Today it was announced that scientists in the Francis Crick Institute in the UK would be allowed to use CRISPR-Cas9 technology to edit the genome in human embryos. There has been a lot of controversy surrounding CRISPR technology (apart from patent rights and giving proper credit, there have been lots of ethical issues with the technology) especially when one Chinese group used the technology (perhaps prematurely) to edit human embryos. This time, the scientists, led by Kathy Niakan, have received official permission from the UK Human Fertilisation and Embryology Authority (HFEA) to be able to conduct their research. The main interests in their research revolve around infertility. For more information, check out Nature News.
The internet blew up last week when Eric Lander published his historical perspective on CRISPR in Cell, titled: The Heroes of Crispr. Part of the controversy comes from the fact that Lander seems to downplay the contributions of others in developing the technology (Especially WOMEN, like Jennifer Doudna). The other issue is that there is currently a huge legal battle over the patent rights for this technology, and none of this seems to be mentioned. Rightfully, social media freaked out. Jezebel has a nice opinion piece on the topic:
On January 14, Eric S. Lander published an article in the journal Cell celebrating the “heroes” of CRISPR-Cas9, a revolutionary DNA-editing technology that may be the most important genetic engineering development in decades.
“It’s hard to recall a revolution that has swept biology more swiftly than CRISPR,” Lander, a biologist at MIT and Harvard’s Broad Institute, wrote, noting that, although nearly every molecular biologist is familiar with the technology that allows scientists to easily disable or change the function of genes, they are likely unfamiliar with the manpower that went into its discovery.
“Yet, the human stories behind scientific advances can teach us a lot about the miraculous ecosystem that drives biomedical progress,” he continued, “about the roles of serendipity and planning, of pure curiosity and practical application, of hypothesis-free and hypothesis-driven science, of individuals and teams, and of fresh perspectives and deep expertise.”
What Lander failed to recognize in his article—and what many of his colleagues and commenters on the piece have recently condemned him for—is that his institute is currently involved in a billion-dollar patent dispute with the University of California’s Jennifer Doudna and Emmanuelle Charpentier of the Helmholtz Center for Infection Research in Germany, which played a vital role in developing CRISPR-Cas9. Not only did the Cell paper fail to disclose the potential conflict of interest, it significantly minimized the role of Doudna’s lab in advancing the technology.
In 2012, Doudna and a team of collaborators published a basic guide to using CRISPR to cut DNA at specific spots, according to MIT Technology Review. This spurred a race in the scientific community to see who could get the technique to work in plant or animal cells. Two studies applying the technique to human cells were published at virtually the same time: one by the Broad Institute’s Feng Zhang, the other by Harvard’s George Church. Doudna published another paper demonstrating the same thing four weeks later.
The US Patent and Trademark Office awarded the first patent for the use of CRISPR to edit specifically eukaryotic (organisms with a nucleus) genomes to Zhang in April of 2014, although an application for a similar patent (it’s unclear, and potentially unimportant, whether the patent application was for the use of CRISPR to edit prokaroytes or prokaryotes and eukaryotes) had been filed by Doudna and Charpentier seven months earlier.
Zhang was granted the patent first likely because he applied for fast-track approval, despite the fact that Doudna and Charpentier had been awarded the prestigious Breakthrough Prize for the discovery.
“I think without Zhang fast-tracking his application, the PTO would have flagged it for being in conflict with Doudna’s earlier application,” New York Law School’s Jacob Sherkow wrote in an email to The Scientist. “We may have been living in a world where there were no issued CRISPR patents [until 2017].”
That Lander would attempt to write the definitive history of the development of a groundbreaking, potentially Nobel Prize-worthy technology, especially while in the midst of a legal battle surrounding exactly that, struck many as a bald-faced attempt at excising, in this case, the contribution of women from the scientific record.
