How’s that for a provocative title? But it is technically accurate. The title of the paper in question is: “A DNA robotic switch with regulated autonomous display of cytotoxic ligand nanopatterns.” The study is a proof of concept in an animal model, so we are still years away from a human treatment (if all goes well), but the tech is cool.

First we start with what is called “DNA origami”. These are sequences of DNA that fold up into specific shapes. In this case the DNA origami is used to create a nanoscale “robot” which is used as a delivery mechanism for the kill switch. The skill switch is quite literal – a “death receptor” (DR) which is a ligand of 6 amino acids. These exist on all healthy cells, but when sufficiently clustered on the surface of a cell, DRs trigger apoptosis, which is programmed cell death – a death switch.

The DNA origami robot has six such ligands arranged in a hexagonal pattern on the interior of its structure. The DNA, in fact, creates this structure with precise distance and arrangement to effectively trigger apoptosis.  When it opens up it reveals these ligands and can attach them to a cell surface, triggering apoptosis. The researchers have managed to create a DNA robot that remains closed in normal body pH, but also will open up in an acidic environment.

Continue Reading »

On March 16 surgeons transplanted a kidney taken from a pig into a human recipient, Rick Slayman. So far the transplant is a success, but of course the real test will be how well the kidney functions and for how long. This is the first time such a transplant has been done into a living donor – previous experimental pig transplants were done on brain dead patients.

This approach to essentially “growing organs” for transplant into humans, in my opinion, has the most potential. There are currently over 100 thousand people on the US transplant waiting list, and many of them will die while waiting. There are not enough organs to go around. If we could somehow manufacture organs, especially ones that have a low risk of immune rejection, that would be a huge medical breakthrough. Currently there are several options.

One is to essentially construct a new organ. Attempts are already underway to 3D print organs from stem cells, which can be taken from the intended recipient. This requires a “scaffold” which is connective tissue taken from an organ where the cells have been stripped off. So you still need, for example, a donor heart. You then strip that heart of cells, 3D print new heart cells onto what’s left to create a new heart. This is tricky technology, and I am not confident it will even work.

Another option is to grow the organs ex-vivo – grow them in a tank of some kind from stem cells taken from the intended recipient. The advantage here is that the organ can potentially be a perfect new organ, entirely human, and with the genetics of the recipient, so no issues with rejection. The main limitation is that it takes time. Considering, however, that people often spend years on the transplant wait list, this could still be an option for some. The problem here is that we don’t currently have the technology to do this.

Continue Reading »

I was recently asked what I thought about the Solex AO Scan. The website for the product includes this claim:

AO Scan Technology by Solex is an elegant, yet simple-to-use frequency technology based on Tesla, Einstein, and other prominent scientists’ discoveries. It uses delicate bio-frequencies and electromagnetic signals to communicate with the body.

The AO Scan Technology contains a library of over 170,000 unique Blueprint Frequencies and created a hand-held technology that allows you to compare your personal frequencies to these Blueprints in order to help you achieve homeostasis, the body’s natural state of balance.

This is all hogwash (to use the technical term). Throwing out the names Tesla and Einstein, right off, is a huge red flag. This is a good rule of thumb – whenever these names (or Galileo) are invoked to hawk a product, it is most likely a scam. I guess you can say that any electrical device is based on the work of any scientist who had anything to do with electromagnetism.

Continue Reading »

There is a recent medical advance that you may not have heard about unless you are a healthcare professional or encountered it from the patient side – CAR-T cell therapy. A recent study shows the potential for continued incremental advance of this technology, but already it is a powerful treatment.

Like all technologies, the roots go back pretty far. It was first discovered that immune cells protect against cancer in 1960. In 1986 tumor-infiltrating lymphocytes were used to attack cancer cells. In 1993 the first generation of genetically modified T-cells using the chimeric antigen receptor (CAR) technique was developed. This technique fuses the business end of an antibody to a receptor on a T-cell (hence a chimera) which potentially targets that T-cell against whatever antigen the antibody targets. So you can make antibodies against a protein unique to a specific type of cancer, then fuse part of that antibody to T-cell receptors, put those T-cells back into the patient and they will potentially attack the cancer cells. This first generation CAR-T cells were not effective clinically because they did not survive long enough in the body to work.

In 1998 it was discovered that adding a costimulatory domain (CD28) to the CAR allowed it to persist longer in the body, creating the potential for clinical treatment. In 2002 this technique was used to develop second generation CAR-T cells that were shown for the first time to fight cancer in mice (the first study was of prostate cancer). Then in 2003 CAR-T cells using CD19 instead of CD28 were developed, and found to be more effective. In 2013 the first clinical trial in humans showing efficacy of CAR-T therapy in cancer (leukemia) was published, starting the era of using CAR-T therapy in treating blood cancers. The first CAR-T base treatment was approved by the FDA in 2017.

