Genetics collides with human nature - scared yet?

kw: book reviews, nonfiction, genetic engineering, crispr, futurism, trends

I try to keep up to date with certain trends, including genetic engineering. When a technical field such as that is so productive and active, however, it is easy to get behind, and even to be blind-sided by developments. Prompted by a friend, I saw a podcast about gene editing, an interview with Jamie Metzl, so I got his latest book, Hacking Darwin: Genetic Engineering and the Future of Humanity. I find the possible futures outlined by the author deeply disturbing, even frightening.

Consider a doctor's visit in 2030; you want to have a baby with your spouse. You have been advised to seek pre-natal screening. You find that, rather than starting the baby with "ordinary" sex, it is now advisable to use In-Vitro Fertilization, followed by egg harvesting, and genetic testing of each of the several embryos thus produced (one cell taken from each embryo). Within a couple of days on a follow-up visit, the doctor shows the two of you a kind of dashboard with dozens of indicators showing how the embryos differ. Some will grow a little taller than the rest; some might be smarter; there are even a few subtle shades of skin color available; and while two embryos are likely to grow to be more intelligent, one of those also carries a significant risk of a troubling birth defect. You can't have everything, but you and your spouse go aside and weigh the options. If none is appealing, you can always try another batch, though it'll double the cost. Once an embryo is chosen, it is implanted and the others are frozen, where they will probably remain until you decide they can be discarded. Consider; this could happen before 2030!

Try to wrap your mind around the possibilities after another ten years: 2040. It is likely by then that you don't need to do egg harvesting from the female spouse; a cheek scraping or a drop of blood contains cells that can be turned into stem cells, and after a further process, thousands of ova, which the male spouse's sperm can fertilize. The dashboard not only has many more embryos to choose from, the number of genetic indicators now numbers in the thousands. Thankfully, the flurry of data has been pre-screened using Artificial Intelligence, and profiles for only a handful of embryos are presented, and for each, the top twenty most-important indicators are shown, though you can drill down into them all if you wish. As before, this process may be available before 2040.

Why would you do this? If, quite literally, everyone is having babies this way, there is great competitive pressure to set your baby up to be smart, strong, long-lived, tall, and good looking. If you take the "primitive way" of "winging it" with "ordinary" sex, you are most likely to have a child who would be average, or hopefully a bit above average (if both spouses are already a little above average). But that child will be way, way below average compared to nearly everyone else. Just by having "average" good health, he or she will pay more in medical insurance premiums, in anticipation of living a shorter life in poorer health than the norm.

Is this the kind of world we want to live in? Will we have a choice?

The bulk of Hacking Darwin explains the literal flood of new technologies being developed right now that portend this kind of future. The competitive nature in all of us ensures that any slight advantage to be gained by these new genetic techniques will be extremely popular. Will they be used by the rich (the first to be able to afford all of the techniques) to produce children who will easily become even richer, leaving the rest of humanity in the dust? They will most certainly try! When "designer babies" (not a new term, but now a reality on the horizon) become affordable for the rich, "Boom!", they'll go for it. A generation later, when the price has dropped to 1% of what it was, the middle class can try to play catch-up, but they'll be a generation behind.

In the last chapter or two of the book the author discusses the kinds of regulations that governments the world over will need to implement to even out the playing field. One look at history tells me he's spitting into a strong wind. Firstly, different nations will adopt different regulations and at different times. The present emotional battles over GM (genetically modified) crops and abortion will be as a friendly game of checkers compared to what will result. Medical tourism is going on now, for procedures that cost less elsewhere (Go to France for a bone marrow transplant, for example, where it costs 1/10 of the cost in the U.S., and the French have a better track record). Genetic tourism will soon be all the rage. Live in a country that outlaws the "big dashboard"? No problem. Take a month's vacation to somewhere less restrictive. Lie through your teeth about why you went…or don't return, if the questioners will be gun-toting officials. 

Put it all together, and an era of post-humanism is rapidly approaching. By 2050 or so, "Engineer your own Baby" kits will be available over-the-counter. By 2100, who will be left that would be recognizable as an "ordinary human" today? Maybe many, maybe few, possibly none. To the friend who suggested I listen to the podcast, I wrote, "I hope Jesus returns while there are still humans to return to."

