Vipassana meditation – reflections after 3 years

1. Exercise is useful to calm a very agitated mind… even the stories during the course highlight this. Strongly discouraging (banning) it for those who enter the course with very agitated minds (or conversely not adequately equipping people in how to assess their mental state to decide if they should go on the course) is missing an important opportunity for a subset of attendees.

Yes, being able to meditate with a very agitated mind is a goal but it is best to walk before you can run. Exercise could be used as a crutch for someone with intense sensations i.e. high sensitivity and low equanimity, to reduce those intense sensations whilst the equanimity is built and might avoid needlessly uncomfortableness.

2. Some people come with very insensitive and unaware minds, others with highly sensitive and aware minds. Spending 3 days building awareness with no mention or guidance of equanimity could explain why some (those who are already sensitive) have entered or re-entered severe episodes of depression or killed themselves. Personalisation of the course would be very beneficial. I personally disengaged from it half way through day 2 to half way through day 4 because it was too painful as I was not yet given the tool for exploring the rest of the body, and more importantly the tool of equanimity for accepting it.

3. Writing materials are “banned” (no ones checks) but I think this is a missed opportunity too. I agree that we should strive to become less emotionally attached to things (objects / ideas / memories of past events / sensations of greed, pleasure etc) and made hostage by those things but the meditation can also be a great creative period. It’s far easier to get the ideas out and securely onto paper, then you can let go of them for those few days whilst you start to build longer term equanimity to them.

Like with all challenges, breaking them down into smaller more manageable steps makes it easier, more efficient and more likely to be succeeded at.

4. There is no support after the course. If your mind is now opened up and sensitive to life, this can be very unpleasant if you have things you were previously avoiding, insensitive to and sheltering from.

Open Science: tackling Corona virus head on

Accurate affordable testing is crucial for lifting the burden of the SARS-CoV-2 virus and associated CoViD-19 disease from our communities, and economies.

With testing you can find the virus. And with contact tracing you can allow people to effectively quarantine themselves, breaking the chain of infections and stopping the spread. With no new hosts the virus will quickly disappear from your communities.

So accurate affordable testing is crucial.


Most groups of people find themselves in companies which often need investment to perform R&D (research & development), manufacture and sell their product.

Investment driven companies need to make a profit, and often a large one. This is not bad, it’s just the way it is.

Aiming to make a large profit is an inherent property of investment. Investors take risks: some of the companies they invest in fail. The more companies that fail, the more money investors loose and the higher the profit margin those other investments need to return to the investors. Otherwise the investors go broke and stop being investors. It’s a pretty self selecting process and at its core is risk and need for profit.


As in software, every once in a while a group of people come along who develop an idea into a robust technology. And then, for various fortuitous and noble reasons, release it for free. This is open-source at it’s best.

Technically patents are open-source too as they’re meant to document all the necessary components of an innovation and expire 20 years later, at which point they’re also free to copy. The time delay is justified by saying they need to recuperated the costs & risks they put into R&D. One of the problems with patents is that they often don’t include all the details, leaving important trade secrets undisclosed for years after the patent expires. This is not open-source.

Open-source SARS-CoV-2 testing

There are now three inspirational open-source projects, two of which I’ve been tremendously grateful to interact with the teams behind the technologies.

1. Open-source RNA purification

A crucial step in testing for the virus often involves extracting viral RNA from the patient sample and purifying it to remove enzymes like RNases (that can destroy the viral RNA before you get a chance to measure it) and other contaminants (that can interfere with the process of measuring it by inhibiting the RT-PCR reactions).

Early on in this pandemic, members of the international team in New Zealand quickly partnered with New Zealand’s largest diagnostic lab to produce an updated protocol suitable for extracting RNA from SARS-CoV-2. This is now being used by multiple labs all over the world. With improvements being made daily.

2. Crick Institute

The Crick institute put together and validated an automated protocol for SARS-CoV-2 detection along with all the well thought through standard operating procedures (SOPs) you need to run it.

3. OpenCell London

Finally, last but not least, OpenCell London started waving the flag earlier than *anyone else* I know.

As you can see I eventually caught up with them. And after they assembled a large international team of volunteers, together we have released their our (still getting used to that) paper on an open-source mobile testing lab in-a-shipping-container. Complete with all the code you need to run the RNA purification protocol and the setup and analysis steps.

All open-source. All free. Anyone one the planet can copy this code and experimental design, start improving it for us and everyone else.

This marks the end of the beginning of this journey. The path is long and I hope the proprietary companies can make sure we don’t have to travel much further along this road. In case they can’t, let’s stack the deck against this virus. Together we’ve made some important steps along that road to accurate affordable testing for as many people as possible.

Some of the other people who have directly helped so far

Catherine Moore and Rocio Martinez-Nunez have been sources of immense wisdom, shared it widely to help others, whilst also doing a heavy workload, and done so patiently, kindly, with dedication. We all owe you a big debt of gratitude.

