APL Forum: Biotechnology for the Nation – BioToday Spotlight Talks

I would like to start off our first
session of the morning and introduce our first spotlight speaker dr. John glass
dr. glass is a professor and leader of the J craig Venter Institute synthetic
biology and bioenergy group he has been at the forefront of microbial genomics
for many years and leads a team which created the minimal cell a bacterial
gene which with only the essential gene set needed for life an organism that
I’ve heard him referred to as the hydrogen atom of biology so truly a
thought leader in the field of synthetic biology please join me in welcoming John
glass okay let’s get going so I’m a practicing biologist and it is an
extraordinary time to be a biologist and when I talked to Ali about what we were
going to do here and so there was first the idea that we’re going to go over all
of biotechnology in about 22 minutes so that you guys get all of this but but
rather I want to offer a few vignettes to show ideas about what the what the
edges of what is possible now and as I said it’s an extraordinary time to be a
biologist so let me move past those this week so among this I had I had the rare
pleasure where it’s not a rare pleasure it was sort of a medium well pleasure of
having an impossible burger now this is a meat substitute that really tastes I
think like beef because it has a biotechnology created heme protein a
heme protein where they took the gene for heme installed it in a yeast in a
yeast genome so that yeast produces this heme which is part of the burger really
super it’s also a time where the fact that I’m alive because I can have
recombinant insulin that has kept me alive for the last you know 50 years
made from biotechnology a one of the early products of synthetic biology if
you will and as another example of remarkable world that we live in now if
I wanted to I could go into my house and for not much money I could produce I
have the skills and and many people in the US and around the world today have
the skills to easily make enough polio virus to cause real mayhem so these are
examples of what the world can see today what we can do today but as I said
rather than do a whole view of synthetic biology I’m part of the J craig Venter
Institute we have labs in Rockville Maryland and San Diego in in San Diego
and we’ve been around for about 25 years now we have our building in San Diego it
overlooks the ocean and it’s the world’s first fully sustainable lab and JCV i
our synthetic biology group is sort of the brainchild of two of my scientific
heroes craig Venter and ham Smith and so what I’m going to do is talk about from
a personal perspective some of the things that our group at the JC VI has
been able to do over the last 15 years that I think has really given an
examples of the edges of what can be done using the new technologies made
from synthesizing DNA the idea that instead of having DNA sequencers now
we’re going to write DNA and so I’m going to offer one vignette about viral
systems because we sometimes refer to what we do is Synthetic Genomics
rather than synthetic biology the idea that we’re building genomes in order to
make new viruses and cells with extraordinary properties so one vignette
will be about viruses another about bacteria and the third about higher
eukaryotic systems so first I want to talk about influenza vaccine improvement
so for the last 60 years the way influenza virus vaccine has been made is
fundamentally the same so there’s worldwide surveillance to
find strains of influenza that epidemiologist think will be important
twice a year the w-h-o makes a recommendation so at the cusp of
February and March they make a recommendation for the three or four
strains of influenza they think will be circulating and important in the
Northern Hemisphere later that year and that gives the vaccine makers six months
to propel the hundreds of millions built to the to create and prepare hundreds of
millions of doses of vaccine which will be available to the public starting at
the beginning of the flu season in September they do the same thing again
at this at the August September cusp for the southern hemisphere now the way this
is done is they say okay this virus that came from some guy and into Indonesia so
they say okay this is the virus that we want to get the hemagglutinin which is a
surface protein and the neuraminidase genes from and we want to put that in a
new strain that is designed to grow in chicken eggs and so that strain from
Indonesia is shipped to vaccine makers who then take that strain of influenza
and they inject it into fertile chicken eggs along with another strain of
influenza called Puerto Rico 8 which is designed which has been adapted for
growth in chicken eggs and Puerto Rico 8 so what they want is to produce a
chimeric virus that has two chromosomes if you will from the snot sample that
came from Indonesia and six chromosomes from the Puerto Rico eight so it’ll grow
well in chicken eggs and that process now takes about 35 days 35 to maybe a
few more days because you have to purify the virus and make sure you’ve got
exactly what you want and Barda came to the JCB eye and then Novartis the
vaccine maker Novartis in 2012 and 11 and 12 and said can we speed this up
because as they point out here when we had the 2009 influenza virus epidemic
for the strain the the pandemic for the the porcine derive strain that came from
Mexico when they declared the epidemic by the time we had sufficient doses of
vaccine to be used for the population you can see so that’s the red line the
increasing amount of vaccine the epidemic had actually begun to wane so
if this had been a really dangerous pathogen the vaccine would not have been
ready quickly enough and so if we could cut a month or more off of the time it
took to go from discovering a new virus a new potential pandemic threat to
actually having the vaccine that would be super and so using a process called
reverse genetics we take the DNA sequence or the sequence digital
information from a virus strain and what we want is to synthesize DNA for each of
these eight chromosomes and so we go from the RNA we can take that digital
information from a sequencer and synthesize the DNA put them in
appropriate plasmid vectors and you see the two yellow chromosomes are from the
neuraminidase and hemagglutinin gene and the other six chromosomes are from the
puerto rico ate the chicken adapted strain those can be transfected into
mammalian cells basically just install them in the cells and three days later
you produce virus this is the first the first dose of the vaccine and so using
this we develop methods that from being given the the sequence of the virus
genes we needed to make in ten hours where we were able to produce the
proteins that we wanted I mean sorry not the proteins that the synthetic DNA that
we needed and we were able to cut the time down in theory from 35 days to
maybe just five to seven days to produce the first dose of vaccine as an example
of the power of this in 2013 on Easter Sunday the Chinese announced the
sequence of this h7n9 influenza strain and we
heard about this Monday morning Easter Monday morning and by the with with no
advance notice by the end of the day we had the genome synthesized and it was on
a plane to our collaborators in Boston who had the first dose of the vaccine in
essence by Friday mornings so this is the way that these sorts of things can
be sped up now by the same notion with my skills and the skills of lots of
people many people in fact in this room they could probably without anyone
noticing that we had ordered the DNA to do this from synthetic DNA makers we
could by 270 360 base oligonucleotides assemble them using a process called
Gibson assembly and then transect them into HeLa cells and produce a lot of
poliovirus really easily in a basement lab and cause all kinds of mayhem if you
were so inclined but that’s sort of the flipside of this ability to make a
vaccine quickly we imagine s GI DNA as part of the offshoot of the vaccine
project I just told you about in just a couple of years ago built this device
called AB digital to biological converter the idea is that you can go
from digital information on this platform to producing whole synthetic
chromosomes by the end of the day on this one one machine with robotic
capabilities so that say and this would be a more advanced version of this so
craig Venter has talked about the idea that eventually maybe in the very near
future so at the at the Holly Springs vaccine manufacturing facility in Holly
Springs North Carolina where it used to be Novartis but now I think it’s crk
it’s an Australian vaccine maker who owns it the idea is that you could
in an epidemic in a pandemic we could send digital information to this
facility they could make the DNA there they would never have any need for
anything that came from outside of this facility but they could quickly produce
hundreds of millions of doses but imagine a time in the future when we
have the device that you saw here something much smaller in a hospital and
you decide that this patient needs this a given designer vaccine so it could be
made quickly in essence at the bedside and delivered to a patient this idea of
digital information to producing a drug very quickly and there are all kinds of
applications for this that I can see in the future the idea of really
personalized drugs personalized vaccines that would enable medicine to advance at
least to be more widely distributed using simple systems able to produce
these remarkable biological entities so that’s one example so the other that the
next thing I want to talk about is this idea of making synthetic life and this
had been one of the JCV I am ambitions when I joined the organization in 2003
we were trying to say that we were going to build a minimal bacterial cell in
order to use this to study the first principles of cellular life and it
didn’t seem possible at the time to whittle down an existing bacterium and
