25 ms·

We’re working on 1M Covid-19 testing capacity per day

684 points by dvdt 6y ago

robomartin 6y ago
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 6y ago
  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 6y ago
    > 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 6y ago
      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 6y ago
        > 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.
dvdt 6y ago
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-coronavirus-test-anyone-this-country-its-possible/ https://www.washingtonpost.com/world/2020/04/02/free-coronav...). 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%20Scalable%20and%20Rapidly%20Deployable%20RNA%20Extraction-Free%20COVID-19%20Assay%20by%20Quantitative%20Sanger%20Sequencing-final.pdf?dl=0 https://www.dropbox.com/s/07esyehsvfpmllc/A%20Highly%20Scala...
thelean12 6y ago
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 6y ago
  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.
  - treis 6y ago
    >Our initial data show no false-positives and no false-negatives out of all specimens assayed. Your test is perfect? Color me skeptical.
    - dang 6y ago
      That's obviously not what he said. Please stick to the site guidelines: "Have curious conversation; don't cross-examine." "Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
      - 6y ago
bb88 6y ago
Hmm... website seems overloaded atm.
Turukawa 6y ago
Why advertise before you've got FDA approval?
- nomel 6y ago
  The FDA is the lock.
  - snorrah 6y ago
    There’s a reason for that
- billiontoone 6y ago
  CEO of BillionToOne here. We have already generated and put into our scientific manuscript the data that FDA requires for EUA. As a high-complexity CLIA-licensed clinical laboratory, we don't see significant risk in getting the authorization in 2 weeks. However, we need to start working with clinical laboratories across the country today if this is going to scale to hundreds of thousands of tests as soon as we get the EUA. Also, international laboratories don't need EUA and can start using the test immediately. We did not think it would be responsible to hold off on making the technology public when every day is so critical in our response to the current pandemic.
rspeare514 6y ago
Amazing work!!! Thank you for working on this
voz_ 6y ago
LMK if you need help making your site work.
supernova87a 6y ago
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 6y ago
  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
tbenst 6y ago
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-researchers-test-3200-people-for-covid-19-antibodies https://www.stanforddaily.com/2020/04/04/stanford-researcher...
- dvdt 6y ago
  Thank you for your efforts as well! Sample collection and accessioning (accessioning is unpacking test tubes one by one and aliquoting them into plates in the lab) is definitely going to require a lot of manpower. I'm hopeful that patients "self swabbing" can help alleviate some of the manpower needs. (Self-swabs are not allowed currently under FDA guidance).
  - sgw928 6y ago
    A self-swab surveillance program has been launched in Seattle: https://publichealthinsider.com/2020/03/23/introducing-scan-the-greater-seattle-coronavirus-assessment-network/ https://publichealthinsider.com/2020/03/23/introducing-scan-... . Is self-swabbing allowed there because it's for research purpose, not clinical purpose? The program does tell users whether they test positive though.
    - dvdt 6y ago
      My guess is that self-swabbing is allowed in the Seattle SCAN study because it is a research study. The SCAN study is super fascinating because it would be crazy unusual under normal times for a research study to return results back to patients; I'm very happy they are able to do that, and it speaks to the severity of this pandemic. The FDA has recently made clear that no at-home self-collection tests are allowed (for now): https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2 https://www.fda.gov/medical-devices/emergency-situations-med...
deleted 6y ago
[deleted]
dang 6y ago
Since the site response has been intermittent, here's Internet Archive's copy from earlier today. https://web.archive.org/web/20200407224229/https://www.billiontoone.com/covid-19 https://web.archive.org/web/20200407224229/https://www.billi...
- exabrial 6y ago
  Archive.md: http://archive.md/cUzP9 http://archive.md/cUzP9
lvs 6y ago
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 6y ago
  Since people seem to be reacting to the word "unlocking" in the title, I've replaced it with "working on".
  - lvs 6y ago
    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.
    - dang 6y ago
      It looks like David answered that here: https://news.ycombinator.com/item?id=22808525 https://news.ycombinator.com/item?id=22808525. I agree that it's better not to use buzzwords, and have edited the top text to say "linear regression" instead of "machine learning". (This is actually part of the standard advice we give to YC startups who are launching on HN: don't talk like you would to investors—talk as you do to fellow implementors.)
    - billiontoone 6y ago
      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.
ck2 6y ago
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 6y ago
  Because scaling medical testing is the same as scaling web services...
  - dang 6y ago
    The GP wasn't necessarily a helpful comment, but please don't respond by being snarky. It just makes the thread worse for everyone, and you can make your substantive point (the distinction between those kinds of scaling) without it.
  - thoraway1010 6y ago
    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!
    - chipotle_coyote 6y ago
      > 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? No. :) Seriously, these are orthogonal skills. I briefly worked for a communications satellite company that had a pretty godawful web site, but I doubt any of their prospective customers visited it and said, "Wow, if these people can't design a good looking web page, how can we trust them to put a satellite in orbit?"
    - Ididntdothis 6y ago
andarleen 6y ago
The machine learning bit is the buzzword that makes it trendy.
