Part IThe Story
Something to Finish
The thing people remembered at the end was that he would not look up.
David Hankin had walked into many rooms where Al Mann was working. Hankin ran the Alfred Mann Foundation in Valencia, the nonprofit laboratory Mann had seeded with $1 million in 1985. By then it held more than $120 million in assets and employed scientists and engineers building microstimulators that communicate wirelessly through the human body. A few weeks before Mann died, Hankin went to see him and found him as he always did: at a desk, in the middle of something, ninety years old and in no particular hurry to stop. "That's a common thing," Hankin said afterward. "I walk into the room, he's working, and he wants to finish something before we can talk. That is very much Al Mann."
The record does not say what he was finishing in those weeks. It does say what was coming apart around him. On January 5, 2016, MannKind Corporation, the Valencia drug company that carried his name inside a pun, disclosed that Sanofi was walking away from Afrezza. Afrezza was MannKind's only approved product, an insulin powder inhaled from a device about the size of a deck of playing cards. The French pharmaceutical giant had signed on seventeen months earlier, in a deal worth up to $925 million, and had then watched a year of exceedingly slow sales. MannKind shares fell nearly half in a day. Mann had put $975 million of his own cash into the company. His stake was now worth about $113 million.
The previous November his handpicked chief executive had resigned after eleven months, and Mann, at ninety, had stepped back in as interim CEO. A replacement was hired, then un-hired over a noncompete agreement. In mid-January the chief financial officer was promoted into the top job. On February 17, Mann sent the board a notice that he was resigning as executive chairman and director, effective immediately. The company named him Chairman Emeritus and said he would keep advising it "as an employee in a non-executive capacity." It was an odd, almost tender phrase, as if nobody could quite picture him without a job. When the Los Angeles Times asked for comment, the company said Mann declined. On Friday, February 19, MannKind stock closed at 98 cents. It had traded above $10 in June 2014, the month the FDA approved the drug.
Six days later, on February 25, he died of natural causes at his home in Las Vegas.
The obituaries could not settle on a tone, and that was fair, because the story did not have one. There was the triumphal list. His companies had built the solar cells for more than a hundred spacecraft, a rechargeable pacemaker, the insulin pump that changed the treatment of diabetes, a cochlear implant for the deaf, and an artificial retina that gives some blind people rudimentary sight. His companies had sold for a combined total of nearly $8 billion. His name was on institutes at USC and the Technion, and his fortune had once topped $2 billion. There was also the coda. The Boston Globe, running the Associated Press obituary, said MannKind "may also have been his Waterloo, eating up much of his fortune."
Both were true, and neither was quite the point. The man at the desk had a habit he never broke. Whenever something reached the stage other people would call done, a product approved, a company sold, a fortune made, he treated it as the start of the next unfinished thing. When people asked him when he planned to retire, he told them: at 140.
By the Numbers
The Al Mann Ledger
17Companies founded across seven decades, from aerospace to pharmaceuticals
100+Spacecraft powered by electricity from Mann's companies
$3.28BMedtronic's price for MiniMed in 2001, plus $420M for sister firm Medical Research Group
~$8BCombined sale value of the nine Mann companies that were acquired
$975MMann's personal cash invested in MannKind and inhaled insulin
$174M+Total donated to USC, beginning with a $100M pledge in 1998
90%Share of his estate Mann committed to philanthropy in his Giving Pledge letter
The Scientist in a Family of Musicians
There is a Wikipedia disambiguation page for "Alfred Mann." It lists four men. One is a musicologist, born in 1917, who wrote about musical theory. One is a particle physicist, born in 1920, who measured neutrinos from the sun and from a supernova, and who as a young man spent two years on a uranium-enrichment method that he later learned belonged to the Manhattan Project. One played rugby league in England. The fourth is the man this piece is about. That a single name divided cleanly between the concert hall and the physics laboratory is an accident of nomenclature, and accidents prove nothing. It does describe the fork in the road that ran through one house in Portland, Oregon.
The house belonged to Charles and Anna Mann. Charles had come from England and ran a grocery. Anna had come from Poland and was a pianist and singer, and she raised three children who could all play. Robert took up the violin and became a founder of the Juilliard String Quartet. Rosalind became a concert pianist and married into the name Koff. Alfred, born November 6, 1925, played cello, oboe, and piano. Decades later, asked by a reporter for his favorite piece, he named Rachmaninoff's Prelude in C-sharp minor, a piece built on three heavy descending chords, the kind of thing an earnest teenager plays loudly in a family parlor.
He did not become a musician. The household had the grocer's side too, and the Depression made it the louder one. Forbes's capsule biography, written when Mann was eighty and worth $2.2 billion, begins with the detail that he "sold magazines, lemonade during Depression." A Las Vegas paper later dated the lemonade stand to age five. Every self-made fortune has a lemonade stand in its creation story, and a skeptical reader is entitled to wince. The more revealing story is what happened in his last year of high school.
He took chemistry and physics as a senior. "That changed my life," he said, a sentence he repeated in some form to interviewers for seventy years. He finished as co-valedictorian and graduated at sixteen. Then, nearly unheard of for a valedictorian, he asked the school to let him stay an extra semester so he could take more physics. The school said no.
It is a small refusal, but it set a pattern. An institution had a rule about who could stay and for how long, and young Mann wanted it bent for one obvious reason: there was more physics to learn. Half a century later, he would offer America's research universities hundreds of millions of dollars on condition that they bend their rules, and several of them would also say no.
He spent a couple of years in college, then the war took him into the Army Air Corps. He served stateside and never saw combat. Afterward he went to Southern California, as hundreds of thousands of veterans did, and enrolled at UCLA, where he took both a bachelor's and a master's degree in physics in 1949. He settled in Los Angeles and stayed for most of the rest of his life. The city, for most of that time, did not know who he was.
The Army Set Him Up in Business
Mann told the origin of his first company with a passive construction that is easy to read past. "I came from humble beginnings and grew to become a young scientist pioneering in a field of electro-optical physics," he wrote in 2012, in his letter to the Giving Pledge. "The US Army needed my help and actually set me up in business in 1956. Two years later the Air Force came to me for help with our country's first spacecraft."
