Replies

• Wen Jiang

  28 July 2008 | 02:08

  First I would like to thank Ai Lin for the generous introduction and an opportunity to share my personal journey in the field of nanotechnology and how I ended up where I am today.

  To start things off, my name is Wen Jiang, I just completed my Ph.D. degree in Biomedical Engineering at the University of Toronto specializing in the design of nanomaterials-based systems for cancer detection and therapy. I will be starting my Postdoctoral Fellowship this coming September at Harvard Medical School, trying to incorporate nanotechnology into fundamental cancer research.

  Everyone has childhood dreams of what they would like to become when they grow up. For me, becoming a scientist was certainly not what I envisioned. Influenced by my parents who are both artists, I was inclined to become a painter or a musician, imagine the freedom of expressing oneself through one’s work! However, this changed when my family moved to Canada. The teaching and the learning style of the West was drastically different compared those of the East. For the first time, I enjoyed the flexibility in science and math classes as I did in the arts while learning about the world around us. I decided to major in Electrical Engineering for my undergraduate degree, hoping that one day I would become a Chief Engineer to design the next generation of microprocessors or artificial intelligence. With this goal in mind, my life seemed ordered, as my future was mapped out for me.

  Then, in 2001, I lost my grandmother due to cancer.

  There are moments in our lives that will change our lives forever. For me, this was definitely one of them. Although I was doing well in school, I began to question what it was that I wanted to do with my life. The same circuit boards and layouts that used to fascinate me somehow lost their purpose. I wanted more. I wanted to help people like my grandmother so that they will one day have hope in defeating this deadly disease. Therefore, following my graduation in Electrical Engineering, I decided to pursue graduate studies in a cancer-related field. I knew that this was the turning point of my life.

  Although it is easy to make decisions, following it up with action takes a lot of courage and effort. Considering that I practically had no medical or biological training, even my parents were trying to convince me to give up this naive and idealistic plan. To make matters worse, when I first showed up at the office of my potential supervisor, Prof. Warren Chan at the University of Toronto, I didn’t really have a clue about what nanotechnology was. Not surprisingly, Warren was reluctant to accept me as his graduate student, with the explanation that he was just starting his position as new faculty and that the available funds were limited (Sure, Warren!!). However, persistence did pay off. After continuously dropping by his office, my determination and commitment to work in his lab changed his mind and with that, I became one of his first graduate students. It turned out that the lab did in fact, have very limited funding. In order to save money, we made desks for the lab using wooden boards purchased from Home Depot.

  Everyone’s graduate school experience is unique. For me, it was a wonderful ride. Compared to sitting in front of a computer all day long and designing circuit layouts, performing experiments and chemical reactions using real reagents was an exciting and refreshing experience. In fact, this is what I did for the first two years of my Ph.D.: nanomaterial synthesis, characterization, polymer and surface chemistry. Day in and out. On top of these, I took as many undergraduate courses as I could in inorganic chemistry, organic chemistry, molecular and cell biology to complement my lack of formal training (The courses themselves are fun, except I did get tired to constantly explaining to professors and teaching assistants why a Ph.D. student would take their courses). Despite the extremely demanding time commitment, the hands-on lab component for these courses really helped me in the long run. The Chan lab was small back then: only 3 graduate students plus a couple undergraduates. We were a very tight group. Although initially, the lab did not have a lot of space, it was still a fun place to be. We had a small TV set for video capture that was connect to a microscope. During the 2004 Olympic games, a fellow graduate student and I really did not want to miss any games whenever we came to the lab to work. So we scavenged our building outside (which coincidentally was undergoing construction at the time) and found a couple of wires to make a TV antenna so that we could get the reception. The image quality wasn’t so perfect but it was clear enough for us to see who won the game. I guess my undergraduate training was not wasted after all.