Messing with DNA — it's what we do

kw: book reviews, nonfiction, genetics, domestication, genetic engineering, sociology

DNA is practically designed to be tinkered with. It isn't hard to do. At age ten I was hybridizing tulips. I produced some pretty varieties. Then a master of DNA tinkering showed up: an infection by the Tobacco Mosaic Virus produced many "parrot" coloration varieties. Within a couple of years, things settled down, and some of the tulips went back to being the mostly solid-colored ones Mom had originally planted, plus a few of my 2- and 3-color hybrids, but some striped ones remained, apparently now breeding true to their new appearance.

Some time between 15,000 and 40,000 years ago, a subtler change occurred in an animal that hung around human encampments. Wolves had probably been stealing from garbage dumps for thousands of years already. Some, most likely younger ones, got used to continuing to gnaw on cast-off bones even if a human showed up, if the person didn't make threatening noises or moves. Did people domesticate wolves, did wolves domesticate themselves, or did both species domesticate each other? I suspect most humans were originally rather displeased about having scavengers around, so I favor the latter version. 

Whatever narrative appeals to you, at this remove of time, the main thing we know is that even very wolf-like dogs remain like juveniles. It's like dogs all have Peter Pan syndrome and never grow up. If you ever get acquainted with a wolf, as I have, you'll realize that an adult wolf is all business. Reach out a hand, and get back a stump. Make the kind of "hand-on-knees" play gesture that'll make almost any dog trot over to play tag, and a wolf will most likely fix you with a cold stare, "Seriously, human?" That's if it knows you well enough to stand there to watch your antics.

The critters we call "farm animals", "pets", and "livestock" are genetically very different from their ancestors. Cattle came from Aurochs, for example. On a camping trip I once awoke in the tent to find cattle grazing all around. I went out and swatted a few butts and said things like, "Get along now, my wife has to get up." They placidly moved on. Try that with Aurochs (you'd need a time machine), or even Bison. Your remains will soon be well mixed with mud.

Domestication and selective breeding are the traditional way to mess around with DNA. More recently we've gone from simple domestication to hyper-tinkering, still by cross-breeding and such. Your great-grandma's chicken weighed a pound and a half. Now a roasting chicken can weigh as much as eight pounds, and they cook twice as fast as a turkey of the same size, so when my wife and I have Thanksgiving alone (that may be what we have to do this year…will 2020 never go away?), we roast a chicken. But even fryers in the 3-4 pound range frequently have broken legs so frequently, because they have been bred to grow so fast their bones can't keep up.

Then there are all the plants we call "crops", plus "garden plants" and "house plants". Unless you go to the wilderness to get plants for your garden, everything in your environment has been genetically changed in the past centuries or longer. A long time ago I collected ferns for a large terrarium I made from a leaky fish tank. Forty years later I still have two or three of them. They are "wild", even thogh I keep them in "captivity". But the vegetables in one garden, and the lilies and irises and such in others, are far removed from their wild ancestors.

Dogs and domestic animals of all kinds are the backdrop to the opening chapters of Life Changing: How Humans are Altering Life on Earth by Helen Pilcher. The various kinds of selective breeding are just the start. Hybridization is another, like what I was doing with tulips, but more persistently and permanently. The mule is an ancient hybrid. Even though it is famously stubborn, it is stronger than a horse or donkey and eats less. It's the prototype of a sterile hybrid, which makes it a made-to-order animal that won't breed a herd of wild mules and take over a chunk of forest or field. Other hybrids are fertile and sometimes they settle down to become a new, stable species.

There are chapters that get into molecular engineering and genetic engineering, mainly the newest tool: CRISPR-Cas9. Humans didn't invent this tool, we discovered it. Microbes have been using it for a couple of billion years for their own purposes. It turns out that we can use it to cut-and-paste DNA however we like. Getting DNA from some cells and patching stuff in and out is pretty easy these days. The next step is harder. So hard, we're very early on the learning curve for putting the edited DNA into a working cell or a virus that can insert it into a living cell without horrible or fatal side effects. The next couple of decades ought to be interesting.

