Ludwig has a long history of pioneering cancer discoveries. Today, Ludwig scientists around the world are collaborating on new projects, and on ways to move breakthroughs toward the ultimate goal of patient benefit. These are some of the novel ways Ludwig researchers have teamed up to advance our understanding and control of cancer.
Unboxed: Q&A with Sangeeta Bhatia, investigator at Ludwig MIT
What inspired you to adapt technologies developed in the computer industry for medical innovation?
As the daughter of Indian immigrants, I like to joke that the three career paths open to me were doctor, engineer or entrepreneur. When I was in high school my dad thought I’d be a great engineer. I was strong in math and science and liked tinkering, but had no conception of what engineering was. He took me to visit a family friend in mechanical engineering at MIT who was trying to use focused ultrasound to heat tumors for cancer therapy, and the idea that engineers could use instruments to impact human health grabbed hold of me and has never let go.
Why are tiny technologies important?
Billions of dollars have been invested in miniaturization. Think about how computers transformed our lives when they became small enough for us to carry around in our pockets. The decades of work by engineers that have gone into creating instruments to make our computer chips faster have created a set of technologies that now allow us to address human health challenges like cancer and infectious diseases. So we’ve borrowed these tools to tackle complex problems like drug toxicity, tissue regeneration and cancer therapeutics. In my lab we’re using them to model human disease, monitor the body and make artificial organs.
How are micro-livers used in research?
We developed artiﬁcial human micro-livers by using techniques for semiconductor microfabrication to ‘print’ colonies of human liver cells amidst supportive neighboring cells. We can use them to test new drugs that are potentially harmful to the liver and also study the pathogens that uniquely infect the liver. Our platform is being commercialized through a spin-off company called Ascendance, which manufactures the micro-livers at scale and distributes them to pharmaceutical companies to test drug safety and metabolism in liver cells before doing clinical trials. Today, over 40 companies around the world use them. We’ve also used these micro-livers to study infectious diseases that affect the liver such as hepatitis C, hepatitis B and malaria.
What project really energizes you right now?
That’s like trying to pick a favorite child. One that I’m very involved with at the moment is our cancer detection project. We developed a technology that relies on nanoparticles that interact with tumor-associated enzymes called proteases, each of which can release hundreds of biomarkers that are detectable in a patient’s urine. We are working on ultrasensitive detection of a panel of proteases involved with the spread of colon cancer to the liver (a process known as metastasis). So far, the test is more sensitive than existing blood biomarkers or imaging methods for this tumor type (in mice). We now need to figure out how to bring this technology to patients. This raises many questions that sit at the nexus of our science, oncology, regulatory and commercial landscapes.
How successful has Keys to Empowering Youth been in encouraging young girls to pursue science and engineering as a career?
We don’t have comprehensive data— just 23 years of experience and lots of anecdotes from girls who have come through the program and have been inspired to pursue careers in science and engineering. Several have gone on to the Women’s Technology Program, which is an undergraduate summer residential program here at MIT. One student came to us because her grandmother reached out to say how influenced her granddaughter had been by her early exposure at MIT. We invited her to spend a summer doing research with us while she was at Carnegie Mellon and she’s now pursuing graduate studies in biomedical engineering. Stories like this are one of the main motivators for making myself visible. While it can be more comfortable to stay in the lab and not talk to the press, I believe you can’t be a role model if people can’t see you. Once these girls have been to one of our Saturday workshops and see women training to be scientists and engineers and get hands-on experience in a lab ﬁlled with the coolest technology, we hope they begin to understand and appreciate how much engineering impacts all of our lives. And how they can play a part in it. Whether it’s inside their smartphones or whatever new gadget they’re playing with, engineering is behind it.
How close are you to engineering a liver from scratch?
Engineering complex tissues, like the liver, to be available on demand for patients in need is a grand challenge. It is in the category of ‘truly lifetime difficult’ and clinical trials remain years away, so it’s doubtful I’ll be done in the next decade. One of the biggest challenges is the problem of scale: we need a liver with billions of cells to support a patient. One approach we’re taking is to pair engineering scale-up methods (like 3D printing) with biology scale-up methods (like triggering regeneration). Together with Chris Chen’s lab at Boston University, we’ve recently shown this combination approach can help grow an organ in situ by about 50-fold.
How did it feel to win the Lemelson-MIT Prize?
It was truly incredible. The award is given for both proliﬁc invention and for inspiring the next generation. As a scientist, an engineer, a doctor, an educator, an entrepreneur, a diversity advocate and a daughter of immigrants, I don’t ﬁt neatly into any one box. So, being recognized as an inspirational inventor crystallized all these disparate roles into a cohesive one for me. More than anything, I lead a team. Everything we accomplish is the product of creativity and innovation, of everyone sharing ideas and working hard together. So, the award is really for the whole team, past and present.
Why is it important to encourage a spirit of tinkering in your lab?
We’re in a profession that has a high failure rate and the pace of research can seem unreasonably slow. On top of that, Cambridge is a veritable pressure cooker and the elite institutions are full of brilliant people trying to carve a path for themselves. I think there needs to be a way to remember why you’re here and why you chose this profession. So in order to keep the invention process fun in my group, I have the students spend 20% of their time outside of their difficult and important projects doing what we call tinkering—just playing. To spark creativity, to stay curious, to be inspired. Not all of these projects turn into wonderfully productive ideas. Some of them never go anywhere, but then again, some of our biggest breakthroughs have happened this way, too.