It’s a whole lot easier to study and understand something when you can actually see it. No surprises there. What you might find surprising is that we’ve been doing that for a couple of thousand years. The use of lenses to magnify something small seems to have started all the way back in ancient Rome. The oldest glass lenses that we’ve discovered so far were made over 2,000 years ago. They were more similar to modern-day magnifying glasses than microscopes. Just a simple piece of curved glass used to bend light and magnify something small. These early lenses were capable of making images appear 2 to 20 times larger.

As technology advanced throughout the centuries, microscopes continued to evolve. By the mid 1600s, microscopes were capable of magnifying up to 270 times! This allowed scientists to observe the first-ever living cells. Today, the same principle of getting a closer look is one of the most powerful tools we have in cancer research.

Nowadays, modern microscopes don’t even rely on traditional white light: we use lasers. Certain molecules emit light when they’re hit with a laser. These are called fluorophores. We can modify these fluorophores to attach to specific structures in a cell, like a specific protein. With modern biological technologies, we can even genetically modify cells so that they have these fluorophores built into their natural proteins! So when cells have these fluorophores, we can blast them with a laser. Then, we can collect all of the light that’s emitted by the fluorophores. This lets us track specific targets in our cell with incredible resolution.

This lets us look at more details than just the size and shape of a cell. We can look at specific organelles, which are like the organs of a cell. We can look at different proteins and where they are in the cell. We can also use multiple fluorophores at the same time to watch different proteins interact. The most advanced microscopes are capable of something called “super-resolution microscopy”.

Now, that’s pretty good, but it still has its limits. We still lose some information about the details of smaller structures. So… what if I want an even closer look?

The microscopes we’ve talked about so far use light either in the form of lasers or in the form of regular white light. If we want an even better picture than with light microscopes, we have to turn to electron microscopes. Electron microscopes shoot a beam of electrons at a cell and detect them as they pass through or reflect off the surface. We can then reconstruct an image based on how the electrons were reflected or how their path was altered as they passed through the cell.

That sort of scale is nearly incomprehensible. If you magnified a strand of hair that much, it would appear roughly five kilometres wide. This gives us high enough magnification that we can begin to see the physical characteristics of single proteins, much less organelles.

The use of microscopes in a clinical setting isn’t as common as in a lab, but they’re still an essential tool for diagnosis and even treatment. They’re most often used to help diagnose cancer. Cancer cells appear quite different compared to our healthy cells. They have different shapes and sizes, and they also express certain markers or proteins that our healthy cells don’t. When clinicians take a biopsy, they take a small piece of tissue. That tissue can be sliced and stained with fluorophores that attach to cancer-specific targets. They can then be looked at under a microscope. If they stain positively, we know that there are cancer cells present.

Microscopes can also be used to treat cancer directly. Surgery requires steady hands and exceptional precision. Microscopes can help magnify the surgical site. This makes it easier for a surgeon to remove tumour tissue while preserving healthy tissue in the surroundings. Microscopes are also used in a process called Mohs surgery. This process is most commonly performed on skin cancer. It combines the use of microscopes for diagnosis with surgery. A surgeon will remove a thin piece of tissue at a time. Each time, the removed piece is immediately stained and looked at under a microscope. If there are still cancer cells in the tissue, the surgeon removes another layer. Then, rinse and repeat until there’s no more cancer. This helps surgeons guarantee the removal of cancer while limiting excessive tissue removal.

What’s more intriguing are some of the proposed uses for microscopes to help inform treatment regimens. One of the challenges to cancer care is picking the right treatment. We have a lot of tools at our disposal, so knowing which to choose can be hard. Some clinicians and scientists have proposed using microscopes to help inform that decision, ensuring the correct choice of treatment as soon as possible. Intravital microscopy uses fluorophores, those glowing molecules, injected into the blood. A microscope is then used to observe the fluorophores in the blood so we can reconstruct an image of the blood vessels. This could be used to look at the blood supply to a tumour.

If intravital microscopy finds little to no blood supply at the tumour site, chemotherapy wouldn’t even be able to reach the cancer. This could tell us to stray away from chemotherapy, for example.

Getting a close look at what you’re studying makes a lot of sense. We’ve been perfecting this technique since ancient Rome, where simple lenses were used to make objects appear larger. Nowadays, we use lasers and electron beams to reconstruct images at up to 50 million times magnification. These tools let us dive into a subcellular level in cancer, looking at how proteins interact or how the cell changes in response to treatment. They tell us how cancer works, which helps scientists make discoveries and create new treatments. They’re also a powerful tool in the clinic; they’re essential to cancer diagnosis and even some treatments. They can be used to help ensure treatments are as effective and safe as possible. Getting a closer look is a simple principle, but it’s one of the most powerful tools we have against cancer.

I hope you learned a little something this week, but next week we’re taking a closer look at a wild new way to kill cancer: molecular jackhammers.

See you next week!

If you missed last week’s letter, you can read “A Dangerous Game of Hide and Seek” to learn a little more about how cancer evades the immune system.