12xo 6y ago
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 6y ago
  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 6y ago
    Could you get some of those Sanger machines loaned to you temporarily?
cheriot 6y ago
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 6y ago
  Testing has been ramping up https://covidtracking.com/data/us-daily https://covidtracking.com/data/us-daily
  - cheriot 6y ago
    That's where I've been getting data. We have a long way to go. https://docs.google.com/spreadsheets/d/1Y9_ZrMBhhVLg2xQHtBCcb5ho0p-1OM6fDqRRhriYGbk/edit?usp=sharing https://docs.google.com/spreadsheets/d/1Y9_ZrMBhhVLg2xQHtBCc...
    - ejstronge 6y ago
      Why do you state that our testing capacity has been maxed out? My understanding is that factors like the availability of swabs and the availability of medical personnel to administer tests are a bigger bottleneck than qPCR machines.
      - cheriot 6y ago
        I don't have any insight into the why. Only that the growth rate in tests per day has slowed to an almost stagnant level.
        ejstronge 6y ago
        At least anecdotally, it doesn’t seem that we’re hitting our full testing potential. I think adding in a new technique would only exacerbate the mismatch between test supply and test utilization. https://www.nature.com/articles/d41586-020-01068-3 https://www.nature.com/articles/d41586-020-01068-3
thoraway1010 6y ago
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 6y ago
  The skills required for these fields are very different. They hired someone to do it.
zrgiu 6y ago
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 6y ago
  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.
JetBen 6y ago
Can you promise that this test will not be mass-produced in China? It would be criminal for the Chinese to gobble up all the profits of a virus that they released on the world.
delibaltas 6y ago
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?
hkiely 6y ago
How does this help with RNA decay?
snorrah 6y ago
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 6y ago
  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.
sachinjoseph 6y ago
Thank you! Please also ensure all the countries on the planet have access to this tech.
andy_ppp 6y ago
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-3mhXQY22m4wrs4Kd6nxPhDWM-M/edit?usp=sharing https://docs.google.com/spreadsheets/d/1IPcX2JYt9mXdaTvj-3mh...
aaavl2821 6y ago
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?
daemonk 6y ago
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?
mkagenius 6y ago
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)
thawkins 6y ago
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?
stuartromanek 6y ago
all of the underlined "filling out this form" links are bad
shushpanchik 6y ago
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.
- Palomides 6y ago
  this is more or less being done, under names like "pooled testing"
- Blahah 6y ago
  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
- thehappypm 6y ago
  I have heard many false negatives are an issue. Diluting samples down might make that even worse.
jl2718 6y ago
Isn’t this a log-scale problem? (binary tree)
meheleventyone 6y ago
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 6y ago
  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?
  - thinkingemote 6y ago
    Or other children and their family etc.
  - n8udd 6y ago
    https://www.theguardian.com/uk-news/2020/apr/04/five-year-old-child-among-latest-uk-coronavirus-deaths https://www.theguardian.com/uk-news/2020/apr/04/five-year-ol...
    - grey-area 6y ago
      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.
  - meheleventyone 6y ago
    Kids can get infected although at a lower rate under 15. So yeah and essentially that by keeping contact limited if someone does get sick you only need to quarantine a limited set of people and close a classroom rather than the whole school. I feel like a lot of the success here has been in being aggressive with contact tracing and people able to take the social responsibility to self-quarantine.
poarneemn123 6y ago
'Machine learning algorithms' Nothing to see here, just trying to make a quick buck using the pandemic
zelphirkalt 6y ago
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.
somberi 6y ago
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.
aurelwu 6y ago
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.
limaoscarjuliet 6y ago
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-03-31-20/h_c9b8259b105b4f26a4ade9fb61b954ce https://edition.cnn.com/world/live-news/coronavirus-pandemic...
- rplnt 6y ago
  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.
  - buboard 6y ago
    That works well for low infection rates https://www.biorxiv.org/content/10.1101/2020.04.03.024216v1.article-info https://www.biorxiv.org/content/10.1101/2020.04.03.024216v1.... https://www.medrxiv.org/content/10.1101/2020.04.05.20054445v1 https://www.medrxiv.org/content/10.1101/2020.04.05.20054445v...
  - douglaswlance 6y ago
    You can do a binary search to efficiently locate the positive sample.
    - ced 6y ago
      But what if there are two (or more?) positive samples? It's an interesting problem.
      - bequanna 6y ago
        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.
mhandley 6y ago
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 6y ago
  You can indeed, this was addressed earlier in this thread: https://news.ycombinator.com/item?id=22810002 https://news.ycombinator.com/item?id=22810002
yters 6y ago
Is it possible to create an at home cov2 test with a $25 homemade PCR https://hackaday.io/project/27623-coffee-cup-polymerase-chain-reaction-machine https://hackaday.io/project/27623-coffee-cup-polymerase-chai... 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 6y ago
  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.
thebiglebrewski 6y ago
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 6y ago
Are you reaching out to governments of other countries ?. How does this process work ? and is the canadian government aware of this work ?.
foolinaround 6y ago
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

