Innovation Lessons Learned: With Lloyd Smith

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class="b_main__grid-container"> <div class="b_main__column-content b_main__column-content--marginal"> <div class="b_article__header b_article__header--inline b_article__header--articlepage"> <h1 class="b_article__headline b_article__headline--h1">Innovation Lessons Learned: With Lloyd Smith</h1> <p class="b_article__subline b_article__subline--h2">As a postdoc, Lloyd Smith invented the first automated DNA sequencer – used for sequencing the human genome. Later, he founded a company, Third Wave Technologies, which successfully commercialized molecular diagnostic products. More recently, Smith coined the word "proteoform," which has been wholeheartedly embraced by the proteomics community. So you could say he knows a thing or two about innovation... </p> <p class="b_article__info"> <a href="/authors/lloyd-smith" target="_blank" class="b_article__infolink">Lloyd Smith</a>, <a href="/authors/james-strachan" target="_blank" class="b_article__infolink">James Strachan</a> | <time datetime="2025-01-13"> 01/13/2025 </time> | 11 min read | <a class="b_article__infolink" href="/search?q=%2A&tx_solr%5Bfilter%5D%5B0%5D=assetType%3APractical">Practical</a> </p> <ul class="b_menu-share b_menu-share--xs-only"> <li class="b_menu-share__item"> <vue-bookmark :uid="12753" :user="user" :is-share="true"></vue-bookmark> </li> <li class="b_menu-share__item"> <a 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class="b_textmedia__imagewrap b_textmedia__imagewrap--above b_textmedia__imagewrap--full "><figure class="b_textmedia__figure"><picture><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_0c6ba9368f.webp" media="(min-width: 1280px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_e2d1de87f1.png" media="(min-width: 1280px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_6dc6a19315.webp" media="(min-width: 1024px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_606edfe40a.png" media="(min-width: 1024px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_0a4035c33c.webp" media="(min-width: 835px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_53ce844ea8.png" media="(min-width: 835px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_8fcb803450.webp" media="(min-width: 768px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_dfbb8ae971.png" media="(min-width: 768px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_ff504b9724.webp" media="(min-width: 567px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_79d0cc7bcd.png" media="(min-width: 567px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_93887adc06.webp" media="(min-width: 415px)" type="image/webp" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_8329a9c3d1.png" media="(min-width: 415px)" /><source srcset="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_c455cdd10a.webp" type="image/webp" /><img class="b_textmedia__image" src="/fileadmin/_processed_/f/a/csm_0125-401-Innovation-Lessons-Learned-Lloyd-Smith_In-Article_3d7ec816d3.png" width="374" height="214" loading="lazy" alt="" /></picture><figcaption class="b_textmedia__figcaption"><p class="b_rte__bodytext">Supplied by Author</p></figcaption></figure></div><div class="b_clearfix"></div> <h4 class="b_rte__header b_rte__header--h4">Embrace youthful confidence – what have you got to lose?<br> </h4><p class="b_rte__bodytext">It’s a bit of a stereotype (something you might read about in books), but I’ve noticed that scientists often do their best – or most disruptive – work, when they’re young. Why? Well, when you’re young and just starting out, you really have nothing to lose. That definitely applied to my work on the DNA sequencer. I’d come out of grad school thinking I was a bit of a hotshot, you know, with nine papers, and I went into my postdoc expecting to keep up that pace.</p><div class="b_clearfix"></div><div id='ad-slot-71' class="b_ad"><ga-ad code="71"></ga-ad></div><div id='ad-slot-72' class="b_ad"><ga-ad code="72"></ga-ad></div><div id='ad-slot-51' class="b_ad"><ga-ad code="51"></ga-ad></div> <p class="b_rte__bodytext">But after a while in the new environment, I felt like I wasn’t really getting anything done. I started feeling like I wasn’t as good as I’d thought, and nothing I tried seemed to be working. So when the DNA sequencer project came up, it felt like a real leap of faith because I needed to invent new chemistry. And I wasn’t even in a chemistry lab! But I thought, “Well, I have nothing to lose, so I might as well have some fun.” And since I was looking to enjoy the work, I figured, why not take a chance on something completely different? That drive to go out on a limb and try something unique is something you see a lot in innovation and creativity discussions. I discovered that idea through my own experience, but it’s a well-known concept: young people often make big leaps in innovation because they’re less bound by convention and feel like they have less to lose.