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OCR for page 162
7
Intellectual Property and Access to
Research Tools and Data
Scientific research often leads to the generation of intellectual prop-
erty a term used to refer to a wide range of rights associated with
inventions, discoveries, writings, product designs, and other cre-
ative works (Eisenberg, 1997~. In recent years, the assignment and use of
intellectual property rights have become more common in biomedical
research, in some cases generating considerable controversy in the pro-
cess. Patents in particular have been a recurrent cause for debate because
of their potential effects on the dissemination and use of new knowledge,
and thus on the progress of science. This issue may be especially salient
for large-scale, collaborative projects that generate research tools1 and
products that may be useful to a large number of scientists in the field.
Intellectual property issues may also be especially contentious for large-
scale projects because providing a few scientists or institutions with very
large amounts of money to conduct a large-scale project and then also
rewarding them with many revenue-generating patents on the products
of the research could be viewed as unfair.
The patent system is intended to promote innovation by rewarding
inventors with the right to exclude others from using the invention in ex-
1 The term "research tool" is defined as any discovery or invention that can facilitate or be
used in subsequent research, including such things as reagents, devices, and databases.
However, this term is not found in patent law, and no legal consequences arise from desig-
nating a particular discovery as a research tool.
162
OCR for page 163
INTELLECTUAL PROPERTY ID ACCESS TO RESEARCH TOOLS AND DATA 163
change for an "enabling disclosure"2 of the invention. (For definitions of
terms associated with intellectual property, see Box 7-1~. For the system to
be successful, patents must restrict rights to products that are valuable and
unlikely to be obtained by other means. This can be accomplished through
the imposition of threshold requirements, such as novelty and utility.
Patents are generally thought to promote technological progress in
two ways: by providing an economic incentive to devise new inventions
and develop them into commercial products, and by promoting disclo-
sure of new inventions to the public (Eisenberg, 1997~. In the absence of
patents, competitive forces encourage inventors to protect their ideas by
keeping their inventions secret. Such an environment can lead to duplica-
tion of effort and reinvention because scientists are not aware of the ad-
vances of competitors. In contrast, if patent protection is available, scien-
tists may learn more easily of advances in the field, allowing them to
focus their energies on developing a subsequent invention (Thorner, 1997~.
However, scientists may have incentives for both withholding and dis-
closing research results (see Box 7-2), and disclosure need not necessarily
take the form of a patent. The traditional method of scientific disclosure in
the academic world has been simply through publication in peer-reviewed
journals, rather than through patents.
Numerous developments over the last two decades including in-
creased commercial interest in the field and changes in federal policy to
encourage patenting the results of government-sponsored research have
contributed to the increasing significance of intellectual property in bio-
medical research (National Research Council, 1997~. In 1980, in an effort
to promote commercial development of new technologies initiated by
small businesses and nonprofit organizations, Congress passed legisla-
tion that uniformly3 encouraged patenting of discoveries arising from
federally supported research and promoted their commercial utilization
(see Box 7-3~. Although the Bayh-Dole Act targeted primarily small busi-
nesses rather than universities, the number of university-based patents
has since increased greatly. The largest portion of the increase in univer-
sity patenting has been in the biomedical sciences (National Research
Council, 1997~.
2 Until 1999, when Congress amended the Patent Law, U.S. patent applications were not
published. Disclosure, through publication of the patent, occurred only after the patent had
been granted. In 1999, Congress passed an amendment to the U.S. Patent Law requiring the
publication of most patent applications 18 months after filing, similar to the long-standing
requirement abroad.
3 Previously, universities could use Institutional Patent Agreements to take title of intel-
lectual property generated with federal funding. However, agreements had to be negoti-
ated on a case-by-case basis, and they varied across federal agencies. The new legislation
established a uniform policy across federal agencies.
OCR for page 164
164
LARGE-SCALE BIOMEDICAL SCIENCE
Prior to 1980, the federal government sponsored primarily basic or
"upstream" research, and broad, unpatented dissemination of results in the
public domain was the norm for universities (Heller and Eisenberg, 1998~.
Fewer than 250 U.S. patents were issued to universities each year.4 As a
result, patents belonged almost exclusively to industry, where scientists
4 See .
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INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 165
and engineers were doing product-oriented "applied" research. Most pat-
ented innovations were incorporated into finished or near-market products
and processes, because only then were they considered to be worth the
costs associated with obtaining and protecting a patent. The new legisla-
tion, combined with the advent of biotechnology, has been a factor in chang-
ing this scenario and has contributed to a blurring of traditional distinctions
between basic and applied research. Nonprofit institutions are now much
more likely to patent their discoveries. In recent years, U.S, patents being
issued to universities have exceeded 3,000 per year, with more than 3,7005
issued to Universities in the year 2000 (Pressman, 2002~. Nonprofit institu-
tions now often pursue avenues of research that are similar to those in
private industry, and research collaborations between industry and aca-
demic institutions are now widespread as well. Furthermore, many bio-
technology companies have their origins in university-based research
(Ducor, 1997~. In fact, commercial biotechnology firms have attempted to
fill a niche in research and development somewhere between the tradi-
tional basic science of academic laboratories and the targeted product de-
velopment of pharmaceutical firms (Heller and Eisenberg, 1998~.