“From Cell editor: ‘…the author engaged in substantial fact checking directly with the relevant individuals.’ However, the description of my lab’s research and our interactions with other investigators is factually incorrect, was not checked by the author and was not agreed to by me prior to publication,” Doudna wrote in a PubMed Commons comment.
“I regret that the description of my and my collaborators’ contributions is incomplete and inaccurate,” Charpentier added. “The author did not ask me to check statements regarding me or my lab. I did not see any part of this paper prior to its submission by the author. And the journal did not involve me in the review process.”
In an email to The Scientist, Lander wrote that he had disclosed “real and perceived” conflicts to the journal, and had gotten in touch with Doudna who “did not wish to comment in any way on historical statements about the development of CRISPR technology.”
“He refused to share with me many sections concerning my lab’s research,” Doudna told the magazine. “I never saw the entire piece until publication, and have the email correspondence to prove it.”
George Church also told The Scientist about Lander’s questionable fact-checking techniques:
“As with Jennifer, the fact-checking with me was (unnecessarily) very limited. I sent Eric corrections early morning on Jan 14, and these have not (yet) been included in the online paper. Basic full fact-checking (as I offered in December) would have caught these earlier and with much less drama. Even at this point, these are not hard to fix, and would make a big difference… Overall, Eric’s Cell paper systematically misses the important role of many younger researchers (heroes). ”
When Michael Eisen, a biologist at UC Berkeley and the Howard Hughes Medical Institute, read the article, he took to Twitter to express his outrage.
He continued in a series of tweets: “to those complaining about my calling Eric Lander names, i’m sorry, but when the most powerful person in science abuses his position by promoting a manifestly self-serving version of the history of a field, and tries to pass it off as honoring the field’s pioneers, it’s horrible for science, and i understand that most people don’t feel comfortable calling him out for this kind of bullshit, but i do[.] it so disingenuous that someone who has spent his career manifestly NOT giving credit to people who had pioneered the fields he works in now claiming the mantle of the poor, neglected little people of science when it’s convenient is bullshit, and seriously, screw him[.]”
Cell spokesperson Joseph Caputo has told The Scientist that Lander declared his institutional conflicts, but the journal’s conflict of interest policy only applies to personal financial conflicts, which Lander did not have.
“We are currently evaluating our COI policy to determine if we should extend it to include institutional COIs going forward,” Caputo said in an email to the magazine. “I can’t comment on whether there will or won’t be changes to Dr. Lander’s piece.”
In a post on his blog Genotopia, Johns Hopkins University science historian Nathaniel Comfort described Landers’ account as an instance of what historian Herbert Butterfield called “whig history.” In other words: “It rationalizes the status quo, wins the allegiance of the establishment, justifies the dominance of those in power. One immediate tip-off to a Whiggish historical account is the use of melodramatic terms such as ‘heroes’ in the title.”
The crediting issue evokes that of Rosalind Franklin, the chemist and x-ray crystallographer who was has been largely excluded, despite her crucial findings, from the story of the discovery of the structure of DNA at the hands of her colleagues James Watson and Francis Crick. Watson and Crick received the Nobel Prize, and remain the names universally associated with the double helix.
In the context of a deeply, institutionally sexist research community, there can be no merited exclusion of the contribution of female scientists.
“At its best, science is a model of human interaction: cooperative, open, focused on evidence and reason, unbiased by prejudice of ethnicity, gender, sexuality, or disability,” Comfort wrote in an update to his initial blog post. “But science is no longer done in monasteries.”
“Competition, pride, ego, greed, and politics play all too great a role in determining who gets credit, who wins the prizes, and who gets into the textbooks. As Butterfield recognized, controlling the history is both a perk of coming out on top and, while the battle still rages, a way to cement your team’s role in the crystallizing master narrative.”
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CRISPR IS A powerful gene-editing tool that has upended biology and could revolutionize medicine, but the Crispr controversy of the week has nothing to do with how it’s used or even how it works. From the outside, it’s kind of comically petty: One famous scientist wrote an article that downplays the work of another famous scientist, and this has gotten some people very mad.
