Rewriting the language of life

E. Coli bacteria

The familiar, idyllic scenery outside your door, bucolic in the spring sunshine, is exceedingly weird. And so are you.

What seems ordinary to us, an oak tree, daffodil, blade of grass, or your own body, is made of atoms forged in the furnace of early, distant stars. And these atoms are nearly entirely empty space, vacuum, with only a few protons and neutrons and electrons forming actual matter.

That’s right, your body is more than 99.9999% empty space, and the reason you don’t sink through your chair is that the electrostatic charge of the atoms in the chair repels the atoms of your body.

What’s the point? Only that things are often stranger than they seem.

Take living things, for instance. DNA is often called the blueprint of life. Think of DNA as a construction and operation manual that tells a dandelion how to be a dandelion, a whale a whale, or a you to be human. The instructions in your DNA account for your height, hair color, gender and also control the ongoing operation of your body. This is the miracle of life.

So it was a bit of a surprise earlier this month when synthetic biologists at the Scripps Research Institute announced  they had created bacteria containing artificial DNA. A biochemist not involved in the project, Steven Benner of the Foundation for Applied Molecular Evolution in Gainesville, Florida,  summed up the shocking finding: “Most people thought this wasn’t possible.”

Think of DNA as a kind of computer program. It is information that regulates how amino acids and proteins, the basis of life, are produced. The researchers at Scripps, led by chemical biologist Floyd Romesberg, have found a way to rewrite that program and have created bacteria which live, grow, and reproduce utilizing segments of man-made, artificial DNA. The descendant bacteria also contain the artificial DNA, and pass it on to their successors.

The point of all this is that bacteria can now be programmed to produce a greatly expanded range of amino acids and proteins. Applications range from new cancer drugs to improved vaccines or even anticounterfeiting, improved forensics, and the efficient production of biofuels. The opportunities are mind boggling.

Even before the achievement of artificial DNA, scientists had become quite capable. According to the Wall Street Journal, “With growing mastery, scientists have been tinkering with this natural information-storage system that is found inside every cell. They routinely cut and splice normal DNA to alter plants, bacteria and animals. They have used its ultraminiature storage capacity to encode books, poems and popular music. They even have programmed DNA to perform computer-like calculations.” (Man-Made DNA Opens Doors, 5/8/2014).

But the Scripps accomplishment opens the door to much greater control and specificity. While current gene manipulation relies on repurposing natural DNA, the advent of artificial DNA greatly expands the designer’s pallet. The natural e. coli bacteria used in this experiment can produce 20 amino acids. When augmented with the Scripps artificial DNA, they can create 172 amino acids. Since proteins are built from amino acids, the scope of protein creation is greatly extended.

There are safety concerns. A number of environmental groups had asked that this research be shut down until the safety aspects could be more fully assessed. But a review by the U.S. Presidential Commission for the Study of Bioethical Issues found no reason to call a halt. Their reasoning was that while the technique added some elements to the language of life, it did not fundamentally change the life process. The Scripps researchers did, however, add a safety feature. Their bacteria were designed to grow only in the presence of a specific chemical additive. In the absence of this additive, the bacteria would stop creating artificial DNA, thereby making escape to the wild highly unlikely.

In the end, whenever we think we have a handle on science, it surprises us. This achievement promises great advances in medical science and many other areas. Perhaps even the holy grail, that being the efficient conversion of carbon dioxide directly into biofuel. What a wonderful outcome, should it come to pass.

You can die of a broken heart and other surprising science

"Everything that can be invented has been invented."

In 1899, the Commissioner of the US Patent Office, Charles H. Duell, is said to have exhorted that “everything that can be invented has been invented.” While possibly apocryphal, it was a common sentiment of the time. After all, electricity had been tamed, the light bulb had replaced whale oil lamps, powerful steam locomotives traversed the continent, and Herman Hollerith had developed the Census Tabulating Machine. Indeed, what else could possibly be left to invent?

In retrospect, we see how silly was that view. But that is the nature of scientific certitude. Science is an ongoing process. Things we hold to be true are only working models of reality, and reality is often more complex or strange than we think. When our models (theories) disagree with reality, we must quickly develop new theories.

Science, that is, our view of reality, changes all of the time. For instance, here are a handful of new theories published in just the last few months.

