Thursday, April 30, 2020

Dry Bones: Life in the Time of Corona

Nikki Haley: China’s coronavirus actions are just one of many threats it poses

By Nikki Haley 
April 30, 2020 

Nikki Haley was the U.S. representative to the United Nations in 2017 and 2018.

“I tell you it is no use arguing with a Communist. It’s no good trying to convert a Communist or persuade him.”
— Winston Churchill

As the Soviet Union was spreading its control over Eastern Europe following the Second World War, then-former British prime minister Winston Churchill was prophetic in his description of what it would take to outlast the Communist empire without resorting to war.

“The only thing to do,” Churchill continued, “was to convince them that you have superior force . . . and that is the greatest chance of peace, the surest road to peace.”

At the time, Churchill’s prophesy was unwelcome in the war-weary West. Still, successive U.S. presidents largely adhered to his advice. The Soviet Communists were never converted or persuaded. They were defeated, mostly without war, by superior Western economic, diplomatic and military power, and by a more determined and inspiring vision of humanity.

Today’s challenge from the Chinese Communists must be seen the same way.
As in Churchill’s time, most Americans don’t want to hear about epic threats. We are weary of perpetual battles with terrorists and the massive dangers and disruptions associated with today’s pandemic.

But such threats don’t wait until we are ready for them. Like the pandemic, they arrive on their own timeline.

With lies and coverups, China will continue to try to hide its responsibility for failing to contain a virus that began in Wuhan, is killing hundreds of thousands worldwide and doing untold economic destruction.

But deceit about the virus is not the worst danger Chinese Communism poses. It is just its most glaring symptom. A virus can start in any country. The threats coming from China do not come from any other country.

 In the past month alone, China has brazenly expanded its reach. In Hong Kong, it has arrested leading pro-democracy activists and is attempting to criminalize criticism of the Chinese government. It is increasing its hostile actions in the South China Sea, which one-third of the world’s shipping passes through. And the State Department has reported concerns about Chinese nuclear weapons testing in violation of the Comprehensive Nuclear Test Ban Treaty.

That’s just the past month. China has a years-long track record of brutality and aggression.

Domestically, it has vastly enlarged its military capabilities, created an Orwellian surveillance state and forced more than 1 million of its minority citizens into “re-education” camps.

Internationally, it has stolen intellectual property at unprecedented levels, taken over United Nations agencies such as the World Health Organization, exerted its leverage over poor countries with terrible debt deals and harassed its Asian neighbors, none more so than the free people of Taiwan.

The free world ignores this pattern at our peril.

From the 1970s through the Obama administration, U.S. leaders from both parties operated under the theory that as China grew stronger economically, it would become more free and less aggressive, as had happened in other countries. However, in the case of China, that theory was disastrously wrong. As it gathered economic strength, China moved in the opposite direction, becoming less free and more aggressive.

Why was China different? Go back to Churchill’s explanation. The Communist Party thoroughly controls China’s military, commerce, technology and education. Everything its leaders do is aimed at expanding the party’s power. It is why they ethnically cleanse minorities. Why they impose a surveillance state. Why they cannot tolerate freedom in Hong Kong. Why they insist they will take over Taiwan. Why they claim South China Sea territory that is not theirs. Why they steal intellectual property. Why they seek to dominate poor countries and international organizations. Why they expand their nuclear arsenal. China is a dangerously different power because it is steadfastly committed to a Communist ideology that views its system as superior and seeks its advancement in every way.

China is far from the U.S. homeland. But America’s security depends on preventing distant powers from amassing enough strength to threaten us. In the past hundred years, we have stopped Germany twice and the Soviet Union for that reason. Now we face an expansionist Communist China whose economic power vastly exceeds anything the Soviets had during the Cold War. It is manifestly in our security interests to counter this threat.

This is not America’s challenge alone; free countries must unite to face it. In the Pacific region, Japan, India and Australia recognize the Chinese danger. Our European friends have been slower to the cause, but Chinese duplicity on the novel coronavirus is waking them up. Developing nations that once bought into China’s false generosity are now seeing through a clearer lens.

