Prof. George Church is Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT. He developed methods used for the first genome sequence (1994) & a million-fold cost reduction since (via NGS and nanopores), plus barcoding, DNA assembly from chips, genome editing, writing & recoding. He was one of the founders of the BRAIN Initiative (2011) & Genome Projects (1984, 2005) to provide & interpret the world’s only open-access personal precision medicine datasets. He is also director of the Personal Genome Project, which provides the world’s only open-access information on human Genomic, Environmental & Trait data.
The following has been paraphrased from an interview with Prof. George Church on December 20th, 2017.
(Click here for the full audio version, apologies for the lapses in audio at times)
If a complete understanding of human genetics were a hundred yard dash, how far would you say we have gone in this race?
The problem is the word “complete”. Some things that are hidden in the genomes of bacteria, let alone humans, offered some subtle Darwinian advantages long ago under conditions that we may not have today. Also we may not need complete understanding for a lot of things. We developed effective smallpox prevention back when we had close to zero understanding of virology and immunology. But I don’t know where we are in the sprint, though my guess is it’s not a sprint, it’s a long distance run.
Where is the complexity of human beings stored in light of the fact that we have fewer genes than a flea or a tomato?
I don’t know why people think we are more complex. There are animals that I think are more complex, particularly those that go through metamorphosis, which is a more complex process than human development. In principle, you could have a very small number of genes but high complexity in alternative enhancers, RNA & protein start sites, alternative RNA splicing, post-transcriptional RNA and protein processing, etc. Those vary from organism to organism and can produce complexity through their interactions.
How much useful information do you suspect is hidden in our ‘junk DNA’?
Junk DNA was originally defined as the non-protein coding regions. We know there is a ton of information in the DNA and RNA elements of it. There are transacting RNAs, there are cis-regulatory elements, etc. There is a project called the ENCODE project that is focused on figuring out what every base pair might mean. I wouldn’t be surprised if we find out that every base pair is important for something. Even if only 1% of the human genome is protein coding, additional utility can be seen from sequences which are conserved evolutionarily — on the order of 97% for distant members of a genus, but even the 3% that is highly variable or repetitive and looks like junk DNA can still be useful (for example CRISPR).
Do you believe everyone should get their genome sequenced?
There will be exceptions but yes I think almost everyone should. I think most people could benefit from doing so and society as a whole would also benefit. 5% of babies are born severely affected by genetic diseases, which is preventable by the relatively modest costs of sequencing and genetic counseling at about a thousand dollars combined. Contrast that with the consequences of the babies that are born with a harmful mutation, which is about a million dollars for a lifetime of treatment plus the impact on the family. Though people should have the choice to selectively hear about their genetic information after they are sufficiently educated on it, which is part of what we are trying to do with the Personal Genome Project.
You’ve stated that you believe we will be able to reverse aging within the next 10 years, does this include the affects of aging on our brains?
It looks like there is some evidence that our nervous system is already better protected than other parts of the body from aging. But a lot of the things that we are looking at that impact aging in animals do also positively affect the nervous system. There are also some aging reversal protocols that involve estrogen or blood-born factors that look like they impact the nervous system. I’m sure there will be many more to come. This is particularly important as we have an aging population experiencing more cognitively decline.
What role will synthetic biology play in giving us better models of the brain?
We and other labs are getting more and more accurate brain organoids. They are initially for assessing genetic impact and for testing new therapies, but these organoids could also get better and better until they are suitable as transplants. We are also seeing synthetic biology used to make unique barcodes for each cell to track developmental lineage and connectomics(maps of connections within an organism’s nervous system).
One of the big hopes for synthetic biology is the advent of molecular machines that can repair our bodies better than they can repair themselves, what is the state of this research and when might this be a reality?
These could be molecular machines that are already present in nature, we just improve them. An example is radiation resistance which has been increased 10,000-fold with only 4 genetic changes. Many of the changes that we would refer to as aging reversal are actually just putting the epigenetics of the cells in the body at a younger state, giving youthful levels of repair to older people. Synthetic cells could enable even better repair mechanisms which could be particularly useful for people who go to space where there is a lot of radiation and other sources of stress that are not found on earth.
Proponents of synthetic biology have claimed that it will perform all sorts of wonders: bringing back extinct species, synthetically growing meat that will end our dependence on farm animals, creating cyanobacteria that will sequester co2 emissions and halt climate change, unraveling the origins of life, molecular computers better than our electronic ones, or the ability to engineer our own species and put an end to natural selection. Do you worry that there is too much hype surrounding synthetic biology?
I think occasionally there is hype but there is also overdone anti-hype where people get carried away labeling someone else’s vision as hype. The key is just differentiating between the future and the present. But it is usually harmless. I am more concerned that the future will arrive without adequate discussion and hence we make hasty, reactive decisions.
To your specific examples…
With de-extinction, there are already several genes and even whole viruses that have been returned from extinction and tested for their properties. Two Mammoth genes have been de-extincted already.
Synthetic meat replacements are already on the market. Certainly there is recent awareness of the impact of cows on methane production, as well as zoonotic diseases, water use, antibiotics, etc. Synthetic biology could help address these issues.
Sequestration of CO2 and methane can not only halt climate change but could reverse it. This is an area where synthetic biology can certainly help and involve fewer sacrifices as people don’t like to be told what to do. This is not hype, this is something that is worthy of more discussion.
We may not learn the exact origins of life, but we are learning ways to accelerate evolution, including the transition from non-living to living as well as more recent changes in morphology. We could make huge changes that would look like new species and get accelerated evolution to possibly produce new kingdoms or domains of life.
As far as molecular computers go, this one could be hype, but we have not ruled out this possibility. The reason we say it is possible is that DNA has far higher density, it is inexpensive to copy(we made 70 million copies of my book using DNA), and it lasts longer than conventional disks/tapes. But more work is needed on cost of synthesis, sequencing and integration and other data sources to make it a practical applications. I don’t think it is worthy of calling hype, we have had a million-fold improvement in our ability to read and write DNA in a very short period of time, that makes this worthy of further exploration.
On the last point, we already engineer our own species, synthetic biology is just accelerating that process. Natural selection does not just include mutation and selection of DNA, it also includes mutation of our culture, and our culture includes DNA. We can now mutate and select DNA much faster than before. Whether it’s cultural or DNA based or anything in between, it now might take just years or months whereas it took millions of years to make a new species by the old method. Also it’s not just biology that is engineering our species but also physics and chemistry, our ability to go to the moon is due more to culture and physics than evolution.
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Continued success in your Parkinson pursuits during 2018, Ben!