What You Can Learn From History's Greatest Innovators | Walter Isaacson | The Knowledge Project 121

All citizens need to participate in CRISPR governance discussions, not just scientists, because technology governance is inherently a democratic and social question, not a technical question for experts alone.

“my book is about uh this uh part of the uh last half of the book is about going step by step saying when should we use it and when should we not we all have to be part of this discussion we can't seed it to the scientists to be in charge of this”

Benjamin Franklin was skilled at forging collaboration, cooperation, and compromise among the founders—a different style than the intellectual honesty of Steve Jobs—and his role as 'glue' holding people together was essential to building teams even though he was sometimes considered too diplomatic rather than intellectually honest.

“ben franklin you know he's somebody who was good at forging collaboration and cooperation pushing compromise smoothing over differences he was definitely not known for intellectual honesty in fact sometimes he was considered being too diplomatic which is a euphemism for not being all that infam uh intellectually honest but in building a team like our founders you needed passionate people like john and sam adams you needed people of high rectitude like washington and smart people like jefferson and madison but you also needed somebody who could be the glue”

Leonardo and Michelangelo had a poor relationship due to differences in personality and sexuality; Leonardo was openly gay, gregarious, and surrounded himself with diverse collaborators, while Michelangelo was a solitary figure who struggled with his sexual orientation and religious anxiety—and Isaacson was drawn more to Leonardo because of his collaborative nature.

“leonardo was proudly and openly gay had a boyfriend salahi who he draws and writes about and brings with him wherever he goes but michelangelo it was sort of known as the agony and the ecstasy he feared the wrath of the lord he was much more religious than leonardo da vinci was agonized about his um you know sexual orientation and many other things and so they're not destined to be the best friends”

Intellectual honesty—being brutally honest with people about their performance and shortcomings—is important for strong management and creates motivation and accountability; however, it must be balanced against building team cohesion and collaboration, and different leadership styles have different tradeoffs.

“intellectual honesty is something that can push people make people a great leader is something that's i've been a manager i've run companies i know that being really brutal and intellectually honest uh to people is important first of all you motivate them you drive them you let them know where they're not performing and how they can and you make sure that you don't have a team as steve jobs said that's filled with b players you only got a players on the team”

CRISPR is a gene-editing tool that bacteria have used for a billion years to fight viruses; scientists adapted this bacterial immune system into a programmable cutting tool to edit human DNA at targeted locations by using guide RNA to direct where cuts should occur.

“crispr is just a pretty simple tool that we can reprogram to cut our own dna if we decide that there's a sequence in our dna we don't like like a sequence that causes sickle cell in our blood or causes us to be short or maybe some days sequences that uh predispose us to be depressed or whatever crispr is a tool where you can edit them out it's a tool that jennifer doudna and her colleagues won the nobel prize for this past year uh inventing and what they did was they adapted something that bacteria have been using for a billion years”

Alan Turing wrote a paper called 'Can Machines Think?' where he addressed 'Ada Lovelace's objection'—the claim that machines cannot be creative—and argued that machines would eventually be able to think and exhibit artificial intelligence, though this debate remains unresolved today.

“alan turing a century after ada lovelace writes her notes on the different uh the analytical engine writes his book uh his uh paper called ken machines think and he writes about what he calls ada lovelace's objection lady lovelace's objection he calls it which is that machines can't think that they'll be able to process any symbols we give them but they won't be able to be creative thought and touring sort of pushes the opposite approach which is yes machines will be able to think we will have machine learning we'll eventually have artificial intelligence”

Eric Lander led scientists calling for a moratorium on heritable genetic edits and was initially in disagreement with Jennifer Doudna on this point; Lander preferred an outright moratorium while Doudna preferred guidelines and allowing research to continue—representing a schism in the scientific community about governance approach.

“a couple of years ago there was a dispute or disagreement among scientists about whether to have an outright moratorium in other words to say on on inheritable edits in other words don't use it in reproductive cells or early-stage embryos and after the chinese doctor did that to cut out the receptor uh for hiv the virus that causes aids there was an uproar and a group of scientists said let's have a moratorium and those scientists were led by eric lander a truly brilliant charismatic scientist who ran the broad institute where fong jiang worked he's now the chief science advisor to president biden so eric lander and his camp were in favor of a moratorium and that included fung jiang jennifer doudna was in a slightly different camp which said we don't want to do this right away let's have some guidelines about when you would make inheritable edits but let's keep the research going and let's not use the word moratorium”

Fish move faster through water than birds move through air because water is denser and provides more resistance to push against; Leonardo investigated this through observation of bird wing flapping patterns and duck webbed feet, then experimented with flowing water—illustrating how observational curiosity leads to understanding physical principles.

