Category Archives: Must watch or read

Sapiens – A Brief History of Humankind by Yuval Noah Harari

Sapiens: A Brief History of Humankind is an extraordinary book. Very similar to Guns, Germs, and Steel: The Fates of Human Societies by Jared Diamond. It may not be directly related to innovation and start-ups, but below are some extracts I found striking. This is a must-read book…

By It is believed that the cover art can or could be obtained from the publisher.
Fair use,

“Consider the following quandary: two biologists from the same department, possessing the same professional skills, have both applied for a million-dollar grant to finance their current research projects. Professor Slughorn wants to study a disease that infects the udders of cows, causing a 10 percent decrease in their milk production. Professor Sprout wants to study whether cows suffer mentally when they are separated from their calves. Assuming that the amount of money is limited, and that it is impossible to finance both research projects, which should be funded?

There is no scientific answer to this question. There are only political, economic and religious answers. In today’s world, it is obvious that Slughorn has a better chance of getting the money. Not because udder diseases are scientifically more interesting than bovine mentality, but because the dairy industry which stands to benefit from the research, has more political and economic clout than the animal-rights lobby.

Perhaps in a strict Hindu society, where cows are sacred, or in a society committed to animal rights, Professor Sprout would have a better shot. But as long as she lives in a society that values the commercial potential of milk and the health of its human citizens over the feelings of cows, she’d best write up her research proposal so as to appeal to those assumptions. For example, she might write that ‘Depression leads to a decrease in milk production. IF we understand the mental world of dairy cows, we could develop psychiatric medication that will improve their mood, thus raising milk production by up to 10 percent. I estimate that there is a global market of $250 million for bovine psychiatric medication.’ […] In short, scientific research can flourish only in alliance with some religion or ideology.” [Pages 304-305]

So how science developed in apparently useless fields?

“The key factor was that the plant-seeking botanist and the colony-seeking naval officer shared a similar mindset. Both scientist and conqueror began by admitting ignorance – they both said ‘I don’t know what’s out there.’ They both felt compelled to go out and make new discoveries. And they both hoped the new knowledge thus acquired would make them master the world.

European imperialism was entirely unlike all other imperial projects in history. Previous seekers of empire tended to assume that they already understood the world. Conquest merely utilized and spread their views of the world. […] European imperialists set out distant shores in the hope of obtaining new knowledge along new territories.” [Page 317]


[Page 279] “Modern science differs (mention Steve Weinberg here?) from all previous traditions of knowledge in three critical ways:
a. The willingness to admit ignorance. Modern science is based on the Latin injunction Ignoramus – ‘we don’t know’. It assumes that we don’t know everything. Even more critically, it assumes that the things we think we know could be proven wrong as we gain more knowledge. No concept, idea or theory is sacred and beyond challenge.
b. The centrality of observation and mathematics. Having admitted ignorance, modern science aims to obtain new knowledge. It does so by gathering observations and then using mathematical tools to connect these observations into comprehensive theories.
c. The acquisition of new powers. Modern science is not content with creating theories. It uses these theories in order to acquire new powers, and in particular to develop new technologies.”

[Pages 320-2] “The first modern man was Amerigo Vespucci.” [And not Columbus who contrarily to this lesser-known Italian sailor, was always convinced he had arrived in India and not on a new continent.] […] “Columbus stuck to this error for the rest of his life.” […] “There is poetic justice in the fact that a quarter of the world, and two of its seven continents, are named after a little-known Italian whose sole claim is that he had the courage to say, ‘We don’t know’. The discovery of America was the fundamental event of the Scientific Revolution.”

[This reminds me the day of my PhD oral presentation. A colleague of mine was surprised I dare answering ‘I don’t know’ to a question of a member of the jury. My colleague had also missed the point, I think…]

Chapters 14-16 describe how science, politics and economics are interconnected. They may be less surprising but are as convincing. Here is a disturbing extract: “Conversely, the history of capitalism is unintelligible without taking science into account. […] Over the last few years, banks and governments have been frenziedly printing money. Everybody is terrified that the current economic crisis may stop the growth of the economy. So they are creating trillions of dollars, euros and yen out of thin air, pumping cheap credit into the system, and hoping that the scientists, technicians and engineers will manage to come up with something really big, before the bubble bursts. Everything depends on the people in the labs. New discoveries in fields such as biotechnology and nanotechnology could create entire new industries, whose profits could back the trillions of make-believe money that the banks and governments have created since 2008. If the labs do not fulfill these expectations before the bubble bursts, we are heading towards very rough times.” [Page 352]

The Halo Effect by Phil Rosenzweig

When I read that Nassim Nicholas Taleb said this is “one of the most important management books of all time”, I was intrigued. Usually I do not like general business books. But here, not only is it a great book, but fun to read!

What is the halo effect? A tendency to make inferences about specific traits on the basis of a general impression [Page 50].

