
We’re working on 1M Covid-19 testing capacity per day - dvdt
https://www.billiontoone.com/covid-19
======
dvdt
I'm the co-founder and CTO at BillionToOne. I'm happy to answer any questions
here. I've also posted a slightly more technical explanation of how the test
works and why it can scale here:
[https://twitter.com/dtsao/status/1247642005510873088?s=21](https://twitter.com/dtsao/status/1247642005510873088?s=21)

Edit: Since our site seems to be overwhelmed at the moment, here's a recap:

We’ve been working hard at BillionToOne on a new COVID-19 test that scales
testing to everyone in the US. Our test (1) re-purposes existing
infrastructure, (2) eliminates time-consuming RNA extraction, and (3) enables
a distributed system for COVID-19 testing.

We need 1 million tests per day to end the stay-at-home orders. Schools are
still open in Iceland because they test 15x more than the US does, per capita
([https://www.washingtonpost.com/world/2020/04/02/free-
coronav...](https://www.washingtonpost.com/world/2020/04/02/free-coronavirus-
test-anyone-this-country-its-possible/)).

The first thing we figured out is how to run COVID-19 tests on existing
automated Sanger sequencers. One sequencer can process up to 3840 samples per
day. There are hundreds of sequencers of excess capacity because they were
built for the Human Genome Project over 20 years ago.

It would take only 2 sequencers to surpass the current test capacity for all
of California. There are far more than 2 sequencers in California (some
individual labs have 10 or more).

We tweaked the protocol so COVID-19 could be detected from sequencing data
using linear regression. Basically, we add ~100 copies of a known DNA sequence
to help us calculate how much virus nucleic acid is in the specimen. It works
just as well as gold-standard RT-qPCR.

Lab workflow for COVID-19 testing is traditionally 1. Specimen accessioning,
2. RNA extraction, 3. RT-qPCR 4. Reporting. RNA extraction, in particular, has
been a huge bottleneck in terms of reagent shortages and labor-intensiveness.

We showed that we can skip RNA extraction entirely without affecting test
sensitivity and limit of detection.

By skipping RNA extraction and using automated Sanger sequencers, we think we
can get to an additional 200,000 samples per day test capacity in existing
clinical labs.

A distributed system is often the only way to operate at massive scale. A
fully distributed system could have different sites and labs responsible for
each process and dynamically re-allocate resources based on availability and
capacity.

The Broad institute COVID-19 lab has already started doing this. They are
asking for specimens to be submitted in a standardized tube format and pre-
barcoded. They have essentially distributed the specimen accessioning work.

Because there is a highly developed service industry for Sanger sequencing
with <24 hour turnaround, there is an opportunity to further scale up testing
by distributing the work to their (currently) idle sequencers.

Distributed testing could scale from 200k to >1 million tests per day, but
would require a change in regulations that currently prohibit it.

Thanks to the BillionToOne team for pulling this work together! Next step is
to start manufacturing test kits and obtain Emergency Use Authorization from
the FDA. We’re eager to work with clinical Lab Directors and contract kit
manufacturers.

Edit 2: Link to scientific manuscript:
[https://www.dropbox.com/s/07esyehsvfpmllc/A%20Highly%20Scala...](https://www.dropbox.com/s/07esyehsvfpmllc/A%20Highly%20Scalable%20and%20Rapidly%20Deployable%20RNA%20Extraction-
Free%20COVID-19%20Assay%20by%20Quantitative%20Sanger%20Sequencing-
final.pdf?dl=0)

~~~
abhisuri97
Hey, lowly Bio undergrad here, but how are you able to skip the RNA extraction
step? I read the paper and you use the viral transport medium, but wouldn't
you have to also purify RNA from that (or is it just much easier to extract
RNA from that medium)? I also dived into the paper behind the "skip the RNA
extraction step" methodology and it basically seems to swap out one RNA
extraction kit for another (Qiagen RNeasy Mini kit and the Qiagen RNeasy Micro
kit). Couldn't shifting kits from one provider to another introduce supply
chain strain? (or am I just oversimplifying it?)

~~~
dvdt
Thanks for the question! The goal of skipping RNA extraction is to decrease
the amount of labor necessary for processing samples and also to eliminate a
dependency on RNA extraction reagents that have recently become difficult to
find. The FDA is very strict about the specific brand and model of kit you
use, so showing that you can swap out one RNA kit for another is actually very
useful because you will have alleviated some of the supply chain strain
(although I agree at high enough load both supply chains will then become
limiting).

