The ScienceBlogs Book Club

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Imagine that mad scientists defied nature and violated the barriers between species. They injected human DNA into non-human creatures, altering their genomes into chimeras–unnatural fusions of man and beast. The goal of the scientists was to enslave these creatures, to exploit their cellular machinery for human gain. The creatures began to produce human proteins, so many of them that they become sick, in some cases even dying. The scientists harvest the proteins, and then, breaching the sacred barrier between species yet again, people injected the unnatural molecules into their own bodies.

This may sound like a futuristic nightmare, the kind that we will only experience if we neglect our moral compass and let science go berserk. But it is actually happening right now. Today millions of people with diabetes will inject themselves with insulin that was produced by E. coli.

The fact that no one is disturbed by this state of affairs says a lot. It’s like the curious incident of the dog in the night-time Sherlock Holmes notes in the story “Silver Blaze.” When a Scotland Yard detective replies, “The dog did nothing in the night-time,” Holmes replies, “that was the curious incident.” But thirty years ago the dog was barking loudly.

In the early 1970s, a handful of scientists realized that they might be able to insert genes from other species into E. coli. They chose E. coli because, as I explain in my book Microcosm, it was the organism they knew best. With that knowledge came the power to manipulate it. Scientists figured out how to use some enzymes made by E. coli to snip segments of DNA out of the cells of animals. Then they loaded the segments onto tiny rings of DNA called plasmids, and injected the plasmids into E. coli. In 1973 Herbert Boyer, a biologist at the University of California, San Francisco, announced that he and his colleagues had endowed E. coli with DNA from an African clawed frog.

i-4c45ccae66f485d1c9de7df9476e126c-carl_zimmer.jpgBoyer and others wondered if engineered E. coli might not just be able to carry alien DNA. Maybe it could read those new genes and make proteins from them. The bacteria could become biochemical factories.

A race began. Boyer and colleagues in California vied with a team of Harvard scientists headed by Walter Gilbert to be the first to engineer E. coli carrying the human insulin gene. At the time, diabetics could only get their insulin from the pancreases of pigs. E. coli might be able to create it in vast amounts from little more than sugar. By 1980 the race was won: Boyer’s team had created an insulin-spewing E. coli. Their start-up company, Genentech, passed on the bugs to the pharmaceutical giant Eli Lilly, which breeding it in gigantic fermentation tanks.

In those few frenzied years of scientific research, the world shuddered at the thought of E. coli carrying alien genes. It could trigger unspeakable disasters, they thought. Insulin-producing E. coli might escape from their tanks, take up residence in people’s guts, and cause epidemics of diabetic comas. They might spread cancer viruses, or some other unnatural plague. Erwin Chargaff, an eminent Columbia University biologist, called genetic engineering “an irreversible attack on the biosphere.”

“The world is given to us on loan,” he warned. “We come and we go; and after a time we leave earth and air and water to others who come after us. My generation, or perhaps the one preceding mine, has been the first to engage, under the leadership of the exact sciences,in a destructive colonial warfare against nature. The future will curse us for it.”

At the same time, people warned that we were doing the unnatural, something that humans were not meant to do. “We can now transform that evolutionary tree into a network,” declared Robert Sinsheimer, a biologist at the University of California, Santa Cruz. “We can merge genes of most diverse origin–from plant or insect, from fungus or man as we wish.”

It was not a power that Sinsheimer thought we could handle. “We are becoming creators–makers of new forms of life–creations that we cannot undo, that will live on long after us, that will evolve according to their own destiny. What are the responsibilities of creators–for our creations and for all the living world into which we bring our inventions?”

Engineering E. coli came to be known as the Frankenstein project. The protests sometimes took on almost religious tones. Tampering with DNA, the MIT biologist Jonathan King declared, was “sacrilegious.” Two political activists, Ted Howard and Jeremy Rifkin, condemned genetic engineering in a book called Who Should Play God?