“leonardo says wait water uh is heavier it's harder to go through why can fish go faster than birds and he looked at how birds flap their wings he notices which species flap them up faster flap them down faster when they take off he notices how the webb feats of duck work he does experiments with flowing water so does ben franklin when he gets to london”

The Mona Lisa was renowned even in Leonardo's lifetime; cardinals from Italy visited France specifically to see it and wrote about it—it became famous gradually through history and is now arguably the most famous painting in the world, but this fame grew over centuries, not through theft.

“first of all it was a grand painting even in his time and even by his bed in paris i've done paris in france he's uh uh you know in a uh chateau in france where the king has brought him to france and become his patron cardinal comes by from italy and admires the painting and writes about it so it was known by the end of leonardo's life that it was going to be a masterpiece”

When studying historical figures, going to primary sources (original notebooks, papers, manuscripts) rather than secondary interpretations reveals not just the intellectual content but also the mind's movement—doodles in margins, leaps from one idea to another—and there is something inspiring about seeing the original physical artifact.

“that's why i when i did leonardo da vinci we're so blessed we have more than 7000 pages of his notebooks i mean paper is a great technology for the storage and retrieval of information it has a battery life that's almost infinite it operating system never goes out so i can go around the world and look at leonardo's notebooks and not only sort of read in a secondhand way what information he had in it but see the doodles in the margins the way he drew little designs to see how his mind leaped on the page”

For contemporary subjects, biographical research requires triangulation: reading secondary sources and original documents, then interviewing people who knew the subject to understand context, motivation, and meaning behind their words and actions.

“if i read the books about steve jobs that'd be fine if i read some of the memos he wrote but then i have to do the third part of the triangulation you have to talk to people so if i read the books about steve jobs that'd be fine if i read some of the memos he wrote but then i have to say why did he write that email or what was that memo really designed to do and then you get the interviews”

Albert Einstein's 1905 paper on special relativity is gloriously written and could be assigned to college physics students instead of secondary sources, demonstrating that going back to original sources is important and often more accessible than modern commentary.

“the really cool thing about special relativity which was this first one done in 1905 which is basically the speed of light is constant you can't surpass the speed of light eventually leads him to his equation that becomes equal mc squared special relativity is not the harder one general relativity is and especially on special relativity you can actually read the paper you want if i were a college physics professor instead of assigning books about relativity i'd say read that 1905 paper it only has one footnote to it and it's gloriously written”

CRISPR can treat diseases like sickle cell anemia and also enable enhancement of traits (faster muscle reflexes, blood cells with higher oxygen capacity), and within 20-30 years genetic enhancement of children may become commonplace—creating a scenario where we must decide whether to permit enhancement.

“if we can cure as we have sickle cell this past year by making blood cells that aren't sickled and can carry more oxygen well there are other genetic traits of blood cells including mutations that a lot of sprinters and great bicyclists have that allow your blood cells to carry more oxygen that would be a pretty easy fix if you wanted uh to you know win the tour de france but more importantly if you decide you want to edit your children so that they will be great athletes and they can have faster muscle reflexes or blood that carries more oxygen and that's something that is doable in the next 20 30 years or maybe before then but that could be commonplace in the next 20 or 30 years”

Leonardo's scientific curiosity began in service of his art—he dissected neck muscles to understand how to paint Saint Jerome correctly—but eventually his curiosity became an end in itself; he studied heart valves not because it was useful for painting, but because he was curious and it delighted him.

“he wanted to know everything and that he starts off wanting to understand things including science in furtherance of his art like he's dissecting neck muscles in order to do saint jerome in the wilderness or he's studying the math or perspective in order to get the adoration of the magi correct but then after a while he's dissecting uh cadavers you know to study the muscles and the skeletons but he's going down he's studying the heart he's studying the heart valves this is not what you need to know for your paintings he's doing it not because it's useful but because he's curious and i think what surprised me was that leonardo da vinci's curiosity was driven not because there was some utility to it but because it delighted him”

Biographers should not write how-to or self-help books; instead, they should present real, flesh-and-blood people in chronological narrative so readers can understand their struggles, values, and approach—and then extract lessons by studying multiple lives, not by following a simple 7-step formula.