The Army set him up. The Air Force came to him. In Mann's own telling, he never went out looking for a market. Customers arrived at his door carrying problems that had his specialty written on them. The company was Spectrolab, an electro-optical firm, and among its early work was guidance equipment for the Army's antitank missiles. When the space program needed electricity in orbit, Spectrolab and a sister semiconductor company Mann founded in 1960, Heliotek, made solar cells. By the National Academy of Engineering's later accounting, Heliotek was "a vital technology contributor to the then-nascent US space program." Mann's companies eventually powered more than a hundred spacecraft, supplied cells for what he called America's first space probe, and built one of the experiments left on the Moon.
Before the space business had really begun, he sold it. Both companies went to Textron in 1960, the same year Heliotek was founded. That timing reads like either very good instincts or very little capital, and the second is more likely. Mann kept running both companies as a Textron employee for another twelve years, until 1972. Spectrolab went on to belong to Boeing. The habit started here: sell the equity early, keep the job, and get paid by the larger company to keep building what he had started. He did it again at Pacesetter. He seems not to have needed to own the thing in order to stay devoted to it.
He also took a rule from this period and kept it all his life. It came from his last employer before Spectrolab, an unnamed figure in every telling, and Mann repeated it to a reporter at eighty-three as if he had heard it the week before. When you start a business, figure out how much money it will take. Double that. Then don't go into business unless you have three times that amount.
It is a conservative rule, almost a grocer's rule. It also contains a lesson he seems to have absorbed only halfway. The rule assumes you can estimate the first number. Half a century later, MannKind spent $600 million developing its inhaled insulin before its initial public offering and then burned $8 million a month after it. By then the rule had been inverted. Mann did not wait until he had three times the money. He simply kept supplying it.
A Vest, a Chair, a Battery in the Chest
In 1969 researchers from Johns Hopkins University called on the solar-cell man about batteries.
The problem was straightforward and grim. The implantable cardiac pacemaker, the first electronic device ever sewn into a human body, treated dangerously slow heart rhythms, the condition cardiologists call bradycardia. Early pacemakers ran on encapsulated mercury-zinc batteries that lasted about eighteen months, sometimes less. When the battery ran down, the patient went back into surgery to have the pacemaker cut out and a new one put in. The Hopkins group, led by inventors at the university's Applied Physics Laboratory including an engineer named Robert Fischell, had spent their careers putting electronics into satellites, where nobody can replace a battery. Mann had spent his career powering those satellites. A heart was, in an engineering sense, another place that was hard to reach.
The company he built around their idea was Pacesetter Systems. The National Academy of Engineering and Mann's own résumé both date its founding to 1972. One encyclopedic account places its origins as early as 1965, and I have not been able to reconcile the two. The product was the first commercial rechargeable implantable pacemaker, one of the first to use radio waves for telemetry. The mechanism sounds like something from a midcentury science-fiction magazine. Every so often the patient put on a line-powered vest, sat down in a chair, and let radio-frequency energy pass through skin and muscle to recharge the battery beside the heart.
Then the advantage disappeared. Primary batteries improved, the circuitry became far more efficient, and pacemakers began lasting years without a recharge. The feature that made Pacesetter distinctive became unnecessary. Paul Citron, writing Mann's memorial tribute for the Academy, recorded this without sentiment: "As is common in high tech, the advantages of rechargeability were soon eclipsed." The same passage explains why the company survived anyway: "under Mann's leadership, Pacesetter proved to be an adaptable company with a loyal following."
That is the part of the story most founders' biographies leave out. Pacesetter's reason for existing became obsolete, and it lived on because Mann had built a company of people and not just a product. In 1985 he sold it to the German conglomerate Siemens for about $150 million, then ran the successor company, Siemens-Pacesetter, for seven more years, until 1992. Siemens sold the pacemaker business to St. Jude Medical in 1994. By then Pacesetter was among the largest pacemaker makers in the world, built in the northeast San Fernando Valley by a physicist who had learned his trade on spacecraft.
Siemens had declined one piece of the deal. Pacesetter included a division working on insulin delivery, and the Germans did not want it. "Siemens passed on that portion," Mann told the Los Angeles Times in 2001, around the time he was selling that same rejected division to Medtronic for $3.28 billion.
The Challenge in the Cardiac Ward
Mann's version of how he got into diabetes starts with a scene in a hospital in 1979, while he was still running Pacesetter. He was visiting a cardiac ward when a physician challenged him. The heart patients filling those beds, the doctor told him, were in many cases there because of diabetes. If Mann wanted to help them, he should work on that.
The man who came to Los Angeles to study physics, who believed the Army had set him up in business and the Air Force had brought him its problems, again took a stranger's challenge as an assignment. The insulin work began inside Pacesetter, in the form of an implantable insulin pump that came out of the same Hopkins collaboration. It was spun out as MiniMed in 1983. Siemens did not want it in 1985, so Mann kept it. MiniMed incorporated in 1993 and went public in 1995. It made wearable pumps that delivered insulin through the day, so that people with Type 1 diabetes could manage their blood sugar more precisely than injections allowed, and later it made continuous glucose monitors. Alongside it Mann ran the Medical Research Group, which the Technion's tribute described as building implantable infusion systems and a "prosthetic artificial pancreas." His résumé called MRG a "high-risk research group," in effect a sanctioned place for the ideas the main company could not afford.
MiniMed was his biggest success. By 1998 his stake was worth about $188 million. In 2001 Medtronic paid $48 a share, $3.28 billion for MiniMed and another $420 million for Medical Research Group. Mann's 17 million MiniMed shares came to $816 million. Michael Weinstein, a J.P. Morgan managing director, described the medical device landscape of the previous decade as "littered" with companies that had interesting products and died anyway: "Out of that landscape, MiniMed stands out as a remarkable success. I think a good portion of that is due to Al and his relentless drive."
What Mann said that week stands as the most precise self-diagnosis he ever offered. The ink on the Medtronic deal was barely dry, and he was already planning the next companies: a hearing-implant maker in Valencia and a group of drug-delivery and vaccine startups in Chatsworth and Elmsford, New York. Asked whether letting go of MiniMed hurt, he said:
"I'm most excited and interested in the start-up and seeing it through its adolescence. When it gets to be a mature adult, it has less interest for me."
