Dr. Kiran Musunuru: On designer babies and genetic editing

Dr. Kiran Musunuru, center, an associate professor of Cardiovascular Medicine and Genetics in the Perelman School of Medicine at the University of Pennsylvania.

In his final book of essays — “Brief Answers to the Big Questions” — late scientist and author Stephen Hawking predicted that one day genetic engineering may inevitably alter the trajectory of human evolution with ‘Superhumans’ threatening the end of humanity.

Although the world is not exactly facing such a probability as yet, a Chinese physicist’s bid to change the fundamental genetic code of human babies in a laboratory in Shenzhen last year, has raised alarm among scientists, prompting questions among layman if Hawking’s prediction may indeed become a reality someday.

The Chinese scientist Dr. He Jiankui’s announcement that he had created the world’s first gene-edited babies in November last year caused shock and global outcry among the scientific community across the world, with leading genomic experts in the U.S. like Indian American Dr. Kiran Musunuru noting that this was not a historic scientific achievement as claimed by Dr. He but rather a “historic ethical fiasco, a deeply flawed experiment” on unborn human beings which needs to be regulated.

In the wake of Dr. He’s declaration, a group of 18 scientists from seven countries, including the U.S., Canada, China, France, Germany, Italy and New Zealand called for a voluntary moratorium on all studies involving gene editing of human eggs, sperm or embryos.

What Dr. He did in his laboratory was to alter the genes of recently-born twin girls christened Lulu and Nana while they were embryos to make them HIV-resistant, using a breakthrough technology known as CRISPR-Cas9. The tool makes it possible to operate on DNA to supply a needed gene or disable one that’s causing problems. The technology enables geneticists to edit parts of the genome by removing, adding or altering sections of the DNA sequence.

Dr. He studied at Rice and Stanford universities in the U.S. before returning to his homeland to open a lab at Southern University of Science and Technology of China in Shenzhen, where he also has two genetics companies.

“It was not a hoax by Dr. He, who first claimed the birth of the first genetically-engineered babies in the world at a conference in Hong Kong, but scientifically what he did was a very bad job thanks to his arrogance and ignorance, as he is a physicist and not a physician. Somehow, Dr. He thought he was qualified to do a clinical trial with this experimental technology,” Musunuru, an associate professor of Cardiovascular Medicine and Genetics in the Perelman School of Medicine at the University of Pennsylvania, who was one of the independent experts to evaluate Dr. He’s scientific manuscript, told India Abroad in an interview.

Musunuru studied and trained at Harvard University, Weill Cornell Medical College, The Rockefeller University, Brigham and Women’s Hospital, Johns Hopkins University and University of Pennsylvania. His research focuses on the genetics of heart disease and seeks to identify genetic factors that protect against disease and use them to develop therapies to protect the entire population. In his recent work he has been using gene editing to create a one-shot “vaccination” against heart attacks.

Dr. He gave his story about the genetically-engineered twins to a reputed science journal which rejected his manuscript. He had also offered the “exclusive story” about his feat to the Associated Press but it wanted to first run it through independent experts like Musunuru before publishing in order to check the veracity of his claims.

“I ended up being one of those independent experts, and that is how I came to read his manuscript. When I started looking through it, I immediately realized that things had gone wrong. The technology CRISPR- Cas9 had not worked the way Dr. He expected. It was messy and it looked really bad, and I was convinced that this was real and not a hoax because if it was a hoax, he would have tried to make the data look perfect,” Musunuru said. Musunuru, who was interviewed by the Associated Press and was quoted extensively in their first article titled “Chinese researcher claims first gene-edited babies” which mentioned that there is no independent confirmation of Dr. He’s claim, and it has not been published in a journal for vetting by other experts, said an experiment on human beings was unconscionable and not morally or ethically defensible.

Since then, Musunuru has given dozens of interviews to the media, explaining gene editing of human as well as its benefits and the downside. Musunuru finally decided to write a book called “The CRISPR Generation: The Story of the World’s First Gene-Edited Babies” in November this year, including not just the flawed experiment of Dr. He but also what the future holds for this technology so ordinary people can have a good understanding of gene editing and the CRISPR-Cas9 technology.

Talking about the promise of gene editing in health care, Musunuru referred to two patients, one each in U.S. and Germany, who were suffering from sickle cell disease and beta thalassemia, and received CRISPR therapy a few months ago as part of clinical trials and not only did the therapy work but seemingly both the patients may actually be cured.

“This would be historic because these are diseases that previously were incurable and now with CRISPR we have an answer to these ailments and these two patients who may actually be cured and that is part of the promise that these rare diseases can be cured through gene editing,” he said.

For the last ten years Musunuru has been working in his laboratory to use CRISPR tool to turn off a cholesterol gene in the liver in adults who had suffered a heart attack or have a high risk of getting a heart attack in the future because of high cholesterol.

