“In his latest book, “The Codebreaker. Jennifer Doudna, Gene editing and the future of the human race” published in 2021 in spanish,Walter Isaacson Isaacson shares the life and story of a woman that made her way in a field -dominated by men, and the changing landscape around CRISPR (clustered regularly interspaced short palindromic repeats), and the life sciences The book goes from biohacking, meaning, applications of CRISPR outside institutions and labs, the ethical questions regarding gene editing, to how helpful these tools were during the COVID-19 outrage around the world. Besides the exciting plot behind Doudna’s story, an extra motivation for reading the book is its author: Isaacson has written outstanding biographies like “Jobs”, among others, in which he brilliantly portrays innovators in different areas. Isaacson elige a Doudna para retratar la historia de una mujer que llegó a ganar el Nobel en un campo dominado por hombres, y una década de descubrimientos y avances alrededor de lo que se denominan las CRISPR
Isaacson sets a parallel betwen the digital revolution and the genetic (or life sciences) one, in which Jennifer Doudna is the central character.
Jennifer Doudna The story starts with her early life growing up in Hilo, Hawaii, where she enjoyed long walks exploring nature. There, she read James Watson’s book based on his personal experience around the DNA (deoxyribonucleic acid) discovery that made him win a Nobel Prize with Francis Crick and Maurice Wilkins. In the article “The double helix”, published in Nature in 1953, Watson and Crick discovered how atoms were assembled to give DNA its structure. The article was 2 pages long, and in it they described the structure of DNA. Watson’s book influenced Jennifer deeply: it made her realize that she also could be a scientist, and that the life in the laboratory was exciting, like a search in the wild nature.
According to Isaacson: “The structure was perfect for the molecule’s function; this could transport a code that could be replicated. Crick wanted to include a longer section about the implications for inheritance”,but Watson convinced him to keep the end of the article open to the possibility of a mechanism for copying genetic material (p. 52).” (p. 52). For Watson’s (american) and Crickson’s (british) discovery, it was necesary to use three fields from the 20th century: genetics, biochemistry and structural biology (p. 39). Hence, until this moment, DNA was the star.
Doudna moved to California in 1981 to attend college at Ponoma University In the next summer she got a job as an assistant in Sharon Pasanenko’s lab, and participated as one of the research assistants in an article that was published in the Journal of Bacteriology. For posgraduate studies Doudna applied to Harvard and got herself a place in microbiologist Roberto Kolter’s laboratory where she could see science as a diverse and international activity. But she finally chose molecular biologist Jack Szostak’s lab team, who would become his doctoral advisor. Szostak encouraged Doudna to write her thesis about a subject that wasn’t studied as much as the DNA: the RNA (ribonucleic acid). As a postdoctoral researcher she went to Yale University, and stayed in Tom Steitz lab as a visiting scholar, in 1993 After that, she went to Berkeley and became the head of the lab and of teams that would make her spend almost ten years researching the processes related to the discoveries that will give her a Nobel Prize (2002-2012). Ok, up to this point I’ve made a summary of Doudna’s training.
So, going back to the book main development: it starts with the structure of DNA. While the DNA protected information, the RNA elaborated products such as proteins, which were anidated in the nucleus of cells. The small DNA segment of DNA that codes a gene into a RNA fragment, which moves to the cell production region. There, that messenger RNA facilitates the staging of the right amino acids sequence to obtain a specific protein. Among proteins, “enzymes” act as catalizers, as they are responsibles of triggering, accelerating and adjusting the chemical reactions that all living organisms go through (p. 67-69). Afterwards, the process of copy and paste to select those nitrons and assemble the useful bits of RNA required a stabilizer, a role that generally performs a proteic enzyme. At this point, Doudna y Szostak asked (themselves) if the ARN portions could copy itself
The book is as interesting as it is long, it goes from biohacking (application of CRISPR outside institutions), ethical implications of gene editing and even the pandemic, I make a summary of the timeline of publications “hits” to sum up this story:
1. In 1998, Jennifer y Szostack published an article in Nature, in which they showed how they had created a ribozyme with the ability to cut and assembly a copy of itself. They used different tactics and wrote in this article that “this reaction shows how RNA copies crystalized by the RNA itself are possible” (p. 73). The article was considered a technical milestone because they looked for different ways of creating a “ribozime with the ability of cutting and assembling a copy of itself” If the idea was to show how RNA was the molecule responsible for the origin of life -they thought- it was important to prove how this could replicate itself. This understanding of how small segments of RNA work – states Isaacson- would be key in the two following decades, especially in the field of gene editing and in the fight against coronavirus.
2. In january 2006, Science published Doudna’s article about RNA interferences , just a few months before an article by Francisco Mojica, from the University of Alicante, who was also trying to clarify the purpose of those grouped repetitions or sequences, that had already been found by researchers in twenty different species of bacteria (p. 98-99). In each of these teams, scientists also looked for the commercial possibilities of the discoveries related to gene editing with Crispr-Cas9. Here is what the story starts to get complex as it does the competition between scientists in order to be the first in doing these discoveries around how RNA worked.
It was actually Mojica, who invented the name “CRISPR”, because he didn’t like “tandem repetitions”, which was commonly used. They were called “tandem repetitions”, a name that Mojica didn’t like much, so, in a first moment, he re-baptized them as “short repetitions regularly spaced” (or SRSR). According to Isaacson, even though this name was more descriptive, it wasn’t easy to memorize. Mojica chose later the name we use now, which was inmortalized on an e-mail between him y and Jansen, another researcher from the University of Utrecht (Netherlands). In november of 2010, Jansen made formal the decision to use this name in an article.
