The BBC headline reads: Immune discovery ‘may treat all cancer’. Most health headlines, even of legitimate scientific discoveries, tend to be overhyped. All health discoveries, apparently, will either eventually cure cancer or the common cold. This headline is also overhyped, in my opinion, but this is a legitimate discovery with possible implications for future cancer treatment.

What the scientists discovered was an immune receptor which seems to target most cancer cells while not targeting healthy cells. This certainly seems like the kind of thing that can potentially be exploited in immune therapy for cancer. The actual title of the study is: Genome-wide CRISPR–Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1.

The CRISPR angle is interesting, and not mentioned in the BBC article. It is another example of how CRISPR is turbocharging genetics research. The researchers used it to comb the genome and they found a receptor found on T-cells, the MR1, that seems to target all cancer cells but not non-cancer cells. Further, the targeting seems to be via the cancer cell metabolism. Somehow the receptor is sensing the altered metabolism of the cancer cells. Importantly, it is targeting a feature of that metabolism that is common to most if not all types of cancer:

“The Cardiff team discovered a T-cell and its receptor that could find and kill a wide range of cancerous cells in the lab including lung, skin, blood, colon, breast, bone, prostate, ovarian, kidney and cervical cancer cells.”

This is the point where I need to emphasize that this is basic science research, not clinical research. It is also very early research, which means it has opened up a long list of further research questions that need to be answered. I have been in the field long enough to develop a sense of where research is in the arch of progress from basic science to the clinic. The immunotherapies for cancer that have been coming out in the past few years I first heard about in the 1990s. A 20-30 year delay from when basic science research first suggests a possible treatment, to treatments being approved for clinical use, is typical. The pace may be increasing a bit because of the technology of basic science research. CRISPR is an excellent example of this. But clinical research just takes time. It needs to progress from animal research through multiple stages of human research, even for a single indication. Then subsequent research is necessary to further understand how the treatment works for which diseases and which patients.

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This is going to be a long struggle, perhaps endless. Antivaxxers have been around since there have been vaccines, for over two hundred years, so there is no reason to expect they are going anywhere. Rather, we need an equally permanent anti-antivaxxer movement (otherwise known as the skeptical movement).

After the Disneyland measles outbreak, there has been political pressure to push back against antivaxxers and strengthen our vaccine requirements. This resulted, for example, in SB277 in California, a law to remove personal beliefs as a reason for vaccine exemption. The return of measles in the last few years (1,282 cases in 2019 in the US, more than 140,000 worldwide) has fueled similar push back. But the antivaxxers have not taken this lying down. They are now fired up to defend their debunked conspiracy theories and pseudoscience at the expense of public health.

A recent clash in New Jersey shows the intensity on both sides. Bill S2173 narrowly failed in the senate amid vocal protests by the antivaxxers. The bill would have removed religious exemptions for vaccine requirements for schools and daycare. In order to save the bill, proponents amended it to apply only to public schools, but this only cost more support as some senators correctly pointed out this will only concentrate the unvaccinated in private schools and result in more outbreaks. Proponents of the bill vow to revise it and try again.

It’s clear that there is now intensity on both sides. One side, however, is completely wrong, something I rarely say but there are issues where this is clearly true. Antivaxxers claim, falsely, that vaccines don’t work, they cause more harm than good, they are linked to autism and other serious complications, and even that there is a corporate-government conspiracy to hide these facts. Debunking these claims will take many many articles, but fortunately I and my colleagues have already written them. You can look through here and also here for articles addressing pretty much every antivaxxer claim. But it is an unfortunate reality that there is always an asymmetry in these cases, because it takes much more time and effort to debunk a false claim than to make it in the first place.

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In 1988 there were 350,000 cases of polio worldwide. Polio is a virus that attacks the nervous system and can cause paralysis. Effective vaccines had already significantly reduced polio cases in developed nations, but it was still a scourge in poor countries. The World Health Organization (WHO) and others formed the Global Polio Eradication Initiative with the goal of eradicating polio from the world by the year 2000. They were partly successful. Their massive vaccine campaigns reduced the number of cases to 719 by 2000, and by a total of 99.99%, to just 33 cases in 2018. But the program failed to completely eradicate polio, and in this case close (while still a great reduction in disease) is not enough.

