Zebroo

But What Do We Call Him?

The cloning of humans is on most of the lists of things to worry about from Science,
along with behaviour control, genetic engineering, transplanted heads, computer poetry and the unrestrained growth of plastic flowers.

- Lewis Thomas

Source: I no longer know as I can't find this again. Probably not Mother Nature.

Cuter than Mother Nature Provides?

Bordeaux Mixture

If at first you can't convince people about the benefits of GM crops - cheat.

by Charles Dexter Ward

I'm spraying my tomatoes with bordeaux mixture and it feels great. My wife says I do the tomatoes a disservice, dousing them with Bergerac, when our pension could easily spare Clydebank Cabernet. But the tomatoes love it. No sooner do I get to their row with the sprayer, than their desiccated leaves flush with green; their blooms perk up; their ripening fruits blush with a richer glow. They love me, my tomatoes, and I love them back. Today is special - it's 2090, and my tomatoes and I are celebrating the safe passage of our life-giving Sun through yet another total eclipse.

Anyway, while I'm up there schmoozing, I think how far we've come in just one lifetime. Once upon a time, tomatoes were monotonous plants that took a lot of looking after; constant watering and spraying against greenfly and rot. Today's GM tomatoes are as different from the crop of my youth as the einkorn and emmer they harvested in the Fertile Crescent with obsidian sickles.

I've got rows of them - tomatoes, that is - all the latest kinds: juicy blue ones as big as canteloupes; fluorescent orange fruits the size of pinheads but as hot as habañeros; long thin ones like cucumbers; tetrahedral ones; ones with edible roots; ones that grow like trees which I harvest like apples. And they look after themselves, pretty much; they farm their own mycorrhizae; nurse their own symbionts, kill off the weeds with endogenous antibiotics, and suck what little water they need out of the air. No, I only spray my tomatoes with bordeaux mixture because they enjoy it. They want me to, and, willingly, I oblige.

These days, the word "tomato" seems almost redundant, as everything else in the garden has undergone much the same kind of transformation. If every plant can be made into anything you want, and made to taste like any other crop, it rather breaks down the barriers. If you have lettuces that look like onions and taste like lemon meringue pie, who cares about horizontal gene transfer?

You'd think that this uncertainty about what's what in the garden would worry me, given that I've always seen myself as something of a tomato connoisseur and never knew my onions. What if I found myself growing an aubergine by mistake, an aubergine that looks1ike a tomato? But the fact is I don't care: the tomatoes themselves see to that. It gives me such a thrill to see them practically whoop with solanaceous pleasure as they see me advancing up the garden; such a feeling of contentment as I can hardly describe.

It hardly seems possible that, less than a century ago, people objected so violently to genetic modification, when subsequent history shows it to have been such a wonderful innovation. How silly it all now seems: all those people who trashed test crops seem, in retrospect, like those weavers who broke up power looms. But then, I was doing some of the modification, so perhaps I'm biased.

Now I'm long since retired, and the company I was working for back in 2007 - when everything changed - has gone the way of Microsoft and Tharsis Telomerase, I can tell all. In 2007, GM was so unpopular with the public that bioscience companies had to fund research and development almost in secret. Progress advanced in giant steps, but all behind the scenes. Unknown to the public, there were plants that did everything except talk back; plants that created their own self-sufficient ecospheres. A few were dropped on the martian South Pole. There were no announcements, no press releases. I hear that a few small stands of martian maize still thrive.

Then a few of us at the lab hit on an idea. We transfected maize with genes for human pheromones. With our corporate heads, we thought that this would do wonders for brand loyalty. The thing is, human pheromones influence behaviour subconsciously. To tell people what we were doing would defeat the object, wouldn't it? Late one night we planted a stand of GM maize in California (I forget exactly where) and within weeks there were activists pounding the door of the Capitol in Sacramento demanding GM crops. Success breeds success - we got the same encouraging results with courgettes in Chihuahua, tomatoes in Thailand and greengages in Glasgow.

