Um, and a nifty little protocol That's
really, really cheap. It really easy to run, and in
most cases doesn't even need a centerifuge
and can allow someone to further concentrate
the RNA found in a sample,
uh, to the point that you can increase that
sensitivity down even one virion
per microliter.
At least that's what it looks like
in the RNA controls.
And what's nice about
this and sort of why we were able to do
it, is,
uh, LAMP reaction has proven
itself to be very, very robust
to a lot of things that would normally inhibit enzymatic
reactions.
And so we're able to do this really fast
and cheap and true purification
and the reaction is still able to tolerate
any small amounts of inhibitors that get carried
through.
Yeah, I was gonna ask about that. So
the
additions of chemical agents
to help lyse the cells
and
prevent RNA degradation...
Uh, those don't have any effect on
the color change or the buffers or the other
components of the reaction?
No. So you know, I had the fiddle around with
them to make sure that the reagents I was using
were at the proper pH.
added, but luckily,
they don't appear to have enough buffering capacity
or anything like that, to throw off the reaction.
Well, that's incredible. So what kind of samples
have you tested so far? I know your
paper was mostly focused on
nasopharyngeal swabs,
either sort of with or without
this RNase
protection treatment.
Um,
but what other? Have you tried other samples,
or is that something that's coming in the future?
Yeah, So I've actually tried, and
I think this is something as far as clinical samples
that's in the pipeline. But I've tried with reconstituted
samples, straight saliva,
and that's been something else. Where LAMP
has, I think, outperformed certain
other tests in that
the saliva doesn't appear to be particularly inhibitory
to this reaction. Especially when you run this inactivation
step first.
Um, I think a lot of other
the reaction types
that assays that are being developed,
tend to be much more sensitive to those. But the two
enzymes in LAMP appear to be incredibly
robust. Well, that's
amazing and really promising to
hear. So where do you see Covid
related research heading in the near future?
That's a good question and I have been talking
to a lot of people who are involved in this.
Well, on the one hand, we're sort
of creating... there's a group led by Mike
Springer and HMS
that's going to be comparing a lot of these assays
head to head.
So there will be several different LAMP assays. So
the primer set that I developed
as well as some have been developed
at NEB and Cornell,
and I believe at least one or two other places.
Then Mike Springer's lab has come up
with an RT-RPA based assay.
And then there's a CRISPR based assay coming
out of the Broad,
although those either have LAMP for our RT-RPA backends.
And so they're going to be testing
those head to head
with the exact same clinical samples
in order to get a really good idea as to how
they compare.
Um, outside of the actual diagnostics
has also been a lot of, a lot more
work and more attention being paid to sort of,
um, everything from
can we get enough swabs? So do we need
to go to saliva? Or can we
stick with swabs? To
what sample types actually have
enough virus in them to detect well?
Do we swab other places?
Again, can you just have someone spit
in a tube?
And also sort of
perfecting
a lot of the collection protocols
We've been talking a lot about, you know, what can
a patient do
themselves? That they reduce the
risk of infecting whoever is testing.
Obviously, we think, a patient can spit in a tube on
their own and probably close it and spritz it with
disinfectant.
So we're looking at things like that, and this
is sort of leaving my wheelhouse, very, very quickly.
But there are a lot of people were focused on this.
And then downstream of this, people
are looking at ways of
sort of connecting these results to contact
tracers and things like that so that we can,
uh, hopefully contain any
potential sort of little outbreaks that may occur
in the future.
And then there's just how do we deploy
these things. Do we
collect at a lot of different places and
send samples to one centralized location
for testing?
Do we send sort of little pop up labs
to a bunch of different places? Like
if you were worried about a school, could you send
a team in a van with heat blocks
to a school and have them
run tests? How do you do surveillance?
Things like that. So there's a lot of thought
being put into that as well.
Well, it's really interesting.
Um, yeah. I often
wonder, you know, when we're going to be at the point
where there are sort of, ah, home test
that someone could do. Someone could
spit in a tube at home.
And
could that tube potentially contain
the right reagents, or, you know,
um,
maybe you need to aliquot
some specific volume, you know? Do you envision
this being something that eventually could
move into home use? Or maybe
you spit a tube and put it in the mail?
