The joy of transcending disciplines

Science, like most any aspect of the world, has borders. But some researchers decide it’s best for them to regularly, if not continuously, leap across boundaries in their work.
Published in Protocols & Methods
The joy of transcending disciplines
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For Nature Methods, I did a Lab & Life column on scientists who enjoy being and working in cross-disciplinary ways. Here is a bit more of what I heard from researchers.

Aviv Regev says she has had privilege of spending her entire career thus far in a borderless, boundary-crossing world, so in a sense, this is the only way she knows and “this has brought richness and joy to my work and life.” It’s also a tenet fundamental to how she thinks about accelerating drug discovery and the future of research and early development in her role at Genentech, where she is now executive vice president and global head of research and development at Genentech/Roche. She joined the company in 2020.  

“If you want to exist ‘at the border’ you need to know the fields well and deeply, too,” says Aviv Regev. 

 Even before she started university, she asked herself what does one do when everything is interesting. What she ultimately did was decline to choose, she says. Within the well-defined Israeli academic system, such non-choosing was usually not easy, but she had the opportunity to enroll in the Adi Lautman Interdisciplinary Program at Tel Aviv University, where each student could explore a unique avenue, rather than a specific field or major. Students were expected to learn within each discipline “at the top level of rigor,” she says. This was an important early experience for her: “if you want to exist ‘at the border’ you need to know the fields well and deeply, too.”

Being able to pursue multiple interests at once set her on a path of fluidity and openness that has proven instrumental throughout her academic career. Regev has spent much of her career in MIT’s biology department then at the Broad Institute of Harvard and MIT, where she was also a Howard Hughes Medical Investigator.

 “When I inevitably feel frustrated by the limitations of a given field — for example, a biological problem appearing too big and complicated to address with traditional lab techniques — I tend to also see alternative possibilities: how could another, perhaps seemingly distinct, discipline help me address this limitation or answer this question?”

I love learning from people with other approaches and perspectives, and bringing my own," says Aviv Regev. 

 She does not feel she needs to belong to one specific area, “because I do not want to be restricted and limited by its confines or definitions.” As she explains, she enjoys too much being part of many areas where she can do meaningful, deep and impactful work, “and I love learning from people with other approaches and perspectives, and bringing my own.”

Regev particularly enjoys collaborations in science, both because it opens up further opportunities, within, across and in the space between fields. And because she loves working with other people. Almost invariably, collaborations last and unfold over multiple projects and many years. “The possibilities of what we can unlock together, and the joy we experience in the pursuit, increase exponentially in this way,” she says. For example, this has been her experience in many years of collaborating with immunologists around systems immunology, or with surgeons and clinical pathologists in studying single-cell genomics of tumors, or in her interactions with the large and diverse community of scientists across many disciplines within the Human Cell Atlas.    

“The possibilities of what we can unlock together, and the joy we experience in the pursuit, increase exponentially in this way,” says Aviv Regev.

All of these features play an important role in her Genentech work now. Drug discovery is incredibly difficult, and to be successful, what is needed is to bring together many disciplines: biology, chemistry, medicine, and now also computation.

“This means bringing both science and scientists together in new ways,” she says. At Genentech, we’re building a “lab in a loop” that enables the researchers to iteratively refine our science and our algorithms, she says. This interplay between biology, chemistry, and clinical expertise with new experimental and computational approaches, accelerates the work, takes the researchers in new directions, and will ultimately increase the impact on patients, she says. They are also, she says, constantly forging collaborations and building multidisciplinary ecosystems across industry, academia and other communities to crack some of the greatest challenges in science and drug discovery.

 “I see this type of boundary-crossing, or ‘science without borders,’ not as a challenge, but as an imperative in order to solve big scientific problems and nurture the spirit of scientific curiosity and discovery,” she says. “It’s fundamental to how we all make a bigger impact as scientists and bring greater, multiplicative benefits to patients and society.”

 “I see this type of boundary-crossing, or ‘science without borders,’ not as a challenge, but as an imperative in order to solve big scientific problems and nurture the spirit of scientific curiosity and discovery,” says Aviv Regev

Both her PhD and postdoc mentors are interdisciplinary scientists, says Hattie Chung. They trained in physics and computer science, then switched to biology. Her postdoc advisor Aviv Regev really allowed her “to flourish as an interdisciplinary individual,” says Chung. She had full support to pursue many diverse projects such as developing a new single-cell technique, pursuing big theoretical questions about how sensory systems work or machine learning.