The author has a major question: Is management a science? Pages 12-17 cover that sensitive topic: “In other fields, from medicine to chemistry to aeronautical engineering, knowledge seems to march ahead relentlessly. What do these fields have in common? In a word, these fields move forward thanks to a form of inquiry we call science. Richard Feynman once defined science as “a method for trying to answer questions which can be put into the form: If I do this, what will happen?” Science isn’t about beauty or truth or justice or wisdom or ethics. It’s eminently practical. It asks, If I do something over here, what will happen over there? If I apply this much force, or that much heat, or if I mix these chemicals, what will happen? By this definition, What leads to sustained profitable growth? is a scientific question. It asks, If a company does this or that, what will happen to its revenues or profits or share price?” [Page 12]

“Our inability to capture the full complexity of the business world through scientific experiments has provided fodder for some critics of business schools. Management gurus Warren Bennis and James O’Toole, in 2005 Harvard Business Review article, criticized business schools for their reliance on the scientific method. They wrote: “This scientific model is predicated on the faulty assumption that business is an academic discipline like chemistry or geology when, in fact, business is a profession and business schools are professional schools – or should be”. The notion seems to be that since business will never be understood with the precision of the natural sciences, it’s best understood as a sort of humanity, a realm where the logic of scientific inquiry doesn’t apply. Well, yes and no.” [Page 14]

Rozenzweig concludes this 1st chapter with a beautiful story (page 16), again from Richard Feynman: In the South Seas, there is a cult of people. During the war they saw airplanes land with lots of materials, and they want the same thing to happen now. So they’ve arranged to make things like runways, to put fires along the sides of the runways, to make a wooden hut for a man to sit in, with two wooden pieces on his head like headphones and bars of bamboo sticking out like antennas – he’s the controller. And they wait for the airplanes to land. They’re doing everything right. The form is perfect. But it doesn’t work. No airplanes land. So I call these things Cargo Cult Science, because they follow all the apparent precepts and forms of scientific investigation, but they’re missing something essential, because the planes don’t land. He called that last section Science, Pseudoscience and Coconut Headsets.

Storytelling and science

His criticism in chapter 6 of famous bestsellers In Search of Excellence by Peters and Waterman [page 83] and then of Built to Last by Collins and Porras [page 94] are particularly striking. Stories and science are different and the author explains many delusions created by approximate science:
#1: The Hallo Effect
#2: The delusion of Correlation and Causality
#3: The Delusion of Single Explanations
#4: The Delusion of Connecting the Winning Dots
#5: The Delusion of Rigorous Research
#6: The Delusion of Lasting Success
#7: The Delusion of Absolute Performance
#8: The Delusion of the Wrong End of the Stick
#9: The Delusion of Organizational Physics.
(if you are too lazy to read this great book, have at least a look at

Rosenzweig tries to explain the complexity of measuring company performance. What are the key elements that managers should take into account for excellence? And Rosenzweig shows that storytelling has been as important as research in that quest. He further claims that authors of bestsellers such as In Search of Excellence, Built to Last or From Good to Great who claim their results were based on research, indeed were more excellent story tellers than rigorous researchers.
“It’s not that the important elements are not right. In Search of Excellence gives eight best practice: a bias for action; staying close to the customer; autonomy and entrepreneurship; productivity through people; hands-on, value-driven; stick to the knitting; simple form, lean staff; and simultaneous loose-tight properties.” [Page 85]

“Whereas in Built to Last, Collins and Porras give their 5 timeless principles: having a strong core ideology; building a strong corporate culture; setting audacious goals; developing and promoting people; creating a spirit of experimentation and risk-taking; driving for excellence”. [Page 96]

“Several researchers have studied the rate at which company performance changes over time. Pankaj Ghemawat at Harvard Business School examined the return on investments (ROI) of a sample of 692 American companies over a ten-year period from 1971 to 1980. He put together one group of top performers, with an average ROI of 39 percent, and one group of low performers, with an average ROI of just 3 percent. Then he tracked the two groups over time. What would happen to their ROIS? Would the gap persist, would it grow, or would it diminish? After nine years, both groups converged together toward the middle, the top performers falling from 39 percent to 21 percent and the low performers rising from 3 percent to 18 percent.” [Page 104]

“These studies, and others like them, all point to the basic nature of competition in a market economy. Competitive advantage is hard to sustain. Sure, if you want to, you can look back over seventy years of business history and pick out a handful of companies that have endured, but that’s selection based on outcomes.” [Page 105]

“Interviews with managers, asking them to look back over the ten-year period and recount their experiences (…) these sort of retrospective interviews are likely to be full of halos, as people take cues from performance and make attributions accordingly.” [Page 108]

Again Rosenzwieg has nothing against interviews, he just warns the reader that they have to be meticulously prepared to avoid any bias and answers based on outcomes.
“Another famous study, the Evergreen project, identified eight practices: strategy; execution; culture; structure; talent; leadership; innovation; and mergers and partnerships (Page 110). Yet once we see that performance is relative, it becomes obvious that companies can never achieve success simply by following a given set of steps, no matter how well intended; their success will always be affected by what rivals do” [Page 116].

“Perhaps the most interesting factor in Big Winners and Big Losers is mentioned as a brief aside but not examined closely: Marcus points out that large companies show up more frequently among the Big Losers, while almost all the Big Winners are small or midsize companies. This observation ought to spark one’s curiosity, because large companies got that way in the first place by doing things well – they didn’t grow by being Losers – yet something seemed to prevent them from maintaining that high performance. Extremer performance, for better and for worse, is more common among small companies”. [Page 132]

But a 10 percent difference in performance doesn’t say anything about what will happen at my company – the impact could be more or less or nothing at all. There’s no guarantee, no promise that inspires me to take action. Books, which provide simple and definitive advice and studies of organizational performance, stand in two very different worlds. The first world speaks to practicing managers and rewards speculations about how to improve performance. The second world demands and rewards adherence to rigorous standards of scholarship. Here science is paramount, storytelling less so. The result is a schizophrenic tour de force in which the demands of the roles of the consultant and teacher are disassociated form the demands of the researcher”. [Page 135]

“According to the Economist, Tom Peters can charge corporate clients up to $85,000 for a single appearance, and Jim Collins commands a fee of $150,000. There’s a lucrative market for spinning stories of corporate success. Will anyone hire (a researcher) at $85,000 or $150,000 a pop to talk about a statistically significant 4 percent difference in performance? Somehow it seems doubtful [page 136].