684 points by dvdt 6y ago

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 6y ago
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 6y ago
  > 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 6y ago
    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 6y ago
      > 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.

dvdt 6y ago

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-coronavirus-test-anyone-this-country-its-possible/ https://www.washingtonpost.com/world/2020/04/02/free-coronav...). 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%20Scalable%20and%20Rapidly%20Deployable%20RNA%20Extraction-Free%20COVID-19%20Assay%20by%20Quantitative%20Sanger%20Sequencing-final.pdf?dl=0 https://www.dropbox.com/s/07esyehsvfpmllc/A%20Highly%20Scala...

thelean12 6y ago

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 6y ago
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.
- treis 6y ago
  >Our initial data show no false-positives and no false-negatives out of all specimens assayed. Your test is perfect? Color me skeptical.
  - dang 6y ago
    That's obviously not what he said. Please stick to the site guidelines: "Have curious conversation; don't cross-examine." "Please respond to the strongest plausible interpretation of what someone says, not a weaker one that's easier to criticize. Assume good faith." https://news.ycombinator.com/newsguidelines.html https://news.ycombinator.com/newsguidelines.html
    - 6y ago

bb88 6y ago

Hmm... website seems overloaded atm.

Turukawa 6y ago

Why advertise before you've got FDA approval?

nomel 6y ago
The FDA is the lock.
- snorrah 6y ago
  There’s a reason for that
billiontoone 6y ago
CEO of BillionToOne here. We have already generated and put into our scientific manuscript the data that FDA requires for EUA. As a high-complexity CLIA-licensed clinical laboratory, we don't see significant risk in getting the authorization in 2 weeks. However, we need to start working with clinical laboratories across the country today if this is going to scale to hundreds of thousands of tests as soon as we get the EUA. Also, international laboratories don't need EUA and can start using the test immediately. We did not think it would be responsible to hold off on making the technology public when every day is so critical in our response to the current pandemic.