  On the research side, we were making progress as well. Every graduate student will experience the initial period of uncertainty, in which one constantly questions whether the project(s) will work at all. Will I be asked/forced to quit graduate school? What is left for me to do if I can not finish? For anyone who is going through this process, the answer is rather simple: just do your best, and eventually everything will fall into place. It’s a bit of a cliché, but quite true. After my second year in the lab, I was already conducting research independently and thinking about potential projects. During that time (2003-2005), many proof of principle demonstrations using the tools of nanotechnology were being published in well-recognized journals. In particular, an area of interest was to use quantum dots for in vivo tumour detection and imaging. By the end of 2003, our lab was also investigating the potential for this technology platform. I was involved in a project involving near infrared light emitting quantum dots to detect tumours using mouse models. Initially, we had some promising results in that enhanced fluorescence was detected in the tumour as compared to healthy tissues, but the difference was not visibly significant. We thought that this was a trivial task and could be optimized by simply adjusting the dosage of quantum dots injected, however, we were wrong. After varying many parameters from the injected quantum dot dose to circulation time, we did not observe any improvement. It was at that point that I realized that we may have missed something in our experimental design, something more fundamental.

  During this time, a young neurosurgeon (Betty) entered our lab and wished to pursue her Ph.D. studies under Warren as a co-supervisor. It was a rare scene at the Department of Engineering to see an M.D. going for a Ph.D. degree, and none of us had any prior experiences working with a “real” doctor before. So while introducing one another, we began to talk about science and the state of nanotechnology in medicine, and how my previous project failed with great disappointment. What really surprised us was that despite a string of biomedically-related nanotechnology studies to date, we truly did not understand how these nanomaterials interacted with biological systems at all. Inspired by the conversation, we thought that maybe we should take a step back. Instead of pushing these nanomaterials into clinical or animal studies, we should first study how the most fundamental unit of biological system (cells), interacted with them. So, when I asked Betty if she was interested in doing this seemingly boring, yet important and fundamental study together, Betty said yes, and the rest are just…details (except for the fact that the paper took both us two and half years from beginning to finish).

  The initial adjustment period for both of us was surprisingly short. I assumed that with her molecular biology background, a field that is totally unrelated to mine, some sort of “cultural” clash would arise. To the contrary, we complemented each other very nicely. She is very organized and kept a very clear “diary” of our experiments, which more than offset my spontaneity with lab experimentation. But what’s more important to this working relationship was that subconsciously, we were pushing each other to work harder. During countless times, we had to stay all night to finish an experiment. If I was working by myself, I would probably have given myself yet another break and delayed it for the next day. But since we were in this together, we were obligated not just to ourselves, but to each other, that we gave our best effort forward. In the end, the most valuable lesson I obtained was that there is no shortcut in science, you just have to go through the process to learn. The learning process is the part that is really hard.

  I still remember the day when we received the email from Ai Lin stating that our paper was accepted for publication in Nature Nanotechnology. My feeling was a mixture of joy, relief and little bit of emptiness inside. I was happy because all of our hard work had finally paid off. I was relieved because finally it was over, and the emptiness came from the uncertainty of what I was to do next? For so long, this project was my life. It became apart of me. Now suddenly, this part of my graduate experience was about to end, and I didn’t know how to react. However, it did not take too long for me to move on, and the next project was underway in no time. Regardless of what happened, I think the best thing that came out of the whole experience was that I found the joy and benefit of working in a team with others. I have always enjoyed working alone, since it gave me the freedom, flexibility and total control (the reason why I wanted to be an artist in the first place). But after this experience, I learned that working with others who suit your personality and complement your weaknesses is actually a much more rewarding and enjoyable experience! Will I hesitate to work with Betty again in the near future? Not for a nanosecond!

  Like life, Ph.D. is more about the means than the end. Now with the degree in hand, how do I feel? The truth is, I actually feel I know less now than before. The Ph.D. training is an eye-opening process. Going through it allows you to see what’s out there. For many, 4-5 years of one’s life might seem like a big investment, but believe me, if you are doing something that you truly enjoy, it feels like a blink of an eye! There are many good reasons out there to decide against pursuing such a degree, but being afraid of the time commitment shouldn’t be a one of them.

  With the maturation of the field of bionanotechnolgy, more questions are now being asked. The public and the scientific communities are demanding more from our field, and no longer is it adequate to offer the technology as “potential” platforms. People want “real” applicable results. With this in mind, it is necessary to realize that like any technologies, nanotechnology is there to serve a purpose: a need. To understand such needs, cross-disciplinary communication is necessary. The veils that separated different fields are beginning to come down, as such, scientists who can speak multi-disciplinary languages and understand issues from different perspectives must come to together for a greater goal. It should no longer be a shock to see a physicist performing a Western blot or a molecular biologist calibrating lasers! Graduate training, unlike undergraduate studies is more about learning how to think, than how to use an instrument or following established protocols. With the hardware wired in place, all that is left is to update the vocabulary with languages of different fields to create a truly cross-disciplinary hybrid scientists of the future.