The way currently available COVID-19 testing works is by detection of viral
RNA. Since the amount of viral RNA in a patient sample is too low to detect
directly, we first need to amplify it by PCR. However, this viral RNA is
packaged within all sorts of proteins and lipids that could make it
inaccessible to amplification unless they are first purified away.
Furthermore, the sample is shipped in "viral transport medium", which is
essentially a cocktail of chemicals designed to preserve the virus.
Unfortunately, these preservatives often have the side effect of interfering
with PCR amplification, so these too need to be purified from the sample.

However, since RNA extraction is usually the most laborious part of the assay,
there has been a lot of interest in optimizing the amplification so that it is
resilient to all of these impurities. The preprint referenced in our
manuscript
([https://www.biorxiv.org/content/10.1101/2020.03.20.001008v1](https://www.biorxiv.org/content/10.1101/2020.03.20.001008v1))
gave us the initial idea that this could be possible, and much of it comes
down to the choice of amplification method (e.g. choice of enzymes and
buffers) that you choose.

However, even when you choose a "good" enzyme and buffer, you will still
suffer an amplification penalty, and this will cause you to return a false-
negative on some affected samples because there was so little virus in the
sample to begin with. The innovation we have is to spike-in a correspondingly
low level of DNA to the reaction mixture. That way, if you see the low level
of DNA without seeing any viral signal, you can be assured that the
amplification still worked and that there truly is no virus in the sample.

~~~
mattmanser
In the UK they're saying there's a shortage of swabs and pipettes even, do you
not need these too?

Also, in the UK our independent and uni labs have been saying for almost a
week they could extract the RNA differently but the NHS have a fixed approved
way that they won't change.

\- Are the chemicals you're using more common or would there just be a new
shortage of different chemicals?

\- Is there a risk you'd be creating a test that didn't work very well, and
the US would end up with a bunch of useless tests (e.g. Italy had to abandon a
bunch of Chinese sourced tests, UK's anti-body tests are ineffective)?

~~~
dvdt
Our technique would still be affected by shortages in specimen collection
(like swabs).

Purely speculative, but I think if swabs remain an issue for too long,
alternatives could start coming online, such as even using qtips + saline (no
idea if it works, it's just an example). The current swab + Universal / Viral
Transport Medium combo is optimized for flexibility; it is designed to work
across a very broad range of viruses and bacteria that have different viral
loads and shedding characteristics. The current pandemic is pretty much
COVID-19 only, so I think it's a priori feasible that a specimen collection
procedure can be found that uses common materials. We did try early on to see
if saline or other buffers affected the performance of the assay, and it
worked fine in those conditions.

We use fairly standard chemicals. I haven't heard from our suppliers about
shortages for the chemicals we use. Chemicals and enzymes tend to be
relatively fast to scale up for bulk manufacturing.

There's always manufacturing risk that a product will not work as expected. In
fact, the first COVID-19 test developed by the CDC did not work as expected,
and this delayed testing by several weeks. We de-risk this as much as possible
by performing experiments as early as possible, akin to the fail fast
mentality of checking for the highest risk failure modes first. Since we don't
have a national healthcare system in the US, the manufacturer takes on the
vast majority of the risk of a defective product.

~~~
abfan1127
if the virus is known to live on cardboard or plastic for 48-72 hours, is the
viral transport medium even necessary, assuming rapid shipping and processing?

~~~
542458
Can live up to X hours != Will live up to X hours

Let’s say it’s 50/50 whether it lives 24h without help. That’s would be a
pretty bad false negative rate for your test, but a 50/50 of potentially
getting infected by your mail is pretty high.

~~~
labawi
To be more precise, last info I read modeled the virus with exponential decay,
with half-life measured in minutes to hours. After an hour (or 3h or 0.5h),
half of the virus is already inactive¹.

Even after ~6 half-lives, remaining 1% of viral load is still potentially
dangerous, but it's not a good basis for a test if you want it to be
sensitive.

¹ Inactive does not mean destroyed. It may be possible or even easier to
detect a partially decomposed virus, even with the current tests. Or not.

------
tbenst
Thanks for your efforts! Inspiring to see our broader community spring into
action.

I was part of a volunteer team that tested 3400 people on Friday/Saturday in
Santa Clara country for COVID-19 antibodies [1]. It took a team of 100+
volunteers 10 hours / day just to collect samples.

Stanford, for example, has plenty of automated testing capacity, and even
reagents. IMHO, the limiting factors are not that we need new tests, but
rather we need (1) lighter regulations (2) funding to buy supplies and (3)
massive manpower to scale-up drive through testing

[1] [https://www.stanforddaily.com/2020/04/04/stanford-
researcher...](https://www.stanforddaily.com/2020/04/04/stanford-researchers-
test-3200-people-for-covid-19-antibodies)

~~~
buzzkillington
I find it incredible that no one has done these studies before issuing the
lock down orders. Without knowing what the proportion of people who have been
exposed but aren't sick any response is the wrong response.

