the only reported case of an HIV-infected patient who has been functionally cured of the virus - he may still have a reservoir of infected cells, but the latent viruses have not been detected since, and are incompetent to infect any new transplanted cells. Now, although it is too early to say conclusively that the London Patient has been functionally cured, there may finally be a second patient to confirm that the case of Mr. Brown was not an anomaly.

The London Patient underwent a similar procedure to that of Mr. Brown, in which a new set of cells were transplanted into the patient. These cells had a mutation (“delta 32”) in the cell-surface receptor CCR5, which made them less susceptible to most variants of HIV. In a normal infection, HIV enters a host cell by highjacking two receptors on the host cell: CD4 (necessary for proper immune function) and CCR5 (for which the delta 32 mutation does not effect normal human functioning). Therefore, by transplanting cells that are homozygous CCR5delta32 mutants, the virus will not be able to infect any of the newly transplanted cells.

It is important to note that some less prevalent (1/5) variants of HIV do not need CCR5 and can in-stead infect cells through CD4 and the CXCR4 co-receptor. Therefore, if a patient has even a very small amount of the CXCR4-competent HIV variant in their body at the time of transplantation, there is nothing to stop this sub-population of the virus from rebounding, as seen in another patient who had a similar transplantation. Furthermore, this transplantation procedure is extremely dangerous, difficult to perform, and is reliant on a near-perfect HLA-matching donor (rare), who is homozygous for the delta32 mutation (also rare), among other restricting factors. Thus, this is sadly not an end-all solution for HIV. Nevertheless, these results are promising and may still be an important finding that leads to a later cure.

As a general HIV update, current antiretroviral therapies have made life-long suppression of HIV a possibility for most patients with access to treatment - life expectancy for those undergoing chronic treatment continues to climb and people undergoing treatment can live normal lives. Recently, it was announced that there may soon be a once-a-month combination treatment on the market that can suppress viral replication, which would greatly reduce the risks associated with non-adherence to daily dose drugs. HIV eradication strategies include preventing new infections by pre-emptively treating uninfected high-risk individuals, developing a vaccine (although difficult), mutating the CCR5 gene in the cells of infected patients using CRISPR-Cas9 (this strategy has several issues including potential off-target mutations and the fact that Cas9 is a bacterial protein and will likely illicit a human immune response), and finding a way of re-activating and targeting (the “shock and kill” approach) or suppressing (“block and lock” - what has worked for Mr. Brown) latent HIV that hides in immune cells and persists in patients. Sporadic HIV reservoir reactivation is why antiretroviral therapies need to be taken chronically and has thus been the subject of a good deal of research in recent years.

As an interesting aside, you may have recognized the name “CCR5 delta32” from another story I talked about in a previous bit (byte 1, bit 2). The CRISPR gene-edited babies that made headlines in late November were indeed targeted at CCR5 in the region that would correspond to a delta32 mutation. In other words, the gene mutation that Dr. Jianqui was trying to induce in these two babies might make them immune to the CCR5 variant of HIV, which their father reportedly carries. Playing with CRISPR in embryos, however, may have un-predicted side-effects that could seriously affect the lives of these two children, and may not be worth their theoretically reduced risk of HIV infection.

We often think of insects as a nuisance - for many non-entomologists, the word “bug” has a negative connotation, as though all insects are pests. However, I am surely not the first to tell you that many insects are in fact essential to global food chains, plant survival, and may soon provide us a solution to food shortages. The global diversity of entomofauna is in a steep decline because of human actions and we are starting to see the the consequences. I am no expert in ecology and don’t want to make a display of the Dunning-Kruger effect, so I invite you to read this review on the topic, which I was recently made aware of by a good friend.

As always, I like finding ways of relating what I talk about to Microbiology. The gene drive, first theorized in 2003, is a way of making an experimental gene construct spread from an experimentally-generated sub-population into a much larger population, through progressive gene editing. In short, gene drives make use of gene editing technologies such as Cas9 (see byte 1, bit 2), to both modify the host’s genes, but also to carry forward the gene-editing tool into 100% of the host’s offspring in the next generation. So long as the modification does not reduce the reproductive fitness of the host, such modifications are liable to spread exponentially within a population. Although this technology could be used in virtually any living system on Earth, its most studied use is in how it could become one of our most important tools in fighting and possibly eradicating Malaria in the near future. If you are struggling to understand quite how this mechanism works, or what the consequences of its use may be, I would suggest that you watch two quick videos on the topic here and here. I would also suggest that you sit down and read more on the topic if you get a chance, because it is quite fascinating and its use would break profound moral and ecological boundaries - which could have both good and bad consequences.

I thought it would be fun to expose you all to a couple of interesting concepts in microbiology, in case you weren’t caught up.