so Craig and ham said well if we can’t do it that to get the like a simple cell
like or a bacterium like e.coli and Whittle it down to the minimal set of
genes in order to have something simple to use to understand life let’s just
build the damn thing and so we developed three key technologies for synthetic
biology one was the capacity to build really large pieces of DNA quickly
starting with synthetic oligonucleotides short pieces of DNA
made from four bottles of chemicals and so we were able to synthesize we
developed methods that allowed us to synthesize from building overlapping
pieces of DNA that would self assemble we can synthesize now whole genomes so
we by 2010 we had synthesized a bacterial genome that was over a million
base pairs exactly right every down to the last base everything perfect and
it’s assembled in in vitro and then installed in a nother organism called
yeast where it’s put in yeast as sort of an artificial chromosome so we can park
it there and store it for later use and then the third technology we developed
was the capacity to take this synthetic piece of DNA and install it in a
suitable bacterial chassis cell so that the new genome that were in the new cell
that resulted from this installation is a cell with the genotype and phenotype
encoded by this piece of DNA that we synthesized and so doing this and this
is the method that Dan Gibson my colleague developed to synthesize the
whole DNA really rapidly by 2010 we were able to produce what we called at the
time a synthetic bacterial cell now the rest of the world doesn’t quite call it
that now they they well they called it that then but now many funding agencies
and other countries are trying to make synthetic cells from dead parts and I’ll
get to that later but this was the cell that we made I’d like to have a tattoo
of this but I would want an actual size because I love this organism we produced
papers for the first synthetic cell in 2010 which was an exact copy of an
existing bacterium and then in 2016 we made this minimal bacterial cell that
we’re now using to better understand the first principles of life this is a
little complicated the first this minimal cell has 473 G
and most of those genes you and I have two very similar genes because we have
discovered that life the core the simplest this kernel of living systems
is really pretty similar across life and so what you see here is each each of the
horizontal lines is a comparison of the genes in the minimal cell two genes in
this rain this group of organisms raining ranging from simple bacteria to
man and what we were is that a large fraction of those genes
that are widely conserved across all of biology we don’t know what they do so a
third of the genes and the simplest organism is still fundamentally unknown
to biology so there’s still a long way for us to go to understanding how life
works and this is what we’ve been focusing on mostly for the last couple
of years but using the technologies that we have developed to produce this
minimal cell we have started some other projects so we’ve made a whole cell
computational model that is more more sophisticated than anything has been
developed so far and using these technologies I’ve started this really
novel project so as I mentioned I use insulin but I’d like to see if we can
try to solve the the type 1 diabetes problem I thought by the time I was you
know when I was in my 20s I thought that this would be solved quickly so why get
involved in diabetes research but now that I see that it hasn’t been done I
think you know I should put my two cents into the project so as a diabetic
insulin is a great drug but still life is not perfect on diabetes if you have
to take insulin and so there’s a new understanding of the microbiome you know
there are more bacterial cells in each of us than there are human cells and the
idea that maybe we can take advantage of this recently
was discovered that while we know there bacteria on our skin it turns out that
there are also bacteria in the deepest layers of human skin you know in an
intimate contact with the blood system and so imagine if we took those
organisms some of them are called Staphylococcus epidermidis and I were to
install in those organisms genes that would allow us to have those organisms
synthesize insulin in response to elevated blood glucose and then and we
would have a system so that the sensory information of these sensors that I
install in these bacteria would result in the secretion of insulin that in
theory could control diabetic blood glucose of course we put safety switches
and so then I can imagine that I would get this cream that had it’s that had
these bacteria in it that I put on my skin and instead of having to have you
know devices all over me that control that allow me to control my blood
glucose I could do it simply with this bacterial system that unlike other
approaches being tried to solve type 1 diabetes in to supplant giving people
insulin which involve making new beta cells still the human immune system goes
after those beta cells which is the reason I have diabetes so here you’re
getting a surrogate system of bacteria that we know the immune system can
already tolerate so this is one notion and then it wouldn’t be a modern
biotechnology discussion if you didn’t mention crispers which is this new
technology we’re talking about eukaryotes now that allow scientists to
go in and edit genomes but one of the problems with Krister crispers which is
a remarkable technology as you think about maybe using them in human
therapeutics is unattended unintended consequences because while we’re
beginning to understand crispers we don’t do it fully but we know for
instance that sometimes crispers and stead of just inserting new DNA where
you want it or making the edits you want you get unintended consequences
elsewhere in the genome and my colleagues and I show you here my
colleagues Pam silver and Jeff Way at Harvard and my former graduate student
now postdoc at JC di David Brown we started with this DARPA funded project a
few years ago the idea of building fully synthetic human artificial chromosomes
because here what you’re trying to do is make in essence a small chromosome that
allows you to put anything you want into it that will and then you would want to
install this in a human cell so that it and it would replicate along with the
rest of the chromosomes in order to allow you to produce new proteins or
Gibbs cells new capabilities and so this has been a method that people have been
trying for decades but they’ve been using it they’ve been doing it using
existing small human chromosomes and trying to whittle them down and it just
has not progressed the way people wanted so our idea was to do this with a fully
synthetic system so this is the way people have been trying to do this but
what we want to do is build this fully synthetic system in yeast where you get
all the power of yeast genetics to produce this chromosome and then we
using methods we describe here we’re able to efficiently install this in
eukaryotic cells and in a paper we’re trying to get out the door now what
we’re showing is that these human artificial chromosomes replicate along
with the rest of the human chromosome and they function for months so far as
long as we’ve been able to make them grow so this should allow new
opportunities the idea that I could for instance let’s say I harvest some of
your skin cells and we would then install in those skin cells a human
artificial chromosome identify the the the cells that have this chromosome and
this chromosome would have an of genes for production of great
antibodies let’s say so there are sex workers in Thailand
you never get HIV you could get antibodies to the new diseases that
wander out of the jungle but you could put one chromosome that produced single
chain antibodies that let you make a whole biological repertoire of new
diseases that would protect you from new things or protect troops from new
diseases for instance and another example is we could modify human cells
for therapeutic purposes that need multiple genes because CRISPR I still
wonder if they’re ever going to be widely used because of unintended
consequences here you’re installing a separate fully fully autonomous
chromosome into the genome with safety switches so if something went awry you
could give people tetracycline and those cells would die for instance or
something else but it would allow therapeutics so you could make plant
artificial chromosomes or a number of other remarkable applications for this
technology in engineering hire cells and so I’m gonna sort of stop with that and
say you know here are just some examples of what a team of about 15 people at the
JCB I have been able to get done over the years the numbers of people on the
team have changed but generally we’re about 15 people and this has been over
the last decade and a half and with that I think I will say that you know it
takes it takes a village to create a virus or a cell and I should also
mention that we had support from Barda and some other agencies but if you’ve
got any questions if I still have any time I’m happy to try to answer them hi John we have a question for you on
slide Oh over here okay why target the skin as opposed to other human micro
biomes for the insulin application and what are the policy barriers to this
technology reaching the diabetic community why target the skin relative
to other areas we we thought that this gives us some control that we might not
have in other systems insulin produced inside the gut for instance would
probably be degraded it doesn’t seem to be a suitable system but one of the
collaborators who with the idea that came together was Richard gallo at who’s
a dermatologist he’s chair of the dermatology department at UCSD and he
was the one who discovered that the skin wasn’t sterile deep down so this was the
idea and this was the first thing that we thought of for this sort of
therapeutic approach but we can imagine other approaches where you would use