Inside Crispr circles, it’s easier to see why the historical perspective published in the prestigious journal Cell, titled “Heroes of Crispr,” touched a nerve. For the past several years, the University of California, Berkeley and the Broad Institute (affiliated with MIT and Harvard) have been locked in a patent battle over Crispr, potentially worth billions. Researchers at both institutions claim they invented Crispr as a gene-editing tool first. So when Eric Lander, founding director of the Broad, writes a nearly 8,000-word history of the technique and devotes just two full paragraphs to the work of the Berkeley team, it does provoke hmms.
The patent aside—and this Cell piece will have no impact on the patent proceedings—this looks like a internecine spat among scientists. (Reminder: Scientists have egos!) So why should a non-scientist care? They shouldn’t, I thought at first, content to pop some popcorn and watch the angry tweets roll in. As the conversation expanded though, its importance came into focus: The episode heralds not only how science gets done today, but how the narrative of scientific discovery gets written.
Consider this: Very Important Scientist Eric Lander, who is not involved with Crispr himself, proposes to Very Important Journal Cell that he write a historical perspective on Crispr, which whether he means to or not, casts his own institution in an especially positive light. A decade ago, the resulting article might have provoked some angry whispers and emails in the lab and ended there. But in 2016, Michael Eisen, a Berkeley biologist who is not involved with Crispr, can go on Twitter to repeatedly and even vulgarly denounce Lander. And the comments started rolling in. Not only on Twitter, but also on newly created forums like PubPeer.
The traditional institutions, i.e. the scientific publishers, that could once write science’s history are now losing ground to the wide open Internet. Lots of people have, in fact, made the same observation about the growth of social media and new forums for critiquing scientific studies and new data. Publishers are no longer the only ones who get to the shape the conversation about science.
Cell, for its part, does not seem quite prepared for the firestorm around Lander’s history. The editors had also commissioned a technical review from Jennifer Doudna, the Berkeley Crispr researcher at the center of all this, and decided to present Lander and Doudna’s pieces side by side in the latest issue to give both perspectives. “Fairness and balance was a concern from the start,” says Joseph Caputo, Cell’s media manager. The journal did not attach a conflict of interest statement to either piece.
Over the weekend, Doudna posted an online comment on Lander’s piece on Cell’s website that finally was approved Tuesday afternoon (a delay some found suspicious). “The description of my lab’s research and our interactions with other investigators is factually incorrect,” her comment read, “was not checked by the author and was not agreed to by me prior to publication.” Feng Zhang and George Church, both Crispr researchers affiliated with the Broad, confirmed they had fact checked sections of the piece about their own research for Lander—though Church said in an email to WIRED that he only got to fact check the manuscript the day before print and he has since sent a lengthy list of corrections to Lander. One of his corrections disputes Lander’s claim that Doudna needed his assistance to get genome editing to work in human cells.
Lander said in a statement that he had reached out to over a dozen scientists for their input, and Doudna was the only one who declined: “She confirmed the information about her personal background, but said she did not wish to comment in any way on historical statements about the development of Crispr technology.”
That makes sense, given that Berkeley and the Broad are fighting not only a patent war but also a PR war. And the fight is not entirely one-sided. Doudna herself begins a TED talk about Crispr by saying, “Along with my colleague Emmanuelle Charpentier, I invented a new technology for editing genomes….” The author of a long (and Berkeley-centric) piece about Crispr in the New York Times Magazine last year teaches at Berkeley’s journalism school, but her bio on the piece seemed to obfuscate the connection.
And of course, social media and online comments are opening a new front in this PR war. As the patent proceeding winds its way through the court over the next two years, the fight to claim credit in the public eye will go on. Ironically, an article titled “Heroes of Crispr” reminds us that scientists are not infallible heroes but people—-people with egos, big or small, and occasionally fragile.
