Photo by Alex Tehrani: Tim O'Brien
ON APRIL FOOLS’ DAY 1998, within hours of reading U.S.
patent application No. 08/993,564, the Honorable Bruce Lehman did something no other commissioner
of patents had done in the 200-year history of America’s oldest government agency. He stepped before
a cluster of microphones and announced that the patent would never be approved. No half-human “monsters”
would be patented, Lehman declared angrily, or any other “immoral inventions.”
Legal scholars — accustomed to an office bound by statute to remain silent until patents are approved or rejected — were shocked. Forgoing the traditional 18-month review period, Lehman had issued a marching order to his staff to reject a patent application
they had barely read, rather as if a judge had instructed a jury that the defendant was guilty before the trial began. Furthermore, to support his decision, Lehman cited an 1817 court ruling that excluded
inventions “injurious to the well-being, good policy, or good morals of society.” But patent law had long since been amended to say that if an applicant could claim constructive use for a patent,
he or she could not be denied simply because there might be dangerous or unethical uses of the invention.
“Even attorneys who worshiped the system were horrified,” recalls
former patent examiner Peter di Mauro, who has since left the agency. Research biologists and biotech executives also felt blind-sided, hearing in Commissioner Lehman’s outburst a threat to the hard-earned clearance they had won from the Supreme Court 18 years earlier to patent “anything under the sun made by man” — even living organisms.
Strange as it may seem, the inventor, Dr. Stuart Newman, a soft-spoken developmental biologist and professor at New York Medical College in Valhalla, New York, completely agreed with Lehman that his invention defied the boundaries of human morality. It’s why he filed
for the patent. And it’s why, six years later, as the biomedical community holds its breath, he and the Patent Office remain locked in a legal battle that may redefine what we mean by “human.”
Newman’s patent application is for an intriguing biotechnological contrivance called a chimera [ki-mir-a]. According to Greek mythology, a chimera was a part-lion, part-goat, part-serpent creature that terrorized Lycia until it was slain by the hero Bellerophon.
If biotech continues to run amok, warns Newman, such inventions of legend and allegory could actually be invented.
Created by injecting the embryonic stem cells of one or more species into the embryo of another species and then allowing that embryo to continue development in the womb of either species, a biological chimera is a way to hybridize two or more species that won’t
cross sexually. The exact results are largely unpredictable except for the certainty that the chimera will contain cells of each species proportionate to the numbers placed in the embryo. A
creature made from an equal number of cells from two species could look like one species but contain the genes, organs, and intelligence of the other.
Newman seeks to patent “chimeric embryos and animals containing human cells.” And while his application cites innocuous biomedical uses for human/ animal chimeras — such as toxicological research and the potential for growing rejection-proof human organs in pigs or other creatures — taken to its most extreme but not necessarily impossible end, the technology could be used to manufacture soldiers with armadillolike shielding, quasi-human astronauts engineered for long-range space travel, and altered primates with enough cognitive ability to ride a bus, follow basic instructions, pick crops in 119 degrees, or descend into a mine shaft without worrying their silly little heads about inalienable human rights and the resulting laws and customs that demand safe working conditions.
At first blush, what Newman seeks sounds quite like many patents already
obtained by university laboratories and biotech corporations to insert human genes into mice
and other mammals, creating what is known as a “transgenic” animal. But cross-pollinating using
whole cells containing the entire genomic sequence is a profoundly different and even more morally
charged process, and Newman’s invention presents the Patent Office with a serious legal and political
quandary that could earn the agency enemies either way it might rule. Granting a patent for a half-human
chimera would throw religious, bioethical, animal-rights, and constitutional activists into
high dudgeon. And the biotech industry would boil over the approval of what is clearly a preventive
patent. But decline it and the agency is in court, eventually the highest court in the land. The last
time that happened the Patent Office lost its case. Thus far, however, Commissioner Lehman and
his successors have decided that foiling Newman is worth the risk.
And Newman, a man accustomed to disappointing reversals in and outside
his laboratory, has fought back, claim by claim, for six years, because he knows that with a patent
in hand he can delay what he regards as a deeply offensive technology for the 20-year life of the patent.