skin bacteria at like to treat epidermis bullosa which is an absence of collagen
7 it causes skin so the idea that if I rubbed across if I had that disease and
I did that to my arm I would just tear all the skin off so if you could produce
new collagen 7 but this is why we chose the the this skin and it seemed to make
sense at the time I’m not absolutely convinced that we could put enough
bacteria in the skin to make this work that will take empiricism and then we
might think about targeting other areas of the microbiome as well and then the
question about the diabetes community there are a lot of biological biologists
who are trying to solve diabetes and issues involved with diabetes and this
is just one novel approach that at least you know in the last in the last couple
of weeks we got an award that will let us try this
we’ll see thank you hi John you you mentioned unintended
consequences and then followed and contrasted that with a very innovative
idea for installing immune components in human cells that would function inside a
person excuse me and you mentioned possible control systems for that
can you imagine some unintended consequences that might come from that
system particularly if those control features broke down absolutely which is
why one of the things that we will include in such a Cell would be
redundant kill switches so that should something go awry so let let’s say let’s
say I had Alzheimer’s and I found a way to put new cells into my brain to solve
this and something seemed to RIE with this so we would have ways that I could
give you a drug that would Norman already be approved but would be
designed that if those cells saw that drug the cells would die and so let’s
say that the first the the our first approach at this did you know 99.99% and
then some cells didn’t make it so then you’d go to the backup system or the
backup system but inevitably this would be a way of avoiding some of those
consequences whereas with CRISPR based approaches you put something in and
there’s no way of knowing where it went in or what the consequences were and
there’s no way to get it out once you put it in Thanks sure all right please
join me in thanking dr. John glass all right I’d like to move to our next
speaker now dr. Justin Sanchez dr. Sanchez is the director of DARPA
biological technologies office leading BTO s mission to develop breakthrough
technologies and capabilities for national security as he recently noted
his office is ushering in a new way of thinking as they focus on bio next and
initiate groundbreaking research in neuro technology synthetic biology gene
editing and more I’m honored to welcome Justin Sanchez to the stage thank you so
much for the very kind introduction it’s a real pleasure to be here today and
share with you some of our concepts for the future you know when I heard the
introductory remarks from the team here again it really resonated because there
are some challenges that our world is facing that perhaps traditional
engineering will not be able to address and let me just share with you a few of
the things that we are thinking about imagine a future where we could detect
any threat anytime anywhere imagine if we could deliver near instantaneous
protection to millions of people imagine if we could help prepare a war fighters
for the challenges that they may face in protecting our country enable them to
really scale their effects in ways that we have never seen before these are some
of the things that we think about at DARPA and especially in BTO and at the
center of what we do in BTO is biotechnology and I want to make one
very specific distinction here we’re not just talking about biology we’re talking
about biology plus engineering and applying them to some of the world’s
most challenging problems now with that being said when you think about biology
or biotechnology it’s often very different than things like this okay
most of the world when they think of powerful technologies they think of huge
rocket systems and just these are these massive engineered kinds of systems and
those have had a huge impact in the world over the last you know many
decades but when it comes to biotechnology we have a very different
situation and some of the previous speakers alluded to this
biotechnology is completely democratized okay there’s this is a competition that
happens every year I Jim International genetically engineered machines there
are high school students that are come together from all across the globe to
use very powerful gene editing technologies while they’re at the
conference to try to construct different aspects of organisms and look at where
those students again come from ok United States China you know 36 other countries
again this is not technology that’s in the hands of the few it’s in the hands
of the many and if that truly is the case and we’re going to be using
biotechnology for some of the world’s most challenging problems we must have a
new way of thinking ok and this is a challenge I think for this group today
is what is that thinking going to be what are the capabilities that we need
to develop what are they going to be how are we going to Shepherd investment into
biotechnology how we’re going to be able to build industries of the future in
order to try to solve some of the world’s most challenging problems ok so
that’s that’s a challenge I present to you I’m really looking forward to
talking with all of you throughout the day today to see where we might go now
with that being said what is the the mission in the focus of the biological
technologies office and it’s very clear it’s developed the world’s most advanced
bio technologies to defend the homeland all right and when I say defend the
homeland again I’m not just thinking about kind of the medical side of things
I’m thinking about all of the things on this screen right I’m thinking about how
our adversaries could put either manned or unmanned vessels in our littoral
waters or maybe how a natural engineered pathogen could affect our global travel
hubs and in millions of people and even all the way down to things like our food
supply and transportation and buildings there’s the attack surface is enormous
and traditional engineering may not be able to get us there to ultimately
defend the homeland so we’re thinking very deeply about what
bio technologies can do in order to keep us ahead of any surprises that may occur
in our homeland and even abroad ok so today the point of the whole talk I’m
going to share with you a few of the ideas that we have and some of the
technologies that we’re developing along the way all right so let’s start at the
earliest part all of this how can we do that advanced
threat detection and build countermeasures that effect up millions
of people all right and again because we need a new way of thinking we need to
try to assemble what are the pieces how do they fit together and how does time
and adaptability and all of these aspects of what biotech can do for us
play a role in all of this okay so let’s start with something that we all live
with every day so the threat of an infectious disease again this is either
a natural pathogen or even an engineered pathogen you know that is it’s possible
by some of our adversaries now what’s remarkable about this timeline here is
that for the most part when our country is faced with a threat like this we’re
on the far right side of the timeline it’s only when there’s widespread
illness that our country scrambles to try to try to get ahead of that or try
to deal with that and I would argue argue with you know on that point and
just say look it’s far too late to continue to do that we need to move the
timeline to the left so again from the DARPA BTO perspective
let’s go all the way back to the animal reservoir figure out where pathogens
could potentially emerge from and do something about it right and in much the
same vein what if we could even go to the part where let’s say a human was
exposed to a pathogen not showing symptoms yet but we could intervene in a
much earlier way than we ultimately do all right so again this is the spirit of
what we think about in BTO and we’re asking the question what are the most
advanced biological technologies that we could develop to get us more time to
move the curve to the left and get ahead of any one of these these situations
okay so I’m going to share with you what progress are are we making and the
sounds impossible but we are making some real progress in all of these domains so
let’s start with that first one how can we predict contagiousness so we have a
program called prometheus is run by a program manager in our office his name’s
Matt Hepburn and he asks a question can we from a drop of blood
detective somebody was exposed to a pathogen and can we moreover predict if
they’ve would be shedding virus in the future okay and if we could do that
imagine the capability that it delivers right if you know that somebody’s been
exposed you can immediately in Veen and tried to prevent the spread of
that that pathogen to others okay and what are we looking at so we’re looking
at cytokines DNA RNA any combination of biomarkers that may be in the blood all
right so again this does sound impossible and this is the nature of
what we do at DARPA but let me share with you some very real results so we’ve
only been doing this for a very short period of time about a year and some of
the people that we have supported to work on this problem have some
tremendous results so left side of the screen they’re looking at h3n2 and h1n1
so flu variants and within five hours they could predict if somebody’s been
exposed to a pathogen okay these are real human samples they’re developing
the computational techniques as well as the biomarkers to ultimately do that the
right side of the screen says something even more powerful okay so if you have
been exposed to let’s say influenza you know the state of the art right now is
to look at something like interferon and what’s a difficult part about interferon
