Frankenchicken:

How Scientists Inserted Genes Into Chickens to Make Drugged Eggs

To make new pharmaceutical drugs, you have to break a few eggs.

In this case, you have to break a few genes that produce proteins that are in eggs.

Scientists at the Roslin Institute in Midlothian, UK, inserted genes for interferon alpha 2a (an anti-viral protein often used to treat hepatitis, the active compound in Roferon-A,) interferon beta-1a (used to treat multiple sclerosis, the active compound in Avonex and Rebif,) or an antibody against melanoma (the really bad skin cancer) into chickens. The eggs that the chickens laid then had lots of the protein in them. You can purify the protein from the eggs to make drugs.

The rationale for doing this is that chicken farming is a lot cheaper than bacterial or mammalian tissue culture production in bioreactors, which is the current method of producing most large-molecule protein drugs.

So how do you make a Frankenchicken?

First, Dr. Helen M. Sang and her associates used a retrovirus. The particular retrovirus used was an Equine Infectious Anemia Virus (EIAV), a commonly used, commercial vector. The genes that cause disease and virus production have been removed from this virus so that other genes may be inserted.

Retroviruses break open the DNA of the host they infect and insert themselves into the host’s chromosomes. From within the hosts’ chromosomes, they use the hosts’ own protein-making and cell-making machinery to produce a few new viruses that then go infect other cells. That’s how they ride along for years, causing minimal or no disease. For example, HIV, a human retrovirus, infect human white blood cells and inserts itself into the white blood cells’ DNA.

All the disease-causing genes were removed from the EIAV vector. Then, the scientists added the genes of the drug proteins to the vector. Now, when the retroviral vector inserts into the host’s DNA, it will make the protein drug instead of making viral proteins and new viruses.

So why does the drug only appear in the eggs? Why isn’t the drug in the whole chicken?

The virus figures out where to insert itself into the host’s DNA by comparing its DNA sequence to the host’s. In a place where the virus’s DNA matches the host’s DNA closely enough, the DNA entwines around each other and the virus’s DNA splices into the host’s DNA.

Then, the scientists made some changes to the DNA around the drug genes so that it matched a particular chicken gene: ovalbumin. Ovalbumin is the predominant protein in egg whites.

The virus integrated into the ovalbumin gene’s place because that’s where the DNA sequences matched. Now, in the mature chicken, in cells that are supposed to make ovalbumin, the drug proteins are made instead. The only places in a chicken that make ovalbumin are the organs that make the eggs. Thus, the eggs are filled with the drug protein instead of ovalbumin.

The EIAV vector with the drug gene was used to infect chicken one-cell embryos. The gene in the viral vector replaced the ovalbumin gene in the chicken embryos’ DNA. The embryos were then put back into an egg (like a breakfast egg, like you buy a dozen of in the grocery store.) The one-cell embryo divided and grew normally inside the egg until it hatched, as a transgenic chick.

And that’s how you make a transgenic chicken and drug-filled eggs.

By: TK Kenyon
Author of Rabid: A Novel, coming in April, 2007 from Kunati Books
"-- shady clergy, top-secret scientific research, marital infidelity, lust, love, honor, faith-- "

Hello All,

Just to let you know: my novel RABID is available for pre-order at Amazon. They've discounted it quite a bit, from $27 to $17.79.

If you were thinking about buying it, now is a good time. If you find it cheaper at your local B&N or indie bookstore, you can always cancel an Amazon order.

Thanks,
TK Kenyon

The Other Nobel Prize:

And the Crafoord Goes To … Dr. Robert L. Trivers For Sociobiology!

The Nobel Prize is widely acknowledged as the Big Banana for scientists, but Nobels are only awarded in the fields of chemistry, literature, peace, medicine or physiology, and economics. There is, however, the Crafoord Prize, which has essentially the same status as a Nobel, for other scientists. Crafoord Prizes are awarded in the fields of mathematics, geoscience, bioscience (particularly in relation to ecology and evolution), and astronomy.

