How does it feel to be patented? There was a sense of betrayal. I mean, they owned a part of me that I could never recover. I certainly have no objection to scientific research … but it was like a rape. In a sense, you’ve been violated, for dollars. My genetic essence is held captive.
—JOHN MOORE, THE SUBJECT OF U.S. PATENT NO. 4,438,032
In 1982, the mother of Japanese biotechnology scientist Dr. Heideaki Hagiwara was suffering from cervical cancer.1 When he learned that Dr. Ivor Royston at the University of California at San Diego was developing cell lines to treat cancer, he asked to join the laboratory and, once there, convinced Royston to use tumor cells from Hagiwara’s mother’s lymphatic system to create a therapeutic cell line.
A cell line is a community of cells, usually animal or human, that grows continuously in the laboratory, proliferating indefinitely under glass in precise, artificially maintained conditions, where it is used in research. In a warm living body, with its genius for homeostasis, every cell receives ample oxygen and nutrients in a dynamic environment tailored to its needs. But cells exiled to the cold, sterile prisons of unresponsive glassware tend to die quickly without the most assiduous coddling, although cancer cells live somewhat longer. Cell culture is the meticulous process by which optimal temperature, gas concentrations, and nutrients, which vary with the type of cell being cultured, are maintained, often with great difficulty.
Carefully tended cell cultures boost medical research by providing living human material for risk-free testing of the effectiveness and safety of drugs. But cell cultures can also host viruses and other pathogens, permitting them to be prepared in quantity for the manufacture of vaccines. Polio, measles, mumps, rubella, and chickenpox viruses are currently produced in cell cultures. In the early twentieth century, Ross Granville Harrison of Johns Hopkins University established the technique of maintaining cells in vitro and dubbed it tissue culture.2 Because cancer cell lines are somewhat more long-lived than those of “normal” human cells, many extant cell lines are derived from cancers. By the mid-1900s, cell cultures were commonly used in laboratories.3
Some cell lines retain the characteristics of and produce substances that are peculiar to their cells of origin. Royston was working on a cell line that he hoped would treat cancers by producing antibodies that attack cancer cells. Hagiwara suggested that he use lymph cells from his sick mother, and Royston did so, fusing Hagiwara’s mother’s cells to the line. UCSD researchers soon agreed that this particular cell line possessed unique cancer-fighting properties, so Royston patented the promising cells. Hagiwara then returned to Japan, surreptitiously taking with him a sample of the cell line, which he used to treat his mother, who rallied but ultimately succumbed to her cancer.
Months later, Hagiwara gave the cell line to his father, Dr. Yoshide Hagiwara, who was also a biomedical researcher, for use in the family firm, the Hagiwara Institute of Health in Osaka. He claimed patent rights to the cell line and the antibodies it produced because it emanated from his mother’s body, entitling his family, he said, to a financial interest in the cell lines. The U.S. Office of Technology Assessment disagreed and sued Hagiwara fils for taking the patented cells without permission.4 Hagiwara argued that despite the UCSD patent, the fact that the cell line had originated with his mother’s tissues gave his family rights to the cells as well.
Hagiwara won these rights in a 1983 settlement with the university that gave the Hagiwaras the sole license to the patent throughout Asia.5 Patented entities can be licensed in an exclusive or a nonexclusive manner, and they can be licensed for specific geographic regions, and even for specific uses.6 In this case, the Hagiwaras’ agreement with UCSD permitted them to use the line in research, but not to license it commercially elsewhere.
Twenty years later, another family affair was handled quite differently when FBI agents tracked down, arrested, and jailed Dr. Jiangyu Zhu, thirty, of China and Dr. Kayoko Kimbara, thirty-two, of Japan on June 19, 2002, in La Jolla, California.
The married couple were former fellows of Harvard Medical School who had resigned to pursue new research positions. But their time at Harvard had been very fruitful: from November 1998 through September 1999, Kimbara identified two genes that block the action of calcineurin, an enzyme that signals the immune system to reject transplanted organs. This was a potentially lucrative discovery that could transform organ transplantation by leading to immunosuppressive drugs, medicines that drastically lower the risks of organ rejection. It also was a potential treatment for several diseases that affect the cardiovascular, immune, and nervous systems, which multiplied its commercial potential. Then, on October 22, 1999, Harvard filed a provisional patent on the two genes and their products.
On December 13, 1999, Zhu and Kimbara accepted university research positions at the Institute of Biotechnology at the University of Texas, San Antonio, and when they left Harvard, they took some materials and notes with them, as researchers are wont to do. They were to begin on January 15, and by early January 2000 they shipped some additional materials from Harvard to their new lab.
But the university’s complaint says that in direct violation of the participation agreement signed by both Zhu and Kimbara, Zhu emailed Medical and Biological Laboratories of Nagoya, a biochemical company in Japan,7 indicating that he intended to collaborate with a researcher there to commercialize the antibodies suggested by his Harvard gene research after he left Boston. Harvard says that Zhu also sent three other genes to Japan without its knowledge.
Harvard officials angrily accused Zhu and Kimbara of violating the terms of their agreement by sneaking into the lab in the wee hours to remove contested material, and of lying about having done so. The duo denied this, and the facts were never established in court. But according to the university’s complaint, the Japanese company did succeed in producing antibodies against two of the three genes and then shipped them to Zhu at the University of Texas, where he now ran his own lab.
Removing materials is not a crime and is certainly not prosecuted unless the materials are alleged to be the property of the university, not the researcher. Even removing university property is acceptable if the amounts are not excessive and the researcher has appropriate permission. If the accusations of having lied about the removal of large quantities of university property are true, the couple become less sympathetic.
But it is important to evaluate such actions in the context of research culture: researchers typically remove materials from their laboratories when they leave for other institutions and sometimes do not ask permission to do so. There is no question that Heideaki Hagiwara, for example, had violated the spirit and the letter of the agreements he signed, yet he and UCSD were able to come to an amicable arrangement that recognized his contribution and shared the rights in the contested cell line. Therefore, many in the research community felt that Harvard overreacted when the university decided to play hardball.
Moreover, given that they were sued by Harvard, an academic behemoth of sterling reputation, it is also easy to overlook that Zhu and Kimbara steadfastly denied having taken disputed materials with them and that Harvard’s very public accusations of theft were never publicly backed up with copies of agreements or evidence of wrongdoing.
The school brought criminal charges, and the two were charged with conspiracy, theft, theft of trade secrets, and (since they had left Texas and were now ensconced in new labs in San Diego) interstate transportation of stolen property.8 The case was investigated by the Federal Bureau of Investigation in New England.
The Department of Justice press release, titled “Pair Charged with Theft of Trade Secrets from Harvard Medical School,” focused on the fear of corporate competition, speculating that the two shared an “intention of profiting from such information by collaborating with a Japanese company in the creation and sale of related and derivative products.”
Because any attempt to develop drugs from the pair’s Harvard discovery threatened Harvard’s own ability to patent calcineurin and sell the rights to a biotechnology company or corporation, this was a turf battle between Harvard and Medical and Biological Laboratories as well as between it and its erstwhile fellows. Unlike UCSD, Harvard did not seem inclined to share patent rights with the Japanese firm. The school and the FBI’s public statements, however, focused on Zhu and Kimbara.
“Prosecuting people who steal the intellectual property of individuals and institutions is a very high priority for the Department of Justice,” declared U.S. attorney Michael J. Sullivan. “Congress has enacted a series of laws to assure that innovators get credit for their inventions and if people steal the ideas that belong to someone else and try to use those ideas for their own economic benefit, they will be prosecuted. Protecting cutting-edge ideas is crucial to the creation of new products and our economy as a whole.”
Discovering the genes was Kimbara’s achievement, but the patent “ownership” was governed by her signed agreement with the school, which was never made public. As a research fellow at Harvard Medical School myself, I was required to sign an agreement ceding patent rights for any discovery to the “President and Fellows of Harvard College,” but this was years after the Zhu-Kimbara incident and may not reflect agreements they made. I can’t help reflecting that the oft-voiced virtue of the patent as a means of protecting the rights of “innovators” sounds ironic considering that Kimbara, who discovered the gene, was being assailed for exercising her rights to it.
In fact, the only rights that immediately accrued to the duo were the Miranda rights read to them while being taken into custody in La Jolla. Sitting in the La Jolla jail, the researchers learned that they faced up to twenty-five years in prison and at least $750,000 in fines.9
In the subsequent hearing, the FBI and Harvard made a highly unusual request for a six-month delay. Then Harvard announced that Medical and Biological Laboratories, the Japanese company, had cooperated fully and returned all research data and products to Harvard Medical School.
After Zhu and Kimbara made bail, they were indicted by a grand jury, but there was no trial. Following a July 11 arraignment,10 all charges were dropped, prompting their lawyers to respond: “The indictment returned today abandons any claim that our clients stole trade secrets or attempted to commercialize them, recognition that there was never any truth to those charges.”
As the pair left the courthouse, they were mobbed by Japanese reporters, whose intensive coverage of their case came not only because Kimbara was a Japanese national and a Japanese firm was involved, but also because the life patent was then foreign to Japanese scientific culture. Japan, unlike the United States, had refused to patent life-forms or to bolster a U.S.-style university-corporate symbiosis.
