Beyond the editing metaphor

“Gene “editing” is not a particularly good metaphor for explaining the science of this new technology. With a computer I can easily cut and paste text from one application to another, or make clean deletions—letter by letter, line by line. But CRISPR does not have these precise editorial functions.”

“CRISPR is like a tiny Reaper drone that can produce targeted damage to DNA. Sometimes it makes a precision missile strike, destroying the target. It can also produce serious collateral damage, like a drone attack that accidentally takes out a wedding party instead of the intended target. Scientists often accidentally blast away big chunks of DNA as they try to improve the code of life.”

“CRISPR can also go astray when the preprogrammed coordinates are ambiguous, like a rogue drone that automatically strikes the friends, neighbors, and relatives of suspected terrorists.
Once inside, it can persist in cells for weeks, bouncing around the chromosomes, producing damage to DNA over and over again every time it finds a near match to the intended target.”

Unintended consequences

“It is important to signal a sense of risk or a need for caution in using CRISPR. Other metaphors—like genetic ‘surgery’ or DNA ‘hacking’— have been proposed to replace the idea of ‘editing.’ The idea of genetic surgery suggests that there can be a slip of the surgeon’s knife, creating an unintended injury. Each of these images—the targeted missile, the surgeon’s scalpel, the hacker’s code—offers a perspective on how CRISPR works, even while concealing messy cellular dynamics. In the absence of a perfect metaphor, ultimately I think that technical language describes it best: CRISPR is an enzyme that produces targeted mutagenesis.

In other words, CRISPR generates mutants.”

–excerpted from The Mutant Project by Eben Kirksey

Natural progression?

“Dr. He closely followed the case of Junjiu Huang, the Chinese scientist who caused a moral panic in April 2015 by being the first to use CRISPR to edit non-viable human embryos. After the sensational headlines faded away, scientists in the United States, Europe, and elsewhere began to catch up with their own CRISPR experiments. The top scientific journal Nature celebrated Huang as one of “ten people who mattered” in 2015.

At Sun Yat-sen University—a venerable old institution in Guangzhou, an hour away from Shenzhen by high-speed train—Huang was promoted to full professor.

Dr. He saw an opportunity to cut the competition off at the pass. The atmosphere seemed ripe for embryo engineering in the clinic. He was at the height of his power and was prepared to embrace controversy. As he recruited new staff with the right expertise, one big question occupied his mind: Which gene should he target with CRISPR?

Enhancing humans

Invited to a workshop at Berkley in January of 2017, Dr. He presented his latest findings and hinted that he was thinking about bringing CRISPR into the clinic.

James Watson, the Nobel laureate who had become infamous for his controversial remarks about race and gender, visited Dr. He’s as the embryo engineering experiment moved into the clinic. After Watson gave a public lecture at the Shenzhen International Precision Medical Summit, there was a public Q&A session. Dr. He asked if the possibility of rewriting the genetic code had been on his mind as he published his famous paper with Francis Crick describing the double helix structure of DNA. Watson replied that yes, of course it had.

As a follow-up, Dr. He asked: What should we do with gene editing? Watson simply said: Make people better.”

Designer babies

“CRISPR research in human embryos fascinated one of Dr. He’s biggest supporters—Bingwen Xie, a local Communist Party official who was the deputy head of Shenzhen’s Nanshan district. Xie knew about the devastating social and economic impacts of HIV in China, and he brought the enterprising young scientist to Wenlou village, nearly 1,000 miles north of Shenzhen. There Dr. He saw the impacts of the disease firsthand.

Upon returning to Shenzhen, Dr. He had a fresh sense of purpose. As an entrepreneur, working closely with government officials, he brought fresh optimism to an old and seemingly unsolvable problem of human suffering. It was like he was living in an HSBC Bank commercial. This was a story of human ambition and innovation. If he succeeded in curing HIV by bringing the world’s first CRISPR babies into the world, he would bring glory to the nation.”

–excerpted from The Mutant Project by Eben Kirksey

Risk and reward

“Jay Johnson volunteered to become one of the world’s first edited people in 2009 because he was enamored of this experiments purpose. ‘The need to find a cure for the virus superseded my fear or the concerns,’ he told me. Johnson is African American, has striking green eyes, wears a salt-and-pepper moustache, and has a subtle hoop ring in his right ear. He works for Action Wellness, an organisatiton in Philadelphia that helps people living with HIV and other chronic illnesses secure access to medical treatment regardless of race, gender identity, immigration status, insurance status, or the ability to pay. Throughout his professional career, Johnson has collaborated with other groups in Philadelphia to bring principles of social justice together with effective health care.

Gene therapy ethics

Johnson, who has worked as a nurse, is acutely aware of the many ways that people of color have been excluded from science and medicine. In recent history, black communities have experienced the risks associated with clinical trials, while enjoying few of the benefits. The best-known case of science profiteering in the black community involved Henrietta Lacks, whose cells were collected without her consent in 1951. The infamous Tuskegee by the US Public Health Service (1932-1972) denied penicillin treatments to the ‘negro’ male participants, who were suffering from syphilis. While the more egregious abuses of black research subjects are no longer prevalent in the United States, there is still reasonable mistrust within African American communities when it comes to scientific enterprises and experimental medical treatments.

