By The Medical Futurist | April 13, 2019
Interview with Andrew Hessel, CEO of Humane Genomics
Where is synthetic biology heading? What is cellular agriculture? Why will companies pay people soon to get their genomes sequenced? Is it likely that human-made viruses going to destroy the world? We had a fascinating conversation with Andrew Hessel, microbiologist, geneticist and CEO of Humane Genomics about the progress of biotechnology and genetics, about how thinking about the needs of babies results in ideas about laboratory-produced breast milk, about hand-held devices identifying viruses based on their DNA in seconds or what new biotech products and services could hit the market 10-15 years ahead.
You are an expert in biotech, microbiology, genetics – all of them incredibly progressive fields. What are you the most excited about these days?
Well, in general, I have been focusing on the area of synthetic biology with respect to the design of new organisms. And that’s a pretty broad interest, but there’s a core to it that is quite universal: the fact every living thing on this planet is made up of the same fundamental architecture: the cell and their basic machinery. It starts with the genetic code as coding used for the machinery. This code runs the metabolism of the cell making proteins and doing metabolic functions. So even though my interests are broad, they condense down to a universal set of biophysics and mechanics that is pretty foundational and surprisingly simple to understand.
Many years ago, when I was doing research in genetics I heard about the Mycoplasma experiment: how to narrow down the genome to the minimal viable genome, but I assume that the biggest efforts in synthetic biology today are the opposite of that. How to assemble DNA code into something that can become a living organism. Is that correct?
The comparison I use for synthetic biology is the field of computing: ones and zeros, and how manipulating those has changed just about every industry on the planet. In much the same way, being able to design, engineer, and understand biology by manipulating A’s, T’s, G’s, and C’s is changing so many different industries, from pharmaceuticals to fuels. But it’s just getting started. In the case that you just brought up – taking Mycoplasma, a simple bacterium, and deleting genes to find out what is the minimal set of genes to make a viable living cell – that’s been amazing work.
I remember Ham Smith and Craig Venter working on this back in the eary days of Celera Genomicsaround 1998. And just recently, at the beginning of 2016, they published a paper on a minimal viable Mycoplasma that they synthesized from scratch. I think it was around 472 or 473 genes and, taking into account that a gene roughly corresponds to a single protein, it’s a very small number of genes that are required to make a cell, under 500,000 bases of genetic code.
So that’s one aspect, but there are other groups looking at how you actually take a set of individual proteins and put them into a container to create artificial cells, so-called protocells. Myself, I take a broader view and look at how you use software tools to design genetic code, take that electronic design and turn into physical DNA so that you can put it into a cell to either reprogram it or build its genome from scratch. The result can be a cell that is completely new, but still made from the same systems as any natural cell. And that’s how I look at synthetic biology. It’s really about learning how to program cells.
And what’s the promise for humanity here? What if we can build such organisms based on software? How does that impact us?
Well, first of all, this is a proven technology already. We have software tools for manipulating the genetic code. While the early tools were a lot like word processors, mainly just editors to move bits or blocks of genetic codes around, more sophisticated software tools are starting to develop higher-order programming languages where you can build circuits and/or assemble pre-computed components into more sophisticated metabolism. So, we’re just entering a new dimension of software tools that should essentially allow us to build enough metabolism to make a living cell. Most previous attempts to date in doing genome engineering at a software level has been to essentially to take the genome that has already been sequenced and make very small modifications to it, so you don’t break it. But the process of using a software tool to design genetic code and then print the resulting physical DNA molecule is well-proven now in synthetic biology.
However, even though this field has been developing quickly over the last 15 years, the tools are still relatively crude. The foundation that we’re standing on is amazing, the work that is being done is excellent, but it’s like being back to the early days of computing. The computers were big, slow, expensive, and bulky. It certainly took a lot of time to develop the ubiquitous computing platforms that we have today. That’s essentially where synthetic biology is today. It’s still a small industry, it’s still relatively slow and expensive to do the work, and the things that we can do with the tools and technologies are relatively unsophisticated.
Let me give you an example. The entire first generation of biopharma companies essentially made one type of product: single proteins that they learned how to express in cell culture, purify, package and sell, for example, insulin, human growth hormone or erythropoietin (a small protein that tells your bone marrow to produce red blood cells). The second generation of biopharma companies is merging today. They’re built on synthetic biology, and reprogram larger blocks of metabolism to make more sophisticated molecules or processes in the cell. This moves beyond single proteins to more complex materials that might take multiple enzymes working in a coordinated way to produce the material. Or put an entire circuit into a cell that can respond to stimuli and change its outputs based on what it’s sensing in the world around it. So, this is where most of the synthetic biology industry is today.