Opposed to genetically altering human beings and patenting living organisms, Newman (who’s supported
in this endeavor by techno-gadfly Jeremy Rifkin) sees in the chimera the manifestation of all he
finds immoral about biotech. The technology exists to make chimeric embryos “tomorrow,” he says,
and a chimera of two similar species (say human and chimp) that could survive into adulthood probably
isn’t far off. “This is the prize. The more you can humanize animals genetically, the better they
are for research models and as sources of transplantable tissues.”
With such goals in mind, six Canadian and American biologists gathered
November 13, 2002, at the New York Academy of Sciences to debate in private whether or not to proceed
with chimeric research involving human cells. While two of the scientists raised questions about
the ethics of such research, the rest felt that while it could admittedly lead to outcomes “too horrible
to contemplate,” chimeras still offered enough medical promise to proceed. Dr. Newman has since
notified all six that if they proceed in developing chimeras, they will be in violation of his pending
patent, and litigation will follow.
News of the meeting, immediately reported in Nature, threw
the Patent Office into an even deeper bind. “This goes way beyond the jurisdiction of the agency,”
Deputy Commissioner Stephen Kunin said. “We’re being dragged into a controversy which, from our
perspective, we don’t need to be part of.”
In truth, the Patent Office made itself part of this controversy almost
two decades ago when it began granting patents for genetically altered mammals. At that moment,
it placed itself and the patent process at the intersection of science, commerce, and religion,
and in Stuart Newman’s line of fire.
THE PATENT ACT OF 1793, drafted by Thomas Jefferson, and subsequent
case law stipulated that nature, in any of its forms or manifestations, could not be patented. But
in the late 1920s, research agronomists approached Congress and argued that man-made plant hybrids
were not really products of nature, but rather existed as a consequence of human manipulation and
were thus, in Jefferson’s carefully chosen words, “a new composition of matter.” The 1930 Plant
Patent Act soon allowed for new varieties of plants that reproduced asexually to be patented.
Molecular biology soon produced other techniques for creating new
organisms and genetically altering existing ones. But most required sexual reproduction and
were thus deemed “natural.” Then on June 16, 1980, the U.S. Supreme Court surprised both sides in
an obscure patent case by ruling 5-to-4 that a General Electric scientist named Ananda Chakrabarty
could patent genetically modi-fied bacteria that produced enzymes capable of breaking down crude
oil. In its opinion, the majority concluded that Chakrabarty’s bugs, with their vibrant cells
and shimmering DNA, were “a human-made invention…with markedly different characteristics
from any found in nature.” They were new compositions of matter, and were, for the life of the patent,
the sole property of General Electric, which, fearful of releasing such an engineered life-form
into the environment, never used them.
Soon, thousands of life-form patent applications were before the Patent
Office, which rapidly evolved from an agency opposed to patenting life-forms to an outright booster
of the practice. Biotech scientists, executives, and their attorneys surmised that if whole organisms
were now patentable, then surely inert pieces of them—genes and gene sequences—would
be as well.
A 1986 patent for corn genetically manipulated to produce
tryptophan—the
chemical the human body uses to make serotonin— widened the opening. In 1987, the Patent
Board of Appeals rejected a process to produce bigger oysters through pressure as “too obvious”
but noted that involvement of a multicellular animal was not itself a bar to patentability. On the
strength of that decision, Patent Commissioner Donald Quigg called a press conference and announced
that all “multicellular living organisms, including animals,” were patentable. He did make a
specific exception for human beings, a restriction mandated, Quigg said, by the 13th Amendment,
which prohibits their ownership.
Few realized how much wider the Quigg decision had opened the pathway
to life-form patenting until a year later, when after a five-year court battle, the Patent Office
issued Patent No. 4,736,866 to Harvard biologists Philip Leder and Timothy Stewart for mice transgenically
engineered to develop tumors. The famous OncoMouse® was born, and DuPont, which
funded the research, holds the exclusive license to it and all its progeny, though the National
Institutes of Health is using the mice for cancer research with the understanding that any commercial
application it develops belongs to DuPont.
