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Science / CRISPR

CRISPR, Scientific Discovery, and Women Rewriting History

What if we had the power to rewrite precise portions of DNA, the universal language of biology? The implications would be far-reaching; editing this code would change how we think about crops, disease, and bioethics among a multitude of other fields. Thanks to a scientific tool developed by Jennifer Doudna and Emmanuelle Charpentier, this power is no longer a dream, but a reality. Their method, named CRISPR-Cas 9, typically abbreviated as CRISPR, has quickly become one of the fastest-growing areas of research for microbiologists. However, like the genes that they work with, the story of their success is in danger of being rewritten because of the ways in which gender inequality continues to marginalize female scientists.

Many of our society’s recent efforts to achieve greater gender equality have been focused  on combating sexual violence, especially in relation to Hollywood and the #metoo movement. Gradually, our collective mentality surrounding the role of women in society is shifting as progress is being made, even with bumps along the road. And yet, gender inequality still remains discouragingly out of reach. Of course women deserve to live without the incredibly heavy burden that comes with sexual harassment and the fear of gender violence, but they also deserve so much more. Women deserve to be treated with respect, which includes having their voices and ideas listened to, as well as having their professional accomplishments recognized. In an era when the fight for gender equality has become focused on overt displays of sexism and violence, we must also remember that portrayals of professional women, especially those in scientific fields, must be addressed in order to inspire future generations of female scientists, generations who will, in turn, make great contributions to scientific discoveries.

The silencing and ignoring of the thoughts and work of women has shaped American scientific history, but it also greatly contributes to how we interact with science in the current age. Although many are aware of the systemic bias against women in science that prevents women from  receiving full credit for their accomplishments, few know that this phenomenon is so ubiquitous that it actually was given a name: the Matilda effect. High school science textbooks usually make a point to acknowledge the inequality in the field, but often they do so in a way that relegates the Matilda effect to the past; examples such as Rosalind Franklin and Marie Curie are brought up only to remind us of the shortcomings of our past. Rarely is this problem explored in any sort of modern-day context. Likewise, the Matthew effect, in which scientific credit is more often awarded to already well-known researchers, also goes widely untaught  and unacknowledged in academic settings.

Patterns of de-emphasizing the work of female researchers are often explored through a few key examples that have achieved the status of household names. A classical case study is that of Rosalind Franklin, a chemist whose work was critical in the discovery of the structure of DNA. For this breakthrough, a Nobel Prize was awarded to three men–Watson, Crick, and Wilkins–in 1962. Nobel Prizes are not awarded posthumously and although Franklin died in 1958, it is unclear if the prize would have been shared among the four scientists had she been alive. Franklin’s data was detailed, comprehensive, and accurate; using x-ray crystallography, she captured a photo that was instrumental to the work of the men who received the prize. Preserved in modern-day memory as a story of competition and gender bias in the field of discovery, Franklin’s unrecognized observations should not be relegated to a time of the past, but rather be used to explore how these same forces of oppression and marginalization inform science today.

Far better examples of the invisibility of women’s professional work are the stories of women who, unlike Franklin, never became known for the unjust treatment they received, much less gained recognition for their significant accomplishments. Unsurprisingly, tales of marginalized women in science transcend a broad range of disciplines and generations. Over one hundred fifty years ago, female researcher Nattie Stevens was born. As one of the earlier women to participate in scientific observation, she studied sex determination and linked sex to genetics as opposed to environmental, chemical, or other factors. In our high school biology textbooks, the names recorded with this discovery are Thomas Morgan and Edmund Wilson, despite the fact that Stevens’ work predated them. The men, compared to Stevens, had enhanced access to publishing and the ability to widely disseminate information. From her example, it is clear that the rewriting of scientific discoveries in which women are often excluded is a trend with deep historical roots. As such, efforts to combat inequality must take this into consideration and respond accordingly.

As we’ve seen from the work of Stevens, women’s voices tend to be erased from textbooks–the symbols of knowledge that is passed down over generations. In addition to the body of knowledge preserved in textbooks, scientific achievements are recognized via Nobel prizes and other awards. The work of three other women–Chien Shiung Wu, Jocelyn Bell Burnell, and Esther Lederberg–all went unrecognized in the sense that their names were not included when Nobel Prizes were awarded for the topics that they had diligently studied. The eras of the prizes that featured their discoveries spanned a range from 1957 to 1974 and their topics covered the diverse fields of physics and physiology. Despite these differences, the treatment of these women remained strikingly similar. All three effectively changed the course of the respective fields: Wu helped disprove the physics law of parity, Burnell discovered remnants of supernovas called pulsars, and Lederberg helped develop a method of bacteria transfer that remains in use today. The influences of these women remain visible in society, and yet each of them was excluded from the Nobel Prizes that were awarded to the teams of men with whom they collaborated. Without the public recognition associated with the prize, the names of these women remain largely unknown in modern society.