Polio is a virus that has the potential to be eradicated, meaning completely eliminated from the world, because there is no non-human reservoir. Other viruses, like ebola, can spread in animals, which makes it impossible to eradicate from the world just by vaccinating humans. So eradicating polio is an achievable goal, and we got real close in 2002. Wild cases of polio were limited to three countries, Nigeria, Pakistan, and Afghanistan. Elimination failed in these countries entirely because of political unrest which itself resulted in anti-vaccine sentiments. The vaccine program was portrayed as a Western conspiracy, reducing compliance.

Since that time the GPEI has been fighting a somewhat losing battle, unable to snuff out the last embers of polio. Unfortunately, in 2019 the effort has faced it worse year since 2000, because of continued political unrest, but also because biology has simply caught up to the effort. The story is a bit complex, but here is the overview.

There are three strains of polio virus, wild type 1, 2, and 3. The primary effort to eradicate polio was through a trivalent live attenuated virus vaccine, one that contains weakened versions of all three polio strains. A live virus vaccine uses viruses that have been genetically gimped, so they can cause a mild infection and strong immunity, but are not virulent enough to cause any disease. There is an advantage and disadvantage to live virus over a killed virus or viral particle vaccine. The live virus in this case causes stronger immunity, enough to fully prevent the shedding and spread of virus. So this is most useful in an eradication campaign, as opposed to simply one trying to minimize disease.

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A recently published ethics paper addresses the issue of whether or not it is proper for crowdfunding sites, like GoFundMe, to allow campaigns to fund dubious medical treatments. This question is also part of a more general issue – how tech companies have replaced traditional industries and institutions thereby bypassing existing mechanisms of safety, justice, and quality control. On the medical issue, the authors write:

Recent studies have shown that many individuals are using crowdfunding to finance access to scientifically unsupported medical treatments. Recently, GoFundMe prohibited campaigns for antivaccination groups on the grounds that they “promote misinformation about vaccines” and for treatment at a German clinic offering unproven cancer treatments due to “the need to make sure people are equipped to make well‐informed decisions.” GoFundMe has not taken any additional actions to regulate the much larger presence of campaigns seeking to fund unproven medical interventions on the platform. In this article, we make the ethical case for intervention by GoFundMe and other crowdfunding platforms.

The basic principle is that tech companies still retain an ethical and legal responsibility for how their platforms and technology are used. Most applications and social media outlets begin as an unregulated peer-to-peer environment, just facilitating an individual exchange between two private citizens. In a way this is a Libertarian nirvana. However, as such applications scale up the downsides that have already had to be dealt with in the traditional industries they are supplanting begin to resurface.

We can take any such app as an example, such as Uber. The Uber app, which I use, is very convenient. They have definitely made a better mousetrap. But as Uber has grown huge, we begin to question what responsibility they have to their drivers and riders. How much do they have to vet drivers to protect riders? What kinds of protections and benefits should they offer drivers? Did they just replace a regulated industry with an unregulated one? The same questions have arisen with Air bnb, which critics warn is being used to simply create de facto hotels that skirt regulations.

There are two principles here. The first has to do with the role of regulations in general to protect the public from exploitation of various sorts. I don’t want to go down that rabbit hole entirely, but just summarize my position as this. I support carefully considered and monitored regulation to keep society functioning optimally and prevent exploitation, externalizing costs, unfair competition, and the like. The only truly free market is a regulated one, because an unregulated market will become increasingly distorted over time as the powerful use their power to obtain more power (rather than play fairly).  At the same time we have to be humble regarding unintended consequences, which is why regulations need to be minimalistic and monitored for their effects. If you buy some version of this basic premise, and are not an anti-regulation purist, then it should be concerning that effective regulations are being nullified by an app. This is happening without any elected representatives of the people making any decisions – without any public representation. In the extreme this can evolve into a tech oligarchy.

The second principle is fairness. If one industry that is regulated is competing with another that is unregulated, that gives an unfair advantage to the unregulated one (regardless of what you think about regulations in general).

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Move over CRISPR – enter Prime Editing.

Maybe. What we can say is that the pace of technological advancement in genetic editing is advancing so quickly it’s hard to keep up. Now a new study, published in Nature, details a new method for editing called prime editing. The authors write:

Here we describe prime editing, a versatile and precise genome editing method that directly writes new genetic information into a specified DNA site using a catalytically impaired Cas9 fused to an engineered reverse transcriptase, programmed with a prime editing guide RNA (pegRNA) that both specifies the target site and encodes the desired edit.