He used the language of parenthood, and he had seven children, and it is hard to read the sentence twice without that in mind. He was speaking about companies. Over the same decades, though, he married four times and divorced three, and the sentence fits more than his business. He also mentioned how much he had already put into the next generation: "I put $130 million into those three," he said of the Chatsworth and Elmsford companies, plus "an additional $50 [million] to $60 million in Advanced Bionics. So I've put in lots of money." The reporter noted that he laughed when he said it.
David Kliff, who published a newsletter called Diabetic Investor, later summed up the MiniMed years generously and accurately: "Al touched the lives of millions of patients, mentored several notable executives and most of all never stopped trying to make life better for patients with diabetes."
The last clause is the one to keep in mind. He never stopped. When he sold MiniMed, the most successful insulin company he would ever build, he did not leave diabetes. He went after the needle itself.
Just an Engineering Problem
In February 1998, Jeff Greiner, president of Advanced Bionics, gave a reporter the line that later appeared in almost every account of Mann's life, usually without Greiner's name and usually without the qualification he attached to it. "He's literally working on making the blind see, the deaf hear and the lame walk," Greiner said. "That's a pretty fantastic legacy if it comes to pass."
If it comes to pass. In 1998 most of it had not.
The engine was the Alfred Mann Foundation. It began with that $1 million in 1985, the year Mann sold Pacesetter to Siemens, and he described it as "an operating public medical research organization that has focused mostly on applications of neuromodulation." It employed about a hundred people, almost all scientists and engineers. It was a nonprofit, and it was also a feeder. Its laboratories developed the cochlear implant that became Advanced Bionics' main product. Advanced Bionics, founded in 1993, built implants that restore hearing to the profoundly deaf, along with neurostimulators for chronic pain, migraine, and angina. Its neural-stimulation business eventually went to Boston Scientific. Its hearing business, sold in late 2009, now belongs to Sonova. The foundation also built a long-term implantable glucose sensor that lasted, Mann wrote, "~1½ years," radio-frequency microstimulators, and implantable drug-delivery systems. The Los Angeles Times, which noticed the arrangement in 1998, called it "the hard-boiled pragmatism underpinning his philanthropy." The nonprofit invented things, and Mann's companies licensed and sold them.
Second Sight was where his stubbornness was tested hardest. Mann founded it in 1998 to build a visual prosthesis for people blinded by retinitis pigmentosa: a grid of electrodes on the retina, fed by a camera, producing rough patterns of light where there had been none. For two years of testing, the device kept tearing the eye tissue of the animals it was implanted in. Robert Greenberg, Second Sight's chief executive, remembered a board member saying what any reasonable board member might: maybe this is too hard, maybe it's impossible, maybe we should quit.
Greenberg recalled Mann's answer: "No way. This is just an engineering problem. And it's solvable."
Greenberg was a physician-engineer who later said he had worked closely with Mann for twenty years. He drew the lesson carefully. "It was that recognition of when to quit — and when not to quit — that separates Al from others." In 2013 the FDA approved Second Sight's Argus II, the first artificial retina approved for use in the United States. The next year the company filed for an initial public offering.
— Robert Greenberg, chief executive of Second Sight Medical Products, Los Angeles Times, 2014It was that recognition of when to quit — and when not to quit — that separates Al from others.
Greenberg also remembered something else from Second Sight's first days. Mann took him aside and told him: "I want to make sure you understand the importance of the person who cleans our office because without them we cannot do this." A billionaire's maxim about the janitor tends to sound rehearsed, and readers are allowed to doubt this one. What makes it plausible is how many former employees, years after his death, came back to say that working in "an Al Mann company" was the best stretch of their careers. One engineer said it was "not only highly likely, but highly enjoyable" for a Southern California biomedical engineer to end up in one. Another wrote that he met Mann in 1987 and worked in his companies for thirty-three years.
In January 2014 an acquaintance asked Mann which of his projects excited him most. Hankin was in the room and expected to hear Afrezza, which was then nearing an FDA advisory panel, or the artificial retina. Mann named neither. He named the implantable myoelectric sensor, a small device developed at the foundation that let an amputee's brain communicate with a robotic limb. "I was astounded at his response," Hankin said, "because he has some amazing products in his portfolio."
On January 15, 2014, the foundation announced its first human implant. The recipient was James Sides, a Marine sergeant who had lost his arm below the elbow in Afghanistan in 2012. The sensors, about $500 each, at least six per patient, were placed in the remaining muscle of his forearm. There they detected the faint contractions of muscles told to move a hand that no longer existed and transmitted those signals wirelessly to a decoder on his waist, which sent them on to a prosthetic arm. At eighty-eight, Mann's favorite project was a Marine trying to close a hand he did not have.
A Bridge With a Tollbooth
On Wednesday, February 4, 1998, the Los Angeles Times ran a story under a headline that could have been the title of this section: "Who Is This Mann?"
He had just signed an agreement to give the University of Southern California $100 million and was close to giving another $100 million to UCLA, where he had earned both his degrees. The USC gift alone made him one of the ten largest donors in the history of American higher education. The paper noted that Ted Turner and Bill Gates were household names, "while Mann remains a virtual unknown in his own backyard." The reporter, Marla Dickerson, observed that "the incurable workaholic may never hold court with Barbara Walters or lead the tomahawk chop at the World Series." Turner was then in the habit of doing the latter. Mann, then seventy-two, did not seem to mind.
He explained his reasoning in a single sentence of industrial grievance, the kind of thing a man who had watched American heavy industry lose ground for twenty years might say: "Most of the Nobel Prizes go to scientists in this country, yet all of the products are coming out of Japan and Germany. I want to create a bridge between academia and the industry."
The bridge was meant literally, as an organization. Each Alfred E. Mann Institute would be a separate entity attached to a university, endowed with at least $100 million and staffed by engineers and industry professionals. It would take inventions out of faculty laboratories and develop them into products that could be licensed. Mann's foundation later cited a figure that explained his impatience: universities spent about $37 billion a year on government- and industry-sponsored research and got roughly $1 billion back in commercial licensing revenue, about 2.7 percent. To a man who had sold a pacemaker company and was about to sell an insulin-pump company, that looked less like a scandal than an underused asset.
