Category: A New Look at Biology

Biological Insights

Why would sunlight improve diabetes?

In October of last year, Italian police raided a ‘Ndrangheta mafia strong house in Reggio Calabria, Italy. As expected, they found a hoard of cannabis. But a less expected find was a freezer full of mice. Apparently, the mafia had a tradition of serving plump mice at special feasts of reconciliation between warring factions.

This type of mice, called dormice, was very popular in the Roman times. The Romans would fatten them up in special jars, by feeding them chestnuts and keeping them in the dark to make them believe it was time to get ready for hibernation.

I bring this story up because it’s germane to one of the scourges of modern life: diabetes.

Type 2 diabetes is a curious disease. In my opinion and in the opinion of some scientists (and this is a minority view, not the mainstream orthodox view), it’s not a disease caused by failure of an organ or tissue. It’s a disease where the body becomes mis-programmed and executes a series of metabolic changes that are supposed to be used under a different circumstance. Your body is doing something it’s programmed to do, but at the wrong time.

The changes that happen in diabetes – higher levels of sugar in the blood, increase in fat stores, etc. are all changes that happen in animals when they (and we) get ready for winter. In some species (such as bears and squirrels that hibernate), these changes are pronounced – their glucose, cholesterol, and weight all increase dramatically as they approach winter. In humans, they are usually less pronounced, but we also store up fat for winter.

Type 2 diabetes is an exaggerated, wrongly-timed version of what naturally happens. Something tells your body “winter is coming, get ready for it.” (Type 1 diabetes is something altogether different.)

What causes this? It’s not clear. Some people think it’s the fructose in our diet. Fructose is normally never seen by our bodies except during fall, when fruits ripen. And certainly it is not normally seen in the quantities many of us consume. In studies, you can trigger insulin resistance (the first step toward diabetes) by giving healthy volunteers just a few cans of fructose-containing soft drink for just a few weeks. So drinking fructose-containing soda or eating fructose-enhanced food may signal to the body that winter it coming. (Fructose also wreaks havoc on the liver and increases body weight so it’s just bad all-around.)

Another intriguing possibility, though, is exposure to sunlight. Most organisms use the length of day to sense the change of seasons. And most organisms are biologically programmed to respond to changes in seasons – by changing their habits, metabolism, fur, etc.

In fact, if a scientist didn’t know about Type 2 diabetes, and someone asked her how we might make people gain weight, increase cholesterol, and increase blood sugar levels, one idea that she might come up with might be: make the body think it’s wintertime by reducing the length of sunlight exposure per day.

In modern society, many of us spend more time indoors than outdoors. This might make it hard for our bodies to track seasons.

Or, alternatively, we use a lot of artificial light, including blue light-emitting computer screens. This may confuse our seasonal clocks and may make it difficult for our bodies to tell whether the days are getting longer or shorter, and whether winter is coming or not. And our bodies may just default to the safe choice, which is to store up fat for the winter (and one of the best way to store up fat is for our cells to ignore insulin signaling, and become diabetic). In fact, studies have shown that artificial light correlates with disrupted circadian rhythms and increase in obesisty.

This hypothesis is supported by data. In one study of over 10,000 subjects, increased exposure to sunlight had a statistically significant beneficial impact on blood glucose levels (sunlight also lowered cholesterol levels, as would be expected). To be clear, the cause of diabetes is probably multi-factorial, but this study’s results make sense, since the amount of sunlight probably has a significant effect on your body’s seasonal clock.

Of course, more sunlight may make people more active, which may have a beneficial effect on diabetes. But, recall that the Romans used to keep dormice in the dark to make them think it’s wintertime, which made the mice fatter (and probably also threw them into diabetic state).

This sunlight hypothesis is not widely studied, partly because most scientists believe that diabetes is a failure of our body, rather than a legitimate program that is mis-triggered. (This is, I believe, the same mistake some aging researchers make when they see aging as deterioration of our body rather than a programmed process.)

Interestingly, one of the best medicines for diabetes is bromocriptine. By best, I mean the one with very impressive effect on survival (many drugs that lower glucose actually worsen survival, which is why the FDA now requires pharma companies to prove their drug doesn’t increase mortality before the drug will be approved). One of the hypothesis about how bromocriptine works is that it resets the seasonal clock in our bodies, and pulls us out of the winter-preparation mode.

As I said, this is a minority view, that Type 2 diabetes is a problem of mis-signaling. But as a biologist, I tend to think that our bodies, after billions of years of evolution, is a pretty well-functioning machine. It’s rare that it breaks down in the absence of injury or pathogens. I think it’s more likely that there is something in our modern life that is sending a wrong signal to our bodies, and diabetes is probably a normally a beneficial program that is being executed at the wrong time.

Aging and (Im)mortality

Plants Age Too, Don’t They?

There is quite a bit of debate about whether aging is a degenerative, uncontrolled process or a programmed process. At least, there is quite a bit of debate among zoologists.