Continuous Validation: unlocking accurate mass testing

We are not short on technological solutions for testing [1][2][3]. What’s blocking us is fear of making a mistake. Dr Michael Ryan, Executive Director, WHO Health Emergencies:

anyone involved in emergency response will know this. If you need to be right before you move, you will never win. Perfection is the enemy of the good, … and the problem we have in society at the moment, is everyone is afraid of making a mistake… But the greatest error… is to be paralysed by the fear of failure. (abbreviated)

It is a balance, we don’t want to test someone who has the virus and tell them they don’t, letting them spread it and kill people. Or tell someone who is not infected that they do have the virus and they commit suicide or other significant downsides.

These false negative and false positive results can come from a wide range of sources, from cross contamination chemicals, incorrect temperature of samples, software bugs etc.

Standards, and accreditation, and the things that come with this such as negative pressure labs, appropriate PPE, cleaning rotas, lab access control, documenting chemical batches for tracing, improving protocols, etc help keep lab staff safe whilst reducing these false negatives and false positives. They will never eliminate them. But this is as good as we can get and the test manufacturer and testing lab can say everything has been done. But I believe we can do better, and faster.

The current situation

Imagine you’re an NHS lab with skilled staff, necessary facilities and machines with no reagents [4][5]. Or you are an academic or private lab who are ready to repurpose your facilities and equipment. You don’t have staff who are trained in molecular diagnostic pathology but you’ve run hundreds of molecular biology experiments. You have extensive experience of running robust scientific experiments and research. You read all the regulations, implement them and existing trained pathology lab staff have kindly given you extensive advice from cleaning protocols, sources of sample contamination, good practices for sample handling, avoiding long shifts etc.

Right now you could look to various open-source / generic designs [2][3].

You have facilities for handling patient samples, so you order the components, assemble it “DIY” style, and validate it using commercially available controls [6][7]. The results come back. Your LOD (Limit Of Detection) is comparable with the gold standards. You repeat the samples 10 times. Your false positives stay at 0. You’ve got an accurate, safe and ethical testing facility.

But the tests are running on a new system that’s unaccredited. Or if you’re not an existing pathology lab your lab and staff are also unaccredited. So then they’ll need to be validated by MHRA, process 20 directives for CE marking, 4 ISO standards, UKAS accreditation, HSE accreditation, HSL accreditation. By 2021 you might receive your first sample and test it in the lab.

Continuous Validation: How to quickly approve 100,000 accurate tests per day

(and how other options like EUA can be made more robust)

Test the testers. Not through accreditation. But through correctly identifying control samples in every batch of samples every day.

Let’s call this Continuous Validation. To pass the test the testers will still need to read all the standards and implement them. The tests are cheap enough though (£3-5 each [8]) that we could afford to run two or three tests per sample. In reality you might only need to run 10 tests per batch of 96 to have a good assurance that if those are correctly identified, that the other samples are also correct.

With the USA’s FDA’s EUA policy [9], a larger number of tests have come to market very quickly [1] but as no test is better than a bad test they’ve likely done more harm than good. Continuous Validation of labs avoids that. If we had 20 new labs, capable of processing 5,000 samples per day each, that would need 200 tubes (20 labs x 10 different controls), containing 50 ml (5000 samples per day / 100 samples per batch) of the different control samples. A single technician could make that in an afternoon for under $1,000, put on dry ice and send to each lab. You’d also ship one set back to the central lab and everyone would run their tests, and report all their results.

Continuous Validation in a distributed testing system

This inverts the majority of the necessary quality control effort from a centralised point to become distributed. It scales proportionally with both the number of labs and the number of tests. It distributes the risk of non-compliance to individual labs. And it does this whilst retaining the central point of control over quality.


Untrusted and semi-trusted systems were also explored by the authors. The former likely requiring various degrees of integrating central testing authority with patient sample collection sites and patient record systems. Semi-trusted systems could include the use of smaller one use samples per batch along with live streaming video from labs to increase transparency and provide an additional form of documentation.

Interlab comparisons for free

A component of ISO 17025 is the valuable interlab comparisons. We’d get that for free.

What’s still a bottleneck? HSE to protecting the staff and the environment

If we move to lysing samples at source, prove they’re inactivated and disinfect them before entry to the lab then we remove a significant risk factor, reducing the lab from BSL3 to BSL2+.

We need your help

A bad test is worse than no test, and this post is not about cutting corners. It’s about challenging ourselves to see if there are faster ways to increase testing capacity. If you’ve got a better idea, you think this is not necessary or you think the current situation is the best we can do please let me know by commenting on the live version of this document or contacting or . Thank you.

If you’re a pathology lab manager, what do you think of this approach to getting our testing increased in a responsible and timely manner?

If you’re in policy, what would need to make this happen?

If you’re an accreditation body, in a non-binding and confidential way, would you support this approach?

If you’re in biotech or business and debating setting up to help run tests, does this resonate with you?


In reality this is a very long list but: OpenCell,, OpenTrons, Crick for all being inspiring. Tom at OpenCell for patiently answering questions. For valuable feedback: Charlotte Roach, Ian Robertson.

Vaccines, Regulations and Expediency

When might we get a vaccine and what regulations are or might be relaxed or expedited?

Disclaimer: I have studied biochemistry including immunology (which is still fascinating). I am have little experience with clinical trials, regulations, time lines etc. But I understand it usually takes billions and >5 years. I’m also not going to attempt to discuss the serology of Covid-19, the SARS CoV-2 glycoproteins and their immunoreactivity etc. more than to say there are many smart people working on it to see if it’s possible and I’m glad we have them.

