Most of the publicity in biotechnology usually concerns the discovery of another gene or the development of genetically engineered bacteria that produce a valuable new drug. But there is a more mundane side that is also important: finding efficient ways to "harvest" a new drug from the bacteria or animal cells that produce it. It is a ticklish job, because the drug must be purified of all toxins and other detritus produced by the host cells.

To address that, researchers at [PerSeptive Biosystems] Inc. of Cambridge, Mass., recently patented a separation technology employing novel porous particles that they said speeded purification tenfold.

Until recently, the fastest process has been high-performance liquid chromatography, in which a solution containing the new drug passes through a tube packed with specially coated particles that snag molecules of the drug. These particles are filled with tiny channels, making it possible to absorb large quantities. But the process is still slow.

To speed the process, the new particles are riddled with both wide and narrow channels, which the inventors said are analagous to superhighways and city streets. "If you try to get in to the center of a city by taking the small streets, it can take hours," said Fred E. Regnier, a chemistry professor at Purdue University and one of the inventors. "We solved that problem by creating superhighways that bring you right into the center of the city, within a few blocks of where you want to go."

In the new particles, made from polystyrene, the wide channels serve as the highways that let the solution flow easily to the particle's center, where it can be absorbed rapidly by scores of tiny channels.

Dr. Regnier, [Dr. Noubar Afeyan (born 1962)], president of Perseptive, and Robert C. Dean, a consultant, received patent 5,019,270.

The Beat Goes On

[Let] us examine the case of a new company, now just three years old, and in the newest of emerging technological fields, biotechnology. PerSeptive Biosystems is too young to "prove" anything, but its formative years again show the uncertainty and sometimes even turmoil that need resolution as a start-up finds its own direction and moves forward.

Noubar Afeyan and PerSeptive Biosystems, Inc. Beirut, Lebanon, is the starting point of the story. Noubar Afeyan was born there in 1962 in the Armenian section, the youngest of three sons. His father had had an architecture education in Bulgaria and worked at that profession in Lebanon during the day, but started an import/ export business at night two years before Noubar was born. While Noubar was growing up, his father's business, now a full-time occupation, grew too and Noubar remembers well his childhood impressions of warehouses, the port, unloading ships, rounding up day workers by truck. His childhood was not exactly typical for a to-be biotechnology entrepreneur, with continuing outbreaks of violence eroding the quality of life. But in that polyglot community Noubar received a good education, becoming fluent in Arabic, Armenian, English, and French, while also developing a "street smart" sense. In 1975, the civil war in Lebanon had erupted again and Noubar's parents decided to move the family out of the country. They departed for Montreal, where cousins were already living. One indicator of the trauma they were experiencing is that the Beirut airport closed two days after the Afeyans departed, not to reopen for four years.

During their first year in Montreal, the boys entered Jesuit school while their father tried to start a manufacturing business. Months of frustration led to the elder Afeyan reestablishing his import/export enterprise, which five years later, in 1981, finally led into the manufacture of plastic-covered furniture and related products. Noubar, his brothers, and his mother actively worked at the business whenever needed.

Noubar thought about applying to MIT when he was finishing high school. But concern about leaving his then 86-year-old great-aunt, who had lived with the family throughout his childhood, led Noubar to enroll in McGill University, just one block down the street from his house. Choosing chemical rather than electrical engineering for his undergraduate major was influenced by his father's encouragement that chemical engineering might at least relate somewhat to his plastics activities. The first semi-serious discussions about starting his own company took place regularly with Noubar's undergraduate friend Dave Rich. Together they were going to create ARC-Afeyan-Rich Company, to undertake a variety of creative businesses but nothing real came of these many chats. Noubar's rather remarkable great-aunt, 97 years old in 1990, reminds him that he was always talking about running his own business even when he was a child.

Despite an attractive job offer from Dow Chemical Noubar decided, in 1983, to apply, and got accepted, to MIT's new Ph.D. program in biotechnology process engineering. His work primarily with Professors [Dr. Daniel I-Chyau Wang (born 1936)] and Charles Cooney exposed him to their growing networks of consulting relationships with large and small companies in the United States and abroad, as well as venture capital firms. Noubar generated lots of ideas, leading to impressive experimental findings and he published papers with several MIT faculty. But he had no interest at all in becoming a professor; he clearly wanted all along to be a key player in some company. One of the MIT faculty, Raymond Baddour, gave a seminar on all the alumni of the MIT Chemical Engineering department who had achieved outstanding success (several in association with Baddour's own multiple entrepreneurial efforts; see Appendix, Track 1). That seemed great to Noubar and he wanted to become part of that list.

In 1986, Afeyan enrolled in the New Enterprises course in the Sloan School of Management and had to prepare a business plan. He worked out a semiserious plan, without the financials, for one of his ideas on a protein purification system that he named CARE-Continuous Affinity Recycle Extraction-doing the project alone because he was afraid someone might try to take the idea and run with it. Noubar reports feeling that the Sloan School was entirely foreign to him-the jargon, costume, aspirations of business school students were almost alien to the engineer. Later that year he entered into negotiations with the giant Swedish firms Alfa-Laval and Pharmacia to turn that CARE idea into an actual company, but the deal evaporated when the two large companies had a falling out with each other. The negotiations were not without some lasting benefit; Noubar married one of the women Alfa-Laval had sent over to MIT during the discussions.

In spring 1987, as he was nearing completion of his Ph.D. dissertation, Noubar came to see me for permission to take my course on Corporate Strategies for New Business Development. I initially refused him, as he obviously lacked the formal prerequisite subjects. I told him that I doubted that he could write an acceptable term paper without lots of Sloan School background education. Afeyan's persistence overcame my stubbornness and in the end he prepared one of the best papers in the course, contrasting entry strategies into the biotechnology field of several major chemical companies. 

At the same time Noubar had tired of trying to get his own ideas translated into the basis for a new firm. He reluctantly accepted the notion that he seemed to be hearing from everyone that he was too young and inexperienced and needed industry seasoning and was on the verge of accepting a job in industry. Fortuitously, Professor [Dr. Daniel I-Chyau Wang (born 1936)], his thesis chairman, introduced Afeyan to a much older experienced multicompany entrepreneur who was being pushed out by investors from his latest company creation. Noubar, then 24 years old, and the older entrepreneur, 60 years old and wiser from his several company start-ups, hit it off immediately, and by the end of one intensive day of discussions they had more-or-less agreed to start a new company in the area of biotechnology processing. On the very next day several people began warning Noubar that this relationship would not work out, that his partner was too inflexible and had a reputation of being tough to work with. Noubar had concluded that they were a good complementary match. Now he had the chance to translate his many ideas into a real company. Wistfully thinking back to that time, Noubar recalls, "I thought he knew his limitations and that therefore we'd be able to get along. I could create and promote and he could manage the technology development." 