So, where do I see it heading? Just as with computing: software tools will get better and the DNA printers that turn the design into executable code in the cell will get more sophisticated. It will become possible to design and build complete cells, complete cell metabolism, from the ground up, quickly and inexpensively. Consequentially, this will cause a blossoming explosion of new and interesting projects both in the field of synthetic biology research but also in the synthetic biology industry – targeting everything from foodstuffs through new biomaterials to ultimately new organisms both single-cell, multi-cellular and beyond.
I’m very fortunate to be a co-founder of a genome project, the Genome Project-write, which is essentially the successor of the first Human Genome Project, which introduced DNA sequencing to society and developed the platform to read the human genome. Thereby, it opened up a door to reading and interpreting the genome of any microbe, plant, animal, and person on the planet. Now the goal is to develop synthetic software tools and societal frameworks to prepare humanity for the eventual writing and design of new organisms on planet Earth.
You mentioned how synthetic biology could produce certain kind of foods, biomaterials, I guess even medications. Could you give us a few examples about what we could expect to see in about 5 to 10 years in production lines that in some forms use synthetic biological methods?
Well, let’s start with food because that’s biology that touches each and every one of us daily, often multiple times a day. We all need to consume organic matter to live and so right now, there’s a growing awareness that our methods of food production, which have increased dramatically in the last one-hundred years to support some 7.6 billion people on this planet, are not going to be sustainable to support 10-12 billion people in the future. Food transportation systems are incredibly expensive, in terms of just the fuel required to move food around the world. The agricultural use of land, water, and other resources just don’t scale well. So now, there’s a shift to what is being called cellular agriculture, which involves learning how to take the components of various plants and animals and bring them into a controllable production system.
I’ll give you an example that really excites me. I have two kids, a four-year-old daughter, and a one-year-old son. So, I think a lot about the needs of babies. Now, in terms of food that’s pretty simple. It’s milk. For the first year, they pretty much just consume milk. But they can’t survive on cow’s milk as that has the wrong protein mix, doesn’t have the right vitamins, the right antibodies and other protections that are passed down from mother to child through breast milk. That’s why we have to use formula, which has been refined over the last century to be a supplement for breast milk. Now, it’s possible to use synthetic biology to make milk, take Perfect Day. It’s reprogramming yeast cells to produce proteins necessary to make milk. Milk is mainly water, a few proteins, a few minerals, and if you reprogram yeast to make the proteins, it’s quite straightforward to go and produce milk. Meanwhile, you can also tune the proteins that are being made, you can have the big yeast cells go and make goat milk, camel milk, or human milk. So once you get the milk production started, the factories look very much like a brewery except that now these factories make milk. That’s an amazing advancement.
And you don’t need the whole cow, you only need very small amounts of land to make these breweries and you can produce millions of gallons of nutritionally complete milk to replace cow’s milk or to replace human breast milk. That’s just one example of cellular agriculture, which is fascinating for me. Others are starting to look at how we replace various meats, whether we use plant proteins or whether we’re using muscle cells from animals that had been cultured and turned into meat analogs. The list goes on and on. This is really powerful, plus it combines with other forms of manufacturing techniques such as vertical farms. If we learn to apply and scale these systems, it can help support a larger population on Earth without continuing to encroach on our existing ecosystems.
Another example is building materials, such as wood. Today, you have to chop down relatively large trees, plane them into standard sizes, ship these products all around the world and then assemble them using relatively wasteful, crude ways of construction. Most construction sites waste somewhere between 20-30 percent of the materials that they have delivered in the form of scraps and cuttings. But what if we can take the cellular components of wood and put them into a cell-based slurry? Then we can essentially 3D print or cast wood beams just as we might be molding a plastic part, where the wood just forms from cell-growth in a mold. You can do the same thing with sandstone.
A friend of mine, Ginger Krieg Dosier has a company called bioMASON, where she takes particulates like sand, mixes it with bacterial slurry and turns into sandstone in as little as five days. This can be done using a casting system to make bricks, but with more sophisticated casts you can produce very elegant structures that you could have never carved, all the way into 3D printing stone in the future. Can you imagine a house-sized printer that 3D-prints stone foundations, wood for paneling, metal for wiring, etc. might look like? For me, that’s definitely in our future.