Update 1 (2020-04-25)

Karthik Dinakar from Satori shared the following Stat news article [14].

Researchers rush to test coronavirus vaccine in people without knowing how well it works in animals

Which states that whilst there is no specific regulation requiring animal validation and therefore it is not illegal, there has been no animal testing data that can be relied upon yet.

Additionally it links to their annual SEC 10K filing [15].

The mRNA-1273 program is to develop a vaccine against SARS-CoV-2. Clinical supply for this mRNA vaccine was designed and manufactured in 25 days.

In the UK, the first patient has been injected with the COV001 vaccine according to this BBC article [16].

The post from Imperial COV001 vaccine group on the ambitious 18 month target for mass manufacture of a safe and efficacious vaccine [17].

Original post (2020-04-24)

However I would contend we have already seen some “relaxation” of regulations. I’m not for or against this. I’m just reporting my limited understanding of how clinical trials are usually conducted and why it takes so long. This perception of relaxation of regulations is based on my inability to find preclinical data for Moderna mRNA-1273 after a couple of hours of searching. This has now entered Phase 1 vaccine trial [3]. The closest I’ve found is:

The mRNA-1273 vaccine has shown promise in animal models, and this is the first trial to examine it in humans. [13]

That’s all I’ve got so far. They’ve only got data for other viruses like RSV (Respiratory syncytial virus) linked on their website [4, 5].

We’ve also got a phase 1 / 2 trial of the “COV001” vaccine based on the ChAdOx1 virus expressing the S protein[11]. 800 volunteers will be vaccinated [12]. I can’t find (nor am expecting to find) any preclinical data for that either. Again it might be out there but I just can’t find it.

The vaccine candidates deployed should normally have a lot of pre-clinical testing data[1]:

The development and licensure of an efficacious […] vaccine requires the consideration of many factors, but first and foremost, an experimental vaccine must undergo rigorous pre-clinical testing and demonstrate protection in an appropriate animal model of the disease. This animal model should be susceptible to infection when challenged with the pathogen, or closely related strains, and should ideally recapitulate hallmarks of the human disease

The vaccine is similar to something that’s been tested already

If that were true it does not (normally) matter and for good reason. Even small changes can have disasterous consequences. After the researchers of ZEBOV had sent hundreds of doses for the first phase 1 trial, they found out it had been manufactured using a different protein and therefore was not the same vaccine as use in the animal models[8].

Feldmann believed the switch would have no impact on whether the vaccine was effective. “Quite frankly, from a scientific prospective, it doesn’t matter,” agreed Kobinger. “From a regulatory perspective, it matters a lot.”


It’s obviously very different to compare to Ebola. However:
The 2014-2016 EBOV epidemic likely started in Dec 2013 [1].
On Aug. 8, 2014, the WHO declared the outbreak a global health emergency. [8]
It was coming under control by Dec 2014 [2].

In contrast with SARS CoV-2 there were several very promising vaccines that had already been explored in robust pre-clinical models before the outbreak.

A few days after the WHO made their Aug 8th announcement a vaccine “ZEBOV” was provided for a Phase 1 trial[10].

Due to the circumstances in West Africa, after the phase 1 trial was conducted successfully it went straight to 3 & 2 running concurrently[1].

the lack of an approved effective vaccine combined with the dire circumstances in West Africa led to an expedition of vaccine trials from Phase 1 safety studies directly to Phase 3 efficacy studies, alongside Phase 2 studies

It’s not unreasonable to expect a similar approach might be taken with SARS CoV-2.

This vaccine had been tested and shown to be very effective in a non human primate cynomolgus macaques animal model[9][ref 5-7 within reference 10]. And had been shown to be not dangerous in a human subject[8].

This paper[1] goes into detail about various Ebola vaccines. “VRC-EBODNA023-00-VP”… though it not deployed initially along side ZEBOV (VSV) or ChAd3-EBO Z as the other vaccine mentioned in [8] but it had a phase 1 starting August 2014 [6] and it’s actual first phase 1 (but perhaps is a related compound) was 6 years early in Jan 2008 [7].

The point of this is that it was only August when the first Phase 1 trials emerged. However, yes granted the Ebola outbreak took a lot longer to grow and “smouldered”. But the trials of at least one of the compounds was already well tested in a very good animal model.


I had a quick look at Dengue phase 1 vaccine trials. Again Dengue the disease and circumstances are very different. All phase 1 trials though had a placebo arm (I can’t find it now but I think one did not).

VaccinePlaceboStart dateTrial
189April 2010ref
2412September 2015ref
189February 2010ref
5819December 2011ref
7214May 2010ref
Placebo numbers are sometimes estimates

Compare to Moderna mRNA-1273 has no placebos. COV001 has >300.

Current conclusion?

The fact Moderna mRNA-1273 and ChAdOx1 COV-001 was in someones arm so quickly is unsual. Again, not necessarily good or bad.