rspeare514 6y ago

Amazing work!!! Thank you for working on this

voz_ 6y ago

LMK if you need help making your site work.

supernova87a 6y ago

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 6y ago
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

tbenst 6y ago

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

dvdt 6y ago
Thank you for your efforts as well! Sample collection and accessioning (accessioning is unpacking test tubes one by one and aliquoting them into plates in the lab) is definitely going to require a lot of manpower. I'm hopeful that patients "self swabbing" can help alleviate some of the manpower needs. (Self-swabs are not allowed currently under FDA guidance).
- sgw928 6y ago
  A self-swab surveillance program has been launched in Seattle: https://publichealthinsider.com/2020/03/23/introducing-scan-the-greater-seattle-coronavirus-assessment-network/ https://publichealthinsider.com/2020/03/23/introducing-scan-... . Is self-swabbing allowed there because it's for research purpose, not clinical purpose? The program does tell users whether they test positive though.
  - dvdt 6y ago
    My guess is that self-swabbing is allowed in the Seattle SCAN study because it is a research study. The SCAN study is super fascinating because it would be crazy unusual under normal times for a research study to return results back to patients; I'm very happy they are able to do that, and it speaks to the severity of this pandemic. The FDA has recently made clear that no at-home self-collection tests are allowed (for now): https://www.fda.gov/medical-devices/emergency-situations-medical-devices/faqs-diagnostic-testing-sars-cov-2 https://www.fda.gov/medical-devices/emergency-situations-med...

deleted 6y ago

[deleted]

dang 6y ago

Since the site response has been intermittent, here's Internet Archive's copy from earlier today. https://web.archive.org/web/20200407224229/https://www.billiontoone.com/covid-19 https://web.archive.org/web/20200407224229/https://www.billi...

exabrial 6y ago
Archive.md: http://archive.md/cUzP9 http://archive.md/cUzP9

lvs 6y ago

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 6y ago
Since people seem to be reacting to the word "unlocking" in the title, I've replaced it with "working on".
- lvs 6y ago
  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.
  - dang 6y ago
    It looks like David answered that here: https://news.ycombinator.com/item?id=22808525 https://news.ycombinator.com/item?id=22808525. I agree that it's better not to use buzzwords, and have edited the top text to say "linear regression" instead of "machine learning". (This is actually part of the standard advice we give to YC startups who are launching on HN: don't talk like you would to investors—talk as you do to fellow implementors.)
  - billiontoone 6y ago
    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.

ck2 6y ago

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 6y ago
Because scaling medical testing is the same as scaling web services...
- dang 6y ago
  The GP wasn't necessarily a helpful comment, but please don't respond by being snarky. It just makes the thread worse for everyone, and you can make your substantive point (the distinction between those kinds of scaling) without it.
- thoraway1010 6y ago
  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!
  - chipotle_coyote 6y ago
    > 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? No. :) Seriously, these are orthogonal skills. I briefly worked for a communications satellite company that had a pretty godawful web site, but I doubt any of their prospective customers visited it and said, "Wow, if these people can't design a good looking web page, how can we trust them to put a satellite in orbit?"
  - Ididntdothis 6y ago

andarleen 6y ago

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

12xo 6y ago

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 6y ago
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 6y ago
  Could you get some of those Sanger machines loaned to you temporarily?

cheriot 6y ago

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 6y ago
Testing has been ramping up https://covidtracking.com/data/us-daily https://covidtracking.com/data/us-daily
- cheriot 6y ago
  That's where I've been getting data. We have a long way to go. https://docs.google.com/spreadsheets/d/1Y9_ZrMBhhVLg2xQHtBCcb5ho0p-1OM6fDqRRhriYGbk/edit?usp=sharing https://docs.google.com/spreadsheets/d/1Y9_ZrMBhhVLg2xQHtBCc...
  - ejstronge 6y ago
    Why do you state that our testing capacity has been maxed out? My understanding is that factors like the availability of swabs and the availability of medical personnel to administer tests are a bigger bottleneck than qPCR machines.
    - cheriot 6y ago
      I don't have any insight into the why. Only that the growth rate in tests per day has slowed to an almost stagnant level.
      - ejstronge 6y ago
        At least anecdotally, it doesn’t seem that we’re hitting our full testing potential. I think adding in a new technique would only exacerbate the mismatch between test supply and test utilization. https://www.nature.com/articles/d41586-020-01068-3 https://www.nature.com/articles/d41586-020-01068-3