3. In 2011, Emmanuel Charpentier, a french microbiologist, and her small team found out that the CRISPR-Cas9 system accomplished a mission of defense in front of viruses with three components: the ARNtracr, the ARNcr and the Cas9 enzyme The first one took long chains of RNA and processed them to turn them into small ARNcrs, that would direct towards specific sequences of attacking viruses. With this information, they prepared an article for Nature, that would be published in march, 2011 (pp. 156-157). Charpentier showed her findings at one of the CRISPR conferences, in the Netherlands, in october 2010. But she admits that her 2011 article in Nature didn’t describe the full purpose of the ARNtracr (pp. 157-158) For the next step she needed the help of biochemists that could isolate every chemical components in an test tube and show precisely how each worked. This is why she wanted to meet Doudna at the conference of the American Society of Microbiology in march, 2011, in Puerto Rico.
Simultaneously, George Church (Harvard) and Zhang Fen (Broad, Harvard/MIT, Lander’s protegé) were behind the same clues or tracks, interested in showing how the RNA worked as a guide in the genetic cut and paste process.
4. In 2012, Doudna, with Martin Jinek, at Berkeley, and Emmanuele Charpentier, in Sweden, with Krzysztof Chilinski in France, started a collaboration. In this 3500 words (¡) paper, presented a great amount of details regarding the ARNcr and the ARNtracr worked to assemble the Cas9 protein to the destination DNA. For such a short article –in comparison with 17-20 pages for social sciences- there ought be a huge amount of processed results to be communicated. The article also explained the structure of two Cas9 areas and how this determined that this cut each DNA line in a specific point Lastly, the article included the technique with which they were able to join the ARNcr and the ARNtracr to obtain a unique RNA, showing that this system could be used in genes (pp. 170-171). The editorts at the journal Science received with enthusiasm the article because while many of the functions of CRISPR-Cas9 in living cells had been described previously, this was the first time that researchers had isolated the main elements that were essential to the system and showed their biochemical mechanisms. Also, it was clear that there was an innovation regarding a unique RNA guide that could have potential applications.
Following Doudna’s pressure, Science accelerated the revision process. She knew that there were other articles about the CRISPR-Cas9 system, but she wanted to make sure that theirs was the first one The article showed that CRISPR-Cas9 could be used to edit human genes, but it showed no evidence. Nevertheless, the editors of Science formally accepted it in june 20th, 2012. (p. 172)
5. In January 2013, Cell magazine published Eric Lander’s paper Cell: The heroes of CRISPR . Lander was the Director of the Broad Institute at MIT/Harvard (where researched Feng Zhang, the competition of Berkeley’s Laboratory)in which he maps the different discoveries and key scientists that helped in the most relevant findings regarding CRISPR. But this article was controversial, as, for some in the scientific community, undermined Doudna’s and Charpentiers achievements to emphasize and even maximize Zhang’s, from the Broad Institute, which Lander directed perfil de Eric Lander]. This article was also considered a machiavellian move by Lander, in order to erase Doudna’s “contributions”, and for some scientists it was similar to how Rosalind Franklin’s contributions to DNA were erased from the history of the DNA. There were much more contributors in the decade that was relevant to CRISPR (a team from Lituania, an argentine that started with Feng, among others). But Feng-Lander and Doudna-Charpentier became the most known figures. But, after years of more developments in this field, through a patent war between Berkeley University and the Broad at Harvard/MIT, Doudna and Charpentier received a Nobel Prize in 2020, because, even when Zhang and other researchers had made brilliant applications of CRISPR-Cas9 to cells, Doudna and Charpentier were the pioneers of the technique.
I’m writing here a very short summary of Isaacson’s book, which amazed me in its simplicity to communicate such a complicated issue, in such a complex field. But it also surprised me his accuracy and detail of the “papers war” between each team of scientists and labs. I thought that this is the part that most communications and public relations professionals probably don’t know about science, thus, I search five lessons from the book:
a) It’s all about papers. The book shows the “behind the scenes” of this process, the team work, the pitch and following of editors. In some cases, top scientists such as Doudna exercise an extra pressure on editors, due to the fact that they receive millions of dollars in funding, grants and the recognition of their institution is at stake The paper or scientific article is the product of a researcher/scientist. Scientists communicate with each other through science articles that involve experiments, teamwork, contributions to a field, and even their own media relations with editors from the main journals.
b) The hyper specialization of science in very specific fields also shows that the publishing space is concentrated in three main players: Nature, Science, Cell, as we’ve seen previously. in these three players is where main discoveries and achievements are published Therefore, competition to be featured in those journals is fierce
c) Besides articles, events like seminars and conferences are key for the advancement and communication of researchers of a discipline or field. In the book, Isaacson mentions the Cold Spring Harbor, and the CRISPR conferences held in Puerto Rico, the Netherlands, California, among others.
d) Knowledge is built upon other people’s knowledge: this is why even competing scientists MUST know to which extent they add new knowledge to their field, and must “acknowledge” which steps helped them in getting there. It certainly is about getting first, but there’s no room for ignoring similar achievements or innovations, even when they were made by competitors
e) There is no pitch or press release until the scientists/researchers have pitched their way: through experiments, arguments, and statements regarding their contribution, following certain standards. Media teams and public relations professionals from universities (from the administration) do not participate in the publishing (articles) process. Thus, this is why head labs like Doudna exercise an extra pressure on editors. While each university has marketing and communications machinery, the timeline I shared is exclusively about researchers’ work. This is all about intelectual, techmnical talent, but also, human cooperation and also, lots of ambition
In summary, I hope you find this review interesting, as Isaacson argues that this book shows the possibilities of life sciences and genetic editing for changing our society.
Isaacson, W. (2021). “The Codebreaker. El gen de la vida. Jennifer Doudna, la edición genética y el futuro de la especie humana. Buenos Aires. Debate.
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