Celebrating the 50th anniversary of the Society of Interventional Radiology’s (SIR) annual scientific meeting (29 March–2 April, Nashville, USA), Lindsay Machan’s (University of British Columbia, Vancouver, Canada) Charles T Dotter Lecture turned to innovating innovation, honouring Dotter to show the strides technology has made since interventional radiology’s (IR) inception.
“In the 50th year of SIR, it seems best to talk about how innovation is changing,” Machan said. He recalled how IR pioneer Ernest Ring had described the meeting as ‘a bunch of people excited to see others who were doing the same things they were’—“and that’s actually how I think all of us feel about this meeting today,” Machan reflected.
Sink or swim
Individually, Machan’s relationship with innovation has been unique. He described his first staff job at Hammersmith Hospital in London, UK in 1989, when Hans Walsten was promoting the Wallstent (then Medinvent, now Boston Scientific). “Over 1,200 had been inserted into bile ducts and virtually every artery throughout the body in Europe. All the dogma at the time said that there was a 2% failure rate. Especially in certain places, they were restenosis machines, you could see that,” he described. Machan tried various methods of preventing this outcome to no avail, until encountering a medical student presenting his premedical work on cartilage-derived angiogenesis inhibitors in animal models of rheumatoid arthritis.
“The room was empty, almost nobody was there. Bill Hunter began talking about new blood vessel formation and the fact that tissue can’t grow more than two millimetres away from a capillary unless it’s cartilage or cornea—so in essence, inhibition creates zones of exclusion,” said Machan. Approaching Bill after his talk, Machan admitted that he knew little about animal models of rheumatoid arthritis, but that he believed it would make the ideal stent coating.
Starting their company, Machan, Bill and Larry Arsenault promptly raised CDN$100,000. “And then we made a very important discovery—it didn’t work,” Machan stated. Consulting an expert in biochemistry, the three founders shortly discovered that by coating their stent with paclitaxel, the active ingredient in the chemotherapeutic agent Taxol, they were able to achieve angiogenesis inhibition, creating their desired exclusion zone.
“We’re back in business, baby,” said Machan. “So, we do some bench, small and large animal experiments, but we needed to deal with one big problem and that was that, at the time, Taxol had up to a 30% anaphylactic rate.” Machan notes that this reaction was considered attributable to a solubilisation agent, Cremophor—a castor oil derivative—but there were lingering concerns it could be related to paclitaxel itself, which threatened “to sink us”, he stated.
During this time, however, Machan described a patient who had oesophageal cancer who had had two failed attempts at dilation.
“His grandkids wouldn’t come to visit him because he couldn’t swallow so was always spitting up. He just said he wanted to be able to eat ice cream and drink scotch. So—and I would go to jail for this now—I went across to our lab and we packed as much paclitaxel and ethylene vinyl acetate as humanly possible onto this removable oesophageal stent,” Machan told the SIR 2025 audience. “I sweated bullets overnight. I went in the next morning and there he was with three little dixie cups on his mail stand, and he threw me this presumed scotch-induced grin, so we knew were in business,” recounted Machan.
In 1992, Machan and his other co-patentors signed a co-exclusive license with Boston Scientific and Cook Medical for their paclitaxel-coated stent, despite five years of talks with various companies. “We had received a cash offer, so I went up to Boston and Cook and said, ‘I don’t know if you guys are just being nice to me but if an alternative doesn’t arise, this deal is going to go through on Monday’. By that Saturday at 9am, we confirmed that FOMO [fear of missing out] is still the most important factor in so many ways,” Machan said.
“What did I learn from all of this?”
His trajectory through innovation taught Machan that observing opportunities for innovation is key, he stated. “‘Honour every opportunity to learn something new’—it’s a fantastic quote. My first instinct was to not go to that premedical presentation because it was on something I didn’t understand, but I went and it changed my life. Work with people who have other skills,” Machan continued. “But, boy, are luck and timing everything. Then finally, work on a problem that someone will pay for. It’s great to do research, but if you want to get it into a patient, unfortunately you have to have a commercial alliance.” It is this commercial element that has become a larger part of innovation today, stated Machan, but the “cascade of steps” to take “an idea on a napkin to getting it patented and regulated hasn’t changed, and you can’t skip any of them,” he added.
What has changed, however, is where innovators look for opportunities, Machan said. “First of all, you follow the money,” he stated. On one side, there are the “inconvenient truths” of needing to control unsustainable healthcare costs; at the same time there are significant changes set to transform future healthcare, including casting the patient as a consumer and the integration of artificial intelligence (AI) within the treatment algorithm.
Regarding the former, Machan spoke on the democratisation of cardiovascular care at home. Using the example of smartwatches that can monitor and record your heart rate and sympathetic tone, the speaker stated that “this new era of health has resulted in the combination of digitalisation and consumerisation”. The result of this has meant that companies such as Google and Meta, “who haven’t gone through the slings and arrows that other medical companies have, and with the irrationality of the business of healthcare,” Machan added, create a new landscape for patients and healthcare providers to navigate.
“But I said follow the money,” Machan continued. “Think about efficiencies, quantum leaps, efficacy and safety, while empowering lesser trained members of the healthcare team.” To exemplify this stance and the democratisation of teaching, the speaker described the history of the stethoscope, and how the tool required specialised expertise which created barriers as to who could deliver healthcare.
“Now, in everyone’s pocket there is a device that can interface with a digital stethoscope, recognising heart and lung sounds, and can tell you what these represent,” described Machan. “This means that every general or nurse practitioner now has the expertise of an Ivy League cardiologist immediately available to them. This reduces, for instance, unnecessary referrals from rural areas or for functional murmurs in children.”
AI in the real world
Machan subsequently touched on AI and the introduction of AI innovation at a societal level. Machan noted how Truveta, among a growing number of comparable companies, is able to extract and interrogate healthcare data from millions of patients daily, drawing on these data to further clinical research. Referencing a publication by Monteleone et al, comparing ultrasound-assisted catheter-directed thrombolysis versus mechanical thrombectomy in over 83 million patients, Machan drew attention to the wealth of procedures and outcomes that can be studied.
With the ability to provide real-world data, these emerging AI programmes are bringing to the fore the realisation that “what happens in the real world doesn’t necessarily happen in controlled company-sponsored trials”, Machan stated.
Finishing his talk, Machan ruminated on what Dotter would say to early career interventional radiologists seeking to innovate today. In his view, Dotter would urge them to be curious, collaborate and record what they learn, and to protect the spirit of IR, leaving the speciality better than they found it.
