Better View For Scientific Insights
Medical research is highly dependent on studies on animal models, and our progress in medicine has been deeply influenced by better analytical methods, including all the components of multiomics: genomics, transcriptomics, proteomics, metabolomics, etc.
But sometimes, much less advanced observations are the most useful. For example movements of organs, size of veins, etc. This is trickier than it sounds, as it is not practical nor possible with a reasonable budget to use advanced imaging techniques like scanners and MRI on thousands of mice per month.
Ideally, researchers would like to be able to look directly into the body and organs of the test specimens, and at the lowest cost possible.
This might just become a reality, thanks to the work of no less than 21 researchers at Stanford University. They discovered that a common dye molecule used as food coloring can essentially make the body of mice “transparent” for analysis, and published their results in the prestigious publication Science, under the title “Achieving optical transparency in live animals with absorbing molecules”.
How to See Through Bodies
The research started by observing the limitations of many deep-tissue optical imaging methods, including two-photon microscopy, near-infrared-II fluorescence imaging, and optical tissue clearing.
All of them provide some insights, but either lack sufficient penetration depth and resolution or are unsuitable for living animals. So good internal visualization of living animals is still very much an unsatisfied need among biologists and medical researchers.
The researchers theorized from a physical principle called the Lorentz oscillator model. Without going into deep detail about the implied physics, it is a principle determining how atoms react to electromagnetic waves (which include visible and non-visible light).
From this fundamental principle, the researchers deduce that specific molecules would, when dissolved in water, increase the refractive index of water-based solutions.
In turn, this would make the water and lipids have almost the same refractory index, making the whole body equally transparent to certain light frequencies.
Source: Science
“We predicted that dye molecules with sharp absorption resonances in the near-ultraviolet spectrum (300 to 400 nm) and blue region of the visible spectrum (400 to 500 nm) are effective in raising the real part of the refractive index of the aqueous medium at longer wavelengths when dissolved in water.
As a result, water-soluble dyes can effectively reduce the RI contrast between water and lipids, leading to optical transparency of live biological tissues.”
Finding Tartrazine
From what was a theoretical insight, they went on to look for a real dye molecule that would match the required characteristics. They found that tartrazine, a common food dye approved by the US Food and Drug Administration (FDA).
They found that tartrazine had the effect of reversibly making the skin, muscle, and connective tissues transparent in live rodents. Testing on tissue-mimicking scattering hydrogels and ex vivo (sampled/extracted) biological tissues, they also found that the image resolution could be scaled down to the micrometer level.
Source: Science
“Transparent” Mice
In practice, it meant that under the right light conditions, the researchers could observe the deeper tissues, seeing through the skin and surface tissues of the mice.
Source: Science
By using absorbing dye molecules, we can transform the typically opaque abdomen of a live mouse into a transparent medium. This “transparent abdomen” allows for direct visualization of fluorescent protein–labeled enteric neurons, capturing their movements that mirror the underlying gut motility in live mice.
This approach could be used for other parts of the mouse’s body than the abdomen, like for example “the scalp of a mouse head for visualizing cerebral blood vessels and to the mouse hindlimb for high-resolution microscopic imaging of muscle sarcomeres”.
This also suggests that other similar agents could be discovered and put to use, maybe with even greater efficiency, and lower cost of easiness of use.
Investing In Biological Imaging
Since the beginning of modern medicine, scientific progress has been carried by improvements in observation tools, from the first microscope to today’s genomic sequencers.
This is still true today, with plenty of new techniques emerging, from the discussed here “transparent” mice to advanced 3D visualizations of living tissues.
If you are not interested in picking biotech or medical imaging companies, you can also look into ETFs like Global X Aging Population ETF (AGNG), ARK Genomic Revolution ETF (ARKG), or Vanguard Health Care ETF (VHT) which will provide more diversified exposure to capitalize on the growing longevity healthcare and biotech industry.
Or you can consult our article on the “5 Best Genome Sequencing Companies”.
Medical Imaging & Data Companies
1. Illumina, Inc.
Illumina is the leading genomics company, by far the largest and most established in the industry, with $1.2B in revenues, which grew 11% CAGR in the last 5 years.
