Biochemist and neurobiologist Michael Lin is developing smart biological therapies that may finally provide the “magic bullet” for cancer. Born in Taiwan and raised in the United States, Lin spent most of his life in San Diego before attending college at Harvard and medical school at the University of California, Los Angeles. Since being appointed an Assistant Professor of Bioengineering and Neurobiology at Stanford in 2009, Lin has initiated research projects in protein engineering and neuroplasticity. One of his goals is to create tailor-made viruses that can target cancer cells within the body, providing an alternative to treatments that mercilessly kills healthy cells as well as cancerous tumors (eg. chemotherapy). He sat down with Probe Magazine to discuss his dreams and current research projects, and give a few words of advice to STEM students.
Q: What about scientific research appealed to you and what influenced your decisions to become a doctor?
I have been interested in technology and science from a very young age. I guess I never loss my childish curiosity to discover how the world works and make the world a better place. During my high school AP Biology class, I remember writing an essay about making an artificial eye that had photodetectors hooked up to wires in the brain, which could help restore vision in blind people. I even imagined it to not be attached to the head but allow it to “see” around corners. So I have always been interesting in technological applications, particularly those that improve our health. When writing this AP Biology essay, I never thought I would see this technology in my lifetime, but retinal transplants have been invented and are being used to treat blindness (the see-around-corners feature has yet to be developed). I have been fortunate that technology has developed so quickly that the dreams from a couple of decades ago are now becoming a reality.
I have always wanted to do scientific research, and the academic environment appealed to me for its freedom – as long as you can justify what you are doing and get funding for it, you can do whatever you are interested in. Medical school gave me experience with treating and diagnosing disease, and I gained exposure to clinical problems that could use laboratory based solutions. After medical school, I did not want to wait after residency and internship (would have had to wait another four years) before getting back to research.
Q: What has motivated you to do bioengineering and neurobiology research?
Biology has always been my favorite topic. Some people believe biology is just a random collection of facts, but if you are truly interested in learning how nature works, then every fact fits into a bigger understanding of how physical and chemical mechanisms underlie natural functions. I have been particularly interested in how proteins do most of the work in our bodies. Proteins are like little molecular machines, so if you are interested in machinery and biology, you end up naturally converging on proteins as an interesting research topic.
Neuroscience is interesting to many biologists for similar reasons. Think of the brain as a computational machine - it is incredibly complicated! It is a difficult organ to understand. In order to start understanding it, you need to develop and use all sorts of technological tools. An amateur scientist can create cogent theories but the hard part is understanding functions at the cellular level. So it is a very interesting topic, both from a humanistic and technological point of view.
It is harder to create treatments for the brain compared to other organs, because drugs don’t enter the brain very well and it’s hard to do gene therapy, as we don’t have good anatomical access to brain structures. The amount of funding we have spent on brain research up to date is still only a small fraction compared to the amount spent researching cancer and cardiovascular disease. Basic [background] research can take forever, but there are many cases where technological discoveries lead to faster discoveries and therefore faster medical advancements.
Q: Could you tell us a little more about your current research?
My laboratory is working on protein engineering and the development of new ways to investigate biology, with applications primarily in the neurosciences. We also use synthetic proteins to develop artificial signaling pathways that can be used as biological therapeutics to treat cancer. Our research is motivated by the conviction that we cannot just treat and cure cancer by only somewhat differentiating cancer cells from normal cells and targeting signaling pathways present in every cell. Except for some pediatric cancers, we cannot poison the body and completely eliminate cancer. In adults, cancer always finds a way to mutate and metastasize. Since cancer is a genetic disease, what we really want is a therapy that is specific to the mutations driving cancer. Our laboratory has been developing a method for activating a designed signaling pathway based on whether or not a cell has a particular cancer mutation. The hope is that if we can achieve high specificity and sensitivity with these artificial signaling modules, then we can link them up to whatever therapeutic effect you want - whether it is by killing a cell or driving replication of a virus to kill the cancer cells. So we want to create a smart cancer therapy that can provide long-term solutions.
Q: Many scientific authors have described cancer as an evolving goliath. Do you believe there is a “magic bullet” for cancer?
I think a cure can be developed. We can create therapies that can target any known pathway defect in a cell, which will have a finite number of defects to target. We would create a collection of viruses that can enter and only kill a cell that has this pathway defect, giving us many of these “magic bullets”. Therefore, the treatment my laboratory is developing is a different paradigm from typical cancer treatments like chemotherapy, which are targeting things that cancer cells might use more than other cells but are still present in normal cells. We are trying to use synthetic biology to make responses that are truly specific to cancer cells. We are working on our first pathway - I guess we are not too close to finding the cure for all cancers, but we hope that once we successfully target one defected pathway, it will be easier to construct the treatments for other pathways.
Q: Do you have any advice for students interested in the sciences?
Get involved in research early if you are interested in science or in medicine! However, it is not just about working in a lab - you only get as much from the experience as the energy and time you put in. Doing something as menial as a western blot can be very difficult at first, but it is worth spending the time to master these types of laboratory skills. You want to get to the point where you are technically fast at things. Once you lower the barrier to getting an experiment completed, the faster you get your results and the more things you can test. At least in biological engineering, even with the best ideas, you cannot always predict how things are going to work, so you need time to try a lot of different approaches.
Also, it is important to master the fundamental knowledge taught in science courses. Creativity without knowledge can be very unproductive, which means it is important to stay curious and open minded about the information you learn. There is no substitute for going out there and trying things and truly understanding what you are doing in classes and laboratories.