l*****7 发帖数: 8463 | 1 主导,控制和利益的对决:
韩春雨的阿狗,
不管结局如何,
都已牵涉到了各方,各路大小神仙们的利益,
决不是什么小事
References:
1
CRISPR/Cas9 - Academics fight over patent rights to an important technology
Stephanie Wroe
Two groups of academic researchers are battling in various jurisdictions
around the world to secure patent rights to a revolutionary gene-editing
technology. For the reasons discussed below, it is possible that there could
be a different winner in different jurisdictions. One group is lead by
Professor Doudna (University of California) in collaboration with Professor
Charpentier (formerly at the University of Vienna and now at Helmholtz
Centre for Infection Research) – the Doudna group. The other group is lead
by Professor Zhang (Broad Institute of Harvard, MIT and Harvard College) –
the Zhang group. A substantial amount of money from the exploitation of the
technology is at stake for all parties.
http://www.dyoung.com/article-crispr
2
A versatile technique for editing genomes has been called the biggest
biotechnology advance since the polymerase chain reaction (PCR), and the US
Patent and Trademark Office (USPTO) is set to determine who will reap the
rewards.
On 11 January, the USPTO granted a request to review a key patent awarded
for the technique, known as CRISPR–Cas9. The outcome of the ensuing
proceedings, called a patent interference, could be worth millions to the
research institutions that are at war over the relevant patents. It might
also influence who is allowed to use the technology — and under what terms.
“This is an absolutely humungous biotech patent dispute,” says legal
scholar Jacob Sherkow of New York Law School. “We’re all waiting with
bated breath.”
Related stories
CRISPR, the disruptor
Chinese scientists genetically modify human embryos
365 days: Nature's 10
More related stories
CRISPR–Cas9 is a bacterial defence system that uses the enzyme Cas9 to snip
DNA at sites determined by the sequence of a ‘guide’ strand of RNA.
Scientists can disable, replace or tweak genes by using the technique to
rewrite snippets of DNA sequences. Use of the technology in research has
exploded, thanks to CRISPR–Cas9’s relative simplicity and versatility
compared to other gene-editing methods. Several companies have sprung up to
harness the technique for generating improved crops, research reagents and
therapies for human genetic diseases.
The roots of the CRISPR–Cas9 dispute date back to 2012, when researchers
reported that they had reprogrammed the system to cut strands of isolated
DNA at sites of their choosing1. The team, led by biologists Jennifer Doudna
at the University of California, Berkeley, and Emmanuelle Charpentier, now
at the Max Planck Institute for Infection Biology in Berlin and Umeå
University in Sweden, filed a patent application on 15 March 2013.
By then, publications had emerged from other groups showing that the method
works in human cells2–4 and bolstering dreams of CRISPR-based gene
therapies — the basis for several companies that have sprung up to
capitalize on the technique.
One of those groups, led by synthetic biologist Feng Zhang of the Broad
Institute and the Massachusetts Institute of Technology, both in Cambridge,
filed a patent application for the CRISPR–Cas9 technique in October 2013.
The institutions filed the patent under a special expedited review programme
, and it was granted in April 2014. Zhang has since been awarded additional
patents on the technology. The original Doudna–Charpentier patent remains
under review.
A pitched battle
In April 2015, the Berkeley team asked the USPTO to begin an interference
proceeding to determine which team was the first to invent the technique.
The proceedings will be much like a court case, with both sides presenting
evidence culled from publications and laboratory notebooks. “Once the [
USPTO] declares an interference, that’s really when the fur is going to fly
,” Sherkow predicted in a June interview.
Nature special:CRISPR
The patent interference is also a testament to the high stakes involved:
companies aiming to use CRISPR–Cas9 for gene therapy have raised hundreds
of millions in venture capital and other funds in under three years. One
company, Editas Medicine in Cambridge, Massachusetts, has already filed to
go public.
Arti Rai, a legal scholar at Duke University in Durham, North Carolina, says
that it is unusual for academic research institutions to battle so
intensely over a patent. Instead, such institutions usually come to an
agreement to share rights to the invention. “This seems more bitter than
disputes I’ve heard of in the past,” she adds.
The two patents in question make broad claims to 'foundational' intellectual
property thought to be necessary for most lucrative CRISPR–Cas9
applications. But many patents have been filed on CRISPR–Cas9 technologies,
and there is still the chance that the winner of the interference will face
additional challenges in court. Zhang's group has also reported another
enzyme, called Cpf1, that could provide an alternative to Cas9. Researchers
expect other alternatives to emerge with time.