• Betty YS Kim

  28 July 2008 | 04:42

  Hello! Thank you for allowing us to share our experiences on the Forum, Ai Lin! To start, my name is Betty Y.S. Kim. I obtained my B.Sc. degree from McGill University (Anatomy and Cell Biology), followed by an M.D. degree from McMaster University. As a neurosurgical resident at the University of Toronto, I am currently pursuing a Ph.D. degree (Biomaterials and Biomedical Engineering).

  Unlike the person upstairs, I started my academic career as a molecular biologist rather than an engineer. It was a logical choice, since this was one of the subjects I excelled in school. As an undergraduate student at McGill University, I was first exposed to the beauty of medical research while working with Dr. John Bergeron. During my studies, I first began to appreciate the highly complex and sophisticated design of the human brain. This interest culminated to the point, where I decided to attend medical school to become a neurologist. During my medical training, I forced myself to remain active in the field of neuroscience research. I worked as a research student at John’s Hopkins University, where we studied neuronal proliferation and tumorigenesis. I decided then, that I wanted to become a neurosurgeon. I spent a research fellowship year at Harvard Medical School (Brigham and Women’s Hospital) during which time, I was part of the team that elucidated the mechanism of minocycline in preventing programmed cell death in a neurodegenerative in vivo model. The significance of the study was recognized along with a publication in Nature. At the time, I did not appreciate the full implications of this work. It was much later, when I realized the true significance of this publication. Although the study was conducted by a multidisciplinary team of basic scientists and clinicians with diverse expertise and backgrounds, we all had the same goal to better serve our patients. As a medical student, this research experience left a great impression on me, which later influenced my decision to enter the field of nanotechnology.

  At the end of my medical education, I began my neurosurgery training. After 4 years of surgical training, I decided to go back from the bedside to the bench. I felt that technological advances could be used to improve the field of neurosurgery. Luckily for me, the University of Toronto has always been very supportive for clinicians to participate in fundamental research. The University of Toronto has a program designated for individuals like myself to pursue research during their residency training. It is called the Surgeon Scientist Program. Therefore, all I needed to do was to choose a field, a lab and a project to work on. A feat more challenging than originally anticipated.

  When I decided to study nanotechnology, I must admit that my family, friends and my mentors in Neurosurgery were all a bit nervous. After all, I would be the first clinician scientist in Canada to study this relatively young field. Prior to entering this field, the term “nanotechnology” meant for me that self-replicating nano-robots capable of entering the bloodstream could zap away any traces of disease, but the same robots could one day take over the world resulting in mass destruction. However, I was determined to learn whether this new field could be translated into useful tools that could benefit the practice of medicine.

  After a period of extensive research, I contacted a few labs that were interesting to me. Surprisingly, many nanotechnologists wanted to recruit physicians. The growing mutual interest across disciplines made me realize that I was searching in the right direction. While looking for a lab, I realized that although the general medical community was unfamiliar with nanotechnology, quite a few laboratories around the world were already investigating potential clinical applications using nanomaterials. I was especially amazed by the work being performed by Dr. Samuel Stupp and Dr. Angela Belcher. And, in fact, Dr. Stupp at the time was looking for a neurosurgeon to work with as well. What were the odds?!

  Naturally, I was inclined to fly down to Chicago and start my Ph.D. right away with Dr. Stupp. However, after many sleepless nights, I came to the realization that I needed to stay in Toronto. A major factor being that I could still be involved with the University of Toronto’s Neurosurgery Residency Training Program, viewed as the best training program in North America, if not in the world. Secondly, both my Program Director (Dr. M. Chris Wallace) and Chairman (also my co-supervisor) Dr. James T. Rutka helped me so much and supported me from the very beginning of my nanotechnology journey, that I decided to stay here and complete my doctoral degree. It was also fortunate for me that the University of Toronto recently hired a nanotechnologist from UCSD named Warren Chan.