Methods more similar to the traditional interest me more. In vitro fertilization (IVF: test tube babies were the first human products, including some of my relatives) is one way to speed up the breeding process, or to cause it to happen when there are natural barriers to natural breeding (in humans, these are summed up as "infertility"). For example, IVF is being used to breed corals rapidly or to cross-breed them in an effort to produce varieties that can survive in the oceans as we expect them to be for the next couple of centuries.

That introduces another aspect of "altering life". The life we ignore, except when we go "enjoy nature" or do some "ecotouring", is being affected a lot more than we realize. Consider this: 96% of warm-blooded animals on Earth are domestic; 2/3 are birds and 1/3 are mammals. Most living birds are chickens, about 24 billion. We breed them so fast, though, that there is a total turnover about every six months because worldwide consumption of chickens is 50 billion. Cattle number about a billion. They breed more slowly; about 300 million are slaughtered for food yearly. They outweigh the chickens, probably about ten to one. Besides the space taken up by all the livestock, about half of all farmland grows crops to feed the chickens and cattle, plus swine, sheep, goats, turkeys, and so forth. The 4% of total animals that make up all the wildlife on earth have a much smaller Earth to host them.

It is heartening to read in the later chapters of efforts to "rewild" some places. The author highlights a few, such as the Knepp Estate in Sussex, England and Pleistocene Park in Siberia. Large and largish keystone species such as boars or elephants will, for free, "engineer" a landscape such that it is attractive to such a great variety of other plant and animal species, and the variety and beauty multiplies. Rare creatures (the Purple Emperor butterfly is a great example) are found at Knepp that are seldom seen elsewhere. Sturdy, Arctic-hardy horses are making Pleistocene Park better and better as a habitat for numerous small animals and the plants they favor. Mammoths, or cold-adapted Asian elephants if the Woolly Mammoth cannot be "re-evolved", would do much more to return that area to its earlier splendor.

It was such a pleasure reading this book that when the author put in a plug for her earlier book, I snapped up a copy. Stay tuned on that. In the meantime, this book is a lot more than a "gee whiz" compendium of things we can do with DNA. It emphasizes the hopeful trends that are arising. It points toward an Earth in which humans begin to play a little nicer, as we realize just how interdependent we are with "the rest of nature."

Seeds of discord, winds of change

kw: book reviews, nonfiction, biology, genetic engineering

Contrasting statements:

1. From the Statement of Policy of the FDA, "Ultimately, it is the food producer who is responsible for assuring safety."
2. From Monsanto's director of corporate communications, "Monsanto should not have to vouchsafe the safety of biotech food. Our interest is in selling as much of it as possible. Assuring its safety is the FDA's job."

Dr. Richard Strohman of U. Berkeley has written, "DNA is most definitely not the secret of life...the idea that there is a direct relationship between a single gene and a single trait is completely erroneous...[this is] the myth of genetic determinism."

This myth underlies the entire biotechnology industry today. In Uncertain Peril: Genetic Engineering and the Future of Seeds, Claire Hope Cummings chronicles how the misapplication of genetic ideas is undermining the foundation of the world's farming enterprises. Her charges against the biotech industry are as numerous as they are large. In whatever measure they are correct, they foretell a greater threat to the sustenance of civilization than any other effect of human activities.

Did you know that tomatoes and potatoes, being related and being members of the Nightshade family, are potentially quite poisonous? A large salad of tomato greens can stop your heart. Yet the fruit is nutritious and quite safe to eat! How can this be? The fact is, many, many plants produce various pesticides as they struggle to grow to maturity without being eaten down to the roots, yet their food parts contain no trace of these pesticides. So why are such critters as the Tomato Hornworm able to eat the leaves without harm? In the perpetual arms race that is evolution, this worm is one critter that has evolved a way to inactivate the Nightshade toxin in its food.