UCLA was supposed to go first. USC President Steven B. Sample learned of the UCLA negotiations "last spring — through a passing mention in The Times," as the paper reported with some satisfaction, and began personally lobbying Mann. Mann described the pitch with the admiration of one dealmaker for another: "He pointed out that they" — USC — "are more entrepreneurial than a public institution that is overwhelmed with bureaucracy and politics. He's a very clever guy."
The UCLA gift never happened. The reported reason was patents. Mann wanted to keep control over the patents and patent revenue his institute generated, and a public university would not agree. The money went across town to the private rival, eventually more than $162 million for the institute and, by USC's count, more than $174 million to the university overall. He was made a Life Trustee. The UCLA physics graduate had become a benefactor of USC, the kind of cross-town defection sportswriters would call a betrayal.
The bridge had a tollbooth on it. Mann's terms showed what he thought universities were bad at, which was choosing.
In April 2006, at eighty, Mann and his wife Claude visited Chapel Hill. They toured the University of North Carolina and had dinner with Erskine Bowles, president of the state university system. Bowles had particular reasons to court a man who had built the first insulin pump: two of his sons had juvenile diabetes. Mann liked UNC and offered $200 million for a double-sized institute serving both Chapel Hill and North Carolina State. It would have been one of the fifteen largest gifts ever made to a university.
Bowles turned it down. He wanted the university to decide which inventions went to the institute. Mann wanted the right to look at every medical invention on campus and take the best ones. "If the university can pick and choose what they make available to us," he told Forbes, "it defeats the purpose."
The Forbes article, by David Whelan, was titled "$100 Million, Anyone?" and it was one of the stranger stories of its year. It described a billionaire who had publicly promised to endow at least a dozen institutes at $100 million apiece and could hardly find takers. UCLA had said no. Johns Hopkins, whose researchers had first brought him into medicine in 1969, had said no. Emory, Case Western, Minnesota, and Washington were "dickering." Robert Lowe, a Carnegie Mellon professor who studied technology transfer, explained the academic objection: one entity holding first-look rights over a university's inventions could interfere with academic freedom and could amount to a giveaway. Mann, Whelan wrote, was "puzzled by the rejections." He saw himself as offering expertise to people who badly needed it. The universities saw a man asking for the keys to the building.
The Technion, Israel's MIT, signed in October 2006, eventually for $104 million. On March 16, 2007, Purdue announced a $100 million endowment from the Mann Foundation for Biomedical Engineering, the largest single endowment in the university's history. Indiana's governor, Mitch Daniels, called the day among the state's greatest. The foundation's president said Purdue was "the third of a minimum of 12 such institutes" to be created "by 2012."
By early 2012 the Alfred Mann Institute at Purdue had closed, and the unspent part of the $100 million had been rescinded.
The USC institute outlived Mann by seven years, almost to the day if you count from the start of its unwinding. In 2022, with its endowment grown to $230 million, USC President Carol Folt announced that most of the money would be reallocated to the pharmacy school, the biomedical engineering department, and Children's Hospital Los Angeles. In 2023 USC dissolved the institute, ended its operations, dismissed its staff and its volunteer board, and moved its remaining assets under the university's research office. On February 9, 2023, in a ceremony on Pappas Quad, the pharmacy school took a new name: the USC Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences.
So his name survived, on a building whose purpose he had not chosen, after the university finally did the picking and choosing he had spent his philanthropic life trying to prevent.
Mt. Everest, Without Oxygen
MannKind was supposed to be a joke.
The company existed under other names first. Its official founding date is February 1991, as Pharmaceutical Discovery Corporation, a company in Elmsford, New York, built around a molecule called Technosphere and an inhaler called the Medtone. Mann acquired it from its founder, Solomon Steiner. In 2003 he merged it with two other companies he owned, the cancer-vaccine developer CTL ImmunoTherapies and an allergy-vaccine company called AlleCure, and named the result after himself, "in an attempt at humor," as one account put it. Most founders who put their name on a company want it to last. Mann put his on the company that would test him hardest.
The Technosphere molecules self-assembled into tiny particles that could carry a drug deep into the lungs. Insulin delivered that way peaked twelve to fifteen minutes after inhalation and was largely gone within two to three hours, which was faster in and faster out than injected insulin and closer to the way a healthy pancreas responds to a meal. Mann believed in it completely. "In my view, it's potentially the most valuable medical product of all time," he said in 2005. He estimated the market, including undiagnosed cases, at $300 billion.
Wall Street did not share his view. MannKind went public in 2004, raising $87.5 million, and chose to develop the drug without a big-pharma partner, so it would not have to share the profits. By mid-2005 the stock had fallen from nearly $25 to under $10. The company had about $67 million in cash, was spending $8 million a month, and was about to start Phase III trials involving nearly 2,000 patients that would cost at least $200 million more. Its competitor, Exubera, was years ahead and backed by Pfizer and Sanofi-Aventis. Mann held 48.6 percent of the stock and promised to fund the company from his own pocket if necessary, "to the end."
An analyst at WR Hambrecht, Andrew Forman, wrote the line that has followed the drug ever since:
— Andrew Forman, analyst at WR Hambrecht & Co., in a note to investors, 2005Inhaled insulin is the Mt. Everest of drug delivery and MannKind just left base camp and it does not have much oxygen.
What happened next looked, briefly, like vindication and then like a warning. The FDA approved Exubera in early 2006. Patients avoided it. Its inhaler was large and awkward, and one reporter later wrote that some people likened it to a bong. In late 2007 Pfizer pulled it from the market and took a charge of nearly $3 billion, one of the biggest flops in modern pharmaceutical history. Mann's competitor was gone. So, almost overnight, was the industry's appetite for inhaled insulin. The other major insulin makers dropped their programs.
On Wednesday, April 9, 2008, Pfizer reported that a study suggested Exubera might raise the risk of lung cancer. MannKind lost almost 60 percent of its value that day, falling $3.50 to close at $2.35. Mann had invested $566 million in the company and agreed to lend it hundreds of millions more, for a total commitment of $916 million, close to half of an estimated $2.2 billion fortune. He was eighty-two. "By no means am I unsure of the scientific and clinical benefits of Technosphere," he said that week. "I have no reason to believe there is any safety issue with our drug. I admit the business environment has a lot of negativity around the sector right now, but that's just something we are going to have to reverse."