One subset of “life” that I find extremely interesting are viruses, as they do not fit the standard definition of life (being inert once they exit a host cell and not having their own metabolism), nor do they belong to Carl Woese’s well accepted three-domain tree of life. As an exception to the standard model you may have learned in early biology courses, the heritable material that passes from one virus to the next generation is not necessarily DNA - it could alternatively be RNA that is transcribed into DNA or more RNA before being re-packaged into the next particle (see figure). The evolution of viruses has been tightly interwoven with the evolution of all life on earth, and it has even been conjectured that viruses pre-dated cellular life (in other words, we evolved from viruses a very long time ago). However, this is not the only theory of the origins of life currently in existence. Some viruses are very dangerous (HIV, Ebola, Measles, Influenza, Zika…), but many others cause no harm or even help us function normally. Some viruses are critical in daily carbon cycling within the world’s oceans and others have led to extremely important discoveries in biomedical sciences, including CRISPR-Cas9 (which I discussed in byte 1, bit 2). I hope you find viruses as interesting as I do and take some time to understand them better.

Another very interesting set of molecular infectious agents are prion proteins - essentially, proteins that already exist within us, which can misfold and catalyze the misfolding of other nearby proteins, leading to large protein aggregates that disrupt normal cellular functions. Prion diseases (including Creutzfeldt Jakob Disease (CJD), tied to Kuru and Mad Cow) are transmissible from one person to another, despite the infectious agent having no evolutionarily-driven will of its own to infect people (by virtually no definition are proteins ever considered living entities). Some reports suggest that the molecular agents in Alzheimer’s disease and several other common neurodegenerative diseases may fit within this category, which would make these proteins an important set of human pathogens. Prion diseases are worth reading about if you get the chance, as they introduce a new way of thinking about infectious diseases - read more about them here or here.

I got interested in the history of McGill recently and thought I should share some of what I learned, to pique your curiosity in reading more about it. Here’s a good in-depth account of the history, worth fanning through if you have the time. Following are some compelling things about my uni.

Few people are aware that McGill University is a title given to a portion of a greater educational institution, entitled the Royal Institution for the Advancement of Learning (RIAL). Although RIAL used to administer a number of separate schools, its sole purpose now is to run McGill and its various constituents (incl. Mac campus, several teaching hospitals in Montreal, alongside research facilities in Barbados, the Canadian arctic and New Brunswick, among others). Although we graduate with a degree from McGill, we are governed by RIAL.

McGill and its alumni have been instrumental in founding a number of other universities, including UBC, Johns Hopkins, UVic and UAlberta.

Despite a stellar reputation in Canada and internationally, students might notice that McGill’s city and Mac campuses have a significant number of old buildings in need of repair. This is the result of a number of factors, including the Quebec government limiting educational fees on students, while maintaining provincial austerity measures (leaving McGill between a rock and a hard place), and the research funding framework in Canada directing proportionally lower funding towards host institutions for maintenance than do equivalent frameworks in the US. When structuring an educational system, compromises are always needed in one way or another. I feel extremely lucky to be able to afford a world class education, although I have to remind myself that such affordability may come to the detriment of my campus and thus the quality of professor who may want to work here in the future. While this may harm McGill’s future, the blame for low funding should not fall solely on the shoulders of government officials (although corruption doesn’t help). The more money we divert towards education, the less is available for infrastructure, healthcare, etc. Thus, the state of campus affairs is most dependent on Canada’s economic fortitude and will continue to fluctuate over the coming decades based on where our country stands in the global economy.

With the start of each new year, I often consider the randomness of choosing January first to be the turnover of a new year, as opposed to the relatively close solstice on December 21st or any other day in the year. This decision to have the new year start on January first has a contentious history and was only adopted by Britain and its colonies in 1752, close to 200 years after most of Western Europe transitioned to the Gregorian calendar. Likewise, there are many other turnover dates celebrated by different cultures at various times of the year, which are regularly overshadowed by the Western and Chinese new years just because of our collective cultural and economic dominance. Every time we celebrate long-held traditions or follow passed-down social conventions, I think it is important that everyone take a moment to re-visit the past and understand where these conventions come from, alongside the alliances created and blood shed for the event of each local adoption. I don’t necessarily condone the upheaval of all current traditions. I just think it is important that everyone be aware of the history and make their own informed personal judgements, rather than following every learned behaviour as rote. Here is one of my favourite videos that grazes the topic (despite unfortunate animations).

Nevertheless, I choose to celebrate the Western new year and I internally associate this year’s turnover with a sense of renewal, as I have all the year-ends that I have previously experienced. Resolutions for this year: write new songs, write new articles, read more books, read more articles outside my field and find some way of making a measurable impact on the life of someone I don’t already know at the start of the year.