In August 1987, Noubar Afeyan became the first Ph.D. graduate from MIT's Center for Bioprocess Engineering, and he was already hard at work getting the new company underway with his partner. During October Afeyan brought me a copy of their first business plan, a proposal for launching Synosys Corporation as a rather generic developer and producer of biotechnology processing hardware, with one of Noubar's system ideas as product number 1. He invited me to become a director and an initial stockholder, but after reading the plan I declined. They hoped to enlist major corporations as their principal financiers and collaborators in a series of strategic alliances. Neither the plan nor its timing was great; the stock market's Black Monday occurred one week after I saw Noubar. Among other effects of the market crash, venture capital companies became more conservative and especially skeptical of new companies focused on capital equipment markets, such as Synosys. Despite the apparent problems Synosys was incorporated at the end of November, the two founders each owning half the company, with the bills being paid by loans to the firm from the older partner. 

Months dragged by as they presented their plan to numerous companies and prospective investors. In the meantime Professor Fred Regnier of Purdue University, one of the world's leading experts in separations technology, was recruited to become an advisor to Synosys and began working with Noubar on new approaches to porous materials for biotechnology separations processes. Noubar took a part-time job at MIT in January 1988, working as the technology transfer manager for the BioProcess Engineering Center under Danny Wang's directorship. Much more time was going to  be needed to raise the capital to get going and they could use the income and the contacts the job would produce. They also rented a small office in American Twine Office Park, a converted old mill filled with MIT high-technology spin-offs, located just behind MIT in East Cambridge. 

With all the critical feedback on their first business plan Noubar wrote a new one in March, aimed at venture capitalists not corporations as the potential funders and following to the letter the guidelines in Jeff Timmons' textbook, New Venture Creation (1985). This plan had a dual focus: the porous separations materials and a biotechnology processing hardware system, aimed at new product developers. Noubar started sending around the new plan and visiting venture capital firms. I received my copy in April 1988, read it and decided to visit the founders in their offices. As I entered I was offered a bench to sit on, just being hammered into completion by Danny Wang's son who was working there part time. The co-founders and I talked at length, especially about my feelings that the materials business was attractive by itself and that the hardware system was a confusing distraction. We also talked about the roles of the two co-founders and whether they would be willing to bring in a more experienced partner as CEO or Executive VP (reminiscent of AR&D's hesitation with DEC). Despite some reservations, upon return to my office I called the biotech specialist at First Stage Capital, a venture capital firm I co-founded and serve as a General Partner, and suggested he look into Synosys in depth. First Stage began working closely with Synosys, criticizing many aspects of their plans but also encouraging their overall efforts. 

[Dr. Daniel I-Chyau Wang (born 1936)] began to get more involved and technical progress was being made with the porous materials. But funding decisions dragged on. In June First Stage Capital turned down Synosys because of our unwillingness to fund the hardware part of the company. Noubar borrowed some money from his father and began to pay the bills; his partner was running out of funds and was looking for alternative employment in academia. In August, Wang and several friends invested $200,000 and suddenly things seemed a bit brighter. In September an agency of the Canadian government with which Noubar's father had good relationships indicated that it would be willing to invest $2 million in the company, provided that Synosys would move its hardware activities to Canada. Despite uncertainty as to whether Synosys should or would accept the Canadian funds, that change in prospects was enough to renew First Stage Capital's interest in financing the materials portion of the company. 

By November, still without the major capital infusion needed to move ahead decisively, the Synosys team and its consultants developed "perfusion chromatography", an approach to protein purification that could produce a tenfold speed advantage over existing technologies. Finally, or so it seemed, in mid-January 1989 Synosys reached agreement with First Stage Capital and Noubar signed off on a detailed term sheet. Two days later his older partner suddenly announced he was through, claiming family pressures, thus beginning several months of fighting over stock, roles, compensation. Terry Loucks from Rothschild Ventures, who had met Noubar during the fund-raising period, agreed to come in as full-time chairman and CEO, with Noubar becoming president and chief technical officer. On April 1, hopefully not to be remembered later as April Fools' Day, the checks were signed for $1 million for one-third of the company, First Stage Capital being joined in the investment by Raytheon Ventures and 3i, a large British venture capital fund with an office in Boston. In search of a new identity the firm was reincorporated as PerSeptive Biosystems, trying to put the trauma of Synosys Corporation in the background. Two years had elapsed since the day Noubar and his now former older partner had agreed to start a company. The new team now featured Noubar Afeyan, Terry Loucks, and Fred Regnier from Purdue. 

People began to be hired, several new Ph.D.s coming in from Purdue and MIT. Patents were filed on the concepts, the materials, and the designs for new processing equipment. The now named "Poros" materials began to generate amazing results in lab tests. In November the PerSeptive team stole the show at a technical symposium in Philadelphia, presenting several papers on the technology and its performance and generating instant sample orders from several large companies. 

As of September 1990 PerSeptive Biosystems had 26 employees, a growing group of enthusiastic customers, and newly delivered checks from its second round of venture capital, $3.3 million from its original venture capital investors plus Venrock and Bessemer Securities, the funds needed for expansion of the company and for development of its second product line, an instrument system for automating use of the Poros materials in developmental applications. I asked Noubar what he wanted to accomplish now. "I want to create an analog of Hewlett Packard-tools for a new breed of engineers, bio-process engineers. If the industry grows the way it's expected to, we should be able to reach $40-50 million in sales in five to six years. By the way, becoming rich wouldn't hurt", he added. "There's nothing more motivating to succeed than having to beg for money to get started." N oubar Afeyan was 28 years old. 

Compared with the cases presented throughout this book Afeyan shows strong continuity of the earlier patterns. Noubar's father was a professional and an entrepreneur, and Noubar gained much experience with the process of business development while he was growing up. After receiving his MIT degree he had worked only in an MIT lab before setting up his own company at a young age. In fact, Noubar really started PerSeptive on a part-time basis while he was still in graduate school, and his general interests in running his own firm stem from childhood. The technology was transferred directly from his MIT education and lab work as well as from Fred Regnier's work at Purdue. Initial funds came from his co-founder's savings, then from his family and friends, and only later in two large rounds of investments from venture capital firms. [...]

EARLIER this year as part of his campaign for a new health care system, President Clinton fired a salvo at pharmaceutical companies, criticizing them for the high price of drugs. The Administration is now gearing up for a national fight over a health care package that will include lower medical costs as a goal.

A new biotechnology patent could help drug manufacturers meet that goal on their own. Perseptive Biosystems of Cambridge, Mass., won a patent last week for a tool to purify molecules that it says shaves hours -- and therefore dollars -- from the usual method. The process, called chromatography, is a first step in making groups of drugs like human-growth hormones, insulin and medication for heart disease, anemia and hemophilia.

"It's a complicated technology in an area where there has been very little development in the last 20 years," said the president of the company, Noubar Afeyan. "How can you contain costs if you're using tools developed 20 years ago?"

Chromatography separates molecules like proteins by flushing them through a tube packed with sand-sized polymer beads. The beads are porous and can absorb certain molecule compounds. Molecules needed for drug production stick to the beads; unwanted molecules are flushed out of the tube. The purified molecules are then detached from the beads with a special solution, and collected.

