Genetic Therapy in Utero: Good idea or bad idea?

[MirrorCracked]

So.

Let's suppose, for the sake of argument, that you or someone you love is about a month pregnant. A test has revealed that, if born, the child will have a genetic disorder. It's not a lethal disease when treated properly, and it's unlikely to cause a mental disorder of any kind, but it will cause significant problems for the child if allowed to occur.

A genetic therapy has been shown (unlike current genetic therapies) to be effective and low-risk. It would alter the embryo's DNA to supply a healthy copy of the disease gene in a safe manner.

Given this, would you use the therapy to treat the embryo?

What if there were no embryo yet, but you could treat your own sperm/eggs to fix the problem prior to conception? Would this change your answer?

Conversely, what if the pregnancy had gone far enough for the embryo to develop into a fetus?

What if the disease were lethal? Not lethal, but producing a condition generally recognized as a psychological illness?

I'd, personally, be absolutely willing to tamper with my own sperm, and probably willing to act to modify an existing fetus if the disease were severe enough. But I'd draw the line at altering a fetus for reasons of aesthetics or personal preference, and I'd be especially wary about trying to treat, say, obsessive-compulsive disorder in the womb.

Thoughts?

 

[Mr Master]

I'm not opposed to corrective gene therapy. Replacing damaged genes with healthy genes eliminates a flaw, and that's OK. It's enhancements that are the problem.

It's like my thought on geneneered foods: enhancing, say, corn stock with stronger corn genes is just accelerating what you can do with traditional methods, and I'm in support of efficiency. Putting in fish genes or insecticide genes into corn stock is a step beyond, and the ramifications can't be predicted quite so well.

 

[Nihilistic_Impact]

I would not mind enhancements if everyone was given them.

Sure, it'd make a lot of older people upset; but so long as everyone is getting the same treatment I'd not be concerned beyond possible ramifications as MM puts it. Of course by the time we're to the point of enhancing humans I'd like to think that most, if not all, of the kinks had been worked out of the system.

Sadly biology doesn't work that simple.

 

[darkangel76]

Biology is hardly simple and tweaking small things such as a single protein, or even a fragment, isn't all that easy and often times results in strange mutations. Some of which are all right and are thus 'silent', but some radically change the properties and thus how they work. So, imagine working with the human genome which is MUCH MUCH MUCH bigger. OH MY! However, if we are ever at that point of understanding things, I'm all right with certain sorts of gene therapy. Ones that won't leave lingering issues down the line with that particular individual or even in the next generation assuming the individual who received the gene therapy reproduces. I'm definitely more comfortable using such therapies for fixing genetic defects as opposed to enhancements or basic appearance tweaks. Such things are unnecessary and meddling with genetics is tricky business. Best to only go there when it's needed.

 

[Trygon]

Better > Worse

Always. In all senses.

 

[MirrorCracked]

I would not mind enhancements if everyone was given them.

Sure, it'd make a lot of older people upset; but so long as everyone is getting the same treatment I'd not be concerned beyond possible ramifications as MM puts it. Of course by the time we're to the point of enhancing humans I'd like to think that most, if not all, of the kinks had been worked out of the system.

Sadly biology doesn't work that simple.

The potential problem is that nature has already selected for a pretty effective genome. What if some things we perceive as weaknesses are actually useful?

The classic case is the mutation that causes sickle-cell anemia. If you have two mutant copies, your health suffers - a lot. But if you have only one mutant copy, your resistance to malaria is increased.

Biology is hardly simple and tweaking small things such as a single protein, or even a fragment, isn't all that easy and often times results in strange mutations.

This is why I said that the therapy would introduce a working copy of the gene, rather than "tweak" the copy that is already there. In other words, nothing would be removed; the alteration would be adding one new transgene.

I think a lot of people draw the line at "improving" subjects beyond curing diseases, because of the potential for abuse.

 

[Nihilistic_Impact]

When I think of this subject I think of the film Gattaca, which is a great film and anyone interested in gene enhancement should watch it, and so I was basing it around that concept of designer babies.

 

[Mr Master]

You know how humans are. Once a thing CAN be done, you can bet it WILL be done. And someone will make a great profit from it.

 

[Tathariel]

I'm not opposed to corrective gene therapy. Replacing damaged genes with healthy genes eliminates a flaw, and that's OK. It's enhancements that are the problem.

It's like my thought on geneneered foods: enhancing, say, corn stock with stronger corn genes is just accelerating what you can do with traditional methods, and I'm in support of efficiency. Putting in fish genes or insecticide genes into corn stock is a step beyond, and the ramifications can't be predicted quite so well.