“i say that we biographers don't write how-to books i didn't write ben franklin to say how to be a diplomat or a leader or a how-to book uh with steve jobs saying how to run a company or for that matter jennifer dowden my latest hero of my books you know these aren't seven secrets to success or seven easy lessons for how to run a company in fact when people would come up to me and they'd say i used your steve jobs book like elizabeth holmes would the person who uh invented uh theranose or launched theranos say oh i use your steve jobs as a how-to book i'd go no no no it's not a how-to book don't try this at home first of all there's only one steve jobs there's only one leonardo da vinci you've got to study a whole lot of lives”

People who make great creative advances share an obsessive passion for understanding details and seeing how pieces connect; they believe 'god is in the details' and this manifests across domains—from Leonardo dissecting eye muscles to understand light refraction in the Mona Lisa, to Steve Jobs obsessing over chamfered electrical plugs, to Jennifer Doudna studying how guide RNA structure determines function.

“these type of people who realize that god is in the details those are the people who make great advances and i put leonardo in that category i put ben franklin steve jobs in that category jennifer doudna as she's trying to understand the inner workings of molecules and realizes that the structure of a molecule the structure of a piece of guide rna the way it twists and folds determines how it becomes a key to unlock the mysteries of life that type of passion about the details is to me one of the keys to creativity”

Isaacson's book on CRISPR is not designed to provide final answers about whether gene editing is good or bad, but rather to guide readers through 'first thoughts, second thoughts, third thoughts, fourth thoughts' on different applications (disease treatment, psychological disorders, athletic enhancement, inequality), so readers develop their own thoughtful positions rather than accepting prescriptive answers.

“my book is not about giving the answers i'm going to hurt the sales of the book by telling you there's no last chapter with the answers but their first second third and fourth thoughts in the book about different types about where we should go maybe we should use it here what about depression what about psychology what about schizophrenia what about sickle cell what about better athletic abilities and i want the reader to be like me to go hand in hand with me and jennifer doudna and david sanchez having first thought second thoughts thursdays because it's a slippery slope but slippery slopes are a little bit safer if you do it hand in hand step by step”

In the 1980s-90s, CNN and media organizations aimed for broad, non-ideological audiences and prioritized reliable information because advertisers wanted their products placed in contexts of trustworthiness, not partisan polarization.

“there were two or three news magazines and two or three great national newspapers and two or three television networks and two or three cable networks and uh you just had to get a broad audience and you had to have reliable information so that advertisers would want to put their product in the midst of the information you were giving”

A core tension in CRISPR ethics is between 'why should we do this' (caution about unknown consequences) and 'why not do this' (refusal to help dying children)—both positions have moral weight.

“on one hand we have the why should we do it but on the other hand why not why not do it and how can we sometimes say no how do you say no to somebody whose kid has multiple sclerosis or cystic fibrosis or has huntington's and say we're not going to try to edit that out would it be immoral not to use it”

David Sanchez, a 17-year-old with sickle cell disease, initially resisted germline editing to prevent sickle cell in his children because he believed the disease forged his character and gave him empathy—but later changed his view, recognizing he didn't want his children to suffer the pain.

“he's a 17 year old who loves playing basketball except for when he doubles over in pain in the middle of the court because he has sickle cell and so they're treating him for sickle cell at stanford at one point matthew porteous who's a great genetic engineer there says we may be able someday to edit your sperm or reproductive cells so your children won't have sickle cell and david sanchez says that would be great but then a little later he says but maybe that should be up to my kids after they're born for them to get to decide”

The concept of 'impute' means what something signals or implies when you first encounter it; Steve Jobs applied this principle to product design by ensuring every visual signal—from packaging to unboxable experience to invisible circuit board design—conveyed delight, craftsmanship, and quality.

“impute means what does something signal when you first see it what does it imply and you know i remember getting my first ipod you know a thousand songs in my pocket that's going to be great and as you open the box it opens up as almost as if it's a tiffany jewel box and their cradled in it is this wonderful object of desire your first ipod and it kind of imputes things it it doesn't just say here you know cut open the cellophane here it just has something magical”

Isaacson's role as a biographer and storyteller is to inspire the next generation through stories of creative and innovative people like Leonardo, Franklin, Jobs, and Doudna—so that young people reading his books will be motivated to pursue similarly creative and transformative work themselves.