It is striking to look back at this controversy from 2008. We suffered no epidemic of diabetic comas, no cancer viruses spread by E. coli from host to host. None of the dire warnings about engineered E. coli, in fact, came to pass. It appears that the safeguards put in place were good enough, and that engineered E. coli could not compete with its wild cousins. Scientists continued to engineer E. coli, and today it can make all manner of substances, from blood-thinners to jet fuel.

Despite all these bacteria suffering the indignity of being violated with human genes, no one seems to care. No one thinks the dignity of E. coli has been compromised. I have not heard of anyone refusing blood-thinners or insulin because it was produced from human genes put inside another species. In Europe, where protests over genetically modified plants and animals rage today, few seem to be bothered by the fact that a lot of cheese is produced with a cow’s enzyme, chymosin, made by E. coli rather than cows. In fact, this cheese is labeled organic, because it’s produced with “real” chymosin, rather than “artificial” chemicals.

I think that the story of engineered E. coli is an important one to bear in mind these days. Today we are faced with intense debates about whether it’s right to create chimeras–a mouse that carries human neurons, for example. Headlines assault us with the danger that scientists will be playing God by creating life from scratch. We are revisiting old ground.

There’s no question that scientists must think carefully about the potential risks of engineered organisms. And we must beware that we don’t try to use genetic engineering to fix problems it can’t fix. Diabetes can be controlled with insulin from E. coli, but it can’t be cured with biotechnology. In fact, diabetes has exploded since Lilly started producing the stuff from bacteria.

But it’s also important to bear in mind how easy it is to be terrified by a science-fiction caricature of what’s really going on in synthetic biology labs. We have a profound distrust of what seems unnatural, such as crossing species boundaries. Yet a casual glance at E. coli’s genome demonstrates that nature has been inserting foreign genes into it by the hundreds for millions of years. Our own genome is not immune from these violations. We carry the remains of thousands of viruses in our DNA, and most people on Earth may even carry genes inherited from another species of human–Neanderthals. We may be disgusted by the thought of violating species boundaries because of deeply ingrained instincts. But that disgust is an unreliable guide to the realities of biology, whether that biology is in E. coli or in ourselves.

[Picture: "The Young Family," by Patrician Piccini (2002-3). Wikipedia]

Comments

  1. #1 clear as mud
    June 9, 2008

    I’ve often thought the two statements that need reinforcing are those you make here, but their targets are different.

    To the general public: A good portion of us are probably themselves alive, or have family alive, where they would not be if humanity had not developed genetic engineering. Genetic engineering does not in and of itself, equal monsters roaming the earth. We are right to demand oversight, as with all things that can be potentially risky. But oversight also implies a general acceptance – within certain constraints – of a practice. So try to relax, within reason.

    To the scientific and, more importantly, the biotech community: Every time we construct something new – most specifically if it’s a major shift from before – we should think very long and very hard about the repercussions and plan contingencies. Even then, if we think we know all the factors of life and all that it is capable of, given new permutations and combinations… well, we most assuredly don’t. So try to consider the larger picture, within reason.

  2. #2 qetzal
    June 9, 2008

    If we think we know all the factors of life and all that it is capable of, given new permutations and combinations… well, we most assuredly don’t. So try to consider the larger picture, within reason.

    I don’t disagree with this at all, but I’m very uncertain how to put it into meaningful practice. I wonder if you (or anyone) can offer an example where the larger picture was appropriately considered?

    IMO, the fact that the world isn’t overrun with genetically engineered hypervirulent E. coli superbugs has almost nothing to do with Asilomar and our attempts to consider the larger picture. The reality is that it’s not easy to create superpathogens or world-destroying bacteria. It didn’t happen by accident because the underlying biology makes it very unlikely, not because we were so careful and restrained.

    If the worst of our early fears over recombinant DNA had been well founded, does anyone think we would really have avoided the predicted catastrophes?

  3. #3 clear as mud
    June 9, 2008

    To be clear, I’m less concerned about the results of standard clonings, etc, of the type that are so common today. I was more referring to new things that seem to be on the horizon, for instance, synthesis of customized organisms (viral or beyond, if it’s possible). I’m not saying it’s either (1) about to happen or (2) is inherently bad.