is that if you’re interfering I’m positive you might be shedding virus at
42 hours right but if you’re an interferon negative you’re kind of left
in the dark so we ask the question again go back to that drop of blood look at
those biomarkers and we’re looking at combinations of RNAs and how they’re
modulating either up or down over time and even with those first few biomarkers
we can within 18 hours predict if you’ll be 74 percent likely to be shedding
virus all right so again look at the time differences right being kind of
uncertain at 42 hours or moving to being very certain at 18 hours imagine the
possibilities that that could give our country the capabilities that would give
our country to stay ahead of any one of these pathogens so really encouraged by
these kinds of results and it’s we think it’s going to give us a time advantage
in the grand scheme of things now it’s not just the detection of of that it’s
what do we do about it okay and again in some of the previous presentations today
we’ve already started to hear this concept of time right time is never on
our side when it comes to pathogens again 2009 h1n1 you can see when the
outbreak was was occurring right so millions of cases on the y-axis time on
the x-axis when our first individuals were being
protected as well after the peak of the curve it’s far too late and if we want
to take a pandemic off the table we’ve got to move the curve to the right so
again if we had it our way you know we would like to be in the May June July
time frame in order to try to stop that that pathogen from actually having an
impact so again what is the breakthrough technology that’s ultimately going to
get us there and how would it work okay so we’re thinking about gene encoded
antibodies and let me share with you the fundamental concept for for how we kind
of think about gene encoded antibodies and before I show you how the technology
works you can recall back to the previous presentation if we do
traditional vaccine development it’s months two years to try to find that
countermeasure and then we’ve got to grow it up and bioreactors and all of
those kinds of things so the breakthrough for us is to make a pivot
is not use a lab bioreactor to produce a countermeasure can we fundamentally
change our thinking say can the body be used as a bioreactor so as a part of a
program that we’ve had in our office called a death we started laying the
foundations for this and the idea is if you know the genetic sequence the
blueprint that your cells need to produce the most potent antibody can you
construct it can you get into the right cells and let’s say the muscle cells of
your arm and tell them immediately what they need to produce okay and again this
would be a near instantaneous but transient protection against virtually
any pathogen if we could figure out what that code is again sounds like science
fiction the teams that we have supported to do this have made tremendous progress
right side of the screen this is my challenge with Ebola the mice
that got the gene encoded antibody survived it gives 50 micrograms of kind
of a level of protection the mice that didn’t get it you know did not survive
all right so this is proof of concept that we can make a big impact near
instantaneous protection from even some of the world’s most challenging kinds of
pathogens now being DARPA do we just stop there with the existence proof no
all right so again our our bigger goal here is defend the homeland protect the
homeland how do we kind of scale this to a whole new level so we ask the second
question could we do a pandemic prevention platform and
there’s one thing that’s always amazed me about a biotechnology let’s say
compared to other engineering technology right so if you go to the Department of
Defense they’re gonna build you a big platform technology whether it’s an
aircraft or a ship or something like that when it comes to biotech we don’t
always ask that question can we develop a platform technology but in BTO we did
we said could we develop this pandemic prevention platform and when a pandemic
occurs can we get those samples into a biotech integrator all right so this is
the platform and can the integrator grow enough virus to find the most potent
antibodies to come up with the the manufacturing the formulation for all of
that and actually deliver that gene encoded anybody and as a milestone of
the program again our goals are not just to write papers as a proud of our work
at DARPA it’s a developed 20,000 doses and 60 days or less of gene and coded
antibodies okay so the teams that we’re funding to do this are required to try
to show that demo and if we can get that we believe that we can get those
countermeasures to you know thousands or even millions of people if we can
actually scale it our goal take pandemics off the table and again I
would challenge all of you here today let’s be audacious Alaa deixa sin and
how we actually go about you know setting up the vision for these problems
and then find what is the most high-impact technology that can
ultimately get us there okay so that’s infectious disease now does our thinking
just stop with infectious disease so so viruses and it’s know right so if we
think about the national security landscape there are other pathogens that
threaten our country so there’s bacteria so 99 percent of the bacteria that may
exist in the world are virtually unknown and we’re very interested in
understanding the relationship between genotype and phenotype but we do not
have a way today in order to find the relationship between genotype and
phenotype is phenotype especially in bacteria so we have a new program called
friend or foe s being led by program managers her name is Paul Sheehan he’s
asking the question can you culture bacteria and can you play 20 questions
with that bacteria to see if it’s pathogenic or not again are you
grandpa’s native gram-negative do you resist Tet recycling again come up with
a end-to-end strategy in order to deal with that okay so that’s bacteria what
they’re kinds of threats are on the table and how are we trying to deal with
those so you heard in some of the introductory
remarks today could we do biosurveillance in a profoundly
different way right so most of the world thinks about biosurveillance
engineering a system in order to do the detection we think about that can we
engineer plants to detect any number of the things so Kim Rad nuke whatever it
may be plants are remarkable organisms they’re
persistent they have their own power sources they have three genomes there’s
a lot of genetic capacity through which we might be able to engineer into them
the sensitivity to those threats and maybe even produce a signal that could
be detected at standoff it’s a revolutionary way that we think that we
could solve this problem I know that there’s people in this room that are
thinking very deeply about how we could ultimately do that now this our thinking
stop on the land absolutely not in DARPA vitia we’re also thinking about the
oceans the littoral waters how can we do surveillance in a whole new way to tech
manned or unmanned vehicles and the crazy idea that we have on the table is
could we help solve this by leveraging what natural organisms do in the ocean
so you may or may not know this but submariners when they’re using their
sonar they often have snapping shrimp that create a lot of noise and in their
sonar and we said well you know that’s their problem but let’s invert this can
we take that noise and actually use it to an advantage and we think that we
could develop next-generation technologies that could use those signal
properties in order to detect man or unmanned vehicles so Laurie a tornados
the program manager that’s running this program is called pals okay so with that
let’s pivot real quick here and go to the next step so that that was all about
detecting threats and developing countermeasures can we get critical
resources where and when we need them so again if we’re gonna take broad threats
off the table and even in austere environments like our military operates
and we have need a new way of thinking about how to do that so some of the
technologies that we’ve developed over the years or platform technologies for
doing pharmacy on demand okay so it’s if you’re in an austere environment can you
develop a box that has a precursors for a wide variety of medications that you
may need out in that all-seer environment so small molecules or
biologics you press a button and you get the drug in the field if we have
something like this and it serves the military it could also serve us in terms
of defending the homeland put these boxes at let’s say CVS is all across the
the country maybe you have a whole new way of thinking about how we put
countermeasures out into the field and moreover it’s not just the
countermeasures themselves when our body is subject to injury or illness we again
as I’ve been saying we need to buy ourselves more time we just launched a
brand new program called bio stasis it’s run by Tristan McClure Begley and the
whole idea is during the Golden Hour when military personnel are injured
could we develop a new molecules or interventions kind of slow down the
movement of of all of those molecules essentially buying us some time and then
when we actually get that person to a place where they’re getting their
therapy could we reverse it again sounds impossible at Tristan and his team think
that they can go go about and actually deliver it okay so that’s delivering
resources where you need it the last part of the talk here and the idea set
of ideas that I’d like to share with you is how do we think about accelerating
warfighter performance and repair okay so again the challenge is that our
military personnel are going to face in the future
are going to be very different than the challenges that we see today how do we
prepare them how do we make them more resilient how can we accelerate the