The test of a good story is not whether it is entirely, fully, scientifically accurate – by definition it won’t be. Rather, the test of a good story is whether it leads us toward valuable insights, if it is inspires towards helpful action, at least most of the time. [Page 137]

Strategy and execution

“Here’s how I like to think about company performance. According to Michael Porter of Harvard Business School, company performance is driven by two things: Strategy and execution.” [Page 144]

But both are full of uncertainties: “Strategy always involves risk because we don’t know for sure how our choices will turn out. […] A first reason has to do with customers. […] Sam Philips, the legendary Sun records producer, once cautioned, “Anytime we think you know what the public’s going to want that’s when you know you’re looking at a damn fool when you’re looking in the mirror”. Market reaction is always uncertain, and smart strategists know it. [Page 146]

“A second source of risk has to do with competitors. […] An entire branch of economics, game theory, has grown up around a simple form of competitive intelligence. […] A third source of risk comes from technological change. […] In his groundbreaking research Clayton Christensens at Harvard Business School showed that in a wide range of industries, from earth-moving equipment to disk drives to steel, successful companies were repeatedly dislodged by new technologies. [Page 147]

Jim Collins expressed surprised that [his] eleven Great companies came from ordinary, unspectacular industries. […] I suspect a different interpretation. These industries can be described as dowdy, but a better word might be stable. They were less subject to radical changes in technology, were less susceptible to shifts in customer demand, and may have had less intense competition. [Page 147]

As James March of Stanford and Zur Shapira of New York University explained, “Posthoc reconstruction permits history to be told in such a way that “chance”, either in the sense of genuinely probabilistic phenomena or in the senses of unexplained variation, is minimized as an explanation.” But chance does play a role, and the difference between a brilliant visionary and a foolish gambler is usually inferred after the fact, an attribution based on outcomes. [Page 150]

There are fewer unknowns […], yet execution still involves a number of uncertainties. [Page 151] And that brings us to the best answer I can provide to the question, What leads to high performance? If we set the usual suspects of leadership and culture and focus and so on – which are perhaps causes of performance – we’re left with two broad categories: strategic choice and execution. The former is inherently risky since it’s based on our best guesses about customers, about competitors, and technology, as well as about our internal capabilities. The latter is uncertain because best practices that work well on one company may not have the same effect in another. […] Wise managers know that business is about finding ways to improve the odds of success – but never imagine that success is certain. If a company makes strategic choices which are shrewd, works hard to operate effectively, and is favored by Lady Luck, it may put some distance between itself and its rivals, at least for a time. But even those profits will tend to erode over time. [Page 156]

The answer to the question what really works? is simple: Nothing really works. At least not all the time. […] So what can be done? A first step is to set aside the delusions that color so much of our thinking about business performance. To accept that few companies achieve lasting success. To admit that the margin between success and failure is often very narrow, and never quite as distinct or as enduring as it appears at a distance. And finally, to acknowledge that luck often plays a role in company success. [Page 158]

Rosenzweig finishes his book with examples of bold decisions from leaders at Goldman Sachs, Intel, BP, Logitech. Entrepreneurship inherently involves risks, but not doing anything would be much riskier.

HBO’s Silicon Valley is back – Season 3

What a pleasure to meet again the heroes of HBO’s Silicon Valley. Yet the first two episodes are quite caricatural. First all the hot technologies from the region are mentioned: robotics, virtual reality and artificial intelligence.


Failure is an important component, and does not have exactly the same consequences for everyone.


Of course, the episodes describe the extreme social situations: the problems of the wealthy (money) and the problems of the poor (money). Finally we also see the equally caricatureal opposition between engineers and sales people.


But all in all, the pleasure is there, and that’s what matters!… Even if the last sentence of Episode 2 is “Every day things are getting worse…”

Alexander Grothendieck, 1928 – 2014

What link is there between Andrew Grove (the previous article) and Alexandre Grothendieck? Beyond their common initials, a similar youth – both were born in the communist Eastern Europe they left for a career in the West) and the fact they have become icons of their world, they just represent my two professional passions: startups and mathematics. The comparison stops there, no doubt, but I’ll get back to it.

Two books (both in French) were published in January 2016 about the life of this genius: Alexander Grothendieck – in the footsteps of the last mathematical genius by Philippe Douroux and Algebra – elements of the life of Alexander Grothendieck by Yan Pradeau. If you like mathematics (I should say the mathematical science) or even if you do not like it, read these biographies.


I knew as many others about the atypical route of this stateless citizen who became a great figure of mathematics – he received the Fields Medal in 1966 – and then decided to live in seclusion from the world for over 25 years in a small village close to the Pyrenees until his death in 2014. I also have to confess that I knew nothing of his work. Reading these two books shows me that I was not the only one, as Grothendieck had explored lands that few mathematicians could follow. I also found the following stories:
– At age 11, he calculated the circumference of the circle and deduced that π is equal to 3.
– Later, he reconstructed the theory of Lebesgue measure. He was not 20 years old.
– A prime number has his name, 57, who nevertheless is 3 x 19.
Yes, it is worth discovering the life of this illustrious mathematician.