There were other problems. In late 2007 MannKind had settled a lawsuit from its former chief medical officer, Wendell Cheatham, who alleged the company had made false statements to the FDA and changed the drug's formulation improperly in its rush into Phase III. The company denied wrongdoing, and the settlement terms were not disclosed. Shareholders later sued too. The FDA declined to approve Afrezza twice, the second time in January 2011, when it asked for more studies. That spring the Los Angeles Business Journal reported that the value of Mann's 39 percent stake had fallen 35 percent and his net worth had dropped to $1.5 billion.
Then, in 2011, Mann did something he had seldom done in his career. He narrowed his focus. He ordered his executives to cancel every other project at MannKind, including the cancer vaccines and the allergy work that had been merged in eight years earlier. There were painful layoffs. Everything went into Afrezza.
It worked, up to a point. On June 27, 2014, the FDA approved Afrezza. On August 11, Sanofi signed a global license worth up to $925 million, paid $150 million in cash up front, and agreed to split profits and losses 65-35. A Business Journal columnist who had once spent three straight breakfasts listening to Mann recount his life wrote that if anyone ever deserved the payoff, it was this man, who had put "close to $1 billion" of his own money into the drug. "That's no typo," he added. That September, recovering from two surgeries and still working seventy hours a week at his 17,000-square-foot estate in Beverly Hills, Mann gave the Times his explanation: "I'm trying to help people. How else would I have been able to work until I'm almost 90, if I didn't have something to motivate me?"
The approval came with conditions, and the conditions were where the product struggled. Afrezza could not be prescribed to patients with asthma or other serious lung disease and was not recommended for smokers. Doctors had to test a patient's lung function before writing the first prescription and every six months after that. Endocrinologists already had injectable insulin that worked, and a new requirement of spirometry before every prescription was the kind of friction that kills drugs quietly. The second Mann product to come out of Everest reached the summit and then found that few people wanted to make the trip.
The experience recalled the rechargeable pacemaker. The scientific achievement was real, and the market rejected it for reasons that had little to do with the science. At Pacesetter, Mann had adapted. At MannKind he did what he had done at Second Sight and refused to quit. The difference between those two companies is the hardest problem in his career. The retina had been an engineering problem, and engineering problems give way to effort. The inhaler, by 2015, was partly a problem of doctors and patients, and those do not always give way to anything.
"I have never considered abandoning [Afrezza]," he had said in 2014, "because I firmly believe that Afrezza has the potential to bring significant benefits to the still growing and enormous population of people with diabetes."
Dr. Alan Marcus, a Laguna Hills endocrinologist and an early Afrezza supporter, said what many people felt after Sanofi left: "Everybody wanted him to be successful with this product. I think this is going to be his last go-round. He just turned 90. I think at a certain point, you just get tired."
Mann never said he was tired. The closest he came was in 2008, and he was talking about something else.
First in His Heart, Not His First Priority
He married Beverly first. They divorced in 1957, a year after Spectrolab began. He married Linda next. They divorced in 1973, a year after he left Textron to run Pacesetter full time. He married Susan Kendall, and they divorced in 1997, as he was negotiating his first university gift and MiniMed was approaching its peak. The dates come from public records, and the overlaps may mean nothing. A man is not his calendar. Still, the overlaps are there, and he acknowledged the general point himself. Asked over the years, he said that work had taken a toll on his family life and that the long hours had cost something.
In 2004, at seventy-eight, he married Claude. She was the only wife who stayed to the end, and she was the one who described the arrangement most plainly, in 2014:
— Claude Mann, to the Los Angeles Times, 2014I know I will be first in his heart, but not his first priority. His first priority will always be work and doing what he does best.
Her sentence is not a complaint and is not meant to be. Someone who has accepted a situation clearly is describing it. Six years earlier, at eighty-three, Mann had told the Los Angeles Business Journal about their life together. When the Los Angeles house was being renovated, the couple moved for a while to their second home in Las Vegas, where he set up an office with teleconferencing. He liked it so much that they stayed for much of the year, and he flew a private jet to board meetings in Los Angeles and investor meetings on the East Coast. He enjoyed home-cooked dinners with Claude as a break from his schedule. She had told him she wanted a more boring life.
"And I've come to a point to where I'd like a little more boring life, too," he said. "But I can't see retiring."
The reporter noted that he was tempted to slow down but did not know how. He was working eighty-hour weeks then and said, without apparent irony, that he worked longer hours than when he founded his first company more than fifty years earlier. "Too many people whither away when they retire," he said. "My problem probably is that I've got too much on my plate."
He had seven children from his first three marriages, and by 2011 nine grandchildren and a great-grandchild. Their place in the story is mostly about money he chose not to give them. "I don't believe in creating poor little rich kids," he said in 1998, explaining why most of his fortune would go to research. The Times identified the philosophy as Andrew Carnegie's, that a large inheritance is a curse on the next generation. Forbes, in 2006, framed it more bluntly in its subhead: "Alfred Mann's fourth wife and seven children won't get his billions." In 2012 he wrote in his Giving Pledge letter: "Early I was able to provide modest support for my family so that I intend for at least 90% of my estate to be devoted to philanthropy — almost all directed to advancing medical technology."
The pledge letter is short and earnest and comes close to answering the question this whole story keeps asking. "I want to use those resources to make this a better world — and to do as much as I can during my lifetime," he wrote. In 1998 he had said it more casually: "What else am I going to do with it?"
The music did not leave him. In March 2011 he and Claude gave $4 million to the Walter W. Naumburg Foundation, which sponsors competitions for young classical musicians. In February 2013 he gave $70 million to the Nevada Community Foundation, more than tripling its endowment. That foundation had been started with a contribution from Moe Dalitz, the Las Vegas gaming pioneer, a year before Dalitz's death. Mann was quietly becoming a local figure in a second city, while the first one had still barely noticed him.