“My idea is to use CRISPR and to turn off the cholesterol gene, and what that should do is not just reduce the cholesterol level in blood but reduce that permanently, because when you change the gene you have changed it forever, and so the cholesterol level will come down permanently and you will have lifetime type protection against heart disease,” Musunuru told this correspondent.

“It will be like taking statins, the cholesterol-lowering drugs, for the rest of one’s life but only with a single shot or a single therapy,” Musunuru, a recipient of Presidential Early Career Award for Scientists and Engineers from the White House under Obama, said. He is also recipient of American Heart Association’s Award of Meritorious Achievement, the American Philosophical Society’s Judson Daland Prize for Outstanding Achievement in Clinical Investigation, the American Federation for Medical Research’s Outstanding Investigator Award, and Harvard University’s Fannie Cox Prize for Excellence in Science Teaching, among others.

According to Musunuru, in the next two decades or so, gene editing will enable researchers to confer a mutation in PCSK9, or other beneficial mutations, on people who are genetically prone to have the disease and would be dramatically protected against heart attack and stroke for the rest of their lives.

“This gene editing is not exactly like a vaccination, but the concept is the same. It’s like a vaccine against heart disease,” he said.

Son of Rao Musunuru, also a cardiologist who moved to the U.S. from India in 1976 with his wife Prameela, Musunuru was born in New York city and grew up in Florida. He became interested in the root cause of heart diseases from early in his medical career.

When he was doing cardiology fellowship, for example, he realized that while there were good treatments for patients who have suffered heart-related problems and diseases, there was not much treatment available in terms of medical prevention.

“I used to feel frustrated that while we are very good at treating patients after they already have suffered heart attacks with very sophisticated technology like putting in balloons and stents and giving blood thinners to them, we are not very good at preventing diseases in the first place and the reason for that is that we did not have a good sense at that time as to what causes the disease. Thus, I became interested in genetics as a way to better understand what causes diseases like high cholesterol which in turn causes heart problems,” Musunuru said. With CRISPR one can turn off the gene responsible for cholesterol and thus eliminate the root cause for heart problems.

In his essay, Hawking predicted a world in which the ability to self-design people ultimately divides society, rather than helping to unite it.

“We are now entering a new phase of what might be called self-designed evolution, in which we will be able to change and improve our DNA. I am sure that during this century people will discover how to modify both intelligence and instincts such as aggression,” the groundbreaking scientist warned in the essay “Brief Answers to the Big Questions.”

Musunuru is evidently aware of such a scenario and that is why he favors gene editing only in rarest of the rare cases to fix an otherwise intractable and incurable medical problem, and not for trivial things to ensure enhancements, like changing hair color of a yet unborn baby.

He said there are situations, although it is rare, where the parents will be unable to have a healthy biological child unless editing is done and, in some cases, both the parents may have the same disease and all of their children will have the same disease unless they did editing to fix the problem in the embryo.

“I can be a little more sympathetic in such cases but while I am comfortable in gene editing in adults who have disease or risk for disease, I don’t like the idea of doing it on an embryo and I don’t see a good reason for that.

“If you are unable to have a healthy biological child of your own, there are other options to have a child like one can use sperm cells from a healthy donor and one doesn’t necessarily need to be editing in order to have a healthy child.”

Almost echoing the word of Stephen Hawking that genetic engineering may alter the course of human evolution, Musunuru said a lot of people are uncomfortable with the idea of gene editing for enhancements because it will create major problems in the society.

He said parents someday may like to improve their children’s traits like musical or athletic talents, although he is not sure that is possible because it is a very complicated process and may involve making changes in hundreds of cells. But even if theoretically that can be done, it will create major problems in the society.

“That is where one could have wealthy people using this tool to give their children every advantage whereas poor parents may not have access to this technology and may not be able to afford it. That leads to inequity and it has social and economic implications. So, it is not fair, and it is against the principle of justice,” Musunuru said.

In addition to this there are multiple religious and cultural arguments as well, including that humans should not be playing God, or interfere in the ways of the nature.

To a question if the concept of a “designer baby” is slowly taking hold of people’s imagination or is going to happen in future, Musunuru said he does not believe so.

“I think parents these days who think seriously of gene editing are the parents who have diseases themselves and they want to absolutely avoid their children having the same kind of diseases. So, I would say this technology is going to help, not millions of people but maybe a few hundred people with diseases around the world who have real medical issues,” Musunuru said.

“This Chinese scientist was trying to make the babies resistant to HIV and you can argue if that is really medical or more of an enhancement because these kids were not in any particular risk of getting HIV compared to the average person in the population, and so you can it was not like that they had HIV infection and he was trying to cure them. No, that was not the case, but if you consider that an enhancement you can say ‘well the first designer babies have already been made.’”

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