The Life Sciences Today

The biological sciences have experienced enormous growth over the last century,

fueled by a stream of discoveries — such as the principles of genetics, the structure of

DNA, and the discovery of gene splicing technologies. These have opened new fields of

inquiry and provided the basis for myriad applications in industry, agriculture, and

medicine. Among the technological breakthroughs in the life sciences, genetic

engineering plays a particularly significant role.

Genetic engineering is a technique that permits the artificial modification and

transfer of the genetic material from one organism to another and from one species to

another. This technology is used throughout the world to alter the protein produced by a

gene and to design organisms with desirable traits for applications ranging from basic

research and development activities to pharmaceutical and industrial uses. During the

last 30 years, these recombinant techniques have spawned a vibrant biotechnology

industry focused largely on the development of new pharmaceuticals to fight disease.6

By 2000 the annual investment in the biotechnology industry peaked at nearly $29

billion, while employment in the biotechnology industry reached 191,000 by 2001.7

In response to the opportunities presented by these developments the resources

devoted to the life sciences have increased dramatically, making further discoveries

possible. The government has funded biological research generously through the

National Institutes of Health and National Science Foundation budgets, with few strings

attached; private foundations and the pharmaceutical industry have also made major

contributions. The number of PhDs awarded each year in the biological and agricultural

sciences has increased steadily; 6,526 were awarded in 2001.8

This ever-expanding research activity has resulted in numerous new

biopharmaceutical products that are transforming medicine. Examples include human

recombinant insulin for the treatment of diabetes, a vaccine against hepatitis B, and

medicines for diabetes, cancer therapy, arthritis, multiple sclerosis, cystic fibrosis, heart

attacks, hemophilia, and sepsis. As knowledge of the human genome increases, it may

even become possible to tailor pharmaceutical products not only to specific diseases but

also to specific individuals. Throughout this process, the time between new discoveries

and their applications has grown ever shorter. One example is the very short time it took

the scientific community to identify the coronavirus as the causal agent of the newly

emerging human disease, severe acute respiratory syndrome (SARS).

Biotechnology research is now a truly global enterprise. While industrialized

countries such as the United States, the United Kingdom, Germany, Israel, and Japan

may be the first to develop advanced research and technologies, other countries have a skill base that will enable broad domestic utilization of biological technologies.9 For

example:

China has an aggressive program in plant biotechnology, and as of 2002

plans to increase funding by 400 percent by 2005. This energetic

investment also exists in the Chinese private sector, and the national

scientific establishment is attempting to lure foreign-trained scientists to

return with lucrative financial packages. India is in the process of tripling

funding to its national biotech center, and is promoting the development

and use of genetically modified crops throughout Asia. Singapore has for

many years made a practice of recruiting foreign scientists. Taiwan is

investing large amounts in biotechnology and is seeking citizens to return

home to build up biotechnology in academia and industry. A Brazilian

coalition recently demonstrated sophisticated domestic use of biological

technologies by successfully sequencing the plant pathogen X. fastidiosa in

2000.10

In addition to the dispersed research enterprise, publications and personnel are

also widely spread. Well over 10,000 journals in the life sciences are published

worldwide. Biological Abstracts, an international database on biology, clinical and

experimental medicine, biochemistry, and biotechnology, provides coverage of over

6,000 active international journals and 14,000 archival titles from over 100 countries;

Medline, the online service of the National Institutes of Medicine, provides abstract

information for more than 4,600 biomedical journals published in the United States and

70 other countries; and PubMed currently provides full-text web access to 4,058 journals.

According to Medline, the total number of scientific articles published in the peerreviewed

biomedical literature has increased from 449,109 in 1998 to 491,620 in 2001.

Given the global nature of the biotechnology research and development enterprise, it is

unrealistic to think that biological technologies and the knowledge base upon which they

rest can somehow be isolated within the borders of a few countries.

