Archive for the 'Science and Medicine' Category

Jul 20 2021

We’re Losing the Vaccine Race

In February on SBM I wrote about the Race Against Vaccine Hesitancy. At that point in time the pandemic was receding in the US in the face of a rapid vaccination program, but also the first new variants of SARS-CoV-2 were starting to appear. Essentially I argued that we were in a race between achieving herd immunity and the spread of new variants that might be more contagious or even vaccine resistant. Experts believed that we would know the answer by Summer.

Well, Summer is here, and the answer is in. We lost the race. Vaccine hesitancy won.

This doesn’t mean that the vaccination program has not been massively helpful. It has. As of now 48.6% of the US population is fully vaccinated, with 56.1% having received at least one dose. This includes children under 12, however, who are not currently eligible for any vaccine. A total of 68.3% of adults have been vaccinated, close to the 70% goal set by the Biden administration. From a logistical perspective, this is a success. The program peaked at over 3 million doses given per day. The program meant that the limiting factor was not the availability of vaccines or the ability to distribute and administer them. The limiting factor is people willing to get vaccinated.

While we may have come close, we did not achieve sufficient herd immunity. Part of the problem is that the vaccinated are not evenly distributed throughout the population. Vaccine uptake is patchy, which means there are clusters of unvaccinated people where the virus is free to spread. Arkansas, for example, is only at 35% fully vaccinated.

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Jul 01 2021

In Vivo CRISPR

I know I just wrote about CRISPR, the powerful gene-editing tool that can make targeted specific alterations to genes, but there is another CRISPR news item I wanted to write about. A recent study published in the NEJM reports the results of a treatment trial using a CRISPR-Cas9 treatment injected into the blood. This is an important proof of concept with implications for the clinical impact of CRISPR.

The study itself involved a rare genetic disease called Transthyretin amyloidosis, also called ATTR amyloidosis, which results from the creation of a misfolded protein that causes damage primarily to nerves and heart tissue. From a genetics point of view, this is conceptually straightforward – turn off the gene making the toxic protein and that should fix the problem. CRISPR is really good at that – it can target the specific gene and then makes cuts in that gene to permanently disable it.

While CRISPR technology is extremely powerful, perhaps the bigger challenge is getting the CRISPR-Cas9 into the desired cells. It is easy to do this in vitro (outside the body in a test tube or dish) but harder to get the CRISPR to the correct cells in a living organism. For this we have been relying primarily on viral vectors, viruses which infect cells, delivering the CRISPR.

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Jun 24 2021

EU Report on Glyphosate

Glyphosate is a weed killer widely used by the agricultural industry and also available for consumer use in products like Roundup. Likely because of its widespread use, it has become a political target. It has also become the focus of high profile lawsuits. This means it is essential that we have objective scientific reviews of the evidence on glyphosate safety. People are still free to have varying opinions regarding the use of pesticides in agriculture, but we should be able to agree on the science. But of course we know that often does not happen. People often distort the science to suit their political or legal agenda.

My purpose here is not to cheerlead for weed killers, or defend any corporation, but to have a clear-eyed view of the published science. Fortunately, there is quite a bit of it, and experts have systematically reviewed this evidence with the purpose of distilling it into bottom-line conclusions about the safety of glyphosate. There have been many, but the most recent one, and therefore most up to date, is a thorough review by the European Union (EU). In a June 2021 11,000 page report they conclude that (in their legalese) – “The AGG proposes that classification of glyphosate as for germ cell mutagenicity
genotoxic or mutagenic is not justified.” They make the same determination for glyphosate not being a carcinogen, having reproductive toxicity, or causing organ toxicity. They did retain its classification that it can “cause serious eye damage.” So yeah, don’t get the stuff directly into your eyes. Regarding ecotoxicity, the EU found that glyphosate is generally safe, however they make an exception for aquatic life, concluding that glyphosate is “toxic to aquatic life”. These latter two concerns were already known and present in prior reviews, and so do not represent any change.

Based upon all of this the review recommends glyphosate for approval for use in the EU. Essentially, if used properly, glyphosate is safe for farm workers, consumers, and the environment. Of course the phrase, “If used properly” is doing a lot of heavy lifting there. And this is where a lot of debate can be had. But in that debate it is critical to consider the alternatives to using glyphosate in farming.

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Jun 03 2021

Return of the Bird Flu

Remember the bird flu? Avian influenza (H5N1) was first discovered in birds in 1996, with the first human crossover detected in 1997. Since then it has been discovered in 50 countries and is endemic in six. If you are old enough to remember, there was a bit of a bird flu panic back in the late 90s. Fortunately, so far, those fears have not been realized. But it’s important to remember that the bird flu is still around. Even more important is to remember that there are thousands of potentially pandemic viruses in the world.

Avian influenza adapted to infect birds, and mostly spreads through poultry. Bird to human transmission (zoonotic infection) is rare, and usually occurs in those who work in the poultry industry with long term exposure. The virus is very deadly, with a case fatality rate of about 60%. Worldwide there are 700 reported human cases. However, the virus does not spread easily from human to human. Such transmission is very rare, and is not sustainable. This is why the virus has not caused an outbreak or worse among humans. There are also other strains of flu virus that primarily infect birds, such as H10N5. We now have the first report of an H10N5 infection in a human, in a poultry worker in China. Contact tracing did not reveal any other cases.