The privatization of upstream biomedical research has led to intellec-
tual property claims on research results that, in an earlier era, would have
been made freely available in the public domain (Heller and Eisenberg,
1998~. Indeed, many biotechnology patents are considered research tools
rather than traditional end products, since they are useful primarily for
5 This total, representing 2.4 percent of all utility patents issued in the year 2000, is the
aggregate figure for 190 institutions.
OCR for page 166
166
LARGE-SCALE BIOMEDICAL SCIENCE
further scientific research. Most large-scale research projects, as defined
in this report, also produce research tools. The term "research tool" is not
found in patent law, and no legal consequences arise from designating a
particular discovery as a research tool; nonetheless, some patents that fall
into this category have been the most contentious with regard to their
impact on the progress of science. But the key question relates to access to
the research tools, rather than to whether the tools should be patented or
not. There are many different ways to transfer patented technologies to
other institutions, and the methods chosen can have a significant impact
on the availability of research tools. A research project may require access
to many research tools, and the costs and administrative burden can
OCR for page 167
INTELLECTUAL PROPERTY ID ACCESS TO RESEARCH TOOLS AND DATA 167
mount quickly if it is necessary for researchers to negotiate separate li-
censes for each of these tools.
NONEXCLUSIVE AND EXCLUSIVE LICENSING
There has been considerable debate over the strategies used by NIH
and universities to disseminate patented technologies developed with
federal funds. Ultimately, the value of a research tool is likely to be great-
est when it is widely available to all researchers who can use it, but there
is no universal agreement as to how broad dissemination is best achieved.
Once a research tool has been patented, there is a wide spectrum of op-
tions for exercising the intellectual property rights associated with that
patent. At one extreme is no protection of the patent, in which no effort is
made to prevent infringement. In essence, such a strategy makes the dis-
covery freely available to anyone, but precludes others from restricting
access through a patent of their own. More commonly, patented research
tools are licensed to another party for use in research or product develop-
ment, or for purposes of sublicensing to others. A license may be exclu-
sive with a single company or nonexclusive, in which case anyone willing
to negotiate a contract may have access to the technology (see Box 7-1~. At
many major universities, it is now common for industry-sponsored re-
search agreements to stipulate that while ownership of any resulting pat-
ents will be retained by the university, the sponsoring company will have
a first option to an exclusive license. And with the increase in university-
industry partnerships, this approach applies to more research than in the
past years (Ducor, 1997~. Although the Bayh-Dole Act does not specify a
preference for either exclusive or nonexclusive licenses, it does mandate a
preference for licensing to small firms. But because small companies, es-
pecially start-up businesses, may depend on exclusive rights to establish
a competitive advantage and ensure access to high-risk capital, the law
may indirectly encourage universities to grant exclusive licenses (Henry
et al., 2002~. However, many scholars have suggested that nonexclusive
licenses are more effective in ensuring the development and broad use of
. .
new c discoveries.
Examples exist to support both sides of the debate. The Cohen-Boyer
patent on basic recombinant DNA technology is an early example of a
nonexclusive licensing policy that led to modest pricing and wide distri-
bution of the technology. The decision to negotiate a nonexclusive license
was critical to the industry, as this technology has contributed enormously
to subsequent development of commercial biotechnology (National Re-
search Council, 1997; U.S. Patent and Trademark Office, 2000~. On the
other hand, the technology for DNA sequencing instruments developed
and patented at Caltech was licensed exclusively to Applied Biosystems
OCR for page 168
168
LARGE-SCALE BIOMEDICAL SCIENCE
Incorporated (ABI) at the company's insistence. The technology has since
been broadly disseminated and is widely available to researchers, usually
through core facilities at universities. ABI is currently the leader in the
world market for DNA sequencers, but other companies still have impor-
tant market shares (National Research Council, 1997~.