</p><div class="b_clearfix"></div> <p class="b_rte__bodytext">There is also a willingness to question authority, which is easier when you’re younger. For instance, with the DNA sequencer, I needed four different dyes to make it work. I talked to a famous scientist who told me, “You might find three of the dyes, but you won’t find the fourth. It’s just not possible.” He was partially right – the fourth one was hard to find. But instead of dropping the project, I just thought, “I’ll figure something out.” So, a lot of what worked for me was being willing to take risks, ignore doubts from authority, and try things that others said couldn’t be done. Those traits can be strong when you’re young, which is why young people often make great innovations. </p><p class="b_rte__bodytext">I shall not compare myself to Albert Einstein (who can?), but he had a similar situation. He was a patent examiner in Switzerland – but he barely got that job because he’d managed to rub so many people the wrong way. He was young, confident, maybe a bit arrogant, and it didn’t win him a lot of support from senior people in the field, which he needed back then to get positions. So, he was somewhat cast aside by the establishment, but he could do his patent work quickly and efficiently and then have all this time to think independently. And in that space, he developed theories to explain Brownian motion, the photoelectric effect, special relativity, and mass-energy equivalence.  – the list goes on.</p><p class="b_rte__bodytext">There are always exceptions, of course, like John Fenn inventing electrospray ionization after he retired!</p><div class="b_clearfix"></div><div id='ad-slot-90' class="b_ad"><ga-ad code="90"></ga-ad></div> <h4 class="b_rte__header b_rte__header--h4">Send out tendrils to avoid getting stale<br> </h4><p class="b_rte__bodytext">I don’t know if it’s entirely conscious, but I tend to switch fields when I feel I’m getting stale. I’ve made four big shifts like that in my career. For instance, I work in mass spectrometry now, but I wasn’t trained in it – that’s pretty unusual. Most people who work in mass spectrometry have been in it since graduate school, so I’m kind of an outlier in that way.</p><p class="b_rte__bodytext">I remember a moment in the DNA sequencing field that made me realize it was time to move on. I’d been in the field for about 10 years and had become the person who responds to every new idea with, “Oh, I thought of that. It won’t work.” I was turning into that stereotypical “jaded old guy,” and I didn’t want that. Plus, I was ready for a change. So I started exploring new things and developed a strategy for changing fields. Switching isn’t easy, but the way to do it is by starting with smaller projects in a new area – tendrils.</p><p class="b_rte__bodytext">For example, I was 100 percent focused on DNA sequencing, but I began exploring mass spectrometry on the side. I found a collaborator to co-write a grant, which helped us get a mass spectrometer in the lab. I then hired a postdoc who had expertise in mass spectrometry, which allowed us to get up to speed. Over time, that entry point into mass spectrometry turned into a full commitment, and now I’m fully immersed in it.</p><p class="b_rte__bodytext">I think the key here is having a genuine interest in trying new things. Then, you work out the details as they come – like navigating whatever barriers pop up. Right now, for example, we just submitted our first paper on Alzheimer’s disease. Two years ago, I wasn’t working on Alzheimer’s and hadn’t thought about it much. But we made a discovery relevant to Alzheimer’s, and now it’s all I think about. So, we’re figuring out how to shift resources, build up expertise, and get support in that area. It’s a current struggle and an ongoing field shift.