The reason for the connection I made between Grove and Grothendieck is actually quite tenuous. It comes from this quote: “There are only two true visionaries in the history of Silicon Valley. Jobs and Noyce. Their vision was to build great companies … Steve was twenty, un-degreed, some people said unwashed, and he looked like Ho Chi Minh. But he was a bright person then, and is a brighter man now … Phenomenal achievement done by somebody in his very early twenties … Bob was one of those people who could maintain perspective because he was inordinately bright. Steve could not. He was very, very passionate, highly competitive.” Grove was close Noyce in more ways than one, and extremely rational and according to Grove, Noyce was too lax! Grothendieck would be closer to Jobs. A hippie, a passionate individual and also somehow self-taught. Success can come from so diverse personalities.


Last point in common or perhaps a difference. The migration. Grove became a pure American. Grothendieck was an eternal stateless, despite his French passport. But both show its importance. Silicon Valley is full of migrants. I often talk about this here. We know less that what is called “the French school of mathematics” also has its migrants. If you go to the French wikipedia page of the Fields Medal, you can read:

Ten “Fields medalists’ are former students of the Ecole Normale Superieure: Laurent Schwartz (1950), Jean-Pierre Serre (1954), René Thom (1958), Alain Connes (1982), Pierre-Louis Lions (1994) Jean-Christophe Yoccoz (1994), Laurent Lafforgue (2002), Wendelin Werner (2006), Cédric Villani (2010) and Ngo Bao Chau (2010). This would make “Ulm” the second institution after the ‘Princeton’ winners, if the ranking was the university of origin of the medal and not the place of production. Regarding the country of origin, we arrive at a total of fifteen Fields medalists from French laboratories, which could put France ahead as the formative nations of these eminent mathematicians.

But in addition to Grothendieck, the stateless, Pierre Deligne, Belgian, had his thesis with him, Wendelin Werner was naturalized at the age of 9 years, Ngo Bao Châu the year he received the Fields Medal, after doing all his graduate studies in France, and Artur Avila is Brazilian and French … One could speak of the International of Mathematics, which might not have displeased Alexander Grothendieck.

The business of biotech – Part 3: Genentech

I should have begun with Genentech this series of posts about Biotech (see part 1: Amgen or part 2 about more general stats). Genentech was not the first biotech start-up, it was Cetus, but Genentech was really the one which launched and defined this industry. All this really began with the Cohen Boyer collaboration. Genentech would have loved to get an exclusive license on their patent about recombinant DNA, but the universities could not agree for business as well as political reasons. Genentech was an unknown little start-up and genetic engineering a very sensitive topic at the time. Swanson had tried even to offer shares to Stanford and UCSF (the equivalent of 5% of the existing shares at the time).

Please note I already wrote about Genentech here in Bob Swanson & Herbert Boyer: Genentech. But this new post follows my reading of Genentech – The Beginnings of Biotech by Sally Smith Hughes.


– November 1972 – Meeting of Cohen and Boyer at aconference in Hawaii
– March 1973: First joint lab. experiments
– November 1973: Scientific publication
– November 4, 1974: Patent filing
– May 1975: Cohen becomes an advisor for Cetus
– January 1976: Meeting between Swanson and Boyer
– April 7, 1976: Genentech foundation
– August 1878: first insulin produced
– Q2 1979: 4 research projects with Hoffmann – La Roche (interferon), Monsanto (animal growth hormone), Institut Mérieux (hepatitis B vaccine) and an internal one (thymosin).
– July 1979: first human growth hormone
– October 1982: FDA approval of Genentech insulin produced
– October 1985: FDA approval of human growth hormone

I have to admit I had never heard of the Bancroft Library’s website ( for the Program in Bioscience and Biotechnology Studies, “which centerpiece is a continually expanding oral history collection on bioscience and biotechnology [with ] in-depth, fully searchable interviews with basic biological scientists from numerous disciplines; with scientists, executives, attorneys, and others from the biotechnology industry.”

The invention of new research and business practices over a very short period

Swanson was captivated: “This idea [of genetic engineering] is absolutely fantastic; it is revolutionary; it will change the world; it’s the most important thing I have ever heard.” [… But Swanson was nearly alone.] “Cetus was not alone in its hesitation regarding the industrial application of recombinant DNA technology. Pharmaceutical and chemical corporations, conservative institutions at heart, also had reservations.” [Page 32] “Whatever practical applications I could see for recombinant DNA… were five to ten years away, and, therefore, there was no rush to get started, from a scientific point of view.” [Page 32] “I always maintain” Boyer reminisced, “that the best attribute we had was our naïveté… I think if we had known about all the problems we were going to encounter, we would have thought twice about starting… Naïveté was the extra added ingredient in biotechnology.” [Page 36]

The book shows the importance of scientific collaborations. Not just Boyer at UCSF but for example with a hospital in Los Angeles. A license was signed with City of Hope Hospital with a 2% royalty on sales on products based on the licensed technology. “[…] negotiated an agreement between Genentech and City of Hope that gave Genentech exclusive ownership of any and all patents based on the work and paid the medical center a 2 percent royalty on sales of products arising from the research.” [Page 57]

Even if in 2000, City of Hope had received $285M in royalties, it was not happy with the outcome. After many trials, the California Supreme Court in 2008 awarded another $300M to City of Hope. So the book shows that these collaborations gave also much legal litigation. [Page 58]

In a few years, Genentech could synthesize somatostatin, insulin, human growth hormone and interferon. It is fascinating to read how intense, uncertain, stressful these years were for Swanson, Perkins, Boyer and the small group of Genentech employees and academic partners (Goeddel, Kleid, Heyneker, Seeburg, Riggs, Itakura, Crea), in part because of the emerging competition from other start-ups (Biogen, Chiron) and academic labs (Harvard, UCSF).