The Japanese bewilderment over bitter patent litigation that spilled over into criminal courts continued. In May 2001, the Cleveland Clinic similarly prosecuted researchers over monopolistic patent rights and Japanese journalists thronged its courtrooms as well, to convey the bizarre spectacle of scientists on trial over corporate property rights based on a patent. Today Japan is a major center of drug and biological design and treasures scientific innovation, but, in the words of Science magazine, “The Japanese are ill equipped to deal with stricter US laws on intellectual property.”11
By contrast, Americans seemed unfazed by the interstate pursuit of medical research scientists on charges of the sort normally reserved for Ponzi scammers and mafiosi. For many of us, used as we are to acrimonious turf battles over intellectual property, the salient question turns on whether the Zhu-Kimbara team was guilty, not whether they should have been legally pursued.
But for the purposes of our present discussion, this event is important for a different reason: it dramatizes how the landscape of university medical research has changed in the United States. Medical-research culture has been transformed from a milieu of collegial public-goods resources devoted to the health of the community to a product governed by patents and other monopolies. Once a collaborative haven for independent inquiry and pure research, the university medical-research center is today just another arena of commercial corporate endeavor that takes competition seriously enough to deal harshly with disloyalty and raiding, to the point of seeking to send former colleagues to prison.
How did we get here, and what does the change augur for patients, medical consumers, and other everyday Americans? This acerbic exchange between Harvard and its former researchers was triggered by the potential loss of a lucrative patent that would enable someone—Harvard and its corporate partners, or another institution—to profit from the couple’s research. It illustrates a face of the patent at odds with the very American values of ingenuity and independence upon which medical research has always relied.
However, the contentious climate of the patent gold rush has led to far more than mere turf squabbles, and these issues are the subject of this book. Biological patents, or “life patents,” are those obtained for monopolies on living things such as pathogens, plants, animals, or portions of our own bodies, including, but hardly limited to, our genes. The requirement that U.S. patents be issued only on truly novel substances would seem to preclude U.S. biological patents on things that are commonly found in nature. So might the prohibition against patents on “laws of nature” or naturally occurring material. But the U.S. Patent Office has often issued patents on naturally occurring living things, as long as researchers have “purified,” “isolated,” or otherwise “transformed” the patented version into a new entity that, they argue, is not found in nature. Life patents, patents on products of nature, and related pharmaceutical patents on medications are now rife, highly profitable, and the frequent subjects of legal tugs-of-war between corporations.
Patents on human genes provide an excellent example. In 2000, thirty-four thousand new patent applications listing at least one gene or sequence (and usually more than one) were filed each month. By the end of 2000, five hundred thousand naturally occurring genes and DNA sequences (portions of genes) were patented or had patents pending. Corporations, academic institutions, and the U.S. Department of Health emerged as the major holders of these life patents and pharmaceutical patents.
The latter patents are also key to maintaining and improving human health, through the promulgation of medications, the regulation of drug prices, and the mining of animal and human tissues for medically active substances. Until the 1980s, all this was the province of the academic research center, but today it takes place largely in corporate settings and is largely funded and supervised by for-profit corporations.
To explain how all this came about, we must trace the history of the patent as a shaper of contemporary U.S. medical research in order to understand its medical consequences for good and ill today.
What does the possession of a patent mean? The word “patent” derives from the Latin verb patere, meaning “to lay bare” or “to open up.” This concept undergirds the granting of a patent: the period of monopoly during which the holder enjoys the exclusive ability to profit from the invention is a privilege granted to an inventor or his assignee as a reward for eventually “laying open” his invention—for divulging the nature and operation of a technology, invention, or process and placing it in the public domain so that, after the patent holder’s period of monopoly ends, everyone may exploit and profit from it.
There are many types of patents besides the biological and pharmaceutical patents addressed in this book, including business method patents, chemical patents, and software patents. Patents on new and useful entities such as medications or computer chips fall into the broad class called utility patents. Industrial design rights or “design patents” protect the visual design of objects that have aesthetic as well as practical value; plant breeders’ rights are often called “plant patents,” and some plant patents, because they govern living things with medical utility, are discussed in this book as well. Each has its own regulations and history.
None imparts literal ownership. For a time, though, a patent confers something just as profitable, giving its holder at least twenty years of legal monopoly over the possession, distribution, manipulation, and use of the patented entity. A patentee can prevent others from using, manufacturing, selling, advertising, or importing his invention. However, holding a patent does not automatically confer the right to manufacture or sell the invention; for this, the patentee may have to submit to other legislation or licensing criteria. For example, the inventor (or his assignee) of a medication or medically valuable molecule may patent it, but cannot offer it for sale without obtaining Office for Human Research Protections or Food and Drug Administration approval. Similarly, the designer of a better mousetrap may have to secure rights from the patent holder of any patented component that it incorporates; in the same way, some drug patents require prior access to other patented molecules or even patented research tools. One can use such patented entities only with the permission of the patent holder and, typically, after paying a licensing price.
The period of unfettered profitability is meant to reward an inventor’s ingenuity by protecting his ability to profit without competition throughout the life of the patent. But after these few decades, he must “open up” the patented item and share it to encourage future innovation so that all can benefit from his invention. Thus patents are meant to encourage open communication and sharing of the expertise and creativity of the sort that propels medical advances, a laudable goal.
Where did the concept of patents arise? The granting of monopolies that closely resemble our patents was recorded in Greece as early as 500 b.c., when its wealthy southern Italian colony Sybaris held gastronomic competitions, with the top chef winning the exclusive rights to his favored dish for one year: after this, anyone could prepare and sell it. In the third century A.D., the Greek-Egyptian writer Athenaeus described this decree: “Encouragement was held out to all who should discover any new refinement in luxury, the profits arising from which were secured to the inventor by patent for the space of a year.”12 The victorious dish was oysters stuffed with honey, which passed deliciously—at least according to the tastes of the ancient Greeks—into the public domain after a year of exclusivity.13
By the thirteenth century, several patents were documented for boat-lowering devices in Venice,14 and the Venetian Statute of 1474 provided legal remedies for inventions’ “legal protection against potential infringers.”15 In the sixteenth century, Queen Elizabeth I made royal grants of monopolies which were long to be royal prerogatives in England.16 In 1594, Galileo was granted a patent for a horse-drawn water pump. Over time, patents or closely related monopolies became a pervasive feature of Western laws and culture, a well as in China and Japan.
Conventional wisdom holds that patents reward individual vision and the patent awardee’s personal investment of time, effort, and brainpower. This belief is buttressed by the widespread myth that patents have always been treasured as emblematic of American ingenuity and as a testament to our nation’s pioneer spirit. However, our forebears, including prominent inventors such as Benjamin Franklin, Thomas Jefferson, and George Washington Carver, were deeply suspicious of patents.
Because the United States won its independence just after England embarked on the Industrial Revolution, questions of technology and enterprise loomed large for the new nation’s economic survival and political prestige, including the question of whether to grant patents and under what circumstances.
During the U.S. colonial era and throughout the early days of our republic, patents represented hated royal monopolies through which Britain rigidly controlled commerce, fattening itself on the fruits of American industry. In seventeenth-century England the crown could bestow “letters patent” that granted monopolies over entire key industries, such as salt. England eventually granted so many monopolies that they caused widespread resentment throughout the American colonies.17
These coercive monopolies could be held and granted only by the British colonizers. They exploited and crippled the nascent American economic system in a manner that led our forebears to resent and distrust patents as emblematic of British tyranny, even as the crown bestowed land on favored individuals and companies through a “land patent” system. Even colonial patents, such as those first granted by the Massachusetts Bay Colony of 1624, tended to mimic the English Statute of Monopolies.
Thus it is ironic that the names of Thomas Jefferson and Benjamin Franklin are so often invoked when defending the “American” virtues of patents, because although both were eager and prolific inventors, they long shared a strong aversion to patents.
Benjamin Franklin, the inventor of bifocals, the lightning rod, the Franklin stove, and, less famously, a flexible urinary catheter, shunned patents. He declined the offer of a patent for his famous Franklin stove with “As we enjoy great advantages from the invention of others, we should be glad of an opportunity to serve others by any invention of ours and we should do so freely and generously.”18
The year that Jefferson became U.S. secretary of state he also became the first director of the Patent Office, established under the United States Patent Act of 1790, “An Act to promote the progress of useful Arts.”19 The act established the Patent Commission of the United States. Jefferson shared the Patent Board duties with Secretary of War Henry Knox and Attorney General Edmund Jennings Randolph. As the trio met to consider each invention, Jefferson himself read the application, and he sometimes even laboratory-tested the candidate’s inventions.
Jefferson was a natural in this role. In the finest patrician tradition of his time, he was also an amateur scientist who conducted experimental vaccinations and was an American Mendel who bred four hundred varieties of fruits and vegetables at Monticello. Jefferson’s catalog as an inventor included a plow, a horse-drawn buggy, several types of specialized chairs, and a pedometer. However, although he was avidly pro-innovation and “agreed that inventors should have full rights to their inventions,” he worried about the constitutionality and economic wisdom of patents.