“how do you want your work to be remembered you know there are people in the arena i started early on with a book with a friend called the wise men about the people who created american foreign policy uh right after world war ii and you know they're people like einstein and da vinci and steve jobs and now uh jennifer doudna those are the people who do things they see the world differently they push the human race forward i know that i'm not one of those people but i have a small role to play which is i tell their stories and i think being able to inspire people with their stories it may not make me certainly don't make me a leonardo da vinci or steve jobs or ben franklin but there's a role for some of us as i said growing up in louisiana being told don't be a preacher be a storyteller”

During the pandemic, innovation hubs demonstrated that creativity benefits from in-person interactions that are 'intimate' and 'face-to-face in real time'; this burst of initial collaboration can then disperse as the energy and insights are shared remotely via Dropbox, Zoom, and social media—creating a pattern of local intensity followed by distributed impact.

“if you want some bursts of creativity it helps to have a lot of people actually interacting in real time face to face in an intimate fashion and then you can disperse that creativity whether it's a group that gets together and starts figuring out how to do gene editing technology and then they all go to their labs around the world and do it on dropbox and zoom and other ways of social media”

Competition can have positive effects (driving scientists to work nights and weekends, accelerating discovery) and negative effects (encouraging ethical corners to be cut, as Watson and Crick took credit for Rosalind Franklin's work on DNA structure).

“competition can make you do bad things qriken watson purloin the imagery done by rosalind franklin without her permission but competition also causes you to work nights and weekends so my book is about the good sides and the bad sides of competition”

Jennifer Doudna was inspired as a middle schooler when she found James Watson's 'The Double Helix' on her bed—learning that women could become scientists by reading about Rosalind Franklin—and this inspiration caused her to change her planned major from French to chemistry, ultimately leading to her groundbreaking CRISPR work.

“when she was in middle school jennifer doudna came home one day and found on her bed the book the double helix by james watson that i mentioned earlier and she read it and she saw rosalind franklin this biochemist in it uh and she said oh i didn't know women could become scientists and she was inspired by rosalind franklin but also by watson and crick and others to say i want to become a scientist and so she had been thinking i'm going to study french but no she decides she's going to become a chemist”

Steve Jobs believed that physical spaces are 'the secret hiding in plain sight for creativity'; he designed the Pixar headquarters so that everyone had to walk through a common atrium where they would bump into people and exchange ideas, creating unscheduled encounters and serendipitous interactions that fuel innovation.

“steve jobs who designed the pixar headquarters to make sure everybody had to walk through the atrium and bump into people and exchange ideas to the apple headquarters to all of our places physical places tend to have serendipity to them they tend to be unscheduled encounters they tend to be things where you can actually gauge somebody's interests and emotions perhaps better”

When writing biography, Isaacson applies calibration: determining whether including a controversial or harmful detail furthers the book's purpose and justifies any pain it might cause to people who knew the subject. Near the end of his career, he chose to exclude some harsh statements Jobs made while sick and angry, prioritizing historical value and reader benefit over sensational or clickbait material.

“i took out things uh i used a calibration in a way which is how important is this for the reader to know and how hurtful might it be to somebody else in the book for example if he said something bad about one of his friends or somebody i knew he loved i'd say okay does it is that something that really furthers the goal of the book and is that somebody who'll give a lot of pain something that'll give a lot of pain to somebody who's friends with are very close to steve jobs and so maybe i was at that stage in my career where you don't want to put in everything that could be explosive or be a headline or be click bait because you're trying to do what's good for history and good for the reader”

There are two schools of thought in AI development: the 'Ada Lovelace school' that believes human-computer interfaces and connections will drive progress, exemplified by figures like Doug Engelbart, Alan Kay, and Steve Jobs; and the 'Alan Turing school' that believes machines will eventually acquire artificial intelligence surpassing humans, exemplified by Bill Gates.

“my book the innovators is about exploring the ada lovelace school which includes ada lovelace but doug engelbart and alan kaye and jcr licklider and culminates with steve jobs the people who believe that advances will come from human computer connections human computer interfaces like the graphical interfaces on our computer that make us closer to our machines and then the other school being the allen turing school that goes all the way through people including bill gates who think that machines will be able to acquire an artificial intelligence that will surpass humans and perhaps leave humans behind”

Specialization and silos have become more prevalent in modern institutions (universities, media, companies) than during Isaacson's era at TIME magazine; this trend reduces cross-domain pattern recognition and may limit future innovation.

