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Usually on Journey to the Microcosmos, we spend our time delving into the microscopic world and the surprising things that microbes have to teach us. But today, we would like to talk about Hank Green, and what was his cancer.

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Stock video from:
https://www.gettyimages.com/detail/video/close-up-shot-of-microscope-stock-footage/860443522
https://www.gettyimages.com/detail/video/death-of-gfp-expressing-cells-in-culture-stock-footage/511777412
https://www.gettyimages.com/detail/video/human-prostate-cancer-cells-in-culture-stock-footage/518876990
https://www.gettyimages.com/detail/photo/photomicrograph-of-lymph-node-with-hodgkins-disease-royalty-free-image/1429546115
https://www.gettyimages.com/detail/video/hela-stock-footage/511505228
https://www.gettyimages.com/detail/video/cervical-cancer-under-light-microscopy-zoom-in-different-stock-footage/1196772769
https://www.gettyimages.com/detail/video/non-hodgkins-lymphomas-under-microscopy-zoom-in-stock-footage/903165546
https://www.gettyimages.com/detail/video/radiology-technologist-sitting-in-the-control-room-while-stock-footage/1309331004
https://www.gettyimages.com/detail/photo/classical-hodgkin-lymphoma-mixed-cellularity-royalty-free-image/1409522737
https://www.gettyimages.com/detail/video/hela-cells-in-culture-stock-footage/519876986
https://www.sciencephoto.com/media/907517/view

SOURCES:
https://www.ncbi.nlm.nih.gov/books/NBK542333/
https://royalsocietypublishing.org/doi/epdf/10.1098/rstb.2014.0219
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860064/
https://www.nature.com/articles/bjc2017398
This episode is sponsored by Squarespace.

Go to squarespace.com/microcosmos to get a   free trial and 10% off your first  purchase of a website or domain. Hello.

Some of you already know this  about me, but I’m Hank Green. And this was my cancer. Now, usually on Journey to the Microcosmos,  we spend our time delving into the microscopic   world and the surprising things  that microbes have to teach us.

And oddly enough, that's actually  going to be a part of our journey today. Because yes, everything does  eventually go back to microbes. You and I are made up of tiny cells.

And sometimes those cells don’t  do what we want them to do. For example, lymphocytes are a type of white blood   cell whose job is usually focused on  fighting off infections in the body. And like every other cell in the body, it is  important that they do not grow out of control.

And that’s actually very tricky to manage,  because any trait cells happen   to acquire that allows them to make  more of themselves will result in there being more of them and thus more of that trait. Evolution doesn’t stop just because  cells are part of a larger body. In my case, my lymphocytes did  begin to grow out of control,   leading to a type of cancer  called Hodgkin lymphoma.

And thanks to a number of  factors including good treatment,   the cancer is now, as far as we can tell, gone. And when I started this journey, there  were obviously a lot of feelings to feel. But one of those feelings was surprise over just how  much microscopy was involved in the diagnosis.

Maybe this is less surprising to other people. But in my head, things were  going to come down to some   kind of DNA test or something  vaguely more computer-y. But when I talked to my oncologist, he explained  that the diagnosis was the result of experts   using their eyes and their experience and their tools to decide if what they were looking at under the microscope is cancer.

These slides contain a small portion of my lymph   node that was removed and subjected  to immunohistochemistry staining. Basically, we use molecules that have two parts… one part sticks to specific molecules  and the other part has a visible color. If you put that molecule on the cells,   it will only stick around (and thus be visible)  if the specific molecule in question is present.

These are the “stains,” and we do this  a bunch of different times with a bunch of different stains to see what combination   of molecules are present on or in a cell,  and that tells you what kind of cell it is. Buried in a Hodgkin lymphoma  tumor are a number of   cells that are like lymphocytes, but wrong. Instead of ordered circles, they’re  larger and kind of mushy in shape,   and they have multiple nuclei.

These cells are called Reed-Sternberg Cells,   named for the past masters of  microscopes who discovered them: Dorothy Reed Mendenhall and Carl Sternberg. But to fully confirm what you are seeing,   you need staining to find the molecules that  Reed-Sternberg cells tend to have plenty of. My biopsy report said that, quote, “The large atypical cells are positive for  CD15 and CD30 with dim positivity for Pax5   and occasionally positivity for CD20,  but BCL2 and CyclinD1 were not present…" all of those are surface proteins  that different stains can attach to.

Knowing all of that information,  the result was, quote, that “the histological features are most compatible  with mixed cellularity classic hodgkin lymphoma,” unquote. Which, when I read these words, were  actually a huge relief because, at that point,   we knew that I had cancer, and Classic  Hodgkin’s was the best possible scenario. Anyway, that’s how you can find  cancer under the microscope.

There are other techniques  needed to study biopsies   and confirm the presence of cancerous cells. And there are other tests involved  in diagnosing a person with cancer. But it’s remarkable that,   at the end of the day, this complicated  and destructive disease is something… you can just see.