The right to exclusive profits from an invention is one we take for granted, but it was not a guaranteed feature of the colonial economy, in which the crown could stipulate exclusive commercial rights for a product to whomever it wished. Jefferson believed that inventors should reap the fruits of their inventions by being able to sell or otherwise profit by them, but he was opposed to giving inventors an exclusive right to do so. As he saw it, his role was to encourage invention, not to protect monopolies. He believed in granting patents sparingly so that all could enjoy access to new technologies.20
In fact, Jefferson castigated patents as “embarrassments to the public,” in the sense that they provided hindrances to trade. He spoke often of patents’ potential for exploitation and of his fears that they would delay the public’s access to new inventions. He did not apply for patents on any of his own inventions and expressed his hope that “the new nation would abolish … monopolies in all cases … the abuse of frivolous patents is likely to cause more inconvenience than is countervail[ed] by those really useful.”21
Throughout his two-year tenure at the Patent Office, Jefferson was miserly with his approval, granting only forty-nine applications,22 among them one for Eli Whitney’s famed cotton gin. Jefferson’s negative attitude toward patents eventually softened, and he may have been swayed by James Madison’s insistence that, although “nuisances,” patents were an appropriate reward for revealing the secrets of construction and invention.
Eventually American attitudes like Jefferson’s were tempered. Between independence and the adoption of the federal Constitution, including Article I, Section 8, which established patent guidelines, the initial animosity toward patents yielded to acceptance, and most states generated their own patent laws. Patents grew economically and politically important to the United States, sometimes at a moral or political cost. Eli Whitney’s cotton gin, for example, had encouraged the growth of both the nondiversified Southern agrarian economy and slavery.
In 1793, the new Patent Act incorporated Jefferson’s definition: “Any new and useful art, machine, manufacture or composition of matter and any new and useful improvement on any art, machine, manufacture or composition of matter.” It also stipulated that patents could be awarded only to citizens of the United States; this criterion validated intellectual-property theft by cheating enslaved inventors of credit for, to say nothing of profit from, their creations. Many masters had long taken credit for slaves’ inventions anyway, but the act provided a legal rationale and discouraged those who had been inclined to reward their ingenuity. Despite a wealth of inventions by slaves, not until around 1834 did Henry Blair become the first African American to receive a U.S. patent, for a seed planter. In 1858, U.S. attorney general Jeremiah Sullivan Black further reinforced the practice of withholding recognition and awards from the enslaved when he specifically ruled that an enslaved man could receive no U.S. patents because he was not a citizen of any country and could not take the required oath of citizenship.
The United States Patent Office was formally created in 1802 and granted hundreds of thousands of patents over the next two centuries.23 In 1859, Abraham Lincoln famously declared, “The Patent System added the fuel of interest to the fire of genius.”24 Mark Twain subsequently pronounced patents necessary for continued American progress, writing, “A country without a patent office and good patent laws was just a crab, and couldn’t travel any way but sideways or backways.” By the end of the nineteenth century, the patent was well ensconced in U.S. economics, and Jefferson’s protestations were all but forgotten.25
Yet pockets of resistance persisted. Atlantic Works v. Brady,26 an 1882 Supreme Court decision, waxed poetic in its belief that undeserved patents were being awarded for trivial steps in the discovery process. The case dealt with the bid to patent the use of tanks on a propeller dredge boat for the removal of sand and mud at the mouth of the Mississippi River. The boat used tanks that were filled to settle the boat evenly in the water, keeping it level until it reached the bottom; afterward, the tanks were emptied via powerful pumps in order to raise the boat again. But tanks had long been used to maintain the balance of other watercraft as they were lowered, and such use in New Orleans had been specifically noted in print in 1859. The court found that the invention was not novel and thus not patentable.27
But it went further: the Court questioned the wisdom of granting patents indiscriminately to each step in “the process of development … which the skill of ordinary head-workmen and engineers is generally adequate to devise and which indeed [is] the natural and proper outgrowth of such development.” It advocated for reserving a patent for “substantial discovery or invention”:
It was never the object of those [patent] laws to grant a monopoly for every trifling device, every shadow of a shade of an idea, which would naturally and spontaneously occur to any skilled mechanic or operator in the ordinary progress of manufactures. Such an indiscriminate creation of exclusive privileges tends rather to obstruct than to stimulate invention.
It creates a class of competitive schemers who make it their business to watch the advancing wave of improvement, and gather its foam in the form of patented monopolies, which enable them to lay a heavy tax upon the industry of the country, without contributing anything to the real advancement of the arts. It embarrasses the honest pursuit of business with fears and apprehensions of concealed liens and unknown liabilities, lawsuits and vexatious accountings for profits made in good faith.
Chief among historical patent dissenters is that great American inventor George Washington Carver, celebrated by Time magazine in 1941 as “The Black Leonardo,” and more than a half century later named by People magazine as the most beloved American scientist. Carver turned down a million-dollar industrial salary in order to serve the needy at Tuskegee Institute and dismissed suggestions that he patent his hundreds of scientific and medical inventions, with the words “God gave them to me. How can I sell them to someone else?”28
For most of our nation’s history, the subjects of American patents were technological devices and inventions such as farm implements, telephones, stoplights, and scientific and medical instruments. Patentable American ingenuity was by common consent restricted to inanimate objects.
But in the early twentieth century, U.S. plant breeders lobbied to profit from the advantages of patenting new cultivation techniques and varieties of plants. There were precedents at home and abroad: Finland had granted the first known patent on a living organism in 1843, and Louis Pasteur had obtained a U.S. patent for a pathogen-free yeast in 1873.
To determine the patentability of plants, the patent office had to reconsider the question “What determines patentability?” The legal criteria for granting a patent have been fluid, changing over time and specific to the kind of patent being sought.
Generally, two types predominate: product patents (or “utility patents”) for inventions, and process patents for methods, acts, and operations that are performed to produce a physical result (such as a particular “shopping bag” feature of an internet sales site). There are other more specific types as noted above, but most pertinent to the plant breeders were plant patents, granted for inventors who manipulated the asexual reproduction—such as cuttings and grafting—of plants.29
Patents and their criteria differ widely and finely in the details, making patent law breathtakingly complex. However, some requirements for patenting have remained fairly consistent. Only the inventor may be granted a patent. Patent eligibility requires that the idea must be a novel—a truly new—idea. A patent must be non-obvious, something that would not be immediately apparent to a person who is skilled in the art required. Also the patent must be useful—it must have a practical purpose or a marketable use. And finally, the patent application must describe it fully and accurately enough to be interpreted by a person skilled in the field in which it will be used. Illustrations are often a key component of these descriptions. But because of the requirement for novelty, if the patent application describes information that is already available to the public, it is said to be “prior art” and ineligible for patenting.
In one sense, Pasteur’s ability to patent the strain of yeast is puzzling: as a naturally occurring organism, yeast was not a patentable “invention,” but rather a discovery. However, Pasteur successfully used an argument that persists in the procuring of life-related patents today. He argued that he had purified the yeast from the environs in which it grew, producing a sample that was free of germs and thus would not cause disease. It was therefore considered “an article of manufacture,” and eligible for a patent despite its living status through a “hand of man” argument, which insisted that human ingenuity, not nature, had devised the pure yeast, transforming the nature of the yeast.
The hormone adrenaline was patented under the same rationale in 1911 by Japanese scientist Jokichi Takamine, whose influence spanned two continents. Takamine was born in 1854 in the city of Takaoka to a long line of physicians, and he traveled extensively in Europe before visiting the United States, where he fell in love with both America and Caroline Field Hitch, whom he married in 1884. They settled first in Tokyo, then in New York City, where he established a private laboratory and worked with the pharmaceutical firm Parke, Davis.
Takamine also served as a scientific and cultural ambassador who energetically promoted warm relations between Japan and the United States. If you have ever drunk in the delicate beauty of Washington, D.C.’s cherry blossoms and basked in the camaraderie of its Cherry Blossom Festival, you have Takamine to thank, because he persuaded Japan to donate the trees and promote the event as a goodwill gesture. But he bestowed an even greater gift when he isolated the hormone adrenaline, a neurotransmitter secreted by the adrenal glands that is critical for our “fight-or-flight” reaction and for much subsequent medication. Takamine won a patent for adrenaline, but the patent was challenged in court on the grounds that the hormone was not invented but rather discovered and purified from the adrenal glands.
The courts affirmed the patent’s validity: “Takamine was the first to make [adrenaline] available for any use by removing it from the other gland-tissue in which it was found, and, while it is of course possible logically to call this a purification of the principle, it became for every practical purpose a new thing [italics added] commercially and therapeutically. That was a good ground for a patent.”30
Congress responded by passing the Plant Patent Act of 1930, which extended the right to patent certain plants because they are transformed by grafting and budding techniques devised by man. This rationale similarly invoked the “hand of man” argument, arguing that breeders, not nature, had created the newer strains and breeds. No patent rights were extended to plants that are propagated by sexual reproduction, over which the courts still yielded to nature’s primacy, so that no patent rights then governed commerce in seeds.
Patents on these living things and hormones allowed someone—typically a company—a lucrative monopoly to license and sell the patented version of the living thing for profit. However, most twentieth-century medical researchers tended not to work for corporations but for universities or, sometimes, for private research organizations, including their own (as Takamine did). Thus they were insulated from the commercial zeal of corporations. Also, much university research was funded by the government, and patents from products of that federally sponsored research could not legally be sold to corporations. Even more significantly, medical-research culture also militated against commercialism, which was deeply frowned upon. For example, in 1923, its inventors agreed to sell the patent for insulin to the University of Toronto—but for only $1.
Because a career in medical research necessitated years of study but was not a lucrative field, people without means—the poor, the lower middle class, the ethnically marginalized—were dramatically under-represented in medical research, and the field attracted people who sought rewards other than money. Scientists did seek recognition for their work, and the rewards they sought did change over time, but these riches remained principally prestige, fame, honors, academic advancement, scientific and political influence, being revered as a benefactor, and a sense of altruism.
