It Might Have Happened, We Don’t Know for Sure, But Now We Freak

“We wait until Pandora’s box is opened before we say,”Wow, maybe we should understand what’s in that box.” This is the story of humans on every problem.”
Peter Singer

Louis Brown was born July 25, 1978, for some people she was surprising maybe even scary, you see Louise Brown was the first in vitro fertilized (IVF) baby ever born. Today IVF is a technique that barely causes people to bat an eye. In fact, according to the Society of Assistant Reproductive Technologies (SART) from 1987 – 2005 in the US one million babies have been born through IVF and other reproductive technologies.

We have two more names Lulu and Nana born November 2018. Lulu and Nana might not be their real names, we don’t know their last name, and the public has not seen them. However,according to Dr. He Jiankui of the Southern University of Sciences and Technology in Shenzhen China, they are the first human beings to be genetically engineered. The announcement of the first genetically engineered human beings raises a lot of questions.  Including do these children even have genetically engineered genes?

However, before we get into the issues with Dr. Jiankui’s work,I want to cover a little history to show that it might be possible to engineer humans genetically. Two techniques have been hanging over human reproduction for decades. They are cloning and genetic engineering.

The reason cloning is important is that it makes genetic engineering easier,more on that later.  Most people have heard of Dolly the sheep the first mammal cloned by nuclear transfer from an adult somatic cell she was born July 5, 1996. With Dolly the critical words are adult somatic cells, scientists cloned a sheep from an embryonic cell in 1984.

Dolly was all over the news when she was born. However, who has heard of Polly and Molly? Who is that you say? While Polly and Molly are cloned female sheep like Dolly, however, Polly and Molly were genetically engineered to produce human factor IX in their milk. Factor IX is the clotting factor missing in people with hemophilia B, Polly and Molly were born in 1997.

Here is where cloning helps with producing genetically engineered organisms. Growing cells in culture make it easier to create genetic changes lots of different techniques are available.  Then you can select for cells that have the change — scientists then use the changed cells for somatic cell cloning.  This technique using cultured cells is what produced Polly and Molly.

The critical point is that with regards to humans, theoretically, all the tools needed to produce genetically engineered humans was in place in the late 1990s.  That was the time to start discussing the laws and ethics in the late 1990s or early 2000snot 20 years later. I know some of you are going to say, but that was only sheep (also I didn’t know about factor IX). Well, sheep are mammals just like human beings.

However, there is something that Dolly (perhaps the media’s fixation on Dolly) distract us from, a week after Dolly was born Neti and Ditto were born they are a pair of Rhesus macaque monkeys produced by nuclear transfer cloning in this case the nuclei were from embryos. Then on October 2, 2000, ANDi, a genetically engineered Rhesusmonkey was born.

The genetic engineering of a Rhesus monkey means that everything needed to do human genetic engineering has been done in a primate and was technically feasible in humans by 2000. The only real technical problem remaining was the methods used to introduce DNA at the time they were random and inexact potentially producing unintended effects.

Then from 2005 – 2011 we identified the function of Clustered Regular Interspersed Short Palindromic Repeats (CRISPR)and the CRISPR associated (Cas) genes. The CRISPR DNA sequences and associated genes are a mechanism of adaptive immunity in bacteria and archaea they help these organisms defend themselves against viruses. The important thing about the CRISPR/Cas complex is that it is highly sequence specific. In2012 it was shown that the CRISPR/Cas complex could be targeted to a sequence of the researchers choosing. In 2013the CRISPR/Cas9 system was used to create site-specific gene editing.

While the CRISPR editing process is tremendously useful in basic research it also potentially gives us the ability to make specific gene edits in humans (this point still up for debate). However, again in 2013, it was the time for discussion, not 2018.

In 2015 a group of researchers tried to use CRISPR/Cas9to edit tripronuclear zygotes (human)they got gene edits. However, there were mistakes in the edits and off-target changes.  The scientists recommend further refinement of the CRISPR/Cas9 system before clinical applications.

Which brings us back to Dr. Jiankui and little Lulu and Nana, the most significant technical argument from the scientific community is that Dr.Jiankui shouldn’t have done this because he can’t guarantee the unintentional production of changes.

Beyond the question of whether the procedure produces unanticipated changes, there are other issues. According to Dr. Jiankui, the purpose of the trial was to create children resistant to HIV infection. Couples in which the man was HIV positive, had their embryos treated with the CRISPR/Cas9 system at the single cell stage during in vitro fertilization. They created defects in the CCR5 gene which is the gene used by HIV to enter cells.

Let’s look at some more issues with Dr. Jiankui’s procedure to mutate CCR5.  First, few if any over sight organizations would give genetic engineering of CCR5 approval as a clinical trial since there are already treatments which prevent embryos from contracting HIV. We don’t introduce new and potentially dangerous techniques when we already have a functioning therapy in place.

Second, the embryos were not already HIV-positive so is this a medical treatment or is it something else like genetic enhancement?  Genetic enhancement is something that most organizations oppose.  There is a big difference between treating a disease and make a change without a need.

Third, Dr. Jiankui says he explained the consequences to the parents. Without being able to talk to the parents is impossible to know if they understood the consequences as Dr.Jiankui explained them. Additionally, how can Dr. Jiankui explain the consequences of a procedure when the best scientific studies say we don’t know the consequences.

We now find ourselves scrambling to catch up as a society because some self-centered researcher was more interested in getting himself into the history books that he was in doing his actual job.  Simply put Pandora has opened her box and we all know once something escapes Pandora’s box it’s not going back.

As we try and deal with the appearance of human genetic engineering,we also need to do a better job at looking to the future and dealing with issues before they happen.  As I showed, human genetic engineering has been a possibility for 20 years. Having the ability to talk about the future is why a basic understanding of science is vital to modern society. While science communication needs to be better,it is also reasonable to expect that individuals pay attention to what is happening in the world around them.

We now find ourselves in a situation where something has already happened. There will be a tendency to call everything associated with it wrong and evil.  However, we need to remember that techniques and knowledge are not inherently good or bad how we use them that is good or bad. The atomic bomb is bad; nuclear medicine helps cure cancer that’s good they both come from the same foundational research. The techniques that Dr. Jiankui abused are tremendously useful to science and may someday solve problems that we currently can’t even begin to understand.

Lastly, as we discuss what we want to use genetic engineering for let’s remember that Lulu and Nana are children none of this is their fault.They have every right to live their lives, to grow up, to be happy, and free of abuse and prejudices. Don’t call them monsters, don’t say they are a threat to all of us, and most certainly don’t suggest that they are not human.  In the end,society is measured by how it treats its most vulnerable.

Thanks for Listening to My Musings

The Teaching Cyborg