The Wall That Moved With the Weather
"Al almost single-handedly brought the medical device industry to Los Angeles," Robert Greenberg said when Mann died, and the evidence supports him. Mann's companies were not in Westwood or Pasadena. They were in Sylmar, Valencia, Chatsworth, and Santa Clarita, the hot, inland, unfashionable parts of the county where land was cheap. He built two campuses there, the 120-acre Mann Biomedical Park in Valencia and the nearly ten-acre Sylmar Biomedical Park. In 2014 he sold both to a joint venture of Intertex and Oaktree Capital for a price industry sources put at about $100 million. By then the engineers had absorbed what he built. It was, as one of them put it, "highly likely" that a biomedical engineer in Southern California would end up working for an Al Mann company. Some worked for him twice.
His companies kept selling and kept being absorbed into larger ones. Stellar Microelectronics went to Flextronics in 2012. Quallion, the battery maker, went to EnerSys in 2013 for $30 million. The batteries were for medical implants, soldiers, and satellites, which brought him back to the spacecraft work he started with. In November 2024, a few days after what would have been his ninety-ninth birthday, Boston Scientific closed its acquisition of Axonics, a neuromodulation company whose early technology came out of the Alfred Mann Foundation, by then renamed huMannity Medtec. A man named Jeremy Koff, who shares a surname with Mann's pianist sister and who grew up calling him "Uncle Al," called it the largest neuromodulation acquisition ever in absolute dollars. Greenberg replied in the comments: "We all wish he had lived to 140, like he used to joke."
Another former employee, Thomas Santogrossi, who met Mann in 1987 and stayed thirty-three years, posted the last time he had seen him. It was in a federal courtroom, where both of them were testifying in a patent infringement case. The image fits him: a man in his late eighties in a witness box, arguing about who owned an invention.
Most of what Mann made was meant to cross a boundary nobody else could cross. He sent electricity into orbit and into the chest. He sent insulin into the bloodstream through a pump, and then, by his insistence, through the lungs. He sent sound past dead nerves in the ear and light past a ruined retina. He sent a Marine's intention from a missing hand to a robotic one. He tried, with mixed success and a great deal of money, to move ideas out of universities into companies. His foundations and institutes and the cochlear implant and the infusion pumps all rested on the same belief: the wall between where a thing is and where it needs to be is an engineering problem, and it can be solved.
The house said so too. Mann designed it himself, a mansion on Mulholland Drive above the San Fernando Valley, where the companies were. In 2003 a reporter sat with him there for three breakfasts in a row while Mann told his life story in more detail than the reporter could recall about the day before. The reporter wrote later that he believed he had been sitting with the smartest man he had ever met. What he remembered best from the house was the koi pond.
The pond began in the backyard and ran into the house. Between the two halves stood a translucent wall that Mann had built to rise and fall on its own with the weather: down when it was cold, up when the air was mild. The fish swam back and forth under it, between the yard and the living room, from outside to inside, unaware of any boundary at all.
Part IIThe Playbook
What follows is not a hagiography in bullet points. Mann's career was long, and it contains both the most successful exit in the history of the insulin pump and one of the most expensive personal bets on a single drug ever made by an individual. The principles below come from both. Some are things to copy. A few are things to copy with the warning label he never read.
The principles
- 1.Let your current customer hand you your next market.
- 2.Capitalize at three times the estimate.
- 3.Sell the equity, keep the job.
- 4.Know which stage of a company you are for.
- 5.Build the company to survive its own best feature.
- 6.Put a laboratory upstream of your companies.
- 7.Separate engineering problems from market problems.
- 8.Don't let your own capital drown out the market's signal.
- 9.If you're going to attach strings, own the consequences.
- 10.Build the region, not just the firm.
- 11.Respect the floor.
- 12.Endowments outlive intentions.
M
Seven Decades of Company-Building
Each venture grew out of the problem the previous one exposed.
1956
Founds Spectrolab, an electro-optical company. In Mann's words, the Army "set me up in business."
1960
Founds Heliotek for spacecraft solar cells. Sells both companies to Textron and runs them until 1972.
1969
Johns Hopkins researchers ask him to help build a longer-lasting pacemaker.
1972
Pacesetter Systems builds the rechargeable implantable pacemaker.
1979
A doctor in a cardiac ward challenges him to work on diabetes.
1983
Insulin-pump work spun out as MiniMed.
1985
Sells Pacesetter to Siemens for about $150M. Seeds the Alfred Mann Foundation with $1M.
1993
Founds Advanced Bionics around the foundation's cochlear implant.
1998
$100M pledge to USC. Founds Second Sight.
2001
Sells MiniMed and Medical Research Group to Medtronic for $3.28B plus $420M.
2003
Merges three companies into MannKind.
2013
FDA approves Second Sight's Argus II artificial retina.
2014
FDA approves Afrezza. Sanofi licenses it for up to $925M.
2016
Sanofi exits in January. Mann resigns February 17 and dies February 25.
Principle 1
Let your current customer hand you your next market
Mann almost never told his story as one of choosing a market. The Army set him up in business. The Air Force came to him with the first spacecraft. Johns Hopkins brought him the pacemaker battery. A doctor in a cardiac ward challenged him to take on diabetes. Each move came from someone who already trusted his competence and had a problem one step beyond his last one.
This is a different strategy from the usual entrepreneurial scan of the horizon for big markets. It is adjacency through credibility. A solar-cell maker is plausible as a pacemaker-battery partner because satellites and chests are both places where nobody can change the battery. A pacemaker maker is plausible as an insulin company because the cardiologists' patients are diabetics. Every move used the trust the previous one had earned. The arc from spacecraft to implants looks like a sharp turn only from far away. Up close it is a series of short, sensible steps, each suggested by a customer.
The discipline lies in listening to customers who are describing an adjacent problem, not just complaining about your current product. The doctor in 1979 was not asking for a better pacemaker. He was telling Mann what put people in need of one.
Tactic: Ask your most technical customers, "What's the problem upstream of the one we solve for you?" and treat repeated answers as a product roadmap.
Principle 2
Capitalize at three times the estimate
Mann's rule, inherited from an employer whose name is lost: estimate what the business will need, double it, and don't start unless you have three times the original number. It sounds conservative. In hard-technology fields it is closer to accurate. Medical devices and drugs go through regulatory review, clinical trials, and reimbursement fights that routinely take longer and cost more than the founding spreadsheet predicts.