The OncoMouse® was the first complete, living, breathing
mammal to be patented in the United States, but it was not the last. Scores of transgenic mammalian
patents have since been approved, including those for cows and sheep modified to produce medicinal
milk (“factory pharming”), rats with a propensity to develop in-flammatory diseases, and a mouse
whose cells contain the gene for human insulin. When Newman filed in 1997, his was among 15,000 biotech
patents applied for that year. By 2002 the number had nearly doubled. Most are approved, many of
them conflicting with existing patents, leaving previous owners no recourse but the courts, which
thrills patent attorneys. And, despite Quigg’s 13th Amendment stipulation, applications to
patent human genes also increase, even genes for which there is no known purpose or product. And
they are approved. When objections are raised to this practice, particularly by scientists, the
Biotech Industry Organization argues that the United States would lose its “global competitive
advantage” if a patent slipped away. “Few people realize,” one newspaper article notes, “that
a genetic ‘land grab’ is taking place on a scale that rivals 19th-century colonialism.”
IF NEWMAN’S PATENT seems the stuff of fancy or Planet of the
Apes,
consider that a sheep/goat chimera was made back in 1984. It’s called a “geep.” When fully grown,
it looks a little like a sheep with features of a goat, or vice versa, and the cells of each are fairly
evenly scattered throughout the geep. In a chimera, the two sets of cells remain distinct (unlike
in a hybrid such as a mule, where all the cells are hybridized “mule cells”), ensuring that a geep
will accept skin grafts from either the sheep or the goat whose cells it owns without stimulating
an immune response. And it can be used to test the toxic effects of chemicals on both sheep and goats.
Thus a part-human chimera, even one without obvious human characteristics or rights, could be
used to test for human carcinogens and mutagens without the safeguards currently required for
clinical trials.
In his application, Newman says “the cells composing the embryo may
contain one or more transgenes.” With such a refinement, chimeric technology could one day be used
to engineer specific
tissue characteristics of one species into the organs of another.
That would be the first step toward growing transplantable human organs inside other animals,
a product of enormous commercial interest to biotech companies like Advanced Cell Technology
(ACT), which looks on with envy and distress as Newman does battle with the government.
A Boston-area company, ACT is already inserting human DNA into cow embryos
to produce and patent human stem cells. It is also attempting to design and breed pigs that will look,
smell, and behave like pigs in a feedlot but possess hearts, livers, kidneys, and pancreases so
humanlike in size, shape, function, and tissue type that people will not reject them after transplantation.
Either way the Patent Office rules on Newman’s application is bad news
for ACT. Approval means Newman owns the technology they need to advance their chimeric research,
and ACT executives know that such an activist is unlikely to license it to them or anyone else. Rejection
by the Patent Office sends a chilling signal through the entire biotech industry that the government
has found a moral boundary beyond which it is unwilling to tread.
This may explain why ACT’s high-profile vice president of scientific
and medical development, Robert Lanza, told me that he
supports Newman’s effort “100 percent”
but added, “While I am opposed to creating chimeric animals, I do not approve of tying up any technology
that could save lives.”
ALTHOUGH IT IS NOW THE EXPLICIT GOAL of the Patent Office to complete
patent reviews within 24 months, Newman’s patent is still officially pending, six years after
it was filed. On four occasions patent inspectors have rejected his application, but with objections
so vague and specious that Newman and his attorneys have been able to argue it back to life, only to
be rejected again on new grounds. When the agency objected to using human embryonic cells to help
create a chimera, for example, Newman’s lawyers pointed out it is legal to abort 100-percent-human
embryos, and would make no sense to grant part-human embryos greater protection.
But one objection survives each exchange—that the chimera itself
would be too humanesque. All the recipes in Dr. Newman’s application call for using human embryonic
cells and stem cells, and describe methods likely to raise the ire of anyone who believes that human
life begins at conception or that human cells are more sacred than those of other creatures. Newman’s
chimera could end up looking, feeling, and behaving somewhat like a human being. That so troubled
patent inspector Deborah Crouch, the first of four
examiners to work the case, that she coined
an intriguing expression to justify rejection. “Since applicant’s claimed invention embraces
a human being,” she wrote, “it is not considered to be patentable subject matter.” Newman and the
Patent Office have spent much of the subsequent six years grappling with the meanings of “embrace”
and “human.”
To make matters more bizarre, while Newman and his lawyers argue against
the embraces-a-human assessment, Newman in fact agrees with it. He knows at least four ways to make
a chimera, but he has no intention of ever making one, with or without human cells and features. So
as not to disseminate technology he considers dangerous, his application includes only techniques
to make chimeras that can be found in existing literature, which gave examiners another excuse
to reject his patent—lack of originality. Newman responded that it is not the method for
which he seeks a patent but the “unique application” of using human cells and, of course, the final
product.