One case in which an exclusive license has been widely criticized for
restricting the use of a common research tool is that of the patented
"oncomouse" (National Research Council, 1994b; Institute of Medicine,
1996; Marshall, 2002a). In the 1980s, Philip Leder and his colleagues at
Harvard developed a transgenic mouse that overexpressed the oncogene
c-myc and was thus prone to developing cancer. Harvard has been
granted three related patents on this oncomouse, and all three have
been licensed exclusively to DuPont. The first patent, granted in 1988,
claims rights to all transgenic animals predisposed to cancer. Thus, any
scientist studying a transgenic animal that is prone to cancer must ob-
tain a license from DuPont for permission to use it, regardless of who
created the particular transgenic mouse line or what cancer-related gene
was altered in its germline.
In 2000, NIH brokered an agreement with DuPont in which the com-
pany agreed to provide a "free research license" to any NIH scientist or
NIH grantee doing noncommercial studies with an oncomouse. How-
ever, scientists and their institutions must agree to the terms of the con-
tract, which stipulate reach-through license agreements on the resultant
downstream research (see the next section of this chapter). Anyone who
wants to use an oncomouse in drug screening must obtain a commercial
license and pay a considerable fee.
Some academic institutions have refused to sign a contract with
DuPont, and many have suggested that the broad claims of the patent
would not survive a court challenge; however, universities are reluctant
to pursue costly litigation (Marshall, 2002a). The patents have already
withstood legal challenges in Europe and Japan, but the Canadian Su-
preme Court recently ruled that the oncomouse is unpatentable in Canada.
Restricting the use of trans~enic mice could Neatly impede cancer
- ~ - - --- - - - -I- - -- --- - ~ -- - J r -- - -- --
research because such mice serve as basic research tools and models for
human cancer and can also be used to screen for or test new therapeutics.
Thus, DuPont's aggressive enforcement of the oncomouse patents could
be an obstacle to achieving the goals of NCI's Mouse Models of Human
Cancer Consortium (described in Chapter 3~.
A recent survey of U.S. institutions holding gene sequence patents
showed that companies and nonprofit organizations tend to favor differ-
ent strategies for licensing their discoveries (Henry et al., 2002), perhaps
reflecting different goals or stages of product development. For example,
companies may have more end-stage products for which a nonexclusive
OCR for page 169
INTELLECTUAL PROPERTY ID ACCESS TO RESEARCH TOOLS AND DATA 169
license would generate the most revenue, while nonprofits may have
more upstream products. Whatever the reason, private firms reported
that an average of 27 percent of all licenses granted were exclusive, while
nonprofits reported an average of 68 percent. An earlier survey of aca-
demic technology transfer executives showed that about 50 percent of
licenses granted by universities were exclusive; in contrast only 22 per-
cent of licenses granted by the NIH in 2001 were exclusive (Pressman,
2002).
NIH appears to favor the nonexclusive approach to licensing, given
the set of rules it adopted in 1999 with the intent of promoting greater
sharing of tools and new materials. The guidelines6 for sharing research
tools encompasses four principles:
· Scientists who receive federal funds must avoid agreements that
stifle academic communications.
· Scientists should not seek or agree to exclusive licenses on research
tools (defined as inventions whose "primary usefulness" is "discovery"
and not a product to be approved by the Food and Drug Administration
[FDA]~.
· Academic scientists should "minimize administrative impedi-
ments" on exchanges of materials by refusing "unacceptable conditions"
(such as reach-through provisions).
· Academic institutions should be as flexible in dealing with others
(including companies) as they would have others be with them.
Perhaps not surprisingly, some smaller biotechnology companies, whose
survival may depend on selling such research tools, are not enthusiastic
about these guidelines (Marshall, 1999~.
REACH-THROUGH LICENSE AGREEMENTS
One difficulty in licensing research tools is that the value of the li-
cense is impossible to determine in advance, so it can be difficult to define
mutually agreeable license terms. One of the most contentious issues re-
garding the licensing of patented research tools is the "reach-through"
clause. Reach-through license agreements (RTLAs) give the owner of a
patented invention used in upstream stages of research rights in subse-
quent downstream discoveries. Such rights may take the form of a royalty
on sales that result from use of the upstream research tool, an exclusive or
nonexclusive license on future discoveries, or an option to acquire such a
license. In principle, such agreements could offer advantages to both
patent holders and the scientists who use the patented tools in their re-
6 Guidelines available at .
OCR for page 170
170
LARGE-SCALE BIOMEDICAL SCIENCE
search because they impose an obligation to share profits of successful
research without adding to the costs of unsuccessful research. For ex-
ample, RTLAs could allow scientists with limited funds to use tools and
defer payment until the research yielded valuable results. Patent holders
may also prefer a chance at larger payoffs from sales of downstream
products, rather than certain but smaller up-front fees. In practice, how-
ever, companies fear that RTLAs may lead to stacked, overlapping, and
inconsistent claims on potential downstream products. From their per-
spective, each RTLA royalty obligation becomes a prospective tax on sales
of a new product, and the more research tools are used in developing a
product, the higher the tax burden will be (Heller and Eisenberg, 1998;
Eisenberg, 1997~. RTLAs can also create challenges for universities, as
scientists may find it more difficult to obtain research funding for projects
in which they are entailed.
