SCIENCE AND BUSINESS
Piecemeal Patents The U.S. reconsiders patents on DNA fragments
W
hen]. Craig Venter, chief of re ceptor biochemistry and mo lecular biology at the Nation
al Institute of Neurological Disorders and Stroke, developed a rapid, inexpen sive technique for labeling genes, he expected to advance genetics, not gen erate a major controversy. But for the past nine months, scientists, lawyers and representatives of the biotechnolo gy industry have been furiously debat ing whether the early fruits of Venter's technique-more than 2,700 gene frag ments-can or should be patented by the National Institutes of Health. The dispute is not likely to be re solved soon. Although the U.S. Patent and Trademark Office may issue a pre lirrllnary decision as early as this sum mer on whether the sequences are pat entable, appeals could grind on for years. Meanwhile Louis W. Sullivan, sec retary of Health and Human Services, is formally faced with determining wheth er the
Nlli
will continue to press its pat
ent claims. That question is also being
]. CRAIG VENTER with DNA sequencing machine, one of seven in his laboratory that are tagging human genes. Photo: Randy Santos/Randolph Photography.
aired in interagency discussions coor dinated by the president's science ad
him: Venter's laboratory, equipped with
(IBA) and the Assodation of Biotechnol
The controversy began in October
seven automatic sequencing machines
ogy Companies, initially supported the
1991, after the Nlli applied for patents on 347 pieces of DNA isolated and se
and three robots, is now tagging 150
Nlli But a committee of sdentific ad
genes a day. According to one estimate,
visers to the Human Genome Project
viser, D. Allan Bromley.
.
quenced by Venter. A follow-up appli
Venter's laboratory alone could triple
opposed the
cation in February of this year covered
the work load of the Patent and Trade
American Society for Human Genetics.
another 2, 375 fragments. Each frag
mark Office's biotechnology section.
Nlli
action, as did the
"There is no question that the patent
The initial decision to apply for pat
ing of ESTs . . . will precipitate a race to
sequence tag (EST), contains about 400
ents on Venter's sequences was made
isolate ESTs in many countries," the
base pairs of DNA corresponding to
by Reid G. Adler, the
sodety said in a position paper. "It is
part of a gene that is expressed in hu
technology transfer. Adler realized that
virtually certain that under such con
man brain cells. Venter identified the sequences in commercially available
the sequences would not be patentable
ditions the information would not be
if Venter published them without first
shared between competing groups."
collections of human genes. By searching through computer data
laying claim in the form of a patent ap
Says David Botstein, professor of ge
plication. If nobody could patent the
netics at Stanford University: "A cata
bases to see whether an EST corre
ESTs, Adler reasoned, drug companies
logue of sequences that says 'Kilroy
sponds to a known gene, Venter can
would have little incentive to develop
was here' is of modest value."
ment, which Venter calls an expressed
Nlli'S
director of
guess what kind of gene some of his
products based on them. The Nlli opt
James D. Watson, the co-discoverer
ESTs might correspond to. But Venter
ed to rescue the situation by filing for
of the double helical structure of DNA
knows nothing about most of his ESTs except their sequence. Even so, he esti
patents so it could license the corre
and until recently head of the National
sponding genes and possibly their pro
Center for Human Genome Research at
teins to U.S. companies. Both Adler and
the Nlli
Nlli director Bernadine Healy have re
and publicly disagreed with Healy over
human genes for less than $10 million,
peatedly asserted that the filing was a
the dedsion to file for patents. Watson
far less than the several billion dollars the international human genome pro
defensive move. "We're not in this to make money," Adler insists.
angrily resigned the post in April.
gram is planning to spend to map and sequence the entire genome. Few doubt
The principal U.S. trade organizations, the Industrial Biotechnology Assodation
have also begun tilting toward oppos
mates that his technique could be used to map and partially sequence most
106
SCIENTIFIC AMERICAN July 1992 © 1992 SCIENTIFIC AMERICAN, INC
,
criticized Venter's approach
Recently biotechnology companies ing the
Nlli
claims, according to Lisa ].