What that product would be, exactly, is at least as much the stuff of philosophy
as science. Place a human gene or gene sequence in a pig or dog and you haven’t really moved either
animal very close to being human as we understand it. But place the same genes in a chimpanzee, whose
DNA is so similar to a human’s that only a full genomic scan can tell them apart, and you could create
something almost human, something that perhaps begins to resemble or “embrace” a human. This would
be even more likely if you made a new creature by combining embryonic cells, rather than just the
genes, from two or more species, as in Newman’s chimera. “Different people would draw the line between
nonhuman and human at different places,” says Newman. “The problem is, the material continuity
among all living organisms is such that no matter where you choose to draw it, based on whatever philosophy
and belief system, the technology will eventually enable crossing that line.”
Pull back from the molecular level and the answer to the question “What
is human?” is fairly obvious. Bruce Lehman echoed Justice Potter Stewart’s famous definition
of obscenity when asked what he thought would constitute a chimeric human. “I’m quite certain that
when we see one of these, we’ll know it,” he told the Washington Post a few weeks after issuing his
summary rejection in 1998. But with a chimera’s ability to hide distinct human features, even intelligence,
inside another species, the definition of humanity could be blurred beyond recognition.
Now that he’s stepped down from the Patent Office, Bruce Lehman can talk
about pending patents, and so in August 2002
we met a few blocks from the U.S. Capitol in his
modest office at the International Intellectual Property Institute, an organization he created
after leaving office with a $1 million grant from the Bush administration. IIPI promotes the installation
of patenting systems
in every country of the world. As a private citizen, Lehman is free
to
reveal his true motivations for stifling Newman’s patent, and
as a patent evangelist he’s
happy to expound on the vital role
intellectual-property laws play in industrial development,
eco-
nomic globalization, and the commercialization of biotech inventions. And he is more
than willing to rebuke bio-Luddites such as Newman, whom he regards as anti-science.
“Stuart Newman is promoting an effort that will make it difficult to
engage in biological research and commercialize the fruits of that research,” says Lehman. “It’s
not funny or cute; it is profoundly wrong. Every attempt to stop science has been characterized
by darkness.”
Lehman says he was acting on the concept of ordre public, a European legal
restriction against immoral inventions that does not exist in American patent law. Nevertheless,
he believes that every American public official should be responsible for defending
ordre
public whether or not it is required by statute.
Yet Lehman also told me that had Advanced Cell Technology, Geron Corp.,
or almost any biotech firm applied for the same patent Newman did, he would not have stood in their
way. And though he spoke of “monsters” when he first reacted to Newman’s patent, Lehman now says
he does “not believe there should be a prohibition against a human patent.” It was not the specter
of half-human chimeras or even patenting whole human beings that revolted him, he now says. “I was
just deeply offended by anyone attempting to use the U.S. Patent Office to make a point, or to stop
the advancement of science. I refused to make it easy for him.”
Whatever his motives, by violating the agency’s rules and issuing a
premature and emotional ruling, Lehman may have given Newman adequate justification to appeal
a rejection. By law, inventors are entitled to revise their applications and reapply as often as
they wish in pursuit of approval. But Newman and his lawyers have decided that if the agency persists
in rejecting the invention, they will appeal the decision all the way to the Supreme Court.
NEWMAN AND HIS ATTORNEYS have had only one audience with patent examiners.
The “interview” occurred in January 2001, when the case was transferred to a new examiner. “They
really didn’t know what to make of us,” recalls his attorney at the time, Patrick Coyne, who says
they talked through the “embracing” issue and tried to explain to the new examiner why the invention
was “original.”
For the moment, Patent officials seem content to leave Newman’s application
in limbo while they strategize their next move. They’re faced with four options: They can withdraw
all their objections and grant a patent; they can withdraw legal and scientific objections and
reject the invention because it “embraces a human”; they could drop the embraces-a-human complaint
and reject the patent for lack of originality or utility; or they could stand their ground on all
objections and let the courts decide.
There are vexing questions at work here, both moral and legal. Should
new organisms be created? Should any organisms be patented? And should humans or anything remotely
resembling humans be created or patented? While it is really only the business of the Patent Office
to deal with the second question, Newman’s initiative could eventually force the entire federal
government—executive, legislative, and judicial branches—to consider the others.