SARS-CoV-2 nasopharyngeal vs Saliva – mini lit review

Update 2020-04-25: Health Technology Wales have released a much fuller review with some different papers. Table 2 very useful, will be great when we can split out “only” nasopharyngeal from throat + nasopharyngeal.
Update 2020-04-24: Centre for complex interventions released a higher level report summarising which tests reported to support which sample. are working up to provide SARS-CoV-2 full open-source testing. They’ve been offered a lot of saliva sampling kits. Is saliva a good choice vs oropharyngeal, buccal, mid-turbinate, nasopharyngeal? To help them out answering this question I did a mini litt review.

From what I’ve seen seems like taking samples from as many places as possible is a good idea but saliva has obvious large advantages. It’s simple for people to do, no swab needed, minimises risk of coughing and aerosolization, minimises PPE use, and no trained staff are needed (correct?).

An Italian hospital now requires 2 negative nasopharyngeal and 1 negative saliva before discharging people after finding some people with negative nasopharyngeal were still positive from saliva: Azzi et al. 14 April 2020 Saliva is a reliable tool to detect SARS-CoV-2. n=25 but from severely ill patients so does this generalise?

In the first patient, the salivary specimen was positive on the same day when a nasopharyngeal swab converted to negative, and this result was also confirmed after two days. The second patient showed positive results in two consecutive salivary swabs, while three consecutive respiratory swabs were negative on the same days.

Wang et al. 2004 Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis shows saliva has 1% of SARS virus in cell fraction with 99% in supernatant or N-acetyl-L-cysteine treated supernatant. Split between latter was N-acetyl-L-cysteine treated supernatant had x1.75 that of untreated supernatant. N-acetyl-L-cysteine breaks down mucus. Perhaps mucolytics could boost detection further from all samples? (links to UK DHSC site for crowd sourcing ideas)

One from Yale preprinted yesterday which is causing a stir Wyllie et al. 22 April 2020 Saliva is more sensitive and included 44 severely diseased patients in which they show:

  • higher titre in saliva
  • detected SARS-CoV-2 from saliva but not nasopharyngeal swabs from eight matching samples
  • nasopharyngeal swabs and not saliva from three matched samples

Whilst the data is interesting, the power is low and it points again to the fact that multiple sampling sites would be preferable but if saliva is all you can get then you will detect some cases. Again the time of the disease vs viral load in different sample sites will be really useful to know. We need a clinical trial on this.

There’s more papers to yet review in: under “Source of sample”

Qiagen AVL Buffer safety data sheet

Qiagen RNA extraction kits use AVL buffer. AVL buffer has 50-70% guanidinium isothiocyanate according to their safety data sheet. Their website doesn’t let you link directly to the safety data sheet as the url expires after some time; so I’ve saved it in (the amazing) internet archive:

Hazardous ingredients

Chemical NameCAS-No.Concentration (% w/w)
guanidinium thiocyanate593-84-0= 50 – < 70

It’s important to note that they don’t share what else is in the AVL buffer. And that there’s research to show this buffer may be insufficient to inactivate some viruses: “Buffer AVL Alone Does Not Inactivate Ebola Virus in a Representative Clinical Sample Type”

Head of ICU at the Royal Free – on Covid-19 treatment

Copied from the whatsapp at 21:49 on 2020-04-04 (Saturday)

from the Head of ICU at the Royal Free. Please feel free to disseminate further.

“Dear All,

I have just finished a very useful ICU / NHS Nightingale teleconference, the aim of which was to consolidate experiences about CV19 and how best to manage the disease. I have provided a summary below. Please understand that the information is experience, not evidence. I think it highlights a number of areas that we need to discuss URGENTLY as a group. The take home message is that advice given at the beginning of this journey needs to be adapted as we learn more about CV19. The other important thing to begin to understand is that this disease has distinct phases and treatment will differ as patients move through these phases.

The call had about 80 people on it, most listening. There were about ten “experts” invited to speak, from high volume centres. I represented our site. Others included Georges, GSST & Brompton.


  • Early high PEEP is probably not the right strategy and may be harmful. This is not ARDS in the early phase of the illness.
  • Avoid spontaneous ventilation early in ICU admission as also may be harmful.
  • There is clear microvascular thrombosis happening in the pulmonary circulation, which leads to an increased dead space.
  • Also some evidence of early pulmonary fibrosis reported from Italy, possibly oxygen related, possibly inflammation related.
  • Not many patients have reached extubation yet in London, re-intubation seems to be common. I highlighted our experiences of airway swelling / stridor / reintubation.
  • Brompton are seeing wedge infarcts in the lungs on imaging, along with pulmonary thrombosis without DVT.
  • Proning is essential and should be done early. Don’t just do it once. Threshold for many centres is a PF ratio of 13, but all agreed, do it even earlier.
  • Early on in the disease, the benefit of proning lasts < 4 hours when turned back to supine, as the disease progresses into a more ARDS type picture, the effect is more long lasting.
  • Many centres using inhaled nitric oxide and prostacyclin with good effect. Tachyphylaxis with NO after 4-5 days.
  • Generally people are using humidified circuits with HMEs.
  • A very interesting thing they are doing at Georges is cohorting by phase of disease i.e. early, late, extubation / trachy. It involves more moving of patients but helps each team to focus on things more easily.
  • Leak test before extubation is crucial, others are also seeing airway swelling.
  • Wait longer than usual before extubating, high reintubation rates reported. Do not extubatne if inflam markers still high.