A rich vein of medically themed literature holds a mirror to the era’s culture and how it viewed commercial medical research. Most iconic is Sinclair Lewis’s 1925 novel, Arrowsmith, a masterwork of American realism for which Lewis, who won the Nobel Prize in 1930, also won a Pulitzer.
A passage describes the reaction of fellow scientists when ascetic German immunologist Max Gottlieb, heralded in the novel as “the spirit of science,” goes commercial. Gottlieb (a thinly veiled portrait of the researcher Jacques Loeb) has fallen upon hard times after an ill-advised confrontation with the dean of his medical school leads to his termination. Now a pariah within U.S. academe, and desperate to feed his family, Gottlieb sinks to a nadir: he accepts a job with a pharmaceutical company.
In the medical periodicals the Dawson Hunziker Company published full-page advertisements, most starchy and refined in type, announcing that Professor Max Gottlieb, perhaps the most distinguished immunologist in the world, had joined their staff.
In his Chicago clinic, one Dr. Rouncefield chuckled, “That’s what becomes of these super-highbrows. Pardon me if I seem to grin.” In the laboratories of Ehrlich and Roux, Bordet and Sir David Bruce, sorrowing men wailed, “How could old Max have gone over to that damned pill-peddler? Why didn’t he come to us? Oh, well, if he didn’t want to—Voilà! He is dead.”31
When he hears the news, Gottlieb’s erstwhile disciple Martin Arrowsmith laments to his wife, “God, Leora, I wish HE hadn’t gone wrong!”
Until the last quarter of the twentieth century, medical-research culture retained an animus against patents and profit as moneygrubbing and beneath the dignity of the researcher. Profiting from medical investigation was also regarded as fundamentally wrong, an unworthy motivation that stood in opposition to the scientific mission of the researchers and of the university.32
When Selman Waksman of Rutgers developed the antibiotic streptomycin in the 1940s, it became the first effective treatment for tuberculosis and earned Waksman the Nobel Prize and fame as America’s most esteemed scientist. Waksman patented streptomycin and licensed it to Merck Research Laboratories in nearby Rahway, New Jersey, but he was so worried about the public’s rancor if it learned that a private company was reaping enormous profits from research by a state university that he persuaded Merck to return the license to Rutgers, which enabled streptomycin to be sold generically—and very cheaply.33
The disdain for seeking a lucrative monopoly by patenting medical advances is also revealed by the actions of Jonas Salk. When he developed an effective polio vaccine in 1955, neither he nor the March of Dimes, which had helped fund it, chose to patent the vaccine, which was in tremendous demand. When Edward R. Murrow asked him who owned the patent, Salk countered, “The American people, I guess. Could you patent the sun?”34
But before there could be a vaccine for polio, there had to be a Henrietta Lacks.
In the early 1970s, you could choose your war. True, the War on Poverty had dwindled to a few anemic thrusts and parries and the Vietnam War, once bitterly divisive, languished on life support. However, the Cold War and the War on Cancer held everyone in thrall, and in January 1973, the Russians struck a single blow for both.
With great pomp, Soviet scientists presented the United States with what they described as six tumor-cell samples harboring human cancer viruses, taken from six different Russian patients. The glass cylinders held skeins of whitish human cells spun across translucent lakes of blood-hued nutrients. Many scientists had tried to identify such viruses, but they were elusive, and even if found they were unlikely to survive in culture for long. If the Russian samples indeed harbored viruses that caused human cancers, they could be invaluable because anticancer therapies could be tested on them in the laboratory. No one had yet succeeded in making such cultures, so these medical totems were as important to politics as they might be to medicine. Isolating a human cancer virus was the holy grail of cancer research, and this gift was a step toward détente, an impulse toward political and scientific cooperation with a common medical enemy.
Dr. Walter Nelson-Rees, then curator of the University of California’s cell bank,35 insisted upon extensive tests that would begin by confirming the human source of the cells, declaring, “One must be sure about these things.”36 No one would be more surprised than he had the Soviets managed to produce the elusive human cancer viruses, but he understood that great delicacy would be necessary if his analysis disappointed them.
His analysis shocked them. Every cell had two X chromosomes, a troubling coincidence that meant they were all from women. Moreover, every cell had the same fast-moving A variant of the enzyme glucose-6-phosphate dehydrogenase (G6PD)—a biological marker often, but not exclusively, found in descendants of African peoples. Black people lived in the Soviet Union, of course, but the coincidences were mounting in a troubling manner. In the 1970s, for example, nearly all cell lines were assumed to derive from the bodies of whites because researchers often used cells from their own bodies, or those of their families.
Cell lines from six different black women struck Nelson-Rees as unlikely: it was much more likely that the cells came from one woman. What’s more, Nelson-Rees felt sure that he knew her name: Henrietta Lacks.
The Russians’ tumor cells did not harbor cancer viruses. Instead, they were the progeny of tumor cells that had been taken from Lacks, a Baltimore woman, in 1951, and that have thrived in laboratory glassware ever since. Nelson-Rees theorized that the Russians had been working with Lacks’s cells (conventionally named HeLa, from the initial letters of her first and last name) in their laboratories, and that although they may have begun with human cancer cells at some point, the HeLa cells had contaminated and replaced the cancer lines without their realizing it.
It was a scenario that Nelson-Rees had discovered and described many times before, because the Russians were not alone in their confusion. Like 15 to 20 percent of all cultures of the period, the HeLa cells in researchers’ laboratories had contaminated other cell lines or been misidentified as other cell lines.37 Patrick Burke, of American Type Culture Collection, the country’s premier cell-line bank, explained in 1994, “HeLa was so widely distributed that a lot of contamination ensued—it would overgrow the other cell lines.… People found it pretty traumatic that they were doing research, spending a lot of money, then being told ‘This cell line is not what you thought it was.’ ”38
By 1974, fiery accusations and indignant denials engulfed the normally staid world of medical research after an article in Science revealed the extent of HeLa’s proliferation. Nelson-Rees embarked on a near-messianic campaign to alert scientists around the world to the shocking extent of HeLa contamination, “outing” many labs and making few friends in the process. The popular press gleefully seized upon this scientific embarrassment through headlines that trumpeted, “Dead Woman’s Cancer Cells Spreading” and “Researchers’ Errors Set War on Cancer Back 20 Years.” Within academia, careers faced dissolution as labs backpedaled furiously to trace and prove the integrity of their cultures.
Scientists lost sleep and face, especially because of their penchant for creating cell lines from their own tissues or from those of their children. When “their” cell lines were accused of harboring HeLa’s “black” cells, these scientists faced a distasteful dilemma: they could admit to HeLa contamination or, like one Dr. Monroe Vincent, they could lay claim to “remote Negro ancestry.”
The global panic finally touched the lives of five ordinary people on Baltimore’s New Pittsburgh Street when scientists descended upon the Lacks household to take blood and tissue samples from Henrietta Lacks’s children in hopes of helping researchers differentiate the HeLa from the non-HeLa cell lines in their laboratories.
In the zeal to save their livelihood and careers, scientists found it easy to forget that these medically important cells came from an unwitting benefactor whose family had no idea that their mother’s cells had become a precious medical commodity—against their will.
Henrietta was born on August 18, 1920, to John and Eliza Pleasant in Clover, outside Roanoke, Virginia. She and David Lacks were married on August 15, 1935, and moved to Baltimore. Sixteen years later, in January 1951, disaster disrupted her church-and-family-centered life as a pinkish vaginal discharge was followed by a ceaseless flow of blood. After a month of heavy bleeding, she and her frightened husband drove to Johns Hopkins Hospital, where she received her diagnosis: cervical cancer.
Even in the 1950s, the Lackses could hope for a cure of this small, localized cancer. On February 9, her gynecologist implanted radium capsules in her uterus to dispense the gamma radiation that was then standard therapy—but not before taking two samples of the tumor tissue for a colleague, Hopkins scientist George Gey.
Gey had taken on the daunting challenge of refining human cell-line culture—keeping cells alive outside the body to be used for research. Cell lines were rare, valuable, and delicate, quickly expiring at the least deviation from optimal temperature, light, or nutrient mix, although lines from cancerous cells were somewhat hardier. A few lived for weeks and the truly rugged survived a month. Gey dreamed of cell lines that would live for months, long enough to finish an experiment or test a vaccine.
A specific vaccine. In 1950, parents lived in fear of polio, and a cell line that would survive long enough to test candidate polio vaccines was urgently needed. Gey’s technicians, including his wife, Margaret, constantly swept the hospital, taking cell samples from patients.
“They wanted to take samples and asked if they could take tissue,” Henrietta’s husband, David Lacks Sr., told me in 1994. “Doctors told me it would probably help someone in the future. But I said ‘No.’ I wouldn’t sign the papers.”39 Lacks’s refusal was ignored and the samples were taken anyway.
On February 9, Henrietta Lacks’s gynecologist gave Gey a half-inch-square sample of Henrietta’s cells. Heartened by HeLa’s vigor, Margaret described it as “spreading like crabgrass” and with these hardy cells Gey founded a cell line that ensured his fame.
Meanwhile, in another wing of the hospital, doctors followed Henrietta’s radium implants with X-ray therapy. By July, masses of tumors had filled her abdominal cavity, and on September 26, 1951, a doctor ordered all treatment except painkillers stopped. For a week, she drifted in and out of consciousness, and on October 4 she died. She was thirty-one.
