Tag Archives: CRISPR

CRISPR patent decision: Harvard’s and MIT’s Broad Institute victorious—for now

I have written about the CRISPR patent tussle (Harvard & MIT’s [Massachusetts Institute of Technology] Broad Institute vs the University of California at Berkeley) previously in a Jan. 6, 2015 posting and in a more detailed May 14, 2015 posting. I also mentioned (in a Jan. 17, 2017 posting) CRISPR and its patent issues in the context of a posting about a Slate.com series on Frankenstein and the novel’s applicability to our own time. This patent fight is being bitterly fought as fortunes are at stake.

It seems a decision has been made regarding the CRISPR patent claims. From a Feb. 17, 2017 article by Charmaine Distor for The Science Times,

After an intense court battle, the US Patent and Trademark Office (USPTO) released its ruling on February 15 [2017]. The rights for the CRISPR-Cas9 gene editing technology was handed over to the Broad Institute of Harvard University and the Massachusetts Institute of Technology (MIT).

According to an article in Nature, the said court battle was between the Broad Institute and the University of California. The two institutions are fighting over the intellectual property right for the CRISPR patent. The case between the two started when the patent was first awarded to the Broad Institute despite having the University of California apply first for the CRISPR patent.

Heidi Ledford’s Feb. 17, 2017 article for Nature provides more insight into the situation (Note: Links have been removed),

It [USPTO] ruled that the Broad Institute of Harvard and MIT in Cambridge could keep its patents on using CRISPR–Cas9 in eukaryotic cells. That was a blow to the University of California in Berkeley, which had filed its own patents and had hoped to have the Broad’s thrown out.

The fight goes back to 2012, when Jennifer Doudna at Berkeley, Emmanuelle Charpentier, then at the University of Vienna, and their colleagues outlined how CRISPR–Cas9 could be used to precisely cut isolated DNA1. In 2013, Feng Zhang at the Broad and his colleagues — and other teams — showed2 how it could be adapted to edit DNA in eukaryotic cells such as plants, livestock and humans.

Berkeley filed for a patent earlier, but the USPTO granted the Broad’s patents first — and this week upheld them. There are high stakes involved in the ruling. The holder of key patents could make millions of dollars from CRISPR–Cas9’s applications in industry: already, the technique has sped up genetic research, and scientists are using it to develop disease-resistant livestock and treatments for human diseases.

But the fight for patent rights to CRISPR technology is by no means over. Here are four reasons why.

1. Berkeley can appeal the ruling

2. European patents are still up for grabs

3. Other parties are also claiming patent rights on CRISPR–Cas9

4. CRISPR technology is moving beyond what the patents cover

As for Ledford’s 3rd point, there are an estimated 763 patent families (groups of related patents) claiming CAS9 leading to the distinct possibility that the Broad Institute will be fighting many patent claims in the future.

Once you’ve read Distor’s and Ledford’s articles, you may want to check out Adam Rogers’ and Eric Niiler’s Feb. 16, 2017 CRISPR patent article for Wired,

The fight over who owns the most promising technique for editing genes—cutting and pasting the stuff of life to cure disease and advance scientific knowledge—has been a rough one. A team on the West Coast, at UC Berkeley, filed patents on the method, Crispr-Cas9; a team on the East Coast, based at MIT and the Broad Institute, filed their own patents in 2014 after Berkeley’s, but got them granted first. The Berkeley group contended that this constituted “interference,” and that Berkeley deserved the patent.

At stake: millions, maybe billions of dollars in biotech money and licensing fees, the future of medicine, the future of bioscience. Not nothing. Who will benefit depends on who owns the patents.

On Wednesday [Feb. 15, 2017], the US Patent Trial and Appeal Board kind of, sort of, almost began to answer that question. Berkeley will get the patent for using the system called Crispr-Cas9 in any living cell, from bacteria to blue whales. Broad/MIT gets the patent in eukaryotic cells, which is to say, plants and animals.

It’s … confusing. “The patent that the Broad received is for the use of Crispr gene-editing technology in eukaryotic cells. The patent for the University of California is for all cells,” says Jennifer Doudna, the UC geneticist and co-founder of Caribou Biosciences who co-invented Crispr, on a conference call. Her metaphor: “They have a patent on green tennis balls; we have a patent for all tennis balls.”