Better > Worse

Always. In all senses.

Not always my friend.

In the 1990s, A European biotech company prepared to commercially release a genetically engineered soil bacterium for use by farmers. They were operating under two very reasonable assumptions:

1. Nobody likes plant waste.

2. Everybody likes booze.

Whereas the common man might address these issues by simply not doing any plowing and opting to get plowed instead, scientists at the biotech company thought of a much more elegant solution: Engineer a bacterium that aggressively decomposes dead plant material--specifically wheat--into alcohol. And in 1990, they did exactly that. The bacterium was called Klebsiella planticola, and it nearly murdered everybody; you just don't know it yet.

What the Hell Was It?

Klebsiella planticola is of the enterobacterium family, microbes that typically reside inside the guts of mammals, but this particular strain inhabits the root systems of most terrestrial plants. Actually, every root system that's ever been tested for the presence of K. planticola has come up positive, so it is as near to a universal plant bacterium as there has ever been (you should remember that part, because it's going to come in handy later). In its pre-modified, natural form, K. planticola is partly responsible for the decomposition of all plant matter--a vital step in the natural life cycle--and it's notoriously aggressive in this role. That's why it was picked out for experimentation in the first place: Like an Old Testament God, K. planticola is both omnipresent and incredibly belligerent.

Biotech researchers saw these traits and thought they seemed perfect for an agricultural problem they were working on. Burning off dead plant material, as was the standard practice, severely pollutes the air and damages the lungs of farmers.

So What Did They Do?

What if, instead of the regular old largely useless sludge that decomposing plant material result in, we could alter that sludge into something more useful to humans, thus eliminating the desire to simply burn it away? What if we could ferment it, and turn it into an alcohol, a fuel or a hyper-efficient fertilizer? Or better yet, all three! Why not get blitzed off of it, piss it into your gas tank to power your car and then puke it up into the yard to make your garden grow?

Suddenly alcoholics are useful members of society again. Hell, they're practically heroes: brave men and women sacrificing both their livers and their dignity to bring us power, food and alcoholic-inspired confidence!

Well, that's the noble goal biotech researchers had in mind when they spliced an alcohol-producing bacterium into K. planticola. Once their product was released, farmers would simply gather the dead plant matter into buckets and let it ferment into alcohol. Alcohol that could do everything they hoped: Be distilled into gasoline, sowed as fertilizer, burned as cooking fuel or just drunk by the filthy, dirt- tasting bucketful. Their bioengineered K. planticola would create a beautiful, Eden-like garden paradise. So it was all with the intent of doing good that they engineered this microbe, but you know what they say about "the best intentions," don't you?

That's right: They inevitably result in pestilent, humanity-destroying plagues.

See, it was that fertilizer part where things got, shall we say, fucking horrifying: Once the fermentation process necessary to turn that dead plant material into alcohol occurred, the sludge left over would be rich in nitrogen and other such beneficial substances, making it an ideal fertilizer. The plan was to spread this sludge fertilizer back on the fields, thus eliminating all waste from the whole process.

What Went Wrong?

The fermentation process didn't kill the modified K. planticola--it was still there, ready to turn dead plant material into alcohol. The bigger problem? It didn't even wait until the plants were dead to start. The normal K. planticola bacterium result in a benign layer of slime on the living root systems it inhabits, but the engineered version would also be producing alcohol in this slime--with levels as high as 17 parts per million, and anything beyond one or two parts of alcohol per million is lethal to all known plant life. So the engineered K. planticola basically gives all plant life it touches severe alcohol poisoning, putting them more than 10 times over the lethal limit of fucked up. Like a frat house during pledge week, K. planticola would force all new plants it encountered to drink well beyond their reasonable limits. But unlike frat house rushes, it's not just freshman idiots who are affected, it's everybody. So maybe that analogy isn't entirely accurate: It's more like a bleak dystopian future where frat houses rule the world with a tyrannical fist, hazing and beer-bonging humanity into the grave. Because, you'll remember, K. planticola is present in all plant life.

Every species.

Every variety.

Poisoned.

To death.

