A Resolution Revolution Sheds Light on the Living
At Lux we back companies that are bringing light to solutions to problems that have kept us in the dark. These ideas exist at the edge of possibility and may not seem obvious to the masses. But this exploration and going deep into the seemingly crazy potential of a technology is what brings science fiction into science fact and we love that. Our founders shed light on the future, which is why we’re called Lux, which is Latin for light.
We are currently at the threshold of a biological imaging revolution with new abilities to track in real time the molecular components of life in situ. This “resolution revolution” will allow scientists to ask questions they didn’t know they had and to gain insights previously thought impossible. The potential is limitless, virtually untapped.
Here’s why we’re excited.
Digitization and automation in biological research has introduced additional potential for advancement. In molecular biology, for instance, AI and digitization have enabled the likes of the life sciences company Illumina to make incredible advances into genomics and sequencing, resulting in the changing of diagnoses and disease treatment.
The commercial impact of these advancements has been billions of dollars created. The previously mentioned Illumina, Thermo Fisher, Agilent, 10x Genomics, Guardant Health, Exact Sciences, Foundation Medicine and Twist Bio to name a few, are great examples of this successful molecular digitization and commercialization.
Up until recently, the advancements in structural biology have been far less dramatic. Why?
The simple answer is the technology and tools have lagged far behind those in molecular biology. Think of the microscope, which has been the standard technology for hundreds of years. Innovation has been minimal and slow, at best. Large incumbents like Zeiss Group, Leica Camera and Olympus Corporation have very little incentive to innovate and are not built to fully digitize. If scientists can’t see what they’re studying clearly, insights will be limited. The slow pace of innovation was partly because science wasn’t ready for the output that rapid innovation could produce. Output isn’t useful if there is no system and infrastructure to process it to produce useful findings.
Another drawback has been the limitations in static imaging. When using the microscope, the specimens are dead or frozen and taken out of the organism where we lose the ability to track the dynamics of the molecules inside the cells. The view under the microscope was simply a snapshot of an extracted specimen so the outputs and insights were bound to be limited. Also, staining the cell — the process where key parts of the cell are stained with dyes — can be useful but also produces artefacts created by the chemical properties of the stain rather than revealing an authentic part of the cell. Naturally, this limits a real understanding of multicellular organisms.
With the advent of exciting new imaging techniques, this is about to change to such a magnitude that scientists in the field are breathless at the possibility of a new age of exploration.
Just as imaging democratized space, analytics, business intelligence, security mapping and real estate, the advancements in biological imaging are likely to produce insights that existed only at the very edge of our imaginations, if at all.
Cryo-electron microscopy (cyro-EM), a technique that had languished in the lab due to its low resolution structure, has come of age in the last decade with dramatic breakthroughs in hardware and software. The advancements in the technique can reconstruct the 3-D shape, or structure, of the molecule at atomic resolution. The method has dramatically changed how we can determine the shape of a protein, which previously had been limited by the standard use of X-ray crystallography. A team working on the advancements of cryo-EM subsequently won the 2017 Nobel Prize for Chemistry because of the potential of this technique to enable scientists to examine disease molecules up close. Scientists used cyro-EM, for instance, to compile a detailed structural profile of an enzyme implicated in Alzheimer’s.
Also within the last decade scientist and 2014 Nobel Laureate Eric Betzig and his team adapted a technique used by contemporary astronomers: adaptive optics (AO), combined with lattice light microscopy to create detailed, 3-D “movies” showing intricacies of the cell in vivo.
What’s fascinating about this advancement is the symmetry to Galileo’s age of exploration when he discovered that when he took his telescope that had, up to that point, been fixed on viewing the stars, and used lenses with a shorter focal length, he could produce microscopic images. Fast-forward to the 21st century and it is fascinating to see that AO, which has been used in astronomy to increase the knowledge of distant galaxies, can be utilized on the smallest form of life to bring an unprecedented understanding to living organisms. Combining advanced optics with lattice light microscopy allows scientists to observe 3-D ‘movies’ of cancer cells crawling through blood vessels, spinal nerve cells wiring up into circuits and immune cells cruising through a zebrafish’s inner ear. It’s biology in ‘real-life.’ Adaptive optics is that unicorn technology that will provide scientists with exquisite resolution AND viewing penetration of virtually any layered, 3-dimensional tissue. Embryos to organoids can now be viewed at any GPS location on the x, y and z axis while maintaining tissue integrity and hence a greater parallel to seeing what actually happens inside an organism.
Calling this a biological revolution is no exaggeration and the future is swiftly coming into focus. Knowing the potential impact of these imaging advancements, scientific teams behind both of these imaging techniques are working to make the technologies more affordable and mainstream with an open source approach. Plans for scientists wanting to make their own microscopes based on Eric Betzig’s are readily available and his desktop version of the microscope is available to those who apply to use it.
Today, these kits still require the expertise of engineers, physicists and biologists but the day is fast approaching when these democratizing technologies are “out-of-the-box” systems. Henderson, who won the 2017 Nobel Prize for Chemistry for improving the Cryo-EM technique, is campaigning for companies to develop more inexpensive but useful cryo-EM microscopes that could lend themselves to greater adaptation of the technique.
As these imaging techniques become mainstream and affordable, there will inevitably be more research that will yield more data; there is potential for a tsunami of data, which will create completely new questions to explore.
This presents an entirely novel and exciting challenge. This influx of data will create a demand for a system or infrastructure to handle the vast amounts of data. For example in the past few months, submissions to the Electron Microscopy Data Bank (EMDB) have increased exponentially. We liken it to what Adobe Photoshop did for digital images in photography. If we want the research and findings to progress at the pace of the imaging advancement, research institutions will need to invest in this area so that the data is useful for additional scientific discovery. And let’s not forget about what the role of deep learning and AI can play in this data. It can produce completely new datasets and will create additional need for computational biologists and data scientists. Just as nearly every new biotech venture formed today incorporates sequencing, bio-informaticians and data scientists, our prediction is that over the coming years new ventures will wrap in functional departments with imaging expertise.
We’re only beginning to imagine what we will be able to do with the new insights from structural biology combined with the advances in molecular biology. It’s entirely possible that, as in Galileo’s time, we could adopt an entirely new worldview with an unprecedented context. Revolutionary imaging in biological research can produce radically improved insights, understanding and discoveries, which ultimately will result in new, efficient therapies for patients.
We are poised at the edge of a newly-enlightened age in biology. The future certainly looks very bright. To get there, we partner with founders with insatiable curiosity working on technologies that seemed possible only in science fiction. It’s through this magical combination that biological research is finally coming out of the darkness of stagnancy and advancing with intricate imaging that is literally using light in an entirely new way to view the very essence of life.
