Volume 4, Issue 2 
December 2009


Recombinant DNA and Self-replicating Molecular Manufacturing: Parallels and Lessons

James B. Lewis, Ph.D

This article was adapted from a written presentation by James B. Lewis, Ph.D. for Terasem Movement, Inc.’s 5th Annual Workshop on Geoethical Nanotechnology on July 20, 2009 at the Terasem Island Amphitheatre in the virtual meeting environment of “Second Life”.

Dr. Lewis expounds on why an Asilomar-like conference, as well as other venues involving relevant members of the scientific and technical communities, should be explored to identify and avoid immediate threats to public safety at such time when self-replicating nanotechnology is imminent. 

Several papers published in 1972 showed that it was possible to cleave virtually any DNA molecule so that the pieces could be spliced together in the test tube to create a new biologically active DNA molecule—a recombinant DNA molecule that joined together genes from very different organisms to form a molecule that could self-replicate in bacteria to produce huge numbers of copies. It was immediately recognized that this capability offered great potential to advance fundamental knowledge of biology and possibly to alleviate human health problems, but some concerned scientists objected that it also might produce hybrid molecules that could prove hazardous to laboratory workers and to the public (for example by multiplying genes from a cancer-causing virus inside bacteria living in the human gut, perhaps leading to more cancer) [1]. The crux of the concern was the potential that artificial self-replicating molecules might have unknown properties that would cause nasty surprises. As a result of these concerns, a high-level committee of prominent scientists proposed voluntarily deferring certain experiments until further evaluation of potential hazards had been done, and appropriate procedures and guidelines to minimize risk had been developed. They declared, "[A]n international meeting of involved scientists from all over the world should be convened early in the coming year to review scientific progress in this area and to further discuss appropriate ways to deal with the potential biohazards of recombinant DNA molecules." [2]

As a result of the Asilomar Conference [3], the three-day meeting held in February 1975 to consider the moratorium on recombinant DNA experiments, strict procedures were spelled out for working with recombinant DNA. Various methods of physical containment (specially equipped laboratories, special procedures and training) and biological containment (fastidious bacteria that could only survive under laboratory conditions and vectors that could only multiply in certain hosts) were specified, with the most stringent containment methods matched to what were considered the most hazardous experiments.

Most of the scientists involved felt that there was little risk involved in most of the experiments that were to be regulated, but there was little hard data available on which to base rational risk analysis, and few wanted to chance being catastrophically wrong.

The meeting had been called by scientists in response to concerns about threats to public safety that had been raised by scientists themselves, and members of the press were invited to attend and report the proceedings. As a result, the “meeting was widely hailed as a landmark of social responsibility and self-governance by scientists” [4]. The immediate effect of the meeting was to end the moratorium so that research could proceed under the new guidelines, and to help convince the US Congress that no further restrictions were needed because the scientists could govern themselves. As a consequence, recombinant DNA technology became the basis for a profound explosion of knowledge. Genes and genomes were no longer abstract entities, but instead segments of DNA that could be manipulated and studied in detail. Numerous therapies and diagnostics were developed, and within 30 years the human genome and many other genomes had been sequenced. The technologies that grew from the recombinant DNA technology of the 1970s have brought us to the verge of deep knowledge of biology and of the ability to manipulate genes and cells to cure diseases and improve human health.

Over the years as experience and knowledge of the real risks accumulated, the guidelines were substantially loosened or eliminated so that experiments could legally be done in open laboratories, or eventually even in someone’s basement. We now know that organisms have exchanged DNA for millions of years as a common feature of evolution. Indeed, in the 34 years since Asilomar, there have been no documented hazards to public health attributed to recombinant DNA. Those scientists who, at the time, thought that the new recombinant DNA technology posed no significant risk turned out to have been correct. (For perspectives on Asilomar 25-30 years later, see [4], [5], [6] and [7].)

References

[1] "Guidelines for hybrid DNA molecules," Singer, M.F. and Soll, D., Science 181,  1114 (1973).

[2] "Biohazards of Recombinant DNA," Berg, P., Baltimore, D., Boyer, H.W., Cohen, S.N., Davis, R.W., Hogness, D.S., Nathans, D., Roblin, R., Watson, J.D., Weissman, S. and Zinder, N.D., Science 185, 303 (1974).

[3] This was actually the second Asilomar conference organized by Paul Berg to consider safety issues related to molecular biology research. An earlier one to begin evaluating the risks that DNA from animal viruses capable of inducing tumors would end up in intestinal bacteria of laboratory workers had been held in January 1973. “The Paul Berg Papers: Recombinant DNA Technologies and Researchers' Responsibilities, 1973-1980” http://profiles.nlm.nih.gov/CD/Views/Exhibit/narrative/dna.html
 
[4] "Asilomar Revisited: Lessons for Today?" Marcia Barinaga, Science 287, 1584 - 1585 (2000). http://dx.doi.org/10.1126/science.287.5458.1584. Also available at http://www.biotech-info.net/asilomar_revisited.html.

[5]"The recombinant DNA controversy: Twenty years later," Paul Berg and Maxine F. Singer, Proceedings National Academy of Sciences USA 92, 9011-9013 (1995), http://www.pnas.org/content/92/20/9011.full.pdf+html

[6]“An Asilomar moment,” Gregory A Petsko, Genome Biology 3 (2002) http://genomebiology.com/2002/3/10/comment/1014

[7] “Asilomar and Recombinant DNA,” Paul Berg (2004) http://nobelprize.org/nobel_prizes/chemistry/articles/berg/index.html

 

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