After her death, Gey swiftly obtained more tissue samples, but they were normally delicate tissues that soon expired. The only “immortal” samples were those that had been collected earlier, but there were plenty of these: they were doubling in size every twenty-four hours.
As her cells overran their petri dishes, her family laid Henrietta Lacks to rest. Henrietta’s cells transformed medicine. The first continuous human cell line meant that vaccines could now be tested and lengthy experiments completed that would have been unthinkable a few months earlier.
One advance was immediate and dramatic: after nearly seven years of focused research, the Salk polio vaccine was tested and perfected only a year after Henrietta Lacks died. Dr. Jonas Salk used HeLa as the host cell for calibrating the effectiveness of the vaccine’s action as, every week, a laboratory at Tuskegee University that was dedicated to HeLa production dispensed twenty thousand tube cultures.40
But HeLa’s usefulness did not stop at the polio vaccine. Gey did not patent HeLa, so no financial barriers impeded its global use and dissemination. HeLa became and remains a versatile tool in the laboratory, and many treatments and cures were predicated on its use. In 1995, Victor McKusick, MD, a professor of medicine at Johns Hopkins Medical Center, verified that “the number of medical advances due to HeLa are too numerous to list. I think, in the aggregate, a tremendous number of advances have relied on the use of HeLa. In lecturing on the history of medical genetics, I point out that the single individual who contributed most to the fields of somatic cell genetics is Henrietta Lacks, not a scientist.”
A company named Microbial Associates began selling HeLa widely, and laboratories that were not perfectly scrupulous in their handling of the cells contaminated their other cultures with HeLa, leading to the global identity crisis that threatened the work of so many researchers and laboratories.
The Lacks family remained unaware of the scientific whirlwind driven by their mother’s cells’ unique properties, because her identity was kept secret. Medical and news accounts variously identified her as Helen Larson and Helen Lane, pseudonyms Gey had employed as a “subterfuge to protect the Lacks family from journalists,” according to McKusick.41
“I don’t know what he thought he was protecting,” scoffed David “Sonny” Lacks Jr., her son, as we discussed his mother over Cokes on a steamy day in May 1994, in downtown Baltimore’s Old Town Mall. “I think they didn’t want people to know that she was a black lady helping the world.”
In appropriating the biological treasure of her cells, researchers hid more than Henrietta Lacks’s name. A quarter century after her death, waves of worried researchers attempting to separate HeLa from their other cultures appeared at the Lackses’ door. “They said they wanted to see if my wife’s illness affected any of the children,” Mr. Lacks recalled in 1994. And this time, he permitted the taking of periodic blood samples from them “to protect my children.” But the story was always the same. “They would promise to get back to us, but we would never see them again. Dr. Gey promised to tell me what he found in my wife’s blood. But it’s been so long now, he died.” The samples from the Lacks family allowed researchers to identify the interloping HeLa cells and to regain the purity of their cultures.
Today HeLa cells proliferate with undiminished vigor in laboratories and tissue banks, and no other cell lines have surpassed their longevity. Gey gave HeLa samples away, but HeLa has also been bought and sold around the world for sixty years and is still available from cell banks such as American Type Tissue Collection. In 1989 the ATTC mailed thirty-five thousand specimens throughout the globe, but the company refused to say how many were HeLa.
The true value of HeLa cell lines lies not only in the perfection of the Salk vaccine but also in the many medical advances they have enabled and will enable still, all without patenting or licensing headaches and expense because they were never patented. Yet the scientists who proclaimed HeLa “priceless” shied from affixing a dollar value. In 1995 McKusick called HeLa’s value inestimable: “I think you cannot price them.”
In their zeal to procure Henrietta Lacks’s cells, George Gey and his colleagues ignored the fact that they were morally and legally bound by the need to obtain her or her husband’s consent. This requirement had been established by the Nuremburg Code, by a 1947 Atomic Energy Commission ruling, and subsequently by a variety of U.S. professional and hospital guidelines that seem to have been honored more in the breach than the observance, especially where African Americans were concerned.
Interestingly, many medical and journalistic discussions of HeLa cells celebrate not their intrinsic value but the technical expertise of George Gey, who consistently reinforced his image as the “father” of HeLa. He paternalistically referred to HeLa as his “precious baby” and had a penchant for delivering cultures personally to other researchers, keeping the tubes in his breast pocket, where, as he often explained, his body warmth served as their incubator, supplying the optimal temperature for their survival.42
Henrietta Lacks’s husband complained, “As far as them selling my wife’s cells without my knowledge and making a profit—I don’t like that at all. They are exploiting both of us. If they’ve been making a profit they should give me some kind of restitution.”43
By the time the Lackses learned that medical scientists had appropriated their mother’s body for profitable global research, the statute of limitations for any suit they might bring for conversion, or the illegal appropriation of her tissues, had long ago expired. It is questionable whether the courts would have been sympathetic in any case, because they have typically dismissed such claims, ruling that the purloined tissues were “discarded.”44
Because HeLa was not patented, there was no monopoly hampering its wide distribution. “Because of the culture of the 1950s, no one would have thought of patenting HeLa,” McKusick assured me when we spoke by telephone. “HeLa was developed with public funds, but the ethos at that time was that the findings of a researcher remained in the public domain. Neither scientists who made the discovery nor anyone else would think that personal profit would be derived from the affair. It’s a very different atmosphere now.”
If there is a silver lining of this medical theft, deception, and betrayal, it is the plethora of medical advances that have depended upon the free distribution of an unpatented HeLa. It remained cheap and ubiquitous, a freely available medical blessing, and many people lived and enjoyed restored health as a result of Henrietta Lacks’s sacrifice. This perspective cannot excuse the exploitation of the Lacks family in the service of HeLa, but its common use as a medical tool lends a measure of counterweight to the harms done them.
By the latter half of the twentieth century, living things and other products of nature continued to receive the occasional U.S. patent. Even in Europe, which was far less patent friendly, some life patents were granted under the terms of regulatory meetings such as the Paris Convention of 1961, the 1967 Treaty of Budapest, and the European Patent Convention of 1973. And in 1975, U.S. plant patents expanded to include a product of sexual reproduction, long barred as a bastion of natural processes: University of Illinois researcher Earl Patterson was granted a utility patent on a new corn hybrid seed in 1975.45
However, patents were not sought on most medically important living things, and for a decade after HeLa’s discovery, human cell lines were not patented.
This changed when the human cell line named WI-38 (because it originated at Philadelphia’s Wistar Institute) was developed in 1962 by University of Pennsylvania microbiologist Leonard Hayflick. Hayflick is best known for identifying the microorganism, a mycoplasma, that causes atypical pneumonia, commonly known as “walking pneumonia” in humans. And, in a finding of great significance for research on aging, he had demolished the myth that human cells are immortal, capable of dividing indefinitely. Instead, he determined that normal human cells have a limited capacity for dividing before they essentially commit suicide: the “Hayflick limit,” which equals about fifty divisions.46
Hayflick sought to patent cell line WI-38, but the U.S. Patent and Trademark Office initially rejected his application on the basis that patents were not granted on living cells.
The suit was complicated by the fact that Hayflick’s work was supported by federal grants and the university had filed its own patent application for the line, though no decision had been made. When the government funds research, it has the right to hold the patent, and profit-making corporations are legally prohibited from buying such patents. The federal funding statutes did, however, allow Hayflick to disseminate his unpatented cell line to companies that manufactured measles and mumps vaccines, and these companies made a handsome profit while Hayflick, who had created WI-38, received nothing.
Hayflick decided not to accept this state of affairs, and in 1972 he founded a start-up company to market WI-38 to manufacturers and entered into a contract with Merck that gave the drug maker options that would entitle it to buy $1 million in cells.
Hayflick was also short-listed for an important position at the National Institute of Aging. As part of his background check, James W. Schriver, head of management survey and review at the National Institutes of Health (NIH), discovered Hayflick’s income from the cell line and charged among other things that he was illegally profiting from the sales of WI-38.
The government contended that WI-38 was solely its property and shared detailed documents supporting its views with the national press, exposing Hayflick to nationwide criticism. When Stanford learned of the NIH investigation, it undertook its own, which seemed likely to result in disciplinary action. Instead, Hayflick resigned.
Out of a job, his reputation shadowed by government charges, and his income from WI-38 suspended awaiting the resolution of the NIH investigation, Hayflick found himself standing on the unemployment line for weeks until he obtained a position at Children’s Hospital Medical Center in Oakland, California, where he secured grants that allowed him to continue his research.
Then, in 1975, the National Institutes of Health sued him, not over the ethics or hubris of patenting human life, but rather in a squabble over the ownership, patent rights, and potential profits of cell line WI-38.47 The NIH claimed that even without a patent, WI-38 was the property of the government because federal funds had supported the line’s development and dissemination. Hayflick responded with a lawsuit challenging the basis for the NIH’s ownership, seeking damages and demanding title to and profits from the sales of WI-38.48
WI-38’s anonymous “tissue donor” was not party to the suits, and in fact she never knew of them, for the line was developed from the lung cells of an aborted fetus.49 For years, the wheels of justice ground at a glacial rate, keeping Hayflick, and the case against him, suspended in a legal and professional limbo.