But that was long ago, and anyway, when I'm up here with the tomatoes, all that matters is the continuous present, when I am surrounded by the rapturous cacophony of my gorgeous plants - all mine - the plants I love and that love me so much in return, filling the green ether with triumphant shouts of radiant joy.

Charles Dexter Ward hopes to be the first writer-in-residence on the Space Station. A collection of his fiction, God Among the Robots and Other Stories , will be published in 2000 by Unicorn Gardens Press.

Source: Nature Vol 404 23 March 2000 "futures" column

I love tomatoes, too, but really!

/ [A New Slant on the Future from Greg Bear]

Source: Scientific American September 2001

The Awful Truth

by Philip Cohen and David Concar

Why would anyone in their right mind want to clone a baby when animal cloning can go disastrously wrong?

Zita the supercow was a beast in a million, the highest-ranked Holstein in the US. In her prime her milk yield was nearly twice the average, and cattle breeders paid top dollar to get her genes into their herds. Then, alas, she got old and died.

But dry your eyes. This is the age of the clone, and the genetic blueprints of prize cows can now be saved from the grave. Grazing on a farm in Maryland are Zita-2 and Zita-3, two three-month-old calves cloned using two cells from Zita's ears.

American cloning companies are busy making multiple copies of just about every top pedigree cow and bull in the land. In time, they hope identikit supercows and superbulls will be bred, milked and even butchered for profit, just like the old ones. "We're cloning some of the highest-level bulls and think we can sell hundreds," says Ron Gillespie of Cyagra, the Massachusetts company that cloned Zita. For prize breeding animals, which can fetch $40,000 or more, cloning is economic even at today's going rate of $15,000 to $25,000 per cow. And as more animals are cloned, the cheaper it will get. "Push the price down to $10,000 and there would be 100,000 animals that it would be economic to clone, and in the $5000 range, millions."

That's millions of cloned cows and bulls. Created just to make food. In the US alone.

Ever since Dolly the sheep was born, fears about cloning have been tempered by hopes that the technology will one day save thousands of human lives. And so it might. Already cloning is enabling scientists to produce animals capable of secreting valuable drugs in their milk, and to look for ways to clone tissues for transplantation. But developing these medical spin-offs could take up to 10 years. Cloned beef steaks and milkshakes could be with us much sooner.

So far, it's the baby cloners who have been in the firing line. Now, as companies like Cyagra forge ahead, the prospect of cows being cloned en masse for food is provoking alarm as well. And not just among animal welfare campaigners.

Ian Wilmut, the scientist who led the Dolly team, says it is vital that controlled farm trials of cattle cloning are carried out before any commercial production of cloned meat and dairy food is allowed. Companies need to prove that large-scale farm cloning involves no undue animal cruelty, that clones are as healthy as ordinary animals, and that food from cloned animals and their offspring is as safe and nutritious as conventional food, Wilmut said. The cattle cloners "ought to be making systematic comparisons between clones and animals produced by embryo transfer, looking not just at their milk yield but also their health and lifespan." Until then, he says cloned food ought to be banned from shops and restaurants. "If companies start marketing this food and there are problems it will bring the whole technology into disrepute."

Herds of identical cloned animals would be a welfare disaster, says Joyce da Silva of Compassion in World Farming. "There would be a huge loss of genetic diversity with unforeseeable results in terms of animal illness."

A more immediate fear is that four years on from Dolly, cloning is still a waste of animal life. For every Zita-2 or Zita-3, say scientists at the sharp end, scores of clones die in the womb or develop deformities, and even clones that look healthy could be "ticking time bombs" destined to go awry. Until recently, the full extent of the problem was hidden, largely because the cloned animals that don't survive don't get much space in scientific papers. A rare exception is a 1999 paper that appeared in the journal Theriogenology (vol 51, p 1451) under the heading "Clinical and Pathological Features of Cloned Transgenic Calves and Fœtuses". The paper is an eye-opener.

