A CHINESE scientist, He Jiankui shocked the world last week, with the claim that he has genetically modified the embryo of two twin sisters, using the CRISPR/Cas9 gene editing tool. According to news reports, one couple has already given birth to twin girls and another one is on the way. His experiment violates the voluntary guidelines regarding human genetic engineering adopted by the scientific community, which has been maintained so far. It also appears a Lone Ranger kind of science, meaning very much a solo venture, not backed by either his institute – Southern University of Science and Technology, in Shenzhen, China – or his laboratory.
The worldwide reaction has been sharp, with the overwhelming opinion within the scientific community faulting He’s experiment on a number of counts. The Chinese Academy of Sciences and He’s institute, where he is currently on unpaid leave, have also been critical of his genetic engineering experiment. China’s National Health Commission is launching an investigation on He’s work and has halted all further work on the project.
Why is human genetic engineering such a fraught subject? The obvious concern is that such engineering potentially could give rise to designer babies, or the re-birth of “scientific” eugenics. In a highly unequal society that we are now in, this could result in coding inequality in our very genes, and creating a biologically unequal society as well.
The key red line to genetic manipulation was not to tinker with editing of germlines, modifications that would carry on through successive generations. All gene therapies till now have been restricted to what are termed as “somatic gene editing”, or adding genes that the body can reproduce but not transmit to offsprings. These therapies are currently undergoing clinical trials.
The voluntary ban on germline editing was drawn up during an international summit in Washington DC, December 2015, held by the US National Academy of Sciences, the Royal Society of the UK, and the Chinese Academy of Sciences. The three bodies had concluded then that it would be irresponsible to proceed with any clinical use of heritable "germline" editing at that time.
He’s experiment shows that the scientific community cannot protect itself against individual scientists turning rogue, and breaching such self-imposed regulation. There is concern that this rogue experiment could lead to a backlash against the field of human gene editing itself; or lead to laws that would make further research into genetic changes for protecting against severe, heritable diseases more difficult. This is why Francis Collins, the well-known scientist and head of the US National Institutes of Health (NIH) has called He’s experiment “an epic scientific misadventure”. Speaking in the second international summit of the above three scientific bodies in Hong Kong, he called for “binding international consensus” on setting limits for this kind of research.
The organising committee of the Hong Kong conference issued a statement on November 29 that “the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time.” However, it left a window open for the future by suggesting that “it is time to define a rigorous, responsible translational pathway toward such trials.”
Why did the scientific bodies warn against heritable germline editing? The CRISPR/Cas9 tools, though far more precise than what we had till now, still has uncertainties. The degree of precision, meaning the ability to make exactly the change we want, still leaves open the possibility that it could create unwanted changes in other areas also, and even cause cancer. That is why the recommendation by all scientific bodies has been to conduct such trials for germline modifications only when, clear unmet medical need exists, and no other option is viable. This is akin to the “translation pathway” consensus of the Hong Kong conference quoted above.
If we take the clear unmet need as the basis of permitting such germline genetic experiments, then He’s experiment does not meet the bill. The modification that He carried out was to knock out a particular gene, CCR5. This gene provides a possible pathway for AIDS or HIV infections. The father of the twin girls was an HIV patient. The issue here is that today, HIV can be treated, and the disease contained. Even if it is considered to be incurable, as it can be only contained, it would have been much easier to separate the infected sperms from the uninfected one by “straining” the father’s sperm, a fairly standard and far cheaper procedure. Apart from the possible side effects or unintended consequences of CRISPR/Cas9, CCR5 also protects against the Nile virus, and therefore knocking this gene out has known adverse consequences.
The other criticism against He’s experiment pertains to the protocols used. We do not have clear data of what was there before the gene editing and how accurate the gene editing has been. The few slides that He has put on YouTube and other platforms, provide information of questionable scientific value. We have yet to see details of his experiment. Nor do we have clear protocols on how the twins will be monitored in the future to see whether this gene modification does have benefits, or has adverse consequences.
Lastly, who pays if the experiment backfires and causes serious side effects such as cancer? Or other disabilities? Or will these babies and their parents then be responsible for all the consequences?
There is little doubt that the pace with which genetic technologies are developing are going to pose ethical, moral and societal problems for us. Are these life saving treatments, which indeed they could become in the future, be limited to those who can pay? Will these technologies be only limited to addressing disease, but not to the improvements of the “human stock”? Or will unbridled greed of an industry which has survived on profiting from disease, feed itself further on the desire of the rich for super babies? Are we entering a world, where we can buy our children’s health, looks and IQ, provided we have the money?
Professor Rath, in his speech at EMS Smrithi this year, had raised the possibility that improvement of CRISPR/Cas9 tools could, in the future, bring about “heritable” traits which could then be used to permanently stratify society. This is indeed a scary thought. Fortunately, it is still scientifically some distance away, as we know far too little about the genetic basis, if any, of desirable traits such as intelligence, creativity, leadership, etc. Before we reach such knowledge, we need to ensure that we create a far more humane and an egalitarian society than we have today. Another reason to dismantle the capitalist system, this time coming from within science as well!