Focusing on China’s reprehensible actions in this pandemic is necessary, but the virus is just a small part of the threats China poses. The sooner the world recognizes that, the better prepared it will be to stop it. And as Churchill noted, preparation is the surest road to peace.

Wednesday, April 29, 2020

People Are Willing to Risk Their Lives for a COVID Vaccine. Should We Let Them?

“The death toll indicates there’s absolutely a strong ethical case to ask people if they’re willing to do this.”

By Shayla Love   

There are currently more than 3,900 people willing to be infected with the new coronavirus—if it could mean developing a vaccine more quickly. 
The volunteers have signed up through the grassroots organization 1 Day Sooner to show their support for human challenge trials, a kind of study where subjects are intentionally exposed to a pathogen to see if a treatment works. This differs from a typical vaccine clinical trial, where people given a new vaccine wait to be infected naturally—part of the reason why vaccine trials can take years.
While 1 Day Sooner is not affiliated with any group officially making or studying coronavirus vaccines, more researchers and lawmakers are speaking out about the potential benefits of doing such trials. In March, Rutgers University bioethicist Nir Eyal argued in the Journal of Infectious Diseases that human challenge experiments would speed up the vaccine development process, and last week in Vaccine, Stanley Plotkin, a vaccine expert at the University of Pennsylvania and Arthur Caplan, a bioethicist at New York University, outlined how coronavirus challenge trials could be carried out. Also last week, a bipartisan group of 35 U.S. Representatives sent a letter to the Food and Drug Administration (FDA) and Department of Health and Human Services (HHS) calling for them to support human challenge trials.
There are more than 70 vaccine candidates right now, but the most optimistic estimates for when a coronavirus vaccine might be available to the public are between March and August 2021. We’ve done human challenge studies before for less deadly diseases, like influenza. But the risks of challenge trials are real. In 2001, a 24-year-old woman died in a challenge experiment for an asthma treatment. Researchers who conduct human challenges have said a COVID-19 trial would be riskier since there’s so much we still don’t know about it.
“Where you’re going to give somebody a virus on purpose, you really want to understand the disease so that you know that what you’re doing is a reasonable risk,” Matthew Memoli, an immunologist at the U.S. National Institute of Allergy and Infectious Diseases who conducts human challenge studies of influenza, told Science Magazine.
The pandemic has already altered or sped up many of the fundamental processes that guide scientific research, from the reliance on preprint studies that are not peer reviewed to the testing of interventions without clinical trial evidence. Some scientists have worried that taking these short cuts could lead to greater health risks and confusing data.
VICE spoke to Caplan, the bioethicist and co-author of the Vaccine paper, about why he thinks human challenge trials are still worth the risk.
This interview has been edited for length and clarity.
VICE: There’s been a lot of discussion about the best ways to proceed with research and trials given that we need solutions as soon as possible, but we also don’t want to put people in danger or do shoddy science. You and Stanley Plotkin wrote in Vaccine that "extraordinary diseases require extraordinary solutions." Can you define what you mean by "extraordinary?" What other situations from the past would you also classify as extraordinary?                We’ve got one of the most highly infectious viruses we’ve ever seen, combined with very serious fatality, and serious [health consequences] even if you survive it. This is a public health challenge that the World Health Organization classified as a "Public Health Emergency of International Concern." When those get declared, that’s the kind of trigger for me to call something an extraordinary circumstance.
We have some precedents. Ebola was threatening to become this. Swine flu, smallpox, yellow fever, polio. These were infectious diseases that created tremendous health burdens for which we don’t have treatments and for which there’s nothing that can be done other than behavior modification— isolation, quarantine, those sorts of things.
What you’re calling for in response to this is a human volunteer challenge study. Can you describe what makes this different from a typical vaccine clinical trial? 
Normally in vaccine development, you start out in the lab and you find something that seems to attack the virus in a Petri dish—either kill it or stop it from growing, proliferating and invading cells. Then you move on to try it in animals to see if what looks like it might be useful in a dish has any sort of biological impact.
Then, you try it in human volunteers in safety studies. Those are normally just healthy volunteers and you're looking to see if there's any adverse events at very low doses—you're not looking for any benefit or protection [from the virus]. Then you start to escalate up [to] a little bigger dose.