Take the short life of "Calf 1". Its placenta was bloated with six times the fluid of a normal pregnancy. Yet at birth it appeared normal. It mooed, started breathing and tried to stand. But appearances were deceptive. Its blood oxygen levels were 1/3 of what was expected, and carbon dioxide was up to three times normal. A day later, oxygen was pumped into its lungs and it was sedated with valium, but to no avail. The calf was soon dead. Its lungs had never properly inflated, it had an enlarged heart, and its liver, which should have been a smooth crimson organ, was a roughened orange slab.

And those, remark some cloners wryly, were the "good old days". "We saw consistent defects, so we thought we'd find consistent solutions," says Jim Robl of the Massachusetts-based company Hematech. Over-sized calves, lung and heart problems were the major themes. But now the more cloners you talk to, the longer the list of defects you hear about: enlarged tongues, squashed faces, bad kidneys, intestinal blockages, immune deficiencies, diabetes and shortened tendons that twist the young animal's feet into useless curves. "There's no pattern," says Robl. "It's perplexing."

Nor are the clones the only victims. The cow that carried Calf 1 suffered a fatal fall in blood pressure after the birth. In fact, 4 of 12 surrogate mothers in the study died from pregnancy complications. Such deaths still happen despite improvements to cloning, says Michael Bishop of Wisconsin-based cloning company Infigen. "We sacrifice the cow and the clone... all the heroics in the world can't rescue those animals."

Despite this, some commercial cloners claim that cloning is no more wasteful than cattle breeders' standard artificial insemination methods. The figures to date suggest otherwise. While artificial insemination has a 40% success rate, at best only 5 - 10% of implanted cloned embryos become live calves. Around 75% die in the first two months of pregnancy but miscarriages and terminations happen right to the end. And every fourth clone born is either stillborn or suffers from a lethal defect.

Even clones that survive and look healthy may harbour subtle defects. When Jon Hill from Cornell University examined the behaviour of newborn cow clones, he found they scored lower on average than typical cows in tests of attentiveness and intelligence. And mouse cloners say that one in three clones born looking normal become massively overweight a few weeks later. "Researchers who study obesity in mice say they have never seen such fat animals," says Ryuzo Yanagimachi of the University of Hawaii at Manoa. Yanagimachi's team is now taking a close look at gene activity in newborn mouse clones. And things aren't looking good. "All cloned babies have some sort of errors," he says. "I'm surprised they can survive it."

Of course in some species, they don't survive at all - witness the countless failed attempts to get cloned cat and dog embryos to develop into living, breathing animals.

Back at the cloning companies, scientists see this outbreak of negativity as little more than propaganda orchestrated to put off the baby cloners. What happens with mice is no guide to what happens in other animals, insists Robert Lanza of Advanced Cell Technology in Worcester, Massachusetts. Lanza says his company has carried out fresh, and as yet unpublished, tests on virtually every surviving cow it has cloned and claims they are healthy and normal. "People have said they don't believe there is a single normal clone alive. That is just total nonsense."

In any case, say the cattle cloners, even if clones are quite different from other animals, that doesn't make them unhealthy. Infigen has amassed a huge database of blood tests from apparently healthy cloned cows. "The data suggested to the vets that some of them should be dead," says Infigen's Michael Bishop. "I think that shows we don't really know what normal is."

Perhaps. But whether that is the sort of reassurance needed to silence the sceptics seems debatable when even small imbalances in hormones, proteins or fat levels could alter the quality of milk and meat. According to Britain's Food Standards Agency, in Europe cloned meat and milk would be classed as novel foods and so sellers would need a special licence. But unlike GM foods, there is no legal requirement for cloned food to be labelled. And nothing to stop British farmers importing cloned cattle.

Meanwhile, there's one thing virtually every animal cloner agrees on: human cloning ought to be unthinkable. The idea of screening cloned embryos for chromosomal abnormalities, and using imaging to keep tabs on the fœtus, is "sheer nonsense", says Don Wolf, who is attempting to clone monkeys at the Oregon Regional Primate Research Center in Beaverton. Fœtuses that look robust at 60 days may die at 61. And a clone that dies after 5 days of life can have normal chromosomes and genes while still in the womb. "How in the world," asks Wolf, "will they screen out problems when they don't know what to look for?"