Bigger Holes

"You can obtain very high levels of purification if you do it several times," Mr. Afeyan said. But it currently takes several hours for the molecules to pass through and be absorbed into the beads. Mr. Afeyan said Perseptive Biosystems' invention cut that to less than five minutes because its beads have holes big enough to allow liquid to help transport the molecules.

"The bottleneck is in the rate of diffusion of the molecules" into the beads, Mr. Afeyan said. "We have created channels through the particle beads that are big enough to allow liquid to flow through. The difference is in the flow rate at which the molecules can get into the beads. They get there much faster."

He acknowledged that improving absorption by making bigger holes seemed "phenomenally obvious."

"But it's only in the last three or four years that people have started trying to make large quantities of these products," he said. "So only now has the speed and productivity of the technology been in question."

Mr. Afeyan added that studies supported by his company had shown that the new technology could reduce purification costs for drugs by 50 percent to 75 percent. Perseptive Biosystems' patent is number 5,228,989. 

[...]

The [Perkin-Elmer Corporation] said yesterday that it had agreed to acquire [PerSeptive Biosystems] Inc., a maker of laboratory kits and instrumentation used by biotechnology companies, in a stock swap valued at $360 million.

Perseptive, based in Framingham, Mass., is a leading producer of equipment used to separate and identify intact proteins, which form the basis of most biotechnology drugs, and has also developed advanced products for the separation and purification of biological molecules in the life science market. [Perkin-Elmer Corporation], through its 1993 acquisition of [Applied Biosystems] Inc., is a leading provider of DNA sequencing and synthesizing equipment to biotechnology companies.

The acquisition will allow [Perkin-Elmer Corporation] to add greater value to gene-based drug discovery than it has had as a tools provider, said Peter Barrett, Perkin-Elmer's vice president for business development. Making the company a player in the emerging field of genomics, rather than just an instrument vendor, has been a key strategy of [Tony Lee White (born 1947)], who joined Perkin-Elmer two years ago as chairman, president and chief executive.

''If you look at the genomics companies, like Human Genome Sciences or Incyte, the value created by these companies is driven by our systems,'' Mr. Barrett said in a telephone interview. ''What we're trying to do here is move to another level of platform delivery, to move closer to the information.''

The deal valued Perseptive at $13 a share. Its shares surged 17 percent, or $1.8125, to $12.4375 in Nasdaq trading. Perkin-Elmer shares rose 62.5 cents, to $78.6875, on the New York Stock Exchange.

Analysts said the deal would strengthen Perkin-Elmer's product line on the biotechnology side, which is growing, and help offset the slowing of its traditional business in chemical analysis tools. Because Perseptive has not yet been profitable, the deal will reduce earnings per share in the near term, but should provide a long-term income boost, they said.

''They're trying to expand their exposure to biotechnology instrumentation,'' said Lawrence W. Borgman, an analyst with Josephthal Lyon & Ross. ''They're very big in DNA synthesis because of Applied Biosystems; with this they add a presence in proteins as well,'' he said. ''The biotech side of the business is growing and has good margins.''

For Perseptive, which expects revenue of $85 million in its fiscal year ending Sept. 30, the deal removed uncertainties about future financing and distribution.

''We felt that under the value proposition presented to us by Perkin-Elmer, our objectives would be better accomplished by the merger,'' [Dr. Noubar Afeyan (born 1962)], Perseptive's chairman and chief executive officer, said in a telephone interview. ''The constraints we've had will be eliminated.''

The genetic information business is not for the timid. Consider the stock prices of two leading genetic database companies, Incyte Genomics (formerly Incyte Pharmaceuticals) and [Celera Genomics Corporation]. When Celera entered the market last May both these companies were selling for well under $20. By the first of March, Incyte and Celera's share prices had soared to $289 and $278 respectively. But investors who were popping champagne corks in March were crying in their beer just six weeks later as the value of both companies fell to less than one-third of the March high.

The meteoric rise and subsequent precipitous fall of these companies' stock prices is based largely on investor perceptions of the value of intellectual property rights the companies hold-perceptions that are not always based on a sound understanding of what the value of intellectual rights really is.

Intellectual property rights are so fundamental to American commerce that they are actually specifically mandated by the U.S. Constitution which, in Article I, Section 8, grants to Congress the power, "To promote the progress of science and useful arts, by securing for limited times to authors and inventors the exclusive right to their respective writings and discoveries." In 1980, no less a body than the U.S. Supreme Court extended those rights to cover the patenting of genes when the patenting party can prove a specific utility.

Enter Celera and Incyte, which are focused on obtaining genetic data and using it to make money. As more information reached the public about the potential of genetic data to help create drugs and diagnostic tests with enormous commercial potential, the stock prices of these companies climbed rapidly. Celera made headlines with its claim of how it would complete the genome years before the government- and charity-funded Human Genome Project. More public attention came with dozens of feature articles and news announcements, such as those following Celera's filing of 6,500 provisional gene patent applications last October. The stock price peak came just before President Clinton and Prime Minister Tony Blair made a joint announcement that it was their policy that the public should have free access to genomic data, which appeared to throw a major stumbling block in the genetic information companies' path to profit.

As is often the case when rapidly changing science and investment come together, the history of genetic information is largely a history of misperceptions. At least three very important mistaken ideas have contributed to the confusion. First, there are erroneous ideas generally accepted about exactly what is actually being patented and what those patents mean. Secondly, the nature of the genetic database products these companies will sell is not clearly understood. And thirdly, there is a vast misunderstanding about biotechnology in general and how and when it will bear fruits.

The first point has been the subject of headlines that border on yellow journalism. "Who Owns Your Genes?" asks CNN in an editorial that is typical of many others that have appeared recently.

Michael Hunkapiller, president of PE BioSystems, told IBO, "I think it's a misperception of what's being patented that has caused most of the problem. There's [a misperception] that you can patent somebody's genes. Well, you don't patent somebody's genes. You patent a gene with a particular utility for use in a different circumstance than what it was used for in the context of a person."

The question of a gene's utility is critical, and the law regarding this is not firmly set at this point. Patent rules on utility of gene patents have recently been tightened, but it remains a gray area that will require testing in court to clarify. This is a process that, though slow and often expensive, has been the basis of establishing intellectual property ownership through 200 years of the most rapid technological change in history.

The second important misperception is that patent ownership will mean the difference between success and failure for the genetic information companies, and that they are basing all their hopes for profits entirely on their patent applications. Noubar Afeyan, president and CEO of NewcoGen Group, founder of PerSeptive Biosystems and the former senior vice president of PE Corporation, who oversaw the creation of Celera, says that idea is absolutely wrong.

"In the case of Celera...I can tell you that patents are not-are not-the strategy for deriving commercial value, and they've said that many, many times. The converse, that is [the idea that] patents therefore should not be gotten on anything that is valuable and could be potentially a source of revenue [is also not valid.] The one doesn't follow the other. It's one thing to say, 'our strategy is based on getting patents on everything and licensing it.' The other thing is to say, 'that's not my strategy, but oh, by the way I still think that if we get genes that have meaningful function that might be valuable targets and we've done the real rigorous work to show it, then those are patents we might get.' Those are completely consistent statements."