Observers didn’t quite buy that topspin. If Caribou is playing tennis, it’s looking like Broad/MIT is Serena Williams.

“UC does not necessarily lose everything, but they’re no doubt spinning the story,” says Robert Cook-Deegan, an expert in genetic policy at Arizona State University’s School for the Future of Innovation in Society. “UC’s claims to eukaryotic uses of Crispr-Cas9 will not be granted in the form they sought. That’s a big deal, and UC was the big loser.”

UC officials said Wednesday [Feb. 15, 2017] that they are studying the 51-page decision and considering whether to appeal. That leaves members of the biotechnology sector wondering who they will have to pay to use Crispr as part of a business—and scientists hoping the outcome won’t somehow keep them from continuing their research.

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Happy reading!

Essays on Frankenstein

Slate.com is dedicating a month (January 2017) to Frankenstein. This means there were will be one or more essays each week on one aspect or another of Frankenstein and science. These essays are one of a series of initiatives jointly supported by Slate, Arizona State University, and an organization known as New America. It gets confusing since these essays are listed as part of two initiatives:  Futurography and Future Tense.

The really odd part, as far as I’m concerned, is that there is no mention of Arizona State University’s (ASU) The Frankenstein Bicentennial Project (mentioned in my Oct. 26, 2016 posting). Perhaps they’re concerned that people will think ASU is advertising the project?

Introductions

Getting back to the essays, a Jan. 3, 2017 article by Jacob Brogan explains, by means of a ‘Question and Answer’ format article, why the book and the monster maintain popular interest after two centuries (Note: We never do find out who or how many people are supplying the answers),

OK, fine. I get that this book is important, but why are we talking about it in a series about emerging technology?

Though people still tend to weaponize it as a simple anti-scientific screed, Frankenstein, which was first published in 1818, is much richer when we read it as a complex dialogue about our relationship to innovation—both our desire for it and our fear of the changes it brings. Mary Shelley was just a teenager when she began to compose Frankenstein, but she was already grappling with our complex relationship to new forces. Almost two centuries on, the book is just as propulsive and compelling as it was when it was first published. That’s partly because it’s so thick with ambiguity—and so resistant to easy interpretation.

Is it really ambiguous? I mean, when someone calls something frankenfood, they aren’t calling it “ethically ambiguous food.”

It’s a fair point. For decades, Frankenstein has been central to discussions in and about bioethics. Perhaps most notably, it frequently crops up as a reference point in discussions of genetically modified organisms, where the prefix Franken- functions as a sort of convenient shorthand for human attempts to meddle with the natural order. Today, the most prominent flashpoint for those anxieties is probably the clustered regularly interspaced short palindromic repeats, or CRISPR, gene-editing technique [emphasis mine]. But it’s really oversimplifying to suggest Frankenstein is a cautionary tale about monkeying with life.

As we’ll see throughout this month on Futurography, it’s become a lens for looking at the unintended consequences of things like synthetic biology, animal experimentation, artificial intelligence, and maybe even social networking. Facebook, for example, has arguably taken on a life of its own, as its algorithms seem to influence the course of elections. Mark Zuckerberg, who’s sometimes been known to disavow the power of his own platform, might well be understood as a Frankensteinian figure, amplifying his creation’s monstrosity by neglecting its practical needs.

But this book is almost 200 years old! Surely the actual science in it is bad.

Shelley herself would probably be the first to admit that the science in the novel isn’t all that accurate. Early in the novel, Victor Frankenstein meets with a professor who castigates him for having read the wrong works of “natural philosophy.” Shelley’s protagonist has mostly been studying alchemical tomes and otherwise fantastical works, the sort of things that were recognized as pseudoscience, even by the standards of the day. Near the start of the novel, Frankenstein attends a lecture in which the professor declaims on the promise of modern science. He observes that where the old masters “promised impossibilities and performed nothing,” the new scientists achieve far more in part because they “promise very little; they know that metals cannot be transmuted and that the elixir of life is a chimera.”

Is it actually about bad science, though?

Not exactly, but it has been read as a story about bad scientists.

