There are many news reports about gene therapy, about how we may be able to ‘fix’ genetic diseases such as sickle cell anemia, cancer, and cystic fibrosis. Simply put, scientists and doctors are trying to find ways to deliver a rectifying normal gene into a patient. This type of procedure is called somatic cell gene therapy and turns out to be far from easy, although there are some modest successes.
But that’s not what I’m going to write about in this column.
What I want to discuss are changes in the germ line, methods by which you create a transgenic human in which the genetic modification is heritable and passed down from generation to generation. This doesn’t get much play in the media because it is ethically dubious. Or, to put it another way, government grant agencies will fund somatic cell gene therapy but not the creation of a new breed of transgenic human. They won’t create their own team of X-Men. At least not openly. Here’s the kicker though: creating a transgenic human using germ line cells is almost easy. Much easier than somatic cell gene therapy.
Why do I say it’s easy? Because scientists have already made a whole host of transgenic animals, including mice, pigs, cows, and even primates, and expressed an astounding range of genes in them. Transgenic mice in particular are made routinely at universities and institutes around the world. If you want an idea of a genetic change that has been made in mice, and could be made in humans, check out the video for “Mighty Mouse” from my earlier Spec Tech column, “Of Mice and Scientists.”
Although there are a number of recipes used for making transgenic animals, I’ll stick to just one here.
First a couple of terms. Germ cells are those that give rise to eggs and sperm, the cells by which we pass on our genetic information to future generation. Somatic cells are everything else; a genetic change in them just affects you, not your progeny.
Ingredients:
1 foreign DNA sample (containing the gene that you want to introduce into the human, along with a selectable marker gene such as one for antibiotic resistance)
1 blastocyst (an early embryonic structure, which in humans has about a 100 cells, and which when properly cared for will give rise to a happy, healthy embryo)
100’s of embryonic stem cells (you can harvest these from blastocysts. Convenient, huh?)
1 surrogate mother
Directions:
1. Introduce foreign DNA into the embryonic stem cells (Assume about 2% efficiency for incorporation, but you can increase this to 70% by using an infective virus).
2. Grow the stem cells under selective conditions to eliminate those that don’t contain the foreign DNA (i.e. grow in the presence of an antibiotic so that only those with your antibiotic resistance gene will survive).
3. Inject the surviving stem cells that contain your transgene into a blastocyst (this blastocyst will now contain a mixture of normal cells along with cells containing your gene of interest).
4. Place the blastocyst into the womb of the surrogate mother (put the bun into the oven).
5. Incubate for nine months.
Done? Not quite.
The blastocyst contains a mixture of cells—some normal and some transgenic—and so the embryo and eventual adult that grows from it will contain a mixture of cell types. As a result, you won’t have the special characteristics you want quite yet. Also, you don’t know yet if the germ cells (eggs or sperm) of this chimeric human are derived from the normal or transgenic cells. So…
6. Genetically screen to identify an individual with transgenic germ cells. This individual can pass the transgene on to its progeny.
7. Allow growth of this individual to reproductive age (14-18 years old by law, depending on the country).
8. Mate.
9. Genetically screen the babies to determine which are transgenic.
10. Grow to adult. These individuals will no longer be chimeric as all their cells will express the transgene.
Is that it? Well, sort of.
Whether your transgenic human shows a change as a result of the genetic modification will depend on whether the genetic change you made is dominant or recessive. A dominant change only requires one copy of the transgene to affect the individual. For example, the gene for antibiotic resistance just requires one copy. So would introduction of a gene for production of additional growth hormone (for instance, if you wanted to make a giant). Right now, your transgenic human has a single copy of the transgene and would only display such dominant genetic characteristics.
But you might be interested in a change that is recessive, in which case, because humans are diploid, you need the genetic change to occur in both copies of the gene. An example of a recessive mutation you might like to make is for the gene CCR5 that gives resistance to HIV and bubonic plague; you need to mutate both of your natural copies to get resistance. So, if this is the case:
11. Mate your transgenic adult with the recessive change to another transgenic adult containing the same recessive change.