performance to ultimately deal with all those challenges and the lens that I
would like to share with you at least are some of our initial ideas and we got
a lot more coming in this space is first through the through the lens and neuro
Technology ok so again you heard a Ralph talk about how there’s been a lot of
work that’s been done here APL and laying the foundations for neuro
technology but let me just walk you through like where did this come from
it’s amazing to me to think that in 2001 scientists write the world’s most
esteemed scientists we’re saying that it was near impossible to put sensors in
the brain read out information in real time to actually do something useful
with it DARPA started a program back in that
time to work in non-human primates to prove out that foundational technology
and we did but again being DARPA we didn’t just stop there we took a next
major step and okay 2005 let’s go directly to humans
let’s not just do movement but let’s also do sensation show that it actually
could work okay so look we’re building complexity we’re building knowledge and
how we can do this again does DARPA just stop there no we keep going 2013 we
launched a program to do direct neural interfaces closed-loop neural interfaces
in humans for memory we push the envelope again 2013 said can we do two
more complex functions of brain let’s say neuropsychiatric health again
restore neuropsychiatric health to our military personnel who have been under
extreme kind of conditions and service of our country all right so again the
take-home message in all of this is that there are some challenges that seem near
impossible but when some of the most brilliant minds come together in a very
focused way we can deliver those technologies and show that they actually
work now one last stuff you flip in this chart that I would like to show you is
that all of that that I’ve shown you so far has been in the medical domain but
we see a huge potential and possibility for neuro technology for those of us
who’s that do not have medical conditions so we’re asking the question
can we develop non-invasive neuro technologies that have the same
resolution that the invasive kind do and let’s ask the question will what might
you do with your brain in the future okay so that’s a progression of what
we’ve done in DARPA BTO but you know that the point of all of this is about
what neuro technology does for people in their lives and let me share with you a
couple of videos to show you what people can actually do with neuro technology in
their life alright so the first one is about the peripheral nervous system so a
person living with amputation they have a direct neural interface and we can not
only read signals to infer what their movement is but we can write signals
back into the peripheral nervous system today and actually feel something in the
environment and it’s not just the physical world that this person is
interacting with it’s a virtual world okay so let me play the video and this
is what a person can do right and again for a person living with
amputation this is transformative for them okay and yes this is a medical kind
of a condition this is how neuro technology can change that but I truly
think that an example like this it fundamentally changes how humans and
machines and even virtual environments what will ultimately you know change
over time all right so that’s peripheral nervous system that’s virtual
environment let’s take another step okay so this is Nathan here he’s paralyzed
from the neck down he was injured in an automobile accident he has a direct
interface to his brain okay so sensors in the motor system as
well as in the sensory system of his brain you can see that robotic arm
that’s there that robotic arm was actually developed here at the Applied
Physics lab and the experiment is he’s blindfolded can you touch the fingers of
the robotic arm and can he tell you which fingers that you’re actually
touching okay middle index and middle all right so he has
individual finger resolution through that robotic arm directly to his brain
so I can remember that statement where’s our profound change in how humans and
machines are interacting this is the first example of what may be possible in
that space now again this is you know pressing on fingertips a question that
was naturally asked here at the Applied Physics lab will is well can we sense
things other than just forces applied to the finger tips okay and the question
that came up in the engineers that were working on this problem was could we
place an infrared camera on the palm of the robotic hand and could we put a
infrared source in the environment again the person cannot see what this is and
can you actuate the arm under direct brain actuation and then if you can feel
where the infrared sources stop the robotic arm and again remember this
person is feeling with their brain that kind of infrared signal so this is what
Nathan was actually able to do as a part of this test
all right so the robotic arms in a start position there’s a target that’s on the
screen you can see in the far right corner where the actual infrared target
was all right this is gonna start in one second right so it’s in the upper right-hand
part of the screen is where the infrared sources again Nathan can’t see this but
the camera that’s on the palm of that robotic arm is sending signals from the
environment directly back into his sensory cortex and then when he gets the
arm actually over that target he hovers the hand and he signals to us that he
can feel that’s where the infrared target is all right so kind of the first
time ever that a person has felt infrared game-changer for how we think
about humans interacting with machines okay now again the the extraordinary
engineers that the Applied Physics lab didn’t just stop there they were asking
the questions well look if we can rican troll a robotic arm what else can you
control just by thinking about it and they ran this extraordinary experiment
with Nathan again control a primary aircraft but also control two additional
unmanned aircraft and canyou can control all three just by thinking about ink and
this is an example of what Nathan was able to achieve
he’s flying that primary aircraft again using direct brain signals in order to
change the direction of the airplane at the top of the screen you can see the
two additional aircraft that are there he gets a cue that he’s got to move
those additional aircraft to two locations while still maintaining
control of the primary aircraft and he was able to actually do that so what
natural question emerges from an initial proof-of-concept like this is you know
how much can you control under your you know your direct a volition through a
direct brain interface again the possibilities are really opening up for
us to answer questions like that okay now did we just stop with movement and
sensation I showed you that trajectory of neuro technology as a part of our
work the answer is no we got into the memory domain again why did we work in
memory domain there are hundreds of thousands of military personnel that
come back from their service which romatic brain injury memory is often a
function that is affected by that we asked could we develop a direct neural
interface to help them form and recall declarative memories again in the
example that I’d like to show you today again this is very different than
anything we’ve ever shown in this domain we have enough understanding about
the neural codes for declarative memories that we can provide somebody
let’s say a an image that we want them to memorize and let’s say it’s just a
gray square and but if we can write a specific neural code into the memory
center of the the brain we can associate that that gray square with a particular
image out of a set of images that that were interested in having them remember
okay so the experiment goes like this before I play the video person touches a
screen after they touch the screen they’re shown this gray square while
they’re shown the gray square we write the neural code for a particular one of
those images that you see in front of you and then we’ll hear what the person
what their recall was as a part of this task okay so here goes so touch the screen they’re showing that ambiguous image we
write the neural code for one of the images that you saw before and then this
is what the response I have to pick the one that we wrote the neural code says she likes that one but I think it
was this one that was actually the one that the neural code was written to
great once you take the one you lectures once I was Oh okay and that was a breakthrough moment
for us again we have enough understanding about how the brain forms
in and recalls memories that we can actually use a direct neural interface
for a task like that think of the implications for all of us in the future
of what it could do okay last video before I wrap up here again
we’re building in complexity we started with movement and sensation we’ve gone
to memory now what about extreme neuropsychiatric illness this is a
person that has epilepsy they’re undergoing monitoring for that epilepsy
but she also has extreme anxiety there’s a direct neural interface that went to
multiple locations of the brain that can assess how the neurons of the brain are
involved in that neuropsychiatric state it can deliver a direct targeted kind of
intervention to help this person with their extreme anxiety and this is what
she actually experienced so this is stimulation off this is how she’s living
with their anxiety and now we turn the stimulator on
closed-loop neural interface our excitement maybe there we go it’s
good okay that go that do you think that do I don’t actually my goodness all of a
sudden I have some energy but I like energy feels good
it really is Wow what do these do this is excellent is
due to this kind of it oh good days okay oh yeah there are so
many things I just love love to do when I’m not having yeah and this is normal
love is excitement it’s a think about what you just saw here there’s a