RESEARCH EXEMPTIONS
One potential way to prevent technology licenses from impeding the
progress of scientific research is an experimental-use license exemption,
or research exemption, for patented research tools. In principle, such an
exemption allows scientists to use research tools without obtaining a li-
cense if the research is purely experimental and is not aimed at develop-
ing a patentable or marketable product. The goal of this exemption is to
facilitate widespread use in subsequent research while preserving the
financial interests of the patent holder. Most European countries and la-
pan have included the principle of research exemption in their patent
statutes, but the U.S. Patent Act has not.7 U.S. courts have recognized a
research exemption in theory, but most court cases have arisen in in-
stances in which the commercial stakes are high, and the exemption is
unlikely to be sustained (Eisenberg, 1997~. Unfortunately, it is difficult to
define experimental use in such a way as to maintain the commercial
value of research tools for the patent holder. According to Eisenberg (1997:
13~:
The problem is that researchers are ordinary consumers of patented re-
search tools, and that if these consumers were exempt from infringe-
ment liability, patent holders would have nowhere else to turn to collect
7 Congress has enacted laws for two specific research use exceptions. The first permits
basic research on an invention during the life of a patent if the research is to develop and
submit information to FDA (the Drug Price Competition and Patent Term Restoration Act,
35 U.S.C., Section 271 leg. The second permits the use and reproduction of a protected plant
variety for plan breeding or other bona fide research (Plant Variety Protection Act, 7 U.S.C.
2321 et seq., Section 2544~.
OCR for page 171
INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 171
patent royalties. Another way of looking at the problem is that one firm's
research tool may be another firm's end product. This is particularly
likely in contemporary molecular biology, in which research is big busi-
ness and there is money to be made by developing and marketing re-
search tools for use by other firms. An excessively broad research ex-
emption could eliminate incentives for private firms to develop and
disseminate new research tools, which could on balance do more harm
than good to the research enterprise.
Furthermore, some industry executives have noted that although in-
dustry previously often gave university research a de facto research ex-
emption, they are now often more reluctant to do so because in many
cases, university researchers are seen as competing directly with their
own research.8 As a result, companies may feel burdened by the require-
ment to license the results of university research that have been patented
(but formerly would have been freely available) when the universities
continue to expect an exemption for use of the companies' patented re-
search tools.
A recent court rulings may also make it more difficult for universities
to a claim research exemption if they are sued for patent infringement. In
ordering a district court to reevaluate its decision in an infringement case
brought against Duke University, a U.S. Court of Appeals for the Federal
Circuit found that the district court had applied an overly broad concept
of the very narrow and strictly limited experimental-use defense
(Ergenzinger and Spruill, 2003~. In ruling against Duke, the appeals court
stated that even if a university is pursuing research "with no commercial
application whatsoever," the institution should not presume that its ac-
tions automatically qualify as an exception to infringement.
Duke had argued that its use of patented laboratory equipment did
not constitute infringement because the equipment was used under the
authority of a government research grant and was covered by an excep-
tion for experimental uses. However, the scientist claiming infringement
offered the counter argument that Duke is in the business of obtaining
grants and developing possible commercial applications for the fruits of
its academic research, and therefore the research exemption should not
apply.
Previous court rulings have established that the experimental-use ex-
ception can be claimed only for actions performed for amusement, to
satisfy idle curiosity, or for strictly philosophical inquiry. The defense
~ Personal communication with Richard Nelson, School of International and Public Af-
fairs, Columbia University.
9 Madey v. Duke University, USCAFC, 01-1567. Decided October 3, 2002.
OCR for page 172
72
LARGE-SCALE BIOMEDICAL SCIENCE
does not apply when the use is undertaken "in the guise of scientific
inquiry" or in furtherance of a party's legitimate business. The new appel-
late ruling states that in the case of a major research university such as
Duke, such business includes research that educates students and faculty
members, attracts additional grants, and helps "increase the status of the
institution and lure lucrative research grants, students, and faculty." Sev-
eral major research universities are now petitioning the Supreme Court to
review the decision because they believe it will hinder research by forcing
scientists to obtain permission before using patented technologies (Mala-
koff, 2003~.