If it turns out that it's already spread to most everybody lock downs are just
a way to create more homelessness. If it turns out that the only people with
the antibodies are the ones in the hospitals we need martial law.

~~~
yters
Yes, if you google "coronavirus iceland" you'll see they've tested almost
their entire population. They found 1586 confirmed cases, of whom only 6 died,
which gives a fatality rate of 0.4%.

Turning this around, if we multiply confirmed deaths by 264, that gives us an
estimate of how many cases there are. So, for example, with UK's death count
of 6159 this means about 2.4% of the population is infected. Furthermore, on
the Diamond Princess only 20% of the people onboard caught the virus under
poorly quarantined conditions. So, to extrapolate even further, this would
imply that over 12% of the UK population has already been exposed to SARS-
CoV-2. This means that the UK should peak at about 50k deaths, without any
protective measures.

In 2018, the UK had 50k deaths due to flu in excess of normal flu deaths.

[https://www.telegraph.co.uk/news/2018/11/30/winter-deaths-
hi...](https://www.telegraph.co.uk/news/2018/11/30/winter-deaths-hit-highest-
level-40-years-experts-blame-ineffective/)

~~~
JamisonM
Iceland has only tested 28,992 of its residents as April 6th, so that throws
the rest of this conjecture out the window. (Although regardless the
conjecture was probably not a great idea.)

[https://covid.is/data](https://covid.is/data)

~~~
yters
The point is Iceland has the best statistic on death rate due to comprehensive
testing.

~~~
JamisonM
I think the real point is that your original claim was a small sample that you
were extrapolating wildly from turns out to be 10x smaller than you claimed.

Furthermore you are focusing on a tiny portion of available data instead of
all that is available.

Given that New York State has 4,000+ deaths your "model" would indicate that
1MM residents have COVID-19? So if it rips through the remaining 19MM
residents in the course of a few weeks the result will _only_ be 80k deaths?
And of course the healthcare system won't break down?

Also you said that the Diamond Princess only had a 20% infection rate but the
Greg Mortimer is reporting a 60% infection rate. Seems like you've got a lot
of facts wrong on the first pass, IDK.

~~~
yters
It seems that 'all available' would diminish the signal of Iceland's good
stat. What we really want is 'all good stats'. I think only South Korea is the
other country with extensive testing.

According to my model NYC should only have a max of 13.5k deaths, without any
mitigation.

Based on the Greg Mortimer stat, this bumps up to 41k for NYC.

~~~
JamisonM
It doesn't seem to pass just a basic level of consistency with present
experience to believe that with no mitigation New York would only have 13.5k
deaths when they already have 5.5k+ (and we know many more that have not and
maybe will never be confirmed).

Even the idea of 41k at this point beggars belief, they are already well over
capacity with some mitigation and the bodies are _literally_ piling up.

I find it hard to wrap my head around the logic here.

~~~
yters
My thought is since this is a new virus it will spread faster, and hit peak
sooner. Also, those who are most affected are a small portion of the whole
population, which will again imply faster time to peak.

------
shushpanchik
I'm wondering, if the bottleneck in testing is number of tests per day
available, could we use Bloom filter methodology for it? Like, for example,
take samples of 1024 people, assign them 10-bit IDs randomly, mix samples of
everyone with bit 1 in position 0 in one pool, with bit 1 in position 1 in 2nd
pool and so on. Then do 10 tests, and whoever has negative result in any of
set bits of his ID, does not have virus. If too many people of 1024 have
virus, add another set of random IDs and do 10 more tests, etc. If there are
no technical limitations, that would allow to get negative results to, let's
say, 900 people from 1024 with only 10-30 tests. Other 124 could be tested
personally. That's 85% reduction in number of tests needed.

~~~
Blahah
This is the basis for several sequencing-based test protocols in development.
It's called barcoding, and the massively parallel sequencing of tens of
thousands of barcoded pooled sequences is called bar-seq.

See e.g.
[https://twitter.com/hsalis/status/1241121806473461760](https://twitter.com/hsalis/status/1241121806473461760)

------
thelean12
Your site seems to be getting hugged to death. Can you answer a few questions
here:

\- Is this test to see if someone currently has it, or if they have the anti-
bodies and are (presumably) immune?

\- What are the false-positive/false-negative rates? How does this compare to
current leading tests?

