Asilomar Conference (1975)

In February 1975, leading biology researchers and lawyers participated in what became known as the Asilomar Conference, a meeting to discuss and recommend policy regarding novel recombinant DNA, or rDNA, technology. rDNA is DNA that scientists create in a lab by combining genetic material from two distinct sources. A group of researchers, including Paul Berg, Maxine F. Singer, and David Baltimore, organized the Asilomar Conference, which was held at the Asilomar Conference Grounds in Pacific Grove, California. The purpose was to discuss how to manage the risk of researchers unintentionally creating harmful or deadly pathogens through rDNA research. The conference resulted in the creation of the NIH Guidelines for Research Involving Recombinant DNA Molecules in 1976, which outlines biosafety guidelines for researchers working with rDNA. The Asilomar Conference was one of the first instances when scientists gathered independently to discuss and establish precautionary guidelines for research using rDNA, a technology with the potential for wide-reaching applications for medicine, biology, and reproduction.

1. Paul Berg and early rDNA experiments
2. The First Asilomar Conference - 1973
3. Gordon Conference - 1973
4. Meeting of Assembly of Life Sciences - 1974
5. Making of the Asilomar Conference
6. The Asilomar Conference
7. Legacy and Impacts

Paul Berg and early rDNA experiments

Since the early twentieth century, scientists have known that viruses can cause tumors in animals. In 1910, Peyton Rous, a researcher at the Rockefeller Institute for Medical Research in New York, New York, identified a virus that caused cancer in chickens. Scientists eventually named it the Rous sarcoma virus and determined it to be an RNA virus. Since Rous’s time, researchers have found many viruses that cause tumor growth in animals, including both RNA- and DNA-based viruses.

About a decade prior to the Asilomar conference, researchers began conducting experiments involving the bacterium Escherichia coli, or E. coli, and viruses. Paul Berg was one of those researchers. He worked as a professor of biochemistry at Stanford University in Palo Alto, California. According to Donald S. Fredrickson, a previous director of the National Institutes of Health, Berg was initially inspired by parallels he saw between phages, a type of virus that attacks and replicates in a bacterium, and the viruses that infect animal cells. Phages can enter and modify bacterial genomes. Berg wondered if he could use an animal virus, such as simian virus 40, or SV40, to transfer a foreign gene into cells of an animal, to study how genes work in animal cells. In the late 1960s, Berg took a sabbatical to work with Renato Dulbecco at the Salk Institute in San Diego, California. Dulbecco at that time was researching tumor viruses.

When Berg returned to Stanford after his sabbatical, he decided to focus on SV40 as a potential carrier for introducing new genes into animal cells. Fredrickson notes that, as a first step, Berg, along with two coworkers, decided to incorporate a gene isolated from bacteria into the SV40 genome. The scientists first deleted certain parts of the SV40 genome and then added the bacterial gene. In 1971, the team was ready to use the modified SV40 virus to insert the bacterial gene into animals cells but halted the experiment due to concerns that SV40 might cause human cells to turn cancerous. Prior to Berg’s experiment, scientists found that SV40-infected cells caused tumor growth in hamsters.

Because E. coli is a common bacterium that also lives in the human gut, Berg’s planned experiment raised the possibility of creating a highly transmissible virally caused cancer were the recombined bacteria to escape from the lab. Robert Pollack, a cancer researcher at Cold Spring Harbor Laboratory in Long Island, New York, heard about Berg’s experiments with rDNA when one of Berg’s research fellows presented the work in a summer course that Pollack was teaching. On 28 June 1971, Pollack called Berg, pointing out that if the recombined bacterium with SV40 genome escaped Berg’s lab, it could potentially infect the scientists in the lab or even the broader community, raising the possibility of spreading a virally caused cancer. Pollack proposed that Berg halt his experiments to avoid such events, but Berg disagreed. Pollack even offered to fly Berg from San Francisco to Long Island to speak about the matter in person, but Berg declined. 

After speaking with Pollack, Berg opened the discussion with other researchers regarding their concerns about rDNA research, and those conversations led him to halt his experiments towards the end of 1971. According to Matthew Cobb, writer of As Gods: A Moral History of the Genetic Age, most of the researchers Berg conversed with believed there were only small risks to rDNA experiments, yet they still did not see a strong argument for Berg continuing that particular line of work. At a conference in Sicily, Italy, in July 1971, Berg faced criticism in the form of ethical and moral concerns from researchers who did not approve of his work. After that conference, Berg faced criticism in yet another informal conversation, this time at a dinner party with Singer, Singer’s lawyer husband Daniel Singer, as well as other guests. Singer’s husband and other attendees also pointed out ethical and legal issues that Berg had not considered prior to that conversation. Eventually, after numerous interactions with his colleagues, Berg stopped his experiment and, later in 1971, informed Pollack of his decision, admitting that Pollack was correct about the hazards of using SV40.