My conclusions from this are:

  • Less aggressive PEEP strategy at the beginning of the disease and go straight for proning.
  • Thromboembolic disease is prevalent, look for it. No one is sure about whether we should anti-coagulate everyone, this is probably too risky.
  • An extubation protocol is needed immediately.
  • We should consider using inhaled prostacyclin again (like we previously did) as it seems to be working early in the disease.

Fluid balance

  • All centres agreed that we are getting this wrong.
  • Most patients come to ICU after a few days of illness where their temp was 38-40 and they were hyperventilating i.e. severely dehydrated.
  • High rates of AKI being caused by over zealous driving with frusemide, leading to unnecessary CVVHF.
  • Hypovolaemia leads to poor pulmonary perfusion and increased dead space.
  • Centres echo’ing their patients are seeing a lot of RV dysfunction without raised PA pressure.
  • Many have improved oliguria by dropping the PEEP i.e. these patients are really hypovolaemic.
    [On nights I have observed many of our patients with a zero fluid balance and temperature of 39 i.e. they will be 2-3 litres negative in reality.]
  • Most centres are therefore now backing off of strict zero balance, particularly in hyperpyrexia. They are moving more towards avoidance of large positive fluid balance.
  • Lung ‘leak’ not as prominent in this disease as classic ARDS

My conclusions from this are:

  • Avoid hypovolaemia as it will impede gas exchange and cause AKI. Progression to CVVHF increases mortality.
  • Avoid hypervolaemia
  • How we achieve this is difficult, but the frusemide and noradrenaline cocktail needs to be carefully tailored, especially in pyrexial patients.
  • Echo patients to understand their volume status.


  • Higher than predicted need for CVVHF – ? Due to excess hypovolaemia.
  • Microthrombi in kidneys probably also contributing to AKI.
  • CVVHF circuits clot frequently. Georges and Kings now fully anticoagulant the patient (rather than the circuit) as it is the only way they can prevent this. One centre using full dose LMWH as they have run out of pumps.
  • Kings now beginning acute peritoneal dialysis as running out of CVVHF machines.

My conclusions from this are:

  • Aggressive anticoagulant strategy required for CVVHF, potentially systemic.
  • If we run out of machines, PD may / may not help (our previous experiences with it are not great, but I have no alternative other than using CVVHF like intermittent dialysis and sharing machines)


  • A ’tactical commander’ is essential on every shift, who is not directly responsible the care of ICU patients.
  • Most centres now getting towards 1:6 nursing ratio with high level of support workers on ICU.
  • Training has largely fallen by the wayside as it is too large a task. People are being trained on the job.

My conclusions from this are:

  • On call consultant to coordinate but not be responsible for patients (as is the model we have now adopted).
  • We need one support worker per patient. Other centres are using everyone they have. From med students to dental hygienists. We are behind the curve ++ with this. Last time I was on a night shift, theatres were full of non-medical staff refusing to help ICU – this is unacceptable.

There were some brief discussion about CPAP:

  • Proning patients on CPAP on the ward is very effective, I tried it the other day – worked wonders.
  • Prolonged use of CPAP may (I stress the word may) lead to patients being more systemically unwell when they get to ICU.
  • Considerable oxygen supply issues with old school CPAP systems.

My conclusions from this are:

  • As per local guidelines, assess the effectiveness of CPAP after an hour, if it isn’t effective then bail out and consider intubation.
  • If effective, regular review is required. If at any point it is failing, bail out and consider ventilation.
  • Whilst we may have a shortage of ventilators, holding people indefinitely on CPAP may be short-sighted as it may be converting single organ failure into multiple organ failure.

OK, that’s all I have.

I will stress again that this is simply a summary of discussions, none of which are backed up by large, robust multi-centre RCTs.

My conclusions after each section are nothing more than suggestions to be discussed.

We need to adapt fast to what we learn about this disease and learn from our colleagues at other centre. We are all in this together and joined up thinking is required.

Lastly, we desperately need to look at our own data to understand whether we are getting this right or not.

Good luck, stay stay safe and be kind to one another.

Daniel Martin OBE
Macintosh Professor of Anaesthesia
Intensive Care Lead for High Consequence Infectious Diseases
Royal Free Hospital

Reckless: “it is not the healthy who need a doctor, but the sick”… wrong.

If you test “the healthy” and find they are infected. They can self isolate and effectively quarantine… that means they won’t pass it onto to 3 other people, one of whom will become “sick” and need a doctor. The lack of simple logic in Vice President Pence’s statement is baffling… except it’s not. Because the real reason he’s said it is because they can not do the level of testing they know they need to do.

Worried about Ventilators, PPE, supply chains, the economy? You’re focusing on the wrong thing.

** Update ** Finally the UK government has changed strategy to focus on wide scale testing!

There’s a shortage of ventilators. A shortage of PPE. Supply chains have and will become increasingly disrupted. The fragility of our societies and industries streamlined only for profit is clearly apparent.

Our front line medical workers and other heros lack the PPE to keep them safe whilst they keep our society running. Meanwhile the rest of us are struggling not to touch our faces before we wash our hands and understand the simple message of physical distancing (social distancing).