As for the various CRISPR–Cas9 companies, Zhang remains involved in Editas,
which was founded by both Zhang and Doudna, among others, in 2013. Doudna
has since severed ties with Editas and thrown her support behind Intellia
Therapeutics, also in Cambridge. Charpentier, meanwhile, co-founded CRISPR
Therapeutics of Basel, Switzerland.
Licensing looms
For now, it is unclear how the dispute will affect researchers who use
CRISPR–Cas9, if it does so at all. Academics who might use the technology
for basic research make unattractive targets for patent lawsuits, says
Rodney Sparks, a biotechnology patent counsel at the University of Virginia
in Charlottesville. “Patent holders might send out a few cease-and-desist
letters, but they probably won’t sue academic researchers,” he says. Doing
so would take time and money with little reward: the spoils in a patent
lawsuit are typically damages or a share of royalties from a marketed
product. That leaves little to gain from suing academics who are not selling
anything. But those who intend to use their research as the basis for a
start-up company will need to be wary, Sparks says.
Some patent holders do ask that even scientists doing basic research take
out a licence on a patented technology, typically for a fairly small fee.
Such was the case for PCR, says Warren Woessner, a lawyer at Schwegman
Lundberg and Woessner in Minneapolis, Minnesota. Woessner recalls how,
during his previous career as a scientist, his institution decided to patent
a method he developed. Officials at the institution later noticed that
someone had published a paper that used the technique without a licence. “
They sent the professor a little note,” recalls Woessner. “‘We have a
patent on this. Pay up.’” The professor did.
The Broad Institute has noted on its website that it will continue to make
CRISPR–Cas9 reagents available to the community, and has given no
indication that it will pursue licensing fees from academics. But Sherkow
warns against assuming that the spirit of academic camaraderie will prevail:
licensing revenue has become increasingly important, particularly for major
research institutions, he says. “We’re just living in a brave new world
these days.”
http://www.nature.com/news/bitter-fight-over-crispr-patent-heats-up-1.17961 | j******i 发帖数: 939 | 2 这是CRISPR的争端 有提到Ago吗 Ago除了韩春雨其他人都不会用 CRISPR初中生教一下
立马就会用 | P****R 发帖数: 22479 | 3 现在就看春雨怎么变成冬雪了。
【在 j******i 的大作中提到】![](/moin_static193/solenoid/img/up.png) : 这是CRISPR的争端 有提到Ago吗 Ago除了韩春雨其他人都不会用 CRISPR初中生教一下 : 立马就会用
| l*****7 发帖数: 8463 | 4 http://www.nature.com/news/the-unsung-heroes-of-crispr-1.20272?WT.mc_id=TWT_NatureNews
The unsung heroes of CRISPR
The soaring popularity of gene editing has made celebrities of the principal
investigators who pioneered the field — but their graduate students and
postdocs are often overlooked.
Heidi Ledford20 July 2016
When Blake Wiedenheft started studying microbes, his work was both remote
and obscure.
He spent his PhD sampling hot springs in Yellowstone National Park, then
created artificial versions in the laboratory to study the microorganisms
that lived in the inhospitable water. “We wanted to understand how life
could survive in boiling acid,” he says.
Over time, Wiedenheft became more interested in how microbes fend off
viruses. He read around, and came across a peculiar bacterial immune system
called CRISPR. In 2007, he approached Jennifer Doudna, a molecular biologist
at the University of California, Berkeley, and found that she shared his
interest. Join the lab, she said — and he did. Over the next five years, he
studied the structure and biochemistry of CRISPR systems, landing a first-
author publication in Nature1.
Today, CRISPR is a household name for molecular biologists around the world.
Researchers have eagerly co-opted the system to insert or delete DNA
sequences in genomes across all kingdoms of life. CRISPR is being used to
generate a new breed of genetically modified crops and may one day treat
human genetic diseases. Doudna and other principal investigators involved in
the seminal work have become scientific celebrities: they are profiled in
major newspapers, star in documentaries and are rumoured to be contenders
for a Nobel prize. “When I came to the lab, I was the only person studying
CRISPR,” Wiedenheft says. “When I left the lab, almost everyone was
studying it.”
Wiedenheft, however, has hardly achieved the same fame as his mentor — and
nor have the other students and postdocs who toiled at the bench to make
CRISPR genome editing a reality. They certainly reap benefits from their
work: support and reflected glory from their supervisors, as well as
expertise in a coveted technique. But some also face a difficult transition
to becoming independent scientists as they try to establish themselves in a
hypercompetitive field.