Nature News&Comment (@NatureNews) August 26, 2015
Nature has published a news article by Heidi Ledford about the use of CRISPR by recreational biohackers, people who are do-it-yourself biologists for many different reasons (art, fun, culinary). As a genome editing technique, CRIPSR definitely has interesting applications for both good and evil, in terms of biohacking. And the article does a good job exploring these. However, the article implies that CRISPR is feasible for biohackers, only ending with:
But Dan Wright, an environmental lawyer and DIY biohacker in Los Angeles, California, thinks that such a scenario is still beyond the ability of most amateurs. Constructing such a system would surpass the relatively simple tweaks that he and his colleagues are contemplating.
“It’s too difficult,” Wright says. “Just knocking out a gene in one plant is enough of a challenge for a biohacker space at this point.”
As a member of a lab that has used CRISPR for a number of in-depth research applications, I read the whole article with skepticism, and can firmly say that the troubleshooting and time involved in complex uses of CRISPR is definitely beyond most biohackers. At least for the time being. Hopefully the technique will be improved and simplified in the future, for both researchers and biohackers alike.
Check out this podcast episode from Radiolab focusing on CRISPR and its potential applications.[tweet https://twitter.com/CauseScience1/status/611576799013769217]
Out drinking with a few biologists, Jad finds out about something called CRISPR. No, it’s not a robot or the latest dating app, it’s a method for genetic manipulation that is rewriting the way we change DNA. Scientists say they’ll someday be able to use CRISPR to fight cancer and maybe even bring animals back from the dead. Or, pretty much do whatever you want. Jad and Robert delve into how CRISPR does what it does, and consider whether we should be worried about a future full of flying pigs, or the simple fact that scientists have now used CRISPR to tweak the genes of human embryos.
Explainer: CRISPR technology brings precise genetic editing – and raises ethical questions
A group of leading biologists earlier this month called for a halt to the use of a powerful new gene editing technique on humans. Known by the acronym CRISPR, the method allows precise editing of genes for targeted traits, which can be passed down to future generations.
With this explainer, we’ll look at where this technique came from, its potential and some of the issues it raises.
CRISPR stands for clustered regularly interspaced short palindromic repeats, which is the name for a natural defense system that bacteria use to fend off harmful infections.
Bacteria are infected by other microorganisms, called bacteriophages, or phages. The intricate details of the mechanism were elucidated around 2010 by two research groups led by Dr Doudna of the University of California Berkeley and Dr Charpentier of Umeå University in Sweden.
The CRISPR system recognizes specific patterns of DNA from the foreign invaders and decapacitates them by cutting the invader’s DNA into pieces. The way that the bacteria target specific DNA and cleave it gave scientists a hint of its potential in other applications.
In 2013, two research groups, one lead by Dr Zhang of Massachusetts of Institute of Technology and the other by Dr Church of Harvard University, successfully modified this basic mechanism and turned it into a powerful tool that can now cut human genomic DNA at any desired location.
The ability to cut DNA or genes at specific locations is the basic requirement to modify the genome structure. Changes can be made in the DNA around the cleavage site which alter the biological features of the resulting cells or organisms. It is the equivalent of a surgical laser knife, which allows a surgeon to cut out precisely defective body parts and replace them with new or repaired ones.
Tool for gene discovery
Scientists have long sought after this sort of genome editing tools for living cells. Two other technologies, called zinc-finger nucleases and TALEN (transcription activator-like effector nuclease) are available to achieve the same result. However, the CRISPR technology is much easier to generate and manipulate. This means that most biological research laboratories can carry out the CRISPR experiments.
As a result, CRISPR technology has been quickly adopted by scientists all over the world and put it into various tests. It has been demonstrated to be effective in genome editing of most experimental organisms, including cells derived from insects, plants, fish, mice, monkeys and humans.
Such broad successes in a short period of time imply we’ve arrived at a new genome editing era, promising fast-paced development in biomedical research that will bring about new therapeutic treatments for various human diseases.
