
The Long-Shot Bid to Put Crispr in the Hands of the People - sandGorgon
https://www.wired.com/2017/02/long-shot-bid-put-crispr-hands-people/
======
jfarlow
For better or worse, it now appears the Crispr system is an entire generic
'immune system' with many variants found across many species. It is not a
singular exotic find. Though the most used variant of Cas9 was first found in
the bacteria that causes strep throat, we've since found similarly effective
proteins in all sorts of other organisms. Just a couple of weeks ago a few
more variants of the system were published after being found in archaea
through a large bioinformatics search.[1]

Some of the new CasX, and CasY proteins [2] in these alternative crispr
systems are actually even smaller than the original Cas9 proteins. I'm not
sure how related it is, but the land grab associated with a broad patent has
come with a large exploration effort to find alternatively systems that still
provide similar utility.

As these kind of synthetic biology tools come online there definitely needs to
be some reanalysis of how the tools should comport with the patent system, it
being ultimately for the public good. As what's being built today in synthetic
biology is very much the nascent infrastructure, the comparison to the rollout
of the internet is not an unfair comparison.

[1]
[http://www.nature.com/nature/journal/v542/n7640/full/nature2...](http://www.nature.com/nature/journal/v542/n7640/full/nature21059.html)

[2]
[https://serotiny.bio/api/parts/10465](https://serotiny.bio/api/parts/10465)

~~~
doctorpangloss
> it being ultimately for the public good

I think what pisses people off is the preponderance of insiders. People who
buy Editas before the court results go public, but have enough inside
information to deduce Broad would win the ruling. If you think it's impossible
for insiders to figure out how a court ruling will go based on private
proceedings, you're forgetting that they discovered CRISPR in the first place
and are way savvier overall.

It doesn't matter if Broad loses an appeal. It doesn't matter if there is even
a single therapy ever developed with Cas9. The stock jumped 29%. Every insider
made huge money off information that wasn't public.

You can't go and investigate every trade, I'm not saying that. I'm just saying
that's what pisses people off. It's not the public good part. Believe me, no
one cares about the million other patents the MIT licensing office owns that
won't make any money. Nobody even cares about your new invention that will
take decades to develop.

They just care about the preposterous get-rich-quick scheme that is the stock
market reacting to court cases.

~~~
adventured
I cleared several hundred percent off of call options on EDIT. I did so based
on closely tracking the USPTO case, its filings, studying both sides of the
argument, etc. The oral arguments made it overwhelmingly clear who was going
to win.

You didn't need to be an insider to see the obvious outcome.

If you did nothing else but follow Jacob Sherkow's posts on Twitter, a novice
investor could have taken his information lead, done some further due
diligence, and come to the same conclusion.

Or here, read document 891 in the case:

[https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106...](https://acts.uspto.gov/ifiling/PublicView.jsp?identifier=106048&identifier2=null&tabSel=4&action=filecontent&replyTo=PublicView.jsp)

That's Berkeley desperately attempting to respond to having been smoked at the
oral arguments. Look at how the panel chose to respond to Berkeley trying to
submit new evidence. The panel had already made up its mind by that point in
my opinion. There were numerous things the panel could have pursued further
after the first (and only) oral arguments, that they chose not to tipped their
hand again.

Still don't like the odds involved in buying call options on EDIT? Ok, easy,
hedge: NTLA also had call options available. To make matters even better, both
CRSP and NTLA had sold down heavily leading up to the verdict (CRSP crashed by
~40% in a month). NTLA was available for $12 or $13 per share for the whole
month prior to the verdict (it's IPO price was $22 or so). When an outcome is
so dramatic for a stock as this verdict, if you hedge call options, the huge
spike will trivially compensate for the downside on the other stocks.

~~~
peller
A (perhaps stupid) question, are USPTO judgment dates public ahead-of-the-
fact? In other words, how do you prevent being too early and your options
expiring worthless?

~~~
adventured
No. That was certainly part of the risk calculation.

I sat on most of my calls for two to four months prior to the verdict, with
most of them having a May expiration. So a few points:

1) I made some guesses on how long the verdict was likely to take based on
history and based on how the case was going. For example, did they follow the
oral arguments up with a round of interviews involving some of the prominent
people involved. Sherkow I'll note nailed the verdict date almost exactly and
provided his own reasoning for why he thought it would be in February.