The First Asilomar Conference - 1973

After pausing his experiments, Berg began to push for the scientific community to formally discuss laboratory containment of viruses that might prove dangerous, leading to the first of two conferences at the Asilomar Conference grounds. Berg, who was a member of the Human Cell Biology Steering Committee, an advisory group organized by the National Science Foundation, convinced his colleagues to hold a formal conference on the topic, in 1973. That conference is often referred to as Asilomar I since it shared the same location with the later, more well-known Asilomar Conference of 1975. The participants, who were mainly from the US, discussed the then-current research on cancer-causing viruses and biohazards. The conference discussed up-to-date information on viruses and pathogens in light of the potential for a viral form of cancer. At the time in 1973, laboratory experiments were not linked to cancer cases, meaning experiments conducted in laboratories did not have any known causal relations to cancer. Despite that, participants urged continued caution to prevent possibly exposing the public to cancer and other potential biohazards. As of 2024, scientists have found that some viruses such as Epstein-Barr and human papillomavirus can cause cancer in humans.

At Asilomar I, participants’ discussions about biohazards resulted in some increased precautions for experiments. For example, they decided to create safety guidelines for scientists looking for viruses that cause cancer in humans. However, according to Fredrickson, some scientists feared that research money would not sufficiently cover the necessary safety requirements, studies, or facilities associated with the proposed precautionary measures. They argued there needed to be increased funding for facilities to better contain biological materials. The conference did not address rDNA experiments explicitly, which allowed research on genetic recombination to continue even though it had the potential to expose scientists, as well as the general public, to unknown biohazards such as lab viruses causing cancer.

Gordon Conference - 1973

In the summer of 1973, researchers at the Gordon Conference on Nucleic Acids, an annual conference separate from Asilomar, considered the potential hazards of rDNA, leading to the creation of a committee that could determine best practices for rDNA research. While there, participants wrote a letter, later published in the journal Science, to the National Academy of Sciences and the Institute of Medicine requesting that they form a committee to review rDNA research and give recommendations on how best to protect against potential hazards of rDNA. Philip Handler, then president of the National Academy of Sciences, referred the letter to an internal committee called the Assembly of Life Sciences. The assembly agreed with the concerns outlined in the letter, and thus planned to form a committee. The Assembly of Life Sciences reached out to Singer, who was a researcher at the National Institutes of Health, or NIH, at the time and a co-chair of the 1973 Gordon Conference, asking her to propose a leader of the new group, and she recommended Berg. Berg accepted the position and formed a small initial group of six researchers to make early recommendations for dealing with rDNA research. One of those researchers was David Baltimore, who was a tenured professor of biology at the Massachusetts Institute of Technology, in Cambridge, Massachusetts, and later became involved as an organizer of the Asilomar Conference of 1975.

Meeting of Assembly of Life Sciences - 1974

The Assembly of Life Sciences committee met for the first time in April 1974 to discuss advancements in rDNA research, and after that meeting, they made four recommendations to prevent biohazards. First, they called for a voluntary moratorium on two main types of experiments that they viewed as potentially dangerous. One was the creation of plasmids containing genes for antibiotic resistance or for dangerous toxins. A plasmid is a small circular molecule of DNA found in bacteria that is separate from the bacterium’s main chromosomal DNA. Bacteria can pass those plasmids, including ones for antibiotic resistance, to other bacterial cells. Antibiotic resistance is when bacteria garner the ability to defend themselves against the antibiotics that typically kill them. Bacteria that are resistant to antibiotics can cause widespread sickness, making experiments that create plasmids with antibiotic resistance genes particularly dangerous. The other type of experiment they called for a moratorium on was ones combining DNA from oncogenic, or cancer-causing, viruses with plasmids or other viral DNA. The concern there was the worry that such experiments might create highly transmissible forms of cancer.

Second, they recommended that researchers carefully weigh the risks of experiments that combine animal DNA with that of a plasmid or phage DNA. Third, they requested the director of the NIH to form an advisory committee on rDNA to gauge the threats of rDNA, construct procedures to reduce those hazards, and arrange guidelines to follow when working with rDNA. Finally, they proposed for there to be an international conference in 1975 to review the potential biohazards of rDNA and come up with ideas to deal with those hazards.