Despite that we are making progress to slow the spread. And we’re also building ventilators and trying to hack enough PPE to keep our key workers safe [1]. That’s good but we need to focus on the key to unlocking the solution to this problem: Effective quarantine.

The solution to this problem: Effective quarantine

Effective quarantine allows us to temporarily stop infected people from infecting others. For every 30 infections you prevent, you save 3 hospitalisations and the need for a ventilator [see ref 2, table 1 – depends on the age of your population]. You also save the risk of exposing our medical workers and everyone else. You don’t need to worry about PPE. You don’t need to worry about supply chains.

So effective quarantine sounds really useful. How can we get there?

We need to do testing. Testing allows us to tell who is infected. Then we need to do contact tracing to find those people who the infection might have passed on to. And we need to ask them to isolate themselves and then test them after a short period of time.


Why can’t we do enough testing? A UK government representative finally admitted on March 31st:

that the government’s testing capacity is being constrained by the supply of specific chemicals, but the government is working with academics and the private sector to increase the number of test centres


The test used in the UK is a type called qRT-PCR. The viral RNA (the thing which contains the instructions to make more viruses) must first be extracted before the test can be performed. The current manufacturers of those chemicals can not scale up their supply fast enough. They’re holding on to their IP and not even licensing let alone releasing it more freely. This contrasts with ventilator companies who released their IP under time limited copy left licence [4][5].

But what can I do?

Write to your member of parliament and demand the intellectual property around the testing reagents is released or that they license their technology more widely.

For example I sent my MP the following message:

Dear __,

I would be very grateful if you could publicly threaten Qiagen with compulsory licensing of their RNA extraction technology. This is permissible under WTO TRIPS laws. We need this vital intellectual property (IP) in order to scale up testing and defeat this challenge placed upon our communities.

> If a compulsory licence is issued, adequate remuneration must still be paid to the patent holder — Article 31h.
> Compulsory licensing must meet certain additional requirements. [...] usually it must be granted mainly to supply the domestic market.
WTO TRIPS regulations:

Thank you for your time and for serving the community through this difficult period.
Stay safe,

Mr Alexander James Phillips
Co-founder of the 15,000+ volunteer group

=== Interviews ===
BBC (11:45+)
Also interview with FT, The Times, NYTimes and Vox.

What can I do? – part 2

Put pressure on Qiagen, Roche and others publicly. Use the hash tag #FreeTheTest to encourage them to license their technology to help scale up production of the tests OR release it for free. Remembering that we only need this whilst the demand for testing can not be met by them.

Stay safe everyone. Please share this message!




How coronavirus can be stopped in eight weeks

Nafeez Ahmed‘s article was published for free here, you just had to sign up:

Am reposting this from behind its paywall as it is a moral obligation to minimise harm. Our doctors, nurses, paramedics, others caring for vulnerable people, people who put food on our shelves, and keep us safe need everyone to have access to this information. Reposting because the national strategies have been misguided but it’s not too late to recover the situation. We just have to act NOW.

As America becomes the centre of the pandemic and health services around the world face disaster, former WHO chief Anthony Costello tells Nafeez Ahmed it’s not too late to regain control of the situation

Former WHO director: 8-week suppression strategy could stop US coronavirus crisis in its tracks

By Nafeez Ahmed

“We know we can get this under control,” says Dr Anthony Costello, a former Director at the World Health Organization (WHO) where he headed up maternal, child and adolescent health. “The problem is that Europe has been too slow to act compared with Asia; and America is now facing a huge crisis.”

Costello, who is Professor of Global Health at University College London where he previously headed up the UCL Institute for Global Health, spoke to me via telephone from Yorkshire, England, where he is currently isolating from his family members, many of whom are experiencing symptoms of the novel coronavirus.

Costello, who joined the WHO from 2015 to 2018 before returning to UCL, pulls no punches about the failures that, he says, have allowed the new coronavirus to rampage across Western countries.

“America is now the epicentre of the pandemic”, he warns, arguing that the United States may experience the highest rate of fatalities anywhere in the world. London, too, he tells me, “will face a health service disaster within two to three weeks, because it’s been allowed to let rip there. I really fear for our people and my health colleagues.”

The reason the US and UK are on track for disaster is due to the failure to take early action, explains Costello. This allowed the virus to spread undetected among communities for as long as two months, setting us up for levels of exponential growth which are now bound to overwhelm healthcare facilities.

But he insists that it’s not yet too late to regain control of the situation. And the data suggests we could do it in as little as seven to eight weeks. 

“We know that the virus has been circulating in the US at least since mid-January, when a guy flew into Seattle from Wuhan. He seems to have seeded the virus, and since then we have had exponential community transmission,” Costello says. 

The Trump administration, however, rapidly changed course on its previous inaction after White House officials read a paper released on March 16th by Imperial College London’s COVID-19 Response team. 

That paper, produced by the same scientists advising the Boris Johnson government in the UK, used a mathematical model to estimate the consequences of the US and British government’s prior strategies of minimalist mitigation. 