“On August 25, 1978 – four days after Goeddel’s insulin chain-joining feat – the two parties signed a multimillion-dollar, twenty-year research and development agreement. For an upfront licensing fee of $500,000, Lilly got what it wanted: exclusive worldwide rights to manufacture and market human insulin using Genentech’s technology. Genentech was to receive 6 percent royalties and City of Hope 2 percent royalties on product sales.” [Page 94] They managed to negotiate a contractual condition limiting Lilly’s use of Genentech’s engineered bacteria to the manufacture of recombinant insulin alone. The technology would remain Genentech’s property, or so they expected. As it turned out, the contract, and that clause in particular, became a basis for a prolonged litigation. In 1990, the courts awarded Genentech over $150 million in a decision determining that Lilly had violated the 1978 contract by using a component of Genentech’s insulin technology in making its own human growth hormone product. [Page 95] Perkins believed that the 8 percent royalty rate was unusually high, at a time when royalties on pharmaceutical products were along the lines of 3 or 4 percent. “It was kind of exorbitant royalty, but we agreed anyway – Lilly was anxious to be first (with human insulin)” […]The big company – small company template that Genentech and Lilly promulgated in molecular biology would become a prominent organizational form in a coming biotechnology industry. [Page 97]

The invention of a new culture

Young as Swanson was, he kept everyone focused on product-oriented research. He continued to have scant tolerance for spending time, effort, and money on research not tied directly to producing marketable products. “We were interested in making something usable that you could turn into a drug, inject in humans, take to clinical trials.” A few year before his premature death, Swanson remarked, “I think one of the things I did best in those days was to keep us very focused on making a product.“ His goal-directed management style differed markedly from that of Genentech’s close competitors. [Page 129]

But at the same time Boyer would guarantee a high quality research level by encouraging employees to write the best possible scientific articles. This guaranteed the reputation of Genentech in the academic world.

A culture was taking shape at Genentech that had no exact counterpart in industry or academia. The high-tech firms in Silicon Valley and along Route 128 in Massachusetts shared its emphasis on innovation, fast-moving research, and intellectual property creation and protection. But the electronics and computer industries, and every other industrial sector for that matter, lacked the close, significant, and sustained ties with university research that Genentech drew upon from the start and that continue to define the biotechnology industry of today. Virtually every element in the company’s research endeavor – from its scientists to its intellectual and technological foundations – had originated in decade upon decade of accumulated basic-science knowledge generated in academic labs. […] At Boyer’s insistence, the scientists were encouraged to publish and engage in the wide community of science. [Page 131]

But academic values had to accommodate corporate realities: at Swanson’s insistence, research was to lead to strong patents, marketable products, and profit. Genentech’s culture was in short a hybrid of academic values brought in line with commercial objectives and practices. [Page 132]

Swanson was the supportive but insistent slave driver, urging on employees beyond their perceived limits: “Bob wanted everything. He would say, If you don’t have more things on your plate than you can accomplish, then you’re not trying hard enough. He wanted you to have a large enough list that you couldn’t possibly get everything done, and yet he wanted you to try.” […] Fledging start-ups pitted against pharmaceutical giants could compete mainly by being more innovative, aggressive, and fleet of foot. Early Genentech had those attributes in spades. Swanson expected – demanded – a lot of everyone. His attitude was as Roberto Crea recalled: “Go get it; be there first; we have to beat everybody else… We were small, undercapitalized, and relatively unknown to the world. We had to perform better than anybody else to gain legitimacy in the new industry. Once we did, we wanted to maintain leadership.” […] As Perkins said “Bob would never be accused of lacking a sense of urgency. “ […] Even Ullrich, despite European discomfort with raucous American behavior, admitted to being seduced by Genentech’s unswervingly committed, can-do culture. [Page 133]

New exit strategies

Initially Kleiner thought Genentech would be acquired by a major pharma company. It was just a question of when. He approached Johnson and Johnson and “floated the idea of a purchase price of $80 million. The offer fell flat. Fred Middleton [Genentech’s VP of finance], present at the negotiations, speculated that J&J didn’t have “a clue about what to do with this [recombinant DNA] technology – certainly didn’t know what it was worth. They couldn’t fit it in a Band-Aid mold”. J&J executives were unsure how to value Genentech, there being no standard for comparison or history of earnings.” [Page 140]

Perkins and Swanson made one more attempt to sell Genentech. Late in 1979, Perkins, Swanson, Kiley and Middleton boarded a plane for Indianapolis to meet with Eli Lilly’s CEO and others in top management. Perkins suggested a selling price of $100 million. Middleton’s view is that Lilly was hamstrung by a conservative “not invented here” mentality, an opinion supported by the drug firm’s reputation for relying primarily on internal research and only reluctantly on outside contracts. The company’s technology was too novel, too experimental, too unconventional for a conservative pharmaceutical industry to adopt whole-heartedly. [Page 141]

When Genentech successfully developed interferon, a new opportunity happened. Interferon had been discovered in 1957 and thought to prevent virus infection. In November 1978, Swanson signed a confidential letter of intent with Hoffmann – La Roche and a formal agreement in January 1980. They were also lucky: “Heyneker and a colleague attended a scientific meeting in which the speaker – to everyone’s astonishment given the field’s intense competitiveness – projected a slide of a partial sequence of fibroblast interferon. They telephoned the information to Goeddel, who instantly relay the sequence order to Crea. […] Crea started to construct the required probes. […] Goeddel constructed a “library” of thousands upon thousands of bacterial cells, seeking ones with interferon gene. Using the partial sequence Pestka retrieved, Goeddel cloned full-length DNA sequences for both fibroblast and leukocyte interferon. […] In June 1980, after filing patent protection, Genentech announced the production in collaboration with Roche.” [Page 145] Genentech could consider going public and after another fight between Perkins and Swanson, Genentech decided to do so. Perkins had seen that the year 1980 was perfect for financing biotech companies through a public offering but Swanson saw the challenges this would mean for a young company with nearly no revenue or product.

