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Report from an Exosome conference

I spent five days at the ISEV 2024 meeting in Melbourne and I would like to share some thoughts about the experience. TL:DR (too long, didn’t read)?  The bottom line is that no-one is an expert in extracellular vesicles. ISEV is the International Society for Extracellular Vesicles.

What we know


ISEV was originally registered as a Swedish non-profit organization and was headquartered in Gothenburg, Sweden. The first ISEV annual meeting took place in the Gothenburg in 2012, attracting more than 400 participants. The annual ISEV meetings have taken place ever since; Boston (2013), Rotterdam (2014), Washington (2015), Rotterdam (2016), Toronto (2017), Barcelona (2018) and Kyoto (2019). The eruption of a global pandemic in 2020, moved the ISEV meeting online for 2020 and 2021, with the return to face-to-face in 2022 in Lyon. Each one saw growth in attendee numbers.  In 2023, the annual meeting was held in Seattle, welcoming just under 1,200 participants. This week’s event in Melbourne attracted 1050 participants from over 50 countries.

I watched dozens of presentations and learned that scientists know many of molecules that make up the vesicles (bubbles) that constitute extracellular vesicles. They know how to label, track, image, count, and isolate them to a magnificent degree.

I also learned they like to party and have a wonderful community that is brilliant, supportive, courageous, and warm.

 

What we know we don't know

I would say that the really important things we know we don’t know are important.

1) How does the cell decide what to put into exosomes?

2) Are there differences between exosomes made inside the cell in batches (small EVs) versus the bigger ones that bud from the surface (ectosomes)?

3) How much of what we are measuring is being lost or changed by methods of isolation, storage, and isolation?

4) Do the cells use exosomes primarily as communication, resource sharing, or as a fundamental way of being?

What we don't known we don't know

We don’t know how cells decide how, when, why, and where to produce exosomes as a function of how they are “feeling”. We don’t know if the proteins that coat the surfaces of exosomes are there by chance or design and what the implications of that might be. We don’t know how much of the isolation procedures like ultracentrufigation are creating completely new micelles and structures that wouldn’t exist. And we don’t even know how or why the exosomes are taken up in many cases and what factors may determine their fates once internalized.

Hubris and Humility

I would like to make some anthropological observations of the 5-day experience as a clear outsider. Like Margaret Mead being pranked by Samoan teenage girls, I may be way off in my observations, but I will nonetheless attempt it.

Firstly, I was the only non-scientist in attendance other than the Audio-visual staff. A particularly humbling experience was sitting next to a PhD candidate who is nodding in response to details  of scientific methodology whereas my head was shaking side-to-side in confusion.

The folks in attendance were clearly three or more standard deviations above the average IQ (i.e. 145+) as evidenced by their ability to understand complex scientific methodology despite the very thick non-American accents of nearly all the presenters.

The ethos of the event reminded me of the Silicon Valley startup conference I attended about ten years ago- where founders and gazillionaires boasted about their failures. 

For these researchers, they seemed to delight in being wrong about nearly every dogma that they once believed and espoused and wore their previous naivete as a true badge of honor. 

In a field where you are only one paper away from ridicule or one chemical reagent away from worthless results, the order of the day appears to be humility born from hubris.

"Vienna Waits for you"

By rapidly typing into my phone, “Falco”, in response to identifying the 80s-era video “Vienna is Calling,” I was fortunate to be one of the five free admission (a $1300 value) recipients for next year’s ISEV2025 in Vienna. Will I go? Perhaps. But I’m not sure this is my tribe given the very strong bias towards winning Nobel prizes by inventing a test for some disease or some magic bullet to treat some disease with some blockbuster synthetic extracellular vesicle. They know that clinicians have never really heard of extracellular vesicles and don’t seem to have strong opinions about it. Explaining that I had been using MSC exosomes for over five years was met with pretty deep concern rather than curiosity in most cases.

Like a chimpanzee learning sign language in preparation for a job at the UN, I took copious notes and pictures of slides. Could I do a deep dive and understand most of what was said? Most likely. Will I? Probably not. 

When I struck up conversations, I was careful to not reveal too much about what I was doing in clinical practice because although most had an inkling that the use of MSC exosomes was common in the USA, their opinions were quite prejudiced against such perceived recklessness

Ironically, if no concerns over safety, ethics, regulation, or scientific rigor were in play, I am fairly certain that nearly 99% of them would say that there is little reason to believe that MSC exosomes would not be helpful in many cases. 

That said, I’m sure that 99% of them also took some form of Covid vaccination despite the majority of them being able to clearly articulate why viral spike protein therapy might not be a good idea. I can’t count on one hand the number of times these scientists boasted about the success of the Covid exosome vaccination regimes: zero.

When the topic of whether Pfizer and Moderna mRNA “vaccines” were engineered EVs came up once with a key opinion leader during our private conversation, the response I got was like what you might get from a German socialist in the 1950s who wanted to dissociate the word “socialist” from Nazism (the German workers socialist party).

In other words, none of these exosome scientists wanted to be associated with the nearly 13 Billion exosome vaccines given in the name of Covid mitigation. A researcher even told me the Lancet Journal threatened a scientist when they did submitted an article touting the benefits of hydroxychloroquine.

Interestingly, in recent days, the drug Ivermectin has also been undergoing rehabilitation in the curated landscape of pubic opinion.

What is the lesson from this? Don’t “trust the science” if the scientists are being paid, threatened, and cajoled. But do trust a scientist who admits they have been wrong. In the field of extracellular vesicles, despite the truly jaw-dropping caliber of their work, there are still no absolute truths, like the cover image of this blog suggests.

Mind-blowing

In the interest of ending on a positive note, the scientists I met and listened to were generally open-minded, humble, brilliant, articulate, funny, and passionate. They invented ways to track and identify single exosomes and single molecules. They invented tiny electrical circuits, nanometer cubes of gold, microfluidic devices, and tricks to identify and visualize things smaller than the limits of light detection. 

They are using machine learning, collaboration, and sheer genius to invent technologies and methods that will help decode much of what is happening in nature. 

Although I have questions about whether deductive reductionism can lead to organic theoretical wisdom, I have to confess that I am truly in awe of the human spirit and the intellectual rigor and courage it takes to discern biological systems of unimaginable complexity.

In closing, I will paraphrase my favorite joke from the lectures. 

God was called by Saint Peter to greet three scientists who simultaneously died in car accident. The first scientist said, “I work with DNA” and God said, “That is really hard, you can probably enter!”. The second said, “I work with proteins” to which God replied, “That is even harder! Come on in.”  The third scientist said “I am an expert in RNA” to which God removed his robe and handed it to the man saying, “Then you should probably take my job!”

1 thought on “Report from an Exosome conference”

  1. Hi Dr Park. Thanks for the work. The cognitive differences you heard must have been confusing. I’m still confused as to why you are so behind ivermectin.

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