In the 1970s, two inhuman creatures — one hairy and tall, another with orange eyes — were spotted in New England. The mayor of Cambridge, Massachusetts, blamed these monsters not on unreliable testimonies, but recombinant DNA technology, then a new and promising laboratory technique.
This outrageous claim was levelled by one Alfred Vellucci, a Cambridge mayor who reserved a unique animosity for academia, and Harvard, especially. He was fond of threatening, for example, to pave the university's grassy quad over for a parking lot — obviously the best solution to Cambridge's parking woes.
Needless to say, when the university decided to build a special lab for experiments involving recombinant DNA — a DNA-manipulation technique in which genes from one species are combined with another that was, at the time, new and controversial — Vellucci was quick to evoke the spectre of Frankenstein. Stoking this controversy was obvious political theatre for Vellucci, who fought famously hard for town against gown, but his rabble rousing actually reflected a larger scientific debate over the new technique that was unfolding at the time.
Recombinant DNA was in its infancy then, its risks and rewards still largely hypothetical; and so, in July 1976, the Cambridge City Council issued a moratorium on certain recombinant DNA experiments. Such a ban would be unfathomable today, in a world where recombinant DNA technologies and their dividends are ubiquitous. A few examples: The human insulin gene has been spliced into yeast to scale up production, making the drugs that save the lives. A bacterial gene lives inside GM corn that is resistant to many pests. Scientists routinely insert human genes into mice for every kind of biomedical research.
Today, molecular biology is on the cusp of yet another revolution. So-called CRISPR-Cas9 technology allows scientists to edit genomes with previously unimaginable precision. And with new power come new responsibilities, as Harvard biologists discovered in 1976.
"Strange, orange-eyed creature"
In 1972, Paul Berg at Stanford published the first paper on recombinant DNA. He and his colleagues had successfully inserted a snippet of the monkey virus SV40 into E.coli. So far, no Frankenstein monster. But SV40 was believed to cause tumours, and scientists began to worry that the modified E. coli could escape the lab, spreading tumour-causing genes with it.
Not two years later, Berg and ten other scientists — including Nobel prize winners James Watson and David Baltimore — penned a letter in the journals Science and Nature calling for a voluntary moratorium on dangerous recombinant DNA experiments. This "Berg letter" held sway until a conference led to official research guidelines from the National Institutes of Health (NIH) in June 1976.
At this point, Harvard became interested in building a special lab to handle riskier types of recombinant DNA research, per the new NIH guidelines. The lab would be equipped to contain modified organisms that could become pathogenic or disrupt the environment. Perhaps even more controversially for some, scientists were interested in working with human genes.
Mayor Vellucci caught wind of the plan, and what had been a relatively dry scientific debate exploded into the public consciousness. "They may come up with a disease that can't be cured — even a monster!," he said with typical brio, "Is this the answer to Dr. Frankenstein's dream?"
The City Council chamber here was packed to overflowing late on the night of 7 July as the Council of seven men and two women, used to dealing with taxes and street closings and similar civic matters, tried to grapple with one of the most perplexing problems in contemporary biology — the safety of certain types of research involving recombinant DNA.
Harvard and MIT professors slung it out at the city council meeting. Most of them opposed the ban. Harvard biology professor Ruth Hubbard, going against the scientific establishment, said, "I am frankly terrified at the idea of playing evolution, because it is an exceedingly dangerous game whose rules we will not know until it is too late."
The council ultimately voted for a 3-month moratorium as a citizen panel was convened to discuss and investigate the risks. That panel extended the moratorium for another three months, as Harvard biologists watched nervously. Tom Maniatis, then a young assistant professor, took his lab to Cold Spring Harbour because of the controversy. Maniatis would go on to develop groundbreaking techniques for easily isolating genes, so that they could be used to create recombinant DNA.
The panel ultimately decided to allow the research to happen with municipal oversight. In 1977, Cambridge became the first city to regulate manipulation of DNA, and the Cambridge Recombinant DNA Technology Ordinance stands to this day. And a debate over federal legislation would begin before it eventually ran out of steam. Science moved forward.
But Vellucci, for his part, was not finished with his political haymaking. In 1977, he sent this letter to the president of the National Academies of Science:
In today's edition of the Boston Herald American... there are two reports which concern me greatly. In Dover, MA, a "strange, orange-eyed creature" was sighted and in Hollis, New Hampshire, a man and his two sons were confronted by a "hairy, nine foot creature."
I would respectfully ask that your prestigious institution investigate these findings. I would hope as well that you might check to see whether or not these "strange creatures" (should they in fact exist) are in any way connected to recombinant DNA experiments taking place in the New England area.
Thank you in advance for your cooperation in this matter.
A CRISPR future
Earlier this month, several top scientists wrote a letter in Science warning about the risks of using CRISPR-Cas9 to modify human genomes. The first two names on the letter? David Baltimore and Paul Berg. It was a direct echo of the "Berg letter" from 1974.
"At the dawn of the recombinant DNA era," the letter concluded, "the most important lesson learned was that public trust in science ultimately begins with and requires ongoing transparency and open discussion."
Faced with groundbreaking new technology, the future can look uncharted and hazy. But rarely are all the unanswered questions being posed for the first time. CRISPR-Cas9 is a considerable advance over the crude genetic manipulation of 1970s recombinant DNA, but the ethical and social issues that surround are not new. The Frankenstein epithet, too, has persisted; if Vellucci were alive today, perhaps we'd be hearing about orange-eyed creatures, as well.
Picture: Screenshot from the Cambridge City Council meeting of 1976 / MIT Oral History Program