Every day, someone is looking under  the microscope to see whether the   slide in their hands holds someone’s cancer. But there’s something else that  cancer has made me think about. It’s this idea that maybe a cancer  is kind of its own type of organism,   a reversion of sorts to a past that  is of course also very much present: the life of single-celled organisms.

We spend our days here on Journey to  the Microcosmos swimming among them,   watching bacteria swarm and ciliates attack. And it’s not that a cancer is a person's cells becoming those organisms. But rather, maybe something even weirder.

But to get there, let’s look  at the reverse and talk about   how organisms were able to become  multicellular in the first place. Within the microcosmos, one of the  organisms that has helped scientists   understand the transition from unicellular  to multicellular life is the Volvox. It looks a bit like a green golf  ball studded with large craters.

But what we’re really looking at  is a group of thousands of cells— something that resembles multicellularity. Volvox is a member of a group of  algae called the volvocine algae. And as we sift through its relatives, we can see  what feels like a reversion to single-celled life.

There’s the slightly simpler pleodorina,  then simpler again with the eudorina. And from there, we go to the pandorina,  the gonium, and then the simplest of all: a unicellular flagellate chlamydomonas  that looks similar to these algae. It’s like a tightly edited evolutionary  flipbook, played in reverse.

The cells feel less and less connected,   their groupings becoming smaller and they feel less purposeful compared to the volvox. And we’re highlighting the volvox in  particular because it’s a story of   transition that scientists have been studying to  better understand how life became multicellular. It of course cannot encompass the entirety of that transition, nor can this single organism   answer the question of whether cancer  is a reversion to single celled life.

But the differences across the volvocine algae,  and the way that the volvox in particular   survives, highlights the very features  that our own bodies rely on to survive— features that cancers subvert. Volvox requires its cells to cooperate. The cells have specialized purposes,   with the tiny somatic cells on the outside  helping to move the volvox around, and the   giant gonidia cells on the inside serving as  the volvox’s reproductive organs of a sort.

And they’re all embedded in an extracellular  matrix that holds them in place. For the organism to survive as a whole,  the cells have to know their place. One idea that scientists have about cancers is  that the cells involved in these diseases are   essentially finding ways to defy the aspects  of cooperation that multicellularity built.

Things like division of labor, the  maintenance of an extracellular environment,   and the way that resources are allocated— cancers cheat at those. Now based on what I’m saying, you might  be wondering if that means that the   transition from unicellular to multicellular  life is also marked by the presence of cancers— whether we can find the disease in  other seemingly simpler organisms. And the answer is maybe surprisingly, yes.

Sort of. A 2015 paper called “Cancer  across the tree of life: cooperation and cheating in multicellularity”  looked at cancers and cancer-like phenomena   across a variety of organisms, including  some Journey to the Microcosmos favorites,   though we have not personally  observed these phenomena. For example, planarians that have been  exposed to carcinogens develop tumors.

And in the cnidaria phylum, both corals and hydra  have been observed with their own sorts of tumors. Now we should note that it’s not just that  these organisms are developing tumors. It’s that those formations involve behaviors that  seem similar to what we see in cancers, whether   that’s something going wrong in differentiation or  a loss of the division of labor or something else.

And even our friend the volvox can have  its own cancer-ish thing, with mutations   messing up the identities of  those distinct cell types. The idea of cancers as a return to something more  ancestral is called the atavistic model of cancer. And the scientists pursuing this theory are  grounding it in the specific genetic and   cellular pathways that contain components present  in both unicellular and multicellular life,   and the way those pathways can  become dysregulated in cancer.

And there are also other models of cancer  with their own implications for how   we understand the disease and for possible treatments. At the end of all of this is the feeling that cancer just… looks like something— something that isn’t us, even if  it is made from the same stuff as us. It has the same DNA, and it's housed in the  same body, but if I am a bunch of cells working   together to get my genes passed to the next  generation of human, then my cancer cells were not me… they were something new.

They were a single celled organism whose most  recent ancestor was me, but they were not me. Cancers exist in opposition to the  foundations that were laid for them,   not just in ourselves, but in the  billions of years that lead to us all. Thank you for coming on this journey with us as  we explore the unseen world that surrounds us.

And thank you to Squarespace  for sponsoring this episode. Squarespace gives people a powerful and beautiful  online platform to create their website. So whether you’re looking to  create an online portfolio,   start a blog, or open an online  store, Squarespace can help you out.

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The folks on the screen right  now, they are our Patreon patrons,   the people who make it possible for us  to continue doing weird stuff like this. They are the people who are in my head  when I am emailing my doctor to say, “Hey, can you send me those slides? Because I got a really weird thing that I want  to do with my own cancer cells.” So you're great.

Thank you so much. If you want to be one of these people,  you can go to Patreon.com/JourneytoMicro. If you want to see more from our  Master of Microscopes, James Weiss,   you can check out Jam and Germs on Instagram.

And if you want to hear more from us, there's  probably a subscribe button somewhere nearby.