George Church #54

 Portrait by Alan Savenor

Portrait by Alan Savenor

The Robert Winthrop Professor of Genetics

Harvard Medical

 

Eventually, Galileo was completely accepted by the same religion that rejected him. And in science we often reject things until we can prove they are right. Until then, there's more heat than light.

This Interview was first published in the print Business section of the Boston Globe

 

Interview by Heidi Legg

George Church, The Robert Winthrop Professor of Genetics at Harvard Medical has the largest research lab at Harvard and wants to build a culture in the field of genomics based on sharing and transparency in an effort to bring us all into the discovery.

The work Dr. Church conducts in his lab is mind-blowing in an industry that is already changing rapidly. A new CRISPr technology [The Technique called CRISPR – short regularly interspaced short palindromic repeats – was developed in 2012 by scientists in California and in Europe. Many think they are an obvious for the Nobel Prize] is having an enormous impact. Church’s lab did early work to show the technique could be used to “edit” genes in human cells.  We sat down to discuss why he wants regulation and transparency in an industry that will vastly change lives, why his Personal Genome Project will advance research at a faster rate, the return of wooly mammoths, wiping out Malaria by changing the gene in mosquitoes that carries it, and why he thinks we should all get our genome sequenced. If that’s not enough to use the word visionary, I’m not sure what is.

 

What are you most excited about with your work?

I am most excited about the Malaria work we are doing with mosquitoes and gene therapy that has come back from the dead. There was a little premature action about a decade ago when it wasn't mature or ready.

With gene therapy, essentially we are able to reverse rare diseases that have a genetic component by putting in a copy of the gene that's missing. In principle, if you get it at the right stage in development, you can reverse things that cause blindness, blood disorders, and so forth. Either you put in gene that covers for a missing gene or you can fix a gene that is part of a process that is either hyperactive version and take out a gene: knock-ins and knock-outs. In the early days these weren't ready for clinical practice but today there are about 2,000 clinical trials using gene therapy in phase one, two, and three and some are already being approved. What we are seeing is great tolerance for genetic engineering for making drugs like insulin and growth hormone and even genetically modified humans in an environment where genetically modified food is not approved but all these things that impact health are.

I think that gene therapy could impact almost every aspect of health. And it's not just about rare diseases, almost everything that happens to us has something to do with our gene environment. Our lab has been one of the few academic labs for reading and writing DNA and once you can read and write DNA you can read and write cells, organs and whole living organisms.

Take aging. We all have aging as a genetic disease. Cancer also has genetic components and the reason that some animals die in less than two years and some of them go on to live 200 years is genetic.

What drew you to genomics and was this an interest from an early age?

My dad was a physician and from a very early age, I was interested in the technology he used for his work. A computer seemed really interesting. My friends and brothers would take things apart, while I would try to build little analog computers and models.

I was always drawn to anything that involved mixing biology, computers and math. It took me a while to find the mix. The first element was crystallography and the second was genomics.

[In July 2012, the United Nations proclaimed that 2014 would be the International Year of Crystallography]

Do you remember when you knew you were onto something?

I’m not sure I’m onto anything, yet. In graduate school, I worked in crystallography where a lot of things were automated. It was almost the only field of biology and chemistry that was fully automated. You could stick a crystal into this device in the dark and it would rotate around three axes, collect all this data, and it watch this beautiful dance for days on end. I thought, 'that's really cool. Can we apply that to other fields of biology?' And genomics was one of the first to try.

I also happened to land in Wally Gilbert's lab and Gilbert was onto something in terms of inventing DNA sequencing and it put the two together for me.

You started the Personal Genome Project. What is it?

The Personal Genome Project (PGP) is the only source in the world that we know of where you can get open access to genes, environments, and traits for human beings. The PGP enables all kinds of studies: to share stem cells, to test out gene therapies, test out drugs, and test out a lot of ideas in these shared resources.

Who can access it? What's the cost?

It's free. Anybody in the world can access it. You don't have to prove that you're a researcher. In fact, some of the most out of the box thinkers are the least credentialed people on the planet. PGP allows anyone to use this data for research.

Is The Personal Genome Project the Gutenberg Printing Press of genomics?

I think we're analogous to Wikipedia. There was a time where most encyclopedic type information, even post-Gutenberg, was in the silos of proprietary books and then Wikipedia completely changed that. Today, if I were trying to put genetic information in little silos and protecting them the way we used to protect encyclopedias, I would be looking over my shoulder at the Wikipedia version, which is the Personal Genome Project. With PGP, we are contributing to it and making it better.

Do you want everyone sequenced?

I think everybody should get sequenced if it's accompanied by a pretty simple preliminary test that shows that you're not going to freak out no matter what you see, and that you're going to follow up calmly.

The point is not to know how you're going to die. The point is to know how you can avoid premature death, premature disability, and premature senescence.

Do you think most people can handle it?

With a little education, yes, I think people can handle it. Today, as a society, we're handling lots of medical information already, including genetic. For some reason people have convinced themselves that genetics is special and isn't here yet, when it's just as here as other medical things.

Should we be wary of insurers having this info?