KEEPING YOU CURRENT IN TODAY'S CHANGING WORLD
The Eagerly Awaited Revision of a Groundbreaking Book
MOLECULAR CELL BIOLOGY Second Edition
James Darnell, Harvey Lodish, and David Baltimore A Scientific American Book The most authoritative, comprehensive guide to the molecular biology of the cell, MOLECULAR CELL BIOLOGY is the only book to fully present modern techniques and findings and tie these developments to basic principles.
Thoroughly updated to cover the latest advances and fully revised for greater accessibility and convenience, MOLECULAR CELL BIOLOGY is an ideal reference. The Second Edition features a brand new full color art program that adds a wealth of visual detail. Don't miss it!
Order your copy today and save 20%! 1105
pages,
1095
illustrations,
hardbound. Your satisfaction matters!
BIOCHEMISTRY,
Return any book in good condition within 15 days of receipt and we'll send you a prompt refund.
Third Edition
Lubert Stryer
"Destined to remain one of the 'bibles' of our subject for many years to come. "- Trends in Biochemical Sciences The world's leading biochemistry book is an indispensable desk reference for anyone in the biochemical sciences.
1988, 1098 pages, 1476 illustrations, hardbound
To order, mail this coupon or a copy to: W. H. Freeman and Company 4419 West 1980 South Salt Lake City, UT 84104 D I enclose my check or money order made payable to W. H. Freeman and Company. D Please use my: DVisaDMasterCard Exp. Date_________ Account # _________
AN INTRODUCTION TO GENETIC ANALYSIS
Signature
F. Griffiths, H. Miller, and Richard C. Lewontin
David T. Suzuki, Anthony J. Jeffrey
---;: I C,,=:: ,, d::t;:i = ":::i ,d-=o:::i ,d=",:-Cm=u=,, Lb:C < ,=;g=n,"'d):-
Name______________
Fourth Edition
Address___________ City/State/Zip, _________
Title
This profusely illustrated book is an accessible intro duction to the principles, methods, and findings of
Molecular Cell
Author Darnell et at
genetic analysis. Including all recent advances, it pre
BioIOOY, 21e
sents balanced coverage of classical and modern genetics.
Biochemistry ,lie Siryer
1989, 768 pages, 831 illustrations, hardbound
Intra to Genetic
Suruki
et a!.
Analysis.4/e
I.
W. H. Freeman and Company The book publishing ann of ScI8nlfflc AmerIcan © 1992 SCIENTIFIC AMERICAN, INC
ISBN
Price
1981·1
$45.99'
184J.X
$56.95
1956-6
$46.95
Total
Subtotal (Add $1.95 for shipping & handling of first book, $1.25 for each additional book.) Sales Tax (NY, CA, UT) TOTAL •
Darnell. et al. regular price
$56.95
# For Canadian residents add $2.25 for postage and handling. $1.50 each additional book. Please allow four weeks for delivery. All orders should be prepaid in US dollars.
4917
Raines, vice president of government affairs at the rnA. "A typical biotechnol ogy patent on a gene is the result of 300 person-years of work," Raines says. "These claims are based on an average of 20 person-minutes of work. Many companies question whether the NIH should have the right to license what is really no more than a research tool." Some companies fear that if the NIH receives its patents and licenses the genes to companies, it could invoke a clause that any products developed with them are "reasonably priced." (The AIDS drug dideoxyinosine, or ddI, which the NIH licenses to Bristol-Myers Squibb, is subject to such a restriction, Raines notes.) Small companies are worried about having to search through thou sands of patented EST sequences to see whether a gene has been tagged by the NIH And licensing could be a night mare if different ESTs from the same gene have been claimed by different re searchers or countries. Raines emphasizes that rnA members think the crucial question is whether a gene of unknown function can be pat ented. A patentable invention has to be useful and novel, as well as not obvi ous. The requirements are roughly simi lar in other countries. Venter's technique is based on procedures well known to molecular biologists, raiSing questions about its nonobviousness. And it is far .