PATENT POOLS
Perhaps a more viable approach to reducing potential licensing ob-
stacles associated with research tools is to establish patent pools. Over the
last 150 years, patent pools have played an important role in shaping
other fields, such as the automobile, aircraft, and telecommunications
industries. These patent pools have emerged, sometimes with the help of
government, when licenses under multiple patent rights have been neces-
sary to develop important new products (Heller and Eisenberg, 1998; U.S.
Patent and Trademark Office, 2000~. A patent pool is an agreement be-
tween two or more patent holders to license their patents to each other or
to third parties. In theory, this type of arrangement can simplify research
and reduce transaction costs by allowing interested parties to gather all
the tools needed to practice with a certain technology in one place ("one-
stop shopping") rather than obtaining licenses from each patent owner
individually (see Box 7-4~. Patent pools can also facilitate information
exchange and the distribution of risks associated with research and devel-
opment. But patent pools can also potentially have detrimental effects
(see Box 7-4~. For example, a patent pool could theoretically shield invalid
patents, eliminate competition, and inflate prices.
Patent pools can also conflict with antitrust laws that were designed
to prevent the creation of monopolies and restraints on interstate com-
merce (U.S. Patent and Trademark Office, 2000~. As a result, the Depart-
ment of Justice evaluated all patent pools prior to the 1960s and created a
list of patent licensing practices that were per se antitrust violations. More
recently, the Department of Justice and the Federal Trade Commission
(FTC) have recognized that patent pools can have significant procom-
petitive effects and may also improve a business' ability to survive in a
time of rapid technological innovation in a global economy. In 1995, the
Department of Justice and the FTC issued Antitrust Guidelines for the
Licensing of Intellectual Property and set forth enforcement policies (see
Box 7-5~. These guidelines can be summarized in two broad questions:
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INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 181
Protein Patents
Analysis of the human genome sequence has led to the conclusion
that the genome may contain significantly fewer genes than the previous
estimate of 100,000. Although current methods for identifying functional
protein coding sequences may underestimate the actual number of genes,
recent estimates suggest that there are fewer than 50,000 (Lander et al.,
2001; Venter et al., 2001~. Nonetheless, researchers speculate that there
may be as many as 2 million different proteins, suggesting that many
variant proteins can be produced from a single gene. The difference be-
tween the two numbers lies in alterations in DNA transcription and RNA
splicing, as well as post-translational modifications of the protein prod-
ucts, all of which can have a profound influence on the function and
activity of the resultant proteins. According to the U.S. Patent and Trade-
mark Office, researchers can make separate patent claims on these variant
proteins even if the parent gene is already patented, as long as the identi-
fied changes lead to new and unclaimed functions and uses. The result
could potentially be a confusing landscape of competing gene and protein
patent claims, perhaps setting the stage for legal battles for control over
further research and development. This may be especially true if a protein
variant shows a stronger correlation with disease than is the case for the
earlier gene that was patented (Service, 2001b). To avoid the possibility of
expensive litigation, companies may find themselves cross-licensing many
related patented discoveries. On the other hand, some companies are
hoping to develop ways of circumventing the claims of genomics compa-
nies that have patent rights for making proteins from patented gene se-
quences in bacteria. For example, GeneProt, a new proteomics firm, plans
to synthesize proteins chemically (Service, 2001a).
Many companies appear to be banking on the patentability and prof-
itability of identifying and characterizing unique protein variants. Doz-
ens of new biotechnology firms have emerged in the past few years either
to conduct large-scale searches for proteins (proteomics) or to sell re-
search tools to those doing the searching. Most pharmaceutical compa-
nies have also launched their own proteomics efforts. All are now racing
to find and patent as many proteins as possible. One of the leading com-
panies intended to file 4,000 patents on proteins whose functions are
known and linked to disease by the end of 2001. Investors also initially
appeared to have confidence in the profitability of this approach. Pro-
teomics companies attracted more than $530 million in venture capital
funds in 2000 and 2001, and stock offerings have raised hundreds of mil-
lions more (Service, 2001c). More recently, however, investment in pro-
teomics companies has declined because of predictions of lower profit-
ability (Warner, 2002~.
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182
LARGE-SCALE BIOMEDICAL SCIENCE
Because of all the competing efforts, many proteomics researchers are
concerned that all the data will be locked up by various private compa-
nies. As a result, there is great interest in undertaking publicly funded
proteomics projects whose results would be deposited and organized in a
freely accessible database. In October 2001, scientific leaders in the field
met with representatives of NIH and other government funding agencies,
as well as proteomics companies, to discuss launching a coordinated ini-
tiative, perhaps modeled after the NIH-funded Alliance for Cell Signaling
(see Chapter 3~. The group recommended pilot projects in three areas-
profiling protein expression in selected tissues, detailing proteins' func-
tions, and creating new bioinformatics tools (Service, 2001c).