Now you might start to look to see if the vaccination does anything that seems to trigger any kind of immunity. If all that works, and you're still pretty sure nothing bad has happened, you go to a big trial for vaccines. You're looking over time in the vaccinated people, compared to a group of people who didn't get vaccinated, if they seem to get the disease less often and, if they get it, does it seem to be less severe?
But you're depending on nature to infect those people. They just wander around and do whatever they're doing. If they happen to get infected, then you study to see whether that group is less sick or less dead than a comparable group. And that can take many, many years. That's why vaccine development is slow.
The clinical trials that are taking place right now are happening in this framework?                                                                                                Yes. The challenge study tries to shorten things in two ways. One, you may shorten the animal study period and jump into volunteers that are humans and literally challenge them for safety with doses that you think are very low, but you haven't really proven it in the animals. That speeds you up by months.
You're probably restricting who you try—people that are 20 to 35, because the death rate is much lower than older people. And obviously you wouldn't do it in kids because they can't consent to this kind of no-benefit safety exposure.
If things look okay, instead of waiting for people to get naturally infected, which may take years to see a significant number of cases, you deliberately give the disease to people who have been vaccinated to see whether they are protected.
How would you decide what kind of volunteers for a human challenge study would be ethical to accept? 
First, you need to have competent researchers. Not somebody like Elon Musk or Peter Thiel setting up a vaccine study in a hotel room in Saint Kitts, which has happened. We don't want that. We need to have real, experienced vaccine experts doing this. You have to have people who can make very high-quality doses of the vaccine and the virus itself.
You need to have a place where you can let people reside so you can watch them and make sure that, at the first sign of trouble, they get either medical care or get isolated. You want to have some sort of dedicated medical research facility.
Then you want to make sure that the people in the study are actually fit physiologically. You have to examine them and make sure they don't have any underlying diseases that might make them more at risk [to the virus]. Then you want to make sure their consent is sound. You want to make sure that they get the information about the risks and that they could die.
You need to have the consent done a couple of times to verify it and have somebody look at it who is there as an advocate for the person [and] who doesn't care if they sign up or not. I sometimes call it a subject advocate. We use them in things like living kidney donation to make sure that the person really wants to do it.
In addition to written consent, I would make them answer a quiz that shows they really comprehend what's going on. You want to make sure if you're going to volunteer for a high-risk study that you really know what's happening, you understand it's not going to benefit you.
In my view, you probably are not going to pay them except expenses because you don't want anybody signing up just for money. You would give them their meals and their housing, but you don't want to incentivize them to say, “Oh I’ll sign up for this because they’re giving me a million dollars.” You could offer them compensation for death, which isn't just to reward their bravery, but also to kind of bring home the fact that you could die.
It is possible that somebody could die doing this, and you argue in the paper that people will also die if the vaccine trials take too long. From an ethical standpoint, how do you go about making death count comparisons? Is it a difficult rationalization to make in your mind when either way you’re still talking about human lives?
In this case, it’s not a really difficult calculation. We’ve already seen over 50,000 deaths in the U.S. If we go at the pace that vaccination normally takes, it's probably four to five years to get everything done. We’re presuming the virus rebounds aren’t going to come back less nasty. The [death toll] indicates there's absolutely a strong ethical case to ask people if they're willing to do this. There is a group that formed to see whether people would be willing to do it. It’s called 1DaySooner and they already have over thousands people after just a week of looking.
1DaySooner is a grassroots effort that's not affiliated with any of the groups or companies developing the vaccines. What do you think about this initiative coming from the community, instead of experts, and have you vetted their consent process at all? 
I've talked to them loosely. They haven't gotten to the point of developing a consent form, they’re just saying: Would you be willing to do this? This group has been involved with living organ donation, that’s the background of the founder, so they know a little bit about consent and doing risky things to benefit others. But I absolutely think [experts should be involved]. You’d have to really subject this to careful review. I’m not even saying that this is the pool of people you’d use, there may be a whole slew of other people who volunteer.