Genetic data companies will not rise to success and prominence based solely on ownership of intellectual properties. Their challenge is to organize, process and package raw genomic data into information products that have a high value. Without effective product development to synthesize genetic information-both proprietary and public-into products that have significant value to customers, the information will not result in successful businesses.

Perhaps the biggest misperception is how soon the genetic data will bear fruits in the form of dramatic new products. Dr. Afeyan believes the expectations for products based on the genetic information now being accumulated are unrealistic. He describes the process as an incredibly complex "reverse engineering of nature."

"One thing that people haven't understood, in my view, is just how massive the challenge ahead in getting value out of genomics is, and how unpredictable it will be as to who can find commercial value out of all this information...If I give you a computer and you don't know what anything in it is and you take it apart, it's very hard to reconstruct...[Then if] you could take all the parts and grind them down to the atomic level-silicon-and you could count how many silicon particles there are per square angstrom, would you ever be able to figure out that it was a computer if you took it to the silicon level? So let me tell you that [researching] the basic genetic level is that...But I think that [the questions about patents on genes] will sort out when people realize just how difficult and far away we are in making useful sense out of all this information. If you believe that we are within weeks and months of making useful sense out of this information, then it's time to fight over patents. If you believe, as I do, that we are years and decades away [you won't.]...That's my view and that's why I don't get all hot and bothered about all this patent stuff. I just think it's rhetoric."

One other misperception is the motivation behind much of the current rhetoric. While it may appear from the recent news stories that in the debate money is on the side of those asking for gene patents and altruistic science is on the side demanding free access, on closer examination it's hard to find anyone involved who has no financial interest in the question. To understand this, it's important to see one critical point: It is overwhelmingly in the interest of drug companies to put genetic information in the public domain. They would very much like to have the information they use to develop drugs available free to them, while the drugs they develop using that information should be proprietary and priced as high as the market will bear.

So when a Knight-Ridder headline reads, as a recent one did, "Gene Patents Inhibit Usage of Diagnostic Screening Tests," it appears to be an illustration of the most cynical greed. But the headline might just as well have read, "Drug Patents Inhibit Use of Disease Cures", since the drug companies have made no movement to make their discoveries available for free as some people are suggesting genetic information companies should.

The organizations behind the Human Genome Project-the government and the Wellcome Trust-give the impression that they are objectively acting solely for the public good when they call for open access. But with drug companies spending tens of millions every year on government lobbying, government objectivity is far from pristine. And the charitable Wellcome Trust holds a large block of stock in the pharmaceutical company Glaxo Wellcome, which also stands to reap significant benefits from making genetic information free to drug companies, and thus cannot be considered wholly disinterested.

The stock market, ever the fickle suitor, was mistaken twice-first when it overvalued bioinformatic companies believing the human genome gene patents were in themselves the key to enormous instant wealth, and again when it spurned the same companies based at least in part on the suggestion that their intellectual property rights might be weakened.

The reality is that for genetic information companies, like any other company in the analytical and life sciences industries, patents are a part of business, but not the most important part. The completion of the human genome is not the end of a race with big bucks automatically going to the winner, but the beginning of an infinitely complex process of trying to gain an understanding of the interaction of proteins. The real fruits of that process are decades rather than months away; a timescale that will seem geological to the minds of most Wall Street investors. Furthermore, the success of genetic data companies will depend on their ability to create and market valuable information products based on genetic information, far more than it will depend on patent rights. While patents will clearly have some value in this arena, the process of proving a patent enforceable is slow and expensive, especially in a field like this where the court system will have to clarify exactly which gene patents will hold up. For companies in this industry, this means they must be prepared for legal battles. Small companies will need either deep pockets of their own or partners that can sustain them through protracted litigation, including appeals.

Dr. Afeyan, who has extensive first-hand experience with the legal vicissitudes of the patent system, puts it this way: "It's easy to say the system doesn't work. It's like saying taxes don't work, it's like saying a lot of things don't work. I don't see the evidence of that. And, to be honest with you, I'll go even a step further. This whole notion that I hear these days about people saying that 'but for the patentablilty of genes the pharma companies wouldn't develop drugs on these things'-I don't buy that either."

A bigger danger to bioinformatic companies than the tightening of governmental policies is an investment community that alternately overvalues and undervalues companies based on their intellectual property rights. The investors are always seeking certainty, and patents appear to offer a sort of guarantee. But the guarantee is an illusion. Patents, even if they can be enforced, are no assurance that a company can produce quality products or stay competitive when another company comes up with an alternative technology. Conversely, lack of a patent is no sure sign that a company cannot be competitive.

Another way to look at it is that intellectual property rights are purely defensive. They do not gain customers, and they do not bring profits. They only prevent others from using very specific ideas for which clever competitors can often find alternatives. One does not win a battle or a ball game or become a market leader purely on the defensive. Strong businesses are the result of robust competition to create superior products and get them into customers' hands. The real test of the genetic information companies will be to see what information products they create and how well those products make genetic data useful.

As President Clinton got ready to announce at the White House last month that Celera Genomics Group [which became Celera Genomics Corporation]  had discovered the genetic directions for building and running a human body, the company's chief executive filed in with hundreds of others and took a seat to the side of the stage, three or four rows from the rear.

[Tony Lee White (born 1947)] could have had a spot at the podium, one that Celera President [Dr. John Craig Venter (born 1946)] shared with Clinton. But it was his way of remaining behind the scenes, a curiously anonymous chief executive in a spectacularly visible company.

Staying in the shadows also belied his role in one of science's monumental achievements. The sequencing of the human genome has been compared to the completion of the periodic table of the elements and the moment of its announcement with the landing of men on the moon.

But it was White, a salesman by training, who orchestrated the race to map it largely because of the opportunity to sell.

From pushing for the development of the machine that sequenced it to forming the company that did it to choosing scientist Venter to run it, it was White, former company director Joseph F. Abely Jr. recalled, who led Celera's parent company "to come to grips with the human genome."

Still, [Tony Lee White (born 1947)] remains one of the least known minds in biotechnology, an industry hurtling into a future where the building blocks and worker bees of life's cells are being used to develop everything from drugs designed to choke cancer to cotton that grows in color.

[Tony Lee White (born 1947)], 53, also may be among the industry's most unlikely captains. Raised alternately amid a Cuban revolution and North Carolina poverty, he wandered through economics studies at Western Carolina University in Cullowhee before graduating without distinction.

Raised amid uncertainty, he became a master of gut instinct, a man who built a career at conventional, old-line businesses by breaking with convention.

White's successes include turnarounds at medical-supply company Baxter International Inc. and PE Corp [see PerkinElmer Incorporated]., the Celera parent company he now runs. Those successes largely have been based on avoiding the propensity of some CEOs to become wedded to a single -- and ultimately outmoded -- plan. They also have been based on a disdain for cumbersome detail that forces him to focus on the big picture, relying on experts for the rest.

Now, the man behind the curtain in the sequencing of the human genome is using the same instincts as he maps where to take his company next. It is -- once again -- a bold plan.