�
from clear whether ESTs have any uses other than as tools for more research. Adler argues that the ESTs can be used as markers to find genes. But some pat ent lawyers are not sure. On the other side of the coin, rnA members worry that if the U.S. does not patent but other countries do, U.S. companies could be locked out. Norton D. Zinder, a biologist at the Rockefeller University and former head of the board of science advisers to the genome proj ect, derisively calls the NIH filing "pre emptive patenting" and points out that a "gene race" is already under way. Workers in Britain, France and japan, he says, are churning out ESTs as fast as or faster than Venter is. Indeed, the British Medical Research Council was to file for patents on some 4,000 ESTs in May and was keeping the sequences secret until it did so. Zinder also points out that jonathan Marc Rothberg of Yale University has discovered that some of Venter's ESTs contain parts of the commercial molec ular systems used to copy them. That provides further evidence that "every thing is not being done SCientifically," Zinder says. Venter counters that such errors are an insignificant result of pub lishing the data as quickly as possible. And he contends there would be a race to tag genes whether ESTs are patent able or not.
British officials say they, too, are only filing defensively: they are seeking an international understanding on when DNA sequences can be patented. "It's the prevailing view that it is inappro priate to receive patents on sequences of unknown utility," says David Owen of the British Medical Research Coun cil. Owen says Britain, like most Eu ropean countries, supports a "patent bonfire" for ESTs. The rnA also sees a possible solution in an international agreement that would make sequences of unknown function unpatentable. Ac cording to Raines, the NIH might be able to fulfill its legal obligation to commer cialize its discoveries without taking out patents. The NIH was scheduled to partici pate in late May in a public meeting on its patent claims. Other countries, including Britain, were considering us ing the occasion to urge the NIH to withdraw. And in May,> Healy gave a hint that the NIH may ee ready to lis ten, provided other countries agree to play along. All eyes are now on japan, which has been keeping its options open. But the public meeting might, Healy said, lead to a decision to put a hold on a third large patent filing planned for june. For his part, Venter would be "delighted" if an agreement made gene fragments Tim Beardsley unpatentable. -
u.s. Semiconductor Toolmakers Regain Ground
er an excruciating slide in market share, the U.S.
last year in japan. Sales were up in their home market as
companies that make equipment for manufactur
well, reversing the steady erosion that has been taking
ing semiconductor memory and integrated circuit
place. "Americans now seem more willing to buy Ameri
chips are inching back. According to the San jose-based
can eqUipment," declares jerry Hutcheson, chief executive
consulting firm VLSI Research, the U.S. toolmakers in
officer of VLSI Research.
creased their worldwide market share by about 3 percent
Hutcheson attributes much of the equipment makers' comeback to the support extended to the industry by Se
last year-the first increase in a decade. The U.S. gains came in spite of a tough year for chip
matech, the semiconductor manufacturing research con
machine makers worldwide. Total purchases of semicon
sortium sponsored jointly by industry and government. "I
ductor manufacturing equipment dipped from $10.2 bil
don't see anything else out there that would have caused
lion in 1990 to $9.9 billion. Only U.s. toolmakers posted a
the increase," he says.
gain; japanese manufacturers as well as other producers suffered losses.
tinued funding is up for debate in Washington. When Se
That assessment can only help Sematech, whose con
Until last year, the story of U.S. makers of such equip
matech was established in 1987, the U.S. government
ment as chemical-vapor deposition and optical lithogra phy tools was one of decline. In 1981 U.S. producers con
promised to carry half of its annual $200-million budget;
trolled more than 73 percent of the international market
five-year honeymoon over, Sematech, like any other pro
for semiconductor manufacturing equipment. That share
gram, must now cajole the government for support.
industry provided the remaining half of the tab. With the
had slipped below 43 percent by 1990. After the 1991
In its fiscal 1993 budget proposals, the administration
gains, however, U.S. and japanese chip toolmakers may
leaned toward shaving its contributions to Sematech, of
be standing head to head. Half the top 10 firms in the in
fering only $80 million. Not surprisingly, Sematech is ask
dustry are based in japan; the other half are in the U.S.
ing for an increase above its previous allowance. Con
Those who read the tea leaves of the semiconductor
gress aims to resolve this and all other funding squabbles
trade found last year's results particularly heartening be cause sales of U.S. producers rose both at home and
before the fiscal year begins on October 1. According
abroad. U.S. firms won more than two thirds of their gains
to keep Sematech's budget intact.
