Part I, A time to reflect: Scientific discovery and its perceptions by society

Feb ,16 2017

The public discussion surrounding the 2012 discovery of Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-Associated protein (Cas) ranges from ground-breaking advantages in curing diseases and solving world-hunger to apocalyptic fears of clone armies and collapsed ecosystems. Marton explained in his entry from 2015 that the CRISPR/Cas system is an immune system of bacteria defending it against invading viruses. It is comprised of two components: an enzyme which cleaves invading viral DNA like a pair of scissors (Cas) and a piece of RNA - which is complementary to the targeted DNA - used as a guide for the scissors. Jennifer Doudna and her colleagues noted in the discussion of their results that these components could be manipulated to be used in eukaryotes such as plants and animals, including humans. These remarks were readily picked up by the press and the outcry over the possibility of designer babies and monstrous experimentation re-emerged. Whilst the pressure of publication, limitation of funding, and licencing of patents pushes scientists to focus on rapidly advancing their field of research, scientists do as well pause for thought, and halt their work to reflect on the impact of their discoveries. The best known example is the “Asilomar conference on recombinant DNA molecule research” held in 1975, which was initiated by concerns raised by leading scientists in the emerging field of recombinant DNA research. Similarly, the scientists who discovered CRISPR called for a meeting held in Napa, California in January 2015 to discuss the implications of CRISPR.

Asilomar conference on recombinant DNA

In the 1960’s scientific research was fairly unregulated and experiments were conducted at the open bench with few exceptions, including work with radioactive material, known tumour-inducing viruses, and the use of human subjects. The helical structure of DNA was discovered, but none of the techniques commonly used nowadays were available.

In 1972-1973 experiments conducted by the research groups of Paul Berg, Andrew Lewis, and Stanley Cohen changed the field radically. They discovered bacterial enzymes which function like molecular scissors, adapted to protect the bacteria against invading viruses. These molecular scissors, termed ‘restriction enzymes’ could be isolated and used to cleave any DNA segment. Further, they observed that viral genomes cleaved by a restriction enzyme could subsequently recombine to reform an intact genome. These and other observations led to the realisation that one could virtually cut any gene or DNA segment from a genome and insert it into a carrier. This carrier could be the genome of a virus, or of a so-called ‘plasmid’ – a small circular DNA molecule, which is used by bacteria to exchange genetic information. The carrier harbouring the inserted DNA segment could be introduced into bacteria and the bacterial host would then produce the trait dictated by the inserted DNA fragment.

Presentation of these results at the “Gordon conference on nucleic acids” in 1973 raised concerns amongst attending scientists regarding the potential risks and hazards posed to animal and human welfare as well as the environment by this novel technique. To address these issues the organisers, Peter Söll and Maxine Singer decided to send a joint letter to the National Academy of Science (NAS) and the National Academy of Medicine (NAM) located in the USA, enquiring about setting up an advisory committee on this subject. Paul Berg was appointed by the NAS to lead the “Committee on recombinant DNA molecules, assembly of life sciences” and this group agreed upon limitation of experiments involving recombinant DNA until hazards were assessed and guidelines were provided. Their recommendations were published in two leading scientific journals – “Science” and “Nature“ in 1974. A misprint in the latter led to the general understanding that the authors were calling for a voluntary moratorium on all experiments involving recombinant DNA, which was subsequently invoked in most research centres and was adopted by commercial research suppliers. The so-called “Berg letter” also announced the discussion of potential hazards at the “Asilomar Conference on recombinant DNA” in 1975.

153 participants, including 16 journalists and 4 lawyers, attended this meeting, the aim of which was to provide the National Institute of Health (NIH), located in the USA, with recommendations on the biohazards of recombinant DNA research and how to control for these risks. The results of these heated debates were:

1) Classification of experiments into 6 groups ranked by risk level
2) Lift of the voluntary moratorium – exception (risk level 6): known carcinogens, DNA fragments producing toxins and antibiotic resistance, and large scale production of recombinant DNA molecules
3) Requirement of microbiological training for any scientist wanting to perform recombinant DNA research
4) Establishment and maintenance of physical (e.g. hoods, pressure chambers…) and biological barriers (e.g. “disarmed” plasmids, viruses and bacteria, which are unable to survive outside the laboratory)

These recommendations were handed to the NIH and formulated into guidelines by 1976. Similarly, governments and research organisations worldwide, such as the British Medical Research Council, adopted them into their regulations and/or legislation.

The Asilomar Conference was heavily criticised from many sides, in particular by public organisation, which demanded more inclusion in the discussion, and by attending as well as non-attending scientists, who questioned the expertise of the participants, since the field of recombinant DNA had just recently emerged and data on the associated hazards risks were too limited to give recommendations on safety measures. However, it was the first time in scientific history that researchers would self-impose a voluntary moratorium – which literally meant ceasing research – to reflect on the potential disadvantages the bourgeoning field might lead to. Back then, and more so now, the pressure to rapidly produce great results and the limitation of funding do not foster a culture of reflection upon the advances one has made. It was a risky, but responsible endeavour to “call for help” as the organisers of the Gordon conference in 1973 did.

Nowadays biomedical research is strictly regulated, and health and safety procedures are in place to assess anticipated risks of upcoming experiments, to adopt appropriate safety measures and to control that the latter have been implemented correctly to ensure the safe handling of hazardous material. In addition, national laws determine the range of experiments allowed to protect human and animal welfare as well as protection of the environment.