    What I’m meaning, in terms of “big picture”, is when trying something new – dramatically new – just to consider the potential dangers and plan accordingly. When people use the term “playing God” as a bad thing they often mean scientists usurping a role that should be only allowed to a true “Creator”. However, I view that term to mean “playing” at being someone who knows all the factors involved in their creations and, as a consequence, do not expect any unforeseen outcomes.

    Most scientists, I think, would never be that cavalier – not by a long shot. But we’re all human, and some people are more prone to feelings of omniscience than others. Putting some reasonable precautions in place would help reduce the risks.

    The initial fallout of the early genetic engineering bru-ha-ha (spelling?) was a series of rigid guidelines of how to contain genetic constructs – down to the minutia (if I remember) of not pouring cultures down the drain.

    I guess all I was saying was that giving similar careful thought and caution would be a wise thing for any radically new endeavor. On the one hand, I imagine this is obvious. And, as I tend to do, I make the assumption that those respective researchers or engineers will do precisely that.

    I’m just reiterating the point, because, well, it never hurts.

  4. #4 maxwell
    June 9, 2008

    Sounds similar to one particular case in my dermatology lab, where I work as a technician.

    We’ve bred transgenic mice who homozygously carry the human gene for NC16A, a very small segment of the hemidesmosome protein BP180. Granted, they show no physical signs whatsoever, but their skin now carries the antigen for human bullous pemphigoid and some other conditions, and test positive with immunofluorescence and ELISA.

    I suppose if any of these mice escaped and bred in the wild, the gene would spread along Mendellian lines. It would be virtually meaningless, but it freaks out laymen friends and relatives of mine who know only because of me!

  5. #5 Mr. Gunn
    June 9, 2008

    Most of the breast-beating about playing god and how we really need to think carefully about what we’re doing comes from people who aren’t familiar with just exactly how much we DO think about what we’re doing and the implications thereof.

    It doesn’t take much effort to say, “genetic engineering is wrong!”
    It takes considerable effort to say, “under this specific set of circumstances, genetic engineering is OK”, but who other than the people who do it as a career(either as a scientist or professional oppositionist) has the time, today, to expend the effort required to learn what those circumstances are?

  6. #6 clear as mud
    June 9, 2008

    Er… I’m not sure what about my comments was offensive or which part was breast-beating. I think I made it clear that I felt most – if not, in fact, all – researchers are responsible professionals about this.

    My initial comment was, I felt, a pretty even handed statement. But perhaps I’ve stepped on a landmine.

  7. #7 Noni Mausa
    June 10, 2008

    A couple of miscellaneous comments:

    — Heinlein tackled some of the “problems” of gene engineering in his 1947 short story “Jerry Was A Man”. (Apparently there was a TV show too, I can’t attest to the quality of that.)

    –The painting of the Young Family, while sort of evocative, has structural problems. What’s with the spaniel ears? Tetrapod ear flaps, no matter what the mix of genes, develop and surround the opening of the ear, which is located just behind the hinge of the jaw, not on the top of the head. Also, her hips look pretty human — probably not good for birthing litters. (Has she got a uterus, or uterine horns? I bet even the artist doesn’t know.)

    Besides, if we want a bizarre and atypical anthropoid to depict, humans already look pretty odd compared to ordinary mammals like dogs, baboons and musk-oxen.

    Noni

  8. #8 Stephanie Chasteen
    June 10, 2008

    I’m not really sure where I stand on the issue, to be honest. I don’t have an emotional reaction to mixing species — the “disgust” response outlined above. But I am cautious about introducing new creatures to our world, as the law of unintended consequences often seems to hold. But I feel somewhat powerless to make a stand one way or the other. I was not in favor of putting GMO corn out in the cornfields, and now look where we are — GMO corn has spread all over North America on the wind. Did we used to have more control over these new innovations, or has the public always felt unable to enter the debate about what is done in their world?

    I also wanted to take the chance to point you to WNYC Radio Lab’s (So-called) Life episode, which talks about just this — what is life, what counts as natural? Brilliant radio. Listen to it!