Over the last 8 years CAR-T therapy has become standard treatment for blood-born cancers (lymphoma and acute lymphoblastic leukemia). T-cells are taken from patients with cancer, they are then genetically modified into CAR-T cells, reproduced to make lots of them, and then given back to the patient to fight their cancer. In the last decade scientific advance has continued, with research targeting other proteins to potentially fight solid tumors. In 2017 scientists starting using CRISPR technology to make their CAR-T cells allowing greater control and improved function.

Continue Reading »

Japan is planning on releasing treated radioactive water from the Fukushima nuclear accident into the ocean. They claim this will be completely safe, but there are protests going on in both Japan and South Korea, and China has just placed a ban on seafood from Japan. In a perfect world we would just have a calm and transparent discussion about the relevant scientific facts, make a reasonable decision, and go forward without any drama. But of course that is not the world we live in. But let’s pretend it is – what are the relevant facts?

In 2011 a tsunami (and poor safety decisions) caused several reactors at the Fukushima Daichi nuclear power plant to melt down. These reactors were flooded with water to cool them, but heat from continued radioactive decay means they need to be continuously cooled. The water used has become contaminated with 64 different radioactive isotopes. In the past 12 years 350 million gallons of contaminated water has been stored in over 1,000 tanks on site, but they are simply running out of room, which is why there is urgency to do something with the stored contaminated water. How unsafe is this water?

Over the last 12 years the short half-life isotopes have lost most of their radioactivity, but there are still some long half-life isotopes. This is good because the shorter the half-life the more intense the radioactivity per mass, by definition. Really long half-life isotopes, like carbon-14 (half-life 5,000 years), have much lower intensity. Also, the contaminated water as been treated with several processes, such as filtration and sedimentation. Most of the remaining radioactive isotopes have been removed (to levels below acceptable limits) by this process, although carbon-14 and tritium remain.  How much radioactivity is left in this contaminated but treated water? That is the key question.

Continue Reading »

Decades of complex research and persevering through repeated disappointment appears to be finally paying off for the diagnosis and treatment of Alzheimer’s  disease (AD). In 2021 Aduhelm was the first drug approved by the FDA (granted contingent accelerated approval) that is potentially disease-modifying in AD. This year two additional drugs received FDA approval. All three drugs are monoclonal antibodies that target amyloid protein. They each seem to have overall modest clinical effect, but they are the first drugs to actually slow down progression of AD, which represents important confirmation of the amyloid hypothesis. Until now attempts at slowing down the disease by targeting amyloid have failed.

Three drugs in as many years is no coincidence – this is the result of decades of research into a very complex disease, combined with monoclonal antibody technology coming into its own as a therapeutic option. AD is a form of dementia, a chronic degenerative disease of the brain that causes the slow loss of cognitive function and memory over years. There are over 6 million people in the US alone with AD, and it represents a massive health care burden. More than 10% of the population over 65 have AD.

The probable reason we have rapidly crossed over the threshold to detectable clinical effect is attributed by experts to two main factors – treating people earlier in the disease, and giving a more aggressive treatment (essentially pushing dosing to a higher level). The higher dosing comes with a downside of significant side effects, including brain swelling and bleeding. But that it what it took to show even a modest clinical benefit. But the fact that three drugs, which target different aspects of amyloid protein, show promising or demonstrated clinical benefit helps confirm that the amyloid protein and the plaques they form in the brain are, to some extend driving AD. They are not just a marker for brain cell damage, they are at least partly responsible for that damage. Until now, this was not clear.

Continue Reading »

Despite robust efforts to fight it, malaria remains one of the most significant infectious diseases affecting humans. According to UNICEF – ” In 2021, there were 247 million malaria cases globally that led to 619,000 deaths in total. Of these deaths, 77 per cent were children under 5 years of age.” Efforts to minimize malaria cost about $7 billion per year, through vaccination, drug therapy, and spraying pesticides to kill the mosquitos that carry the disease. Mosquito populations are developing resistance to the pesticides, however, which could raise the costs of control, while available funds can fluctuate.

One potential solution is using genetic engineering to fight malaria, and there are several approaches being developed that are close to being ready for deployment. They all use an approach known as a gene drive, which causes a desired trait to spread more quickly through a population than regular Mendelian genetics would allow. This idea is actually 60 years old, but newer techniques, such as CRISPR, are making it much easier and more powerful.

With sexual reproduction, each offspring has two sets of chromosomes, one from each parent. So organisms have two copies of each gene (each copy is called an allele). They then pass one of their two copies onto each offspring. Mendelian genetics assumes that there is a 50% chance for each allele to be inherited, and this is mostly true. The gene drive phenomenon refers to situations in which one allele has an advantage over the other, so it is more likely to be inherited. There are naturally occurring gene drives, but we’re going to focus on the latest synthetic gene drive, which involves CRISPR.