thoraway1010 6y ago

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 6y ago
The skills required for these fields are very different. They hired someone to do it.

zrgiu 6y ago

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 6y ago
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.

JetBen 6y ago

Can you promise that this test will not be mass-produced in China? It would be criminal for the Chinese to gobble up all the profits of a virus that they released on the world.

delibaltas 6y ago

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?

hkiely 6y ago

How does this help with RNA decay?

snorrah 6y ago

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 6y ago
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.

sachinjoseph 6y ago

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

andy_ppp 6y ago

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-3mhXQY22m4wrs4Kd6nxPhDWM-M/edit?usp=sharing https://docs.google.com/spreadsheets/d/1IPcX2JYt9mXdaTvj-3mh...

aaavl2821 6y ago

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?

daemonk 6y ago

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?

mkagenius 6y ago

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)

thawkins 6y ago

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?

stuartromanek 6y ago

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

shushpanchik 6y ago

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.

Palomides 6y ago
this is more or less being done, under names like "pooled testing"
Blahah 6y ago
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
thehappypm 6y ago
I have heard many false negatives are an issue. Diluting samples down might make that even worse.

jl2718 6y ago

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

meheleventyone 6y ago

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 6y ago
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?
- thinkingemote 6y ago
  Or other children and their family etc.
- n8udd 6y ago
  https://www.theguardian.com/uk-news/2020/apr/04/five-year-old-child-among-latest-uk-coronavirus-deaths https://www.theguardian.com/uk-news/2020/apr/04/five-year-ol...
  - grey-area 6y ago
    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.
- meheleventyone 6y ago
  Kids can get infected although at a lower rate under 15. So yeah and essentially that by keeping contact limited if someone does get sick you only need to quarantine a limited set of people and close a classroom rather than the whole school. I feel like a lot of the success here has been in being aggressive with contact tracing and people able to take the social responsibility to self-quarantine.

poarneemn123 6y ago

'Machine learning algorithms' Nothing to see here, just trying to make a quick buck using the pandemic

zelphirkalt 6y ago

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.

somberi 6y ago

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.

aurelwu 6y ago

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.

limaoscarjuliet 6y ago

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-03-31-20/h_c9b8259b105b4f26a4ade9fb61b954ce https://edition.cnn.com/world/live-news/coronavirus-pandemic...

rplnt 6y ago
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.
- buboard 6y ago
  That works well for low infection rates https://www.biorxiv.org/content/10.1101/2020.04.03.024216v1.article-info https://www.biorxiv.org/content/10.1101/2020.04.03.024216v1.... https://www.medrxiv.org/content/10.1101/2020.04.05.20054445v1 https://www.medrxiv.org/content/10.1101/2020.04.05.20054445v...
- douglaswlance 6y ago
  You can do a binary search to efficiently locate the positive sample.
  - ced 6y ago
    But what if there are two (or more?) positive samples? It's an interesting problem.
    - bequanna 6y ago
      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.

mhandley 6y ago

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 6y ago
You can indeed, this was addressed earlier in this thread: https://news.ycombinator.com/item?id=22810002 https://news.ycombinator.com/item?id=22810002

yters 6y ago

Is it possible to create an at home cov2 test with a $25 homemade PCR https://hackaday.io/project/27623-coffee-cup-polymerase-chain-reaction-machine https://hackaday.io/project/27623-coffee-cup-polymerase-chai... 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 6y ago
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.

thebiglebrewski 6y ago

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 6y ago

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

foolinaround 6y ago

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