2) At the time I purchased a lot of my calls, May was the furthest out date
available. There was almost no liquidity (I purchased some of the first calls
ever available on EDIT). Once I bought, I knew I'd need to commit or take a
beating trying to unload them near-term. However, over the months, August
calls became readily available (so one could have taken an opportunity to roll
them; eg sell some calls on an upswing, which EDIT was prone to due to its
very low float, wait for a drop, if one occurs then load the August calls at
potentially cheaper than what you sold the May calls for).

3) I specifically began buying after EDIT's stock was, in my opinion,
bottoming out. It went into the $40s almost right after the IPO, due to a
hyper low float and lock-up (plus fuzzy understanding + hype about CRISPR at
that point in time). It dropped for about five straight months from those
highs. By October 1st it looked to be near a floor, so I began stalking it, it
proceeded to double then triple bottom right before the election.

If you had timed it freakishly well, you could have gotten May 2017, $17.50
calls for around ~$1.75 ($175 per contract) right before the election. They
peaked recently at $11.x.

4) By timing the stock itself moderately well on bottoming - that is, by
paying what I considered to be a cheap price on a well sold down stock - I was
able to buy the calls very inexpensively. Why did that matter? Part of the bet
was that it wouldn't just stay on the floor for the coming months leading up
to the patent verdict and hearing (NTLA for example rallied significantly at
one point before crashing back down). By the time it was ~$18 / share, my
calls had already appreciated considerably, giving me a convenient exit if I
wanted it, or I could just pull my principle. I didn't need to hold through
the verdict, I could just take a 100% return or so and walk. That angle helped
to offset (if I wanted to sell some) the risk of being forced to wait it all
out and watching my position potentially expire worthless.

I also did one other thing that ended up being extremely profitable. I sold
some of my calls for a nice gain in the $18s before the verdict came out.
Keeping in mind I had no idea it would 100% be in February. So let's say I
sold some $17.50s for May 2017 at that point for a good profit. I took some of
those gains (not the principle), and acquired even more calls than I had sold,
but for the $17.50s calls for March, on a very heavy discount. I paid $1.25 or
something for those in the weeks before the verdict. When EDIT spiked in the
days following the verdict, those were worth six to eight times what I paid
for them and they were purchased solely with prior profit (if I ended up being
wrong and the verdict didn't come out in time for the March expiration, I only
put my gain at risk on the May calls I sold to do that).

------
dmix
> The law’s original intent was to patent mature discoveries, things like a
> genetically modified crop, or biofuel-farting yeast. Over the years,
> however, universities started filing patents further upstream—on everything
> from protein structures to bits of DNA. This frenzy of molecule-grabbing can
> actually work counter to Bayh-Doyle, locking up promising discoveries that
> don’t need help getting commercialized. “Crispr totally epitomizes that,”
> says Michael Eisen, a Berkeley biophysicist and long-time advocate of open
> science. “Everybody in the universe is chomping at the bit to use it. But
> patents are an obstacle to that happening right now.”

I recently read "Basic Economics" by Thomas Sowell and each chapter
highlighting an economic concept included examples of government policy
relevant to the subject. Such as rent control, price controls in agriculture,
zoning, industry licensing, etc. Almost all of them had similar unintended
side effects as seen here (ie, rent controls intended to reduce rent prices
resulted in a _shortage_ of affordable housing for poor people in NYC,
Toronto, etc). They almost always create an imbalance where the negative side
effects largely outweigh the intended benefits.

I'm not sure leaving such highly technical debates, such as whether or not you
can patent a low level protein, should be left for random courts to decide.

How do we solve such a prevalent problem? Should the legislation then become
more specific to make sure it has it's intended purpose? Or would that
ultimately lead to endless complexity in law? Creating loopholes and increased
difficulty/cost to implement?

The easy answer that some people take is that government should largely not be
involved in this type of stuff but I'm always interested in exploring
alternatives. But otherwise this stuff is largely ignored outside of the usual
generic complaints about regulations coming from business groups each year,
yet it continues to persist as a black/white issue in politics.