For Wiedenheft, the key to survival has been seclusion. When he struck out
from Doudna's lab, he opted for a return to Montana State University in
Bozeman, where he did his PhD, over an offer from a larger, better-known
institution. “At the end of the day, the opportunities for solitude and
being outdoors make me more creative and a better scientist,” he says. But
like other young scientists who graduate from powerhouse labs, he can't help
but wonder how different life might have been if accolades in biomedical
science were given to the first authors on a paper, rather than the last.
Now and then, he admits, he doesn't feel quite appreciated enough. “Some
days it matters, some days it doesn't.”
An edited history
The history of CRISPR–Cas9 gene editing has become a subject of fierce
debate and a bitter, high-stakes patent battle. Researchers and institutes
have been jostling aggressively to make sure that they are credited for
their share of the work in everything from academic papers to news stories.
“I get a lot of phone calls from lawyers about what I did and when,”
Wiedenheft says.
In January, Eric Lander, president of the Broad Institute of MIT and Harvard
in Cambridge, Massachusetts, tossed into this minefield a historical
portrait called 'The Heroes of CRISPR'2. It was instantly controversial.
Some said that it marginalized the contributions of certain researchers, and
they questioned the decision to publish the article without a conflict-of-
interest statement noting that the Broad Institute is embroiled in a patent
dispute that hinges on determining who invented CRISPR–Cas9 gene editing.
But for George Church, a geneticist at Harvard Medical School in Boston,
Massachusetts, who is also a pioneer in the field, it was particularly
painful to see statements attributing key discoveries to him rather than his
postdocs and graduate students. “Eric said my name too many times,”
Church says.
Lander says that there was no intended slight in the 'Heroes' story. He was
mindful that there were dozens of other co-authors on the key papers, “But
I couldn't figure out how to collect and tell their stories within a nine-
page article.” If anything, he adds, the article widened the CRISPR
spotlight: most discussion up to that point had focused on 3 major
contributors to the field, whereas his piece featured 17 major players and
acknowledged that there were many others.
Any lack of attention to CRISPR's junior discoverers comes despite fervent
advocacy on the part of their advisers. Junior investigators in the Church
lab praise their leader's unwavering support, along with the unique
intellectual environment he has fostered in the lab. Doudna is a fierce
champion of the scientists she has mentored. “It's really important for
junior investigators to get the credit they deserve,” she says. “They
really drive the scientific enterprise.” What is more, academic papers
often set out each author's contribution to the work.
But those details often get lost simply because, broadly speaking, credit in
science goes to the leader of the lab, as do any prizes that follow. “That
's just how the system works, and I accept my role in this system,” says
Martin Jinek, another Doudna lab alumnus. “But yeah, it's something you can
't help but think about.”
Sometimes people may take note of the first author, but not in a meaningful
way, says Rachel Haurwitz, a former Doudna graduate student and now
president of Caribou Biosciences in Berkeley, California. “They'll say 'the
2012 Jinek paper' but most people have no idea who Martin Jinek is,” she
says.
“The idea that scientific discovery involves just one, two or three people
is so nineteenthcentury.”
Jinek was co-first author on a seminal paper3 showing that the enzyme Cas9
can be programmed to target specific sequences of DNA using only a short
strand of RNA — and he found that his life became defined by CRISPR. When
he entered the job market, he couldn't even discuss the work in interviews
because the patent had not been filed. Even so, he got an attractive offer
from the University of Zurich in Switzerland, and has since built a lab
there that focuses on the basic biology of CRISPR more than its applications.
As interest in CRISPR–Cas9 gene editing grew, his schedule became packed:
he now travels to talks two to three times a month. Although he appreciates
the professional boost that the CRISPR frenzy has given him, he also
struggles to find a balance between running his lab and other obligations.
Haurwitz has faced obstacles, too. She spent her PhD characterizing the
CRISPR-based microbial immune system and the structure of a CRISPR-
associated enzyme called Cys4 (ref. 4). In 2011, she co-founded Caribou
along with Doudna and others to commercialize research tools based on CRISPR
. The early days were tough, but Caribou has since formed partnerships with
major industry players, and the company announced in May that its latest
round of fundraising had brought in US$30 million. Yet as the firm has grown
, some investors have pushed to replace Haurwitz with a more seasoned leader
. Doudna has quashed the idea. “There's no reason to replace her,” says
Doudna. “She keeps showing that she has the talent to be successful.”
Riding the wave
For many early career scientists, working in such a hot field has clear
advantages. As a postdoc, bioengineer Prashant Mali helped to launch the
CRISPR project in Church's lab. He was a co-first author on the lab's 2013
paper5 demonstrating that CRISPR–Cas9 could be used to edit the genome in
human induced pluripotent stem cells.