108
to congressional aides, the legislators seem inclined to try
SCIENTIFIC AMERICAN July 1992 © 1992 SCIENTIFIC AMERICAN, INC
-Elizabeth Corcoran
Piecemeal Patents The U.S. reconsiders patents on DNA fragments
W
hen]. Craig Venter, chief of re ceptor biochemistry and mo lecular biology at the Nation
al Institute of Neurological Disorders and Stroke, developed a rapid, inexpen sive technique for labeling genes, he expected to advance genetics, not gen erate a major controversy. But for the past nine months, scientists, lawyers and representatives of the biotechnolo gy industry have been furiously debat ing whether the early fruits of Venter's technique-more than 2,700 gene frag ments-can or should be patented by the National Institutes of Health. The dispute is not likely to be re solved soon. Although the U.S. Patent and Trademark Office may issue a pre lirrllnary decision as early as this sum mer on whether the sequences are pat entable, appeals could grind on for years. Meanwhile Louis W. Sullivan, sec retary of Health and Human Services, is formally faced with determining wheth er the
Nlli
will continue to press its pat
ent claims. That question is also being
]. CRAIG VENTER with DNA sequencing machine, one of seven in his laboratory that are tagging human genes. Photo: Randy Santos/Randolph Photography.
aired in interagency discussions coor dinated by the president's science ad
him: Venter's laboratory, equipped with
(IBA) and the Assodation of Biotechnol
The controversy began in October
seven automatic sequencing machines
ogy Companies, initially supported the
1991, after the Nlli applied for patents on 347 pieces of DNA isolated and se
and three robots, is now tagging 150
Nlli But a committee of sdentific ad
genes a day. According to one estimate,
visers to the Human Genome Project
viser, D. Allan Bromley.
.
quenced by Venter. A follow-up appli
Venter's laboratory alone could triple
opposed the
cation in February of this year covered
the work load of the Patent and Trade
American Society for Human Genetics.
another 2, 375 fragments. Each frag
mark Office's biotechnology section.
Nlli
action, as did the
"There is no question that the patent
The initial decision to apply for pat
ing of ESTs . . . will precipitate a race to
sequence tag (EST), contains about 400
ents on Venter's sequences was made
isolate ESTs in many countries," the
base pairs of DNA corresponding to
by Reid G. Adler, the
sodety said in a position paper. "It is
part of a gene that is expressed in hu
technology transfer. Adler realized that
virtually certain that under such con
man brain cells. Venter identified the sequences in commercially available
the sequences would not be patentable
ditions the information would not be
if Venter published them without first
shared between competing groups."
collections of human genes. By searching through computer data
laying claim in the form of a patent ap
Says David Botstein, professor of ge
plication. If nobody could patent the
netics at Stanford University: "A cata
bases to see whether an EST corre
ESTs, Adler reasoned, drug companies
logue of sequences that says 'Kilroy
sponds to a known gene, Venter can
would have little incentive to develop
was here' is of modest value."
ment, which Venter calls an expressed
Nlli'S
director of
guess what kind of gene some of his
products based on them. The Nlli opt
James D. Watson, the co-discoverer
ESTs might correspond to. But Venter
ed to rescue the situation by filing for
of the double helical structure of DNA
knows nothing about most of his ESTs except their sequence. Even so, he esti
patents so it could license the corre
and until recently head of the National
sponding genes and possibly their pro
Center for Human Genome Research at
teins to U.S. companies. Both Adler and
the Nlli
Nlli director Bernadine Healy have re
and publicly disagreed with Healy over
human genes for less than $10 million,
peatedly asserted that the filing was a
the dedsion to file for patents. Watson
far less than the several billion dollars the international human genome pro
defensive move. "We're not in this to make money," Adler insists.
angrily resigned the post in April.
gram is planning to spend to map and sequence the entire genome. Few doubt
The principal U.S. trade organizations, the Industrial Biotechnology Assodation
have also begun tilting toward oppos
mates that his technique could be used to map and partially sequence most
106
SCIENTIFIC AMERICAN July 1992 © 1992 SCIENTIFIC AMERICAN, INC
,
criticized Venter's approach
Recently biotechnology companies ing the
Nlli
claims, according to Lisa ].