Making of the Asilomar Conference

On 10 September 1974, a committee consisting of Berg, Singer, Baltimore, and other scientists joined together at the MIT Center for Cancer Research in Cambridge, Massachusetts, to support the organization of the Asilomar Conference in February 1975. Additionally, three researchers were appointed as chairmen to three independent panel groups. Those chairmen, as well as other researchers, worked in specific groups focused on plasmid-cell DNA recombinants, plasmid-phages, and animal viruses. The committee instructed those working groups to begin preparation for the Asilomar Conference in February 1975. Each of the three-panel groups’ reports were fundamental to the discussion at the conference since attendees used each panel’s information as key evidence in deciding what should be done with the usage of rDNA. The committee planned for each working group to present on the areas of research and risks at the actual conference.

At the 1974 meeting, the committee decided that the Asilomar Conference should bring some of the best scientists from around the world together to discuss rDNA. While the committee discussed possible participants of the conference, Berg had the final say as to who was on the invitation list. Berg decided that approximately ninety invitees from the US and sixty participants from twelve different countries would represent the international scientific community. Sixteen press members were allowed to attend the 1975 conference on the condition that they not release any reports until after the conference. Four lawyers were also present. Representatives from public interest groups were not included. The conference committee allowed the meeting to be taped, for archival and review purposes rather than for public release.

The Asilomar Conference

On 24 February 1975, Baltimore opened the discussion at the Asilomar Conference, describing the events that led to the voluntary moratorium and stressing the need for the attendees to reach a consensus, as they were the ones with the expertise to make sound judgements. He argued that though advancements in science might emerge as a result of rDNA experiments, the regulation of potential biohazards of rDNA was more important than those potential advancements. Baltimore noted that the organizing committee would release a summary statement and consensus on the last day of the conference. Following Baltimore’s talk, Berg gave the first of many academic presentations at the conference. Berg also informed participants that on the last day of the conference, a group of lawyers would join them to present their stances on the topics at hand. 

On the second day of the conference, the working group on plasmid-phages presented recommendations for how to classify, monitor, and design experiments. The NIH later used those recommendations as a template for future guidelines. That same day, there was a controversy among researchers, some even calling for an end to the moratorium on rDNA research without the establishment of experimental guidelines. Those researchers did not want to adhere to the strict guidelines set by the plasmid-phage working group.

In the afternoon, the animal virus working group was meant to present on the possibility of viruses causing human cancer from the creation of rDNA. However, the group spent the majority of their final report making an argument to support further research of rDNA rather than discussing the hazards of such research, as the conference organizers originally requested. The group recommended that all experiments, except those involving highly pathogenic viruses that can cause diseases, follow the guidelines for moderate-risk cancer viruses outlined in the National Cancer Institute guidelines for work involving oncogenic viruses. That meant that most research on rDNA fell into categories below that exception because they were not working with highly pathogenic or oncogenic viruses, and the virus working group recommended they be allowed to continue their studies, if and when the moratorium was lifted. That working group mentioned potential scientific and social benefits of rDNA research but did not expand upon specific examples of said benefits. Since the virus working group went against what the organizers of the Asilomar Conference requested by focusing on potential benefits rather than hazards, the group issued an amended report the next day that supported physical and biological containment for research that involves inserting viral DNA into bacterial cells.

On the third day of the conference, the working group on eukaryotic recombinant DNA, part of the plasmid-cell DNA working group, presented on three potential hazards of eukaryotic rDNA. The term eukaryotic refers to organisms made up of cells that have a central nucleus, a group that includes animals, plants, and fungi. First, they explained that experiments involving putting eukaryotic rDNA into bacteria might potentially produce a toxic product. Second, the introduction of eukaryotic DNA to bacteria might make the bacteria more pathogenic or alter the range it lives in. Third, a piece of eukaryotic DNA might become incorporated into the DNA of a plant or animal and alter its cells, potentially in a detrimental way.

Then, the working group on eukaryotic rDNA classified experiments into levels of hazard where the highest level of hazard involved experiments where rDNA might contaminate entire genomes of other organisms. Those experiments raised concerns about how to contain what might become pathogens for humans, which required high containment facilities due to elevated safety concerns. Depending on an experiment’s level of risk, containment could involve physical containment, such that experimental materials could not come into contact with other genomes, and biological barriers, such as using hosts unable to survive in a normal environment. Fredrickson writes that those recommendations alarmed some researchers since research facilities might not be able to meet the containment requirements due to cost and resource availability. Fredrickson also notes that those concerns also caused researchers to argue over what types of experiments are appropriate for specific hazard levels of containment. 