• You can literally die of a broken heart. Researchers in the U.K. studied 30,000 people whose spouses had died and found a significant (nearly double) risk of heart attack or stroke. This risk fades in subsequent months and is correlated with higher levels of inflammatory cells in the blood (which gradually return to normal). (JAMA Internal Medicine, April 2014)

• We may have company in other dimensions. Researchers using a sophisticated telescope in Antarctica have for the first time discovered primordial gravitational waves, thus buttressing the case for inflationary expansion. This theory posits that during the first trillionth of a trillionth of a second, the universe expanded from an invisible speck to near its current size. If true, our universe may be “one of many universes floating like bubbles in a glass of champagne.” (Scientific American, March 31, 2014). 

• Beans beat beef, but even then in temperance. Two recent studies support a theory that too much protein has negative effects on human health. The primary study found that people age 50-65, with a diet where protein is restricted to 10% of total calories, suffered cancer and diabetes at significantly lower rates. Those eating a moderate protein diet (up to 19%), were three times more likely to die from cancer. Oddly enough, the effect reversed after age 65, when a moderate protein diet seems slightly protective. In good news for vegetarians, vegetable protein was found to be more healthy than animal protein overall. (Cell Metabolism, March 2014)

• Dark skin is evolutionarily superior in the tropics. An English researcher studying 40 years of data found that albinos living in areas of high ultraviolet radiation (e.g., Africa, Central America) contract skin cancer and often die young before reproducing. Theorizing that early hominids were pale skinned and largely hairless (to control body temperature in tropical heat), he proposes that nonmelanoma skin cancers killed the lighter skinned and spared the darker skinned. This evolutionary force self-selected dark skin as a superior attribute for survival. (Proceedings of the Royal Society B, January 2014)

• Death rays may not be just science fiction. Physicists at the University of Maryland have demonstrated a one-two combo punch that opens the way for laser weapons. High power lasers tend to heat the atmosphere as they pass through it. The low-density air thus created acts like a lens, defocusing and weakening the beam. Instead, by pulsing a low-power laser several times over 7 billionths of a second, a “tunnel in the sky” is created through which a high energy blast could follow. In addition to death rays, such technology could be used to power high altitude aircraft. (Physical Review X, February 2014)

Science is constantly evolving, constantly surprising. To not be open to multiple possibilities is crippling to a scientist. A close-minded scientist is like a blind marksman; brilliant, perhaps, but unable to hit a moving target. That is why the most prized scientific quality is a finely honed sense of skepticism.

A major mistake for a serious scientist is to follow the herd, but it is oh so hard to resist. Usually grants and funding follow the herd; taking another path can lead to poverty. Disagreeing with the herd will also get you shunned, criticized, and sometimes demonized. For instance, Professor Lawrence Torcello seriously proposes jailing those who disagree with him on climate science.

Here’s a famous example. Dr. Barry Marshall and research partner Robin Warren were all alone in their thinking. The entire world’s scientific community ridiculed their theory, but they persevered. Peptic ulcers are caused by bacteria, not spicy foods or stress. Next time you get a simple antibiotic to cure one, won’t you be glad that they remained steadfast?

We are not alone

Science News Magazine has been published since 1922, over ninety years. The news arm of the non-profit Society for Science and the Public educates and informs the public about current happenings in science and technology. It has covered such seminal events as the first man-made nuclear reaction, the first electronic computers, man’s first walk on the Moon, and the first jet aircraft. For some time, the editors have selected the top science story of each year.

For 2013, there were plenty of candidates. The amazing rise of miniature unmanned aerial vehicles (drones). Gene therapy advances in managing blood cancers. The ability to grow replacement organs from scratch. The Nobel prize in physics for the discovery of the Higgs boson.

But what was the top science story of 2013? Bugs.

Or more precisely, bacteria and other organisms which make up the microbiota living on and within the human body.

In a steady stream of studies and reports throughout the year, we learned more and more about our remarkable little cousins. For instance, the fact that only 10 percent of your cells are human; the other 90 percent are a mixture of bacteria, fungi, and viruses. (That microbes are so tiny and human cells relatively huge accounts for the fact that, by mass, our microbiota only amounts to a few pounds).

Scientists are even beginning to argue that we should view the human body as a superorganism defined by this mixture of human and microorganism DNA (microbiome). The advantage in doing so is that it might help us better understand the effects of diet, chemical exposure, and other factors on our health.

It is important to note that our community of microorganisms is for the most part beneficial. They help us digest food and convert it more efficiently to energy. They influence the immune system, training it to identify and fight true pathogens. They produce hormones instructing our body to store fats, and create necessary vitamins. To understand the workings of the human body without considering our microbiome is, we are finding, impossible.