This year, the Crafoord Prize was awarded to Dr. Robert L. Trivers, who was one of the pioneers in the field of sociobiology. While Darwin discussed some aspects of sociobiology in his seminal books on evolution, most of these concepts lay dormant as biologists pursued the minutiae of the descent of man and fruit flies. Trivers and his colleagues, however, picked up the gauntlet that Darwin threw down and used it to expand our understanding of why humans and animals behave the way we do.

Sociobiology is based on the idea that behavior that is determined by genes can be adaptive and passed from generation to generation. The most controversial behaviors studied are aggression and antisocial behaviors. Some people don’t like the idea that there is a biological basis for murder and evil. It’s anathema that Satan isn’t in your soul, he’s in your DNA.

Trivers's current research follows a group of Jamaican children and attempts to correlate their degree of symmetry (both behavioral and physical, i.e., genetic blessedness and developmental physiology) with attractiveness, dancing ability, aggressiveness, number of friends, health status, growth rate, academic achievement, and athletic ability. He also studies genetic components in deceit and self-deception. He proposed the theories of reciprocal altruism (1971,) parental investment (1972,) and parent-offspring conflict (1974.)

TK Kenyon

If The Sun Is So Hot, Why Is It So Darn Cold?

If the Sun is producing so much energy and burning at 15 million degrees Kelvin, why is it so amazingly cold in the winter?

First myth debunked: The sun does not get hotter or colder. The sun stays the same temperature.

Second myth debunked: The Earth goes around the Sun in nearly a perfect circle. Yes, you’ve been told it’s an ellipse, which is an oval, but the Earth's orbit is barely elongated and very close to a circle. It isn’t cold because we’re nearer or farther from the sun during the year.

Besides, when it’s winter here in the U.S., it’s summer in the southern hemisphere. Australia is just as far from the sun as we are, but they’re at the beach.

So how can it be icy-cold winter up here in the Northern Hemisphere, but nice and toasty warm south of the equator?

The Earth’s axis, the imaginary line through the center of the Earth through the poles, is tilted. That’s why globes lay back on their sides some instead of spinning straight like a top.

To simulate this, hold a pencil in your right hand, make a fist around it (thumb up), now tilt it until the top of the pencil is pointing to ten o’clock.

That’s the way the Earth looks from space.

Rotate your wrist forward and back around the pencil, so that the pencil doesn’t wobble. That’s the Earth spinning.

Now, whatever you’re drinking is the sun. Assuming you’re holding the pencil in your right hand, put it on the left side of the cup. With your knuckles closest to the pitcher, er, cup, you can see that the sun will strike your pinkie knuckles directly. This is summer in Australia. The sun’s rays are close together and strike Australia dead on.

Now look at your first knuckle. Though it’s farther away from the beer, um, coffee, that’s not what we want to look at. Think about the Sun’s rays striking your knuckle. Your knuckle is slanted away from the sun, so the rays are more spread out. There’s more space between each ray. This is winter in the northern hemisphere, where the Sun’s rays are spread out, and the same amount of sunlight hits a bigger area of land, so it isn’t as strong.

Now put your hand on the right side of the pitcher and look at summer in up here and winter in the Down Under. The top of the pencil should be pointing toward the Corona . . . or latte.

To feel the effect of spread-out rays, try this with a light bulb: feel the heat with your hand flat in front of it, then slant your hand back and feel that it is cooler when the same amount of light spills over more of your hand.

Don’t you wish you were in Australia, catching some rays?

TK Kenyon

If you found this story helpful, please Digg it.

For more literary pursuits, try TK Kenyon's column Recommended Reading at Suite 101.com.

For very literary pursuits, try reading the first chapter of RABID: TK Kenyon's blockbuster novel coming in April, 2007. Read starred reviews of RABID here.

If The Sun Is So Hot, Why Is It So Darn Cold?