Now those wonderful traits that made it such a good candidate for modification in the first place--its notorious aggressiveness and near omnipresence--are no longer such good things, are they? Because if there's one thing you really don't want your poison to be, it's "notoriously aggressive." And if there's one place you absolutely do not want your "notoriously aggressive poison" to be, it's "everywhere." Keep in mind that this was not a theoretical scenario; far-flung, fictional and unlikely to ever actually occur. This bacterium was going to be released; it had all of the necessary approval. It was only a matter of proper marketing and shipping at this point. It was only by virtue of a random review by an independent scientist (Dr. Elaine Ingham, a professor at Oregon State University and possibly the savior of all mankind) that it was caught in time.

How the Fuck Could This Possibly Happen?!

How did the leading biotech researchers of the day not realize that they had engineered a bacterium that would kill all plant life it touched? Did they not test it on any, you know, plants?!

Well, for all intents and purposes: No, they didn't.

See, the Environmental Protection Agency was the only overseer for all biotech releases, and their policy was to test new bacteria in sterile soil. The problem here being that the real world is not sterile; it is the antithesis of sterile. The whole point of sterility is to zap all normal, unexpected elements out of a sample environment so that the scientists can see its effects in a pure, untainted environment. They deemed the modified K. planticola to be safe in sterile soil, but apparently just totally forgot that its intended use was in the fucking dirt, which is a notoriously dirty place, isn't it?!


Luckily, Ingham and her group took it upon themselves to study the bacteria in a more realistic scenario, using normalized samples of unsterile soil and three different sample groups. There was a group absent of K. planticola entirely, a group with the normal K. planticola present and a group with the genetically modified K. planticola in it. They planted wheat seeds in all three groups, and then let it sit for a week. When they came back they found the first two groups doing fine, while all the crops from the GM sample were dead. Dead in less than a week. If released from the lab--which, I cannot stress enough, it very nearly was--the modified K. planticola would have spread worldwide in a matter of months, killing all plants it touched within a week, and turning all soil-based plant life into sweet, sweet liquor.

Like a twisted hillbilly fantasy, the world really very nearly drowned in moonshine.​

 

[Mr Master]

Again: things it's not supposed to do is not jump-starting nature, it's more twiddling to make it do new tricks. That's like grafting in fish genes.

Things like this is why the unwashed hoi polloi doesn't trust scientists. But things like this aren't propelled by scientists. Scientists did the three-sample testing. It's business and politics that only requires the sterile soil sample test; streamlines approval and lets companies get their products out faster and cheaper. Bet millions of dollars in lobbyist money went into that particular rule, and companies have saved trillions of dollars because of it. So what if we've nearly died because of it? Blame it on the science.

 

[darkangel76]

It's definitely not the scientists. We do the appropriate experiments and the like to seek answers and truths. To look for new questions and so on. We report accordingly and what happens after that isn't our say. Most of us get upset when our findings get disregarded or pushed to the side. Nowadays, that doesn't happen as much. But when it does... yeah. Take from me. A 'used-to-be' scientist who's worked both in biopharma and biotech.

 

[Mr Master]

It's definitely not the scientists. We do the appropriate experiments and the like to seek answers and truths. To look for new questions and so on. We report accordingly and what happens after that isn't our say. Most of us get upset when our findings get disregarded or pushed to the side. Nowadays, that doesn't happen as much. But when it does... yeah. Take from me. A 'used-to-be' scientist who's worked both in biopharma and biotech.

I know! It's unfair, isn't it? Most scientists I've talked to would rather test and double-check and find things out. But they're not the ones writing the checks or demanding results.

 

[darkangel76]

It's definitely not the scientists. We do the appropriate experiments and the like to seek answers and truths. To look for new questions and so on. We report accordingly and what happens after that isn't our say. Most of us get upset when our findings get disregarded or pushed to the side. Nowadays, that doesn't happen as much. But when it does... yeah. Take from me. A 'used-to-be' scientist who's worked both in biopharma and biotech.

I know! It's unfair, isn't it? Most scientists I've talked to would rather test and double-check and find things out. But they're not the ones writing the checks or demanding results.

It very much so is unfair. We could care less about the marketing and distribution of the end product. Our concern is learning the truths of what we're studying/developing. If we had our way, it would probably take double the time it takes to get FDA approval. But nowadays, there are some pretty stringent guidelines that go with human trials and eventual public distribution of medications and the like.

There was a time when it wasn't as strict, definitely before my time as a scientist. Though, having worked in biopharma, I can say that the company tends to push distribution and such pretty hard. Even to a point where the scientists suffer. It's absolutely ridiculous. But anyway, in the end, most of the problems that occur such as those are not a direct result of the science nor of the people doing the science. You can blame the power hungry higher-ups as that's really who is at fault. At least, in my opinion and from my own experiences.