New role models

The 1980-81 period would see the creation of a fleet of entrepreneurial biology-based companies – Amgen, Chiron, Calgene, Molecular Genetics, Integrated Genetics, and firms of a lesser note – all inspired by Genentech’s example of a new organizational model for biological and pharmaceutical research. Before the IPO window closed in 1983, eleven biotech companies in addition to Genentech and Cetus, had gone public*. […] But not only institutions were transformed. Genentech’s IPO transformed Herb Boyer, the small-town guy of blue-collar origins, into molecular biology’s first industrial multimillionaire. For admiring scientists laboring at meager academic salaries in relative obscurity, he became a conspicuous inspiration for their own research might be reoriented and their reputation enhanced. If unassuming Herb – just a guy from Pittsburgh, as a colleague observed – could found a successful company with all the rewards and renown that entailed, why couldn’t they? [Page 161]

*: According to one source, the companies staging IPO were Genetic Systems, Ribi Immunochem, Genome Therapeutics, Centocor, Bio-Technology General, California Biotechnology, Immunex, Amgen, Biogen, Chiron, and Immunomedics. (Robbins-Roth, From Alchemy To Ipo: The Business Of Biotechnology)

Following these three posts, I might write a fourth one about academic licenses in the biotechnology if and when I find some time…

Elon Musk and the Secret Sauce of Entrepreneurship (according to Tim Urban)

A student of mine (thanks 🙂 ) just sent me a link to amazingly great blog articles about Elon Musk. I had never of heard of the author, Tim Urban, and his blog Wait But Why but I will certainly follow his work from now on.

Tim Urban has written four articles about “the world’s most remarkable living entrepreneur.”
Part 1: Elon Musk: The World’s Raddest Man.
Part 2: How Tesla Will Change the World.
Part 3: How (and Why) SpaceX Will Colonize Mars.
Part 4: The Chef and the Cook: Musk’s Secret Sauce.
These 4 posts represent hundreds of pages if you print them. No kidding. I’ve read part 4 and it was a real (positive) shock. Tim Urban explains Musk’s entrepreneurial strengths. I just give some extracts but if must read it all (if you find the time).

“I think generally people’s thinking process is too bound by convention or analogy to prior experiences. It’s rare that people try to think of something on a first principles basis. They’ll say, “We’ll do that because it’s always been done that way.” Or they’ll not do it because “Well, nobody’s ever done that, so it must not be good.” But that’s just a ridiculous way to think. You have to build up the reasoning from the ground up —“from the first principles” is the phrase that’s used in physics. You look at the fundamentals and construct your reasoning from that, and then you see if you have a conclusion that works or doesn’t work, and it may or may not be different from what people have done in the past.” […] Musk is an impressive chef for sure, but what makes him such an extreme standout isn’t that he’s impressive — it’s that most of us aren’t chefs at all. […] “When I was a little kid, I was really scared of the dark. But then I came to understand, dark just means the absence of photons in the visible wavelength—400 to 700 nanometers. Then I thought, well it’s really silly to be afraid of a lack of photons. Then I wasn’t afraid of the dark anymore after that.” That’s just a kid chef assessing the actual facts of a situation and deciding that his fear was misplaced. As an adult, Musk said this: “Sometimes people fear starting a company too much. Really, what’s the worst that could go wrong? You’re not gonna starve to death, you’re not gonna die of exposure—what’s the worst that could go wrong?” Same quote, right? […] That’s Elon Musk’s secret sauce. Which is why the real story here isn’t Musk. It’s us. […] People believe thinking outside the box takes intelligence and creativity, but it’s mostly about independence. When you simply ignore the box and build your reasoning from scratch, whether you’re brilliant or not, you end up with a unique conclusion—one that may or may not fall within the box.


Then Tim Urban quotes Steve Jobs from his famous speech at Stanford in 2005 (I think): “When you grow up, you tend to get told the world is the way it is and your life is just to live your life inside the world. Try not to bash into the walls too much. Try to have a nice family life, have fun, save a little money. That’s a very limited life. Life can be much broader once you discover one simple fact. And that is: Everything around you that you call life was made up by people that were no smarter than you. And you can change it, you can influence it, you can build your own things that other people can use. Once you learn that, you’ll never be the same again.”


And all this reminds me about an essay I mentioned in the conclusion of my book, an essay by Wilhelm Reich, the great psychoanalyst, who he wrote in 1945: “Listen, Little Man”. A small essay by the number of pages, a big one in the impact it creates. “I want to tell you something, Little Man; you lost the meaning of what is best inside yourself. You strangled it. You kill it wherever you find it inside others, inside your children, inside your wife, inside your husband, inside your father and inside your mother. You are little and you want to remain little.” The Little Man, it’s you, it’s me. The Little Man is afraid, he only dreams of normality; it is inside all of us. We hide under the umbrella of authority and do not see our freedom anymore. Nothing comes without effort, without risk, without failure sometimes. “You look for happiness, but you prefer security, even at the cost of your spinal cord, even at the cost of your life”.

Tim Urban is absolutely right and you need to read his piece about dogma and tribes. He made me think again of my readings of the great French philosopher Cynthia Fleury and how we need to balance the individuals and the groups and why democracy is a fragile jewel of societies…

PS: I totally forgot to mention a video that a colleague of mine (thanks to her now 🙂 ) mentioned a few days ago. BY one of these nice coincidences of life, it is precisely one of the arguments of Tim Urban about why some people are “cooks” (followers or incremental innovators) and others “chefs” (disruptive innovators). Enjoy!