Now Jay Johnson sits on a community advisory board that oversees scientists who conduct HIV research. ‘Most of the principles that are involved with the studies are of the white persuasion,’ he told me. In these white spaces, Johnson serves as a persistent advocate for members of marginalised groups, including people of color and members of the transgender community. ‘People in these groups are already isolated a lot of times,’ he said, so it is a challenge to make them feel included. When Johnson helps recruit other potential participants, he tells them: ‘We have been in these studies. It’s okay. Come listen to our stories.'”

Silence = Death

“As a veteran of ACT UP – the AIDS Coalition to Unleash Power – Matt Sharp has long been fighting inequality in science and medicine. While Jay Johnson was working toward the same goals – carefully, quietly, behind the scenes – Sharp was out in the streets. Sharp was among those arrested at the National Instituted of Health in MAy 1990 during an unruly protest with rainbow-colored smoke bombs and signs with powerful messages: ‘Clinical Trials Now,’ ‘Silence = Death,’ ‘Red Tape Kills Us,’ and ‘One AIDS Death Every 12 Minutes.’ When he signed up to join a genetic engineering experiment in June 2010, he did not know that he would soon be reliving battles from decades ago. After Sangamo Therapeutics altered his DNA, Sharp became entangled in a high-stakes struggle over the future of gene editing.

By embracing risks associated with trial gene therapy that others would find unacceptable, members of the HIV-positive community also opened up broader experimental possibilities for humanity.

If gene therapies become increasingly common, as predicted by the FDA regulators, many more of us will owe a debt to these early moral pioneers.”

–excerpted from The Mutant Project by Eben Kirksey

Science fiction and opportunity

“Suffering from a genetic disease, HIV activists have struggled for survival in a complex moral landscape, much like the mutants of classic Marvel comic books. They forged alliances with people who were not essentially good or evil, and learned to switch sides as circumstances changed. HIV activists, much like the X-Men, have found moral certainty through battles with government agents, corporations, and scientific researchers who did not always have their best interests in mind.

Unholy alliances, made between people with conflicting interests and values, allowed for a livable future. From the get-go, activists learned how to transform their allies. As they recruited people from the medical establishment, the activists used surprising tactics to turn scientists and doctors into radicals.”

Progress?

“A multimedia display in the main exhibit hall of China’s premier genomics company (BGI)  featured a looping video about ‘future applications of cell storage,’ where scientific facts bled into science fiction. A lamb fetus was moving inside an artificial womb, a clear plastic bag with tubes that act like an umbilical cord. The fine print on this multimedia display indicated that the experimental work had been done elsewhere: the Children’s Hospital of Philadelphia (CHOP). Researchers at CHOP had incubated premature fetal lambs for four weeks until they were ‘born.’

Rearing babies in artificial wombs has also long been a dream of radical feminist thinkers. While many celebrated ‘natural’ childbirth, in the 1970s Shulamith Firestone openly called for a revolution in reproductive technology that would liberate ‘women from the tyranny of their reproductive biology by every means available.’ A fundamental injustice is hardwired into the human condition, she wrote in The Dialectic of Sex, since it involves ‘reproduction of the species by one sex for the benefit of both.’ Firestone died in 2012, so I can only imagine her ghost as a haunting presence at BGI’s exhibit about the future of reproductive medicine. The blurred boundaries between facts and fiction in the exhibit would not have given Firestone pause, since she argued that ‘imaginative construction precedes the technological.’ In other words, she insisted that we take technological dreams seriously before they become reality.

A close reading of The Dialectic of Sex reveals that Firestone was a shrewd thinker—aware that scientific innovations can liberate some people even while reinforcing other social inequalities. Firestone warned: ‘In the hands of our current society and under the direction of current scientists (few of whom are female or even feminist), any attempt to use the technology to ‘free’ anybody is suspect.’ Echoing the sentiments of many disabled intellectuals and deliberately using charged language, Firestone also warned about the coming ‘genocide of cripples and retards for the sake of a super-race.'”

Fiction in the clinic

“Prior to CRISPR experiments, profit driven companies were already offering a host of expensive and scientifically unproven “extra” procedures tacked on to IVF. Chemical treatments like ’embryo glue’ and surgical procedures like ‘womb scratching’ had been rolled out in the clinic before they were scrutinized according to rigorous scientific standards and without randomized control trials.

Now it is also routine to inject sperm into an egg as part of standard fertility treatments, but this procedure was discovered by mistake. No rigorous tests were conducted, but after this accident it was just taken up as a new practice, adding to the history of IVF clinics making money from couples who have little chance of actually getting pregnant.”

–excerpted from The Mutant Project by Eben Kirksey