Databases
With the recent increase in large-scale biomedical research projects
that generate immense datasets have come concerns about the organiza-
tion and accessibility of databases. To optimize the progress of science,
scientists may have to combine data from a variety of academic and com-
mercial sources, but this data aggregation can present a serious obstacle
for both technical and proprietary reasons. A lack of uniformity or stan-
dardization in quality control can be a serious impediment to combining
data from different sources. Attempts to protect the intellectual property
value of data add additional challenges. Over the past 5 years, both
academic and commercial biologists have attempted to use "pass-
through" rights that place restrictions on data even after they have been
incorporated into other databases. This practice creates opportunities for
gridlock. But biotechnology companies in particular worry about making
a large financial commitment to a project if there is a risk that the under-
lying data could belong to someone else. U.S. companies have resorted to
a sophisticated assortment of strategies to prevent copying, including
contracts, download restrictions, and frequent updates. At the other end
of the spectrum, the "open source code" model that was used to develop
free computer software was discussed as an option for the public data-
bases containing human genome sequences, although that strategy was
ultimately rejected (Sulston and Ferry, 2002~. In such a model, anyone
could freely use the information in the database to conduct research, to
develop products, or to redistribute the information in any form. How-
ever, anyone who did so would not be allowed to place new restrictions
on further development or redistribution of the data.
Intellectual property law in the United States does not cover data-
bases. Recently, however, the concept of database protection has been
discussed frequently, in part as the result of a 1996 directive from the
OCR for page 183
INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 183
European community to its members to create in Europe a new type of
database that restricts use of the information. In fact, several unsuccessful
attempts have been made to pass similar legislation in the United States
since that directive was issued (Maurer et al., 2001~. Although the Euro-
pean approach has been offered as a model to address the complex issues
of database access and use, the legislation is actually unlikely to alter the
strategies currently used to protect databases. In fact, critics have argued
that the European Community directive has eroded the public domain,
overprotected synthetic data of doubtful value (e.g., telephone numbers),
and raised new barriers to data aggregation (Maurer et al., 2001~. The
threshold requirements of the directive have proven to be quite low, and
most lawsuits have been brought by a small number of companies that
create synthetic data, in essence making such data more valuable than
genuine information.
A recent report of the National Research Council (1999) examines
trends in access to scientific databases and makes recommendations for
striking a balance between legitimate rights to protection and open access
for the public good. A symposium hosted by the National Academies in
2002 further examined the potential negative effects of a diminishing pub-
lic domain for scientific data, caused in part by pressures to commercial-
ize and legislative efforts to protect intellectual property rights (Jenkins,
2002b).
Patient Confidentiality and Consent
Many of the theoretical large-scale projects described in chapter 2, as
well as many of the ongoing projects described in chapter 3, entail the
collection and analysis of human samples. As such, these endeavors re-
quire additional considerations with regard to data access and research
on human subjects. There is an inherent tension in biomedical research
between the need to protect the confidentiality of individuals and the
need for access to information in order to make progress in understand-
ing and treating disease. Because the data collected in large-scale projects
are often placed in publicly accessible databases, considerations of pri-
vacy, confidentiality, and informed consent must be taken into account
before, during, and after the study.
A common approach to obtaining informed consent for the use of
human samples in specimen banks is to develop a very general consent
form that will allow future, unspecified research to be conducted without
the need to reacquire consent for every subsequent study. However, such
an approach may come into question if a future project entails such objec-
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184
LARGE-SCALE BIOMEDICAL SCIENCE
fives as genetic analysis with linkage to health information or the inclu-
sion of data in public databases, or even if the samples are shared more
widely within the scientific community than was originally anticipated.
Because of the potential for a breach of privacy and subsequent discrimi-
nation or other repercussions, great care must be taken to protect the
identity of sample donors. The NCI has developed guidelines for protect-
ing the identities of tissue donors while still maintaining links to data on
clinical information, but researchers and their institution are respon-
sible for protecting human subjects in studies carried out under their
purview.
The tremendous concern about patient confidentiality in the United
States is due in part to both hypothetical and actual lapses in the routine
practice of medicine for example, the management of the medical rec-
ords in the ordinary setting of day-to-day hospital business, or the misuse
of patient information by health care insurers. However, recent legisla-
tion aimed at redressing such lapses could also affect researchers' access
to patient samples. Known as HIPAA, or the Health Insurance Portability
and Accountability Act, the legislation contains rules that protect indi-
vidually identifiable health information (Box 7-7~. Because the enforce-
ment of the rules will only begin in April of 2003, the impact of HIPAA on
biomedical research is not yet known, but there is great concern within
the biomedical scientific community.