</p><p class="b_rte__bodytext">I think it’s great to be driven by the science itself – by the opportunities that present themselves. If you notice something intriguing, and you’re interested in it, you can just go for it and see where it leads. I feel fortunate that, in the United States’ academic sector, there’s a lot of funding available, especially through the federal government. If you can write a compelling grant proposal, you have a good shot at getting funding to explore new ideas. The NIH, for example, has a multi-billion dollar budget, and a lot of it goes to researchers like me, spread across universities around the country. It’s competitive writing, but it’s the world we live in, and it’s a big part of enabling these kinds of explorations.</p><div class="b_clearfix"></div> <h4 class="b_rte__header b_rte__header--h4">Don’t shoot your balloons too early – but you do need to shoot them<br> </h4><p class="b_rte__bodytext">I often tell my students to think of each idea as a “balloon.” If you have a creative mind, you’ll have many of them floating in the air. That’s the creative phase – generating new ideas and exploring new areas. Being overly self-critical at this stage can really hold you back, stifling creativity.</p><p class="b_rte__bodytext">Once you’ve got plenty of balloons in the air, you do need an analytical phase where you start shooting some of them down. Maybe 99 percent of your ideas won’t hold up, and you’ll be left with a few ideas that might be worth pursuing. At that point, if they seem interesting, important, and feasible, you devise a fail-fast strategy to quickly see if you can make any headway.</p><p class="b_rte__bodytext">But if you start out with too few balloons, you’ll be left with nothing worth trying. I’d go as far to say that one of the biggest barriers to innovation is self-criticism in the early stages. Another thing I like to emphasize is the idea of converting “science fiction” into science. Science fiction is full of amazing concepts – like faster-than-light travel, teleportation, or time machines – that are fascinating but fundamentally unreasonable.</p><p class="b_rte__bodytext">However, there are other science fiction-like ideas that aren’t impossible and might be worth exploring. For example, with epitranscriptomics, it might seem like science fiction to imagine understanding every molecule in an RNA population and tracking all the modifications, their locations, abundance, generation, degradation, control, and function. It’s an incredibly complex question, almost sci-fi in scope. But by framing it as an ideal, you can start nibbling away at it. Maybe there’s a smaller, more manageable question you can tackle, like some specific part of that bigger question. By starting with these achievable parts, you get your foot in the door. As you gain success and knowledge, you can progressively build toward that larger goal, even if it seems impossible at first.</p><div class="b_clearfix"></div> <div class="b_elementframe b_elementframe--brandcolor "><h4 class="b_rte__header b_rte__header--h4">Areas Ripe for Innovation<br> </h4><p class="b_rte__bodytext">Nanopore technologies are fascinating. They’ve already made a big impact, especially in nucleic acid sequencing, and they’re beginning to show potential in protein sequencing, which is a field in dire need of new technology to tackle proteome complexity. Right now, we’re just scratching the surface of what’s possible with proteomics.</p><p class="b_rte__bodytext">Another area we’re just beginning to explore is epitranscriptomics. This field is in its infancy, but it’s somewhat similar to the proteoform problem. Proteoforms refer to the many variations in which proteins can exist, as there are over 400 known post-translational modifications (PTMs) that can alter proteins. Ideally, we’d want to know exactly what modifications are present, where they are located, and the abundance of each species. We want to capture the complete picture, which is quite a tall order.</p><p class="b_rte__bodytext">Similarly, <i>epitranscriptomics</i> is about identifying and understanding post-transcriptional modifications in RNA molecules. Unlike proteomics, though, our technology for analyzing RNA modifications is still quite basic. Carolyn Bertozzi’s recent discovery of glycans attached to RNA molecules is an example of this – an exciting new area. We’re just beginning to unravel why these modifications exist on RNAs and what roles they may play biologically.</p><div class="b_clearfix"></div></div> <h4 class="b_rte__header b_rte__header--h4">You have a duty to have fun<br> </h4><p class="b_rte__bodytext">Everyone has their own way of thinking about things, and we’re all different as humans. Another thing I try to do is to make sure my students are having fun. I tell them, “If you’re not having fun, we need to work on that, because this should be enjoyable.” Years ago, a student of mine, who was from a different cultural background, challenged this idea. She said, “In my culture, duty is more important than fun. It’s more about doing your duty than enjoying it.” It was an eye-opener for me and made me think more deeply about why I emphasize fun.