\- What's the cost per test? How does this compare to current leading tests?

~~~
dvdt
Thanks for letting me know about the site!

This is a test to see if someone has a current COVID-19 infection. The
antibody tests (serological) tests are also important, but since it is
estimated that only ~1% of the US has previously contracted COVID-19, it will
be a while before serological testing becomes useful at a population level.

Our initial data show no false-positives and no false-negatives out of all
specimens assayed. However, it is early days still and _none_ of the leading
tests have real-world data on false-positive and false-negative rates. The
crucial parameter here to compare test performance is limit of detection
(LOD). We showed we could detect as few as 10 molecules of virus, which is on
par with the best RT-qPCR tests.

Cost is definitely an important consideration for roll-out of a widespread
test. We anticipate that the cost will be about $15 per test.

~~~
zepto
Dismissing the value of serological testing seems like a self-serving move.

Such tests are immediately of very high value because they allow us to
understand immunity to Covid-19, and to actually validate the estimates of
cases amongst those who haven’t sought treatment.

These are both of huge value regardless of the percentage of the US population
estimate to have previously contracted Covid-19.

By all means market your test which seems like an awesome contribution, but
please don’t do so by devaluing other important tools.

[edit: the parent post has been edited to be less dismissive without
acknowledgement since I made this comment]

[edit: looks like I’m wrong about the post being edited. Sorry for that. I
stand by everything else I say here:

Serological tests are useful and needed right now, not at some future stage.
It’s not hard to google to verify this, and it’s irresponsible to downplay the
value of a test we need now.]

~~~
billiontoone
I don't think we are in any way undervaluing the serological tests. A great
serological test would be very useful. However, because of the indirect
measurement, they tend not to be very sensitive or specific, so it is fair to
say that they become more important not at the peak of the pandemic but at the
post-pandemic period.

By the way, as a company, we really don't have much to gain from this test. If
it does not get adopted, we'll go back to building our core business which has
been growing 100% quarter over quarter. We have poured resources into the
current development, because it is the right thing to do. No investor in our
Series B round will take into account any non-recurring sell-almost-at-cost
revenues that we get from a once-in-a-century pandemic.

~~~
zepto
You are downplaying the value by saying they will be useful in the future,
rather than now.

This is not so. They are valuable right now.

~~~
mrkurt
For what? "Google for answers" isn't very helpful. It sounds like they're
saying serological tests are valuable, but not viable for immediately testing
a large population.

~~~
zepto
Answering questions about immunity is absolutely critical _right now_.

[https://www.newscientist.com/article/mg24532754-600-can-
you-...](https://www.newscientist.com/article/mg24532754-600-can-you-catch-
the-coronavirus-twice-we-dont-know-yet/)

[https://www.ksbw.com/article/new-study-investigates-
californ...](https://www.ksbw.com/article/new-study-investigates-californias-
possible-herd-immunity-to-covid-19/32073873)

------
cheriot
This would be HUGE. Not only has the testing capacity in America been maxed
out, but the % of positive results has been more than 20% and trending upward.
In order to quarantine effectively (read: end the shut down) we need to test
the family, coworkers, and contacts of every positive result.

~~~
s_y_n_t_a_x
Testing has been ramping up [https://covidtracking.com/data/us-
daily](https://covidtracking.com/data/us-daily)

~~~
phantom0308
It's plateaued and has been hovering around 100k per day for 2 weeks (outside
California clearing its backlog on 4/4). The White House promised 27M by 3/31
and we were at 1M. It doesn't look like it's ramping up.

~~~
cyrux004
I WA we were doing around 7k-8k tests/day 2 weeks back, now its between 4-5k

------
limaoscarjuliet
Germany decided to mix 10 specimens and run a test, only then - if positive -
test individual samples. They increased their testing capacity 10x (roughly)
overnight. [https://edition.cnn.com/world/live-news/coronavirus-
pandemic...](https://edition.cnn.com/world/live-news/coronavirus-
pandemic-03-31-20/h_c9b8259b105b4f26a4ade9fb61b954ce)

~~~
rplnt
There was a study, IIRC from Israel, which said this is still reliable with 64
samples mixed.

The next question is, do you need to test the individual samples then? Not
sure how much available material for testing you have, but you might be able
to just divide the mix to eliminate bigger groups first.

Or even mix parts with new samples. There must be an ideal procedure
(throughput-wise) if you know how the range of positives to expect.

~~~
douglaswlance
You can do a binary search to efficiently locate the positive sample.

~~~
ced
But what if there are two (or more?) positive samples? It's an interesting
problem.

~~~
bequanna
If the initial test size is 64 and contains a positive, split into two groups
of 32 and test each. Continue splitting and testing when a positive is
encountered.

~~~
ced
Yeah, but this version is not necessarily optimal. If you have 4 positive
samples, then you will test 2+2+1+1+1+1 = 8, instead of 4 in the naive case.