CRISPR is such a critical and important technology, it'd be a shame if it was
held back by unintentional interpretations of law.

~~~
djsumdog
I feel like the original supreme court decision that allowed the patenting of
DNA needs to be overturned. The suit was brought by General Electric for an
organism they didn't even use. Now the entire farming industry is radically
different with companies like DuPont, Monsanto and BASF controlling the seed
supplies for many major crops.

~~~
Cpoll
> Monsanto

The corporation everyone loves to hate.

On the flip-side, I haven't heard any compelling way for Monsanto to
recuperate the costs of R&D on their engineered crops. I'm sure a lot of
people would be happy to see GM crops go away altogether, but I don't think
that's a compelling solution.

~~~
djsumdog
I listed the two others too, yet you focused on the one. Why did we need them
in the first place?

Prior to seed companies, seed stock was bread by farmers, universities and
done in a way that was more open an accessible.

We have been in overproduction of corn, grain and rice for over a decade. They
haven't saved the world from hunger. Hunger still exists and has always been a
distribution problem. In 2008, the food crisis was caused because investment
companies started trading in grain futures and wouldn't let go (where as a
food producer invests in a grain future because they plan on buying it in x
months in order to make cereal or pizza crust or whatever). There was plenty
of food though. The food shortage was literally manufactured.

> any compelling way for Monsanto to recuperate the costs of R&D on their
> engineered crops

It wasn't a problem that needed to be solved. On the flip side, now we have
all this corn and grain that needs to be sold. Sure some of that can be turned
into fuel, but a lot of it is pushed out in starchier food. We're consuming so
much starch and sugar that we're now in an obesity epidemic. The food industry
keeps pushing out advertising so people consume more of it. It's a cycle
that's not been beneficial for many people.

------
hprotagonist
The Broad hands out licenses like candy if you're doing research.

If you're a commercial entity, it's 100M.

~~~
hacker_9
Take from the rich, give to the poor.

~~~
QML
Not all commercial entities are rich. If you were a scientist who found a
novel application of CRISPR and wanted to develop a product and bring it to
market, you'd be effectively screwed.

~~~
hprotagonist
Well, you'd develop a proof of concept and angle to be acquihired by Editas. I
don't know that that counts as "screwed".

~~~
QML
Acquihired implies you being acquired for your talent, but then what happens
to your idea? Editas could just scrap it.

~~~
adventured
Editas and Broad only control the US market. It's extremely unlikely Broad
will acquire such a strong position in Europe or Asia (in fact it's
practically guaranteed they will not).

If you had such a stellar therapy, and you couldn't get it past Editas, you'd
go to Europe and partner with any number of a dozen other entities there that
would be guaranteed to be interested (such as Novartis, which owns part of
NTLA).

------
nickthemagicman
Where's the line between benefiting the creator of a tool and putting a wall
up around a tool that can benefit all of humanity?

~~~
QML
I don't know much about patent law, but why not just allow for open use? If a
person wants to use that tool in a for profit company, then they just pay
royalties. Else, just let it. S.

~~~
amelius
Imho, patents should work like this:

Company or private person submits a patent.

The government determines what they would pay to make the technology open
(i.e., benefits to society). This is similar to the process of determining the
subsidy to develop new technology.

Government makes an offer. Submitter can accept or reject.

If rejected, the patent remains secret, but other companies have the right to
independently invent the same technology.

If accepted, the patent is published. If other companies want to use the
technology, they will need to buy a license from the government. Submitter has
no control over who may or may not use the technology.

------
torbjorn
Is there some kind of letter to your congress person type thing that can be
done for this? I would gladly sign a petition or write an email as part of a
campaign to demonstrate public support for making access to crispr as open as
possible.

~~~
djsumdog
Your opinions and letters to congress do not affect public policy at all; not
unless you're in the top 10% of income earners:

[http://fightthefuture.org/videos/does-voting-make-a-
differen...](http://fightthefuture.org/videos/does-voting-make-a-difference/)

------
djsumdog
> like Wi-Fi or the internet, and license it on a “fair, reasonable and non-
> discriminatory” basis. No favorites.

Wi-Fi patents are held by the Australian government and feed back into their
University system.