In the perpetual struggle of science to imitate nature, and it is hoped, do her one better, biotechnologists have sought to take potent natural pesticides such as the toxic proteins of B. thuringiensis and cause their expression in food plants. These plants then grow with less need for the application of chemical pesticides. Getting them to produce their own "BT toxin" has been seen as a simple matter of getting the right gene from the BT bacterium into the genome of the plant you want to grow. But there is a catch, a big one.

The scatter-shot methods being used to get novel genes into the genomes of crop plants seldom work, but when they do, they work too well. "BT corn" (BT maize), for example, expresses the BT toxin proteins in equal amounts in all its cells, even though the pests that BT affects mainly attack the roots, and the leaves a bit less. They don't attack the kernels much at all, leaving that to a different array of pests that aren't bothered by BT! The problem comes when we find that many people are harmed by BT residues.

Many farmers rely on sprays of BT organisms, the natural bacteria. These effectively kill pests, and the toxins can be washed right off the kernels after harvest. People can't avoid ingesting BT toxin if it was produced right inside the cells of the kernels.

So why haven't folks done the extra work to get the BT genes into a section of the genome that is "turned off" in the kernels? There is a nice, convenient stretch of DNA that contains the plant's natural pesticide-making genes, which are switched off in the seed cells.

Such precision of placement is quite out of the question with "modern" technology. Simply developing the methods that would allow it is prohibitively costly. Oh, it will get done anyway, but slowly, almost as a side effect of other studies. But this is only one instance, and in this case, the relevant target is pretty well known. For most plants, they'll also have to do more science to figure out exactly where to put new genes, to take advantage of such natural switching mechanisms.

All this digression is my own, an introduction to the troubles we are getting ourselves into by creating GMO's, Genetically Modified Organisms. And this is just one of those troubles. Ms Cummings outlines several areas of peril, but the greatest is the loss of seed diversity.

Industrial processes rely on control, and control requires uniformity. Industrial agriculture, which is now almost universal in the West, controls its markets by controlling seed varieties. Each seed company boasts of its "broad line" of varieties, and such lines do seem broad: ten or twenty varieties of a particular species. But contrast that with the contents of seed banks, that have existed or do exist today, with their tens of thousands of natural varieties per species.

For example, around the world there are more than five thousand varieties of rice being grown, and most of this diversity is in the hands of small planters who share seed among themselves, continually seeking the best variety for their combination of soil type and climate. Because all the grains are wind-pollinated, rice growers know that their own fields will produce best if they and their neighbors all grow good, strong varieties. It is thus in their interest to give the seeds of better varieties to any of their fellows who are having trouble with their harvests, in hopes that the winds will carry a good mix of the strongest rice varieties, to the benefit of them all.

Contrast this with the grower who buys seeds of only one variety for a million-acre planting, a variety that is a sterile hybrid, so that he cannot even keep back a part of the harvest for planting the following year. Not only that, he must sign a contract not to try to do so, in order to get these special seeds at all!

The dirty secret behind the bumper crops that super-seeds produce is that their harvest will utterly fail without constant, costly application of fertilizers and "crop protection" chemicals. The upshot is this: the small farmer using traditional seeds may have a lower yield per acre, but the cost to produce it was much less.

The risk of large monocrops is not just that a new pest will arise to decimate the entire season's crop. It is that a huge number of non-patented varieties is ignored, many are no longer planted, and many go extinct.

This is a tiny tip of the iceberg. Author Cummings sees hope, in spite of the perils. Increasing numbers of farmers, seeing the hypocrisy in the two statements I began with above, are rejecting the industrial model of agriculture. One promising trend is illustrated by Wes Jackson of the Land Institute in Salina, KS. He has sought to produce a plot of ground that will "produce like a farm field but act like a prairie". A healthy bit of prairie, say a meter square, contains dozens or even hundreds of species. It has the wherewithal to respond effectively to the vagaries of almost any year's weather.

I remember reading, years ago, of the efforts at Malabar Farm in Ohio, Louis Bromfield's experimental farm at which he sought to rebuild the topsoil. He was a particular advocate of multi-cropping, though in his book Malabar Farm he primarily illustrated the idea with a duo-crop of alfalfa and corn. Organic farmers are busily working at ways to extend this idea, taking advantage of natural synergies that abound around us.