KEEPING YOU CURRENT IN TODAY'S CHANGING WORLD
The Eagerly Awaited Revision of a Groundbreaking Book
MOLECULAR CELL BIOLOGY Second Edition
James Darnell, Harvey Lodish, and David Baltimore A Scientific American Book The most authoritative, comprehensive guide to the molecular biology of the cell, MOLECULAR CELL BIOLOGY is the only book to fully present modern techniques and findings and tie these developments to basic principles.
Thoroughly updated to cover the latest advances and fully revised for greater accessibility and convenience, MOLECULAR CELL BIOLOGY is an ideal reference. The Second Edition features a brand new full color art program that adds a wealth of visual detail. Don't miss it!
Order your copy today and save 20%! 1105
pages,
1095
illustrations,
hardbound. Your satisfaction matters!
BIOCHEMISTRY,
Return any book in good condition within 15 days of receipt and we'll send you a prompt refund.
Third Edition
Lubert Stryer
"Destined to remain one of the 'bibles' of our subject for many years to come. "- Trends in Biochemical Sciences The world's leading biochemistry book is an indispensable desk reference for anyone in the biochemical sciences.
1988, 1098 pages, 1476 illustrations, hardbound
To order, mail this coupon or a copy to: W. H. Freeman and Company 4419 West 1980 South Salt Lake City, UT 84104 D I enclose my check or money order made payable to W. H. Freeman and Company. D Please use my: DVisaDMasterCard Exp. Date_________ Account # _________
AN INTRODUCTION TO GENETIC ANALYSIS
Signature
F. Griffiths, H. Miller, and Richard C. Lewontin
David T. Suzuki, Anthony J. Jeffrey
---;: I C,,=:: ,, d::t;:i = ":::i ,d-=o:::i ,d=",:-Cm=u=,, Lb:C < ,=;g=n,"'d):-
Name______________
Fourth Edition
Address___________ City/State/Zip, _________
Title
This profusely illustrated book is an accessible intro duction to the principles, methods, and findings of
Molecular Cell
Author Darnell et at
genetic analysis. Including all recent advances, it pre
BioIOOY, 21e
sents balanced coverage of classical and modern genetics.
Biochemistry ,lie Siryer
1989, 768 pages, 831 illustrations, hardbound
Intra to Genetic
Suruki
et a!.
Analysis.4/e
I.
W. H. Freeman and Company The book publishing ann of ScI8nlfflc AmerIcan © 1992 SCIENTIFIC AMERICAN, INC
ISBN
Price
1981·1
$45.99'
184J.X
$56.95
1956-6
$46.95
Total
Subtotal (Add $1.95 for shipping & handling of first book, $1.25 for each additional book.) Sales Tax (NY, CA, UT) TOTAL •
Darnell. et al. regular price
$56.95
# For Canadian residents add $2.25 for postage and handling. $1.50 each additional book. Please allow four weeks for delivery. All orders should be prepaid in US dollars.
4917
Raines, vice president of government affairs at the rnA. "A typical biotechnol ogy patent on a gene is the result of 300 person-years of work," Raines says. "These claims are based on an average of 20 person-minutes of work. Many companies question whether the NIH should have the right to license what is really no more than a research tool." Some companies fear that if the NIH receives its patents and licenses the genes to companies, it could invoke a clause that any products developed with them are "reasonably priced." (The AIDS drug dideoxyinosine, or ddI, which the NIH licenses to Bristol-Myers Squibb, is subject to such a restriction, Raines notes.) Small companies are worried about having to search through thou sands of patented EST sequences to see whether a gene has been tagged by the NIH And licensing could be a night mare if different ESTs from the same gene have been claimed by different re searchers or countries. Raines emphasizes that rnA members think the crucial question is whether a gene of unknown function can be pat ented. A patentable invention has to be useful and novel, as well as not obvi ous. The requirements are roughly simi lar in other countries. Venter's technique is based on procedures well known to molecular biologists, raiSing questions about its nonobviousness. And it is far .