12. Genetically screen the babies to determine which contain two copies of the genetic change (the odds are 1 in 4 that any particular baby will).
13. Grow to adult. This individual will be homozygous for the recessive gene and display its effects.
If you’re doing the math, it takes two generations (36 years) to get an 18-year-old adult who displays the effects of a dominant transgenic change, three generations (54 years) to get an 18-year-old adult who displays the effects of a recessive transgenic change.
I titled this column as an ‘easy’ way to make a transgenic human.
I didn’t say it was fast.
But this recipe for making transgenic animals was established 30 years ago. So, if some government set up a eugenics program to create a transgenic super-soldier back in the 1980’s, they could be well on their way by now.
Clarion Blog 
Sounds easy enough. I’ll try it this weekend, although being a sci-fi nerd I need to do more research to understand step 8.
On a more serious note, it does annoy me when genetic engineering is presented as a “simple” thing, something any mad scientist can do in an afternoon with a few test tubes. I’ve spent a little time in research laboratories (as a guest, not a researcher) and I’m always impressed by how much time and effort goes into doing the “simplest” things.
James,
Thanks for the response.
In one of my earlier blog posts on Spec Tech, I discussed the myth of the mad scientist and how it does not fit with how research is actually done: https://clarionfoundation.wordpress.com/2010/06/24/spec-tech-the-lone-scientist-not/
But I also think that an opposing myth exists about how hard it is to do science, so much so that many students are scared off from taking science courses. Time, effort, and training does go into performing the procedures I outline above. But the basic principles are not that difficult and can be approached by any well-trained graduate student in molecular biology. In fact, many undergraduates who work in university labs have the necessary molecular background, and some have no doubt actually generated transgenic mice using these basic procedures.
Where I hope this information is useful from a Spec Tech perspective is in indicating: (1) that scientific procedures currently exist for making transgenic humans, and (2) the time frame involved.
–Eric
My high school fascination with re-engineering ourselves at the germ cell level for inheritable change led to the Sevolites of my novel series. Sevolite stands for “Self-Evolved Limited”, the company that ultimately created the wacky, larger-than-life subraces of man in my saga. Of course, since it’s SF, things went wrong. But the initial idea, as told in my “origins” novella for the saga, “The Lorel Experiment”, was to bioengineer smarter people with a long-term horizon for planning, to save the human race from its short term thinking.
If only the Sevolites were made CEOs for our own large corporations, then maybe we wouldn’t be in our current financial mess.
Another excellent and thought-provoking article (love the illustration). The whole notion of chimerism has always fascinated me, but I never thought of it in this context. But what really grabbed me (because of my current obsession with viral information sharing) is the use of “infection” to get the DNA into the germ cells. This leads inevitably to the apocalyptic notion that one does not necessarily require labs and scientists to create transgenic humans at all. Consider a plague, either artificially or naturally created by mutation, spread by some common vector, which introduces a virus into the body which then merrily goes about the business of injecting its modified strings of genetic material into the host’s cells, including reproductive organs. The sociological fall-out from such a plague makes my head hurt.
It not just could happen–DNA from viruses getting into our germ line–but it has happened. A lot, based on the human genome sequence. Some analyses place the amount of viral DNA as amounting to over 50% of our genome. Most of this viral contamination is found in the form of ‘junk DNA’, stuff that doesn’t have any apparent purpose, but doesn’t seem to hurt us either. But some of the viral sequences are used by us, and others serve as a basis for increasing our mutational capacity. The reason that so much viral DNA has been able to hitchhike along in our genomes is because the viral DNA is generally inserted randomly, and so insertions that don’t harm us can be carried along. Any viral DNA insertions that were damaging would have been lost during evolutionary selection.
However, you could envision a plague along your lines using a virus that is targeted to a certain region of the genome (and so knocking out a gene of interest), or one which introduces a specific transgene of interest, so that children pick up some interesting trait. This would most likely arise from specific engineering of the virus.