"This guy is a free-swinger," said Vernon Loucks Jr., former CEO at Baxter, where White worked for 26 years. "He isn't afraid once he's got an idea to go after it, and he did that with Celera in spades. That's Tony's game."

[Tony Lee White (born 1947)] was born in Havana to a Cuban mother and a North Carolinian father who met after his mother came to the state in the early 1940s for college. He grew up bilingual, watching his educated and wealthy Cuban grandparents lose everything in a revolution in the midst of which White was once forced to hit the floor of a bus as soldiers fired shots.

He also watched his father leave job after job. Today, White describes him as "kind of a hillbilly" who did not contribute to the support of the two-child family after his parents divorced. His mother made ends meet by working as a secretary at a cigarette paper plant 40 minutes from their Asheville home.

"Those struggling years were a big influence on my brother, because he didn't like the struggle," said Marco White, eight years Tony's junior and now in middle management with Coca-Cola Co. in Atlanta.

It was amid this uncertainty that Tony White learned to take life as it came, throwing himself into jobs such as loading furniture trucks and honing an engaging personality that landed him a part in the play "Cheaper By the Dozen."

He married his junior-high sweetheart but he never made a plan. Still, he knew as he walked through a career fair that what he was looking for was "my ticket out of there." He bypassed the booths of well-known companies, J. C. Penney among them, and headed up the steps to interview on a whim with a company he'd never heard of.

"I'd rather die," he told the Baxter Laboratories interviewers when asked, "than be your personnel manager in Kingstree, S.C." They offered him a career in sales instead.

At Baxter, White hit his stride. He repeatedly finished among the company's top sales producers and -- aided by his ability to speak Spanish -- was handed a job as export manager for a Baxter product line in Latin America.

It was a Baxter cesspool where salespeople followed the custom of the day by paying bribes to get accounts. White cleaned it up by setting sales targets, outlining his expectations for clean dealing and firing employees who didn't comply.

White was promoted to running the company's Latin American operation, and results were spectacular.

Revenue in the region climbed from about $50 million to several hundred million by the time he left it.

A White-inspired turnaround in Canada followed, and White's reputation took off.

He was one star in a constellation at Baxter, a company filled with young men who would go on to lead, from current Genzyme Corp. CEO Henri Termeer to Wilbur H. "Bill" Gantz of PathoGenesis Corp. James R. Tobin, now chief executive officer of medical-device manufacturer Boston Scientific Corp., was among them. He often used White to help diagnose problems.

On one occasion, when Tobin was in his early 30s and the new head of Baxter's operations in Spain, he was stumped by a broken-down business unit he had just inherited.

The business was supposed to make and market intravenous solutions, but the production plant had been shut down for months because of a mysterious contaminant, inventories were wiped out and the business was losing money on sales.

"Tony came over and wandered around awhile," Tobin recalled of how White began to evaluate the problems. A bottle-washer was spraying particles into bottles it was supposed to be cleaning, and the head of the IV business needed to be fired. "Get rid of that turkey," White told Tobin.

Tobin took the advice. But years later, after White's blunt assessment of another situation had offended a peer for what seemed like the umpteenth time, then company President Gantz called White into his office.

Penchant for straight talk

"You do a great job" Gantz told him, but he warned that White's blunt style was hurting his chances for advancement.

Ultimately, White rose to become part of a four-man "office of the chief executive," but he never got Baxter's top job. He would later conclude that his lack of a Harvard Business School pedigree had hurt him, along with his penchant for straight talk.

Loucks, the longtime Baxter CEO and chairman who retired last year, said it was none of those things.

"Perkin-Elmer [now PE] was in a situation where you started at rock bottom," Loucks said about why White's free-swinging aggressiveness has played well at the company he now heads, but wasn't suited to the top spot at Baxter.

"Heroic kinds of actions fit better there than they do in an organization that's not all that broken," Loucks said.

White stayed on at Baxter, but he felt the tension between himself and Loucks increasing. One day, he said, Loucks asked him when he was going to retire. White was stunned. He was 48.

Loucks denies the incident, but when a call came to interview at Perkin-Elmer Corp. for the top spot, White went ahead.

What he found was a potential cleanup job that intrigued him. Perkin-Elmer Corp. had made its mark in a business with now-unspectacular returns, selling garden-variety lab gear and instruments used in the environmental and chemical industries to test for contaminants. Its departing CEO and board had recognized a future in life sciences in 1993 when they bought [Applied Biosystems], a Foster City, Calif., company whose products included DNA-synthesizers and analyzers, but they had let it languish.

White's due diligence included meeting with the company's investment bankers, who told him a third of Perkin-Elmer's stock-market value was because of the fact that investors thought it was about to be taken over.

White took the job in the fall of 1995 and began studying it, piece by piece.

"I've got to go through here and look at what can and can't be turned around," he told his brother in a phone call.

To White, it quickly became apparent that the cash-generating life sciences business was being robbed to prop up the declining old lab business. He reversed the emphasis, using revenue from the old division to support research and development in life sciences.

One of his first steps, he recalled, was to light a fire under development of a next-generation DNA sequencer, a market he did not want the company to lose to competitor Amersham Pharmacia Biotech.

"If anyone wants to make obsolete what we do today, it's going to be us," White said he thought at the time. He gave [Applied Biosystems]' head Michael W. Hunkapiller $8 million more to pursue the job.

To Mike Albin, head of a Biosystems unit formed to do "blue sky" thinking about future products, the change was palpable. White, despite years with an old-line medical-supply company, seemed to have a Silicon Valley mentality. After White came on board, he said, "The level of support for what we wanted to do went up significantly."

Even with all his experience at Baxter, White was in some ways an unlikely choice to lead what would become a genomics company -- one based on exploring the detail of the 3.2 billion-unit genome. Notoriously impatient with minutiae, White turned to an illustrated paperback guide called "The Cartoon Guide to Genetics" for some of his first lessons on genes and proteins after becoming CEO.

But scientists soon began to respect him. White's ignorance seemed to give him the curiosity to explore ideas, and his focus on the big picture helped him cut to the chase in meetings when his scientists began debating and massaging tangents, said company director Georges C. St. Laurent Jr., who has known White for years.

Stephen A. Martin, now director of the company's nascent Proteomics Research Center, said White seemed to have a good sense of when scientists were just "blowing smoke."

White had also softened his style because of Gantz's advice. At Perkin-Elmer, he acted more like a quiet but forceful facilitator, a behind-the-scenes direction-giver curiously overlooked by nearly all who later would pass out credit for the genome.

Taking the next step

White had realized almost immediately that reversing the emphasis at Perkin-Elmer wouldn't be enough.

The life sciences division, if it were to be the foundation of the company, would have to be strengthened through acquisitions. He gave himself three years to increase revenue to more than $1 billion from the $350 million he inherited. He planned to cut the old business loose once the new one had enough mass to stand alone.

A hunt began, leading in part to Framingham, Mass.-based [PerSeptive Biosystems], a manufacturer of machines used for, among other things, determining the structures of proteins -- the worker bees of cells.