So actually this is built off of CRISPR technology, using a Cas9 component, and then pairing it with a bit of RNA (pegRNA) that both targets the bit of the genome you want to edit and also has the new code you want to insert. Insertion is accomplished by the enzyme reverse transcriptase. How does this compare to existing methods for gene editing? The authors again:

“Prime editing offers efficiency and product purity advantages over homology-directed repair, complementary strengths and weaknesses compared to base editing, and much lower off-target editing than Cas9 nuclease at known Cas9 off-target sites. Prime editing substantially expands the scope and capabilities of genome editing, and in principle could correct about 89% of known pathogenic human genetic variants.”

It is more precise and has fewer errors, and is able to target 89% of known genetic diseases. It cannot fix errors where a gene is entirely missing, or where there are too many copies of a gene. They tested the method on two human genetic diseases in human cells, Tay Sachs and sickle cell anemia, with success.

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In the US we have semi-compulsory vaccination. Keeping up to date on the vaccine schedule is required in order to attend public school. However, families always have the option of attending private schools, which can determine their own vaccination policy, or they can home-school. Also, each state can determine its own exemption policy. Medical exemptions are uncontroversial – if you medically cannot get a vaccine, that is up to your doctor, not the state. However, some states have religious or personal (philosophical) exemptions. These have been under increasing scrutiny recently.

Other countries have different systems. In the UK, for example, there is no compulsory vaccination to attend school.

These policies are all being reexamined in the wake of the burgeoning anti-vaccine movement and the resulting return of previously controlled vaccine-preventable illnesses. Let’s take measles, for example. As you can see by the chart, measles cases have increased by greater than 20 fold from 2010 to 2019 in the US. But if we pull back even further, in 1980 measles caused 2.6 million deaths worldwide, with cases in the US alone measured in the hundreds of thousands. By 2000 routine use of the MMR vaccine had prevented an estimated 80 million cases of measles.

Also by 2000 measles had been eliminated in the US – that means there was no circulating virus in the wild. All cases came from outside the country. Outbreaks were also very limited, because there was no fertile ground for the virus to spread. The antivaccine movement has changed that.

The rate of children getting MMR has not changed much in the US due to compulsory vaccines, ranging from 90-93% over the last two decades. It has dipped to around 91.1% recently, but the overall number remains high. However, this statistic hides what is really going on. Vaccine refusal clusters, by neighborhood and by school. If a private school does not require compulsory vaccination, then anti-vaxxers will cluster there. These pockets of very low vaccination rates then serve as potential locations for outbreaks, and that is exactly what happens. In recent years these outbreaks have been large enough to spread into the general population.

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A recent systematic review and meta-analysis of studies comparing humans to artificial intelligence (AI) in diagnosing radiographic images found:

Analysis of data from 14 studies comparing the performance of deep learning with humans in the same sample found that at best, deep learning algorithms can correctly detect disease in 87% of cases, compared to 86% achieved by health-care professionals.

This is the first time we have evidence that the performance of AI has ticked over that of humans. The authors also state, as is often the case, that we need more studies, we need real world validation, and we need more direct comparisons. But at the very least AI is in the ball park of human performance. If our experience with chess and Go are any guide, the AI algorithms will only get better from here. In fact, given the lag in research, publication, and then review time, it probably already is.

I think AI is poised to overtake humans in diagnosis more broadly, because this particular task is right in the sweet spot of deep learning algorithms. Also, it is very challenging for humans, who fall prey to a host of cognitive biases and heuristics that hamper optimal diagnosis. A lot of medical education is focused on correcting these biases, and replacing them with clinical decision-making that works better. But no clinician is perfect or without blind-spots. Even the most experience clinician also has to contend with an overwhelming amount of information.

There are a couple ways to approach diagnosis. The one in which human excel is the gestalt approach, which is essentially based on pattern recognition. With experience clinicians learn to recognize the overall pattern of a disease. This pattern may include signs or symptoms that are particularly predictive. Eventually the pieces just click into place automatically.

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Acupuncture is defined as an intervention involving placing thin needles into specified acupuncture points in order to relieve symptoms or promote healing. What is special about the acupoints? They are supposed to be locations where the flow of life force (chi) can be manipulated. There are a few problems with the claims made for acupuncture. First, there is no place for vitalism – belief in a life force – in modern science. There is no evidence that it exists and no reason to hypothesize that it exists. It is worse than wrong. It is unnecessary. There is also no convincing evidence, after a century of research and thousands of studies, that acupuncture works for anything.