It feels like a problem for information theory.

~~~
bequanna
I didn’t say it was optimal, but it is a huge improvement on doing 64 tests
for 64 samples.

~~~
ced
Oh, sure!

------
12xo
This is awesome. Thank you for all your work.

One million a day seems like a lot until you realize it would take about a
year to test everyone in the US... How can we increase this to 10m per day? Is
that possible?

~~~
billiontoone
I think we can scale it to significantly more than 1M a day, but it would
require the relaxation of certain regulations that currently prevent
collaboration between clinical laboratories and other institutions that have
Sanger instruments. FDA and CMS require that clinical laboratories process the
sample end-to-end, so it prevents a distributed model of initial processing in
the clinical laboratory followed up with send-out for Sanger sequencing.

California CLIA and FDA regulations for COVID-19 testing have been relaxed
significantly over the last few weeks, so the above is perhaps not impossible.

~~~
empath75
Could you get some of those Sanger machines loaned to you temporarily?

------
supernova87a
Can someone here explain in a couple of points what the idea is? While the
site is overwhelmed?

Edit, is the idea (for the non-expert):

1) Repurposing idle gene sequencing equipment left over from Human Genome
project

2) Reducing / removing the step of having to extract the RNA of the virus as
the marker

3) Making these tests / machines available widely across the country so that
the delay to getting a result is minimized ?

~~~
dvdt
1) and 2) are exactly right.

3) is almost right--these sanger sequencing instruments are already widely
available across the country for research use. Here in the Bay Area, I can
choose from at least 4 different Sanger sequencing services that will run
10,000 samples at $2/sample in 24 hours. For example, see:
[https://www.mclab.com/DNA-Sequencing-
Services.html](https://www.mclab.com/DNA-Sequencing-Services.html)

------
dang
Since the site response has been intermittent, here's Internet Archive's copy
from earlier today.

[https://web.archive.org/web/20200407224229/https://www.billi...](https://web.archive.org/web/20200407224229/https://www.billiontoone.com/covid-19)

~~~
exabrial
Archive.md: [http://archive.md/cUzP9](http://archive.md/cUzP9)

------
daemonk
Cool technique that uses existing Sanger sequencing equipment that has been
optimized for decades. So you are sanger sequencing the loci + a synthetic
frame-shifted oligo that you spike in. Then you essentially "demultiplex" the
chromatogram knowing the two molecules are frame-shifted and compare the peaks
to get a relative measure.

I guess the trick is to find a loci that is specific enough to covid-19, but
can still produce a good frame-shifted oligo that allows you to maximize the
resulting chromatogram signal.

I am surprised that the detection limit of a no-extraction PCR can be this
sensitive. But it looks like the data checks out. Does this work for every
type of sample? I would assume differing buffers, collection methods will
influence the PCR?

------
mhandley
Is the 1M/day figure for individual tests? When the expected number of
positives is low, can't you run group tests? Mix the first samples from 16
patients together and test them as a batch. If the result is negative, all 16
are negative. Otherwise re-run the second samples. Depending on how many
samples you take from each patient, you can binary search, or just run 16
individual tests on the second samples. By doing this, you can get something
upwards of 10x increase in people tested per day.

~~~
benchtobedside
You can indeed, this was addressed earlier in this thread:
[https://news.ycombinator.com/item?id=22810002](https://news.ycombinator.com/item?id=22810002)

------
mkagenius
What is the expected false positive rate/range? A number or range will be
helpful (rather that extremely rare, which is what I get when I ask about rt-
pcr test)

------
somberi
On a separate note - DVDT and billiontoone (David and Bobby) - you guys have
been impressive on how you have handled the conversation in this thread. You
are polite, informative and a template for me to follow. In addition to what
you guys are doing, kudos on your PR skills.

------
snorrah
Your site states you use a “proprietary machine learning algorithm”. As
someone who has seen a gamut of companies use the machine learning phrase to
justify almost any conceivable product, could you share any non-confidential
information about what you achieve using ML?

~~~
dang
That was discussed here:
[https://news.ycombinator.com/item?id=22808414](https://news.ycombinator.com/item?id=22808414).

Don't miss the off-topic collapsed subthread, if you like that kind of thing.