If the Sun is producing so much energy and burning at 15 million degrees Kelvin, why is it so amazingly cold in the winter?

First myth debunked: The sun does not get hotter or colder. The sun stays the same temperature.

Second myth debunked: The Earth goes around the Sun in nearly a perfect circle. Yes, you’ve been told it’s an ellipse, which is an oval, but the Earth's orbit is barely elongated and very close to a circle. It isn’t cold because we’re nearer or farther from the sun during the year.

Besides, when it’s winter here in the U.S., it’s summer in the southern hemisphere. Australia is just as far from the sun as we are, but they’re at the beach.

So how can it be icy-cold winter up here in the Northern Hemisphere, but nice and toasty warm south of the equator?

The Earth’s axis, the imaginary line through the center of the Earth through the poles, is tilted. That’s why globes lay back on their sides some instead of spinning straight like a top.

To simulate this, hold a pencil in your right hand, make a fist around it (thumb up), now tilt it until the top of the pencil is pointing to ten o’clock.

That’s the way the Earth looks from space.

Rotate your wrist forward and back around the pencil, so that the pencil doesn’t wobble. That’s the Earth spinning.

Now, whatever you’re drinking is the sun. Assuming you’re holding the pencil in your right hand, put it on the left side of the cup. With your knuckles closest to the pitcher, er, cup, you can see that the sun will strike your pinkie knuckles directly. This is summer in Australia. The sun’s rays are close together and strike Australia dead on.

Now look at your first knuckle. Though it’s farther away from the beer, um, coffee, that’s not what we want to look at. Think about the Sun’s rays striking your knuckle. Your knuckle is slanted away from the sun, so the rays are more spread out. There’s more space between each ray. This is winter in the northern hemisphere, where the Sun’s rays are spread out, and the same amount of sunlight hits a bigger area of land, so it isn’t as strong.

Now put your hand on the right side of the pitcher and look at summer in up here and winter in the Down Under. The top of the pencil should be pointing toward the Corona . . . or latte.

To feel the effect of spread-out rays, try this with a light bulb: feel the heat with your hand flat in front of it, then slant your hand back and feel that it is cooler when the same amount of light spills over more of your hand.

Don’t you wish you were in Australia, catching some rays?

TK Kenyon

For more literary pursuits, try TK Kenyon's column Recommended Reading at Suite 101.com.

For very literary pursuits, try reading the first chapter of RABID: TK Kenyon's blockbuster novel coming in April, 2007. Read starred reviews of RABID here.

THE FLU:
Influenza or a “Stomach Flu?”

Sometimes, I’m stickler for vocabulary.

I’m not trying to be prissy, but “The Flu” is one of those medical terms that should be used accurately, and a lot of people misuse it.

“The Flu” is commonly used to refer to two different maladies: influenza and the so-called “stomach flu.”

Influenza is the real flu. It begins suddenly with a high fever, aching joints, and a cough. The cough can persist for weeks.

The influenza virus infects the lungs, and thus influenza is spread by aerosolized droplets. When a person with influenza coughs, they spray miniscule droplets of saliva, diseased lung tissue, and virus into the air. It’s highly infectious, and a whole bunch of people near them will get the flu by inhaling those droplets.

The annual flu shot or other immunization protects you against influenza. The influenza virus mutates easily and regularly, and thus several new strains of the flu float around every year. That’s why you need a flu shot every year.

The “Bird Flu” is a hypothetical variant of influenza. Birds get the flu, too. They have their own strains of the influenza virus. If a bird strain and a human strain infect the same bird, the two viruses can recombine their chromosomes, and thus a very deadly new strain of the flu may emerge.

The so-called “Stomach Flu,” on the other hand, is a group of stomach maladies that is not the flu and is not related to influenza.

This includes classical food poisoning, like from undercooked chicken or eggs, and a whole host of gastrointestinal viruses, like the Norwalk viruses that are sometimes are found on cruise ships, that are spread either through food or, more likely, by the “fecal-oral route.” (Yep, it’s as gross as it sounds.) These viruses are contagious but not by aerosolized droplet spread.