During the pandemic, a lot of the ways we do other kinds of science have been sped up, or changed. For example, we've been relying a lot on preprint papers, partly out of necessity. But it means we're not able to go through the normal peer-review process. We've gotten some really interesting work out of that, but there have been some problems too—like questions about the French hydroxychloroquine studies or theSanta Clara antibody study . Are human challenge studies in the same realm as this? Do you consider it a shortcut that could potentially lead to some issues?  
Challenge studies have been done in the past—it's not like no one ever did them. Even Walter Reed’s yellow fever experiments involved infecting Reed and his coworkers with mosquito bites from mosquitoes known to have yellow fever. There have been challenge studies for pollution, industrial products, household products.
What you’re describing we wouldn’t normally put up with except under extreme conditions. Challenge studies we have put up with even without extreme conditions.
In Science, Alex London and Jonathan Kimmelman wrote a paper titled "Against Pandemic Research Exceptionalism," where they argued that a crisis is not an excuse for changing our scientific standards. 
And I agree, and point out that these challenge studies are not a change in science. We’re not calling for no consent or no review. We’re not calling to abandon the ethics that have governed research. I don’t think we should run around deliberately injecting people. You wouldn't want to do these studies in poor nations where they might be exploited. But it’s wrong to think that we’ve never done the challenge study work that we have.
I’m seeing a kind of distinction you’re arguing for, which is that there’s science that's accelerated or rushed, but then what you're talking about is a study that’s more risky but not necessarily with lower scientific standards. 
Exactly. I think people worry, “Well are they going to go do this to prisoners or poor people?” No. We’re not arguing for any suspension of the ethical rules on how to do experiments. We may be arguing that the risk/benefit facing the world justifies offering the opportunity, but no one would be forced coerced, tricked, exploited.
So because a human challenge trial carries higher risk, the study design and ethical considerations would be more rigorous?
To the highest standard. There’s no way you're going to launch a [human challenge trial] without the absolute best experts agreeing with the design. We can't afford to have muddied results about the only thing that's going to ultimately save us from this plague.
And, as strange as it may seem, the toughest ethics questions aren't just asking someone to knowledgeably, competently consent in an informed way. I think we can get that, I'm sure we can get that. Look at the kinds of work people are already doing: First responders going in with inadequate equipment and taking the same risk we're talking about. Those people are out there, we’re calling them heroes.
What I am worried about is that we better figure out that the science is sound enough that we can get the benefits in a quick enough way through manufacturing that we think are worth doing. It may be that you get a wonderful vaccine and it takes five years to make a million. That's not good. You don't ask people to take that [infection] risk if you're never able to make the thing in bulk.
The stakes are too high to chase a number of different vaccines and try to test them all. We've got to get it right as to which one's the best. Knowing, by the way, we almost never get anything close to 100 percent efficacy. We’ll have a decision to make: If you do the challenge study and let's say 60 percent of people respond. Is that good enough? I'd love to have that problem. But it is a problem.
Then we’ll have to watch a subsample of people just to make sure there's no side effects from the vaccine later on. And that we could make this in big enough quantities that would make a difference.
What do you make, ethically, of some of the more radical claims that taking risks is worth it, like the reopening Southern states or the Las Vegas mayor offering her entire city's population as a control group to see what happens when people don't have social distancing. 
If somebody was to offer their city, offer their grandparents, to be experimented on, I think that they should go first. I mean, it’s silly. You don’t volunteer others. You don’t say, “Hey, the people who own the casinos in my town are willing to kill the workforce.” Come on.
That seems like a good ethical baseline: You don’t volunteer others. 
You can’t decide to just let this thing sweep through and knock out the weak. And it’s easier to [suggest] if you’re going to be isolated inside a hotel with pretty good room service or living in a mansion on the outskirts.
There is another situation here which is that, while we're bemoaning stretching the research in trying to get a fast answer to various antiviral drugs that are rattling around, we at the same time allow the president to stand up for two hours every day and direct absolute nonsense at the population with no one standing there to correct his risk and benefit calculations. Instead we try to interpret if Tony Fauci is grimacing or Dr. Birx is frowning. In a society that is willing to tolerate letting people poison themselves because they're afraid to take on the president, arguing about a challenge study seems a bit of a luxury.