Apparently, the botanists have long ago come to the conclusion that aging is programmed. Read this: “Senescence, the final stage in the development of an organ or whole plant, is a genetically programmed process controlled by developmental and environmental signals.” That’s in a paper published by scientists at the USDA. And they’re not alone, there are multiple other groups that take the same view.

I’m not sure why the plant scientists have so much faster come to this conclusion than animal scientists. It may be because in plants, certain parts of the organism can age and dies separately from rest of the plant. For example, leaves can age and die every year on a plant. Or it may be because the signaling molecules for aging have been identified. For example, ethylene and jasmonic acid (yes, the scene of jasmine), triggers senescence in leaves. (And those signals can be blocked, by the way–some insects block aging so that they can stay in their “homes”).The aging process in plants is very defined, with clear molecular cascades, and under control of chemical signaling molecules. I supposed that if there was chemical that would trigger people to age, there wouldn’t be a debate about humans either.

I should note, that per my Red King Theory, that two things most likely to trigger or accelerate aging are 1) parasites and pests and 2) sex. Jasmonic acid is a signaling molecule triggered by insects eating the plants. If my theory is correct, it makes absolute sense that jasmonic acid should accelerate aging.

What does this mean? Well, it means either 1) aging in plants and animals are fundamentally difference or 2) aging in animals is a programmed process. I think #1 strains all reasonable credulity.

Aging and (Im)mortality

Why Would Late Puberty Make You Live Longer?

In a recent issue of Science, there is an article about some of the great discoveries flowing out the UK Biobank, a huge registry of 150,000 Britons.

One intriguing set of findings is the discovery that some of the Neanderthal genes that we have held onto are immune system genes, which is what we would expect if viral shockwave theory is true.

But, what I want to focus on in this blog is this discovery from the Biobank project: genes that cause early puberty are rare in people who are likely to live for a long time. Some of the findings are here and here. This means that later you hit puberty, longer you’re likely to live. Continue reading “Why Would Late Puberty Make You Live Longer?” →

A New Look at Biology, Drug Development, Germs, Sleep

Beyond Drugs

Other than surgery, drugs are mainstays of disease therapy. We take chemicals to treat ourselves, but why is that? Why chemical, as opposed to light, ultrasound, electricity, odors, or some other type of intervention? The reason is that plants, from which most of our drugs come, have spent millions of years engaged in medicinal chemistry, and have created some of the most potent biological molecules.

But there are exceptions. For example, one group at Harvard recently published that exposing mice to flashing lights cleared beta amyloid plaque in the brain. This was likely because the flashing light drove gamma oscillations in the brain. Continue reading “Beyond Drugs” →

A New Look at Biology, Aging and (Im)mortality

Immortality for Humans? Perhaps

I remember a patient I saw as an intern. She was 95 years old, and had come in with a kidney stone. When I pulled her medical chart, I was taken aback. It was only 5 pages long. She had never been admitted to the hospital, unlike the typical 65 year olds who had hundreds of pages of records.

A sage attending physician told me that was very common, that 90 year olds often had never been admitted to a hospital. “That’s how they get to be 95,” he said. At the time, I thought it was very odd that the 95 year old looked much healthier than most 65 year olds.

A recent paper in Science, reviewed in NY Times by Zimmer, may shed some light on this. It found that your risk of dying starts decreasing after age 80 and raises the possibility that there may be no limit to human lifespan. More importantly, it lends support to the hypothesis that aging is genetically programmed, and that it’s under evolutionary selection.

Continue reading “Immortality for Humans? Perhaps” →

A New Look at Biology, Aging and (Im)mortality

Are We Programmed to Get Cancer?

When my son was in kindergarten, he somehow talked us into getting him two rats as pets. It’s not as bad as it sounds. Rats, apart from their unattractive tail, make great pets. Very friendly, intelligent, and clean. Although I did take offense to the fact that they insisted on cleaning themselves for five minutes each time after being touched by humans…

They eventually got old (2 to 3 years old), and succumbed to cancer, as they often do.

They got old… and got cancer…

That doesn’t sound odd unless you step back and ask, why did they get cancer when they were only 2 or 3 years old? And why do “old” dogs get cancer when they get to be 7 or 8 years old? We humans don’t get cancer, for the most part, until we are in our 50s, 60s, or older. Why is it that we don’t usually get cancer when we are 2 or 3 or 8 years old, but animals with shorter lifespans do?

This exposes a critical flaw in the current thinking about etiology of cancer. The current thinking is that after a certain number of cell divisions, and after a certain length of time, our cells accumulate too many mutations and then we get cancer.

That theory is demonstrably, and patently wrong. If that theory were correct, rats would never get cancer. But they get cancer quite often when they’re more than couple of years old.

And if that theory were correct, then large animals should get cancer a lot more frequently than small ones, because the cells have to divide so many more times in order to create a larger animal. This paradox is called Peto’s paradox. There are some efforts to rationalize away this paradox, such as arguments that large animals have increased number of tumor suppressor genes, but that just begs the question: why don’t small animals evolve more tumor suppressor genes themselves to live longer, or why don’t all animals evolved enough tumor suppressor genes to never get cancer?