“nowadays we tend to be more siloed whether you're at a university and you specialize in a silo or for that matter your journal your a media thing and you're not a general interest magazine there's not a market that much for general interest magazines so you become a podcast with a particular focus”

Jennifer Doudna had a nightmare about her CRISPR invention being used by Hitler, which shook her and motivated her to lead efforts to establish ethical guidelines, bringing together scientists, ethicists, and politicians to debate when CRISPR should and should not be used—recognizing that CRISPR poses both great promise and peril.

“after she invented this technology was shaken because she had a nightmare that somebody wanted to understand the technology she invented she goes into the room and it's adolf hitler and she realizes that in the wrong hands with the wrong sets of of social guidance on what we're going to use this tool for it could be both something of great promise but also of peril so my book is about her not only inventing these tools with her colleagues but also then gathering scientists as well as ethicists and politicians and ordinary people to say what are the rules of the road”

Isaacson receives daily emails from families of children with genetic diseases (Angelman syndrome, cystic fibrosis, sickle cell, Huntington's disease, multiple sclerosis) asking if he can connect them with Jennifer Doudna to save their child's life—these requests create emotional pressure to accelerate CRISPR research and weigh against caution about unknown risks.

“i'm heartbroken i'm looking my cell phone right here i could pull one up for you which is the emails i get every morning of people who've read the book and they say my child has you know engelman syndrome my child has cystic fibrosis my child here's a picture of him he's four years old but he can't go to the bathroom by himself and they say he's going to die in three years or here's my granddaughter and they say she has another you know five years to live because she's got this genetic uh condition can you get me in touch with jennifer doudna can you save my baby”

Cradles of creativity burn out when intolerant or authoritarian forces impose cultural restrictions, book burnings, or bonfires of vanities—as happened in Florence with Savonarola's backlash, and is happening currently with anti-modernity movements in parts of Europe and the United States.

“they tend to burn out sometimes when the tolerance and the diversity that distinguished say florence in the 1470s get hit by a saving a roller or somebody who's going to ban and burn books and have bonfires of the vanities and we see the backlash against creativity innovation and diversity happening we had happened in this country uh in over the past uh four or five years it's happened in europe some and in hungary”

Leonardo da Vinci had the ability to make no distinction between art and science—he saw them as unified ways of understanding reality—and this integration of artistic beauty and scientific precision characterized his approach to every project from painting the Mona Lisa to engineering water systems.

“like jobs he was at the intersection of technology and arts only in a very different era i think you said leonardo had the ability not just to connect art and science but to make no distinction between the beauty of art and science”

The pandemic enabled workers to relocate to places like New Orleans because they could work remotely, and many chose to move to locations with greater cultural richness, better food, more music, or higher perceived quality of life—suggesting that once people can work anywhere, they will gravitate toward communities with cultural amenities and existing innovation ecosystems.

“people during the pandemic moved to places like my hometown of new orleans because they could work anywhere and they decided they wanted to work in a place that was more fun or edgier or had more music or more food whatever they liked”

Jennifer Doudna initially opposed heritable genetic edits (germ-line editing in reproductive cells and early embryos) but became more open to the possibility after COVID-19 demonstrated the value of rapid medical innovation, and after learning that a Chinese scientist had already performed heritable edits—illustrating how thinking on gene editing evolves.

“when they do she's initially against the use of crispr especially to make inheritable edits called the germ line be able to edit sperm and egg cells and early stage embryos so that the edits will affect the entire all the cells of the newborn child and will be inherited by all future generations says that's where you should draw the line but at a certain point she became more and more open and certainly coveted helped open our minds to maybe the fact that one chinese doctor already edited the embryos of babies to give them inheritable edits to not have the receptor for hiv the virus that causes aids so maybe covet opens our minds a bit and says well maybe we should edit the species to have fewer viral receptors if we can do it safely without unintended consequences so jennifer dowden's thinking evolves”

Steve Jobs did not define himself by material possessions; he was not driven by accumulating fancy mansions or expensive houses, and took a long time before even acquiring furniture—in contrast to many other billionaires who accumulate status symbols, suggesting that spiritual grounding protects against materialism.

“steve jobs never had the fanciest mansions and he took quite a long time before he even got furniture for them because he didn't define himself by material object”