But again.... such things are not nearly as frequent due to the potential law suits that can (and will) occur, not to mention the poor reputation that will follow the company as a result of everything. People need to recall the semi-recent issues that happened with several of Pfizer's drugs. About 5 - 10 years ago they had massive recalls. As a result, the FDA stepped in and not only recalled the drugs, but slapped Pfizer pretty hard making many lose faith in them and look down on them for quite a bit. Plus, they (ie, the FDA) made their guidelines much much tougher in regards to getting to the point where human trials are deemed acceptable. And nowadays, human trials are taking much longer to complete as well so as to better determine long-term results/effects (and long-term typically means 10 - 20 years, at least in most cases). Again, a result of the FDA's stringency on guidelines prior to mass distribution to the public.

All of these rules and such by the FDA are great in my opinion. And needed. I think it places companies in check, meaning those who are geared toward distributing a product meant for human use that may or may not cause risks. Of course, some risks are going to be there. But they should be minimal and rare. But that's a side point really.

 

[Mr Master]

The FDA is still subject to rule-making and exceptions imposed by political groups. There's plenty of examples during the Bush years where political appointees "encouraged" this or that situation, or "discouraged" certain applications and tests. But I agree with you: it serves a useful and necessary purpose. And yet people still rag on the government for that stuff, for taking up too much money in taxes. Guess you don't like to have the purity of your food checked, do ya, bub? Or the safety of your pharmaceuticals? Can you even look up thalidomide?

And none of that would have helped if all the plants in the world had died due to alcohol poisoning. Sure, apportion out the blame as we all get to starve to death over the next few months as the food runs out.

 

[MirrorCracked]

Tathariel: That's a lovely piece from cracked.com. It is so lovely that I wish I hadn't had to Google to find out who really wrote it.

Now, if you go back to what Dr. Ingham herself had to say, it is not that the organism would have spread worldwide; rather, it would kill wheat when the slurry was applied to local soils, and that it might be possible to engineer a version that would spread. The Cracked writer then exaggerated, of course, without explaining how, exactly, this bacterium would spread at any reasonable rate, given that the first few people to use it in tests - and there WOULD be more tests! - would get a field of dead plants.

Either way, think about it! If this bacterium kills the plant it grows on, how on earth does it have an advantage over the non-alcoholic kind? Where is it going to find hosts that can survive it? It would be outcompeted by its non-GMO brethren in the wild. Here's an analogy: we all have E. coli bacteria in our guts, and there are dangerous varieties of E. coli. But we haven't been wiped out by those dangerous varieties, and even though there's nothing stopping us from making super KILLER E. COLI, it's not exactly going to sweep the world in a pandemic, as far as I know, without further help.

 

[Mr Master]

This doesn't invalidate the ancillary comments and observations about business and politics mucking about in science, of course. But your analysis of epidemiology and bacteriological propagation (as well as identification of the original writing source) are well-taken.

 

[MirrorCracked]

It doesn't invalidate the comments, but it does raise a key point: the popularized, sensationalized accounts of science that the general public sees rarely reflect the reality of these situations.

It's definitely not the scientists. We do the appropriate experiments and the like to seek answers and truths. To look for new questions and so on. We report accordingly and what happens after that isn't our say. Most of us get upset when our findings get disregarded or pushed to the side.

Unfortunately, while I generally agree that scientists are generally more responsible than not, I think that some scientists do deserve a share of responsibility for some pharmaceutical fiascoes. Here are some of the problems:

* Negative results are minimized or don't get reported fully. This is as much of an issue of publication competition as it is the fault of any particular scientist, but it seriously skews the data on treatment.

* Studies are designed by researchers who, on a conscious or unconscious level, want positive results, leaving subtle biases in play. The way reporting periods were designed in a famous Vioxx study led to major problems down the road and minimized some worrisome results; did this imply deliberate deception? Not really. It was more likely careless science than fraudulent science.

* Publicity-hungry scientists (who are almost never good scientists) quickly try to get a result in the press before it's peer-reviewed, or who overstate the significance of their results.

Scientists are not the main source of problems here, but it does no good claiming that, as a lot, they're entirely sober, innocent, and diligent people at all times. The truth is that the intersection of the private sector, public policy, and medical research is a messy place, and clinical trials are a high-pressure monetary gamble.

 

[Mr Master]

That's a worthy and universal point: people are people, and no matter the profession, they're subject to the same flaws and oversights, as well as the same nobility and idealism. Humans are a complex species, which is what makes it so difficult to deal with them.