�
from clear whether ESTs have any uses other than as tools for more research. Adler argues that the ESTs can be used as markers to find genes. But some pat ent lawyers are not sure. On the other side of the coin, rnA members worry that if the U.S. does not patent but other countries do, U.S. companies could be locked out. Norton D. Zinder, a biologist at the Rockefeller University and former head of the board of science advisers to the genome proj ect, derisively calls the NIH filing "pre emptive patenting" and points out that a "gene race" is already under way. Workers in Britain, France and japan, he says, are churning out ESTs as fast as or faster than Venter is. Indeed, the British Medical Research Council was to file for patents on some 4,000 ESTs in May and was keeping the sequences secret until it did so. Zinder also points out that jonathan Marc Rothberg of Yale University has discovered that some of Venter's ESTs contain parts of the commercial molec ular systems used to copy them. That provides further evidence that "every thing is not being done SCientifically," Zinder says. Venter counters that such errors are an insignificant result of pub lishing the data as quickly as possible. And he contends there would be a race to tag genes whether ESTs are patent able or not.
British officials say they, too, are only filing defensively: they are seeking an international understanding on when DNA sequences can be patented. "It's the prevailing view that it is inappro priate to receive patents on sequences of unknown utility," says David Owen of the British Medical Research Coun cil. Owen says Britain, like most Eu ropean countries, supports a "patent bonfire" for ESTs. The rnA also sees a possible solution in an international agreement that would make sequences of unknown function unpatentable. Ac cording to Raines, the NIH might be able to fulfill its legal obligation to commer cialize its discoveries without taking out patents. The NIH was scheduled to partici pate in late May in a public meeting on its patent claims. Other countries, including Britain, were considering us ing the occasion to urge the NIH to withdraw. And in May,> Healy gave a hint that the NIH may ee ready to lis ten, provided other countries agree to play along. All eyes are now on japan, which has been keeping its options open. But the public meeting might, Healy said, lead to a decision to put a hold on a third large patent filing planned for june. For his part, Venter would be "delighted" if an agreement made gene fragments Tim Beardsley unpatentable. -
u.s. Semiconductor Toolmakers Regain Ground
er an excruciating slide in market share, the U.S.
last year in japan. Sales were up in their home market as
companies that make equipment for manufactur
well, reversing the steady erosion that has been taking
ing semiconductor memory and integrated circuit
place. "Americans now seem more willing to buy Ameri
chips are inching back. According to the San jose-based
can eqUipment," declares jerry Hutcheson, chief executive
consulting firm VLSI Research, the U.S. toolmakers in
officer of VLSI Research.
creased their worldwide market share by about 3 percent
Hutcheson attributes much of the equipment makers' comeback to the support extended to the industry by Se
last year-the first increase in a decade. The U.S. gains came in spite of a tough year for chip
matech, the semiconductor manufacturing research con
machine makers worldwide. Total purchases of semicon
sortium sponsored jointly by industry and government. "I
ductor manufacturing equipment dipped from $10.2 bil
don't see anything else out there that would have caused
lion in 1990 to $9.9 billion. Only U.s. toolmakers posted a
the increase," he says.
gain; japanese manufacturers as well as other producers suffered losses.
tinued funding is up for debate in Washington. When Se
That assessment can only help Sematech, whose con
Until last year, the story of U.S. makers of such equip
matech was established in 1987, the U.S. government
ment as chemical-vapor deposition and optical lithogra phy tools was one of decline. In 1981 U.S. producers con
promised to carry half of its annual $200-million budget;
trolled more than 73 percent of the international market
five-year honeymoon over, Sematech, like any other pro
for semiconductor manufacturing equipment. That share
gram, must now cajole the government for support.
industry provided the remaining half of the tab. With the
had slipped below 43 percent by 1990. After the 1991
In its fiscal 1993 budget proposals, the administration
gains, however, U.S. and japanese chip toolmakers may
leaned toward shaving its contributions to Sematech, of
be standing head to head. Half the top 10 firms in the in
fering only $80 million. Not surprisingly, Sematech is ask
dustry are based in japan; the other half are in the U.S.
ing for an increase above its previous allowance. Con
Those who read the tea leaves of the semiconductor
gress aims to resolve this and all other funding squabbles
trade found last year's results particularly heartening be cause sales of U.S. producers rose both at home and
before the fiscal year begins on October 1. According
abroad. U.S. firms won more than two thirds of their gains
to keep Sematech's budget intact.
108
to congressional aides, the legislators seem inclined to try
SCIENTIFIC AMERICAN July 1992 © 1992 SCIENTIFIC AMERICAN, INC
-Elizabeth Corcoran