Tuesday, April 28, 2020

Marco Rubio: China's threat to U.S. national security is not a game

Two years ago:

If the world’s most powerful country is a dictatorship, a country that has no respect for privacy, a country that has no respect for free speech, a country that has no respect for religious liberty of its own people, a country that has no regard for human rights anywhere in the world. If that is the most dominant nation on Earth, what do you think the world is going to look like in 20 or 30 years?

Monday, April 27, 2020

Boris Is Back!

I am sorry I have been away from my desk for much longer than I would have liked

and I want to thank everybody who has stepped up
in particular the First Secretary of State Dominic Raab
who has done a terrific job
but once again I want to thank you
the people of this country
for the sheer grit and guts
you have shown and are continuing to show
every day I know that this virus brings new sadness and mourning to households across the land
 and it is still true that this is the biggest single challenge this country has faced since the war
and I in no way minimise the continuing problems we face
and yet it is also true that we are making progress
with fewer hospital admissions
fewer covid patients in ICU
and real signs now that we are passing through the peak
and thanks to your forbearance, your good sense, your altruism, your spirit of community
thanks to our collective national resolve
we are on the brink of achieving that first clear mission
to prevent our national health service from being overwhelmed
in a way that tragically we have seen elsewhere
and that is how and why we are now beginning to turn the tide
If this virus were a physical assailant
an unexpected and invisible mugger
which I can tell you from personal experience it is
then this is the moment when we have begun together to wrestle it to the floor
and so it follows that this is the moment of opportunity
this is the moment when we can press home our advantage
it is also the moment of maximum risk
because I know that there will be many people looking now at our apparent success
and beginning to wonder whether now is the time to go easy on those social distancing measures
and I know how hard and how stressful it has been to give up
even temporarily
those ancient and basic freedoms
not seeing friends, not seeing loved ones
working from home, managing the kids
worrying about your job and your firm
so let me say directly also to British business
to the shopkeepers, to the entrepreneurs, to the hospitality sector
to everyone on whom our economy depends
I understand your impatience
I share your anxiety
And I know that without our private sector
without the drive and commitment of the wealth creators of this country
there will be no economy to speak of
there will be no cash to pay for our public services
no way of funding our NHS
and yes I can see the long term consequences of lock down as clearly as anyone
and so yes I entirely share your urgency
it’s the government’s urgency
and yet we must also recognise the risk of a second spike
the risk of losing control of that virus
and letting the reproduction rate go back over one
because that would mean not only a new wave of death and disease but also an economic disaster
and we would be forced once again to slam on the brakes across the whole country
and the whole economy
and reimpose restrictions in such a way as to do more and lasting damage
and so I know it is tough
and I want to get this economy moving as fast as I can
but I refuse to throw away all the effort and the sacrifice of the British people
and to risk a second major outbreak and huge loss of life and the overwhelming of the NHS
and I ask you to contain your impatience because I believe we are coming now to the end of the first phase of this conflict
and in spite of all the suffering we have so nearly succeeded
we defied so many predictions
 we did not run out of ventilators or ICU beds
 we did not allow our NHS to collapse
and on the contrary we have so far collectively shielded our NHS so that our incredible doctors and  nurses and healthcare staff have been able to shield all of us
from an outbreak that would have been far worse
and we collectively flattened the peak
  and so when we are sure that this first phase is over
and that we are meeting our five tests
  deaths falling
 NHS protected
  rate of infection down
  really sorting out the challenges of testing and PPE
avoiding a second peak
then that will be the time to move on to the second phase
in which we continue to suppress the disease
and keep the reproduction rate, the r rate, down,
but begin gradually to refine the economic and social restrictions
 and one by one to fire up the engines of this vast UK economy
 and in that process difficult judgments will be made
and we simply cannot spell out now how fast or slow or even when those changes will be made
though clearly the government will be saying much more about this in the coming days
 and I want to serve notice now that these decisions will be taken with the maximum possible transparency
 and I want to share all our working and our thinking, my thinking, with you the British people
 and of course, we will be relying as ever on the science to inform us
as we have from the beginning
but we will also be reaching out to build the biggest possible consensus
across business, across industry, across all parts of our United Kingdom
across party lines
bringing in opposition parties as far as we possibly can
because I think that is no less than what the British people would expect
and I can tell you now that preparations are under way
and have been for weeks
to allow us to win phase two of this fight as I believe we are now on track to prevail in phase one
and so I say to you finally if you can keep going in the way that you have kept going so far
 if you can help protect our NHS
to save lives
and if we as a country can show the same spirit of optimism and energy shown by Captain Tom Moore
who turns 100 this week
 if we can show the same spirit of unity and determination as we have all shown in the past six weeks
 then I have absolutely no doubt that
we will beat it together
we will come through this all the faster
 and the United Kingdom
will emerge stronger than ever before