In the late evening of the third night, the conference chair introduced Daniel Singer, who guided the panel of lawyers for the conference. He stressed the importance of the public and their say in the outcome of the Asilomar Conference since they were the ones funding portions of the research. Other lawyers joined in to emphasize the need for the scientific community to consider the roles of the government, the US Occupational Safety and Health Administration, or OSHA, and their potential involvement since they may have the final say in research involving rDNA. Set up by Congress, OSHA works to ensure that workplaces and workers are safe in their environments, free from known hazards to safety and health such as exposure to a viral form of cancer. The lawyers’ statements about potential government regulation convinced the scientists that they needed to come up with definitive recommendations for regulating rDNA.

On the fourth and final day of the conference, on 27 February 1975, participants ended the voluntary moratorium on rDNA research and created the NIH Recombinant DNA Advisory Committee, which met the same day. The committee came up with a provisional statement stating that scientists could continue research on rDNA with safeguards in place for the containment of biohazards. To gauge support among members of the conference, Berg took a vote by show of hands, which confirmed that the majority of attendees supported that initial statement.

The NIH Recombinant DNA Advisory Committee followed the guidelines made in that provisional statement created at the Asilomar Conference as temporary rules for laboratories funded by the US federal government to continue research on rDNA. A couple of months later, on 29 April 1975, the organizing committee of the Asilomar Conference submitted their final report to the National Academy of Sciences’ internal Assembly of Life Sciences. The Assembly of Life Sciences committee reviewed the report and then approved it on 20 May 1975. The academic journal Science published the report on 6 June 1975.

Legacy and Impacts

In the judgment of many scholars, the Asilomar Conference was a milestone in both scientific research and science policy. It was one of the first times that scientists gathered independently to establish guidelines for an emerging scientific field, one whose risks were not entirely known. The Asilomar Conference prioritized protecting public safety above other, competing aims, such as unfettered scientific exploration. With the Asilomar guidelines set in place, rDNA research was able to continue and expand. By 1995, experiments with rDNA dominated all other areas of biological research. According to Berg and Singer, writing in 1995, for twenty years after the conference, researchers conducted millions of rDNA experiments, with no documented hazards to public safety and health.

As Berg and Singer also note, rDNA techniques have led to useful medical treatments. Recombinant DNA technology allowed scientists to produce a synthetic version of the hormone insulin, which is needed to control the level of body sugar in the body. Genetically engineered E. coli can produce insulin in a laboratory, eliminating the need to obtain insulin from animal sources such as the pancreas of cattle. Recombinant DNA is also used in the treatment of hemophilia, which is an inherited bleeding disorder where blood does not clot properly due to a lack of blood clotting proteins. Prior to rDNA technology, hemophilia treatments relied on products made from donated blood, which in the 1980s and 1990s had the risk of being contaminated with HIV.

Research on rDNA has also led the development of vaccines, such as those for the human papillomavirus, or HPV, which is one of the most common sexually transmitted infections, and capable of causing cancer. Other vaccines that use rDNA technologies include ones for HIV, tuberculosis, and malaria. Vaccines that use the rDNA technology are often safer and have lower production costs than traditional vaccines.

The discussion of science policy at the Asilomar Conference served as an example to other industries and fields for the management of actions in the face of uncertainty. The self-regulation by the scientific community surrounding rDNA set a precedent for how research could be conducted responsibly in the face of potential biohazards. In the years since 1975, researchers in many other areas of science have hosted their own Asilomar-like conferences, modeled on the original. Some scholars have questioned whether the Asilomar model, in which scientists are responsible for regulating themselves, is the best way to handle controversial developments in science and technology that broadly affect the public. Some call for more public engagement up front. Berg himself acknowledged, in a 2004 article, that the Asilomar model might not be an effective means to deal with the highly politicized issues confronting scientists and the public in the twenty-first century, including embryonic stem cell research, genetic testing, gene therapy, and genetically modified organisms. Nevertheless, as Berg notes, for its time Asilomar was unprecedented and it succeeded in its aims.

As of April 2024, the conference’s main contribution, the NIH Guidelines for Research Involving Recombinant DNA Molecules, now called the NIH Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules, is still active. It was last edited in April 2024.