possibility for the future that people don’t have to live with extreme
depression extreme anxiety extreme PTSD we have a deep enough understanding of
the brain that we can start to break into these spaces where we think we can
develop medical technologies that could be transformative for people okay so let
me just wrap up here there’s one last very important topic that I’d like to
share with you everything you’ve seen here today they’re very powerful
technologies and because they are very powerful technologies we have a
responsibility to think about the ethical legal social implications of all
of them and I’m so happy that I’m at a meeting here today that that topic is
also on the table thinking about who has access to biotechnology is biotechnology
a right or a privilege how does it impact our daily lives not only our
national security lives I would share with all of you answers to those
questions are not just for the technologists they’re for all of us okay
so let’s make sure that we do a really good job at addressing those while we’re
trying to develop some of the world’s most advanced biotechnology so thank you
so much and I’d love to open up the floor for questions I just and we have a question from slide
Oh our our own us ethical constraints a problem for us to compete with other
countries experimenting with cutting-edge biotech whether cloning or
building super soldiers most of these concepts are met with cultural
antibodies you know that’s a terrific question and you know what’s the issue
that’s on the table ethical legal social implications are not uniform o’clock
across the globe alright that’s just the reality of what
we’re dealing with and you know what I would say is that we need to come
together technologists as well as a meth assist to understand that landscape to
to take actions so that we’re never surprised by what may come across the
globe and to make choices as humans to help to protect what we feel is really
important and valuable for us as a society and the only way we’re going to
get there is to be thoughtful about it to be open about it and to address the
issues head-on so again this is one thing that I think it is a challenge for
all of us and we need to look at it from multiple angles but terrific question
other questions sure I have another question from slide oh how will the 60
days from virus to twenty thousand doses work within the current regulatory
framework ah yeah another terrific question so you know let me preface this
with this statement while I’ve served at DARPA one of the things I’ve always
tried to do is build new partnerships with the FDA again right government to
government we can come together and you know I’ve seen a real partnership emerge
the FDA absolutely wants innovation for our country okay at the same time they
want things to be safe and effective and that is absolutely something that they
must do and the questions that we often ask together when we meet and try to
form these new pathways is okay there’s a technology that’s emerging you’ve
never seen before how do we work together to define a regulatory pathway
to ultimately get there and then moreover it’s not just government to
government that’s involved in these conversations we encourage the people
that we fund to engage with the FDA unless and we say look let’s have some
open conversations there are going to be things that again the the regulators
have never seen before let’s talk about what those technologies are let’s make
sure we’re doing all of the tests that we need to do in order to get through
that regulatory pathway and again DARPA will fund work to do that and and again
I think what we’ve been able to define over the last handful of years again
DARPA are performers in the FDA is a entirely new vision and perspective on
how to do this right so again if anybody is uh you wants to
learn more about how to do it right you know come talk to me I’d love to share
with you some of the lessons that we’ve learned over the years but I see a very
I’m very optimistic about how even with gene encoded antibodies we can find a
way to actually put those technologies into play ok other questions I see I
just had a question it seemed so you’re able to code a
thought right that that’s what a generative memory some memories a very
comp or memories very complex we did one small sliver of memory so far right what
seems interesting I think you know in your application
it’s a miracle for the person but can’t you be using that for pacification or
correct thinking you know in future applications that thought of if you can
program memories or work with the brain in a way that you can be telling it
exactly what it should be doing how do we prevent you know malicious use of
that or use for mass control that type of thing because it seems like something
that could make populations that you don’t feel are tractable more tractable
so get tremendous question and what you’re what you’re getting at is dual
use ok so again let’s be very direct about everything that you’ve seen here
today and I would even argue almost every technology has dual use right is
we are trying to develop technologies for the most beneficial use of that but
there are people in the world that may not use it for those beneficial purposes
and you know I say part of our mission is to understand all of the
complexities of technologies so that we won’t be surprised by all of those okay
so that’s kind of issue one let’s address that yes there’s dual use let’s
understand all about that that Julius and prevent dual use from happening and
again that’s the kind of the second part of it we need to make good decisions
along the way in order to to prevent that dual use from happening okay but
it’s a very complex issue and and one that we think about not only from the
technological side but also the ethical legal social implications of it so again
thank you very much to the question okay I’m sorry that will have to be our last
question please join me in thanking all right I’d like to turn to our final
speaker of the session now dr. Megan Palmer dr. Palmer is currently a senior
research scholar at the Center for International Security and Cooperation
at Stanford University she’s founded and led numerous programs aimed at
developing and promoting the best practices policies and the responsible
demonstration and development of biotechnology a self-prescribed
scientist and engineer turned policy wonk
please welcome Megan Palmer to the stage it is really such a pleasure to be with
you here today and I am really grateful that you are asking these questions
these ethical questions upfront and in an integrated way with exploring the
potential uses and misuses of biotechnology I call my comments here
how to be smart and secure in a biological age and I pose it as a
question because this was a question that a do-it-yourself biologist asked me
and I think that the answer to this actually lies in asking Andry asking the
question continually over time what does it mean to be smart and secure as we
continue to develop these technologies and if we think about the capabilities
that we need I think that there are capabilities around asking these types
of questions that we need to experiment with I’m gonna start off with a
disclaimer some of you may have seen early on that all Tatara was supposed to
join us today and I bring this up because my first disclaimer is I am NOT
Alta I am also not an ethicist and I am certainly not a lawyer but I am an
advocate for engaging with ethical legal social questions continually I am an
engineer and I engineer and I study these engagements and so I hope that we
you can join me in continuing to do that Engineering is a little bit of
background I work here at the Center for International Security and Cooperation
at Stanford University and I’m really grateful to be here because we bring
together natural scientists and engineers along with scholars and the
social sciences and in the humanities to study critical questions around our
shared security so we work a lot in nuclear as well as in cyber and
increasingly in bio technologies and are able to draw lessons across these
different domains but as an engineer some of my favorite places to be are
here so several of you in the audience were with me just a week ago in Boston
this is the International genetically engineered machine competition that
Justin mentioned where thousands of young excited genetic engineers came
together to share their designer organisms and Here I am up on stage
trying to appear cool holding my globe and convincing them that talking about
responsibility in the world is critical to their shared future I am very lucky that I’m not alone in
this pursuit I have many collaborators some of which are in the audience today
and many people that I’ve worked with and again I think that building teams of
many shared disciplines is really critical to be able to ask and answer
these questions so what’s happening with all of these exciting new developments
in biological technologies is that we’re seeing a proliferation of technology
policy puzzles we haven’t talked today yet about gene drives but the ability to
actually develop technologies that can propagate genetic traits through
populations right there can be really exciting for certain applications but
also somewhat puzzling and and disturbing we develop technologies to
develop new custom drugs how do we make sure that they’re not misused how do we
you know work in these technologies that can enable better health but can also
enable selection of traits and what do we do when the technologies are not
under just our control but our you know so-called democratized how do we make
sure that our values are embedded in these types of technologies and the
reality is these are really old questions this is just one example this
is from the Rolling Stone magazine in 1975 that I have up in my office the
Pandora’s box Congress where scientists and the first generation of genetic