Source: Illumina
Like most genome sequencing companies, Illumina makes money when selling the sequencers, but mostly when selling the consumables used by the sequencers, with revenue per machine usually growing over time as it gets progressively used to full-time capacity.
The company’s new genome sequencer model, NovaSeqX, is a hit, with 390 shipments in total for 2023. This has accelerated the adoption of mass genome sequencing among Illumina’s clients with more multi-omics analyses (mixing multiple “-omics” techniques) and larger scale for single cell and spatial analyses.
When discussing Illumina, a long explanation is required for a new genomics application, cancer detection in a blood sample called liquid biopsy. Illumina worked on this technology and then spun it off into a company called Grail.
Grail is very successful from a technical and commercial standpoint, with 7,500 providers prescribing Grail’s tests and passing the 100,000 tests performed milestone. It also detected 92% of cancer relapse across 6 different blood cancers.
Several years later, Illumina would reacquire this company at a much higher price.
This caused several problems. First, regulatory authorities in both the USA and the EU raised concerns about monopoly risk, with Illumina the supplier of genome sequencing machines to many of Grail’s competitors.
This resulted in a €432M fine from the EU. If this ruling forbidding the acquisition is not solved, “Illumina will divest Grail within a year if it does not win its challenge in EU court.”
Source: Illumina
Another set of problems came from the conditions of the costly Grail spin-off, money raising, and re-absorption into Illumina.
Activist investor Carl Icahn has attacked the company’s board and implied that potentially dishonest or malicious dealings were done in favor of insiders against the interests of the company’s shareholders. The SEC is also investigating the question.
So far, the CEO has been changed, another board member has departed, 4 new board members have been instated, and Illumina has published a “Stewardship-Focused Update.” You can also read more about these suspicions and accusations in this series of articles by Non-GAAP investing.
The company stock has fallen steeply from its highs of July 2021 by almost 80%, back to its 2013 levels.
This was a rather shocking situation for a large and established company like Illumina, no matter how true these accusations are or not, as it reflects poorly on its management decision to divest Grail in the first place. At the very least, this has proven to be a costly mistake.
Investors will want to assess if they are ready to tag along with Carl Icahn, a legendary and controversial activist investor with an impressive track record.
And if the poor governance of the last few years is now fully priced, and maybe has damaged the company’s valuation excessively compared to its very strong business leadership in genetic sequencing.
2. 10x Genomics, Inc.
10x Genomics is a leader in spatial biology, which studies the genome and transcriptome in 3D, allowing visualization of the activity of genes at the cellular or even intracellular level.
The company was founded in 2012, with Serge Saxonov among its founders, the director of R&D of the personalized genome testing company 23andMe.
10x Genomics grew using a mix of R&D ($1B+ investing in R&D so far) and acquisitions. Notably, its Visium platform was obtained through the acquisition of Spatial Transcriptomics in 2018.
Source: 10x Genomics – 10x Genomics acquisitions timeline
This is also how 10x Genomics would acquire its Xenium platform by acquiring Readcoor and Cartana in 2020.
In 2020, it would also launch the Chromium platform, which was updated the year after to Chromium X.
Through the acquisition of Tetramer Shop in 2021, 10x Genomics would also launch BEAM (Barcode Enabled Antigen Mapping) in 2022. It allows researchers to identify components of the immune system in detail. This could be very impactful in research on immunity and new diseases.
Revenues grew by 17% year-to-year in Q2 2023, driven by Xenium sales, with the 100-unit sold milestone passed in August 2023.
The company also earned in September 2023 a critical victory against its main rival, Nanostring. Nanostring is for now banned from selling its CosMx Spatial Molecular Imager (SMI) instruments in most of the EU for infringing on 10x Genomic patents.
The company is still at an early stage, somewhat similar to the early days of Illumina. For now, spatial biology is confined to the world of academic and fundamental research. But like many biotechnologies, it might one day become widespread, slowly become a medical tool, and then into a “routine” test. In any case, the growing pool of installed machines should drive sales of consumables and revenue growth.