For now we have experienced rare bird to human zoonotic transmission of flu strains primarily adapted to birds (colloquially “bird flu”) without any significant or sustainable human to human spread. So what’s the concern? As was originally raised by in the 90s, the concern is that every time a virus jumps from an animal reservoir to a human there is the potential that it will either mutate or will combine with another virus to cause a new strain that is highly contagious to humans. It happens, as we are now experiencing with the SARS-CoV-2 virus. So what do we do about it?

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May 27 2021

Red Flags of a Crank Study

The pandemic has brought into sharp focus the potential danger of misinformation. There are times when we need to act collectively as a society to accomplish certain goals. This is particularly challenging in a society that is organized around a principle of individualism – a principle I endorse and value. Liberty is a precious right to be jealously defended. But it is not the only right, or principle of value. So at times we have to delicately balance various competing interests. I like my freedom, but I also really like not catching a deadly disease, or spreading it to my family.

In a perfect world (one we definitely do not live in) there would be no need for restrictive or draconian measures. All that would be necessary was distributing information – hey, if you want to protect yourself and others, wear a mask, socially distance, wash your hands, and get vaccinated. If you’re really interested, here are the facts, the published studies, the expert analysis, to back up these recommendations. Here are the error bars and level of uncertainty, the risk vs benefit analysis, and comparison to other options.

This approach is necessary, and works to a degree, but it is insufficient. There are two main shortcomings of the information approach. First, people are only semi-rational beings, not Vulcans. We are susceptible to tribalism, motivated reasoning, confirmation bias, and a host of cognitive biases, faulty heuristics, and logical fallacies. Our intuitions about balancing risk and benefit are also flawed, and we have a hard time dealing with very large numbers. Just peruse the comments to any blog post on this site that is even slightly controversial and you will find copious examples of every type of flawed thinking.

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May 17 2021

Regulation of Supplements Lacking

A recent audit of natural products manufacturers in Canada reveals how lacking regulations are in this industry. Scott Gavura does a good review of this over at SBM. I want to amplify some of what he says and add further context.

For background, so that everyone knows where I am coming from, I tend to take a nuanced approach to regulation. I believe in the power of capitalism and a free market to allocate resources in an organic way that will reflect, at least in part, actual merit. But free markets do not exist in a vacuum, they need to be crafted by an agreed upon set of rules. Further, there are always going to be people who try to work the system, bend the rules, and exploit others. Further, the evolutionary forces at work within a free market do not always favor acceptable outcomes. We know from history what happens in unregulated markets (we don’t have to guess) – they lead to fraud, exploitation, and monopoly. People will use wealth and power to rig the system so they gain more wealth and power at the expense of everyone else. The people who do this best will tend to succeed over time. While 1% of the population displays psychopathic traits, the figure is 4-12% among corporate CEOs.

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May 07 2021

COVID Vaccines Are Safe and Effective

We are at a critical point in this pandemic. Worldwide the pandemic is actually more active now than ever. There have been over 156 million cases, and the world is seeing almost 800k new cases a day. The recent peak is mainly due to India, but infections continue throughout the world. The high number of cases also increases the risk of new variants emerging. India also shows us how quickly medical resources can be overwhelmed with catastrophic results. They ran out of oxygen – which is critical to keeping severe COVID patients alive.

Yet, with each wave there was the prevailing sense that this was the worst we’ll get, and now we are rounding the corner. So far, this has been wrong every time. Of course this pandemic must end eventually, the question has always been how much death, morbidity, and economic damage would it cause in the meantime. The primary reason for the next worse wave of the pandemic has largely been that people eased off on pandemic protocols. They stopped wearing masks and social distancing and started gathering in large groups. And each time the virus made us pay for it.

But now, despite being in the middle of the biggest wave so far, the situation is changing, because now we have multiple safe and effective vaccines. In the US there are two mRNA vaccines, from Moderna and Pfizer-BioNTech, in addition to the J&J vaccine. Other than a minor hiccup with extremely rare blood clots, these vaccines have a great safety profile. In states with high vaccine uptake the virus is getting under control, and restrictions are starting to be safely lifted. Life is partly getting back to normal – thanks entirely to the vaccines.

But we are facing two problem – entirely of our own making. The first is that we are in a race against time. We have to vaccinate enough of the world to achieve herd immunity before new variants emerge that are resistant to the vaccines. Also, we don’t know how long immunity from the vaccines last, but it may be something around a year. So when we get to a year out from the first vaccines given, we need to do it all over again with booster shots. Perhaps even more importantly, we are running up against vaccine hesitancy, which may ultimately prevent us from getting to herd immunity. That would be a tragedy.