------
andy_ppp
I really think this explanation of how the number of people in the population
who have the disease affects the chances of a positive test being incorrect,
it is very unintuitive but look at the video as it explains that even very
Sensitive and Specific tests can be problematic to see who in the population
has a disease:
[https://www.instagram.com/tv/B-qZLJoAf3V/](https://www.instagram.com/tv/B-qZLJoAf3V/)

Spreadsheet to play with is here:
[https://docs.google.com/spreadsheets/d/1IPcX2JYt9mXdaTvj-3mh...](https://docs.google.com/spreadsheets/d/1IPcX2JYt9mXdaTvj-3mhXQY22m4wrs4Kd6nxPhDWM-M/edit?usp=sharing)

------
zelphirkalt
You can test all you want, with a spread like in the USA, there will be
trouble to have proper treatment for all the cases. If such testing had begun
earlier, then maybe lock down or near lock down scenarios could have been
avoided. I see little chance, even with such 1 mio tests, to get it back under
control without some kind of lock down or similar restriction to slow the
spread. Where do you put all the infected people without locking down? If
everyone infected is just told to stay at home, even if everyone complies, it
is like a self quaranteen, like a lock down for those people.

------
yters
Is it possible to create an at home cov2 test with a $25 homemade PCR

[https://hackaday.io/project/27623-coffee-cup-polymerase-
chai...](https://hackaday.io/project/27623-coffee-cup-polymerase-chain-
reaction-machine)

and some synthetic DNA derived from cov2 (seems to cost about $0.09 per base
pair)?

[https://www.twistbioscience.com/products/genes](https://www.twistbioscience.com/products/genes)

~~~
roosterdawn
Wow, very cool idea. While obviously this wouldn't be a substitute for lab
grade testing, what makes me excited is that it could make sense as something
folks produce for themselves as a precursor to getting a proper test done.

------
delibaltas
Hi and thank you for the efforts of your team. What can I do to have my
country becoming ready for your solution when and if this will be available?

------
aurelwu
Great work, a friend of mine is molecular biologist and she is furious about
how in germany they don't use alternative methods for RNA Extraction like
Phenol/Chloroform (labor intensive but no shortage of material) / SPRI (with
magnetic beads) or skipping it altogether.

------
foolinaround
How will the process for the "last mile" be implemented?

There still needs to be tests taken from individuals and conveyed to the labs?
many of these tests will be repeats from individuals who might have taken it
earlier? etc

------
sachinjoseph
Thank you! Please also ensure all the countries on the planet have access to
this tech.

------
aaavl2821
am i reading correctly that you packaged synthetic viral RNA into viral
particles and then suspended in transport medium? do you plan on studying
actual patient samples and comparing to gold standard tests?

------
thawkins
How quickly can this method be retooled for other pandemics, if there are
1000s of potential corvid-19s out there how quickly can it be adapted for the
next one?

------
thebiglebrewski
Can we fund this directly? Meaning can we donate to your effort directly? I
believe it's one of the most important things to return society to normalcy!

------
quadrature
Are you reaching out to governments of other countries ?. How does this
process work ? and is the canadian government aware of this work ?.

------
Turukawa
Why advertise before you've got FDA approval?

~~~
nomel
The FDA _is_ the lock.

~~~
snorrah
There’s a reason for that

------
rspeare514
Amazing work!!! Thank you for working on this

------
stuartromanek
all of the underlined "filling out this form" links are bad

------
hkiely
How does this help with RNA decay?

------
meheleventyone
I’d like to point out that schools are not open in the normal sense in
Iceland. All the older kids school is stopped and Universities are shut. Our
youngest is three and is in her leikskoli on alternate days so they can
maintain small group sizes with no contact between them. Our eldest is six and
only in school for a few hours in the morning, skips a bunch of more risky
activities and is again segregated from other classes. As many businesses are
working from home or shut completely a lot of parents have also opted to have
their kids at home.

We’re currently in a better situation than a lot of places but it’s by no
means without significant changes to daily life. It’s also a lot to do with
the early response.

~~~
arcticbull
Interesting, children are at basically zero risk (no child under 10 has died).
I assume they don't want to spread it between parents via children?

~~~
n8udd
[https://www.theguardian.com/uk-news/2020/apr/04/five-year-
ol...](https://www.theguardian.com/uk-news/2020/apr/04/five-year-old-child-
among-latest-uk-coronavirus-deaths)

~~~
grey-area
A five year old with pre-existing conditions sadly died, and some babies have
died in the US, but the risk to children is thankfully very very low
(percentages tend to 0% for that cohort at present the deaths are so rare),
and infections among children are probably being massively undercounted.

------
zrgiu
Say I had a lab with the sequencers needed for this test. I can't claim to
understand the work needed to onboard into this new process, but my question
is: how long does the onboarding take before the lab can process these
3840/day ?

~~~
billiontoone
Thanks for the question. Last week, I sent half-a-page of instructions in a
hastily written e-mail to a scientist working for the Switzerland government
response team, and they told me that it worked beautifully in their first try
this week.

With the details described in the manuscript, the onboarding can be only a few
days (or even self-onboarding based on instructions). The only part that is
somewhat tricky is the bioinformatics algorithm for positive vs. negative
calls, which we can supply.

------
robomartin
We are seeing example after example of the power of entrepreneurship and
private enterprise. I hope we remember this going forward and weave it into
our national culture deeper and wider than it already is.