Michael Pollan, in an in-depth New York Times Magazine article (“Some of My Best Friends are Germs”, May 15, 2013), details his research into this new frontier. Starting with a submission of swabs to the BioFrontiers Institute at the University of Colorado, he received a detailed report of his personal microbiome. Pollan interviews the scientists involved in the project and describes how our microbiome, unique as a fingerprint, is developed. Soon after birth, a community of microbes takes hold in the infant gut. Its composition from there is influenced by environment and, mostly, diet. In fact, the BioFrontiers scientists can identify from a person’s swab samples both where they live in the world and what is the makeup of their diet.

Researchers have observed that obesity may be encouraged by a certain mix of gut flora. And that mix of flora is a result of diet. Meat eaters have a distinct pattern of gut flora from vegetarians. Diets high in sugars and fats are quickly absorbed, denying nutrition to our little minions. They prefer diets high in fiber and complex carbohydrates; these take much longer to digest. What a surprise, then, to see that independent research into low glycemic index (GI) diets have concluded that diets high in fiber and complex carbohydrates are highly preferable for health. The microbes are the key, and they live or die by our dietary choices.

So what might this flood of human microbiome research mean? Perhaps we’ll find that our war on bacteria, with a plethora of antibiotic soaps and cleaning products, might be taking a toll on our little helpers. Certainly we need to be concerned with pathogens, but perhaps we are overdoing it.

We might find that diet books of the future will focus on cooking for our whole selves. Lightly cooked vegetables, whole grains, al dente pasta, for instance, all take longer to digest and provide the fiber that our gut bacteria thrive on. Feed them well and they will serve us well. It would be a complete change in perspective and provide a grand new toolset for managing obesity and optimizing health.

There is much research yet to do and understanding to be gained. But it is exciting that we are beginning to comprehend the owner’s guide to the whole human being.

Thin can be contagious - really!

In the old days, our moms would paint our scratches and nicks with Mercurochrome or, heaven forbid, Merthiolate, which stung like the devil. The goal was to hold the germs at bay. We had a pretty clear idea that our skin was a clear dividing line between that which is us and that which is not. And germs of all kinds were to be kept out.

But to our surprise, we are increasingly finding that some germs, species of bacteria called gut flora in particular, are not only harmless but downright beneficial.

The human digestive system contains trillions of bacteria weighing in at two to four pounds and actually outnumbering the human cells in our body. Gut flora help us process nutrients, harvest energy, create certain vitamins, and provide protection from pathogens. This symbiotic relationship is very complex, one of which we are still just scratching the surface.

Now a new study (Science, September 6) has given us a fresh sense of wonder about our tiny cousins. The surprising finding is that, not only do fat people and thin people have different species of bacteria in their guts, but those bacteria can actually influence obesity.

The study centered around a set of rare human twins, one of which was fat and the other thin. When laboratory mice received bacteria from the obese twin, they started to become fat. Mice receiving bacteria from the lean twin stayed thin. Here is the really interesting part: when the mice were comingled and bacteria in their guts were able to compete, the “thin” bacteria won the competition, infected the guts of obese mice, and kept their new hosts from gaining weight.

So far so good. But if these thin bacteria are naturally dominant, why aren’t there raging epidemics of leanness spreading across the continent?

The answer is diet. The thin bacteria were dominant when the mice were fed a low-fat, high-fiber diet. But when researchers changed that to a high-fat, low-fiber diet (more typically American ), the thin bacteria lost their dominance. They were still able to keep lean mice thin, but they were unable to establish a presence in the guts of obese mice.

The research is promising and bacterial weight therapy may be in our future. But, unfortunately, nothing that will overcome a diet of cheeseburgers and fries.

Why do we care? Because the negative effects of obesity are so severe. The CDC cites research showing that when weight increases to “overweight” or “obese,” the risk of the following conditions rises significantly:

•     Coronary heart disease
•     Type 2 diabetes
•     Cancers (endometrial, breast, and colon)
•     Hypertension (high blood pressure)
•     Dyslipidemia (for example, high total cholesterol or high levels of triglycerides)
•     Stroke
•     Liver and Gallbladder disease
•     Sleep apnea and respiratory problems
•     Osteoarthritis (a degeneration of cartilage and its underlying bone within a joint)
•     Gynecological problems (abnormal menses, infertility)

The health effects are enormous; the impact on quality of life is tragic. And the economic impact is huge, estimated at $147 billion per year. Now that we are all in the same taxpayer-subsidized health insurance risk pool, that should make you take note.

Michelle Obama is right. As a nation, we need to begin moving to a diet which is more low-fat and high-fiber on average.In fact, if we were all to pretend we were pre-diabetic and took up a low GI (glycemic index) diet, our collective weight loss would be measured in megatons.

An apple a day, indeed, may keep the doctor away.