  I remember the first day when I was introduced as the new addition to the Chan lab. People in the lab were extremely friendly and helpful, showing me how to use instruments that I had never heard before, answering my questions and concerns. However, one particular Chinese student seemed very “unfriendly” at the time, where upon my initial “Hello”, I failed to exist. At that moment I thought to myself that I hope I would never be asked to work with this character on any future projects. Only if my wish came true…

  Due to some unexpected turn of events, we ended up working together on the project studying the size-dependent effects of nanomaterials and cells. Initially, the project seemed so far removed from what a future neurosurgeon should be pursuing. There were no technical surgeries to perform and no brain-related diseases or tissues to analyze. In the end however, since I was barely able to crawl on my own as a beginner ‘nano-resident’, I thought that this project could be used as a way to learn fundamental techniques in nanotechnology.

  At first, working with Wen required some readjustments on my behalf. As a surgical resident, among other things, we are encouraged to pay attention to the smallest details, focusing on the task at hand, meticulously performing our tasks one at a time and always planning ahead for the unexpected. I realize now, that had we adopted this approach, both Wen and I would still be doing experiments. I learned to ‘let-go’ a little, adopt his spontaneity for performing multi-experiments. I became accustomed to this highly creative student/teacher, whose fast-paced style complimented with my working habits. Looking back, the most memorable experiences working with Wen occurred between experiments. Wen would teach me the basics of nanoscaled systems. Using everyday analogies at first, he would explain quantum confinement and ‘dangling bond’ theories. These teaching sessions developed into discussions where we began to exchange ideas and to discuss science in general, while debating about the latest research updates we received from various scientific journals. It was during these times, that I began to really appreciate how far we, had come in the field of Nanotechnology. We just need that extra leap toward clinical applications!

  At some point in the life of a graduate student, we experience a sense of ‘disillusionment’ and self-doubt with our research, as experiments fail to work for months. For me, this experience occurred nearly 6-8 months of working on this project. We had worked for more than 80-90 hours per week on this project. Most of this time was spent optimizing the materials and methods, so that we could use these for our experiments. Had I been working in a molecular biology lab, the essential materials could be purchased along with a set of instructions that worked every time. To make these materials ourselves and to develop our own protocols (not to mention that we had not even come close to doing the actual experiments), I was getting a little nervous. Naturally, I began to question whether I had made the right decision to enter this field. What if we could not get this to work? What if in the end, we could not find any significant difference? What if someone else publishes before we do? What if…?

  It was yet another late night in the lab while imaging cells with the confocal microscope, when suddenly, Wen leaped out of his chair with joy and broke out into a weird dyskinetic dance-like movements. This was the first time that I had seen Wen in this state, and therefore, without even looking at the results, I knew that something he had initially observed, was significant. We were finally observing what we had predicted would be happening! There are two key moments in our journey together as graduate students that I will vividly remember. This was one of them.

  This initial excitement was quickly met with the reality of verification. All experiments had to be triplicated, re-repeated and re-validated using different techniques. Essentially, every possible error-eliminating procedures that we could think of, had to be performed. Upon completion of these experiments, I was relieved that I was at last, writing my first Nanotechnology paper.

  Little did I know, that this was only the beginning of more experiments and hard work. It would take us another year from the completion of our experiments to seeing our work published in Nature Nanotechnology. Checking the status of our manuscript submission online was truly anxiety-filled. We were extremely excited about our findings, but do others share the same view? Then, there was this ‘Lab Legend’, where it was always best that we did not hear from the editors at Nature journals for at least 2 weeks following manuscript submission. This would imply that the manuscript was sent for external review. Nervously, I began to check the Nature Nano’s “Online Submission” section. Multiple times a day, I never failed to check the website, wanting to know the outcome, but not too soon. As each day passed, I clung to the notion that the likelihood of our paper being reviewed increased. Imagine how tough the first two weeks were on us!

  When Ai Lin sent us the letter stating that the paper was sent for peer review, a huge relief was met with a different kind of anxiety. The fate of the paper was in the hands of the reviewers now. When the first round of reviews came back, we were quite relieved that the paper was not rejected (actually, we were ecstatic!). The bad news was that additional experiments were suggested (the reviewer’s comments spanned 15 pages, single spaced!). However, many of the comments and suggestions were legitimate, and in the end, along with additional experiments and Ai Lin’s help, the quality of our manuscript improved from our original draft. The additional two months of being in the lab until the crack of dawn to address the reviewers’ concerns was all worth it for us.