~~~
mrkurt
What we're seeing is how agile a small, functional, and motivated group can
be. Private enterprise as whole is every bit as f'd up as the government.

~~~
robomartin
> Private enterprise as whole is every bit as f'd up as the government.

This is wrong. What's the basis for this comment/idea?

I have founded and run multiple companies. I have worked for small, medium and
large (8,000 employee) companies in various capacities. In a 30+ year career I
could not name even one company that I would say fits your assertion at all. I
am sure they exist. Yet, I am also sure they are an insignificant percentage
of the total.

There's a key difference between private enterprise and government: Failure
kills.

Again, except for corner cases or companies that exist due to government money
(I don't include these in "private enterprise") entrepreneurship, private
industry, capitalism if you will, is a survival of the fittest contest. Like
it or not, this is reality.

Government operates with completely different metrics. Failure, for the most
part, has no real consequences. A simple example of this is the "high speed"
train project here in CA. I've lost track at this point. I think the last time
I looked they were at $100BN and the whole thing is a massive smelly pile of
manure. Nobody, except for taxpayers, will pay for the consequences of that
failure...sadly, one of many at the hands of government.

This crisis is highlighting just how messed up things are under government
control. Last night my son, who is in university pursuing a degree in CS, said
"Dad, do you know COBOL?". When I asked why, he said New Jersey is trying to
hire a bunch of COBOL programmers because their payment systems are badly
broken, the code is done in COBOL and it is in need of fixing so they can pay
people the aid funds the federal government is providing. I mean, this is
typical, sad and ridiculous.

No, private enterprise is a universe away from almost anything government
touches. The only service I can identify in government that lives (or dies) by
similar metrics is the military. They have real and non-trivial consequences
for incompetence. Death. And that means they can't run like a state payment
system that's 40 years old and grossly outdated. I am sure the military have
issues as well, yet, for the most part, given their mission, could not survive
in the long run if they did not operate at a certain level of competency.

~~~
mrkurt
8,000 people is still pretty small.

I don't disagree with you about capitalism being survival of the fittest, or
that companies should die. I don't think the US is a capitalist country
though. We're living with corporate socialism.

I mean, look at the pandemic bailout. Nobody, except for taxpayers and
employees, is paying for the failure of the airlines to operate responsibly.
This is exactly the time every badly run company in the US should collapse and
die, and it's not gonna happy. Restaurants, bars, small businesses, maybe some
startups will crash and burn. But even private equity firms are getting bailed
out.

This is not a one off. The same thing happened in 2008.