In the United States, it's against the law for them to charge you more based on your genetics. The Genetic Information Nondiscrimination Act of 2008 made it illegal for employers and health care insurance companies to discriminate. You can still have discrimination based on long-term care, life insurance and the military, but even before the law, I think for the most part there were very few examples of it.

I would say we always worry. Worry is a good thing. You should worry about unintended consequences; you should worry about technologies; you should worry about privacy.  Know the facts.

How can the public get involved?

If you're interested in signing up and learning more about the PGP and deciding whether it's for you and your family go to personalgenomes.org. We have blood drives in multiple cities because blood has a higher quality genome. We sometimes use skin for establishing stem cell lines. We also need money because we provide it as a free service.

How are you funded?

We have a lot of volunteers that work on the project and who donate blood, and we have some rich friends that occasionally give us a little money but it's extremely challenging.  We could scale this up much faster and help a lot more people if more people would contribute.

When we met you told me you are trying to wipe out Malaria. Can you explain?

A huge environmental risk, especially in developing nations, is infectious disease in the vectors that carry them such as mosquitoes and ticks and flies. Malaria is one of the big ones with 600,000 people per year dying of Malaria. One of the new things that we've just started working on is called CRISPR Gene Drives, although its roots are back to 2003 with Austin Burt who was an evolutionary geneticist from the UK.

Basically, you can put a pay-load into a mosquito that says, 'this mosquito is resistant to malaria' and every time it mates, all of its offspring will have the same position of that same chromosome and it spreads exponentially through the population starting with one designed mosquito. It basically does it itself but there are a lot of discussions we have to have about how to do this safely and how to test it in the laboratory. I think that's going to be a pretty awesome.

How far away are we from trying this effort to wipe out Malaria?

We’ve done the first Gene Drive test in yeast, not in mosquitoes. It works great. Very close to 100 per cent get the gene drive. We've begun in mosquitoes.

And how about the wooly mammoth you are bringing back?

We are working on mammals, or at least taking wooly mammoth genes. We are introducing them into elephants and testing ideas that come out of the genome sequence. Rather than just staring at them and saying, 'we think this is going on', we can test them in cells and in tissues and if that looks interesting, and safe, and effective then we can move it over to elephants.

How far away are you from that?

We've already made fifteen changes in elephant genome using the CRISPr technology and we're testing those out for their physiological effects in organ culture. We could be within a year or two before making a decision as to whether we want to test it in animals.

Where will you put the wooly mammoth?

There are a lot of people that would like to have them. The land where they like to grow is severely under-populated and called the Arctic Circle, (he laughs. Church has a wry sense of humor.) It's not the sort of place where you want to make your suburb or business for the most part. Some land has already been set aside for the return of the mammoth in Siberia.

Do you want to create a human from scratch?

It depends what you mean by 'create.' I think I wouldn't mind changing myself, or allow other people to change themselves, radically. Each of these things has to be vetted, but if you are cautious and you don't make something that's deleterious to the individual or to society, it works. The more radical it is, the more discussion we will have to have before we approve it, and the more tests we will have to do in the laboratory environment that are focused on safety and effectiveness.

The sensational questions to ask are: Do you believe in God? Are you conflicted with people creation? But I’d rather know, how should we, as a society, keep having conversations in a meaningful way so you can continue to innovate?

Some of the controversial topics are either religious or almost religious in nature. Even things like global warming and genetically modified foods (GMO) have become religious in that the debaters stop holding the facts as their top priority. They may listen to them, but they're not really actively participating in the experiments that could prove whether GMOs are safe, or whether global warming is an immediate threat or a distant threat. 

I think in some of these cases they will get solved with time. Eventually, Galileo was completely accepted by the same religion that rejected him. And in science we often reject things until we can prove they are right. Until then, there's more heat than light.

Personal genomics is something that is extremely accessible. You can prove whether a particular food has an effect or not, whether a microbe is present or not, whether you're sending your kid to day care with an allergy, or with H1N1, or with Ebola. It makes a difference, right? You want to have facts and genomics is a place where you can get the facts.

It's much harder to get the facts about when the first cell crawled up on the land…But determining whether your kid has a disease that's contagious or not is well within our capability.

“If you're a synthetic biologist or have any synthetic biology training, there's absolutely no reason why you should have any privacy,” says Church on the future ethics of Human Genomics and Synthetic Biology.  “Nobody forced you to become a synthetic biologist and so you should acknowledge that everything you do, on and off line, is going to be looked at deeply.”

I think you're lucky to be an early adopter.

I love being an early adopter. It has its down sides. You will try things out that may not be good for you, or mostly don't work, but the benefits definitely outweigh the risk.

People with those big cell phones the size of their head, they might have fried their brain. So, in a way it's good that we test these technologies out on the rich folks first because they can pay the medical costs of fixing the stuff. Then they quickly come down in price and get transferred out to everybody else if they actually are safe and effective.

An event you're looking forward to?

I think the next event is almost certainly, and this is something I can count on happening on a regular basis, the breakthroughs that the people in my lab, or my colleagues outside my lab, discover. It does bring me such joy to see the creativity and we're essentially seeing reality for the first time with each of these little breakthroughs.