Gods and Monsters
News: Talking apes, flying
pigs, superhuman with armadillo attributes, and other
strange considerations of Dr. Stuart Newman's fight to
patent a human/animal chimera
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.
Mark Dowie discovered this story about the paradox of the chimera patent while researching a longer article on the patenting of life-forms. Dowie is a former publisher and editor of Mother Jones and teaches graduate course in scientific writing at the University of California, Berkeley.