The discovery sent CRISPR excitement to fever pitch — a wave of enthusiasm
that Mali rode into the job market later that year. “I definitely got a lot
of endorsements,” he says. (There is, however, no mention of him in '
Heroes of CRISPR' — a sore point with Church.) Eventually settling at the
University of California, San Diego, Mali continues to study stem-cell
development and develop CRISPR-based tools. He accepts the intensity of the
field as a small price to pay. His lab is just 18 months old — too young to
have been scooped yet, he says — but competition is inevitable. “There
will obviously be a lot of overlap of good ideas.”
CRISPR threw open doors for Luhan Yang, the other first author on the 2013
Science paper from Church's lab. Soon after the paper was published, the lab
was contacted by several researchers who study organ transplantation. They
wanted to know whether genome editing could now be used to engineer pig
organs so that they would be less likely to provoke an immune response in
humans. Yang seized the idea with gusto, says Church.
The pig genome is home to retroviral DNA, and concern that those
retroviruses might become reactivated in a human host led many researchers
to flee the field in the late 1990s. Yang reasoned that the retroviral
sequences are so similar to one another that a single CRISPR–Cas9
experiment might knock out many of them at once. She and her three co-first
authors now hold the world record6 for the largest number of sequences
targeted in a single CRISPR–Cas9 experiment: 62. And Yang is raising money
to launch a company with Church called eGenesis, to further the work. “
George always gave me the opportunity to establish my leadership,” she says.
Across the Charles River from the Church lab, graduate student Le Cong
worked side-by-side, late into the night with his mentor, bioengineer Feng
Zhang at the Broad Institute, to develop CRISPR gene editing in mammalian
cells. Zhang was himself a young investigator just launching a lab when Cong
joined; Cong remembers opening the box containing the lab's first
centrifuge and sitting with Zhang at a computer googling 'DNA-binding
protein' to look for new ways to edit genomes. The two became a tightly knit
team.
When they embarked on the CRISPR project, it seemed like a long shot as Cong
screened enzymes and reaction conditions, trying to find those that would
work in human cells.
But Cong was willing to take the risk. He and Zhang had previously pioneered
the use of a different gene-editing system, called TALENs, in mammalian
cells, and he reasoned that this early success would be enough to allow him
to graduate if the CRISPR project failed. He never had to test that
hypothesis: in 2013, Cong and his fellow graduate student Fei Ann Ran co-
first authored a Sciencepaper7 showing that the system works in mammalian
cells — the paper was published simultaneously with that of Mali, Church
and their team.
At that point, Cong was advised that he could skip the postdoc and go
straight to a faculty position. But he worried that doing so would limit him
that,” he says. “I was not only looking to develop technology.” Instead,
Cong opted for another postdoc; he is now embarking on a faculty job search,
and plans to use his lab to study allergies and autoimmune disorders.
Cong says that he feels no resentment at being largely excluded from the
CRISPR media frenzy and attention centred on Zhang. “I do think I've been
recognized,” he says; Zhang has been generous in giving him credit within
the scientific community, and has encouraged Cong to give talks in his stead.
And Cong, like others interviewed for this story, is himself insistent about
giving credit to others in the field. He sprinkles in references to work
done in other labs, including some of the earliest microbiology work
characterizing the CRISPR system. Wiedenheft says that's characteristic of
the CRISPR community. “It's competitive, but it's friendly.”
Outside that community, however, the accolades continue to be heaped on
senior investigators. “We need to invent ways to expand the medals podium,
” says Lander. “The idea that scientific discovery involves just one, two
or three people is so nineteenth-century.”
There are many more unsung heroes of CRISPR than this article could do
justice to. One often overlooked group is headed by Virginijus Siksnys at
Vilnius University in Lithuania — where Giedrius Gasiunas began his PhD in
2007. He plugged away for years, tackling the biochemistry of CRISPR–Cas9
and, like Jinek, eventually came to the conclusion that the Cas9 enzyme
could be programmed to cut isolated DNA at specific sites.
In 2012, the lab sent a paper to Cell, where it was rejected without review.
Gasiunas then submitted the paper to the Proceedings of the National
Academy of Sciences and waited. A few months later, while his paper was
still under review, the now-legendary Jinek paper appeared in Science. The
two papers had key differences, but reached similar conclusions. Gasiunas
had been scooped8.
Seeing other scientists collect awards for CRISPR gene editing sometimes
irks Gasiunas, now a postdoc in Siksnys's lab. But the experience has not
entirely soured him on the subject. Although he has since been scooped again
, he finds it no longer stings as much as it did. “It's a risky field,” he
says. “But I think if you want to achieve something great, you need to
take risks.”
Nature 535, 342–344 (21 July 2016) doi:10.1038/535342a |
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