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Mar 08 2021

COVID Race Against Time

We know a lot more now about SARS-CoV-2 and COVID-19 than we did a year ago when this pandemic was just getting into full swing. One of the big questions was about the emergence of new variants – how fast does the virus mutate, and what is the probability of variants with new properties emerging? Scientists have been tracking the variants since the beginning. It’s actually a good way to track the spread of the virus, and our ability to sequence the genome of specific viruses is fairly advanced.

As of August 2020 scientists had identified six strains or variants of SARS-CoV-2, without any significant difference in biological function among them. This was encouraging – the hope was that this virus mutates slowly and that no functionally new versions would emerge. This is important for two reasons. The first is the question of whether or not someone who has already suffered COVID-19 or been infected without symptoms could become reinfected. This is partly about the strength of the immune response to infection, but also about whether or not new strains would be able to bypass immunity to older strains.

However, by the beginning of 2021 two things were happening, one good, one bad. Vaccine distribution was ramping up. Several vaccines were approved toward the end of 2020 and while initial distribution was slow, it is speeding up. By now almost 59 million Americans have received at least one dose of a vaccine, and we are being promised availability for everyone who wants a vaccine by May. At the same time daily new cases of COVID are dropping fast, although still relatively high compared to the Spring and Summer of 2020.

But the bad news is that three new variants of SARS-CoV-2 have now been identified that are functionally different – one identified in the UK, one in South Africa, and one in Brazil. These variants have several mutations affecting the structure of the spike protein that gives coronavirus its name, and is responsible for its ability to infect cells. Spike proteins are also a target of antibodies produced by infection or vaccine. As news about these variants comes dripping it, it’s not good. All three appear to be more infectious. They spread more easily than the older variants, which means more robust protection might be necessary to prevent spread. Further, because of their increased infectivity, they are rapidly becoming the dominant strains where they spread.

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Feb 01 2021

Protein Switches and COVID Testing

Researchers report in Nature the development of a new technique for designing protein switches that can be used as biosensors. The recent development of the technology to design specific protein switches is an underreported story, in my opinion, and represents a technology with incredible possibilities. Reporting on the recent study emphasizes one possible application – development of a new rapid test for SARS-CoV-2. It is understandable why this would garner the most interest – but the underlying technology is perhaps a bigger science news story.

A protein switch is simply a protein that can change its 3-dimensional configuration in response to binding with something, such as another protein or a hormone or some biological signal. When a protein changes its configuration, it changes its function. This can turn a function of the protein on or off, open or close a pore or channel, or alter its activity. Protein switches are a basic component of biological function as they allow for the sensing of internal biological states and reaction to those states by altered cellular function.

It was only in 2019, less than two years ago, that scientists reported the design and creation of the first completely artificial protein switch. Again, this story did not make a huge splash, but looking back this may have been as momentous as the development of CRISPR as a tool for genetic engineering. It’s hard to tell how much of a long term impact it will have – but just as CRISPR (and related tools of genetic engineering) gives us unprecedented control over a fundamental aspect of biology (genetics), protein switches also potentially give us a similar level of control, arguably more direct.

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Jan 19 2021

Be Skeptical of Video Showing Vaccine “Side Effect

This was inevitable. We are in the midst of a massive rollout of two new vaccines for COVID-19. Anxiety and fatigue levels from the pandemic are already running high, and there is a pre-existing anti-vaccine movement who is sure to exploit this. But perhaps most significantly, we are now living in a post-social media world. Information, even medical or scientific information, may get to the public unfiltered, ripe to be misinterpreted by people who do not understand the relevant science. Such is the case with a “viral” video showing a woman who claims her symptoms are a side effect of the Moderna vaccine (short answer – they almost certainly are not).

Messaging is critical to the success of public health measures. Normally information about possible side effects from a drug or vaccine would be filtered through medical experts. When millions of people are involved there is going to be a lot of noise. Coincidence alone would result in many negative outcomes occurring by chance alone shortly after getting a vaccine. Epidemiologists need to look for patterns in the data that indicate there is likely to be an actual causal relationship to the vaccine. It helps if there is also a plausible mechanism. This system has captured vaccine side effects in the past, so you cannot reasonably argue that the system is rigged not to find such associations. The swine flu vaccine in the 1970s caused cases of Guillaine Barre Syndrome. A specific flu vaccine (Pandemrix – no longer on the market) likely caused cases of narcolepsy in 2009. So if any of the current COVID vaccines have a similar side effect, we will catch it.

Reporting scary anecdotes that have not been scientifically evaluated to the public is not a good idea. This is likely to misinform rather than inform, and will have a death toll attached to it. But with social media there is no way to stop this from happening, so we just have to do damage control when it does.

As a side note, I have to point out that I usually refrain from commenting on a specific individual’s medical condition in public. This is to respect the privacy of those individuals, and also because if I have not personally examined them and taken their history, commenting is inappropriate. But medical science communicators can comment about topics relevant to a public case or issue. I can speak generally about the relevant topics. There is also an exception when a private person puts their own medical history into the public domain, especially if they also use that history to make recommendations to the public, and doubly so if those recommendations are false and harmful. They have surrendered any expectation of privacy and they have made their own personal history relevant to the discussion about a public health issue. That is the case here.

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