Just a year after the NIH sued Hayflick, and a quarter century after the illicit procurement of the HeLa cells, doctors appropriated the body parts of another person without his knowledge. This time, however, the story spun out differently. In the fall of 1976, John Moore, a Seattle surveyor who was working on the Alaska pipeline, learned that he had hairy-cell leukemia, or HCL, a rare and usually fatal cancer of the white blood cells. Moore’s father, a doctor, urged him to come back home to Southern California, where he could be treated by UCLA blood specialist David Golde, MD, a specialist in HCL. Golde told Moore that his grossly enlarged spleen had to be removed, and on October 5, 1976, Moore dutifully signed the consent form for the splenectomy. Moore, who was not expected to survive long, recovered, and the surgery was a success. It was a success for Golde as well, because although he did not tell Moore, the twenty-two-pound spleen was producing an unusual volume of blood proteins that had triggered an extraordinarily effective immune response against his cancer.
Golde surreptitiously moved Moore’s spleen to a research wing of the hospital, establishing a lab where he used it and other of Moore’s tissues to develop a cell line from a key component of Moore’s immune system, his T-cell lymphocytes. For several years, Golde insisted that Moore travel at his own expense from Alaska to Los Angeles for frequent follow-up visits, during which Golde extracted blood, cells, tissues, and semen, always explaining that this solicitousness was to ensure against a recurrence. Actually the tissues were used for Golde’s anticancer research based on Moore’s body parts.
Then, 1980 arrived, a year that saw a confluence of laws that dictated the medical fate of John Moore and many Americans who followed him.
In the 1970s, as Dr. Hayflick began grappling with the NIH and John Moore learned he had a life-threatening blood cancer, Dr. Ananda M. Chakrabarty50 left academia to join research and development at General Electric Company in Schenectady, New York. He was searching for an intellectual challenge that would yield commercial value, and he hit upon the idea of manipulating a class of bacteria—pseudomonads—that were blessed with “nutritional versatility.” That is, they were able to assimilate or “eat” unusual organic compounds such as camphor, naphthalene, and petroleum. They could also convert crude oil into protein-rich biomass, making these pseudomonads a potential gold mine because, as Chakrabarty wrote, “In some parts of the world oil was cheap but protein expensive.”51
He hoped the bacteria would generate cheap food sources that would provide GE with a profitable way to alleviate world hunger. But each type of bacterium could transform only a few types of oil, as dictated by the DNA contained within genes in each bacterial cell’s plasmids, energy-generating organelles. Chakrabarty manipulated a bacterial strain that contained DNA from many plasmids into a single plasmid, which allowed one strain of bacterium to digest many types of oil. This was a prerequisite of transforming the bacteria into protein factories—a great achievement, especially because he accomplished it before contemporary genetic recombination techniques were available. Unfortunately, by the time Chakrabarty perfected this process, oil had risen in price and its use to produce food protein was no longer economically feasible.
However, Chakrabarty and his colleagues reasoned that his custom-designed “oil-eating” microorganisms could profitably be used for cleaning up oil spills. In June 1972, GE decided to patent not only the oil-consuming bacterium itself but also the process of constructing these organisms. Otherwise anyone, including GE’s competitors, would be able to construct and use the valuable bacteria.
In 1973 the U.S. Patent and Trade Office (USPTO) granted GE and Chakrabarty a patent on the process of engineering the microorganism, the first time such a patent had been given. But it rejected the patent application for the organism itself on the grounds that a microorganism is a product of nature, and as such cannot be patented. Over the following years, recombinant genetic techniques were developed and gained currency, allowing the wholesale manipulation of many organisms, for which some patents were applied. But the USPTO did not grant a patent on the “oil-eating” bacterium. Instead, because these additional patent applications had begun rolling in for living things, the Patent Office turned to the Supreme Court for a ruling on the patentability of living microorganisms.
In June 1980 the Supreme Court decided in a 5–4 vote to permit the patenting of life, ruling in Chakrabarty v. Diamond that Chakrabarty’s “oil-eating” bacterium in question was not a product of nature but rather a man-made invention that deserved patent protection.52 In granting the patent on his bacterium, the Court quoted the congressional report leading up to the 1952 Patent Act stipulating that “anything made by man under the sun” should be patentable. Yet the Court’s ruling made it clear that the decision was meant narrowly, due to the extensive manipulation and particular circumstances in Chakrabarty. The Court did not address the larger questions of patenting higher forms of life.
Yet the USPTO interpreted the decision broadly, and no one professed as much surprise as Chakrabarty himself:
Even though the Supreme Court based its decision in a focused manner centered on a genetically engineered bacterium, the USPTO interpreted the decision in a much broader manner, granting patents on genetically altered plants, animals, human cells and tissues, disease genes, and the like … an outcome wholly unforeseen but to some extent anticipated or feared during the controversy surrounding the patenting of the oil-eating pseudomonad.53
Chakrabarty v. Diamond was not the only paradigm-shattering patent development of 1980. A report by the U.S. comptroller general posited that innovation was being stifled because universities and corporations did not want to invest in developing technology that they did not own. This included patented discoveries that had been financed by federal funds but lay undeveloped because the government funding placed them in public domain and laws prohibited corporations from owning them. The university could own them but did not have the funds or incentive to develop them.
As a result, American technological innovation was stifled, according to Senator Birch Bayh, an Indiana Democrat, who complained that the vast majority of twenty-eight thousand patented discoveries made in universities with $30 billion in taxpayers’ dollars were “lying there, collecting dust”: only 5 percent of these patented items were being developed into commercial products with public utility.54 Kansas Republican Bob Dole agreed, and together in 1980 they sponsored the Government Patent Policy Act of 1980,55 commonly known as the Bayh-Dole Act, to foster the commercialization of inventions based on university-held patents financed by government grants.
Not everyone approved of this proposed marriage of academia and industry. Dissenters included the influential Admiral Hyman Rickover, “Father of the Nuclear Navy,” who voiced his unambiguous, strident, and frequent objections on the grounds that corporate ownership of university innovation would spawn ungovernable monopolies: “In my opinion, government contractors—including small businesses and universities—should not be given title to inventions developed at government expense. That is the gist of my testimony. These inventions are paid for by the public and therefore should be available for any citizen to use or not as he sees fit.”56
The powerful senator Russell Long of Louisiana, a Democrat, agreed. On September 24, he proclaimed to Congress, “I am adamantly opposed to the House bill. I urge you to join with me in taking whatever steps are necessary to prevent this monopolistic provision from being included in the final form of any patent policy legislation.” In private, he railed to Bayh’s staff that “this is the worst bill I have seen in my life.” The Carter administration agreed, Congress was convinced, and the Bayh-Dole bill died in the regular sessions of the Ninety-sixth Congress.
By December, however, Jimmy Carter was a lame duck, and when Congress was briefly revived for a necessary budgetary session, Bayh wanted the bill slipped in for another vote and another chance at passage. But Bayh had lost the election, too, and so wielded even less political clout than earlier. Long had the power to withhold the bill from consideration during the budgetary session.
However, good ol’ boy sentiment trumped congressional fears of renegade monopolies. Russell Long, in a farewell act of respect for the departing Bayh, called him to say, “Birch, take that patent bill, you’re entitled to it. You’ve earned it.”57 Long released the bill for consideration and withdrew his opposition; following his lead, so did the other representatives.
Thus Bayh-Dole became law on December 12, in the last hour of the last congressional session during the waning days of 1980, reversing more than three decades of public policy that reserved to universities the sole right to own inventions that resulted from federally funded research.58
Moreover, not only could colleges now sell and license the patents developed with taxpayers’ dollars59 to private companies, they could do so without publicly disclosing the deals. To abet the patenting and development of new and useful inventions, colleges and universities were now actively encouraged to court the very industries with which they formerly had been prohibited from partnering.60
The Stevenson-Wydler Technology Innovation Act was yet another piece of 1980 legislation that supported federal funding to pay for university research.61 This act encourages technological innovation by fostering cooperation among government researchers, universities, large corporations, and small businesses, notably biotechnology start-ups. Bolstered by such laws as the 1981 Economic Recovery Act,62 Stevenson-Wydler provides incentives in the form of tax credits to companies that contribute research equipment to universities, and a number of amendments have reinforced these laws’ aim of establishing intimate government-university-corporate research ties.63
What did this newly cozy relationship between the university and industry betoken? Corporations, notably pharmaceutical companies, now work closely with universities and their researchers in order to catalyze research, businesses innovation, and profitability. In the medical arena, the goal is to encourage the production of new drug treatments and to make large profits while doing so. This and subsequent laws encouraged universities and private corporations to form closer ties while allowing them to exploit profits from research and development conducted by universities and paid for with federal funds.
The laws passed in 1980 also changed the trajectory of Leonard Hayflick’s and John Moore’s lives. Suddenly, the fact that WI-38 was living no longer presented a bar to Hayflick’s patent application. Just as suddenly, Hayflick’s stratagem for gleaning corporate profits from taxpayer-funded research was no longer illegal: instead, it was legislatively encouraged.
Accordingly, he and the NIH signed a settlement that ended their legal dispute. Under its terms, all charges against Hayflick were dropped. He kept $90,000 of proceeds from the sale of WI-38 as well as patent rights over some of the cell line, enabling him to sell WI-38, although the government retained patent ownership on most of the line. The settlement merely dictated the terms under which the cells and patent would be shared, but did not answer the larger legal questions of what rights should accrue to scientists whose discoveries are licensed and sold, questions that still bedevil us today.
On January 15, 1982, eighty-five prominent U.S. scientists signed a letter in Science applauding what they called Hayflick’s exoneration and warning that similar prosecution over the patenting of their inventions could await other researchers in the future. The government largely maintained silence except to deny that its about-face constituted an “exoneration” of Hayflick.