Even though at times it feels as though we have made great progress in terms of the Matilda effect, much work remains. The coinciding of the women’s march, #metoo movement, and the paradigm-altering discovery of CIRSPR-Cas 9 technology has created a crossroads that has the potential to evolve into a major turning point for women in science. Working out of a lab at the University of California Berkeley, Jennifer Doudna and Emmanuelle Charpentier successfully harnessed the power of CRISPR by proving that it could be used to edit DNA in test tubes. The process is remarkably simple; a protein is provided with a string of letters found in DNA and upon finding the matching sequence within a gene, the tool makes an incision. Once the DNA has been cut, novel sequences of nucleotides can be introduced, altering the DNA code and the corresponding protein that is produced. The implications of this discovery are huge and have the potential to alter the genes of crops, humans, and other animals. For example, scientists are already studying how CRISPR might be utilized to correct specific mutations in DNA that underlie debilitating genetic diseases. Sickle cell anemia, cystic fibrosis, Huntington’s disease, and SCID (also known as Bubble Boy Disease) all make excellent candidates for treatment via CRISPR since the specifics of the genetic causes are well-understood and relatively simple to correct. However, even if CRISPR is destined to become wildly successful in the medical field and beyond, the two women who put countless hours into its development may never experience corresponding success because of a brutal patent war and uncertainties about the Nobel Prize.

Photo by Thor Nielsen / Norwegian University of Science and Technology (NTNU)

Doudna and Charpentier filed for a patent on CRISPR-Cas 9 technology in May of 2012. Although their scientific paper on the use of the technology did not extend to living cells, they were cognisant of CRISPR’s versatility. In her book entitled A Crack in Creation, Doudna writes:  “We included a statement in the abstract of the paper pointing out the utility of a programmable DNA-cutting enzyme for genome editing. In addition, we concluded the article with a brief but significant nod to uses of CRISPR outside of bacteria, including in other cell types.” Six months later, researcher Feng Zhang working with the private Broad Institute of MIT and Harvard also filed for a patent. Much of his research overlapped with that of the women and it also extended previous work on CRISPR to living cells. One other important detail: Zhang’s team applied for an accelerated patent. With vast applications and a huge commercial market at stake, the scientific community waited in eager anticipation for a decision regarding the patents. Who would ultimately win: Doudna, who filed first and developed an original technology within a public institution; or Zhang, who applied the technology to living cells and chose an accelerated path backed by private universities? In 2014, the U.S. Patent and Trademark Office sided with Zhang and the Broad Institute. When the ruling was contested by Berkeley, the office ruled in February of 2017 that the two requested patents did not interfere, thus giving Zhang an enormous advantage: control over CRISPR’s use in eukaryotic cells, encompassing human medical applications.

Patent decisions can be difficult to judge especially when they contain copious amounts of technical jargon. However, it’s indisputable that in the case of CRISPR, whomever should obtain the fundamental patent for the technology will receive immense scientific recognition, monetary benefit, and control over the usage of the technology. For the moment, it appears that the patent decision aligns with historical trends; Zhang, a male researcher of well-known Harvard and MIT triumphed over Doudna and her affiliation with a public institution despite Doudna’s prior publication and application date. Although the decision cannot be completely reduced to these binary factors, the situation is certainly worth considering given this information as well as the stories of historical female scientists. For Doudna’s team and UC Berkeley, the decision is certainly a setback in terms of research and recognition. But what if we also view it as a more general defeat in terms of the battle to cultivate strong female leaders in scientific fields?

The patent decision largely concerns the economic side of the debate; beyond this dimension lies the question of scientific recognition, of how the story of the conception of CRISPR will be remembered. Attacks and counter-attacks have already been launched from the teams of each coast in attempts to record the history of CRISPR in a way that highlights the role of the respective key players. Most notably, Eric Lander, founding director of the Broad Institute published an article in Cell entitled “The Heroes of CRISPR” in which the role of Zhang’s team is overstated while the role of Doudna’s researchers are underemphasized. He also failed to adequately acknowledge the conflict of interest created by his affiliation with the Broad Institute. Despite the substance of these critiques, the California scientists have been accused of communicating similar inflations of their role in the development of the technology. Ultimately, the novelty of CRISPR means that the record of the discovery is still plenty malleable and unlikely to be locked into a singular narrative by a handful of conflicting articles at this point. Rather, the single largest factor in determining the history of the technology other than the patent will be the Nobel Prize.

Because of the revolutionary nature of CRISPR technology, most agree that a Nobel Prize is in the pipeline. The question is not if, but when. Beyond these two questions, it’s worth pondering who will be among the recipients, and what this will mean in terms of the modern day fight for gender equality. While the arguably sexist patent decision aligns with the historical treatment of women in science, a Nobel Prize will have the ability to set the record straight or reaffirm the marginalization of women. Will the prize honor Doudna and Charpentier for their initial discovery and implementation? Will the Nobel committee follow the lead of the US patent office and choose to celebrate the accomplishments of Zhang and his team? Or will a Nobel encompass some combination of researchers such that unique developments and applications can each be recognized for their own merits? The rewriting of DNA via CRISPR had led to a pivotal moment in numerous ways, the majority of them science-related. However, it also possesses the incredible potential to reshape how society views the interaction between women and science, and to become a symbol for equality within the context of a renewed feminist movement.