PerSeptive Chief Executive Officer [Dr. Noubar Afeyan (born 1962)] was a serial entrepreneur who had never worked for anyone but himself. After six years of running his latest company, he itched for both a way to cash out and a change. He grew to admire White's entrepreneurial bent as the two negotiated the sale of PerSeptive. To Afeyan, White's plan for reinventing Perkin-Elmer gave the old company the feeling of a start-up.

When White asked him to accept a job plotting strategy at Perkin-Elmer, Afeyan accepted.

Transforming the company, White told Afeyan in their initial conversations, is "going to involve some subtraction and some addition. What I want you to worry about is how we extend the business model."

As Afeyan waited for federal antitrust regulators to clear his company's acquisition by Perkin-Elmer, he began mapping out a plan with multiple options, including a genomics information company.

About November 1997, he presented the options to the board of directors in an introductory meeting. The same month, at a meeting of 20 or so Perkin-Elmer executives in Foster City, Calif., the planning took on sharp focus.

Afeyan, still new to his strategic role and a relative stranger to most in the room, sat by White and listened to one of [Applied Biosystems]' employees make a presentation on a machine the company would dub the ABI Prism 3700. It could sequence DNA at breathtaking speed. Afeyan did some quick back-of-the-envelope calculations and blurted, "You know, we could do the whole genome with a couple hundred of these." White was intrigued.

Applied President Michael W. Hunkapiller wasn't so sure. Afeyan recalled that Hunkapiller -- later widely given credit for coming up with the idea -- told the group that sequencing the genome would compete with customers, the research institutions and pharmaceutical companies that bought its products to do just those sorts of calculations. PE was a products company, he pointed out. Perhaps the company should stick to its knitting.

In an interview, Incyte Genomics Chief Executive Officer Roy Whitfield said Hunkapiller had raised the same concern years earlier. Incyte, already a genomics information company like the one Celera would become, had pitched the idea of Incyte and Applied sequencing the genome together in a nonprofit venture, Whitfield said. Hunkapiller declined.

"This was way back in '92," Whitfield said. "Mike said, 'There's no way we can do that. We're an instrument company and there is potential for us being viewed as competing with customers.'"

Afeyan, new in his strategic role, felt chastened by Hunkapiller's concerns at the meeting. Hunkapiller was a pioneer in the development of DNA analyzers and an influential voice.

White felt differently. As the meeting continued, he leaned over with a reassuring order. "Don't back off," he told Afeyan. "I really want us to think about this."

After considering several scientists for the invitation to run the genomic information company he decided to form, White tapped Hunkapiller to call and invite Venter to take a look at the 3700.

Venter, White decided, was above all a brilliant sequencer who also would have the drive and experience to complete the human genome.

Once Venter was on board, White arranged to meet him while they were both in the Virgin Islands on separate family vacations. With their families gathered around them, the two men discussed the project at the Bitter End Yacht Club, and White made his expectations clear.

Venter may have been a rebel when he parted ways with drug development company Human Genome Sciences Inc., but "this was clearly a corporate environment," White said, "and we couldn't do that."

Brave new world

It has been just over a month since the sequencing of the genome was announced.

Celera sister company Applied Biosystems has just released its first microtechnology product onto the market, and the company promises more are coming. Such inventions promise to move discovery to smaller, cheaper and easier-to-use means -- even to "labs on a chip."

At  [PerSeptive Biosystems], engineers are testing a new, high-speed protein analyzer for shipment to Celera. A bevy of the machines, it is hoped, will allow Celera to explore the structures of proteins involved in creating and curing disease faster than any other on the face of the earth.

Last week, [  Tony Lee White (born 1947)] and [ Dr. John Craig Venter (born 1946)] explained more about what that will mean to the company's future, saying  [PerSeptive Biosystems]'s new protein analyzer will be the basis for starting a drug-discovery business at [ Celera Genomics Corporation].

While Celera probably wouldn't manufacture, test or market the protein-based drugs itself, the strategy would allow it to earn royalties on sales of drugs developed using Celera discoveries.

Exactly how the effort will be focused hasn't been decided. Plenty of other companies have microtechnology products on the market, and others are far ahead on discovering useful proteins. As a result, for at least the past month, White has been wrestling, somewhat fitfully, with this latest inspiration.

He talked it over with his old colleague Bill Gantz on a flight to California about a month ago. White's corporate jet had picked Gantz up, and the two headed out to a Goldman Sachs conference together.

As the miles flew by, the two old friends commiserated about the fact that, even with an accomplishment like mapping the human genome, the world quickly moves on. It wants to know what's next.

"It's the life of a CEO: You're expected to have all the answers," Gantz said."And guess what? Sometimes you don't.".

Armenia’s foreign minister criticized Turkey on Thursday over its angry responses to what he called the growing and “irreversible” trend of global acknowledgments that the killings of ethnic Armenians by Ottoman Turks 100 years ago was a genocide.

The minister, Edward Nalbandian, also expressed hope that President Obama, who had described those killings as a genocide before he was elected president, would use that terminology while still in office, which he has not yet done. “Of course if the president uses the G-word it would be a strong and important message,” Mr. Nalbandian said.

He spoke by telephone from Washington, where an official delegation led by Armenia’s president, Serzh Sargsyan, has been visiting to participate in centennial commemorations to remember victims of the genocide and honor groups and individuals who helped Armenians escape death.

An estimated 1.5 million Armenians were killed and their property destroyed or confiscated during the period of 1915 to 1923 when the Ottoman Empire collapsed, and many survivors and their descendants scattered into a diaspora that has placed Armenian enclaves in more than 100 countries. Some of the biggest Armenian communities are in the United States.

Turkey’s government has expressed condolences to Armenians but has denied that the killings constituted a genocide, arguing that many Ottoman Turks also were killed in that era of war and upheaval. It has responded angrily in recent weeks to declarations by Pope Francis, the European Parliament and others that Turkey should acknowledge the killings as a genocide. The word was invented in the 1940s by a Polish-Jewish jurist, Raphael Lemkin, who said he created it in part because of the Armenian killings.

The latest target of Turkey’s anger was Luxembourg, which on Wednesday adopted a resolution recognizing and condemning the Armenian genocide, becoming at least the 22nd country to do so. Turkey recalled its ambassador to Luxembourg in response, denouncing the resolution as a distortion of history.

Mr. Nalbandian, who has been deeply involved in the centennial events in Armenia and abroad, suggested that it was unlikely that a normalization of relations with Turkey would happen soon, partly because of the unresolved genocide legacy issue. The Turkish-Armenian border is closed, and there is virtually no trade between the countries.

“We are where we are,” he said. “Turkey is just continuing its policy of denial. They are criticizing, but the process of recognizing genocide is irreversible.”

Mr. Nalbandian said he was encouraged that an increasing number of Turks appeared to be questioning their government’s official policy of genocide denial. He also said a Turkey-Armenia reconciliation was necessary.

“We have no other alternative,” he said. “We have to live together, not with a policy of denials, but with joint efforts to turn the dark pages.”

