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.
Dr. Marshall refutes the commonly held idea that cells are just bags of watery enzymes. He runs through his “Top 10 List” of unexpected and amazing things that individual cells can do. These including growing to be huge, navigating mazes, and performing feats that seem to belong in science fiction.
If you took #IceBucketChallenge you need to read about these fruit flies
By Mohit Kumar Jolly, Rice University
If you have a Facebook account, you are likely to have seen someone pour an ice bucket on themselves in the name of raising awareness for amyotropic lateral sclerosis (ALS). ALS is a disease that affects nerve cells in the brain, and it falls into a class of diseases known as neurodegenerative, which include diseases such as Parkinson’s, Alzheimer’s and Huntington’s. All of them are incurable and claim many lives around the world. These diseases can be caused by genetic mutations, but our understanding of what causes these remains poor.
A study, conducted by Manish Jaiswal and colleagues and led by Hugo Bellen and Michael Wangler at the Baylor College of Medicine, just published in Cell, takes a key step forward. They identified hundreds of new mutations in specific genes that are associated with various aspects of the development, function and maintenance of neural system in the fruit fly Drosophila melanogaster. The fruit fly is a stand-in for humans, and allows investigation of the molecular mechanisms of 26 human diseases, including ALS.
Researchers could use Drosophila melanogaster, because it is a well-established model organism to understand the molecular mechanisms of many human diseases. This is because: about 75% of human disease-causing genes are found in the fly in a similar form, it is easy to work with and breeds quickly, and many tools are available to manipulate any genes in it.
Messing with a fruit fly
The standard way of learning about genes is by studying the effect on the fly when a specific gene is “knocked out” from its genome. However, this strategy is sometimes ineffective – for instance, if the gene knocked out is an essential gene required for growth and development, then the fly will not fully grow, rendering the effort useless.
The authors overcame this limitation by inducing mutations in just a few cells in the fly, so that even if an essential gene is mutated, it does not kill the fly during its embryo-to-adult development. The effect of that mutation can be studied by looking at the tissue or organ where that mutation was supposed to act.
This is an important method because it helps to do experiments that can’t be done in humans. For instance, looking at the full genetic data of two siblings suffering from microcephaly – a disease in which size of the head is much smaller than expected – the researchers found that a specific gene, called ANKLE2, was mutated in both. This could be coincidence. But given there are 20,000 genes in the human genome, the chance of such a coincidence are quite low. To find out whether ANKLE2 is causing microcephaly, the researchers would need to conduct gene manipulation experiments in humans. Such experiments, however, are unethical.
That’s when studying fly and human genetics together becomes crucial. The authors found that flies with mutations in the same gene had small brains too. However, when the human ANKLE2 gene was introduced in these mutant flies, they had a normal brain size, providing evidence from the fly that ANKLE2 is the culprit.
This technique allowed the authors to isolate 614 new mutations in 165 genes that affect the development, function and maintenance of a functional neural system. But what is perhaps more important is that, these results have helped the authors to suggest a new method for identifying various disease-causing human genes by looking at the mutations in the genomes of patients alongside the mutations in corresponding Drosophila genes. They find that the disease-causing genes in humans have more than one copy of them in the fly, so if one can enlist which genes have more than one copy in the fly, they are likely to be disease-causing in humans.
As more people use this method, we will get closer and closer to finally understanding the genetic basis of many neurological and neurodegenerative diseases.
Mohit Kumar Jolly does not work for, consult to, own shares in or receive funding from any company or organisation that would benefit from this article, and has no relevant affiliations.