The findings were frightening, forecasting that as many as 1.1 million Americans and 260,000 Britons would die even if more ambitious measures were pursued to slow the epidemic. The only way to avoid this outcome, the Imperial College team recommended, is a comprehensive epidemic suppression strategy enforcing social distancing for 18 months – until a vaccine becomes available. 

Since then, the US Centers for Disease Control have adopted the 18-month suppression strategy as part of their official response plan. Meanwhile, Trump has already expressed his reluctance to pursue such a protracted lockdown due to its impact on the global economy.

Seemingly vindicating his approach was a separate model produced by Oxford University which made national headlines, claiming that as much as 50 percent of the British population may have already be infected and built up “herd immunity” to the virus – implying that social restrictions could be lifted far more quickly. 

The study was also amplified by conservative commentators in the US, who suggested that it means the US lockdown policy should be ended.

But according to Costello, “both these mathematical models cannot be right. I suspect that the truth might in fact be somewhere in the middle.”

While the Imperial College’s modelling of the potential high fatality rate of a ‘do nothing’ approach has been widely accepted by the scientific community, its 18-month solution strategy has been questioned – as has the Oxford model’s opposite approach assuming a build-up of immunity. 

study by the New England Complex Systems Institute at New York University found that the Imperial College scientists had ignored data from East Asia demonstrating the efficacy of mass testing and contact tracing in suppressing the outbreak and minimising fatalities within around 5 weeks. Epidemiologists and public health experts had also pointed out that the Oxford paper’s optimistic modelling was already contradicted by fatality data from Italy. And neither model has supported the best tried-and-tested responses to dealing with an epidemic.

As a result, says Costello, “The United States is now the epicentre of the pandemic. Currently, Britain is a bit ahead of the US, and two and half weeks behind Italy, which is only a few days ahead of Spain, France and Germany.

“But the problem is that government has placed the modellers in the forefront of decision-making. SAGE [the UK government’s Scientific Advisory Group on Emergencies] strikes me as having downplayed the public health view. Which is that you’ve got to act fast, find the virus, test test test, trace the contacts of those who are infected, isolate and quarantine, and implement strong social distancing. You do all that and what we’ve seen in East Asia is that you can really contain this, suppress this within 7 weeks.”

This won’t make the virus simply disappear but it buys valuable time and drives down the death rate. According to Costello, while there is nothing wrong with bringing in theoretical experts to do mathematical national modelling, the real problem is that the British government’s scientific experts lack significant experience in staving off real-world epidemics:

“They are all good academics. I have a great deal of respect for them. But none of them have successfully managed a public health crisis like this. The Imperial College paper for instance didn’t model the impact of mass testing, and talked only about case isolation. Yet these are precisely the tactics that we know work so well. Mass testing for the virus is already working in places like South Korea, where they’ve managed to find a way to keep this at bay without draconian lockdowns.”

Costello is sceptical of the official claim that the reason we didn’t rapidly bring in mass testing is the lack of capacity. 

He cites virologist Professor Julian Peto of the London School of Hygiene and Tropical Medicine who, Costello tells me, has “rightly rubbished the idea that we don’t have the capacity for testing. Just one real-time PCR machine can be used to undertake as many as 10,000 tests over two weeks. All we would have needed to do was ramp this up, mobilising local research labs around the country to reach hundreds of thousands, if not millions. We haven’t done this, and the question is, why?

“We knew at the end of January that a crisis was developing in Wuhan, and any crisis management team would ask, is there a chance it could come to London, or Washington. And the answer at that time from public health experts was simple: yes. We should have started preparing for the worse case scenario. We didn’t.”

There is still time to get ahead of the crisis, Costello says. “We have London surging. Many parts of the US are similarly surging. In the UK we also have the West Midlands and some other areas. But there are other places where we don’t really know what’s going on, because we just aren’t doing much community testing. Testing of health-workers is essential, but without community testing we can’t see what’s going on, we can’t tell how the epidemic is spreading. It’s being able to tell that which allows us to move in rapidly to isolate cases, and this is the key to being able to slowly return to some degree of normalcy.”

After announcing the end of the community testing earlier in March, the government U-turned and declared it would ramp up community testing, with Boris Johnson promising 25,000 tests a day. But it still hasn’t happened. “Community virus testing hasn’t properly kicked-off. We are still doing a maximum of around 5,000 tests a day. This is way too low.”

Costello is also concerned about tepid government messaging. “It’s not enough to just have modellers, virologists, and behavioural scientists. You need people who can translate this into action. Social scientists. Public health experts experienced in community mobilisation. Right now we are locked into this strange idea that the Prime Minister or President makes a speech and suddenly the entire country changes its mind. That’s just a fantasy. Throughout my career I’ve seen that just giving people a few of the right messages won’t necessarily change behaviour. We need a more serious decentralised approach and to share data with local communities.”

He refers to some of China’s mass communications measures. “The Chinese managed to suppress the virus in provinces outside Wuhan without the same sort of total lockdown by operating quickly. They had a TV station giving out information on the virus round-the-clock on a 24-hour basis. We had policing of supermarkets and pharmacies. But most importantly we had a comprehensive mass testing and contact tracing programme. And proper protection for frontline health-workers. And that’s how this was brought under control within 7 weeks.”