Noubar Afeyan, a prominent American venture capitalist of Armenian descent who is chairman of the national committee that organized the centennial events in Washington, said many members of the post-genocide generation had moved beyond grief, embracing the tenacity of the Armenian diaspora, which now totals 10 million.

“As an Armenian who was born in Lebanon, grew up in Canada and lived in the United States for 35 years, I believe it’s the natural result that Armenians are maturing in relation to this tragedy,” Mr. Afeyan said in a telephone interview. “It’s extending to be not only about crimes and victims, but survivors and their saviors.”

It’s a sign of the times: Eight human bodies produced immune responses to an experimental COVID-19 vaccine, and all over the world, people took a deep breath of hope.

The results of early trials are usually just a footnote to the news. But in this case, the Dow surged. [Moderna, Inc.], the company working on the vaccine said it planned a bigger trial with 600 people. And the White House announced Operation Warp Speed to hasten the pace of vaccine development.

Cambridge, Mass.-based [Moderna, Inc.], is one of more than 100 companies that venture firm Flagship Pioneering says have grown out of its unique process. I interviewed founder Noubar Afeyan a few years ago, and wrote a short piece for Forbes.com. I’m publishing an extended piece today based on the interview.

I was fascinated with Afeyan’s expansive approach, because it was subtly and yet importantly different than investing in high-tech entrepreneurship, which places a premium on speed and growth. In Afeyan’s world, complications represent opportunity, because they open up other avenues for exploration.

In the next few years, we’ll likely see a huge surge in biotech investing on top of record-breaking years of investor cash flowing into the sector. Silicon Valley VC firm Andreessen Horowitz, for instance, has announced another biotech fund.

Financial returns have been good in the public markets and elsewhere: Returns from health care IPOs hit records in 2018, according to Silicon Valley Bank. They continued to be strong in 2019.

The coronavirus vaccine will be a big test of whether the modern biotech industry can produce equitable social good as well as financial returns. It’s clear that it won’t be a winner-take-all model, because no single company can produce billions of vaccine doses for global distribution. As The New York Times noted:

Dozens of companies and universities are rushing to create coronavirus vaccines, and human trials have already started for several manufacturers, including Pfizer and its German partner BioNTech, the Chinese company CanSino and the University of Oxford, which is working with AstraZeneca.

Afeyan and I covered three areas in the interview: Armenia, and his philanthropy there; entrepreneurship; and biotech investing.  Born in Lebanon, Afeyan is the grandson of an Armenian refugee who landed in Lebanon after he was saved during the genocide by German officers. Afeyan’s father was an entrepreneur, with a small import/export business. But when the civil war in Lebanon came, the family moved to Canada.

The Legacy Of Armenia

Afeyan is one of three founders of a major philanthropic initiative that seeks to honor people who helped Armenians during the genocide in 1915. The other two are  [Vartan Gregorian (born 1934)], president of the Carnegie Corporation, and [Ruben Karlenovich Vardanyan (born 1968)], an Amermian who made a fortune in Russian banking.

Afeyan realized that his own healing came out of the recognition that there weren’t only two categories of people involved in the horror of the genocide. There were victims, perpetrators, and there were also people who helped; Afeyan had an example in his own family.

Borrowing an idea from the world of physics, Afeyan recognized that moving on from the genocide was a “three-body problem, not a two-body problem.”

If Armenians could redefine themselves as people acting in gratitude, as the children of survivors, he thought, they could overcome some of the trauma of the past.

The founders committed to giving away $1 million a year to a humanitarian at work in the world today. Previous recipients have been Dr. Tom Catena, the only surgeon working in Sudan, in an area of 1.3 million people; and Marguerite Barankitse, who founded community centers to care for orphans in Burundi and Rwanda.

The humanitarian in turn designates projects around the world for aid. So far, those number 28, in 16 countries, according to the Aurora organization. The Initiative also sponsored the Aurora Dialogues, bringing thought leaders around the world to come up with solutions to humanitarian crises. (Disclosure: They invited me as a journalist and covered my travel expenses in 2016.)

To be a survivor is almost by definition to be a paranoid optimist. To Afeyan, “paranoid optimism” is one of the hallmarks of a successful entrepreneur.

Entrepreneurs should always be worried about what could go wrong, and yet believe that in the long run thing will go right. “You need a gas pedal and a brake pedal,” Afeyan said.

A Formula For Entrepreneurship

Afeyan got a degree in chemical engineering from MIT. There by chance, at a National Science Foundation meeting, he met an electrical engineer in his 50s, who described to him how he had built a company that supplied tools to the new and burgeoning field of electrical engineers. That man? David Packard.

Noodling on the idea of building tools for biomedical engineering, Afeyan went on to found PerSeptive Biosystems, which was acquired. After that, Afeyan turned to his passion, which is startups — not founding individual companies, but creating a process for startups.

“I became interested in figuring out out whether I could start companies for a living, professionally,” he said.

At Flagship Ventures, which has more than 3,000 employees, teams of scientists explore companies through four phases, from idea (which focuses on building a product from the start), through to market. The successful ones are spun out into companies. The firm says it produces six-eight a year.

Here’s how Afeyan wrote out his formula for me in an email — or at least, his suggestion for the way to think about the process of entrepreneurship.

I would say it this way – first envision several possible future states where in each case some combination of new science or technology can deliver value by addressing an unmet need.  From among those, chose the one future state you want to pursue by trading off likelihood of reaching that state as well as the impact and value created by doing so. Then evaluate various paths to reach that future state. Keep in mind that the future states you envision will necessarily seem unreasonable at first (given that the technology/science and need are not yet clearly established). An entrepreneur’s goal is to define incremental steps from the present to that envisioned future each of which may seem reasonable but which in combination can take us to a place that initially seemed unreasonable to aspire to.

Afeyan suggests entrepreneurs follow a process of variation-selection-iteration. One of the key insights here is that it’s not just products. Silicon Valley is very focused on products, but in the biotech space, you can also use this process with hypotheses, jobs or marketing messages in your company, among many other things. “The pace of the variation is only limited by the resources you can deploy,” said Afeyan.

Recognize what creates value. Your company is not necessarily a product-building engine; it is a value-creation engine. Your ideas have value, too. “You sell the idea to gain credibility and trade in credibility to get money. The more you build stuff from your ideas, the more credibility you have,” Afeyan said.

What Can We Learn About Biotech Investing

When I interviewed Afeyan in 2016, I was struck by how different the process was that he was describing. Though it bears some similarities to venture capital – Flagship raises funds, for instance – its approach keeps the entrepreneurs/scientists employed until an idea is fully developed. Flagship retains a majority stake in the companies that it spins out.

Biotech investing has been riskier than traditional venture investing, which is often focused on software companies, because there were fewer exits in biotech. That may be changing now. The changing landscape for returns could put Flagship in a good position. It seems to have found a low-cost way to invest in many biotech ideas, by focusing scientists on product and value development and keeping them in-house.

Within Flagship, teams of about 20 hypothesize in as many different directions as possible, but always with the aim of creating a use for a new discovery.