Hayflick went on to become one of the most important and prolific American scientists, winning more than twenty-five major awards in the United States and Europe, and authoring 275 papers that are frequently cited in biochemistry, biophysics, cell biology, enzymology, genetics, and molecular biology. Today he is a professor of anatomy at the University of California at San Francisco.
And John Moore? As we have seen, Golde was taking frequent tissue samples from an unprotesting Moore, but the latter’s suspicions were triggered when Golde began pressuring him to sign a new blanket-consent form that would belatedly give Golde absolute rights to Moore’s “discarded, worthless” tissue samples. A wary Moore checked and signed the box that read “I do not consent,” and an agitated Golde immediately called and wrote him, urging him to rectify his “error.” Instead, Moore hired a lawyer, who quickly discovered that the Regents of the University of California had responded to the bounty of corporate-friendly legislation of the 1980s with alacrity: they had applied for a patent on John Moore’s “Mo” cell line, made from his spleen and the samples that Golde had been harvesting during Moore’s supposedly therapeutic visits. The patent, U.S. Patent No. 4,438,032: “Unique T-Lymphocyte Line and Products Derived Therefrom,” was granted the next year.
Moore’s lawyer also discovered that UCLA, on the heels of the Stevenson-Wydler Act, had used the patent to sign lucrative contracts with the Genetics Institute, Inc., and Sandoz Pharmaceuticals.64 Between 1981 and 1983, Golde was showered with seventy-five thousand shares of stock as a token payment and shared $440,000 from Sandoz, Ltd., with his partners. The cell line’s estimated worth was then $3 billion. UCLA could not have done this without the Chakrabarty decision, Bayh-Dole, and the subsequent rulings that allowed it first to secure a patent on a living entity—John Moore—and second, to transfer the patent to Sandoz.
Moore lost no time in suing the UCLA Medical Center for misappropriating his valuable tissues—for “converting” them (in legal argot), for hiding their lucrative commercial nature, and for deceiving Moore about the true nature of the medical attentions he had received. The California courts denied Moore’s claims, but the state court of appeals ruled that a person’s tissues are his personal property, opening the way for Moore to lay a claim on the patent and part of the profits of any genetically engineered commercial products developed from them.
Biotechnology companies, pharmaceutical firms, and researchers objected vigorously and scientists complained that this ruling could sabotage biomedical research—and with it, the welfare of future patients. Many research institutions and corporations filed amicus curiae briefs urging that Moore’s claims be invalidated in the interests of science. Although the California courts also found that Golde had violated his “fiduciary duty” to warn Moore about his tissues’ lucrative nature, they repeatedly upheld Golde’s patent and specifically denied that Moore retained any rights in his own tissues.65 In 1990, the justices of the California Supreme Court, swayed by these arguments, ruled against Moore, expressing their concern that allowing patients to sue for rights to their cells and tissues would set a precedent for a “litigation lottery.”
However, the courts also determined that Moore had been deprived of the legally mandated right to informed consent and that patients must be informed of and agree to the use of their tissues for research. The court opined that upholding this right to informed consent was sufficient to protect Moore’s interests in his tissues as well.
This aspect of the decision is more than a little hazy: If a patient gives such consent, does it cover everything done with his tissues by researchers in perpetuity? Does it cover abdicating rights to market use and profits? Before being asked to give such consent, how much information should the patient be given about the possible commoditization of his tissues?
For that matter, from whom should the researcher seek informed consent? In the case of Hayflick’s cell lines, which came from a fetus, should consent have been elicited from the parents? When you consider that the researchers themselves cannot always know the eventual value and uses of excised tissues, or even their specific origins, the complexity of this issue becomes apparent, and it has only deepened with biotechnological advances.
Finally Moore’s appeals reached the U.S. Supreme Court, accompanied by the usual flurry of amicus briefs from research institutions, but the high court also upheld UCLA’s patent in 1990, ruling that Moore had no property rights in the cells taken from him, a move that was widely regarded as a triumph for biotechnology companies.66 Notably, the Supreme Court also expressed concern that extending “property” to include organs would exercise a chilling effect on medical research. This concern seems to have trumped the individual’s property rights in his own body.
“My doctors are claiming that my humanity, my genetic essence, is their invention and their property,” Moore lamented. “They view me as a mine from which to extract biological material. I was harvested.”67 Throughout his legal battles he remained a tireless and vocal advocate for patients’ rights until his death in 1990 as he lost his final battle in the Supreme Court. He was fifty-six and died in a hospital where he was undergoing experimental treatment for his illness.
John Moore’s story illustrates how the same courts that grew to welcome patent claims from universities like UCLA, from researchers like David Golde, from biotechnology start-ups like Hayflick’s, and from companies like GE and Sandoz have dismissed claims brought by patients themselves and their survivors, the primal sources of those valuable medical innovations.
Since these events, a flood of life patents, or biological patents, has been granted to researchers not only for simpler organisms such as bacteria and yeast but also for medically important higher animals, such as Harvard’s cancer-prone “oncomouse.”68 Human genes, cells, tissues, and “products” that include revolting human-animal chimeras have been granted patents. In fact, everything has been patented short of an entire human being. Perhaps to allay fears of such an eventuality, the USPTO in 1987 offered reassurances that it would not allow the patenting of human beings.69 Although it did not cite case law or explain its legal reasoning, antislavery statutes are thought to preclude such patenting, even though body ownership and body patenting are legally distinct. But pragmatically speaking, the distinction is not that comforting because the courts have tended to treat control over a person’s body and body parts as a property issue, and they have repeatedly ruled that in these circumstances, people hold no property rights to their bodies.
Disease genes and parts of genes have been patented, often even before their function was known, which would seem to violate the insistence by the USPTO that a patent application specify the use of the patented entity. Other potentially lucrative technologies have been patented as well, including a human hematopoietic stem cell patented by a Stanford University researcher. Hematopoietic stem cells are medically valuable because they are tabulae rasae, able to develop into many types of tissues, and devoid of compatibility problems. Unlike the unique tissues of John Moore and Henrietta Lacks, such stem cells are ubiquitous, harvestable from embryos and newborns.
These developments mean that the medical-industrial complex takes a fiscal interest not only in patents that ultimately emanated from the extraordinary tissues of John Moore and Henrietta Lacks but also in patents on the tissues of everyday people.
In 1991, the financing structure of the USPTO, which had relied upon tax revenue, was changed so that it became largely funded by fees from those who sought patents. Seventy percent of the USPTO budget comes from such maintenance fees,70 and in the eyes of many, this reliance upon funds from applicants compromises the office’s independence. Some tie the pressure upon patent examiners to approve applications to the desire for fees. Other factors exert pressure upon the patent office to accept rather than to reject patent applications.71 Some applications filed by pharmaceutical companies are four hundred thousand pages long,72 and firms often employ fleets of lawyers to fight rejections and patent-office challenges. Patent officials are often simply unable to resist applicants’ legal pressure, and discussions on USPTO websites are filled with complaints from examiners who bewail the pressure they feel to approve applications.73
As 1991 drew to a close, I was oblivious to these developments. I was working as a newspaper editor and a classical-music announcer, having left the positions as a technician in hospital laboratories where I’d worked a decade earlier, just before the accelerated commercialization of research. Back then, the laboratories I frequented had been staffed by investigators whose ambitions turned toward academic advancement, tenure, fame, and the alleviation of human suffering, not always in that order. No one I knew there entertained dreams of riches. Every day, to enter our lab, I passed a door adorned with a cover from Travel & Leisure magazine that featured well-heeled vacationers lounging in luxurious surroundings: the typewritten legend below it read, “If you’re looking for leisure, keep traveling.”
In 1992, I began two years of study at the Harvard School of Public Health on a journalism fellowship. In my naiveté, I expected classrooms helmed by Martin Arrowsmiths, but I was instead introduced to a transformed medical-research culture. During the traditional first-day-of-class exercises, I internally cringed as we were asked to introduce ourselves and to say a bit about our backgrounds, our work, and what we hoped to take away from the school. As I listened, I learned that impressive scientist-humanists who held MDs, PhDs, or both made up most of our class. Some had spent years rendering care to the poor in developing nations, others had mounted campaigns to care for traditionally underserved patients at home, while still others had already tasted success in the laboratory, conducting research into HIV, tropical disorders, or multidrug-resistant TB. An astonishing number had done all three, and still others were young idealists fresh from schools of medicine. Then, it was my turn.
“I’m a journalist,” I muttered, fighting the temptation to slip a bit lower in my seat. A look of disdain from the professor would not have surprised me. Instead, I soon became accustomed to the sudden, galvanized attention my admission tended to draw from professors. Most flew to my seat to give me their cards and to chat about the nature of their work. I was invited to lunch, to visit their labs, and to tour their biotechnology companies. Initially I was flummoxed, but I soon realized that in addition to their work as professors of immunology or toxicology, most of my biomedical science professors were nursing biotech companies. They let me know, subtly or overtly, that they would welcome any press attention I could garner for them in the pages of the New York Times, USA Today, or even the Boston Globe. One fellow, who will remain nameless, eagerly asked, “Can you help me get on Oprah?” Positive press attention enhanced their fledgling companies’ visibility and could help attract a large pharmaceutical company’s financial attention.
