Can we keep CRISPR responsible?

Feb 19

THE FUTURE OF CRISPR WITH JENNIFER KUZMA

Jennifer Kuzma talks gene editing ethics

Designer babies, agricultural mishaps, extinction via gene-drive – all possible now that CRISPR has placed into our hands the awesome power to “edit life” in all its forms. So, how to keep the good while preventing the bad? How to safeguard our future? Is that even possible?

I asked Jennifer Kuzma, global expert on biotech responsibility, to shed light on one of the most important governance challenges of our time: gene editing ethics and how to put guardrails around CRISPR.

MEETING JENNIFER KUZMA

Jennifer Kuzma is a world expert on biotech responsibility and governance. She is Distinguished Professor in the Social Sciences and co-founder of the Genetic Engineering and Society Center at NC State University, and her career spans Humphrey School of Public Affairs, University of Minnesota, U.S. National Academy of Sciences, Engineering and Medicine, the American Association for the Advancement of Science and the U.S. Department of Agriculture and 125 scholarly publications (and counting). She contributes frequent public commentary on biotech policy in publications such as the New York Times and Wired magazine. She cares, and she’s working hard to create a better future!

We had a wonderful, wide-ranging conversation. I was struck by her pragmatism and clear-headedness – assets that doubtless serve her well as she navigates all the competing interests in the biotech world. We talked about how to create more ‘techno-realists’ to balance the techno-optimists who drive the US innovation economy. We discussed skills versus resourcing deficits in policymaking, and the need to broaden government risk assessments beyond narrow, department-specific responsibilities to include proper assessment of ‘ecosystem-scale’ effects.

Thank you Jennifer, for inspiring me with your dedicated work on such a ‘wicked problem!’

Scroll down below the podcast for links to the examples and case-studies we discussed. You will also find comments, predictions, and suggested further reading. I encourage you to explore, because every decision-maker who takes a moment to reflect on the risks & implications is a small step towards a better, safer future.

Oh, and if you are interested in working in this space, do it! The world needs more Jennifers and we cannot (responsibly) clone her :-)

Enjoy the podcast!

CHECK OUT THE PODCAST TRANSCRIPT →

RISK VERSUS REWARD

At various points when we were discussing CRISPR opportunities, global biomass and CRISPR science priorities, I mentioned my day with Rodolphe Barrangou, one of the absolute legends in the CRISPR space who is working day and night to use CRISPR to do good for global agriculture, food production, and sustainability.

Rodolphe’s lab is also located at NC State University, and I narrowly missed teeing up my interview with Jennifer on the same visit. For an excellent counter-balance to this discussion of risks and controls, listen to Rodolphe’s explanation of the truly stunning global benefits on the table.

GENE-EDITING MISHAPS AND NEAR MISSES IN AGRICULTURE

Jennifer gave examples of some gene editing mishaps that led to serious consequences, and some ‘near misses’ that might easily have led to serious consequences. (Note that I’m using the term gene-editing in the broadest sense here, to encompass GMO/transgenics and CRISPR edits).

The phenomenon of genetically engineered herbicide-resistant crops producing herbicide-resistant ‘superweeds’ as a harmful secondary consequence is described in this Harvard article, of which a salient line is, “Twenty-four cases of glyphosate-resistant weeds have been reported around the world, 14 of which are in the United States,” and this Scientific American article canvassed possible future solutions and quoted Jennifer extensively.

The 1999 ‘near miss’ in which cross-pollination saw corn genetically-modified to contain a pesticide and approved for animal feed, only find its way into taco shell products for human consumption, is summarised in this UC Davis article and discussed in the context of more positive future directions in this Harvard article.

A 1999 piece in Nature documented how transgenic pollen harmed monarch butterfly lavae – a ‘near miss’ because further studies concluded that the risks from concentration-levels found in the field were negligible. Unfortunately the butterflies were not entirely off the hook; a greater and more direct threat to Monarchs turned out to be the killing of milkweed, their principal food source.

GENE-DRIVES AND ECOSYSTEMS

I consider gene-drives to be one of the most perilous applications of gene-editing technology in terms of potential unintended and irreversible outcomes spanning ecosystems. We are quickly moving towards field trials of gene-drives to modify or eradicate entire populations of mice and mosquitos.

Jennifer authored this excellent public-friendly report on gene drive environmental impacts and governance for the International Risk Governance council. Nature has a scientific breakdown of different gene drive approaches and a plain-English article on the dilemma was published in the New York Times.

HUMAN GERMLINE EDITING – AKA ‘DESIGNER BABIES’

I mentioned He Jiankui in our conversation, the scientist who made the first (unauthorised, and subsequently widely criticised) germline genome edits on human embryos to produce the world’s first gene-edited babies.

Germline edits (as opposed to somatic edits) are controversial because they are conducted at the very earliest developmental stage which means they propagate to all cells, including reproductive cells, to be passed on to future generations. I.e. the edits are heritable.

Like it or not (I do not) I consider human genome editing services to produce “designer babies” a 100% certainty in our future.

MODIFICATION THERAPIES

The trial I mentioned where a New Zealand patient’s liver has been edited to lower LDL cholesterol is a recent and especially important milestone because the ‘future arrow’ is very directly pointed at gene therapies to reduce cholesterol in people who DON’T yet have heart disease but might simply want to reduce the possibility – ie for ‘modification’ as opposed to curative purposes.

The trial is being conducted by Verve Therapeutics. I was recently lucky enough to meet one of the co-founders, Kiran Musunuru, a seriously impressive and thoughtful scientist who is committed to saving lives with genetic diseases. He aims to create a ‘one and done’ therapy, first to cure sufferers of familial hypercholesterolemia then for all heart attack victims (as a one-shot treatment before they leave hospital) then, once proved as a safe approach, for use by anybody to prevent them from getting heart attacks in the first place.

I predict that many hundreds and perhaps thousands of such ‘modification therapies’ will enter the market, which will multiply the regulatory challenges of deciding between (a) edits that are clearly in the best health interests of the patient versus edits which also embody significant downside risk, and (b) edits that can be clearly categorized as ‘medicinal’ versus those that should be categorized as ‘cosmetic/lifestyle.’

It’s going to get a LOT harder deciding between the responsible and irresponsible!

THE CRISPR ‘PROLIFERATION PROBLEM’

One area we grappled with but didn’t sketch out any kind of solution was the ‘proliferation’ problem regarding CRISPR technologies. This remains my biggest overall concern in this field.

In my view, CRISPR will most certainly be employed by many thousands of very small businesses, groups, and even individuals to edit life on this planet. A few such entities will be malicious, which is one part of the problem (weaponization). Many many more will be either irresponsible or incompetent.

Remembering that one bad edit irresponsibly introduced has the potential to destabilize an entire ecosystem, it is the latter that concerns me the most. Creating some kind of framework to monitor and manage THOSE risks, globally, is going to take some doing.

EXAMPLES OF ‘LIGHT TOUCH’ REGULATORY APPROACHES

Jennifer mentioned some examples of regulatory approaches to gene editing ethical issues worth looking at.

The Norwegian Biotechnology Advisory Board recommendations for how GMOs and gene-edited organisms should be regulated, including allowing gene-edited crops to be regulated as ‘conventional’ as long as a notification is submitted to the government, is written up in this document.

Here is an overview in Nature of Australia's decision not to regulate CRISPR edits and also a solid contra view pointing out the inadequacies of this approach and proposing an alternative based on ‘scale of use’ by Prof Jack Heinemann of the University of Canterbury in New Zealand. I agree with Prof Heinemann’s logic.