Isaacson’s The Innovators (final thoughts) – is the future about thinking machines?

It is always very sad to end reading a great book, but Isaascon’s beautifully finishes his with Ada Lovelace considerations (during the 19th century!) about the role of computers. “Ada might also be justified in boasting that she was correct, at least thus far, in her more controversial contention that no computer, no matter how powerful would ever truly be a “thinking” machine. A century after she died, Alan Turing dubbed the “Lady Lovelace’s Objection” and tried to dismiss it by providing an operational definition of a thinking machine. […] But it’s now been more than sixty years, and the machines that attempt to fool people on the test are at best engaging in lame conversation tricks rather than actual thinking. Certainly none has cleared Ada’s higher bar of being able to “originate” any thoughts of its own. […] Artificial intelligence enthusiasts have long been promising, or threatening, that machines like HAL would soon merge and prove Ada wrong. Such was the promise of the 1956 conference at Dartmouth organized by John McCarthy and Marvin Minsky, where the field of artificial intelligence was launched. The conference concluded that a breakthrough was about twenty years away. It wasn’t.” [Page 468]

Ada, Countess of Lovelace, 1840

John von Neumann realized that the architecture of the human brain is fundamentally different. Digital computers deal in precise units, whereas the brain, to the extent we understand it, is also partly an analog system which deals with a continuum of possibilities, […] not just binary yes-no data but also answers such as “maybe” and “probably” and infinite other nuances, including occasional bafflement. Von Neumann suggested that the future of intelligent computing might require abandoning the purely digital approach and creating “mixed procedures”. [Page 469]

“Artifical Intelligence”

Discussion about artificial intelligence flared up a bit, at least in the popular press, after IBM’s Deep Blue, a chess-playing machine beat the world champion Garry Kasparov in 1997 and then Watson, its natural-language question-answering computer won at Jeopardy! But […] these were not breakthroughs of human-like artificial intelligence, as IBM’s CEO was first to admit. Deep Blue won by brute force. […To] one question about the “anatomical oddity” of the former Olympic gymnast George Eyer, Watson answered “What is a leg?” The correct answer was that Eyer was missing a leg. The problem was understanding “oddity”, explained David Ferruci, who ran the Watson project at IBM. “The computer wouldn’t know that a missing leg is odder than anything else.” […]
“Watson did not understand the questions, nor its answers, nor that some of its answers were right and some wrong, nor that it was playing a game, nor that it won – because it doesn’t understand anything, according to John Searle [a Berkeley philosophy professor]. “Computers today are brilliant idiots” John E. Kelly III, IBM’s director of research. “These recent achievements have, ironically, underscored the limitations of computer science and artificial intelligence.” Professor Tomaso Poggio, director of the Center of Brain, Minds, and Machines at MIT. “We do not yet understand how the brain gives rise to intelligence, nor do we know how to build machines that are as broadly intelligent as we are.” Ask Google “Can a crocodile play basketball?” and it will have no clue, even though a toddler could tell you, after a bit of giggling.
[Pages 470-71] I tried the question on Google and guess what. It gave me the extract by Isaacson…

The human brain not only combines analog and digital processes, it also is a distributed system, like the Internet, rather than a centralized one. […] It took scientists forty years to map the neurological activity of the one-millimeter long roundworm, which has 302 neurons and 8,000 synapses. The human brain has 86 billion neurons and up to 150 trillion synapses. […] IBM and Qualcomm each disclosed plans to build “neuromorphic”, or brain-like, computer processors, and a European research consortium called the Human Brain project announced that it had built a neuromorphic microchip that incorporated “fifty million plastic synapses and 200,000 biologically realistic neuron models on a single 8-inch silicon wafer. […] These latest advances may even lead to the “Singularity” a term that von Neumann coined and the futurist Ray Kurzweil and the science fiction writer Vernor Vinge popularized, which is sometimes used to describe the moment when computers are not only smarter than humans but also can design themselves to be even supersmarter, and will thus no longer need us mortals. Isaacon is wiser than I am (as I feel that these ideas are stupid) when he adds: “We can leave the debate to the futurists. Indeed depending on your definition of consciousness, it may never happen. We can leave “that” debate to the philosophers and theologians. “Human ingenuity” wrote Leonardo da Vinci “will never devise any inventions more beautiful, nor more simple, nor more to the purpose than Nature does”. [Pages 472-74]

Computers as a Complement to Humans

Isaacson adds: “There is however another possibility, one that Ada Lovelace would like. Machines would not replace humans but would instead become their partners. What humans would bring is originality and creativity” [page 475]. After explaining that in a 2005 chess tournament, “the final winner was not a grandmaster nor a state-of-the-art computer, not even a combination of both, but two Americans amateurs who used three computers at the same time and knew how to manage the process of collaborating with their machines” (page 476) and that “in order to be useful, the IBM team realized [Watson] needed to interact [with humans] in a manner that made collaboration pleasant” (page 477) Isaacson further speculates:

