Out of order: Asilomar remembered

Consensus tends to be lacking as to the dividing line between permissible germline genome modification to treat human disease vs. questionable attempts at human enhancement, and that is something we need to sort out

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In some ways, scientists can appear much like a colony of meerkats.
On a typical day, they are completely focused on the tasks literally at hand, heads perpetually down, the only permitted distraction the next shiny question that remains unanswered. And if there is any chatter in the room, it is among small groups of researchers, nattering away on a common issue—mostly cooperative, but sometimes adversarial.
But every now and again, however, even the most focused of meerkats can be startled by something that doesn’t make sense or by possible danger on the horizon, his or her head popping skyward to survey the suddenly questionable landscape. And like a string of reverse dominoes defying gravity, the rest of the colony pop their heads skyward, security reinforced with more eyes looking for threats.
Such was the case in the early 1970s when recombinant DNA technology burst onto the scientific landscape. Within a span of years, the days of being hamstrung by the limitations of genetic analysis via cross-breeding experiments gave way to the freedom of being able to identify, isolate and shuffle genes and smaller DNA fragments not just within organisms, but also between organisms.
The identification of enzymes and buffer systems that would allow scientists to precisely cut and splice genes, to insert them behind alien promoters and to change the phenotypes of accepting organisms or to mass produce the gene products in a fermenter, opened a brave new world of possibilities in agriculture, biology and medicine.
But whereas most of the scientific community salivated at those possibilities, a brave few souls raised their heads from the marvel they held before them and cried “Wait a minute. Should we really be doing this?”
The soft voices of question percolated through the scientific community and, in February 1975, biotechnology pioneer Paul Berg and 140 leading biologists, clinicians and lawyers met on the shores of the Pacific Ocean to hold a meeting known as the Asilomar Conference on Recombinant DNA.
“This meeting was organized to review scientific progress in research on recombinant DNA molecules and to discuss appropriate ways to deal with the potential biohazards of this work,” wrote Berg and colleagues in PNAS later that year, a paper that outlined the outcomes of the conference.
Thanks for the history lesson, you may say, but what does this have to do with the price of coffee?
This March, almost 40 years to the month of the Asilomar Conference, groups of scientists called once again for a possible moratorium and at least a conversation on the safety of biotechnological interventions related to recombinant DNA.
Publishing in Nature and Science and with a position statement from the International Society for Stem Cell Research (ISSCR), these researchers are holding up a yellow card of caution to any work involving gene editing, with a particular focus on modifying germline cells.
Over the last few years, the ability to replace mutated disease-related genes with normal or “healthy” versions in human cells has been greatly facilitated by the advent of new gene-editing technologies such as zinc-finger nucleases (ZFNs), TALENs and CRISPR. When coupled with advances in stem cell technologies, this facilitation dramatically increases the feasibility of correcting heritable diseases in patients at the root.
But, while everyone applauds these advances, the same methodologies used to alter T cells for immunological conditions, for example, can also be used to modify germ cells—sperm, ova, embryo—and already have been in several experimental animals. It is the possibility of applying these technologies to human germ cells that has attracted the caution flag.
“In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations,” wrote Edward Lanphier and colleagues in Nature. “This makes it dangerous and ethically unacceptable.”
And no one would question Lanphier’s credentials. Not only is he president and CEO of Sangamo BioSciences, a company developing gene-editing technologies, but also chair of the Alliance for Regenerative Medicine, the group that champions such innovations.
For Lanphier and a growing group of scientists like him, it is time to take a breath and open a discussion on the future of these technologies with respect to germline alterations.
“Consensus is lacking on what, if any, therapeutic applications of germline genome modification might be permissible,” wrote the ISSCR. “For example, some argue that the ability to eradicate disease justifies attempts at therapeutic editing of the human germline, while others emphasize the difficulty of drawing clear distinctions between applications in human disease and attempts at human enhancement.”
Until such consensus can be found, both the ISSCR and Lanphier’s group suggest a voluntary international moratorium on such research might make sense. That sounds like a very good idea, and I applaud Lanphier’s suggestion that any such discussions should also include members of the public.
And as to reaching that consensus, I hear Asilomar is beautiful this time of year.
Look for more on these technologies and their implications in a Stem Cells Special Report in the August 2015 issue of DDNews.

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