  Looking back, I have found graduate studies challenging at times, but also extremely rewarding. Unlike my previous experiences, there was no deadline to finish, no studying to obtain better grades on exams. In the end, it was all up to me to decide upon my Ph.D. experience. My supervisors were very supportive and gave me enough freedom to figure things out for myself, and I will be grateful for that. For anyone considering graduate school, as long as you are interested and willing to work hard, but at the same time ready to adapt and adopt change, you can achieve almost anything!

  Now with the project finished and the paper past us, Wen will be moving onto his future endeavours down south of the border, while I follow the steps of the many before me to finish the biggest paper of my student career, the Ph.D. dissertation. I often look back on our road to a Nature Nanotechnology publication, but now, from a different perspective. No longer blindfolded by the nervousness of receiving rejections, I am slowly beginning to realize how valuable the entire experience was. It was my first complete exposure to a project from the preliminary planning stages to the eventual publication.

  Working alongside Wen, I realized that although we seemed very different on the surface, deep down we were the same: two people who were interested in science trying do discover the truth.

  Finally, before I sign-off, I would like to mention my mentors and teachers who made my journey possible. I never felt alone. I had the great privilege of crossing paths with outstanding teachers at the University of Ottawa’s Neurosurgery Program where I initially began my training. They allowed me to pursue Academic Neurosurgery, even when this meant that at the time, I had to leave their own program. Thus, I would like to acknowledge these teachers in Ottawa, Dr. Brien Benoit, Dr. Vasco DaSilva, Dr. Howard Lesiuk and Dr. Enrique Ventureyra, who are responsible for redirecting my career path. At the University of Toronto, I essentially belong to two “families”. As a surgical resident, I receive tremendous support from the Neurosurgical Staff at the University of Toronto. In particular, Dr. Christopher Wallace and Dr. James Rutka. Thank you! Overall, these individuals have served as great role models in my life, which I hope that one day, I can do the same for others. As a student of the Institute of Biomaterials and Biomedical Engineering, I also thank Prof. Warren Chan, Prof. William Stanford and Prof. Christopher Yip for having enough faith to accept a clinician into their training program.

• Ai Lin Chun

  28 July 2008 | 13:32

  Thanks very much, Wen and Betty for sharing your story. It was such a delight to read it.

  How did you both decide on Authorship of the Nature Nano paper?

  And how was the PhD thesis decided since the two of you have worked together on the project?

• Eva Amsen

  28 July 2008 | 19:25

  Good to read about some Toronto research on Nature Network =) I’m at UofT as well, but didn’t have such exciting research experiences.

  If either of you are interested (I guess Wen is too far away now) we will probably have another Toronto Nature Network pub night at the end of summer. Keep an eye on this group for details: http://network.nature.com/group/toronto
  It would be fun to share lab stories in person!

• John Anderson

  06 August 2008 | 21:18

  Hi Ai Lin!

  Sorry, I’ve been away the past week.

  To answer your question on the authorship of the paper, both Wen and I are co-first authors (as stated in “nanometer font size” near the acknowledgement section of our manuscript). When the idea for the study was first conceived, our only goal was focused on our experimental design and various strategies to address our hypothesis. We began to work efficiently as ONE team to accomplish this task. Therefore, until we were ready to submit our manuscript, the question of authorship never arose.

  Despite the ‘co-first’ authorship status, the name that appears first on the list is often quoted as being the first author. Some journals attach an asterisk behind each of the co-first authors, while others (including Nature journals) provide a description of the authors’ contributions at the end of the manuscript. Although Wen offered to put my name first on the pecking order, I knew that without Wen’s expertise, this paper would not have turned out the way it did. Thus, ethically, I felt very uncomfortable with the idea of putting my name ahead of Wen’s. To me, which name appeared first on our manuscript was not such a big issue. There will always be more opportunities to be first authors! We were just very thankful and excited that our research was of interest to the audiences at Nature Nanotechnology.

  I am currently working on my thesis right now (which is becoming more difficult than I thought!). A significant portion of my Ph.D. dissertation is comprised of our Nature Nano paper. Luckily for Wen and I, we have other projects and papers that will contribute to our dissertation. Wen discussed little of our initial preliminary findings and the theoretical basis of our study in his thesis. In contrast, I plan to provide a detailed explanation regarding our results. So in the end, things worked out well for both of us.

  Betty

• Betty YS Kim

  06 August 2008 | 21:29

  Sorry for the confusion regarding!

  I forgot that someone else was borrowing my computer at the conference and forgot to logout. So accidentally, I posted under John’s account. Thanks.

  Betty