engineers got together to look at some of the implications of their work and
and again this is the need to continue to ask these questions we’re not going
to come up with all the answers but we know that we’re not you know we’re
already in the situation of risk right where you have to develop these
technologies to solve many of these problems and I like the little quote
here from this article that says you know human sex is a moderate risk
experiment right we are made of biology we are doing risky things all the time
and we need to figure out how to take those risks Martley unfortunately what
happens is our narrative is often caught in this dichotomy right this is not my
article this is Laurie Garrett and foreign affairs a couple years ago
talking about by Allah brave new world and her lesson is to be
happy and worried unfortunately we often think about biology as the technology
that will solve all of our problems right to be to be the root of health and
wealth and flourishing of Nations or otherwise we think about it as being
potentially the end of our civilization and really contributing to insecurity
and the reality is that instead of a weapon of mass construction or a weapon
of mass destruction really biology right now is a weapon of massive ambiguity and
uncertainty about what exactly we should do and so I think that the answer here
is to be happy about a little bit of worrying and to exist in this grey zone
because the inescapable questions are where do we draw lines what do we do if
we see somebody crossing those lines and this question is asked in many different
technologies but it’s incredibly important with this technology because
it is literally what we are made of right and also it has special moral
obligations around the misuse of that technology and so being able to navigate
in this gray space requires serious ongoing integrated engagements with
ethical issues and expertise the things I want to stress here is this is not
free right it is not just a lunch conversation it is not easy and it but
it is also not new right there are models that we can use and it’s also not
about slowing down but moving more smartly forward I just offer this as
well this is science magazine the CRISPR one of the CRISPR articles that you know
is proclaiming this revolution and the ability to use these technologies and in
a tiny little box up at the top there is a in font it says managing biological
risks and in that article myself and a couple of my colleagues at Stanford
argue then unfortunately all of us are
short-sighted in thinking about the fundamental shifts the fundamental
cracks in the foundations of what we think technology and governance looks
like we need to be much smarter about looking ahead so I want to talk about
three key aspects of getting smarter embedding reflection evolving our
policies and thinking about governing in networks and to do that I’m going to
return back to I gem IgM as one of these places where perhaps we can learn from
the kids so how many of you are intimately familiar with ajam how many
you have never heard of it before okay so there you know we have a mixed bag
here um so the quickest introduction that I can give is probably many of you
more familiar with the FIRST Robotics Competition so I did first in high
school and the basic idea is you get a kit of parts mechanical electrical parts
and you get to build a robot that plays a game and I am Canadian
and so of course I had to build a robot that played hockey and even though we go
out to last place it was a transformational experience and I John
works the same way except instead of mechanical electrical parts you have
genetic parts genetic functions and instead of playing a game you get to
choose your game you get to choose to develop the technology that you think is
most useful so this is what it looks like this is the kit of parts the kid of
genetic parts very tiny parts and a genetic and a representation in the
digital space so these are not just physical but digital constructs and then
these teams of largely undergraduates choose what they think is the most
useful application of biotechnology and you’ve heard about some of these already
from Justin and John but these exist across environment and health to new
manufacturing to fundamental technologies so just as one example some
of these are very simple tools so one team this is
in 2009 they just really wanted to see what they were doing and so they
developed pigments pigments that could be expressed by cells and then they
coupled it to sensors developed by other teams and then they didn’t just develop
the tool they tried to explore what that tool might be used for so in this case a
colorimetric sensor right that could be ingested and then it would maybe detect
something in your gut and then you get a really useful readout of what is going
on and so these teams come together and they present they make a website they
present in front of all their peers they present to some of their heroes here at
George church and they also deposit these parts in a repository and then
this is a microcosm of really the world because they both compete against
themselves for achievements but they also compete against each other for
recognition against the back best applications and the best overall prize
and they’re judged by their peers so in this case near peers their mentors and
others there was 175 judges this year I believe that came from across the world
and so what these types of platforms have developed is this sort of virtuous
cycle of problems and people and funding and tools and really the incentives to
grow this over time so when I started at MIT in 2003 2004 it was the size on the
left just a sort of rough cadre of people coming up with this idea and this
year we had I believe about 6,000 students in 340 teams from 48 countries
participating along the theme of today this technology is here today so this is
one of the folks that was in that early picture who presented about a week and a
bit ago about you know the vision for his now I think billion-dollar valued
company that started off as ideas in this competition and he’s pointing and
say the future leaders are in this room and so the question is where tomorrow
what are these kids going to be thinking where will they be working what will
they be doing what questions will they be asking so I’m going to get just a few
vignettes of the what we’ve done with this type of setting that might be
useful inspiration so I’ll start with embedding reflection so we run a number
of programs within this competition to think about these ethical conundrums
they work together one is called human practices the other is the safety and
security program and another is responsible conduct and some of the
leaders of these programs are in the room this is a this is what it looks
like and I leave human practices this is a hugely embarrassing video of me on the
internet talking about how we need to think about human practices as the study
of both how your work affects the world and how your world how the world affects
your work and there’s parts of this program we provide guidance to teams
this is not strong guidance it basically says you need to think about this and
show us how you’ve thought about it and there’s a team really from across the
world that helps to shape this program and this is the key the key here is
providing incentives and these are graded incentives so that collaboration
and the competition teams don’t just compete for the technical savvy and the
best whiz-bang gadget but rather on how carefully they’ve considered the purpose
of their work the risks of their work and they get different levels depending
on how deeply engaged they are with those questions so first is just
compliance but then to get anything else you have to show you’ve gone beyond
compliance and you’ve actually innovated and developed new ways to ask ask and
answer these questions there’s many creative examples there’s
2,500 projects or so I won’t be able to go through them but I think this example
from one team at Imperial College London shows human practices embedded here
within their engineering design loop teams work on many
different challenges from how to engage with their local communities
to ask deep philosophical questions to work on the policies that apply to their
labs that don’t cover synthetic biology and work on accessibility and new
partners and I’ll just give one example from this year of the type of things
that can happen so this is a team from from Germany billfold
that were really concerned about the problem of electronic waste you know how
are we going to deal with these problems and so they thought it would be a really
good idea to come up with a microbe that could degrade electronics because of
these types of incentives to think about whether or not that is such a good idea
these teams put this at the front right and not only did they think about the
dual dual use aspects of their work but they actually developed a system to
educate other teams about the dual use aspects of their work and think about
how that should enter into their design choices so how can we be inspired by
these kids this is just two of the different programs one is sin burkas is
an NSF 10-year multi-million dollar program that I helped to lead and when
we think about the resources involved the research and practice agenda coupled
to these types of questions ended up being up to 20% of the budget
right so think about the types of resources involved and I’ve been really
heartened to see programs like DARPA that really takes some of these
questions and put them at the forefront having panels and questions in their
Elsi and leader programs and having their mission space directed at these
questions of how do we safely develop genetic engineering through the safe
jeans program so a little bit more quickly on these last two aspects the
second is evolving policies so in addition to the human practices program
we have a safety and security program that’s spun out of this effort and my