My comment:

"Boris is Back!" is my reference to September 3, 1939 when Chamberlain appointed Churchill First Lord of the Admiralty and the fleet signaled "Winston is Back!" 

However,  I think he is partly responsible for the high death rate since he did not impose the lockdown earlier and my understanding how that happened can be found here. He will definitely suffer  political consequences, but he has learned his lesson.

Friday, April 24, 2020

1_DAY_SOONER COVID-19 Human Challenge Trials


                How could challenge trials help speed up vaccine development?

Excerpts from

The proposed trial method would potentially cut the wait time for the rollout of an efficacious vaccine. Challenge studies (which always directly expose all participants to a pathogen to assess efficacy) generally require fewer participants, followed over a shorter period than do standard efficacy studies (in which many participants are never exposed). Rollout of an efficacious vaccine to age groups not included in the challenge studies may depend on immunological bridging, but this would be a component of the expanded safety studies discussed above. It is possible that this process could take several months shorter than reliance on standard phase 3 testing to assess efficacy. While rollout to other populations might require initial bridging studies, these could be conducted relatively quickly.

It seems clear that, in the absence of an efficacious vaccine, the global death toll from COVID-19 will be enormous. A recent modelling study suggests that, even with mitigation strategies focusing on shielding the elderly and slowing but not interrupting transmission, there may be 20 million this year [10]. If the use of human challenge helped to make the vaccine available before the epidemic has completely passed, the savings in human lives could be in the thousands or conceivably millions. Intense social distancing and related control measures, held in place for many months between now and the availability of vaccine, will themselves take a toll on economies, societies, and population health. Advancing the registration and rollout of an efficacious vaccine, even by a few months, could save many thousands of lives, and commands enormous societal value.

But a remaining key question, for deeming human challenge studies ethical, pertains to risk. Are the risks to participants, even when they are justified by the social importance of the trial and backed by participants’ willful permission, also being kept to the necessary minimum? And do the risks fall below a postulated cap on the acceptable risk of medical trials, even ones of the highest social value and with participants’ consent [15]?

The proposed challenge studies seek to contain the risk to participants in 6 different ways. First, the study will recruit only healthy patients from age groups in which the risk of severe disease and death following SARS-CoV-2 infection is low. Second, there is the possibility that the vaccine candidate will protect at least some of those who are vaccinated. Third, in the absence of an effective vaccine, a high proportion of the general population is likely to be naturally infected with SARS-CoV-2 at some point [17], including those who might participate in a challenge study; by volunteering to be artificially infected they may be just hastening an event that is likely to occur in later months anyhow. Fourth, only people with an especially high baseline risk of getting exposed during or soon after the trial period should be recruited (eg, people residing in areas with high transmission rates). Fifth, participants would be monitored carefully and frequently following the challenge and afforded the best available care if needed (eg, guaranteed access to state-of-the-art facilities of the health system, notwithstanding the possibility of severe shortages of medical care during the evolving pandemic). Sixth, by the time vaccine candidates are being tested, some therapeutics may be approved, which may reduce participants’ risk of morbidity and mortality further. For these 6 reasons, mortality and morbidity from participation notwithstanding, net mortality and morbidity from participation should remain low or negative.