And it's weird to think only governments are running Cobol. What do you think
the vast majority of hospitals are built on? Or things at IBM? It's the same
problem.

~~~
robomartin
> I don't think the US is a capitalist country though

Pure capitalism has never existed anywhere. So, yeah, agreed. Yet what we have
(not just the US but lots of nations around the world) has elevated society to
levels not attainable through any other system we know.

> the failure of the airlines to operate responsibly

I don't think this is fair. Nobody could have predicted or prepared for this.
Nobody. I mean, how?

I've read people say things like "We could have stockpiled 50,000 ventilators
ten years ago". This is, frankly, silly on many fronts.

Technology being what it is, ten year old ventilators would have likely been 5
year old designs at the time of purchase, which would make them around 15 year
old designs today.

The first level concern would be if those ventilators would be adequate or
acceptable in today's context. I'll assume they could be. That said,
professionals are trained to operate and know the equipment they use every
day. If a dinosaur shows-up they might not be able to (or want to) use them
because of lack of training that could lead to negative outcomes for patients.

People have this idea that a word, like "ventilator" fully defines a product,
its usage and the entirety of the dynamics surrounding it. Things are never
that simple.

Another point is equipment mortality. Anyone who has dealt with hardware in
large quantities and across extended periods of time knows what can happen
with 50,000 units of anything manufactured 10 to 15 years ago and in storage
for ten years. You can end-up with massive failure and reliability problems.
You would have to design and manufacture these devices to failure-tolerant
aerospace/military standards to improve outcomes...and even then you have no
guarantees.

Things are not as simple as "ventilators", not even close.

> The same thing happened in 2008

No, this is nothing --not even close-- to 2008. I lived through that period.
It was an absolute mess precipitated by politicians loosening the rules on
lenders and pushing them to let anyone buy homes. Great for votes but horrible
for the economy, as history has proven. You had people making minimum wage
buying half million dollar homes because the government (both Democrats and
Republicans, BTW) removed all sorts of regulatory requirements on making
loans. The banks operated under the law. And the consequences of the law
ended-up being the opposite of what politicians sold us. Instead of "the
American dream of home ownership" the thing turned in to the world nightmare
of unintended consequences. Frankly, every single US Senator and
Representative who voted for those demented changes should have lost their
jobs and maybe even done some jail time. Sadly most of them are still there.

> it's weird to think only governments are running Cobol.

The issue is one anyone who has built non-trivial software for enterprises is
familiar with. Once software "works" there's very little appetite to spend
more money to continue working on it, much less migrate it to new tool sets,
hardware, etc. It's just one of those things that, in the world of politics at
least, doesn't earn you votes, so you ignore it until people are screaming for
it because the system crashes and they can't get their checks.

Before the massive boost in throughput imposed by this pandemic these payment
systems essentially worked as required, issued checks and payments on time,
accurately and maybe even efficiently (per government standards). Anyone
proposing to re-write the entire system, spend tens of millions of dollars or
more in order to migrate to another language and add capacity would likely be
laughed at. It is only in hindsight that these kinds of things can be
justified.

This also applies to such things as CDC/NIH testing capabilities,
manufacturing dependencies and more. Humanity rarely acts proactively. I can't
think of a single example of this at scale in the history of humanity. For
example, the dams in The Netherlands, brilliant as they are, were the result
of a reaction, not proactivity.

Things are never simple. Sadly the media, politicians, popular conversation
and social media tend to simplify everything beyond the reasonable and people
end-up with distorted models of reality.

------
voz_
LMK if you need help making your site work.

------
bb88
Hmm... website seems overloaded atm.

------
poarneemn123
'Machine learning algorithms'

Nothing to see here, just trying to make a quick buck using the pandemic

------
jl2718
Isn’t this a log-scale problem? (binary tree)

------
andarleen
The machine learning bit is the buzzword that makes it trendy.

------
ck2
Please take 10 minutes to get your site on the free cloudflare cache.

It's not a good first impression (especially promising scale) not be to able
to see it.

~~~
KukicAdnan
Because scaling medical testing is the same as scaling web services...

~~~
thoraway1010
actually, scaling a website is much easier than scaling a medical service.

If you can't be bothered to take some basic steps for web site scaling (google
page speed + a CDN) then the idea that you will carefully and successfully
navigate to a 1 million tests per day moderate to high complexity medical test
seems like it will be a stretch no?

That said, a 100% support MUCh higher test capacity, both this and IGg IGm
(which should allow for home testing). So good luck!

~~~
Ididntdothis
"If you can't be bothered to take some basic steps for web site scaling
(google page speed + a CDN) then the idea that you will carefully and
successfully navigate to a 1 million tests per day moderate to high complexity
medical test seems like it will be a stretch no? "

Their priorities may be on other things than websites.

~~~
thoraway1010
From experience, the clients who can't get some things right struggle to get
many things right.

Seriously.

Someone has a great idea and is able to attract good people to work with them?
Then even though item X is the focus, you see quality in items Y -> Z. It
naturally seems to happen.

I'd love to know WHY this is the case.

------
lvs
So, I can't get to your site, but this seems a little disingenuous as a title.
You're not seemingly "unlocking" anything more than a protocol for Sanger
sequencing that, if it eventually was approved and actually tested against
real samples and people elsewhere adapted the protocols to use for testing,
you would then... at that point... unlock a thing.

~~~
dang
Since people seem to be reacting to the word "unlocking" in the title, I've
replaced it with "working on".

~~~
lvs
Thanks. Make him explain whether the machine learning is real too, since his
linked manuscript doesn't say anything about it. This is a really exploitative
moment to be hyping things.

~~~
billiontoone
Both the methods and David's twitter clearly describe the linear regression as
the method and how it works with spike-in. In practice, it is a lot more
complicated, as the signal-to-noise ratio can interfere with the regression
and primer N-1 synthesis errors need to be accounted for. That is why we are
willing to help other laboratories with our bioinformatics pipeline.

------
thoraway1010
Scaling a static website involves far less technical knowledge than scaling a
high politics / moderate complexity scientific process.

The website looks terribly designed from a scaling standpoint. Have you run
even a basic google pagespeed on it? Why no cache TTL on the custom TrueType
font? Why no CDN backing?

This is a bit random, but if you have a "proud" web developer who "knows best"
find someone with no pride who can get this sort of thing done.

We believe google can scale in part because they seem to be able return web
search / autocomplate / google assistant responses pretty quickly.

~~~
csomar
The skills required for these fields are very different. They hired someone to
do it.

