One researcher, Paul Berg (who went on to a very
distinguished career and died only recently) was working with SV40, a cancer-producing simian
virus (as an aside, SV40 had been accidentally injected into many polio vaccine recipients
in the 1950-1960s). Berg pioneered
using restriction enzymes to cut
DNA loops and then using other enzymes to rejoin them, creating new
combinations of genetic material. Others at the same time were working on similar “recombinant”
technology.
Here’s a video of Berg discussing his work and his belief that a “moratorium” of this technology should be called. Partial transcript of the video:
The point was that we were going to be propagating SV40 genes in E. coli. The concern was that E. coli is a natural inhabitant in humans, and the worry was whether we could inadvertently infect humans with the E. coli we were propagating, potentially leading to cancer. This concern sparked intense debate. Depending on where you stood on the issue, you were either vociferous about it or dismissive, saying, "Forget about it. It's not serious."
After many conversations, I became convinced that I could not dismiss the risk and make it zero likelihood. So, I decided to put the whole thing on the shelf, and for a while, the issue died down.
About a year later, Janet Mertz, a graduate student in my lab, discovered that EcoRI made cohesive ends. She found that she could take any two DNAs and join them together. This breakthrough allowed Stan Cohen and Herb Boyer to begin making recombinants using E. coli plasmids, checking for drug resistance, and showing they could create chimeric DNA molecules.
They presented their work at a Gordon Conference, which sparked a similar reaction among a small minority of the audience. Some expressed alarm, saying, "Oh my God, you guys could really make some dangerous things." At that conference, Maxine Singer and Dieter Soll, the co-chairs, were persuaded to draft a letter to the academy, published in Science. The letter highlighted the great promise of being able to create new kinds of DNA molecules while also addressing the possible dangers and risks.
When the president of the academy received the letter, he asked, "What do I do with it?" Maxine suggested, "Call Paul Berg, because he's thought about this problem."
The papers presented at the 1973 Gordon Conference alarmed the proto-molecular biologist conferees, who voted to send a letter to Philip Handler, President of the National Academy of Sciences, about the possible consequences of the new technology. The letter read:
Guidelines
for DNA Hybrid Molecules
Those in attendance at the 1973 Gordon Conference on Nucleic
Acids voted to send the following letter to Philip Handler, president of the National
Academy of Sciences, and to John R. Hogness, president of the National
Institute of Medicine. A majority also desired to publicize the letter more
widely.
We are writing to you, on behalf of a number of scientists,
to communicate a matter of deep concern. Several of the reports presented at
this year's Gordon Research Conference on Nucleic Acids (June 11—15, 1973, New
Hampton. New Hampshire) indicated that we presently have the technical ability
to join together, covalently, DNA molecules from diverse sources. Scientific
developments over the past two years make it both reasonable and convenient to
generate overlapping sequence homologies at the termini of different DNA
molecules. The sequence homologies can then be used to combine the molecules by
Watson-Crick hydrogen bonding. Application of existing methods permits subsequent
covalent linkage of such molecules. This technique could be used, for example,
to combine DNA from animal viruses with bacterial DNA, or DNA's of different viral
origin might be joined. In this way new kinds of hybrid plasmids or viruses,
with biological activity of unpredictable nature, may eventually be created. These
experiments offer exciting and interesting potential both for advancing knowledge
of fundamental biological processes and for alleviation of human health problems.
Certain such hybrid molecules may prove hazardous to
laboratory workers and to the public. Although no hazard has yet been
established, prudence suggests that the potential hazard be seriously considered.
A majority of those attending the Conference voted to communicate their concern
in this matter to you and to the President of the Institute of Medicine (to whom
this letter is also being sent). The conferees suggested that the Academies establish
a study committee to consider this problem and to recommend specific actions or
guidelines, should that seem appropriate. Related problems such as the risks
involved in current large-scale preparation of animal viruses might also be
considered.
(signed) MAXINE SINGER DIETER SOLL
From this initial burst of activity, scientists reached a consensus that the as-yet unnamed science of Genetic Engineering should be put under a moratorium. Experiments were to cease until the ramifications could be discussed and amelioration put into place.
The conference meeting was held at Asilomar, in Southern California, in February 1975. The outcome was a set of guidelines for handling recombinant DNA, physically (biological containment facilities) and experimentally (using only hosts that would die outside a laboratory).
That was 50 years ago.
I wasn’t a “Genetic Engineer” in those days. I’m old, but not that old. I learned about the conference in 1979, as I studied genetics for my degree.
The burgeoning field of genetics had a vertical take off between the first “restriction
enzymes” in the early seventies and the routine gene engineering of the 21st
Century. In fact, the modern understanding of heredity is less than two hundred
years old: The understanding that for all sexually reproducing species – plant or animal - two
parents provide heritable material to an embryo, which can then pass down half
its own heritable material to its offspring.
A brief timeline:
1. Mendel's experiments showing that various plant characteristics were not “blends” of their parents’ characteristics: 1865
2. The concept of evolution set down in writing by Darwin. The Origin of Species, 1859, The Descent of Man published on February 24, 1871
3. Mendel’s experiments verified (and rediscovered) by Hugo de Vries, Carl Erich Correns and von Seysenegg, 1900
4. Proof of DNA's role in heredity: The Hershey-Chase experiment, which demonstrated that DNA, not protein, was the genetic material, 1952
5. Discovery of DNA structure: The double helix structure of DNA was identified by James Watson and Francis Crick in mid-March 1953, with their paper published on April 25, 1953
6. Experiments showing DNA replication: The Meselson-Stahl experiment providing experimental proof of DNA's semiconservative replication: 1958
7. The first paper describing a restriction enzyme published by Hamilton O. Smith, Thomas Kelly, and Kent Wilcox. The isolation and characterization of the type II restriction enzyme Hind II from Haemophilus influenzae: 1970
8. The Human Genome Project:
• Started in 1990
• Declared complete on April 14, 2003 (covering about 92% of the genome)
• "Complete genome" level achieved in May 2021
• Final gapless assembly finished in January 2022
Recombinant technology has moved on at a tremendous rate
since the seventies. Several other conferences have been held, including this year at the "Spirit of Asilomar and the Future of Biotechnology"
conference in February 2025, and work continues.
The Asilomar conference marked the first significant time
that researchers stopped and thought, “Just because I can, it doesn’t mean I
should.” Scientific Ethics have been in the news again and again after 1975 and
there are very good reasons for that.
Another thing that has been in the news over the past few
years, as well: the possibility of “lab leaks.”
What did people in 1974 know about lab leaks?
“This [genetic manipulation] would call for technical re-education of the average microbial geneticist or molecular biologist, whose manipulation of bacteria chills the blood of anyone accustomed to handling pathogens.” (Emphasis mine.)
Thank you, Professor E. S. Anderson of Colindale. [Nature (250(5464), 278–280. doi:10.1038/250278b0]
For background, reading, please see Paul Berg's video and/or my earlier posts on
Asilomar,
https://peromyscus.blogspot.com/2013/06/genetics-library-project-political.html
https://peromyscus.blogspot.com/2015/03/genetic-engineering-birds-do-it-bees-do.html