Let us assume, for example, that a machine someday exhibits all of the mental capabilitie of a human: giving the outward appearance of recognizing patterns, perceiving emotions, appreciating beauty, creating art, having desires, forming moral values, and pursuing goals. Such a machine might be able to pass a Turing test. It might even pass we could call the Ada test, which is that it could appear to “originate” its own thoughts that go beyond what we humans program it to do. There would, however, be still another hurdle before we could say that artificial intelligence has triumphed over augmented intelligence. We call it the Licklider Test. It would go beyong asking whether a machine could replicate all the components of human intelligence to ask whether the machine accomplishes these tasks better when whirring away completely on its own or when working in conjunction with humans. In other words, is it possible that humans and machines working in partnership will be indefinitely more powerful than an artificial intelligence machine working alone? If so, then “man-computer symbiosis,” as Licklider called it, will remain triumphant. Artificial Intelligence need not be the holy grail of computing. The goal instead could be to find ways to olptimize the collaboration between human and machine capabilities – to forge a èartnership in which we let the machines do what they do best, and they let us do what we do best. [Pages 478-79]

Ada’s Poetical Science

At his last such apperance, for the iPad2 in 2011, Steve Jobs declared: “It’s in Apple’s DNA that technology alone is not enough – that it’s technology married with liberal arts, married with the humanities, that yields us the result that makes our heat sing”. The converse to this paean to the humanities, however, is also true. People who love the arts and humanities should endeavor to appreciate the beauties of math and physics, just as Ada did. Otherwise they will be left at the intersection of arts and science, where most digital-age creativity will occur. They will surrender control of that territory to the engineers. Many people who celebrate the arts and the humanities, who applaud vigorously the tributes to their importance in our schools, will proclaim without shame (and sometimes even joke) that they don’t understand math or physics. They extoll the virtues of learning Latin, but they are clueless about how to write an algorithm or tell BASIC from C++, Python from Pascal. They consider people who don’t know Hamlet from Macbeth to be Philistines, yet they might merrily admit that they don’t know the difference between a gene and a chromosome, or a transistor and a capacitor, or an integral and a differential equation. These concepts may seem difficult. Yes, but so, too, is Hamlet. And like Hamlet, each of these concepts is beautiful. Like an elegant mathematical equation, they are expressions of the glories of the universe. [Pages 486-87]

Issacson’s book last page presents Vinci’s Vitruvian Man, 1492

Halt and Catch Fire – the TV series about innovation (without Silicon Valley and start-ups)

I will always remember the day when one of my former bosses told me I should focus on (watching, making) videos rather than (reading, writing) books. I am a book person so I will probably not follow his advice ! Still from time to time I discover movies about High-tech innovation and entrepreneurship, start-ups.

Halt and Catch Fire is not precisely about start-ups, it is not a documentary, it is not a movie. It is a TV series that is certainly more serious (and less fun) than HBO’s Silicon Valley. It is an interesting accident that I began watching it while reading Isaacson’s the Innovators. Both talk about the early days of Personal Computers in a (rather) dramatic manner.

I am still in the beginning of Season 1 so my comments come as much from what I read as from what I saw! Halt and Catch Fire takes place in Texas (not in Silicon Valley), in an established company, Cardiff Electric (not a start-up) where three individuals who should probably have never met, a sales man, an engineer and a geek (not entrepreneurs) will try to prove to the world that they can change it. So why Texas? According to French Wikipedia: “Season 1 (which takes place in 1983-198) is inspired by the creation of Compaq launched in 1982 to develop the first IBM-compatible portable PC. Compaq engineers had to reverse engineer by disassembling the IBM BIOS to make a compatible version rewritten by people who had never seen the IBM BIOS in order not to violate copyrights.” (My Compaq cap. table below.)

Scoot McNairy as Gordon Clark, Mackenzie Davis as Cameron Howe and Lee Pace as Joe MacMillan - Halt and Catch Fire _ Season 1, Gallery - Photo Credit: James Minchin III/AMC

Scoot McNairy as Gordon Clark, Mackenzie Davis as Cameron Howe and Lee Pace as Joe MacMillan – Halt and Catch Fire _ Season 1, Gallery – Photo Credit: James Minchin III/AMC

I should credit Marc Andreessen for helping me discovering this new AMC TV series. In a long portrait by the New Yorker, the Netscape founder mentions the series: “He pushed a button to unroll the wall screen, then called up Apple TV. We were going to watch the final two episodes of the first season of the AMC drama “Halt and Catch Fire,” about a fictional company called Cardiff, which enters the personal-computer wars of the early eighties. The show’s resonance for Andreessen was plain. In 1983, he said, “I was twelve, and I didn’t know anything about startups or venture capital, but I knew all the products.” He used the school library’s Radio Shack TRS-80 to build a calculator for math homework.” […] “The best scenes with Cameron were when she was alone in the basement, coding.” I said I felt that she was the least satisfactory character: underwritten, inconsistent, lacking in plausible motivation. He smiled and replied, “Because she’s the future.”

According to Wikipedia’s article about the series, “the show’s title refers to computer machine code instruction HCF, the execution of which would cause the computer’s central processing unit to stop working (“catch fire” was a humorous exaggeration).” It the series is not about entrepreneurship and start-ups so far, it is about rebellion, mutiny. There is a beautiful moment where one of the heroes convince his two colleagues to follow when they are about to stop. They are on quest.


I haven’t seen many movies and videos about my favorite topic so let me try and recapitulate:
– I began with Something Ventured, a documentary about the early days of Silicon Valley entrepreneurs and venture capitalists.
The Startup Kids is another documentary about young (mostly) web entrepreneurs. Often very moving.
HBO’s Silicon Valley is funnier than HFC but maybe not as good. Only time will say.
– I saw The Social Network which seems to remain the best fiction movie about all this, but
– I have not seen the two movies about Steve Jobs. It’s apparently not worth watching Jobs (2013) but I will probably try not to miss Steve Jobs (2015)

So as a conclusion, watch the trailer.

The Compaq Capitalization Table at IPO