Yeah, I think any of those are good options.
You know,
if you have a sous vide at home, it's very easy.
We've actually tried that, you know, a
immersion heater in water.
You set it to 65 and
that's really all you need.
So Yeah, I think a lot of people have been looking at how
you would sort of formulate a kit or maybe a device
to make it easy to run.
But yeah, I think a lot of people are looking
at home diagnostics. Yeah
and I'll be really interested to see that study
from the Springer lab of HMS
come out because, you know, certainly there's
been a lot of
fast and furious movement in terms of
developing diagnostics
to detect Covid.
So it would be really great to sort of see those compared
in terms of specificity and sensitivity.
Oh, absolutely. And I have to give a lot of
credit to Mike, uh, he's put together a great
group. He's really, really
built a sense of
camaraderie.
The way he sees it,
you know, his test may work in a different way than
ours, but he likes to think of us
not in competition,
but as sort of supplemental to one another.
We have assays that work in different ways. They may have different
pros and different cons. And really importantly,
different supply lines.
So potentially if
we need to be producing millions
of tests, tens of millions, hundreds of millions
a week if we are thinking worldwide,
having a number of different tests
that are being made in different ways could be really helpful.
Yeah, certainly. And I think that that's a great example
of the global
camaraderie that's really come out of developing
diagnostic tests and the free sharing
of scientific knowledge you know,
that's really surrounded the crisis.
Definitely. So, Brian,
did you find that compared to your normal research,
there was a particular sense of urgency with
this project?
Oh, absolutely. I mean, definitely. You know,
we're always thinking that this pandemic is progressing.
Every time we checked the news,
you see that it's spreading and yet our testing
capacity is not growing enough
to meet the needs. And then of
course states are are beginning their reopening.
And we're worried that without
enough testing capabilities, we could just be
looking at another
outbreak if we don't catch things
quickly. So there's definitely a lot of urgency.
What also, I think, helped was working
with other groups developing these assays. We were
all motivating one another. We were sharing
results. It became a really fluid
and very rapid process.
Um, so tell us something good. Do you have
any good stories or reflections
about your time in
in, you know, the Massachusetts
ah, sort of stay at home
recommendation
that you could share with our audience?
Well, um,
I can say that it's been nice to see
in a lot of places, like, I'm out here in Waltham
and people are definitely taking
things very seriously. I do see
people are really practicing social distancing.
I know
you hear on the news about
you know things happening at various grocery stores and all
that. But here it's been very I think
everyone's been sort of, you know, we're in this together,
uh, kind of kind of spirit. And
those sort of drive by
graduation or birthday party
celebrations of really, really taken
off. I think every evening we see
three or four of them go by.
So it's nice to see people supporting one another
in a safe way.
Um, beyond that, I mean, it's
been nice to keep all the plants in my lab alive.
Lots of time to sort
of focus on
some of the more simple things in life.
Oh, absolutely.
Well, thank you so much for joining us today. And
thank you so much for, um,
you know your work. I think it's
been
really important that, you know, you
picked up this project, you were obviously able
to identify some,
some
primers that made a huge difference
in the sensitivity and specificity of the
test.
And I think that it will go a long way
towards
really bringing a Covid
diagnostic
to more places. To
more rural places. You know, that might not
be able to
afford the instrumentation
to carry out some of the RT-
qPCR tests that are more prevalent now.
Oh, definitely.
And having a lot of family back
in rural Kentucky, that's definitely been something I have been thinking about.
Yeah, it's nice to sort of know,
um, it's nice to know where people's motivations
lie. And I think a
lot of our motivations lie and
in protecting our friends and family and
loved ones from this pandemic.
So thank you so much for your work towards that.
Well, thanks for having me.
Thanks for tuning in for this episode.
As always, check out the transcript of this podcast
for helpful links to further resources.
Please join us for next episode when I'll
be interviewing Fung Zhang
of the Broad Institute, along with
Jonathan Gootenberg and Omar Abudayyeh
of the McGovern Institute of MIT
about their recent publication describing
STOPCovid,
an assay which combines isothermal amplification
with CRISPR based detection methods.
So be sure to catch the next episode
and hear from the scientists currently making
major breakthroughs in coronavirus
detection
and diagnostics.