Ultimately, Frankenstein outstrips his own teachers, of course, and pulls off the very feats they derided as mere fantasy. But Shelley never seems to confuse fact and fiction, and, in fact, she largely elides any explanation of how Frankenstein pulls off the miraculous feat of animating dead tissue. We never actually get a scene of the doctor awakening his creature. The novel spends far more dwelling on the broader reverberations of that act, showing how his attempt to create one life destroys countless others. Read in this light, Frankenstein isn’t telling us that we shouldn’t try to accomplish new things, just that we should take care when we do.

This speaks to why the novel has stuck around for so long. It’s not about particular scientific accomplishments but the vagaries of scientific progress in general.

Does that make it into a warning against playing God?

It’s probably a mistake to suggest that the novel is just a critique of those who would usurp the divine mantle. Instead, you can read it as a warning about the ways that technologists fall short of their ambitions, even in their greatest moments of triumph.

Look at what happens in the novel: After bringing his creature to life, Frankenstein effectively abandons it. Later, when it entreats him to grant it the rights it thinks it deserves, he refuses. Only then—after he reneges on his responsibilities—does his creation really go bad. We all know that Frankenstein is the doctor and his creation is the monster, but to some extent it’s the doctor himself who’s made monstrous by his inability to take responsibility for what he’s wrought.

I encourage you to read Brogan’s piece in its entirety and perhaps supplement the reading. Mary Shelley has a pretty interesting history. She ran off with Percy Bysshe Shelley who was married to another woman, in 1814  at the age of seventeen years. Her parents were both well known and respected intellectuals and philosophers, William Godwin and Mary Wollstonecraft. By the time Mary Shelley wrote her book, her first baby had died and she had given birth to a second child, a boy.  Percy Shelley was to die a few years later as was her son and a third child she’d given birth to. (Her fourth child born in 1819 did survive.) I mention the births because one analysis I read suggests the novel is also a commentary on childbirth. In fact, the Frankenstein narrative has been examined from many perspectives (other than science) including feminism and LGBTQ studies.

Getting back to the science fiction end of things, the next part of the Futurography series is titled “A Cheat-Sheet Guide to Frankenstein” and that too is written by Jacob Brogan with a publication date of Jan. 3, 2017,

Key Players

Marilyn Butler: Butler, a literary critic and English professor at the University of Cambridge, authored the seminal essay “Frankenstein and Radical Science.”

Jennifer Doudna: A professor of chemistry and biology at the University of California, Berkeley, Doudna helped develop the CRISPR gene-editing technique [emphasis mine].

Stephen Jay Gould: Gould is an evolutionary biologist and has written in defense of Frankenstein’s scientific ambitions, arguing that hubris wasn’t the doctor’s true fault.

Seán Ó hÉigeartaigh: As executive director of the Center for Existential Risk at the University of Cambridge, hÉigeartaigh leads research into technologies that threaten the existience of our species.

Jim Hightower: This columnist and activist helped popularize the term frankenfood to describe genetically modified crops.

Mary Shelley: Shelley, the author of Frankenstein, helped create science fiction as we now know it.

J. Craig Venter: A leading genomic researcher, Venter has pursued a variety of human biotechnology projects.

Lingo

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Debates

Popular Culture

Further Reading

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‘Franken’ and CRISPR

The first essay is in a Jan. 6, 2016 article by Kay Waldman focusing on the ‘franken’ prefix (Note: links have been removed),

In a letter to the New York Times on June 2, 1992, an English professor named Paul Lewis lopped off the top of Victor Frankenstein’s surname and sewed it onto a tomato. Railing against genetically modified crops, Lewis put a new generation of natural philosophers on notice: “If they want to sell us Frankenfood, perhaps it’s time to gather the villagers, light some torches and head to the castle,” he wrote.

William Safire, in a 2000 New York Times column, tracked the creation of the franken- prefix to this moment: an academic channeling popular distrust of science by invoking the man who tried to improve upon creation and ended up disfiguring it. “There’s no telling where or how it will end,” he wrote wryly, referring to the spread of the construction. “It has enhanced the sales of the metaphysical novel that Ms. Shelley’s husband, the poet Percy Bysshe Shelley, encouraged her to write, and has not harmed sales at ‘Frank’n’Stein,’ the fast-food chain whose hot dogs and beer I find delectably inorganic.” Safire went on to quote the American Dialect Society’s Laurence Horn, who lamented that despite the ’90s flowering of frankenfruits and frankenpigs, people hadn’t used Frankensense to describe “the opposite of common sense,” as in “politicians’ motivations for a creatively stupid piece of legislation.”