MannKind is the illustration, though not in the way Mann intended. The company had spent more than $600 million before its IPO and $8 million a month afterward, then needed $200 million more for Phase III, and later went through two FDA rejections. Its real capital need was a multiple of any number someone could have estimated in 2001. The triple-money rule assumes you can make the first estimate honestly. In fields with binary regulatory outcomes, you often can't, which is why the margin needs to be that large.
The rule also has a second function. Three times the estimate is more than most founders can raise easily, so the rule screens out ideas that are not worth the effort. That screen only works if you apply it before you begin.
Tactic: Before committing to a hard-tech venture, write down your capital estimate, triple it, and kill the project now if you cannot see a credible path to the tripled figure.
Principle 3
Sell the equity, keep the job
Mann sold Spectrolab and Heliotek to Textron in 1960 and kept running them until 1972. He sold Pacesetter to Siemens in 1985 and ran it until 1992. Both times he gave up ownership early and kept operating authority for years, financed by a parent company's balance sheet.
The pattern separates two things founders usually treat as one: the financial reward of building something and the satisfaction of building it. Selling early limited his exposure to the risky middle years and gave him capital for the next venture, while he kept the part he actually enjoyed. It also gave the acquirer what it most wanted, the founder's continuity. Siemens was not paying $150 million for a rechargeable pacemaker whose main feature was already obsolete. It was paying for an adaptable organization and the person who held it together.
Tactic: When negotiating an acquisition, treat your continued operating role as a separate asset and price it, because to the buyer it often is one.
Principle 4
Know which stage of a company you are for
"I'm most excited and interested in the start-up and seeing it through its adolescence. When it gets to be a mature adult, it has less interest for me." Few founders say this about themselves so precisely, and fewer act on it. Mann did. He sold MiniMed for $3.28 billion and immediately turned to Advanced Bionics and the Chatsworth startups.
He did best with companies that, at the point of sale, had passed what one analyst called the validation stage, where "the technology first needs to be validated before new ownership comes in." He was not trying to build a Medtronic. He built things Medtronic would want to buy, at the moment they became worth buying, and then left before the company's needs shifted from invention to administration.
The cost shows up at MannKind, the one company he could not sell at adolescence because it never got there commercially. A founder who knows he is good at youth will hold on too long to a company that won't grow up.
| Company | Mann's exit point | Outcome |
|---|---|---|
| Spectrolab / Heliotek | Sold within four years of founding | Scaled under Textron, later Boeing |
| Pacesetter | Sold after its core feature became obsolete | Became a leading pacemaker maker |
| MiniMed | Sold at market leadership, 2001 | $3.28B, his largest exit |
| MannKind | Never sold; resigned eight days before his death | $975M invested, stock under $1 |
Tactic: Decide in writing, before you raise money, what milestone marks the end of the stage you are best at, and plan the handoff for that moment.
Principle 5
Build the company to survive its own best feature
The rechargeable pacemaker was Pacesetter's reason for existing, and better primary batteries made it obsolete. A company built purely around the feature would have died with it. Paul Citron's memorial tribute credits the survival to the fact that Pacesetter "proved to be an adaptable company with a loyal following."
Every hard-technology founder should take this seriously. Your differentiating feature is a bet on the state of adjacent technology, and adjacent technology does not stay still. What survives the loss of the feature is the set of capabilities underneath it: regulatory skill, clinical relationships, manufacturing quality, and physicians who trust you. Mann's companies kept being acquired after their founding ideas had been superseded because what buyers were really acquiring was the organization.
Tactic: List the three capabilities your company would still have if your headline feature became irrelevant tomorrow, and invest in those as deliberately as in the feature.
Principle 6
Put a laboratory upstream of your companies
The Alfred Mann Foundation, seeded with $1 million in 1985 and grown to about a hundred scientists and engineers, was legally a nonprofit and strategically a pipeline. It developed the cochlear implant that became Advanced Bionics' main product. Its glucose sensors, microstimulators, and myoelectric sensors went into the broader portfolio. Its technology was at the origin of Axonics, which Boston Scientific acquired eight years after Mann died.
The structure solved a problem every serial founder has: where do the long-shot ideas live while the operating companies are busy hitting quarterly numbers? Mann gave them a permanent home with its own funding and patience. Medical Research Group did the same job alongside MiniMed. The Los Angeles Times called it "hard-boiled pragmatism," and meant both words.
Tactic: Set aside a fixed share of profits for a separate research unit with its own leader, a longer time horizon than your operating business, and a clear path for licensing its output.
Principle 7
Separate engineering problems from market problems
"No way. This is just an engineering problem. And it's solvable." Mann said this about an artificial retina that had torn animal eye tissue through two years of testing, and he was right. Argus II won FDA approval in 2013. Greenberg's summary of what set Mann apart was "that recognition of when to quit — and when not to quit."
The harder lesson is that Mann seems to have applied the same test to Afrezza, where it didn't fit. Afrezza's science was not what failed. Its pharmacokinetics were real, and the FDA approved it. What failed were prescribing conditions: lung-function tests before the first prescription and every six months, exclusion of asthmatics, physicians reluctant to change. Those are adoption problems, and persistence that solves engineering problems does not necessarily solve them.
| Problem type | Mann example | Does persistence help? |
|---|---|---|
| Engineering | Second Sight's retinal implant tearing tissue | Usually |
| Obsolescence | Rechargeable pacemaker made unnecessary by better batteries | Adapt instead |
| Regulatory | Two FDA rejections of Afrezza | Sometimes |
| Market adoption | Afrezza's lung-test requirement and slow sales | Rarely, by itself |
Tactic: When a project stalls, label the obstacle as engineering, regulatory, or adoption before deciding whether to push on, because each one rewards a different response.
Principle 8
Don't let your own capital drown out the market's signal
Mann pledged to fund MannKind "to the end." He did, with $566 million by 2008, $916 million committed, and $975 million in the end. That commitment kept a remarkable drug alive through two FDA rejections and an industry-wide retreat after Exubera. It also removed the discipline outside capital imposes. MannKind went it alone after its IPO to avoid sharing profits, and by the time Sanofi arrived the drug's commercial weaknesses were built into its label.