    Cross-posted on my sciencegeekgirl blog

  9. #9 Joseph Brenner
    June 10, 2008

    How about those of us that lived with Diabetes for 42 years unawares, and didn’t have problems like Arthritis, Fibromyalgia, or Dawn Syndrome until the year GM insulin was added to our medicine chests?
    I refer specifically to myself here, but surely there are others.

  10. #10 qetzal
    June 10, 2008

    Joseph,

    No doubt there ARE others who came down with one or more of those conditions in that same year. That doesn’t mean they were caused by switching to recombinant insulin.

    Would it be better if we still purified insulin from pigs? It would be more expensive, less available, less reproducible from batch to batch, and more likely to be contaminated with a biological pathogen (e.g. virus).

  11. #11 Joseph Brenner
    June 10, 2008

    Maybe you misunderstood me. I was using NO insulin until last year, and not having any of the supposed side effects of Diabetes, other than high blood sugar. In spite of it all I felt fine until they put me on insulin.

    As to the source of the insulin, I have to wonder WHY E.coli? How did they figure they could get pathogen-free insulin by substituting a pathogen for the animal source? Isn’t there some other life form capable of producing recombinant DNA (Perhaps HUMAN STEM CELLS)?

  12. #12 qetzal
    June 10, 2008

    Joseph,

    Most strains of E. coli are not pathogens. Right now, you have literally billions of E. coli living in your intestines. They’ve been there almost since you were born, and they haven’t hurt you at all. In fact, they’re probably beneficial.

    The E. coli strains that are used to make recombinant proteins like insulin pose even less risk. They’ve been grown in labs for so long, and undergone so many modifications, they can’t survive in “the wild” anymore. You could drink a whole flask of them. Not only would they not hurt you, they wouldn’t survive in your intestines. (It’s been done!)

    As for why E. coli – because we know more about it and can do more with it than any other organism on the planet, bar none. We can grow it more reproducibly and control it better. When we use it to make human proteins, we can do all kinds of tests to make sure all the bacterial proteins and other contaminants are removed.

    Of course, there are other cells that can be used to make recombinant proteins. Yeast cells (Saccharomyces cerevisiae) are often used, and I believe some recombinant insulin is made in yeast. Other recombinant proteins are made in mammalian cells. Chinese hamster ovary (CHO) cells are the most common.

    I’m no MD, and wouldn’t presume to counsel you on your medical situation. I have no idea if there’s a possible connection between your symptoms and the start of your insulin treatment. But even if there is, the fact that it’s recombinant insulin from E. coli (as opposed to purified pig insulin) is extremely unlikely to be a factor.

  13. #13 Nessar
    June 12, 2008

    Just want to say that thousands of young people die every year in the developing countries because they have no access to insulin. I myself lost my best friend who died of ketoacidosis in Afghanistan 15 years ago, a 23-years old- freshman in engineering college whose life could be saved by these E. colis. I think the moralists arguing the genitically modified are totally irrelevant.

  14. #14 Cooper
    June 13, 2008

    Am I the only one who finds that sculpture cute rather than shocking?

  15. #15 ediacara
    June 24, 2008

    Joseph, I wonder how on Earth could you or anyone “get” Dawn syndrome as it is a chromosomal disorder that you must be born with…

  16. #16 llewelly
    June 30, 2008

    Joseph, I wonder how on Earth could you or anyone “get” Dawn syndrome as it is a chromosomal disorder that you must be born with…

    ‘Dawn syndrome’? Surely that’s a chronological disorder?

  17. #17 muhabbet
    March 25, 2009

    thanks..

  18. #18 sohbet
    April 1, 2009

    Thanks

  19. #19 komik fıkralar
    April 3, 2009

    Thanks.

  20. #20 maynet
    April 3, 2009

    thanks admin

  21. #21 Mya
    February 27, 2010

    Is that image real or is it just a sculpture?

  22. #22 film izle
    September 22, 2010

    It doesn’t take much effort to say, “genetic engineering is wrong!”
    It takes considerable effort to say, “under this specific set of circumstances, genetic engineering is OK”, but who other than the people who do it as a career(either as a scientist or professional oppositionist) has the time, today, to expend the effort required to learn what those circumstances are?

