“Keep going,” Jack said.
“Now, the goal was to make a PERV-free pig that would produce a customized heart for a specific individual,” Wei continued. “This required knocking out the pig genes responsible for creating the major histocompatibility complex, or MHC, along with the genes responsible for blood groups and then replacing them with the comparable genes from the patient who needs the heart. Again, this was accomplished with CRISPR/CAS9. So far so good?”
“So far,” Jack said.
“Now, here’s where the two approaches differ,” Wei said. “One involved creating only a transgenic pig, meaning a pig containing human genes. This included the genes I just mentioned, as well as the genes responsible for the creation of the heart itself. As it turned out, that was how Carol’s donor heart was created. The decision was made by a coin toss, in which the women participated. Questions?”
“I’m okay,” Jack said.
“Margaret’s heart was created slightly differently,” Wei said. “In her case it was the creation of a transgenic/chimeric pig. What we did was to make a pluripotent stem cell from one of her skin fibroblasts and add that to the developing PERV-free pig embryo containing her MHC and blood groups but without the genes required to make the heart. This information for forming the heart had to come from Margaret’s stem cells, so once again it was a human heart but grown in a pig that was composed of both porcine and human cells, which is what is called a chimera. Are you clear on these two approaches? Obviously, they both worked, but the pure transgenic is easier and results in a higher percentage of piglets.”
“What I’m clear about is your brazen presumption,” Jack said. “I’m appalled that you were willing to do all this with no sanction from any regulatory organization like the FDA or even a legitimate Institutional Review Board.”
“Knowing your reputation as someone who chooses not to suffer fools gladly, I’m surprised to hear you say that,” Wei said with equal disdain. “I for one have little respect for such regulatory bodies. Biological science is moving much too quickly for bureaucrats to comprehend, much less regulate.”
“The goal is patient safety and autonomy,” Jack reminded him. “It’s to prevent desperate people from being taken advantage of.”
“We were absolutely convinced of the safety and the efficacy of what we were doing. We were not taking advantage of anyone.”
“Oh, sure,” Jack sneered. “I’m blown away to hear you say that after both patients died. This was a freakin’ megalomaniacal experiment gone bad.”
“Let’s not be too quickly and falsely condemning.” Wei bristled, clearly taking offense.
“How can it be falsely condemning when the patients died?” Jack demanded. “And not only did they die, they might have started a goddamn pandemic in the process.”
“You are an opinionated, uninformed, self-righteous Western hypocrite,” Wei snapped. “Instead of actually doing something, you’re one of those people who just throw up their hands in the face of twenty-some people dying every day from the lack of transplant organs here in the USA alone and up to five hundred worldwide. And you do this with the solution right there, staring you in the face.”
“But the two patients died!” Jack yelled. “How can you overlook this immutable fact?”
“They died, but their hearts were functioning superbly,” Wei stated. “And both would have died months ago without the organs they received. You saw both hearts. They were perfectly accepted and functioning beautifully. Can’t we have a civilized discussion here?”
“You are too much,” Jack scoffed. “You want to have a civilized discussion over an uncivilized, unauthorized, unethical experiment that took advantage of two desperate young women. Even you said they diedof a retrovirus, which they must have contracted from their pig hearts. That’s the reality.”
“The reality is that they were human hearts,” Wei corrected. “And yes, they died apparently of porcine retrovirus, but not because of our protocol. What we didn’t expect was sabotage.”
Jack was about to shout back at Wei to give further vent to his self-righteous indignation when the meaning of the wordsabotagepenetrated his consciousness. It took some of the edge off his emotions. He stared at the billionaire, wondering if he had heard correctly.
“Just last night, or actually early this morning, we found something that we certainly didn’t expect,” Wei continued. “Both donor hearts contained a PERV, gammaretrovirus B, in very low titers that had been eliminated in our cloned line of pathogen-free pigs. After sequencing it and comparing it to the usual PERV, we found differences, meaning it had been artificially introduced. There is only one way such a situation could have happened. Someone planted the PERV deliberately to sabotage our experiment. And it wasn’t a random choice. It happened to be one of the PERVs known to infect human cells.”
“Why would someone sabotage your work?” Jack asked. He couldn’t help but be skeptical. Was this some other strange ruse from this devious man?
“Obviously we do not know for sure,” Wei said. “But we have suspicions. The Chinese government, which has an oversized presence in Chinese universities, as we all know, requires us to accept a large number of Chinese biotech graduate students as part of their training. Over the last number of years these millennials have been progressively imbued with a new Chinese nationalism that you have probably seen in the newspapers in relation to Chinese students at Western universities. Among this group, there is a growing intolerance to anything construed as negative propaganda directed at the new China. The Chinese government is behind it. I have been aware that some of these students who learned of my interest in getting my assets and myself out of China want me to fail.I have no proof they were behind this sabotage event, but I believe so nonetheless.”
“That’s a rather facile and convenient excuse,” Jack jeered. “I must give you credit for spontaneous creativity.” His cynicism made him dismiss the idea out of hand despite having no idea why Wei Zhao was taking the time and effort to explain all this cutting-edge bioscience to him.
“Do you not believe what I’m telling you about this neonationalistic movement among Chinese millennials? Do you not believe what I told you yesterday about how arbitrary the Chinese Communist government has become in relation to some of us successful businessmen, and how they have restricted the flow of capital out of China to put in jeopardy our overseas investments that are not already self-sustaining?”
“I just can’t relate it all to the deaths of these two young women,” Jack sneered. “It is trying to justify something that is unjustifiable. Carol and Margaret paid with their lives. On top of that, there are four other young people who have also paid with their lives, with the potential of the start of a significant body-fluid-born pandemic here in New York City, London, and possibly Rome. That’s already six people dead and counting.”
“I’m not trying to justify sabotage,” Wei snapped back. “What I am trying to explain is why it is akin to a terrorist attack on me and my company. When we find out who was responsible, believe me, they will be appropriately punished. As for the ‘experiment,’ as you term it, I think it was completely justified, and those women would be alive and well today had this terrorist act not taken place. Human organs grown in pigs is the future, and it is going to save countless lives. As for the potential pandemic, we have already made progress containing it, thanks again to CRISPR/CAS9.”
“Progress how?” Jack demanded.
“In terms of detection and cure,” Wei said. “With the help of CRISPR/CAS9, we have already developed both a rapid test to detect thevirus in an asymptomatic patient and an ex-vivo method of eliminating it. The fact that the illness spreads by body fluids rather than by aerosol is a huge benefit, as it will be infinitely easier epidemiologically to determine who needs to be tested.”
“Okay, okay,” Jack said, trying to control his vacillating emotions. He nervously ran his hand through his hair while he tried to organize his thoughts. “Answer me this! Why are you taking the time and energy to explain all this to me? Why are you trying to convince me about something I obviously don’t believe? It doesn’t make sense to me.”
“That is a good question,” Wei said. “As I listen to you, I find myself asking the same question. Partly it is because I do see you as a potential enemy, and I would rather have you on our side. I want you to join our team.”