</p><p class="b_rte__bodytext">I realized that encouraging people to enjoy what they’re doing is actually very productive. Fun enhances creativity, productivity, and the overall quality of their work. When people are having fun, it brings out their best qualities – like how children play. When they’re not having fun, they’re just slogging through, and that doesn’t encourage the best ideas or motivation.</p><p class="b_rte__bodytext">So, in creating a fun environment, I want everyone to feel free to contribute ideas. I don’t want to be the only one with ideas – that’s not practical, especially because young people are often the ones with fresh perspectives. For example, we got into our Alzheimer’s project because one of my students had the idea, not me. He came up with things to try, and I thought they were interesting, so I encouraged him. Creating an environment where everyone is having fun stirs the pot and encourages creativity. </p><p class="b_rte__bodytext">And let me be clear: science should be fun! It’s a way to explore the unknown, and we’re incredibly fortunate to make a living doing it.</p><p class="b_rte__bodytext">I have a kind of “Pollyanna” perspective that people get the best out of others by being great human beings. But then I read the Steve Jobs biography by Walter Isaacson, and it was a little disappointing to learn how he was often unkind, even mean, to people he worked with. It was eye-opening for me to see that someone could be incredibly effective while treating others poorly. It went against my idealistic view that positive behavior brings out the best in people.</p><p class="b_rte__bodytext">Napoleon, on the other hand, used manipulation and honor to inspire people. There’s a quote where he basically says that men will run into cannon fire for little scraps of ribbon, and he played into that, awarding them these tokens to boost their sense of pride and duty. It’s a bit disappointing to see that this can be effective. Personally, I prefer the more “Kumbaya” view, where we all work together as great human beings, creating and innovating in a positive environment. Even if that’s not the only way the world works, it’s how I choose to approach it.</p><div class="b_clearfix"></div> <div class="b_elementframe b_elementframe--brandcolor "><h4 class="b_rte__header b_rte__header--h4">Fiction Fuel<br> </h4><p class="b_rte__bodytext">I’m currently reading <i>Hamilton</i> by Ron Chernow – the one that inspired the play – and it’s huge, in a tiny font. I’ve been reading it for about a year and I’m only halfway through – it’s incredibly detailed! And it has made me realize how little I knew about American history, and just how much the events back then tie into the news we see today.</p><p class="b_rte__bodytext">I think I got really focused on science in college and kind of went down that rabbit hole. The <i>Hamilton</i> book really exposed that. My son has a much broader outlook than I do and often helps me see things from different angles.</p><p class="b_rte__bodytext">I regularly read science magazines and consume the <i>The New Yorker</i> with coffee every morning. I also enjoy science fiction when I can find something good; for example, I recently read <i>Project Hail Mary</i>, which was fascinating. Spoiler alert: the story’s about the sun dimming and Earth’s desperate mission to figure out why. When the main character finally gets out there, he meets an alien species whose sun is also dimming, and they work together to solve the mystery, which turns out to involve interstellar microbes with nuclear reactions happening inside them. It was like an infection of the sun itself!</p><p class="b_rte__bodytext">I find science fiction expands my thinking beyond the real world. It opens my mind to “out of the box” ideas, not just pegged to how things work in reality – and that definitely fuels my creative mind.