These stomach bugs have symptoms like a low fever, vomiting, stomach cramps, and/or diarrhea. There is no cough. That’s the difference. If you’re not coughing, it’s not the flu.

The flu shot does not protect you from these stomach bugs.

Please use these terms correctly. They are not interchangeable. At the very least, define whether or not you had a “stomach” flu.

TK Kenyon

Preventing Alzheimer's Disease:

Pickle Your Brain With Booze

And other good ideas

That’s right. The best and latest research shows that the best way to avoid, slow, or delay Alzheimer’s disease and preserve your brain is to pickle it with booze, cigarettes, caffeine, ibuprofen, and the occasional fish.

I discussed the most shocking finding, that smoking is negatively correlated with getting Alzheimer’s Disease, in a previous essay. Basically, there’s some good research out there, both on the epidemiological and the molecular scale, that shows that people who smoke are less likely to get AD, that nicotine binds to one of the proteins implicated in AD and reduces its aggregation, and that nicotine exposure increases the number of nicotinic acid receptors in a smoker’s brain. Read the previous article on AD and Smoking to understand what all that means.

But now, the rest of the prissy lifestyle choices will also destroy your brain. If you’re a teetotaling, caffeine-abstaining, chocolate-avoiding, pharmaceutical-abjuring vegan, then you can kiss your brain good-bye.

If you want to keep your brain happy and healthy, first, have a drink. Both wine in particular and alcohol consumption in general decrease risk of AD. One caveat: all of these studies focused on light to moderate drinking, on the order of one to three drinks per day, especially of red wine, and with the lower number of drinks for women. Any source of alcohol seems to help, though red wine is a good source of reversterol and tannic acid, which were helpful at a molecular level in other studies.

Next, eat Indian food or a Mediterranean diet, which has lots of fish, rice or pasta, red wine, and olive oil.

The spice turmeric contains the compounds curcumin and other curcuminoids that amyloid fibrils.

Eating the Mediterranean Diet reduced chances for AD, even when the researchers controlled for cohort, age, sex, ethnicity, education, apolipoprotein E genotype, caloric intake, smoking, medical comorbidity index, and body mass index.

Get married, or at least live with someone.

Stay in school. Go to college and grad school. Increasing educational levels have long been found to delay or prevent AD. If you’re past the college age, being mentally active in a variety of ways helps reduce your chances for AD. Specifically, novelty-seeking behaviors (trying new foods, new activities or hobbies like learning chess or knitting, listening to new types of music, or reading books on new subjects) and social activities that involve the exchange of ideas (talking about politics, but not merely social activities like playing a game you already know, like canasta,) reduce your chances.

Ah, yes, here it is. Eat chocolate! The darker, the better. It has huge amounts of anti-oxidants and other psychoactive peptides. Some people have noted that, if it wasn’t so prevalently and commonly used, if chocolate had been discovered recently, the government would probably regulate it as a controlled substance. Raise a cup of cocoa to lack of government intervention!

An Advil (or other NSAID, like Aleve, or generic ibuprofen) a day keeps the neurologist away. NSAIDs like ibuprofen and naproxen (Advil and Aleve) bind to amyloid plaques in the brain and may help clear them. However, be careful about gastrointestinal problems when you take NSAIDs. They’re rough on your tummy.

Take a walk or get other exercise. Both regular physical activity specifically and not being overweight in general have been found to reduce your risk of AD.

Eat a fish every week. At least one fish a week decreases your chances of getting AD by 60%. That’s HUGE.

Drink filtered water. Even one-tenth (10%) of the EPA allowable limits of copper in drinking water affected the formation of plaques in the brains of rabbits, dogs, and a mouse with Alzheimer’s-associated genes.