In contrast, Costello warns that the situation facing frontline health-workers in the US and UK is nothing short of disastrous. “We simply don’t have enough PPE [Personal Protective Equipment]. Not enough visors, not enough N95 respirators. Government is not following WHO guidelines.”

I saw this first-hand when I had to call the emergency services to come and see to my 75-year old father. He has dementia, diabetes, heart disease and has had multiple strokes. Earlier this week, he tested positive for COVID19. He is currently in a stable condition in a London hospital. When the paramedics arrived, they wore little more than surgical masks – known to be largely useless in repelling coronaviruses – and thin bibs made out of what looked like the same material as plastic bags. It’s quite possible, if not likely, that they were infected as a result of handling my father – and that they may, in turn, be infecting others whom they deal with during the course of their jobs. But while I’ve been advised to self-isolate after my own contact with my father, no one has told these frontline workers to do the same, and they haven’t been tested – the government only announced a ramp up of testing for healthcare staff at the end of March. 

Costello welcomes the measure, but is clear that it is far from sufficient. While the US government has continued to dither on testing, the UK government has announced plans to make test-kits available to millions. “I’m worried about the immune response tests they are bringing in. These tests might only become positive a week or two after infection. So they are not a good diagnostic test for active infection. If a health worker tests negative and, reassured, goes back to work they might be actively infectious.” 

Further, there is no central coordination for the testing. Costello thinks immune tests will give useful population information but may not give data to authorities which they can use to systematically trace contacts, isolate cases, and contain outbreaks.

He points out that in East Asia – Singapore, Taiwan, Hong Kong and beyond – while there have been new outbreaks, their coordinated mass test-trace suppression strategies have proven that a huge resurgence of COVID19 is not necessarily inevitable. The approach means that when outbreaks do reoccur, they can be more effectively contained.

But what about the resurgence of cases, I wonder, occurring in Hong Kong, South Korea and other places? Hong Kong, for instance has had to resort to stronger lockdowns to suppress a sudden upsurge in new cases as restrictions were relaxed.

Costello points out that their success in minimalising fatalities, and their capacity to move fast to identify and isolate outbreaks, puts them in a better position to respond. 

“We are playing for time”, says Costello. And it’s in that that we can learn more about the virus. “We don’t know yet how many asymptomatic people are being infected and building immunity. With these people identified they can get back to work. We don’t how much herd immunity has been created. The more we learn, the more we can get our economy going a bit more with careful monitoring for outbreaks. And we don’t know when a vaccine will arrive.”

What does the next 18 months look like then? In Costello’s view, with the right strategy, it doesn’t need to be a permanent, full-scale lockdown – but this can only be achieved with a nimble, adaptive approach based on the interplay between mass testing, tracing and isolation, and the data that can be developed from doing so.

“The strategy is to firstly get suppression as in China, South Korea, Hong Kong and so on, which takes about two months. And to save lives and not overwhelm the health services in this first phase. Secondly, this buys time to explore other medium strategies for loosening the  lockdown, depending upon the data on immunity and ways to get the economy moving. Thirdly, you get a safe vaccine.”

I ask Costello about the ‘herd immunity’ controversy. Is it possible that we might develop sufficient levels of immunity in the population that prevents the disease from being a problem? Is that how we will eventually beat this? Or are we doomed to have this virus surge back every time we relax restrictions?

In the long run, he told me, it might be possible that populations do eventually build up immunity to the virus. 

“The general idea that we might eventually build up herd immunity has a certain plausibility in the sense that lots of viruses spread around and a lot of people get sub-clinical infections, and immunity can build up that way. It’s a phenomenon that’s well known. We know well that when most of the population are infected and asymptomatic, this can happen. My view is that the truth of what’s in store may lie somewhere in between the Oxford and Imperial models. The bottom line is that we don’t know the quality of that immunity that we get after recovering from this coronavirus, and how long it will last. Virologists say that generally we don’t get long-lasting immunity from coronaviruses. We might also get new strains due to mutations. So even if lots of people have been exposed, we don’t know the quality of the immunity, there may still be a second surge. There are all sorts of unknowns.”

Costello comes back to the importance of coordinated testing. “We need to go out and do mass testing for the virus in communities. This tells us who has it, and where. That information can be given back to communities so authorities and citizens know what’s happening in their area. Whether it’s a nasal swab or an antibody test, we need to do this so that we can base our strategies on actual data. We can only go so far with theoretical models.”

Herd immunity or not, Costello is clear that it is a huge mistake to simply let the virus run. The biggest danger is that if the virus is allowed to simply spread without controls – as it had been for nearly two months – the overwhelming impact on healthcare facilities due to the sheer number of cases requiring hospitalisation could drive fatality rates much higher than anticipated, as is happening in Italy. The model’s warning of the risk of millions of deaths in such a scenario are, Costello says, very possible.

“If I was advising the government, I would give people a more feasible lockdown period as long as we are very strict. That, as in Asia, we can get this under control in about two months. Even Wuhan is starting to open up. My fear is that we will now have a longer lead-time to achieve this, because we have already let it run. But if we focus on an 8-week challenge, with mass testing to inform a systematic approach to tracing and isolating, we may not need an 18-month lockdown.”