</p><div class="b_clearfix"></div></div> <div class="b_teaser b_teaser--article "> <a href="/business-education/how-to-succeed-in-commercial-innovation?utm_campaign=innovation%20lessons%20learned%3A%20with%20lloyd%20smith&utm_source=landingpage&utm_medium=cpc" class="b_teaser__link" title="How to Succeed in Commercial Innovation"> <figure class="b_teaser__figure b_teaser__figure--left b_teaser__figure--small b_teaser__figure--article"> <picture><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_c301ae2254.webp" media="(min-width: 1280px)" type="image/webp" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_f3e3a348a4.png" media="(min-width: 1280px)" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_0e496747b3.webp" media="(min-width: 1024px)" type="image/webp" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_175486ef02.png" media="(min-width: 1024px)" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_fe57cbe2cf.webp" media="(min-width: 768px)" type="image/webp" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_8ce953b283.png" media="(min-width: 768px)" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_b3af7eaadc.webp" media="(min-width: 415px)" type="image/webp" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_b3b61b77b6.png" media="(min-width: 415px)" /><source srcset="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_5e9eb7b4aa.webp" type="image/webp" /><img class="b_teaser__image b_teaser__image--scale" src="/fileadmin/_processed_/4/a/csm_1224-301-IMV-Lloyd-Smith_Teaser_24dbaddec7.png" width="257" height="172" loading="lazy" alt="" /></picture> </figure> </a> <span class="b_category__container "> <a href="/business-education" class="b_category b_category--color-3 b_category--has-topic "> Business & Education </a> <a class="b_category b_category--color-3 b_category--topic " href="/business-education/business"> Business </a> </span> <h3 class="b_teaser__headline"> <a href="/business-education/how-to-succeed-in-commercial-innovation?utm_campaign=innovation%20lessons%20learned%3A%20with%20lloyd%20smith&utm_source=landingpage&utm_medium=cpc" class="b_teaser__link">How to Succeed in Commercial Innovation</a> </h3> <p class="b_teaser__info b_teaser__info--article b_teaser__info--has-margin"> <time datetime="2024-12-12" >12/12/2024</time> | Lloyd Smith | 4 min read </p> <a href="/business-education/how-to-succeed-in-commercial-innovation?utm_campaign=innovation%20lessons%20learned%3A%20with%20lloyd%20smith&utm_source=landingpage&utm_medium=cpc" class="b_teaser__link"> <p class="b_teaser__text b_teaser__text--article">Sell your story, stay alert, be 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L. Hubbell Professor of Chemistry, Department of Chemistry, University of Wisconsin – Madison, USA</p> <p class="b_rte__bodytext b_rte__bodytext--author-teaser-link"> <a href="/authors/lloyd-smith">More articles by Lloyd Smith</a> </p> <hr class="b_divider b_divider--multiple-authors"> <figure class="b_teaser__figure b_teaser__figure--left b_teaser__figure--author"> <picture><source srcset="/fileadmin/_processed_/1/f/csm_James-716_42af0f17c7.webp" media="(min-width: 1280px)" type="image/webp" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_4314dd6d00.png" media="(min-width: 1280px)" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_220c0cab64.webp" media="(min-width: 1024px)" type="image/webp" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_0a49fc586c.png" media="(min-width: 1024px)" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_197730d341.webp" media="(min-width: 768px)" type="image/webp" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_173bb6250a.png" media="(min-width: 768px)" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_0db2794ede.webp" media="(min-width: 415px)" type="image/webp" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_689642b248.png" media="(min-width: 415px)" /><source srcset="/fileadmin/_processed_/1/f/csm_James-716_38b7e2299d.webp" type="image/webp" /><img class="b_teaser__image b_teaser__image--scale" src="/fileadmin/_processed_/1/f/csm_James-716_d6eb266007.png" width="187" height="125" loading="lazy" alt="" /></picture> </figure> <header class="b_teaser__headline b_teaser__headline--h3 b_teaser__headline--author ">James Strachan</header> <p class="b_teaser__info b_teaser__info--author"></p> <p class="b_rte__bodytext">Over the course of my Biomedical Sciences degree it dawned on me that my goal of becoming a scientist didn’t quite mesh with my lack of affinity for lab work. Thinking on my decision to pursue biology rather than English at age 15 – despite an aptitude for the latter – I realized that science writing was a way to combine what I loved with what I was good at. </p> <p class="b_rte__bodytext">From there I set out to gather as much freelancing experience as I could, spending 2 years developing scientific content for International Innovation, before completing an MSc in Science Communication. 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