EFFECTS OF INTELLECTUAL PROPERTY CLAIMS ON THE
SHARING OF DATA AND RESEARCH TOOLS
Although concerns have been raised that intellectual property claims
could inhibit access to data and research tools, little quantitative assess-
ment has been undertaken to determine whether those concerns are valid.
However, a survey of academic life scientists undertaken in 1997 found
that 20 percent of respondents had delayed publication of their research
results by more than 6 months at least once in the last 3 years to allow for
patent application, to protect their scientific lead, to slow the dissemina-
tion of undesired results, to allow time to negotiate a patent, or to resolve
disputes over the ownership of intellectual property (Blumenthal et al.,
1997~. Multivariate analysis indicated that participation in an academic-
industry research relationship and engagement in the commercialization
of university research were significantly associated with delays in publi-
cation. Notably, scientists who reported conducting research on goals
similar to that of the Human Genome Project were also more likely to
~2 .
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INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 185
deny requests for information, data, and materials than were other life
scientists.
More recently, a survey focusing on geneticistsl3 found that among
those who had requested published data, materials, or techniques from
another academician, 47 percent reported that at least one request was
13A stratified sample of 3,000 faculty members was selected. The sample included 219
grantees of the Human Genome Project and 1,547 faculty members in genetics or human
genetics departments. The remainder of the sample (n = 1234) was randomly selected so
that half came from nonclinical departments (n = 617) and half from clinical departments
(n = 617~.
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LARGE-SCALE BIOMEDICAL SCIENCE
deniedl4 (Campbell et al., 2002~. The requests most likely to be denied
were for biomaterials such as mice or viruses (35 percent), followed by
sequence data (28 percent), findings (25 percent), phenotypes (22 per-
cent), and laboratory techniques (16 percent). Figure 7-5 shows the rea-
sons given by geneticists for intentionally withholding from other scien-
tists information, data, or materials concerning their own published
research. A number of respondents reported that such withholding of
data had adverse effects on their ability to reproduce the work of other
investigators, on the timeliness of their own publications, and on their
ability to pursue chosen research directions. These adverse effects on re-
search progress at the individual and field levels were more likely to be
reported by geneticists than by investigators who had experienced such
withholding in other life science fields. Many geneticists indicated that
the situation was having a negative impact on communication within
their field, the education of young scientists, and the rate of scientific
progress.
Even when data are placed into a publicly accessible database, con-
flicts over rights to and use of the data can arise (Marshall, 2002c; Roberts,
2002~. For example, a group of collaborating scientists led by the Marine
Biological Laboratory (MBL) in Woods Hole, Massachusetts, won a 5-
year, $2.6 million award from NIH in 1997 to sequence the genome of a
disease-causing protozoan. Because NIH required rapid availability of
the data, raw sequence data were routinely posted on a public website.
However, the group also posted guidelines that limited database users to
reagent development or mutually agreed-upon projects. When two scien-
tists published a paper that included analysis of data from a variety of
public databases, including the MBL site, the MBL organizers protested
and closed down the website. This is a relatively new issue associated
with large-scale projects that generate databases for use by the scientific
community. Traditionally, scientists are expected to share data and re-
agents following publication, but prior to publishing, scientists have had
discretion in choosing what to share and with whom. However, NIH has
required grantees to release data as soon as they are generated, often well
before publication in peer-reviewed journals. This policy is designed to
speed the pace of research and to allow the field as a whole to benefit
from the large investment made to generate the data, but it clearly raises
new questions regarding the data's use, analysis, and publication.
The advisory committee for the International Nucleotide Sequence
Databases, which includes Genbank, recently endorsed a data sharing
14Respondents estimated that they had made an average of 8.8 requests for information,
data, or materials regarding published research in the previous 3 years, with 10 percent of
those requests being denied.
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INTELLECTUAL PROPERTY ID ACCESS TO RESEARCH TOOLS AND DATA 187
Reasons for denying request for materials or data
Protection of commercial value of results
Protection of patient confidentiality
Requirements of industrial sponsor
Concerns of lack of reciprocation
Cost of transfer
Protection of unpublished work
Protection of students or junior scientists
Effort required for transfer
0 20 40 60 80 100
Percentage saying reason is important
FIGURE 7-5 A survey of geneticists examined the reasons for which requests
for data and materials were denied.