A year later, however, Safire returned to franken- in dead earnest. In an op-ed for the Times avowing the ethical value of embryonic stem cell research, the columnist suggested that a White House conference on bioethics would salve the fears of Americans concerned about “the real dangers of the slippery slope to Frankenscience.”

All of this is to say that franken-, the prefix we use to talk about human efforts to interfere with nature, flips between “funny” and “scary” with ease. Like Shelley’s monster himself, an ungainly patchwork of salvaged parts, it can seem goofy until it doesn’t—until it taps into an abiding anxiety that technology raises in us, a fear of overstepping.

Waldman’s piece hints at how language can shape discussions while retaining a rather playful quality.

This series looks to be a good introduction while being a bit problematic in spots, which roughly sums up my conclusion about their ‘nano’ series in my Oct. 7, 2016 posting titled: Futurography’s nanotechnology series: a digest.

By the way, I noted the mention of CRISPR as it brought up an issue that they don’t appear to be addressing in this series (perhaps they will do this elsewhere?): intellectual property.

There’s a patent dispute over CRISPR as noted in this American Chemical Society’s Chemistry and Engineering News Jan. 9, 2017 video,

Playing God

This series on Frankenstein is taking on other contentious issues. A perennial favourite is ‘playing God’ as noted in Bina Venkataraman’s Jan. 11, 2017 essay on the topic,

Since its publication nearly 200 years ago, Shelley’s gothic novel has been read as a cautionary tale of the dangers of creation and experimentation. James Whale’s 1931 film took the message further, assigning explicitly the hubris of playing God to the mad scientist. As his monster comes to life, Dr. Frankenstein, played by Colin Clive, triumphantly exclaims: “Now I know what it feels like to be God!”

The admonition against playing God has since been ceaselessly invoked as a rhetorical bogeyman. Secular and religious, critic and journalist alike have summoned the term to deride and outright dismiss entire areas of research and technology, including stem cells, genetically modified crops, recombinant DNA, geoengineering, and gene editing. As we near the two-century commemoration of Shelley’s captivating story, we would be wise to shed this shorthand lesson—and to put this part of the Frankenstein legacy to rest in its proverbial grave.

The trouble with the term arises first from its murkiness. What exactly does it mean to play God, and why should we find it objectionable on its face? All but zealots would likely agree that it’s fine to create new forms of life through selective breeding and grafting of fruit trees, or to use in-vitro fertilization to conceive life outside the womb to aid infertile couples. No one objects when people intervene in what some deem “acts of God,” such as earthquakes, to rescue victims and provide relief. People get fully behind treating patients dying of cancer with “unnatural” solutions like chemotherapy. Most people even find it morally justified for humans to mete out decisions as to who lives or dies in the form of organ transplant lists that prize certain people’s survival over others.

So what is it—if not the imitation of a deity or the creation of life—that inspires people to invoke the idea of “playing God” to warn against, or even stop, particular technologies? A presidential commission charged in the early 1980s with studying the ethics of genetic engineering of humans, in the wake of the recombinant DNA revolution, sheds some light on underlying motivations. The commission sought to understand the concerns expressed by leaders of three major religious groups in the United States—representing Protestants, Jews, and Catholics—who had used the phrase “playing God” in a 1980 letter to President Jimmy Carter urging government oversight. Scholars from the three faiths, the commission concluded, did not see a theological reason to flat-out prohibit genetic engineering. Their concerns, it turned out, weren’t exactly moral objections to scientists acting as God. Instead, they echoed those of the secular public; namely, they feared possible negative effects from creating new human traits or new species. In other words, the religious leaders who called recombinant DNA tools “playing God” wanted precautions taken against bad consequences but did not inherently oppose the use of the technology as an act of human hubris.

She presents an interesting argument and offers this as a solution,

The lesson for contemporary science, then, is not that we should cease creating and discovering at the boundaries of current human knowledge. It’s that scientists and technologists ought to steward their inventions into society, and to more rigorously participate in public debate about their work’s social and ethical consequences. Frankenstein’s proper legacy today would be to encourage researchers to address the unsavory implications of their technologies, whether it’s the cognitive and social effects of ubiquitous smartphone use or the long-term consequences of genetically engineered organisms on ecosystems and biodiversity.