But also, an independently fatal flaw in the notion of acupuncture is that there is no evidence that acupuncture points exist. They are a complete fiction. They have no basis in anatomy, physiology, neuroscience, biochemistry, or empirical evidence. A recent study highlights this fact – Accuracy and Precision in Acupuncture Point Location: A Critical Systematic Review. This is a review by acupuncturists in the Journal of Acupuncture and Meridian Studies. The authors reviewed the literature for any studies that looked at the precision and reliability of the location of acupoints and found:

Considerable variation in localization of acupoints was reported among qualified medical acupuncturists. Variation in point location among qualified non-medical acupuncturists is unknown due to lack of any identified study. The directional method was found to be significantly inaccurate and imprecise in all studies that evaluated the method.

So acupuncturists cannot agree upon where alleged acupoints actually are on the body, and the primary method to localize them was both inaccurate and imprecise. The simplest explanation for this fact is that acupoints don’t exist. Even if you want to hold out the illogical conclusion that acupoints do exist, even though they have no basis in theory and they cannot be detected by any objective measure, you cannot avoid the conclusion based on this evidence that acupuncturists don’t know where they are. So how, then, can they claim to be able to stick needles into acupoints? Short answer – they can’t.

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This is a great example of the unintended consequences that can result from making decisions based on scientific conjecture and preliminary hypotheses. In this case, the hypothesis was never a good one. If you are a pet owner, you may have noticed the recent trend toward grain-free dog or cat food. The justification for this trend is the notion that since dogs are essentially wolves, and wolves are pure carnivores, then we should not be feeding our dogs grains. This is basically the paleo diet for dogs.

It should be noted, however, that many carnivores do need to get some plant matter in their diet. They may get this from the stomachs of the herbivores they eat. Wolves will also occasionally eat berries as a minor supplement to their diet. But sure, wolves don’t generally eat grains. But that is not the problematic premise here.

The problem with the grain-free diet claim is that while modern dogs are closely related to wolves, they are not wild wolves. They evolutionarily split from wild wolves 15-40,000 years ago. Over that time their diet has shifted significantly. They no longer hunt in packs, but live off the scraps of human civilization. And they have adapted.

So the grain-free theory is flawed, and we should not base dietary recommendations on theory alone anyway, but actually gather evidence to test those theories. Perhaps we already have, in an unintended ecological experiment. In 2018 the FDA noticed a spike in reported cases of dilated cardiomyopathy (DCM) in dogs. Previous years had 1-3 reported cases per year, in 2018 there were 320, and 2019 is on track to exceed this. This is still a small number compared to the millions of pet dogs in the US, but is likely massive underreporting. There is also likely some reporting bias here – one article on social media might explain the spike, rather than a true increase. But the FDA had to investigate the increase to see if it were real and what the cause might be.

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Vitamins are, by actual definition, essential nutrients for humans. They are substances we need but cannot make ourselves from other nutrients, and therefore must consume. Each of the vitamins have a disease resulting from a deficiency of that vitamin. For some there may also be negative health effects from having an insufficiency (less than optimal levels, but not low enough to cause a deficiency state). This is why you should eat your vegetables, and have an overall well-rounded diet – to make sure you get enough of all the vitamins and other needed nutrients.

But of course if there is a way to exploit a fact to make money, someone will do it. In this case an entire industry has emerged to make money by convincing the public they need to take vitamin pills, the more the better. In 2017 the supplement industry in the US reached $36.1 billion a year. Unfortunately, the path to better health is not so simple, and the science simply does not support the vitamin industry hype.

Yet another meta-analysis was just published again demonstrating that routine supplementation is mostly worthless, and may even be harmful. This one is focusing on vascular outcomes, but since heart disease is the #1 killer, and stroke the #3 killer, vascular risk has a major impact on life expectancy. In 2018 I wrote about a meta-analysis published in the Journal of the American College of Cardiology. This study found:

• Multivitamins, vitamins D, C, A, B6, E, calcium, β-carotene, zinc, iron, magnesium, and selenium had no benefit or harm for vascular disease or all-cause mortality.
• Folic acid and B-complex (Folic acid, B6 and B12) reduced stroke risk
• Antioxidants and niacin increased all-cause mortality.

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