So far that question has been aimed only at the baby cloners. One day it could be on the lips of shoppers faced with shelves bulging with milk and meat from cloned supercows.

Source: New Scientist 19 May 2001

Test Tube Babies And The Risk Of Genomic Imprinting Diseases

The number of "test tube babies" is growing year by year, and in highly developed countries it will soon make 1% to 3% of all newborns. How safe are Auxiliary Reproductive Technologies (ART)? Specialists of the Research Institute of Medical Genetics (Tomsk Scientific Center, Siberian Branch, Russian Academy of Medical Sciences) recently examined one aspect of ART safety - the risk of genomic imprinting diseases.

Normal development in mammals requires that maternal and paternal gene sets differ functionally. In certain genes, only the maternal copy should work and, in others, only the paternal copy should. The mechanism regulating functional differences of parental genomes is called genomic imprinting. This is a complicated, multi-step process which starts in the parental gametal cells, where special enzymes mark and disconnect the required genes (a human being has about 70 of them), and continues after impregnation. Heavy pathologies can be caused by failure of such marking at some stage, and several genomic imprinting diseases are known with human beings.

Genomic imprinting reacts to external factors, and the researchers expected that auxiliary reproductive technologies could influence it. The first example of such influence was discovered in experiments on animals’ artificial impregnation. The "large posterity syndrome" sometimes develops with big horned cattle and sheep after embryo cultivation, the posterity weight often by twice exceeding the norm.

Another important indication is increased fœtus mortality in the course of pregnancy and in labour, at that the pregnancy is long and the delivery is difficult. The deceased fœtus and newborns have internal pathologies. The "large posterity syndrome" caused by derangements of genomic imprinting is very similar on the surface to the Wideman-Beckwith human syndrome arising for the same reason. In case of the Wideman-Beckwith syndrome, infants are born very big and with multiple pathologies. The syndrome frequency is normally one case per 12 to 15 thousand of newborns, but it is several times higher with the children born with the help of ART.

The researchers suggest several hypotheses explaining why genomic imprinting diseases occur more often in case of the ART than in case of traditional conception:

The process may be influenced by methodical peculiarities of artificial impregnation. In case of extracorporal fertilisation, women are injected hormones to stimulate the ovulation. Possibly, gonadotropins accelerate maturation of ovums, which have not finished yet the genomic imprinting process. In some cases ovums have to be cultivated in nutrient medium prior to fertilisation, and after fertilisation embryos are bred on it before transplanting in the maternal organism. The nutrient medium composition and the lack of signals coming from the maternal organism in a normal case can also impact genomic imprinting, which takes place both in maturing ovums and in the developing embryo. It is not improbable that the genome marking can be influenced by cryopreservation of gametal cells and embryos, which is often practiced.
ART enables the events that would have never happen in a natural way. Thus, "anomalous" ovums can mature in case of hormone stimulation, such ovums would have scarcely mature during a natural cycle. Spermatozoa also can have imprinting defects. Normally, their fertility is low but they can be used for artificial impregnation, and then trouble is inevitable.
Artificial impregnation makes it possible that ill children are born from infertile married couples who have predisposition to genomic imprinting diseases.

There is no unanimous opinion among researchers regarding ART and genomic imprinting diseases. Some assume that birth of "test-tube" children is an extremely rare event and it cannot be the reason for rejection of artificial impregnation. Their opponents believe that the genomic imprinting abnormalities cases known to us make only the visible part of the iceberg. We do not know too many things, and the risk of giving birth to infants with imprinting defects is although little, but important.

Therefore, it is necessary to investigate the problem and to make extracorporal fertilisation safe in every respect.

Source: scientificblogging.com (<scientificblogging.com/profile/news>) 19 November 2007