Here is a question for you: Why is the ground kept so clear in an orchard? I lived across the street from fruit orchards as a boy. I remember the farmer saying that the right kind of undergrowth made the trees healthier, rather than "robbing" them of water or nutrients. But the ground was kept clear for the convenience of farm workers and harvesters. A pity.

There are many good ideas in Uncertain Peril, and lots of hope. May the hopes outstrip the perils, for our future rests upon them.

Dinosaur Construction 101

kw: book reviews, nonfiction, dinosaurs, DNA, genetic engineering

About twelve years ago, shortly after Jurassic Park hit the big screen, a colleague told me he was briefly famous for the first recovery of proteins from a fossil. In the '70s, when he got his PhD, he discovered a relationship between the normal body temperature of a mammal and the ratios of certain "structural" amino acids in their proteins.

Brief aside: The structure of a protein shifts with temperature. It won't work outside a certain range. About half the 20 amino acids (AAs) are mainly structural, forming the helices and sheets that form the shape of a protein. Biochemistry is mainly geometry. For a protein to work best at a different temperature, a shift in the proportions of certain AAs is required.

When my colleague published his results, a friend asked him if his method would work on the proteins from an extinct animal. He said, "Why not. But how would you get some?" The friend brought him some bones of Smilodon, the best-known sabre-tooth cat, from the Rancho La Brea tar pits in Los Angeles. When the animals died there, they were quickly dried by the tar, and the proteins in bone cavities were often preserved.

They were able to extract sufficient protein to work the method, and published a letter stating their findings. My colleague was at a conference in England when the letter was published. Suddenly, he got many calls from reporters, and a British paper published a cartoon of him, sneaking up on a huge Smilodon, and carrying a spear-sized rectal thermometer!

Now, the tar pits contain bones aged between 40,000 and 10,000 years. Hardly dinosaur-age stuff, which is between 65 million and 200 million years old. But impressive for 1970 or thereabouts.

It is a long way from body temperature to a dinosaur clone. A small measure of the difficulty is presented in Jurassic Park, both the movie and the book by Michael Crichton. A recent book makes it clear how much harder it actually is. Rob DeSalle and David Lindley, a working scientist and a highly expert science writer, in 1997 published The Science of Jurassic Park and the Lost World, subtitled, Or, How to Build a Dinosaur.

Dr. DeSalle isolated the first dinosaur-age bit of DNA in 1992, from an insect in amber. It was insect DNA, though, not dinosaur DNA. Older bits have been found since, as old as 135 million years. So when he outlines how one might (just barely, maybe) retrieve dinosaur DNA and eventually produce a living dinosaur, he has it right.

He agrees that amber is a good place to begin looking, but he prefers amber from New Jersey, which is the right age, to Dominican amber, which is only 30 million years old. But what guarantee do we have, if we find a biting critter with a belly full of blood, that it was a dinosaur's blood?

I have recently read of the recovery of soft tissue from deep inside a Tyrannosaur hip bone. Perhaps we ought to be looking there, instead. Otherwise, you're more likely to find the blood of a proto-possum than a dinosaur, which is quite a bit harder to bite...we do have samples of dinosaur skin, so we know.

The authors go through, step by step, what is needed to do the task. They make clear the uncertainties at every step. For example, the DNA sequencing method called "shotgun sequencing" is probably most amenable to this, but it cannot tell you how many chromosomes there were. We only learn this when we sequence, say, a chicken, because we can look at living chicken cells and sequence them one chromosome at a time. If you have a DNA soup with the entire genome in little bits (say from 200 to 1000 bases per chunk, each broken out of a 2- to 3-billion base sequence), you can't really tell where the chromosomes ended. Telomeres (repeated sequences at the ends) are too variable from one animal to the next to prove anything; one critter's telomere might be another's internal repeat sequence.

Suffice it to say, the undertaking is too expensive for an ordinary billionaire. Given the rate that DNA work's price is dropping, however, I expect it might be possible in another decade or two, making initially one assumption: that we can actually recover large enough bits of 80-million-year-old DNA, in sufficient quantity, in the first place. That may be the biggest hurdle of all.