colleague Pierce millet also has a similarly embarrassing video online that
you can watch and this is a paper that came out to
describe really ten years of investment in designing these adaptive policy
settings where because we’re at the cutting edge of prototyping technology
we also have to be at the cutting edge of prototyping a policy of to keep pace
there’s many layers of this program I won’t be able to go through them all but
it involves also incentives guidance screening of projects and parts um it
also involves policies so these are some of the policies and I will say this list
changes every year it is updated every year that we go through the competition
because of the surprises kids are really good at questioning the fundamental
rationale of your policies they will find ways to break them and to question
them and show you why they aren’t they aren’t working we also work with the
team to review all these projects early and often and this is part of it is that
it’s not just a review and a yes no it’s actually a mentorship it’s a shared
responsibility between the many different people that work on these
committees and the teams so that they can come up with solutions and so it’s
not just a sort of ad-hoc group of academics that are working on this but
it’s actually now governments and organizations from all over the world
that are investing and figuring out if they can test and adapt their policies
through these test beds right so there are places to begin to test that what
breaks and what works and we’ve had to figure out how do we develop context
specific risks but assessment beyond policies deal with differences in
international rules and regulations around say the use of animals how to
deal with things like cutting edge technology and the prevention of misuse
so this is another example here from the University of Minnesota and about I
think it was about six months or less than a year after the development of the
concept and proof-of-concept of gene drives these teams decided as their
project they developed a gene drive this hit the news
but one of the best things about this hitting the news is it explained how the
teams were actually working on technologies to make gene drives safer
and they did not develop a gene drive and describe the mentorship of the
safety and security and the human practices committees alongside it so
this is key in having the communication the transparency the accountability
around these processes who would explain the justification of why we’re trying to
both push the envelope but not push it too far and we can again adapt and
clarify our policies and these policies are done with representatives from all
around the world and teams again I can give you many more
examples of teams partnering with governments and with industry to figure
out how their technologies can contribute to safety and security and
also expose some of the vulnerabilities in our system in ways that that make us
more secure again what are is our inspiration I think here we’re seeing a
lot of inspiration with programs like the IEEE output program funds e-cat here
developing technologies that are really critical to advancing policies right
being able to to screen and detect things better have more resolute
policies requires us to develop the technology in concert I also see a
little bit of inspiration in the type of strategies that have been developed or
proposed to work and devoting resources to the supplied biosafety and
biosecurity research in our bio defense strategy so in the last minute I’m just
going to come back to this problem of governing networks so this is one of my
favorite comics this is xkcd it’s really a nerdy comic
but this is an attempt to map out online communities this is one of a series
earlier versions of this comic had a large territory occupied by in my space
and now it’s like a small island nation and Facebook has a large territory and I
wonder what does this type of map of who is shaping our activities and behaviors
look like in biotechnology I think I gem is one of those
organizations right one of those platforms that shaping the standards and
the technology what technology standards are we promoting all around the world
but also these norms and values so there are interesting groups investing in
these technologies and the social and technical infrastructure the FBI is one
so the FBI is a sponsor of I gem for two reasons
they see the forefront of the technology and what’s happening and they can also
enlist the help of this whole global community
this is them on stage talking about how you should know your local WMD
coordinator but the key here is actually the reverse this is a team from the
University of Calgary in which my hometown at the biological weapons
convention and here it’s where the kids are coming in to teach the adults about
how they’ve thought about these risks and taste aid on top of the technical
horizon and I think we’re seeing now inspiration from some of these kids that
have grown up and again this is ginkgo Bioworks starting to see commitment to
working together on the platforms and the technologies that can contribute to
our national and international security so I’ll end there and just say let’s
learn to live together in the gray zone let’s develop the capabilities for this
type of ethical reflection and let’s make sure that we keep the kids in mind
thank you the question from slide Oh over here how
do you transition your silver all silver and gold level beyond mere policy
compliance aspirations beyond the competition to other spheres such as
publications tenure and hiring considerations and venture funding I
think that’s a really great question you know we have experimented with some of
this with venues like the National Science Foundation Center that I
mentioned before with with Cimber where we really tried to align the types of
incentives around working on these problems is something that could be a
legitimate research agenda things that could be published on the idea of having
you know technologies and and policies are not decoupled and so we see this in
academics is there being journals that have applied biosafety biosecurity
research and an industry having these funding and incentives and programs
where a company can actually you know work on solving some of these challenges
and some of the deep technical aspects and so I think we need to figure out how
do we align again the incentives for this but also realizing that it takes
resources and money and and leadership hi Megan thanks so much for a great talk
I wanted to get your thoughts on where students go after the item experience so
and and what lessons they’re taking with them over the long term so gingko is a
great example of that I’m wondering if you’re planning on looking at that and
any sort of formalized longitudinal way to say you know how are these practices
being carried forward which are the parts that are resonating and being
carried in to industry academia and Beyond where we don’t necessarily have
some of these programs in place already hey I feel like I planted that question
so one of the reasons that I spend so much time with with I Gemma so I think
it is a possibility to ask these types of questions about both examining a gem
is sort of a microcosm of what’s happening in our world but also as an
intervention and so part of my research program at Stanford is actually being
able to look at can we find out yeah where the kids go when they when they
grow up and so what is it about the environment that
there from the training they’ve received the mentorship that might be predictive
of their attention to risks so we don’t have all the answers to that yet but
we’re starting to ask the questions and would love you know others who are
interested in similar questions to offer you know their potential help or or or
guidance yeah another slide Oh question for you how do we extend the ethical
training in I gem to today’s larger policy environment I would say at the
start invite the kids into the room I think we’ve learned a lot from again
that you know new folks who are training in these areas you know at the at the
intersections of disciplines have a lot to offer right away and so you know
sharing sharing that table is is really important I don’t think it’s the only
answer but I think it’s a really important one and I also think we have a
lot more room for comparative comparative work and there’s a number of
different disciplines that are really need to be engaged here it’s not just
you know an ethicist but there’s many different angles and so that policy
forum it means making sure we have mixed teams right we’re working on these from
the outset negative so the robotics community for kids to learn robotics
it’s a much larger community but they face very similar ideas in terms of the
risk maybe not the risk of destroying the
world but at least the risk to the project and so are there philosophical
differences between the way I gem teaches risk and the way that the
robotics community teaches risk and then are there consequences of those two
different approaches yeah I think well I think first it’s a great question when I
was in first robotics I was not trained to ask these questions in
the context of what I was doing it was more of a sort of whiz-bang gee you know
gee whiz this is cool and so there’s just a different in approach at the
beginning on that we’re trying to develop but I also think it’s
recognizing that yes there are questions that come up with any technology around
its use and misuse but I do think that there are even more fundamental
questions when we are as I said dealing with the thing that we are made of right
we are altering ourselves and our living world and that is you know deserves awe
and respect at the same time and so I think it’s asking the same questions but
more often in a different way and in a way that’s really much more integral to
to what we’re who we are

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