The drug industry was not only buying the technology these professors devised but was also acquiring the most promising start-ups themselves. It was a sage bargain because the pharmaceutical corporations did not have to outlay funds to subsidize the research and development: the federal government and the biotech firm had done that. Thanks to the Bayh-Dole Act, large drug companies had only to pay for the patent (or for the company, in which case the patent came with it) and then, after a relatively small investment of their own, to enjoy the profits from licensing the patent or from selling the resulting medication, tests, or other product.
For their part, the universities understood that there was much money to be made even after giving the researcher his cut. Researchers typically sign a contract with their university that stipulates the terms under which a patent based on their work will be assigned to the university. A third to half of the money generated by a discovery is typically assigned to the inventor, with the rest split between his department and the university. Universities benefit from more than the sometimes enormous cash infusions when they sell or license a patent to a corporation. They can also benefit from payments they receive for conducting clinical trials. Once they have ceded the control of the patent to industry, however, the university no longer dictates the terms of such research, nor can it decide which drugs will be developed and marketed and which will be abandoned.
Unlike researchers and the university, the taxpayers, whose dollars funded the discoveries made and patented in academia and commercialized by drug makers, receive nothing except the presumption that they—we—will benefit down the line from an increased number of medical advances.
Chief among these medical advances were supposed to be new drugs for important diseases. And by the early 1990s, there were plenty of these. HIV disease was still a murkily understood and terrifying plague that had slipped over into pandemic status. Tuberculosis was undergoing a horrible renaissance, recurring in virulent forms that were unchecked by the traditional antibiotic regimens. In fact, antibiotics in general had lost their efficacy from overuse because public-health strategies such as infection control, hospital design, case-finding, and disease surveillance had been abandoned. People were beginning to succumb to old infectious diseases like meningitis that we thought we had conquered, as well as to new terribly virulent ones such as “flesh-eating” necrotizing fasciitis.
We desperately needed new antibiotics. We needed treatments for killers such as heart disease and stroke and a myriad of cancers. Parkinson’s, which was increasingly prevalent among people under forty, Alzheimer’s disease, sickle-cell disease, an array of cancers, serious psychiatric syndromes, and devastating genetic disorders such as Tay-Sachs and Canavan’s cried out for treatments. There was no dearth of medical challenges, and the university–pharmaceutical industry marriage brokered by the government, we were told, would escalate the development of answers and bring those answers to market.
Yet, in a sense, we Westerners had it easy. Malaria, tuberculosis, sleeping sickness, and emerging diseases roiled the developing world, which lacked access to medical care and basic drugs that already existed for long-standing conditions such as cancer. Poor and developing nations were utterly unequipped to treat new ones, such as AIDS and other emerging infectious diseases.
Did the academia-corporation partnerships bring us the drugs and treatments the world needed? Subsequent chapters will discuss this vexing question in detail.
Medical-research practitioners still work and compete to devise ways to alleviate human suffering and to conquer disease. But the culture has changed. Buying, selling, and the desire to make a profit now are integral goals of academic research, as they have always been goals of corporate research.
Bayh-Dole is widely credited with stimulating significant growth in the university-industry technology transfer and research collaboration. And indeed it did catalyze the $43-billion-per-annum biotechnology industry and enrich scientists as they began to organize their university research to ferret out patentable ideas, schemes, and inventions that they developed with the help of industry.74
Colleges and universities obtained only about 260 patents a year before 1980’s Bayh-Dole Act: today universities secure approximately three thousand patents a year, according to the Association of University Technology Managers, which represents the employees of university technology transfer offices.75 (In 2010, the U.S. Patent and Trademark Office approved 220,000 patents of every kind.) These early scientist-entrepreneurs had to figure out their economic strategies and marketing as they went along, but eventually universities chose to dedicate technology-transfer departments to coordinate this lucrative mission. Before Bayh-Dole, only twelve technological powerhouses—including MIT, Stanford, the University of California, Johns Hopkins, and the University of Wisconsin—had set up technology-transfer offices to broker patent and licensing agreements that transformed researchers’ findings into patented, marketable commodities for corporations.
But by 1991, the number of patents and licenses obtained by North American colleges, research institutes, and hospitals had leaped more than a hundredfold to nearly 2,800 patents and licenses gleaning $218 million in royalties. Biomedical research was now big business, and small biotechnology start-ups, including those held by instructors and professors who licensed their patents shrewdly or sold their companies to large corporations, could and did become rich. By 2003, North American university researchers had started 374 companies,76 and academic institutions had completed 4,516 licensing arrangements that earned them more than $1.3 billion.77 By 2006, technology-transfer offices generated at least $45 billion, largely from licensing fees. Some universities did astonishingly lucrative business: Stanford University made $61 million in 2006, and New York University acquired $157 million.78
Technology transfer is an issue for students, too. Students who are inventors can reap 33 to 50 percent of the funds earned by a new product, and the balance of the profits from their discoveries usually goes to the university. The university often also pays the patent fee, which can be prohibitive for a student, reaching $15,000 or more. By contrast, a scientist working in industry usually collects nothing: the corporation takes the patent rights.79
Is there a downside to the collaboration that has proven so fruitful for universities and drug companies? In Science in the Private Interest, Tufts professor of urban and environmental policy and planning Sheldon Krimsky argues that universities harbor several “personalities” that serve essential public functions. Among them is the Baconian model of the university, named after the English philosopher Francis Bacon, who has been called the “father of empiricism” because he championed the scientific method of induction (discovering general principles from empirical evidence) over theories and mathematical models as a way of understanding the world. For Bacon, the collection and interpretation of facts and data were paramount, and he extolled the value of collaboration between investigators in an institutional setting. In the Baconian model, the university’s stores of knowledge are valued for their ability to abet productivity. In this role, the intellectual products of the university contribute to the economic and industrial development of society, and the university itself serves as a wellspring of productivity. The pursuit of knowledge is as valuable as the marketing of products resulting from the university’s intellectual property. In the medical sphere, the university spurs the generation of medicines and therapies because they are needed by the public, not because they are most likely to be profitable.
However, Krimsky notes that the university has also long been recognized as a unique arena where knowledge is a virtue that is pursued not for the development of intellectual property, but for its own sake. This facet of the university as a collegial haven, marked by the free and open exchange of knowledge and by collaboration, is a cultural resource that should be protected to preserve intellectual vigor. Such unhindered collaboration profits society because if researchers had financial disincentives to collaborate, the rate of discoveries would be much slower.
Collegial sharing of data was never flawless. In his 1968 memoir The Double Helix,80 James Watson related how he, Francis Crick, and Maurice Wilkins raided King’s College researcher Rosalind Franklin’s xerographic data in the early 1950s in a conspiracy that helped them become the first to determine the structure of DNA and may have cost her the 1962 Nobel Prize that the men shared. Typically for the times, this act was motivated by a lust for scientific glory, not by monetary motives. But the conspiracy was so shocking because it violated the collaborative norm, or at least the ideal. Sharing of data was the norm and a virtue, essential to maximizing researchers’ chance of success. Collaboration also showed that the results were more important than who discovered them. Today, however, data sharing is more than unexpected, it is viewed as risky behavior and sometimes as criminality, as the Zhu-Kimbara case that opened this chapter illustrates.
But the pure pursuit of knowledge is valuable in its own right because basic science pursuits are a fertile source of important but serendipitous discoveries. Alexander Fleming discovered penicillin when mold destroyed bacteria in a culture whose dishes he had neglected to disinfect; the artificial sweetener aspartame was discovered when chemist James M. Schlatter, who was attempting to produce a medication for ulcers, absentmindedly licked his fingers and was surprised by their sweet taste. Researchers seeking a cancer treatment stumbled upon eflornithine, the best medication devised against African sleeping sickness; Viagra was originally developed as an oral medication for hypertension and angina, but in Phase I trials it did a better job of inducing erections than protecting the cardiovascular system; and lithium carbonate’s ability to temper the mood swings of people with bipolar disorder was discovered when guinea pigs, given the drug in an attempt to increase their urine production, became sleepy. The freedom to pursue basic research is important because discoveries often are not tied to specific research plans, but to happy accidents.
The university and its researchers also play a key role in a third important arena: national defense. As with the Manhattan Project, researchers and the university are trusted to maintain confidentiality as the custodians of important scientific information for our national defense. In this role, the university is depended upon to place national interests above its own and that of its faculty members. “In fulfilling this mission,” Krimsky reminds us, “universities have accommodated to secrecy in defense contracts.”
Finally, there is what Krimsky refers to as the “public-interest model,” which casts the university as dedicated to public welfare in a wider sense. For-profit corporations serve the public interest when to do so dovetails with their financial interests, but the university serves a wider and very different public-interest role.
Instead of capitalist self-interest and competition, the university is an oasis of resources and expertise wielded by researchers whose work is underwritten by the federal government. Its work is dedicated to economic, social, and medical problems without being influenced by the market viability or profitability of these approaches. This is a mission hardly to be found elsewhere, and in the medical arena it again casts the university in the unique role of an entity dedicated to the alleviation of human suffering and the betterment of health for their own sake, not for the sake of profit.
A delicate balance characterized the relationship of the various university roles until 1980. But the slew of laws that fostered cozy relationships between corporations and universities in 1980 blurred the line between the for-profit corporation and the university. As a result, the university has lost these pivotal values that protected the public’s interests as they interfered with profitability and corporate missions.81
As Sheldon Krimsky has observed, “The public ethos of science slowly disappears, to the detriment of the communitarian interests of society.”82