More fatal to the theory is the fact that some animals don’t get cancer, or almost never get cancer. Naked mole rats for example. Horses and other related species for another (except non-metastatic melanomas). Maybe even lobsters.

So what’s the alternative explanation? The most logical explanation is that cancer arises when animals get biologically old. Species that don’t age or age very slowly, like the naked mole rats and lobsters, seem to have very low rates of cancer. In other words, cancer is programmed into our biological clock. When we’re biologically young, we suppress tumors. When we get older, the brakes come off. This is in line with my previous post about how aging is probably programmed. It is also in line with recently findings that we have cancer causing mutations all over our skin (and probably throughout the body), that don’t cause cancer until something else allows cancer to emerge. It’s becoming clear that cancer is not really caused solely by mutations–there are other required factors that must exist before the tumorigenic mutations can cause cancer.

If true, then this theory has important implications. It means that we should be able to prevent cancer very effectively, if we can decipher what is the molecular clock that governs aging.

A New Look at Biology, Biological Insights

Can You Taste with Your Kidneys? Can You See with Your Blood Vessels?

I’ve only seen scurvy once. I was in training at Barnes Hospital in St. Louis, and a homeless man was admitted with weakness, muscle and bone pain, bleeding gums, and shortness of breath. It turned out that his diet consisted solely of hotdogs (no condiments) and Coke. It’s a good thing he came to tertiary care hospital, because scurvy is so rare now that many physicians wouldn’t even consider it in their diagnosis.

I will admit, though, that I’ve been watching a friend of my son for years, expecting to see my second case of scurvy. This friend only eats white rice. Well, he also eats white bread, and a few other things, but only bland things. I thought he would grow out of it but he still hasn’t, and he’s teenager.

I’ve been puzzled about his dietary habits, but I just read something that might explain this.

In The Medical Detective, Roueché describes a baker who suddenly developed a similar problem. The baker, named Rudy, had a perfectly normal sense of smell and taste until one day, he came down with a cold. Then suddenly, his smell and taste perception changed (and persisted). He couldn’t handle the smell in his pizza bakery any more. The ripe tomatoes smelled rotten. The entire kitchen smelled like burnt plastic. Continue reading “Can You Taste with Your Kidneys? Can You See with Your Blood Vessels?” →

A New Look at Biology, New Discoveries

To Sleep, Perchance to Dream… Or Not

You know those people who only need 4 hours of sleep a night, yet who are energetic to the point of making you feel exhausted just by seeing what they do in a day? Well, there’s an app for that. OK, not really, but there is a gene for that. It’s called DEC2 (also called BHLHE41), and the evidence for it is pretty convincing. The group that originally identified this gene even made mice with a mutation in the gene and the mice also became short sleepers, and at least one other group has identified mutations subsequently in the same gene in other families with short sleep phenomenon.

What does this gene do, can I have a copy of that mutation, you are asking yourself. Continue reading “To Sleep, Perchance to Dream… Or Not” →

A New Look at Biology, Germs

Diabetes Drugs for Alzheimer’s Disease?

A recently published paper reported that combination of three diabetes drugs (GLP-1, GIP, and glucagon) improved memory in a mouse model of Alzheimer’s. This is quite remarkable, but not shocking.

There are several competing theories of Alzheimer’s disease. There is the all-but-discredited theory of beta amyloid. I would like to still believe in this theory, having been a proponent of this theory for several years at Elan. It is a compelling theory for several reasons. First, the familial forms of Alzheimer’s disease have mutations that increase beta amyloid. Second, you can cause Alzheimer’s by injecting beta amyloid into the brain. Third, transgenic mouse models targeting beta amyloid can reproduce some of the symptoms of the disease. But unfortunately, data from multiple studies have shown that the theory is incorrect. It is difficult to admit that so much beautiful science (much of it done at Elan) can be so wrong but I think it may be. Continue reading “Diabetes Drugs for Alzheimer’s Disease?” →

A New Look at Biology, Biological Insights

Gout and Cardiovascular Disease

My best friend was diagnosed with gout recently. I told him to stop ingesting fructose immediately.

Only twenty five years ago, when I was in training, gout looked like it was like a disease on its way to extinction, sort of like tuberculosis. We were taught it used to be common hundreds of years ago but that it was pretty rare. Sure, I had a few patients with gout in my clinic with gout but I would see a case once every couple of months at most.

Now, it’s exploded in frequency.

Gout is very, very bad. Not only because it is excruciatingly painful. (In some patients, you can’t even let a gouty big toe brush against tissue paper without unbearable pain. It’s one of the few things that may rival childbirth in the intensity of pain.) And not only because it is a major risk factor for heart disease. Not only because it causes heart disease. No, it’s very bad because your risk of dying goes up by 25% if you have gout. Continue reading “Gout and Cardiovascular Disease” →