Chung is postdoctoral associate at the Broad Institute of MIT and Harvard. She started in Regev’s lab when she was still at the Broad and Regev still advises her. Chung also works with the Broad’s Fei Chen. Chung led development of inCITE-seq for measuring nuclear proteins and RNA in single cells.

“Recognizing connections requires abstractions, which allow us to blur out certain details and focus on the essence that makes comparisons possible,”  says Hattie Chung.  

Interdisciplinary science, says Chung, relies on two things: picking up new techniques and knowledge quickly, and seeing connections across disparate fields. “Recognizing connections requires abstractions, which allow us to blur out certain details and focus on the essence that makes comparisons possible,” she says.  Abstractions also help with classification. Deciding which are the details to blur and which are the essence depends on the problem and it’s a question of taste, too. And it has a huge impact on whether the interdisciplinary approach works, she says.

 Being an interdisciplinary scientist is my way of pursuing a forgone career in the arts and music, she says. A large part of what drives her “is the satisfaction of finding a hidden thread between projects and ideas, even if it may not be apparent to others.”

“These mental habits from my musical training allow me to hold many things at once in my head: the details, which are always critical, and the problem abstracted at a level above,” says Hattie Chung. 

Chung was trained as a classical pianist. This training is about finding recurrent and hidden motifs in compositions. All pieces have patterns, she says. Some are explicit. For others, she was taught to find and build subtle references to motifs, and hold them in her ear as she plays because they subconsciously inform her phrasing, she says. Most listeners might not detect a pattern, but it’s there. The piece will feel different if she plays it without holding certain things in her ear. “These mental habits from my musical training allow me to hold many things at once in my head: the details, which are always critical, and the problem abstracted at a level above.”

Learning across disciplines has, she says, come with practice, mindset, and collaborations with the right people. “I like to thoroughly understand the full spectrum of a problem,” she says. “I’ve also found inspiration from reading fiction, and non-fiction on topics outside of science.”

 The irony is that interdisciplinary scientists themselves suffer from being hard to abstract and categorize with neat labels. “The key challenge that I constantly grapple with is, how to respect the knowledge that has come before us, without letting that constrain how we approach our questions?”

 Science is at a stage in which one can be once again be cross-disciplinary, says Yang Bai from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences (CAS) in Beijing. In Aristotle’s day in ancient Greece 2,000 years ago, scientists usually mastered knowledge in multiple disciplines, such as maths, astronomy, physics, among others. As information exploded in the 20th century, disciplines formed in which there was independent systemic knowledge. This led  scientists to use their limited personal energy to focus on specific areas.

“For example, biology is now highly connected with computational science, maths and chemistry,” says Yang Bai. More cross-disciplinary work will emerge with this trend.

Over the last ten years, the trend seems to have shifted, says Bai. As individual disciplines matured, they can become a tool for others and lead to interaction with other disciplines. “For example, biology is now highly connected with computational science, maths and chemistry,” he says. More cross-disciplinary work will emerge with this trend, says Bai.

In his lab, Bai works on the plant-root microbiome. And he is also part of a virtual center run by CAS and the John Innes Centre in Norwich, UK. In this work, learning and using knowledge from other research areas makes it easier to work on the leading questions in the plant root microbiome field.

When exploring a specific part of nature, he believes that we should first understand all related information about this part before deciding how to start. It’s akin to using existing rails to travel from one point to another. If rails exist, the fastest way is to find and use it rather than building a completely new one.

In practice, says Yang Bai, being interdisciplinary in one’s work is “to free our mind and try to find the best way to reach our goal.” 

In practice, says Bai, being interdisciplinary in one’s work is “to free our mind and try to find the best way to reach our goal.” We all are limited by our own knowledge and experience. “Discussing and sharing our ideas with colleagues or senior scientists who have a different or broader background may bring new ideas,” he says. Regularly learning from and reading in other disciplines also helps. Efficient collaboration is necessary and it usually makes cross-disciplinary work easier. “The farther we move out of the comfortable zone of our knowledge, the more we can achieve,” he says. “It is fun!”

 “Crossing the boundaries is no longer just optional or for fun,” says Kai-Hooi Khoo.

 “Crossing the boundaries is no longer just optional or for fun,” says glycobiologist Kay-Hooi Khoo whose research is about exploring how glycans and proteins interact at Academia Sinica in Taiwan. It has become a norm and a must, he says. Khoo did not have extensive 'omics high dimensional analysis and informatics training. Crossing boundaries means, for him, crossing the boundaries between scientific disciplines as well as across age and generational boundaries.