SOURCE: Campbell et al., 2002.
policy that specifically prohibits use or publication restrictions such as
those described above, as well as licensing requirements (Brunak et al.,
2002~. A recent report of the National Research Council (2003) urges sci-
entists, funding agencies, and publishers to adhere to a uniform policy for
sharing data and reagents. Using the acronym UPSIDE (universal prin-
ciple of sharing integral data expeditiously), the report reinforces an
author's obligation to release data and materials quickly to allow others
to verify or replicate published findings. New guidelines for sharing data
are also being developed by NIH. For instance, the agency will expect
investigators to include information in their research applications about
how they plan to share the resultant data or why they are unable to do so
(Spieler, 2002~. But it is not clear how adherence to the guidelines will be
monitored and enforced, or whether they will lead to real changes in
behavior within the scientific community. In principle, NIH has numer-
ous legal authorities available to assist in improving access to research
tools (see Box 7-8~. In practice, however, the exercise of some options may
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INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 189
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LARGE-SCALE BIOMEDICAL SCIENCE
be perceived as extreme, and may have far-reaching and perhaps unpre-
dictable consequences.
Providing funding to cover the costs of sharing materials could per-
haps also facilitate a greater willingness to provide requested materials to
fellow academic scientists (National Research Council, 2003~.
Ultimately, assessing the impact of the increased assertion of intellec-
tual property rights in academia due to the Bayh-Dole Act is difficult
because few data that could be used for this purpose are reported back
(Bar-Shalom and Cook-Deegan, 2002~. A report of the U.S. Department of
Health and Human Services (DHHS) (1994) notes many deficiencies in
NIH's capability for monitoring patents that result from NIH funding.
Consequently, NIH established a database to monitor invention disclo-
sures and patents. Nonetheless, the General Accounting Office and the
DHHS inspector general have since documented that NIH and other fund-
ing agencies still are not being notified of many patented inventions de-
veloped with federal funding (U.S. General Accounting Office, 1999~. The
General Accounting Office is currently conducting an investigation of the
administration, use, and benefits to federal agencies of intellectual prop-
erty derived from federally sponsored research (Aker, 2002~. The Presi-
dent's Council of Advisors on Science and Technology has also been
charged with assessing the benefits and difficulties of the Bayh-Dole Act
with regard to the commercialization of products resulting from federally
funded research, as well as with providing a review of technology trans-
fer mechanisms. After collecting data and soliciting input from various
stakeholders, such as small businesses and venture capital groups, the
council plans to present the Bush Administration with its technology
transfer recommendations in March 2003. Suggestions for major modifi-
cations to the act are not expected, however (Jenkins, 2002a, 2003a).
SUMMARY
Concerns have been raised in recent years about the willingness and
ability of scientists and their institutions to share data, reagents, and other
tools derived from their research. Many factors contribute to these diffi-
culties, including the time and expense of sharing data and materials, the
desire to protect raw or unpublished data and intellectual property, the
incentive to maintain a lead in a particular research area, and the need to
protect patient confidentiality. Since a primary goal of many large-scale
biomedical research projects is to produce data and research tools these
issues are of great importance when planning and conducting such
projects. NIH should facilitate the sharing of data and the distribution of
reagents to the extent feasible, by providing funds for the maintenance
and distribution of reagents produced through large-scale projects, and
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INTELLECTUAL PROPERTY AND ACCESS TO RESEARCH TOOLS AND DATA 1 Al
by promoting broad dissemination of data and research tools generated
with federal funds.
Over the course of the last two decades, the assignment and use of
intellectual property rights have become increasingly common in the bio-
medical sciences. This phenomenon is due largely to changes in federal
policy and legislation aimed at promoting the commercial development
of discoveries made with public funding. There is evidence to suggest
that biomedical patents assigned to academic research institutions are
indeed generating research funds for those institutions and spawning
research activities in the private sector. However, many questions have
been raised regarding the licensing practices used by institutions to trans-
fer their technologies to other institutions, both public and private. A
number of licensing strategies exists for technology transfer, and the strat-
egy chosen could greatly impact the accessibility of new discoveries to the
scientific community. Unfortunately, however, little effort has been de-
voted to studying the impact of licensing practices on the use of patented
biomedical innovations and on the progress of scientific research.
Patents and licensing practices have perhaps been most contentious
for innovations that can be used as research tools for further research.
Even a basic research project may require the use of several patented
research tools, so it can be difficult, expensive, and time-consuming to
acquire licenses for conducting such a project. Because the goal of many
large-scale projects is to produce data and reagents that can be used as
research tools, this issue may be especially salient for large-scale endeav-
ors. NIH has many tools at its disposal to encourage and facilitate easy
access to tools and discoveries derived from federally funded research.
However, a lack of information on and scholarly assessment of licensing
and technology transfer practices may be hindering effective action on the
part of NIH. Thus, a systematic examination of the ways in which licens-
ing practices affect the availability of research tools produced by and used
for large-scale research projects could be extremely useful in formulating
future NIH policies and actions.
Representative terms from entire chapter:
biomedical science