In their third response to Newman, sent in August 2000, patent officials
acknowledged, “In the absence of clear legislative intent and guidance from the courts, it is incumbent
on the Office to proceed cautiously.” That is tantamount, contends attorney Coyne, to admitting
that the agency has been granting
life-form patents for more than 20 years without congressional
authority. Newman hopes this means that Congress and the courts may soon be forced to reconsider
the entire patent law, which was last rewritten in the early 1950s, long before the biotech era began.
“They’re asking themselves how far they can go,” Newman says. “They
seem set upon turning down the application as an act of prudence and letting me take it to the Board
of Patent Appeals and beyond.” Patent Appeals is an interagency court where inventors and patent
examiners can haggle before administrative judges over what is or is not feasible, novel, and useful
about an invention. But in this case, it is also a place to decide whether to grant a handful of biotech
companies control over the genetic blueprint of evolution and open the larger debate over what
is and is not human. For while Con- gress and the courts have made clear that
humans are not
patentable, they’ve never defined the term “human.”
It’s hard to gainsay any legal mind, especially on the current Supreme
Court, but if the court does eventually hear the case, some arguments and counterarguments can
be anticipated. One justice might argue, for example, that chimeric mice possessing
human
brain cells are still mice, much as
the Patent Office decided that the Onco- Mouse®,
with its array of human genes, was
a mouse—period. Bring a cage full of the brainy little
squeakers before any court and the point will be obvious. They’re rodents.
However, another justice would surely observe that if human cells become
scattered throughout the entire body of a gorilla, a primate that is genetically 98 percent human,
and the chimera looks pretty much like a gorilla, but with some obvious human traits—blue
eyes, for example, or a more functional opposing thumb—perhaps the inventor has created
something that resembles, approaches, or, in the awkward language of an ambivalent patent examiner,
“embraces” a human being. And if the
gorilla grows up with an ability to use its
larynx,
tongue, and lips well enough to articulate a few simple words, “I love you,” for
example,
one might even grant the invention personhood.
Partly in anticipation of human/animal chimeras, legal scholars and
bioethicists have already begun to challenge the strictly human view of personhood. “Personhood
doesn’t come from coded sequences,” asserts University of Pennsylvania bioethicist Arthur Caplan,
“nor does it require human anatomy. It’s really defined by what goes on in a brain. A dolphin, for
example, could conceivably acquire enough additional intelligence to warrant personhood.”
What, then, for “human rights”? And what rights are left for, say, humans
in persistent vegetative states who Caplan and a growing number of his peers say might one day be
considered to have lost their personhood and thereby their right to life? Save the dolphin with
its humanesque reasoning and kill the vegetative patients by harvesting their
organs for
sick humans, or even for a part-
human chimera?
But the real issue here is not with chimps, dolphins, mice, or any of their
rights to personhood, but with our notion of humanity and how it is challenged by chimeras, which
threaten either to erase taboos we still embrace, like bestiality, or reintroduce practices we’d
hopefully sloughed off, like slavery. Could one animal cell make a being suitable for ownership,
forced labor, and medical experimentation, just as “one drop” of black blood once did?
What becomes of human empathy if there are chimeric, quasi-human “flesh
robots”
performing human tasks, or if there are two, three, four, or more genetically separate
hom-inid species of self-conscious, intelligent, soulful beings on the planet, perhaps one
being
genetically enhanced to be stronger, faster, brighter than today’s humans, with enough chromosomal
conflicts to prevent crossbreeding with “lesser” humans?
Will genetically enhanced humans lay claim to the Bill of Rights and
exclude all others, or write their own Bill of Superhuman Rights? Will they regard the gene poor
much as many European whites once
regarded dark-skinned humans—as lesser, subhuman
or nonhuman? And will the gene poor, the “naturals,” be forced by fate, law, or judicial decree to
accept their genetic lot in life? And who will parent the chimeras?
These are questions that Stuart Newman believes must be answered before
a patent is considered for a human/primate chimera, and before a future court is forced by chimeric
technology to determine the legal status of pigs with brains powerful enough to render them self-conscious.
So he continues to fight for approval to devise creatures he hopes are never made.