Don’t eat so much. In a study of mice with human mutant Alzheimer’s-associated genes, merely reducing their food intake (calorie intake, actually, not the volume of food) greatly increased their survival and reduced the pathology in their brains. This may be somewhat associated with the positive correlation between being overweight and being more prone to AD (see above.)

Some things that make no difference: No statistically significant association was found for family history of dementia, sex, history of depression, estrogen replacement therapy, head trauma, antiperspirant or antacid use, high blood pressure, heart disease, or stroke.

To summarize, the general consensus is that some booze, especially red wine, some coffee, a fish a week, some exercise, a dab of chocolate, and doing new stuff will reduce your chances of getting Alzheimer’s Disease.

If you found this article helpful, please Digg it.

TK Kenyon

How to Prevent Alzheimer's Disease:

Light up a cigarette.

No, seriously. Light up a cigarette.

Alzheimer’s Disease (AD) is Hell. It’s pretty close to my own personal definition of a literal Hell.

I’ll do just about anything to avoid AD. Chances are, because my three living grandparents are all over 88 years old, I’m going to live a while, assuming I avoid stepping in front of busses. Recent evidence suggests that damage due to the APOE4 allele only kicks in after the age of 80. Before that, it’s just laziness (or due to other neurodegeneration.)

So I’ve been incorporating all those prim little lifestyle changes that are supposed to guarantee a long, healthy, happy life. I’ve cut down on coffee and chocolate. I’ve never smoked and rarely have a drink. I try to minimize the number and amount of painkillers and other drugs that I take. I’m a vegetarian and eat lots of pretty colors of food every day and take my multivitamin.

If I don’t live forever, it will certainly seem that way.

Here’s the joke: My heart may be in pretty decent shape, but that Baptist nun approach to life is a recipe for Alzheimer’s Disease.

That’s right. The best and latest research shows that the best way to avoid, slow, or delay Alzheimer’s disease and preserve your brain is to pickle it with booze, cigarettes, caffeine, ibuprofen, and the occasional fish. Oh, and eating your vegetables doesn’t help at all.

First of all, the biggest shocker: smoking reduces your chances of getting AD. Ref1 Ref2

Seriously, it’s true. It’s not widely publicized because it’s terribly politically incorrect.

Smoking also reduces your chance of getting Parkinson’s Disease.

Actually, to maximize your chance of avoiding AD and living a long life: smoke for a while, then stop. (Easier said than done.)

Before we go any farther, I don’t think anyone is recommending that you take up smoking. That particular device, the cigarette, has thousands of other compounds that cause heart disease, cancer, halitosis, body odor, and wrinkles. Smoking also vastly increases your chances of getting a vascular form of dementia caused by many small strokes. So, it’s really not a good idea. I don’t smoke. Never have. Never will.

I have considered the nicotine patch or gum, however.

But there’s good evidence that smoking reduces your risk of AD. The studies are pretty good, and they’re not sponsored by the tobacco companies. They have controlled for other risk factors, including the “Hardy Survivor” effect, which basically means that if smoking doesn’t kill you, nothing will. Ref1 Another study controlled for weight of the subjects, which is important because smokers generally aren’t as chubby as non-smokers, and being overweight is associated with AD. Ref2.

One theory as to why smokers are less susceptible to AD involves nicotinic acid receptors. When you smoke, your brain makes more receptors for the nicotine. Ref1. However, people who have dementia with Lewy bodies (DLB) have fewer nicotinic acid receptors. Ref2 People with AD also have fewer nicotinic acid receptors in their brains. Ref3

But can nicotine or smoking reduce your chances of getting AD?

First, some basic neuroscience. One of the most supported theories for the cause of AD (and we aren’t sure what causes AD) is a protein called beta-amyloid, also called Ab, A-beta, or bAP. (Thus, the folks who espouse this theory are called bAP-tists.)

Beta-amyloid protein occurs naturally in your brain, though no one knows what it does. The normal form is soluble, which means that it dissolves in water. Forms of beta-amyloid that are less soluble and tend to form clumps (aggregate) are thought to be more pathogenic. The forms that may be associated with AD are called Ab40 and Ab42. Ab42 is thought to be worse for your brain (more pathogenic) than Ab40.