Continue Reading »

RFK Jr., who is now running for the Democratic presidential nomination, is anti-vaccine. He will vehemently deny this, but I don’t buy it for a second. He is simply playing the, “I’m not anti-vaccine, I am pro-safe vaccine” gambit, which is disingenuous and always has been. We have been covering this topic for years, and David Gorski did a recent excellent review of this at SBM. You can’t claim not to be anti-vaccine, and then defend a long list of anti-vaccine tropes.

RFK has apparently been avoiding his views on vaccines on the campaign trail, but it always seems to come up. On the Joe Rogan podcast RFK found what he must have thought was a friendly environment, and felt free to repeat is claim that vaccine cause autism. This is a topic I have been covering for two decades – vaccines do not cause autism. But let’s do a quick review of this harmful claim.

This first appeared in the 1990, when the anti-vaccine movement hit upon the increase in autism diagnoses as a new tactic. They start with the assumption that all bad things that happen to children are caused by vaccines, so obviously they must also be causing the rise in autism. When Andrew Wakefield came out with his fraudulent and now retracted study claiming an association between the MMR vaccine and autism, he became an instant celebrity of the anti-vaccine movement. Trouble is – the MMR vaccine does not cause autism. Wakefield, it turns out, had a patent on an alternative vaccine and was trying to torpedo the competition. But the anti-vaccine movement does not let science, evidence, or basic logic get in their way. So they simply moved over to a vaccine ingredient, thimerosal, which is a mercury-based preservative.

Continue Reading »

In my last post I noted that even mentioning general vague support for the LGBTQ community was enough to trigger very specific feedback, often making erroneous scientific claims. Each claim requires a deep dive and article-length discussion. Even though the discussion that followed in the comments was better than I thought it would be, it still filled with additional dubious claims. I suspect there are two main reasons for this. The first is that the topic of gender identity is complex and not intuitive. It may feel intuitive, as if your immediate gut reaction is all that is necessary to deal adequately with the topic, but it really isn’t. Ultimate this topic deals with how our brains construct our own sense of self, identity, and reality. These are always tricky concepts to deal with – and as I have pointed out before in other contexts, our brain constructs are counterintuitive by their very nature. In other words, our brains evolved for these constructs to feel real and automatic, and for the subconscious processes that create them to be invisible to us.

Second, the issue of gender identity has been highly politicized. This has resulted in any discussion of the topic being flooded with biased and deliberate misinformation. The usual FUD (fear, uncertainty doubt) strategies apply. And of course – science is hard. Even seemingly straightforward questions are actually quite complex. This makes it easy to create confusion by “just asking questions” or selectively applying skepticism.

One question at the heart of the trans issue is this – what is the rate of regret or even detransitioning after medical transition? One narrative is that adolescents (often conflated with “children”) are being prematurely herded down a road to transition, which they later regret. The other narrative is that, generally speaking, making the decision to transition is taken very seriously, with very low levels of later regret. Which is true?

Continue Reading »

Yesterday’s post was the first in an exchange about the effects of climate change on public health. Today’s post is my response.

Part II

Climate change is a critically important topic for society today, and it’s important that the public have a working knowledge of the facts, causes, effects, and potential interventions regarding climate change, so I am always happy to discuss the topic. Unfortunately, it’s a very complex topic that has been highly politicized and polarized. The science often becomes wrapped up in ideology – the best indication of this is that one’s political affiliation is the strongest predictor of the public’s opinions regarding climate change. The media, as they do in general, is happy to sensationalize the topic and often does not provide good context or background. Scientists have gotten better communicating about climate change, but not enough to override political affiliation.

My sense is the core issue is that the complexity of climate change allows everyone to cherry pick those details that fit their narrative. You can find examples to support whatever narrative you want to believe. You don’t even have to be factually incorrect (although many people certainly are), you just have to be selective in your details and interpretation. Climate change is a Rorschach test of subjective validation and confirmation bias.

I say this all because I think Scott’s narrative comes through very clearly. He contacted me asking fervently for a debate on this specific topic, the health effects of climate change. I thought this was a little odd since I have never written or expressed an opinion about this topic before. It seems he assumed what my position was based on other things I have written about climate change – that I think it’s real, it is primarily being caused by humans, and the effects are likely to be bad for the environment and human civilization. This brings up another aspect of the climate change debate, that people generally take sides and think that everyone fits relatively cleanly into the “for or against” side. Once someone thinks they have detected what side you are on, they then ascribe the entire package of views to you.

Continue Reading »