Founders with large personal fortunes face a specific risk: their own conviction becomes the only investor that matters. Outside skepticism, like the WR Hambrecht analyst's Everest line, the Jefferies downgrade, and Pfizer's $3 billion write-off, carried information about whether doctors and patients would accept inhaled insulin. Mann's money let him treat all of that as noise. Sometimes a self-funded founder is right when everyone else is wrong. Second Sight is the evidence. The cost of being wrong, though, scales with the size of the checkbook.
Tactic: If you are funding your own venture, set a fixed point, such as a milestone or a dollar amount, at which you will require outside co-investment to continue, and treat a failure to find it as data.
Principle 9
If you're going to attach strings, own the consequences
Mann's institute model depended on control. He wanted first look at every medical invention on campus, because he did not trust committees of professors to choose what was worth developing. It is a defensible position. Universities were returning about 2.7 percent on research spending through licensing. It cost him UCLA, Johns Hopkins, and a $200 million deal with North Carolina, and Purdue's institute was shut down within five years.
The lesson is not that the strings were a mistake. Without them the institutes would have become one more university office, and Mann would have been funding the system he set out to fix. The lesson is that strict terms limit how far you can scale. A plan for "a minimum of 12" institutes ended with three, one of which was later rescinded. If control is the point, accept a smaller footprint, plan around it, and stop being surprised when institutions with their own interests say no.
B
The Mann Institute Model vs. Conventional University Tech Transfer
Why the bridge had so few takers.
| Dimension | Conventional tech transfer | Mann institute model |
|---|---|---|
| Who selects inventions | University committee or patent office | The institute, with first look at everything |
| Staffing | Licensing officers | Engineers and industry professionals who develop products |
| Output | Licensed patents | Developed products, licensed when ready |
| Funding | Operating budget | Dedicated endowment of at least $100M |
| University objection | None | Academic freedom, "giveaway" risk |
Tactic: Before offering capital with conditions, decide which single condition is non-negotiable and be ready to give up the rest to close more deals.
Principle 10
Build the region, not just the firm
Mann's companies were clustered in Sylmar, Valencia, and Santa Clarita, on campuses he owned. The result was a labor market. Engineers moved between his companies, worked for him twice, and stayed for decades. "Al almost single-handedly brought the medical device industry to Los Angeles," Greenberg said, and one engineer later described working for an Al Mann company as "highly likely" for anyone in the field there.
That density gave his companies something no single startup can get on its own: a local supply of people who already understood implantable devices, FDA submissions, and Mann's way of working. He also chaired the Southern California Biomedical Council and argued for the region in public, at a time when Los Angeles lagged Orange and San Diego counties in biomedical startups.
Tactic: If you plan to build more than one company, put them close together and make it easy for talent to move among them, so that each new venture starts with experienced people.
Principle 11
Respect the floor
"I want to make sure you understand the importance of the person who cleans our office because without them we cannot do this." Mann said this to Greenberg on Second Sight's first day, and the loyalty that followed suggests he meant it. One engineer spent thirty-three years in Mann companies. Another called his two decades there "the best two decades of my life." People who had worked for him were still writing affectionately about him on LinkedIn eight years after his death.
In a serial founder's portfolio, culture is what moves from company to company. The cochlear-implant team, the pacemaker veterans, and the engineers who worked for him twice are what made each new company quicker to start than the last. That kind of goodwill comes from consistent behavior. People noticed that he cared about the person cleaning the office, and they repeated the story because he acted that way.
Tactic: On a new company's first day, tell its leader explicitly which people in the organization are easiest to overlook and how you expect them to be treated.
Principle 12
Endowments outlive intentions
Mann gave USC more than $174 million to build an institute that would bridge academia and industry under rules he set. Twenty-five years later the university reallocated most of a $230 million endowment, dissolved the institute, dismissed its board, and named the pharmacy school after him. His name lasted. His design did not.
This was not a betrayal. It is what happens to gifts once the giver is gone. Institutions have their own priorities, and an endowment governed by a university will eventually serve the university's purposes. Mann partly anticipated this. He kept most of his research work in vehicles he controlled, including his own foundation, and in his Giving Pledge letter he described "two holding entities to distribute assets to fund my philanthropic activities." The foundation he kept closest, the one that produced the cochlear implant and Axonics, is the part of his philanthropy still doing what he designed it to do.
Tactic: If a philanthropic gift depends on a specific operating model, put that model in an entity you govern and treat university endowments as support for their mission, not for yours.
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Part IIIQuotes and Maxims
In their words
— Alfred Mann, Los Angeles Times, June 1, 2001I'm most excited and interested in the start-up and seeing it through its adolescence. When it gets to be a mature adult, it has less interest for me.
— Alfred Mann, as recalled by Robert Greenberg, Los Angeles Times, 2014No way. This is just an engineering problem. And it's solvable.
— Alfred Mann, Los Angeles Times, February 5, 1998Most of the Nobel Prizes go to scientists in this country, yet all of the products are coming out of Japan and Germany. I want to create a bridge between academia and the industry.
— Alfred Mann, Forbes, 2006If the university can pick and choose what they make available to us, it defeats the purpose.
— Alfred Mann, Los Angeles Times, October 9, 2011I've got more money than I can spend. For me, the satisfaction of changing someone's life — indeed, even giving a person back a useful life — that's what really drives me.
Maxims
- Listen for the adjacent problem. Your next market is often the problem your best customer mentions just after the one you solve.
- Triple the estimate. In hard technology, the honest capital requirement is three times the number you first believe.
- Ownership and authorship are different things. You can sell the equity and keep building the company.
- Know your stage. Be clear about whether you are good at a company's adolescence or its adulthood, and hand it off when it changes.
- Features expire; organizations adapt. Build the capabilities that will survive your headline innovation.
- Give long shots a permanent home. A research unit upstream of your companies keeps them supplied with new ideas.
- Name the obstacle before you push. Persistence solves engineering problems more reliably than market problems.
- Your own money can mute the market. Self-funding should come with a predetermined point at which you require outside conviction.
- Strings limit scale. Conditions protect your design and also reduce the number of people who will accept it.
- The floor matters. People remember how you treated those least likely to be noticed, and they bring that memory to every company you start.