  23. #23 su
    December 1, 2010

    Am I the only one who finds that sculpture cute rather than shocking…

  24. #24 düzce haber
    December 15, 2010

    Joseph, I wonder how on Earth could you or anyone “get” Dawn syndrome as it is a chromosomal disorder that you must be born with.

  25. #25 video
    January 1, 2011

    I’m not really sure where I stand on the issue, to be honest. I don’t have an emotional reaction to mixing species — the “disgust” response outlined above. But I am cautious about introducing new creatures to our world, as the law of unintended consequences often seems to hold. But I feel somewhat powerless to make a stand one way or the other. I was not in favor of putting GMO corn out in the cornfields, and now look where we are — GMO corn has spread all over North America on the wind. Did we used to have more control over these new innovations, or has the public always felt unable to enter the debate about what is done in their world?

  26. #26 orjin krem
    January 1, 2011

    Joseph, I wonder how on Earth could you or anyone “get” Dawn syndrome as it is a chromosomal disorder that you must be born with…

  27. #27 complex 41
    January 3, 2011

    Am I the only one who finds that sculpture cute rather than shocking…

  28. #28 Lexus
    January 13, 2011

    I described as necessary to make a bailout acceptable have not been met. This is still a party for wall Street. That is not a good use of taxpayer dollars.

  29. #29 orjin krem
    April 7, 2011

    Orjin Krem Bitki özlerinin mikro ölçülerde birleştirilmesi ile elde edilmiş naturel bir üründür.
    Orjin Krem Emilimi çok güçlü olduğundan etkisini dakikalar içerisinde gösterir.
    Orjin Krem Bitki özleri sayesinde kasların rahatlamasına ve gerilimin giderilmesine yardımcı olur.
    Orjin Krem 100 ML ve 25 ML set olarak satılmaktadır.
    Orjin Krem iki kutu bir arada bir kutu içerisindedir holagram bulunmaktadır.
    Orjin Krem alındıktan sonra bandrollü sayesinde sahte olup olmadığını kontrol edebilirsiniz.

  30. #30 orjin krem
    April 7, 2011

    Joseph, I wonder how on Earth could you or anyone “get” Dawn syndrome as it is a chromosomal disorder that you must be born with…

  31. Just want to say that thousands of young people die every year in the developing countries because they have no access to insulin. I myself lost my best friend who died of ketoacidosis in Afghanistan 15 years ago, a 23-years old- freshman in engineering college whose life could be saved by these E. colis. I think the moralists arguing the genitically modified are totally irrelevant.

  32. #32 porno
    May 3, 2011

    okay. well let’s see. 1/3 of you all are using big words to try and sound smart and correct (i understand what you say but you accomplish nothing by trying to sound proper); 1/3 of you all are just plain stupid; and the remaining 1/3 of you are making fun of the idiots. yes, the peanut butter example is pretty stupid in many respects but that doesn’t mean creationists are stupid (although i am not quite sure why they had an engineer do this). i have heard evolutionists use examples and excuses that are just as dumb. i could spend 3 hrs telling you why i believe creation but you could spend another 3 hrs giving rebuttles, dumb or not. many times creationists point out possible flaws in simple evolutionary ideas and just stop at that and say, ha you are wrong and i am right, and just walk away. i have more respect for a evo. that is cool headed in a debate and uses logical reasoning than a woosie cre. who ends the debate as quick as possible to avoid having to think about what he believes on the deepest levels.

  33. #33 NJ
    May 3, 2011

    Oh, gee, a link spammer trying to bait people on a long-dead thread.

    Never saw that one before…

  34. #34 gölge sistemleri
    May 18, 2011

    Just want to say that thousands of young people die every year in the developing countries because they have no access to insulin. I myself lost my best friend who died of ketoacidosis in Afghanistan 15 years ago, a 23-years old- freshman in engineering college whose life could be saved by these E. colis. I think the moralists arguing the genitically modified are totally irrelevan

  35. #35 supratall
    May 26, 2011

    OK, I’ll come clean: this reminds me of an embarrassingly recent conversation with my materials science-trained boyfriend.

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