The pandora’s box problem in science

Earth-shaking discoveries

There are many discoveries in science, which make but a small impact on the world, discoveries that are tiny pieces of the puzzle, adding together to answer the grand scientific questions. 

There is another type of scientific discovery, the one which has the potential to impact the fate of humankind in some profound way.

How does it feel for a researcher to make this kind of discovery?

Is it elating?

Terrifying?

A bit of both?

I wouldn’t be able to tell, anything I discovered in my time as a scientist unfortunately (or maybe fortunately) didn’t have the potential to shake the foundations of humanity (or shake the foundation of anything, except maybe my ego).

But what if your discovery does just that?

Shake the foundations of humanity.

Scientific discovery suffers from a pandora’s box problem. Once a finding has been communicated to other scientists, it is impossible to take it back.

Scientists call to action – or non-action

It tells you something about the impact of a technology if the scientists themselves, those closest to the discovery are the ones to sound the alarm bells. 

In the (in)famous 1939 Einstein–Szilárd letter, written  Leó Szilárd and signed by the pacifist Albert Einstein, the physicists warned President Roosevelt about the possibility to develop the atomic bomb (enabled by the first nuclear fission experiments).  They urged the president to act - out of fear that Nazi Germany could be first to develop this weapon of mass destruction.

Some fifteen years, the release of two atomic bombs and the loss of over 100 000 lives later, Einstein (together with a group of other Noble Laureates) signed another document, the Russell–Einstein Manifesto, which highlighted the dangers of nuclear weapons for mankind and besieged decision makers to seek other problem solving strategies than nuclear annihilation.

After the first experiments on recombinant DNA opened the door to manipulating microbial – and, in sight at the horizon, also human - genomes, scientists gathered at the 1975 conference on gene therapy in Ansilomar, CA, to discuss the limits, which were to be imposed to the newly discovered technique.  It was the scientists themselves who committed to a voluntary moratorium, before rules for experiments on recombinant DNA were discussed at the conference.

When scientists found that a component of the bacterial immune system, the CRISPR-CAS9 system holds unprecedented potential for manipulating the human genome, the discoverers of the technology and other scientists called for a moratorium on heritable genome editing; in 2015, a few years after the seminal publication on the CRISPR from the 2020  Nobel Laureates Jennifer Doudna  and Emmanuelle Charpentier, and again in 2019 after the 2018 designer baby shock.

The promise of CRISPR CAS9

What aligns CRISPR CAS9 to those earlier earth-shaking discoveries?

The technique is as elegant, as it is simple, as impactful as it is scary; it allows researchers to precisely alter DNA; the DNA of adult humans, of unborn babies and of the human germline, of animals in the laboratory and of animals in the wild, of cultured crops and wild fauna, of microorganisms that produce biomaterials, drugs and vaccines.

It’s not difficult to imagine the good, the bad and the ugly outcomes of such a technique, ranging from the cure of genetic diseases to engineering desired genetic traits into children, from eradicating diseases such as malaria by releasing genetically modified mosquitos into the wild to causing unforeseeable environmental catastrophes by tempering with ecosystems, from fighting pandemics to newly designed biological weapons.

How much of this potential is already being realized? And how much of it is utopian or dystopian fantasy?

While numerous patients with genetic diseases and cancer set their hope in the potential of CRISPR-based therapies currently tested in the clinic, in 2018 we saw a glimpse of the darker side. The Chinese Doctor He Jiankui , performed a medically useless experiment of genetically modifying two twin girls on the single embryo stage to make them resistant to HIV. He felt the need to shout out his results to the public (on YouTube, a well-known source for high-quality, peer-reviewed scientific results).  But what about the scientists who don’t seek the spotlight? How many more experiments like He’s are performed quietly, despite a ban on germline editing in most countries? And what is happening outside the regulated laboratory environment?

The relative ease of using the technique has sprouted a group of so-called biohackers, which reversed the Don’t try this at home tactic and experiment with CRISPR kits in their living rooms and garages.

While arguably the complexity of germline editing and IVF, currently lies beyond the type of experiment you can perform in your living room, the question remains how dangerous the technique can be in untrained hands?

One thing is clear though - however risky, however promising we might consider the CRISPR technology, it is out in the world – and there is no pushing it back into the box.

Tune in next week for a deeper dive into the science underlying the CRISPR CAS9 technology, the challenges which lie ahead to use it for curing human disease and its use by biohackers.