Category: A New Look at Biology

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”

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”

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.

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?”

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”

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?”

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”