GeneOnline interviewed the legendary Dr. Church, while he was invited to the National Institute of Genomics and Proteomics of Taiwan University, and had him share some of his opinions on the field of genetic engineering with the audience.
The Father of Synthetic Biology
If you want to describe Dr. George Church in one sentence, many people will say that he is “the most daring synthetic biologist.” You may have heard of genetic engineering, but you probably haven’t thought about the crazy things that genetic engineering can do! The fictional genetic engineering ideas that occur only in movies has now been gradually realized. This includes editing DNA to treat hereditary diseases, editing aging genes to reverse aging, replacing USB with DNA to store digital data, engineering cells that are not infected by viruses, transplanting pig organs to the human body (Xenotransplantation), and synthesizing the human genome from scratch. All these admirable ideas came from a Harvard professor, Dr. George Church, who is known as the “father of synthetic biology.” GeneOnline interviewed the legendary Dr. Church, while he was invited to the National Institute of Genomics and Proteomics of Taiwan University.
Dr. George Church is a professor at Harvard Medical School and the Massachusetts Institute of Technology (MIT). He is also the director of the Center for Excellence in Genomics at the National Institutes of Health in the US. He has published > 500 papers and has obtained > 143 patents. Dr. Church also developed the first genome sequencing technology in 1994 and helped lead the biotechnology field into a new era of genomics. In addition to academic excellence, Dr. Church also holds a pivotal position in the biotechnology industry. He founded > 20 biomedical startups, bringing laboratory R&D technology and patents to the industry for gene therapy, stem cell engineering, organ development, xenotransplantation, and many other fields.
Sharing Data is Critical to Move Science Forward
In the interview, Dr. Church talked about the Personal Genome Project (PGP), which he launched in 2005. He said that most public or private gene banks used de-identified methods to collect genetic data, in order to protect the identity of the participants. However, the de-identification resulted in problems in linking back to clinical records, as it is not possible to continuously update personal clinical data or lifestyle changes on the same set of genetic data. Since there are many limitations on the use of de-identified gene banks, Dr. Church initiated the PGP to encourage participants to publicly share their genomic data, health, and experimental data, and establish an international public genome database in a non-anonymous manner. It is hoped that all the countries who participated in the PGP, can share their data with each other to advance genetic research. One of the reasons why Dr. Church visited Taiwan is to discuss the possibility of Taiwan Biobank to join the PGP. Dr. Church acknowledges Taiwan’s willingness to join PGP and says that Taiwan’s participation will enrich the PGP by providing more data on the Asian population.
However, several concerns on the PGP have been raised, including the privacy of the PGP participants, the use of PGP as a criminal tool, and ethical issues. In the face of doubt, Dr. George Church believes that the work on PGP cannot be squandered just because there are problems. He added that while developing genetic engineering technology, scientists also have to concurrently spend a lot of effort in developing a safety net for the technology to make up for security vulnerabilities, and minimize the possible negative impacts.
As the genetic engineering technology matures, its application in real-world use by both academia and the industry becomes a topic of great interest. Dr. Church gave an example of how he has involved both these institutions in his genetic engineering research. The commonly used gene therapy vector adeno-associated virus (AAV) still has several safety concerns in clinical use, such as inducing a systemic immune response, causing abnormal liver index, and low accuracy of infected cells. Dr. Church’s laboratory uses machine learning technology to select a combination of high-efficiency and low-immunity sequences and then use the genetic engineering technology to edit the gene sequence of the AAV shell (capsid). Cellular and animal experiments using the modified AAV found that it evades the immune system and precisely delivers the carrier to the target tissue. This new technology that is developed by Dr. Church’s laboratory eventually evolved to form Dyno Therapeutics, a company focusing on optimizing all aspects of gene therapy through machine learning.
After overcoming the challenges of multiplex gene editing, Dr. Church had an even more daring idea. His laboratory eliminated all the porcine-related genes that might result in immune reactions during xenotransplantation to humans. Those included porcine endogenous retrovirus (PERVs) gene fragments on pig cells, genes related to complement reactions, and genes related to cellular immune responses. The remarkable feat of engineering not only confirms that CRISPR editing technology has sufficient accuracy to edit specific gene fragments scattered throughout the whole genome, but also offers a solution to the problem of organ transplant shortage. Subsequently, Dr.Church established a company named “eGenesis” and co-developed the porcine xenotransplantation technology with “Qihan Biotech” in China.
A Person Who Opened Pandora’s Box?
As genetic engineering technology becomes more powerful, the public has become aware and critical of its limitations. The topics on genetically engineered humans, reversing aging, and man-made creatures have resulted in intense safety and ethical debates. Some have even commented that scientists are playing God. Amidst these controversies, Dr. Church calmly said, “We are not trying to create superhumans! When humans get older, their organs are also aging, and many aging-related diseases develop, including, Type 2 diabetes, heart damage, and osteoarthritis.” Dr. Church’s laboratory has developed > 48 sets of potential gene therapies that can reverse organ aging. However, the goal of these anti-aging studies is not to develop immortal elixir, but to let elderly patients improve their organ function and have a chance to be cured of the aging-related diseases. Hence, Dr. Church established “ Rejuvenate Bio”, a company focusing on the development of anti-aging gene therapy.
The scientific community generally holds a fairly reserved attitude towards “editing germinal cells”, and most of them are careful not to touch on this subject. However, in 2018, a Chinese scientist named He Jiankui edited the CCR5 gene of a twin embryo and the edited embryo was successfully conceived and born. The creation of genetically modified babies drew widespread criticism from researchers in the field, but Dr. Church is one of the few scholars who have maintained a more neutral view. He says that the experimental plan and data of the research should be carefully assessed before he can make any comments. “Editing germinal cells” does not mean creating an evolutionary race, and the action is not completely untouchable. From the perspective of hereditary diseases, Dr. Church believes that editing germinal cells can permanently solve the problem of hereditary diseases in families, and the appropriate use of this technology will bring many positive impacts on society. For example, just like gene therapy, “editing germinal cells” can help some patients break away from the inconvenience of having to take drugs for their entire life. Dr. Church even proposed a radical use of technology, which is to develop a dating application based on genetic data matchmaking. The software will warn carriers of rare recessive diseases from dating fellow carriers of the same disease, so their offsprings will be healthy. This will be an example of the correct use of technology in stopping the spread of diseases from the start.
Dr. Church already has accomplished many scientific breakthroughs and has a successful career spanning several decades. However, at his current age of 65, he still has not stopped or slowed down his research plans. Besides genetic engineering, Dr. Church still has several avant-garde approaches to technology and crazy ideas: (1) He hopes to synthesize the human genome from scratch so that one can be free from the limits of genetic engineering; (2) Help humans adapt to the space environment through genetic engineering. Dr. Church believes that the current research on genetic engineering is only the tip of the iceberg, and there are more possibilities in the future. When asked if he would edit his own genes, he concedes that there is much scope for improvement in clinical validation. However, when the editing technologies mature and is assured of safety, he does not mind becoming the first subject to enroll in a clinical trial to witness the epoch-making scientific development. The world is looking forward to witnessing how Dr. Church continues to make advances in genetic engineering technology and impact our society.
Editor / Alma Wu
Translator / Gabriel Lee
Reviewer / Thomas Huang
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