The CRISPR technology offers a novel tool for scientists to address some of the most fundamental questions that were difficult, if not impossible, to address before.
For instance, the whole human genomic DNA sequence had been deciphered many years ago, but the majority of information embedded on the DNA fragments are largely unknown. Now, the CRISPR technology is enabling scientists to study those gene functions. By eliminating or replacing specific DNA fragments and observing the consequences in the resulting cells, we can now link particular DNA fragments to their biological functions.
Recently, cells and even whole animals with desired genome alterations have successfully been generated using the CRISPR technology. This has proven highly valuable in various biomedical research studies, such as understanding the cause and effect relationship between specific DNA changes and human diseases. Studying DNA in this way also sheds light on the mechanisms underlying how diseases develop and provides insights for developing new drugs that eliminate specific disease symptoms.
With such profound implications in medical sciences, many biotech and pharmaceutical companies have now licensed the CRISPR technology to develop commercial products.
For example, a biotech company, Editas Medicine, was founded in 2013 with the specific goal of creating treatments for hereditary human diseases employing the CRISPR technology.
However, products derived from the use of CRISPR technology are yet to hit the market with FDA approval.
Call for ethical guidelines
With the CRISPR technology, scientists can now alter the genome composition of whole organisms, including humans, through manipulating reproductive cells and fertilized eggs or embryos. Those particular genetic traits are then passed down through generations. This brings hope to cure genetic defects that cause various hereditary human diseases, such as cystic fibrosis, haemophilia, sickle-cell anemia, Down syndrome and so on.
Unlike the current approaches of gene therapy which temporarily fix defective cells or organs through the introduction of corrected or functional genes, the CRISPR technology promises to correct the defect in the reproductive cells, producing progenies that are free of the defective gene. In other words, it can eliminate the root causes of hereditary human diseases.
In theory,then, hereditary features that people consider advantageous, such as higher intelligence, better body appearance and longevity, can be introduced into an individual’s genome through CRISPR mediated reproductive cell modifications as well.
However, scientists do not yet fully understand all the possible side effects of editing human genomes. It is also the case, that there is no clear law to regulate such attempts.
That’s why groups of prominent scientists in the field have recently initiated calls for ethical guidelines for doing such modifications of reproductive cells. The fear being that uncontrolled practice might bring about unforeseen disastrous outcomes in long run.
The guidelines call for a strong discouragement of any attempts at genome modification of reproductive cells for clinical application in humans, until the social, environmental, and ethical implications of such operations are broadly discussed among scientific and governmental organizations.
There is no doubt that the exciting and revolutionary CRISPR technology, under the guidance of carefully drafted and broadly accepted rules, will serve well for the well-being of human kind.
crestwind24 – This morning I am screening through many, many plates of worms. Usually this is very tedious, but today it is very exciting because I am looking for worms that have had their genomes edited using the CRISPR/Cas9 system!!! The CRISPR system allows scientists to make specific genetic changes in the actual genes of bacteria, cells, and animals. In the case of C. elegans, the CRISPR system allows scientists to target genes within the genome to mutate them, change them, delete them, or add things to them. It is extremely powerful, and hopefully I will find some worms that have the genetic edit that I designed!! Cross your fingers for me!
psgurel– Speaking of tedious, I am in the final steps of expressing and purifying protein. Purified protein is a requirement for a variety of biochemical experiments (like the kinetic assay or analytical ultracentrifugation I mentioned earlier). This whole process takes 5 days for the protein I’m expressing, where I’ve had to: grow and express my protein in E. Coli (E. Coli is typically used for protein expression because they grow very fast and yield a lot of protein), lyse the bacterial cells, harvest the protein through various methods of chromatography, concentrate my protein, then store it appropriately. Here I am posing with the FPLC, in the final step of purifying my protein. Looks like I got a good yield, yippee!