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Prof. George Church

Directed evolution: A chat with Harvard Medical School's CRISPR expert


Date: October 16, 2018
Weizmann Magazine Volume 14

Imagine having “editing rights” to the master plan of life. That’s what science has accomplished with CRISPR, a molecular tool that can change, delete, and replace genes in living cells and organisms. One of the foremost authorities on this system is Prof. George Church of Harvard Medical School.

Prof. Church was the first to make the new bacteria-based DNA-editing tool CRISPR usable in humans, in collaboration with the lab of Prof. Feng Zhang at the Broad Institute. Its punchy acronym stands for Clustered Regularly Interspaced Short Palindromic Repeats, but its innovation is hardly anything to be taken lightly: It is capable of fundamentally altering the natural world. Like a molecular scalpel, CRISPR is able to change, delete, and replace genes in living cells and organisms. 

Because it can enable gene drives—wherein a change made in one chromosome would copy itself in every successive generation, so that all descendants would inherit the change—it holds promise for eradicating diseases and making crops resistant to pests.

An initiator of the Human Genome Project, Prof. Church directs the Personal Genome Project, the only open-access information on the human genomic, environmental, and trait data. Co-author of the first direct genomic sequencing method, he contributed to dramatically lowering the cost of sequencing individual human genomes. He also leads the Synthetic Biology lab at Harvard’s Wyss Institute for Biologically Inspired Engineering, where he oversees the directed evolution of molecules, polymers, and whole genomes.

We caught up with Prof. Church after his keynote address at the Global Gathering.

Q    Are we entering an era in which humans determine the future of evolution?

A    I would argue that we have already been influencing our own evolution with existing medical technology, but with CRISPR, we’re able to begin going much faster. Just as there is potential for good, there is potential for bad. I don’t think anyone would argue against “deleting” malaria from mosquitos, or fixing schizophrenia, Alzheimer’s, or HIV. But when we change the nature of an entire species, we don’t know what the effects will be on other species, and on the environment. So we also must ensure that we have the ability to restore an organism to its original genetic composition.

Q    Do scientists working on CRISPR have a responsibility to explain what they’re doing to policymakers and the public?

A    Absolutely. As the potential for CRISPR as a tool in medicine becomes more real, there are many regulatory, political, and social hurdles to cross. Scientists have to make sure the policymakers know what they are doing and educate the public about what’s ahead, so they can be involved in the discussion. Everybody has to be literate about the risks and benefits. Scientists like myself working in this area can often see decades ahead of us. Our job is not only to move the science along, but to consider the ramifications of the various scientific avenues and predict which ones will be most fruitful and which will be fraught with problems. 

Q    Why do you have a bioethicist embedded in your lab?

A    Prof. Jeantine Lunshof is an independent philosopher and bioethicist who has been associated with my lab since 2003. This collaborative relationship is unusual, and what she’s doing is very important. As scientists, we are now able to create and manipulate life. We need to tread carefully, and move forward thoughtfully. She raises questions with us and helps us answer them. Should scientists enhance people’s genetic inheritance—to produce “designer babies”? Where do we draw the line between therapy and enhancement? Should CRISPR editing extend to human eggs, sperm, and embryos? Prof. Lunshof and I have written about a dozen papers together, and there are many more questions ahead. 

Q    Should we feel excitement or dread about the future of gene editing?

A    The biggest thing at risk is diversity. When discussing the use of CRISPR to improve the human species, the first thing people think about is looks. But is the prospect of making people better looking the worst scenario we can come up with? Ok, it would be weird for us all to be tall and blond and blue-eyed, but that’s not a public health threat. 

The implicit point in that worry is the loss of biological diversity: If we all had the same immune system and the same exact genetic makeup—now that would be a problem. The lesson of evolution is that diversity wins. We have to have ways to reverse mistakes, and make sure that this technology stays safe in the hands of well-intentioned scientists.

If we proceed smartly and responsibly, genome editing could revolutionize human health and reduce suffering, make us smarter, improve our memories, and extend our life spans. Also, from an economic point of view, it makes sense to sequence genomes and edit out the really bad stuff because our biggest health expenditures are on the sickest individuals, including children born with devastating illnesses. With CRISPR, children who were genetically destined to be very ill can be born healthy—because we edited out the disease in their father’s sperm before they were even conceived.