How does this work in practice? Afeyan gave me an example of nine or 10 years ago, when researchers were just beginning to be able to measure the microbes that colonize the gut. There were multiple hypotheses for how that new science could be used, from the idea that you could diagnose different diseases by measuring microbes, to the idea that you could potentially come up with a subset of microbes that combatted a particular super-bug, to the idea of enabling fecal transplants. The third hypothesis led to a company, Seres Health. Other companies born out of the Flagship process include CiBO Technologies, which works on increasing yield in agriculture, and Axcella Health, which works on interventions to reprogram metabolism.

“There is nothing like a game about this,” he said. “If the science isn’t there, why are you talking about products?”

Almost all people hospitalized for Covid-19 are not vaccinated — 99.9% as of May to be exact, according to a recent Associated Press report.

Yet 13% of U.S. adults said they will “definitely not” get a COVID-19 vaccine as recently as late May, according to Kaiser Family Foundation COVID-19 Vaccine Monitor. Another 12% wanted to “wait until it has been available for a while to see how it is working for other people.”

Vaccinating the majority of the population is the best way to help avoid further surges from constantly evolving variants, like the current delta variant, which is quickly spreading in the U.S. and other countries.

Still, [Moderna, Inc.] co-founder [Dr. Noubar Afeyan (born 1962)] understands the hesitation to get a new vaccine.

“The vaccines came out in such a [short] timeframe that people assumed automatically, it can’t possibly be safe,” Afeyan said during a talk at a Solve at Massachusetts Institute of Technology event in May.

“In fact, many, many people were on television espousing the view that — experts for that matter — that if it’s done in less than five years, it’s got to be unsafe, all of which is untrue.

“Nevertheless, people get confused.”

What people might not understand is that extensive research was being done on mRNA technology and other mRNA vaccines for years. That decade plus of experience and the innovation of mRNA technology itself is what allowed Moderna to produce its Covid mRNA vaccine so quickly as the pandemic struck. And it could also change the future of medicine.

Here’s what you need to know about how the Moderna Covid-19 mRNA vaccine was developed.

The timeline: A vaccine in under a year

It is true that Moderna’s mRNA vaccine was ready remarkably fast, as was Pfizer’s.

Chinese scientists put the genetic sequence of the novel coronavirus online on Jan. 11. Over the next two days, the NIH and Moderna used it to plot out a vaccine.

Afeyan remembers getting a key call about the development of the Covid-19 vaccine. “January 21st, my daughter’s birthday.... I got a call from Davos [during The World Economic Forum] from the CEO of Moderna,” he says. [Stéphane J. Bancel (born 1972)] had been approached by a number of public health groups at the conference “urging” him to work on a vaccine.

“We literally decided overnight...to try and do this,” Afeyan said at MIT.

Moderna delivered the first doses of its Covid-19 vaccine to the NIH for testing on Feb. 24, 2020, and “the first Moderna shot went into a volunteer’s arm in Seattle on March 16, 2020,” according to Afeyan.

After testing the Moderna vaccine on 30,000 volunteers, on Dec. 18, 2020, the FDA authorized it for emergency public use, and three days after that, the first Moderna vaccines were administered to front-line health workers, according to Afeyan.

Over a decade of research to innovate mRNA as a ‘bioplatform’

One of the reasons Moderna’s mRNA Covid vaccine development moved so quickly is because scientists had been working with mRNA for years.

“Messenger RNA technologies have been in development from a basic science perspective for over 15 years,” [Kizzmekia "Kizzy" Shanta Corbett (born 1986)], the scientific lead for the Coronavirus Vaccines & Immunopathogenesis Team at NIH, who helped make the vaccine possible, told the NIH Record.

And Moderna has been working with mRNA technology “since its inception in 2010 for myriad therapeutic areas,” including cancer therapies, Afeyan tells CNBC Make It (by way of a spokesperson), and with clinical development of mRNA-based antiviral vaccines since 2015.

What Moderna did over many of those years was develop mRNA as what scientists call a bioplatform, which allows for speedier vaccine development. Bioplatforms are systems that can easily be scaled and tailored for many different diseases.

Traditionally, developing any vaccine essentially has been a bespoke effort.

“The benefits of a bioplatform is the ability to quickly redeploy the platform once established and refined — in the case of Moderna’s mRNA platform, to create and test new vaccines based on new viral sequences,” Afeyan tells CNBC Make It (by way of a spokesperson).

All of this makes mRNA vaccines virtually programable. Corbet and Bancel describe the process as “plug and play.”

“MRNA is always made of four same letters, Bancel said on the December Andreessen Horowitz podcast, “Bio Eats the World.” (MRNA is genetic material, similar to DNA, so its “code” is expressed with letters.) It’s “the four letters of life, like zeros and one in software,” said [Stéphane J. Bancel (born 1972)]. “This is like software or LEGO.”

“The only difference between” mRNA vaccines is “the order of the letter; the zeroes and ones of life,” Bancel said. “The manufacturing process is the same, the equipment is the same, with the same operators. It’s the same thing. And so this is why we could go so fast.”

Faster vaccine development in the future

Bioplatforms will effect change way beyond the Covid pandemic.

Judy Savitskaya and Jorge Conde, biotech investors for top Silicon Valley investment house Andreessen Horowitz liken how bioplatforms could change the biotechnology industry to what the advent assembly lines did for the auto industry: It “went from single ‘job shops’ in the early days of automobiles — where raw materials like steel and rubber crafted from start to finish by hand into a trickle of early cars — to assembly line production, with standard components that could be iterated for new models,” they wrote in a January blog post.

(Andreessen Horowitz is not an investor in invested in Moderna, Pfizer or BioNTech, according to a firm spokesperson.)

The Covid-19 vaccine is one example of how mRNA can be used.

Moderna has 24 mRNA vaccines and therapeutics under investigation, and 14 have begun clinical studies, according to the company’s quarterly investment documents published in May. Moderna’s pipeline of mRNA treatments include a zika vaccine, HIV vaccine and a cancer vaccine, to name a few.

The same dynamic enabled Pfizer and BioNTech, who collaborated to create the other mRNA Covid vaccine currently in use in the U.S., “to rapidly redirect its mRNA technology platform from cancer to COVID in a matter of weeks; the company estimates it can manufacture updated versions against emerging mutant strains in as little as six weeks,” Savitskaya and Conde write.

Pfizer and BioNTech are also working on an mRNA vaccine to prevent the flu.

″[T]hese programs are just the first in a long list coming that will benefit from the same underlying [bio]platforms,” wrote Savitskaya and Conde. “The rise of productive platforms will impact much more than just vaccines. It will transform all areas of biotech, from small molecule discovery, protein engineering, genome editing, gene delivery, cell therapy, and more.”

Even with all this hard work and innovation, even Afeyan says Moderna got lucky to be able to move as quickly as it did.

“I’m quite actually amazed,” Afeyan said at MIT. “Murphy’s Law was on vacation, was on sabbatical for a whole year, and so many things that could have gone wrong, simply did not.”