The more pathogenic forms Ab40 and Ab42 are found in higher amounts in non-smokers’ brains than in smokers, Ref1 especially in areas of the brain that are associated with age-related dementia. Ref2. In general, higher concentrations of Ab40 and Ab42 have been found to be associated with AD.

Now can smoking reduce your chances for AD? In a mouse model of AD (and mouse models are imperfect for a whole variety of reasons, but that’s another essay,) mice who produce a mutated human gene for amyloid (that is associated with getting AD in humans) make amyloid plaques in their little mousy brains. When you feed them nicotine, they make fewer gunky amyloid plaques in their little mousy brains.

How can that happen? Well, it’s been found in humans that the chemical that nicotine turns into in your body, (called Nornicotine,) bonds to amyloid and reduces it’s gunking into plaques.

Nicotine also breaks down fibrils of amyloid, which are thought to be what the plaques are made of.

Some recent studies, however, have found that smoking increases your chances of dementia. Ref1. Ref2. Yet, the molecular evidence suggests that Ab disposition is less in smokers and in nicotine-ingesting mice. Why is that?

Well, there’s a whole host of possible reasons.

(1) Alzheimer’s Disease, like all “lifestyle” diseases, is multi-causal. Slightly changing the way you pick your subjects will drastically change your results. Different model. Different study.

(2) Many of the studies found positive links between smoking and dementia, not smoking and AD. You can’t definitively diagnose AD unless you autopsy the brain. (This is contraindicated in people who are still using their brains.) Therefore, these studies may be finding vascular dementia, which is very common and associated with smoking.

(3) The last possibility is that the beta-amyloid hypothesis of Alzheimer’s Disease is wrong, or at least the Ab42-is-bad hypothesis is wrong. This means that all the studies are correct. Smoking, therefore, increases your risk of AD while decreasing your load of Ab42-associated plaques.

One hypothesis suggests that the plaques are formed to keep the Ab42 (or a precursor, like ADDLs) from floating around. The floating Ab42 kills brain cells. Therefore, tying up the Ab42 in plaques is actually a defense mechanism. Thus, smokers have fewer defensive plaques, more floating Ab42, and more AD.

Alzheimer's Disease: Not Just Stupid.

What It's Like To Have AD

Alzheimer’s Disease (AD) scares the beejeezus out of me. The thought of my mind deteriorating while my body rambles on is pretty much my personal definition of Hell.

You see, Alzheimer’s doesn’t just make you stupid. It isn’t just that your standardized testing scores fall. If the effects of Alzheimer’s were merely lowering my SAT and GRE scores, I could deal with that. We’ve all heard the term, “Fat, dumb, and happy.” Doesn’t sound so bad, really.

But the horror of Alzheimer’s lies in the absence of the ability to string two thoughts together. Thus, items appear out of thin air because you can’t remember that they were beside you a minute ago.

Imagine that a stuffed tiger appears on your bed. Poof! You have no idea where it came from. Might be the C.I.A. or space aliens that made it materialize there.
Now, because you’re lying right next to the stuffed tiger, and because you can’t remember that a second ago you reached over and petted the stuffed tiger, you can’t tell how big the tiger is. It’s next to your face, so that tiger looks full-sized. It’s a man-eating tiger.

And, because you can’t remember that it hasn’t ever moved because it’s stuffed, and because it just appeared out of nowhere again, that’s not a stuffed tiger. That’s a friggin’ tiger that is about to eat your head.

Now there are all these strangers around you in this place you’ve been kidnapped to, telling you that it’s all right if the tiger eats your head, and isn’t it a pretty stripy tiger that’s about to eat your head?

And a minute later, poof! A tiger appears.

That's what having Alzheimer's is like. I can't imagine anything worse.

Next article: How to avoid getting AD.

TK Kenyon