Byte 1, bit 5 (23/12/18): birthday bit

It’s my birthday today! I thought I would make this a short bit to share my roots and show some family appreciation before I get back to enjoying a short holiday break.

I was born in Toronto to two architects. My father is from Cardiff and my mum from Glasgow, although both my parents spent a good portion of their youths in Canada and met at the University of Toronto. Both sides of my family tree are highly tied to Britain and Ireland - I have a family kilt and am a slight Britophile as a result.

I have an older sister who is currently mid-way through a Master’s degree in architecture, following a path similar to our parents. As you may know, I study Microbiology and Immunology, making me a bit of a black sheep in the family. I love what I study and do not see myself in architecture, but I feel that everyone should make an effort to befriend an architect at some point. A foot in the door in architecture broadens your interest in exploration and geography, all the while giving you an appreciation for design that does not appear to come naturally to most.

That’s all for today. Happy holidays!

Two years ago, my sister Ros was working in England. My cousin and I coordinated a trip to Iceland with Ros, as a way of meeting up with her somewhere in between Canada and the UK. Being on an undergraduate student budget, we rented the cheapest car available to us (a Toyota Yaris) and drove around Iceland on Highway 1 and into the Western Fjords over the span of one week. Iceland is a wonderful place to go and we had an amazing trip, but we did had some notable problems with the Yaris on gravel roads. I wrote a somewhat sarcastic song on the ukulele with Alex’s help for a couple verses. Thought I might share. Please excuse the lowfi sound quality and my inability to reach high registers with a sore throat. Might re-record with a proper mic soon.

Although I thought that most of my bits would be isolated to the realm of arts and music, I feel that it is worth stressing the importance of continued research into genetic editing, despite recent events. Last Sunday, it was claimed in a Youtube video that Dr. He Jiankui, a Chinese researcher who previously studied at Rice and Stanford, had previously used CRISPR-Cas9 to edit the genomes of a set of human twins who have now been birthed. While these claims have not yet been backed by any published data, this still sounds many alarms in both science and layperson communities. I won’t get into the details about the risks and moral concerns that have just been breached, because others with far more expertise have made far more impressive reporting pieces than I ever could (linked below the figure). However, I wanted to reiterate that this announcement is an outlier in science and does not take away from the importance that gene editing has and will have in our lives over the coming years.

While Jiankui’s announcement seemed to come out of nowhere, it lines up in parallel with a recent paper published in Nature, detailing germ-line gene editing in IVF-generated human embryos, with the important difference being that these were not brought to term. Mainstream science continues to have a strong framework for preventing research into potentially unsafe hereditary human gene editing (or any other moral concerns) and this Nature paper is a good example of mainstream science reaching the boundary of what is acceptable, without surpassing it. To retain one’s position in the academic sphere, one must retain governmental funding and appease the university with which they work, for fear of losing your ability to continue in research. I will not say that these boundaries are faultless and that there are no rogue scientists ready to test their luck on the world’s stage (as evidenced above), but repercussions will keep mainstream science from falling off the deep end.

Before I began my undergrad, I was very interested in CRISPR-Cas9 and had the pleasure of attending a lecture by Emmanuelle Charpentier, one of the technology’s discoverers in the context of its current uses. I have used Cas9 in one of my previous labs, and may be doing the same in my current lab as a later portion of an ongoing project. The tool is extremely useful in biological research and should in no way be abandoned in the context of cellular science if we hope to continue making leaps forward in science at the rate we are. What would have previously taken a year to generate in the lab can now take an undergraduate student a day of treating and a few weeks of testing. Legally stone-walling or publicly stigmatizing the use of Cas9 in any form of cellular research would only lead to rogue science and hampered mainstream progress, as Cas9 constructs are relatively inexpensive and easy to generate/acquire. Now that this technology is available, cash-strapped lab directors are not going to limit themselves to more expensive and time-consuming means of genetic study. Anyone who has understood the scientifically supported concept of de-criminalization (both in the context of gene editing, but also in the context of black market alcohol or narcotic fortification) would appreciate that the only way to move forward with genetic research is to leave it in the hands of mainstream scientists, such that future advances are balanced by maintained scientific and philosophical discourse. In other words, it is important to understand that stigmatizing gene editing in genetic research would only bring out the worst of the field.

Some interesting resources linked to this story include a Vice video and an Associated Press exclusive explaining the issue of He’s work through the lens of a bioethicist at Columbia and an investigative report with multiple expert opinions, respectively. Here is a report from Vox in July, giving a good summary of the technology as we understand it today.

If the mutations induced in Lulu and Nana are confirmed by the scientific community, this would be the first confirmed case of intentional germ-line genome editing in the history of the human species - a somewhat scary thought. Here is a good explanation video that has come out since.