Zhen Xu describes the decade (roughly 2004 to 2014) spent after her initial discovery of histotripsy's cavitation effect figuring out the underlying mechanism, using ultra-high-speed cameras and microscopes to capture bubble events happening in microseconds. She notes this basic research had no clear commercial payoff, so it relied on NIH federal funding rather than investors, and that it took over 20 years total from her 2002 discovery to FDA approval in 2023. She frames the long timeline within the history of surgical innovation, from the 1860s invention of anesthesia to Marie Curie's radiation work around 1900 to 1960s fiber-optic endoscopic surgery, as part of medicine's long trend toward less invasive treatment.
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She says the work required capturing microbubble formation happening within microseconds, which demanded ultra-high-speed camera and microscope setups built specifically for this investigation.
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She contrasts her own gallbladder removal via laparoscopic surgery (four small holes) with her father's 13 centimeter incision as an example of surgery becoming less invasive over time.
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She mentions imagining a Star Trek or Stargate-like vision of fully noninvasive surgery as a long-term motivation during the uncertain research years.
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She notes tenure as assistant professor fell within this same decade-long period of mechanistic research.
586 words · auto-generated from the episode video
28:47Yeah, yeah, okay, that makes total sense. And like when you were going about trying to figure out this non-linearity, like what is the, this was part of like you discovering what is the mechanism by which cavitation happens, right? How much of it was like in the dark, just shooting around? It's pretty much all in the dark. We actually spent, after my initial discovery in 2002, literally we went back and spent almost 10 years developing the equipment and the investigation mechanism. And by one tree investigation mechanism, we had to use
29:27ultra high-speed camera because we're talking about microbubble happening within microseconds. So really, we're looking for this tiny little thing happening within very short amount of time. And it, you know, you were talking about doing treatment for menace, but really what's really happening is within microseconds. So you really have to go in and really test it out and trying to capture the precise timing of these really fast events and also tiny events. So microscope high-speed camera and do experiments day in and day out and hoping
30:08you can capture that moment. And this honest speaking that no sane person will give you money to do, right? Like the companies or the investors would never give you any money to do this kind of work. So it was so fundamental and so, you know, really looking in the dark and turning impossible to possible that kind of thing. And the way, you know, federal funding was so helpful here. We were able to get funding from National Institute of Health saying this is worth looking into and go and figure out to the mechanism on the right mechanism. So we really spent 10 years in and out just trying to figure out how it
30:51works. And almost only by understanding how it works, then we can optimize and design our parameters to do the best non-invasive surgery for human patients. Yeah. I mean, as you said, this is 2004 and then this is 2014. So there's 10 years in between first discovering it and really having some sense of how to control the thing and what's actually happening. So for those 10 years, like, did you ever, was there ever a time where you were like, maybe I need to go do something else? You know, cause that's, that's a long time. People realize that I, you know, the FDA approval was 2023.
31:32I initially discovered 2002. So it was 21 years. And then that people always ask me like, have you thought about, you know, that doing something else really, right? Cause it's like, not just 10 years, it was more than 20 years before I even had any real impact on humans. I would say after 2014, it's like, okay, I've got a good handle on this. Right. But like between 2004 and 2014, that's 10 years. You're like grad school, early career pro-doc. And assistant professor. Yeah. So, you know, 10 years on your mind. Tenure, the professor tenure, not the 10 years, but kind of, yeah. I think two things. One is scientists are programmed differently in
32:18our brain, right? To most people, it can be frustrating that in the dark. To me, I was curious and this potential excitement that this is unexplored, right? Nobody knew. And that's why it's so cool to me that I can make a discovery that can potentially have a big impact. And also it's associated with a real application