The rapid advance of scientific knowledge and applications owes much to a

research culture in which knowledge and biological materials are shared among

scientists and people move freely between universities, government agencies, and

private industry. Large numbers of foreign graduate students and postdoctoral

associates have been an essential ingredient in the success of the biological research

enterprise. The scientific workforce is increasingly international; at the National Institutes

of Health, for example, approximately 50 percent of the technical staff are non-U.S.

citizens. Research results have been widely disseminated, so that even high school

students now routinely perform experiments involving recombinant DNA techniques. In

short, a dynamic national and international research enterprise has evolved, with an

extraordinary record of achievement at multiple centers of excellence. These are values

that should be preserved in any sensible policy for minimizing the risks associated with

the misapplication of the fruits of the biotechnology enterprise.

MOLECULAR BIOLOGY

The great achievements of molecular biology and genetics over the last 50 years

have produced advances in agriculture and industrial processes and have revolutionized

the practice of medicine. The very technologies that fueled these benefits to society,

however, pose a potential risk as well — the possibility that these technologies could

also be used to create the next generation of biological weapons. Biotechnology

represents a “dual use” dilemma in which the same technologies can be used

legitimately for human betterment and misused for bioterrorism.

Events over the 1990s focused growing attention on this balance of risks and

benefits, part of a larger concern about the proliferation of weapons of mass destruction

(WMD) — chemical, nuclear, or biological. In early 1992, President Yeltsin

acknowledged that, despite being an original signatory and State party to the Biological

and Toxin Weapons Convention (BWC), the Soviet Union had maintained a major

clandestine biological weapons program into the early 1990s.1 Yeltsin ordered the

program shut down, but concerns about other possible secret programs remained.

Policymakers in the United States became increasingly concerned that so-called ”rogue

states” would turn to WMD to counter the overwhelming U.S. conventional military

superiority. Secretary of Defense Les Aspin launched the “Defense Counterproliferation

Initiative” in December 1993 to develop additional means to address these threats.

Official statements continue to cite at least a dozen countries believed to have or to be

pursuing a biological weapons capability.2 U.S. and British concerns about Iraq’s

reported biological and other WMD programs were a primary reason for launching

preemptive military action to find and destroy these weapons capabilities.3 The terrorist

attacks of September 11, 2001 and the subsequent anthrax letters accelerated already

existing concerns that terrorists would seek WMD capabilities as well. President Bush, in

a speech at West Point in 2002, said: “The gravest danger to freedom lies at the perilous

crossroads of radicalism and technology. When the spread of chemical and biological

and nuclear weapons, along with ballistic missile technology — when that occurs, even

weak states and small groups could attain a catastrophic power to strike great nations.”4

States, groups, and individuals are pursuing a biological weapons capability — and the

means for them to do so are widely available.

Biological weapons have long been stigmatized as “indiscriminant agents of

unnecessary suffering, [whose] use … contradict(s) the universal principles of war.”5 As

discussed below, since November 1969 the U.S. programs linked to biological weapons

have been restricted to research and development on defensive measures only. Thus

few biologists in the United States today have knowledge of our country’s past offensive

weapons programs or of the concerns of the national security branches of government.

In this respect the life sciences community is in a different situation from that of the

physics community, which in large part has been continuously involved in governmentsponsored

weapons research programs since at least World War II. The scientific

community and the government jointly face a double challenge: (1) to establish a

working relationship with the national security branches of government, and (2) to help

craft a system that will minimize the risk of wrongful use of biological agents or

technology without damaging the scientific infrastructure that has made biological

research so vital to the health of the nation.

microRNAs aid reprogramming

microRNAs specific to mouse embryonic stem cells can substitute for the reprogramming factor cMyc in the generation of induced pluripotent stem cells. The development of reprogramming methods that do not rely on transgenes may facilitate clinical translation of this technology.

Synthetic networks by design

Strategy for rationally assembling gene networks with predictable behaviors. Using mathematical models, they predict the responses of complex synthetic gene networks built from quantitatively characterized promoter libraries, and harness these networks to regulate an industrially relevant yeast phenotype.