Some will undoubtedly argue that this places an undue burden on innovators. Here, again, Shelley’s novel offers a lesson. Scientists who cloister themselves as Dr. Frankenstein did—those who do not fully contemplate the consequences of their work—risk later encounters with the horror of their own inventions.

At a guess, Venkataraman seems to be assuming that if scientists communicate and make their case that the public will cease to panic with reference moralistic and other concerns. My understanding is that social scientists have found this is not the case. Someone may understand the technology quite well and still oppose it.

Frankenstein and anti-vaxxers

The Jan. 16, 2017 essay by Charles Kenny is the weakest of the lot, so far (Note: Links have been removed),

In 1780, University of Bologna physician Luigi Galvani found something peculiar: When he applied an electric current to the legs of a dead frog, they twitched. Thirty-seven years later, Mary Shelley had Galvani’s experiments in mind as she wrote her fable of Faustian overreach, wherein Dr. Victor Frankenstein plays God by reanimating flesh.

And a little less than halfway between those two dates, English physician Edward Jenner demonstrated the efficacy of a vaccine against smallpox—one of the greatest killers of the age. Given the suspicion with which Romantic thinkers like Shelley regarded scientific progress, it is no surprise that many at the time damned the procedure as against the natural order. But what is surprising is how that suspicion continues to endure, even after two centuries of spectacular successes for vaccination. This anti-vaccination stance—which now infects even the White House—demonstrates the immense harm that can be done by excessive distrust of technological advance.

Kenny employs history as a framing device. Crudely, Galvani’s experiments led to Mary Shelley’s Frankenstein which is a fable about ‘playing God’. (Kenny seems unaware there are many other readings of and perspectives on the book.) As for his statement ” … the suspicion with which Romantic thinkers like Shelley regarded scientific progress … ,” I’m not sure how he arrived at his conclusion about Romantic thinkers. According to Richard Holmes (in his book, The Age of Wonder: How the Romantic Generation Discovered the Beauty and Terror of Science), their relationship to science was more complex. Percy Bysshe Shelley ran ballooning experiments and wrote poetry about science, which included footnotes for the literature and concepts he was referencing; John Keats was a medical student prior to his establishment as a poet; and Samuel Taylor Coleridge (The Rime of the Ancient Mariner, etc.) maintained a healthy correspondence with scientists of the day sometimes influencing their research. In fact, when you analyze the matter, you realize even scientists are, on occasion, suspicious of science.

As for the anti-vaccination wars, I wish this essay had been more thoughtful. Yes, Andrew Wakefield’s research showing a link between MMR (measles, mumps, and rubella) vaccinations and autism is a sham. However, having concerns and suspicions about technology does not render you a fool who hasn’t progressed from 18th/19th Century concerns and suspicions about science and technology. For example, vaccines are being touted for all kinds of things, the latest being a possible antidote to opiate addiction (see Susan Gados’ June 28, 2016 article for ScienceNews). Are we going to be vaccinated for everything? What happens when you keep piling vaccination on top of vaccination? Instead of a debate, the discussion has devolved to: “I’m right and you’re wrong.”

For the record, I’m grateful for the vaccinations I’ve had and the diminishment of diseases that were devastating and seem to be making a comeback with this current anti-vaccination fever. That said, I think there are some important questions about vaccines.

Kenny’s essay could have been a nuanced discussion of vaccines that have clearly raised the bar for public health and some of the concerns regarding the current pursuit of yet more vaccines. Instead, he’s been quite dismissive of anyone who questions vaccination orthodoxy.

The end of this piece

There will be more essays in Slate’s Frankenstein series but I don’t have time to digest and write commentary for all of them.

Please use this piece as a critical counterpoint to some of the series and, if I’ve done my job, you’ll critique this critique. Please do let me know if you find any errors or want to add an opinion or add your own critique in the Comments of this blog.

ETA Jan. 25, 2017: Here’s the Frankenstein webspace on Slate’s Futurography which lists all the essays in this series. It’s well worth looking at the list. There are several that were not covered here.