 In this sense, boundary-crossing is a way to become acquainted with the thinking and approaches of the next generation of scientists. This in turn, makes it possible to adapt and leverage experience, resources, and connections to propose new crazy ideas that help the younger generations bring their ideas to life. At the end, the joy is being able to accomplish what otherwise is not possible and see that one's own scientific career and vigor has been extended. And more junior scientists can feel the benefits, too.

No scientist can be like Leonardo da Vinci today and be universally knowledgable. He advises students to gain expertise in something that people the world over will seek them out for and who might be eager to collaborate. But it also matters, says Khoo, to “strive to be as widely informed and knowledgeable as possible.” Activity in multidisciplinary teams lets one pick up the languages and culture of the other worlds, so that one can understand others and be understood. “You can communicate effectively and live a rich life,” he says. “The joy is being not monotonous and too specialized to be so dry, and boring!”

“The joy is being not monotonous and too specialized to be so dry, and boring!” says Kai-Hooi Khoo

Progress in science is enabled by challenging conventional wisdom, he says. “To break your own confined boundaries indeed take courage,” he says. It’s about being prepared for what one aimed for when embarking on a scientific career, knowingly or perhaps it happened unknowingly. When one is driven by strong sense of purpose, “courage is no longer an issue,” he says. “It just comes naturally.”

 A watershed moment for Hari Shroff was when he took the Marine Biological Laboratory physiology course as a graduate student with a background in bioengineering and biophysics. During his PhD research he felt he worked hard to develop imaging tools but, he says, they ultimately failed to find good applications. “So it was a breath of fresh air to immerse myself in an environment where all the cell biologists around me were crying out for better imaging tools - it was so obvious that the science they could directly visualize depended critically on the microscopes they were using, so even an incremental advance could generate new insight,” he says. That’s when he realized that “both knowledge of the scientific problem and​​​ the means to advance the tool could be a killer combination.”

 Another educational experience that mattered to him was working with Eric Betzig and realizing that - for photoactivated localization microscopy (PALM) - the sample was the most important part of the imaging experiment. That respect for making 'good' samples or collaborating with those who could make them or teach him to optimize the sample prep “has stuck with me ever since.”

“I enjoy thinking about the same topic from many different perspectives,”  says Hari Shroff.

Shroff considers himself comfortable in multiple disciplines and “I enjoy thinking about the same topic from many different perspectives.” He has recently moved his National Institutes of Health lab to Janelia Research Campus. Perhaps a more accurate and honest way of describing this joy in thinking from different perspectives “is that 'I feel comfortable being uncomfortable,'” he says.

“I enjoy pushing myself outside my comfort zone and find it increasingly necessary as I get older,”  says Hari Shroff.

Many researchers got into science, as he did, as people who are  naturally curious and who love to learn. A novice and a beginner have much to learn, which is fun, he says. But it can also be uncomfortable, and even scary, to keep learning new things. “I enjoy pushing myself outside my comfort zone and find it increasingly necessary as I get older,” he says.  The temptation to 'coast' in areas that that he feels competent in is powerful and easy but he feels pretty sure it’s “a recipe for getting stale and not doing my best work.”

That’s why he periodically switches up what he is working on, “which also forces me to use different methods and to address different questions.” He also likes to recruit a diverse set of expertise within his lab. Ideally, he says, it’s “so that I can learn from the lab members as well as teach them what I know.” It’s why he also likes to collaborate with researchers in an array of disciplines.

The cross-disciplinary approach helps him to elevate his science and tool-building in each discipline. For example,” I've spent the last decade trying to figure out better ways of imaging worm embryos,” he says. The embryo itself is an excellent and unforgiving teacher, challenging us to find ways of improving resolution and speed while minimizing phototoxicity. Developing better imaging approaches for the embryo enabled us to 'see more' than otherwise possible, allowing us to ask more questions. Biological collaborators demanded even better microscopes - and so it goes, in a delightful circle.

 “I guess as a microscopist I am challenged by the fact that the imaging is never good enough, and if I want to develop better imaging tools, I had better understand the other discipline—biology--well enough to give me a fighting chance of improving the tool. I think frustration about current imaging approaches has driven a lot of what our lab does, but we don't just want to develop tools, we want to work closely with biologists to get feedback on the tools and ensure that they are useful,” he says.

 

A goldfish jumping from one bowl to another, larger one.

Credit/Source: Getty Images/iStockphoto. R. Tavani

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