And you’ve mentioned drugs. Yes, using synthetic biology to make drugs and other therapeutics by reprogramming cells or their outputs is a fascinating path to making new medicines. Today, this is moving closer to the mainstream. If you look at my work, on a day-to-day basis I engineer viruses that can be therapeutic. My company, Humane Genomics, creates designer viruses from scratch, using computer design tools and ultimately printing the viral genomes, which will go on to direct cellular systems to make the virus particles. This makes it possible to make exquisitely targeted medicines for a single patient at a low cost, which could lead to rapid progress in treating cancer. Overall, the trend is that the technology of synthetic biology is becoming cheaper, much more powerful, much more accessible and supported by increasingly sophisticated software tools, which brings in the most sophisticated thinking and supervision of these processes that are far beyond everything we’ve had in the past.
And what if we look into the year 2035 and take someone from the general population. What kind of products do you see in the life of that person made by synthetic biology?
Well, I believe that, given the rate of advancement of the core technologies, these design tools will move very quickly. The field of DNA synthesizers will explode in terms of the number of people coming into it and the number of users. This is similar to the incredible proliferation of apps on mobile phone platforms, and it makes it very hard to imagine the diversity that could start to appear within 10 years. Anything I tell you is really just going to be some anecdotal examples of what could potentially be millions of new products, experiments, and trials, coming to every part of the world and every demographic in society.
Within 15 years, I expect that we’re going to be able to assemble any microbial or viral genome, or reprogram any of the commonly used cells, like Chinese hamster ovary cells, E.coli cells or yeast cells. I expect that making or reprogramming single-celled organisms and viruses will be universally available and inexpensive. This alone opens up a tremendous space for biomanufacturing and the exploration of new products and services. I think the medical field is the area where this could have the biggest impact in the short term. People could start making their own biosimilars of any biotech drug that’s on the planet today. If it’s currently made by a biotech company and it can be programmed in DNA, someone is going to make a similar knock-off or a clone version of that drug. I think being able to protect the intellectual property of today’s biotech industry is going to become extremely hard as the tools of current biotechnology just become incredibly cheap and accessible.
In addition, over the next ten years, we should be starting to get the capability to synthesize the largest genomes, including the human genome. Now, I expect this to remain largely in the area of research because we don’t fully grasp what all the code in a large genome does, but we can write a chromosome and a genome without its full comprehension. It will also be too expensive for most groups to write large chromosomes or genomes, which can run into billions of bases. Still, I think this will start to lay the foundation academically and professionally for a much more sophisticated exploration and understanding of all living systems.
Now, just to jump to the other side of the coin, DNA sequencing. This is a very powerful medical diagnostic tool and an informational feedstock for writing new genetic programs. I’m an advisor to a company called Nebula Genomics, which has partnered with Veritas Genetics, both companies that have come out of George Church’s lab at Harvard University. The big news here is that the cost of human DNA sequencing has been driven down to zero. In fact, instead of a person paying to have their genome sequenced, in many cases, they will be paid to be sequenced. And that’s simply because we’ve hit an economic inflection point where we can now extract more valuable information from a person’s genome than the cost of acquiring that genome. So, this is leading to a race to sequence all of humanity, where the company that sequences and analyzes most people could become yet another trillion dollar company.
These are just a few examples of this acceleration over the next 10-15 years that could radically change the foundations of all biotechnologies relating to humans and the environment.
So do you think it’s a viable scenario that in about 10-15 years from now when I feel like I’m having a cold, I just get my whatever fluid sample and test it at home with a hand-held device that would tell me what kind of virus or bacteria I’m having right now? And maybe it could even direct me to the right treatment or create that for me. I know it’s a very far-fetched idea.
No, it’s absolutely not a far-fetched idea at all. Let me just walk through the technology because I think you raised an excellent point. First of all, unless you’re a bioengineer, you wouldn’t be likely to make that treatment yourself, just as unless you’re a computer programmer today you’re not going to craft a software solution to a concern you have around your home. There are always going to be people that have certain skills and people that don’t. So let’s not worry about that.
But let’s just look at that scenario: you are feeling unwell and wondering if you have a virus infection. There’s no reason today why we couldn’t build a virus detector that could identify the presence of any virus in your home, around your body or in your body. There’s just been no giant push for that yet. However, once it exists, no matter whether you are a new parent, a younger or older person, that virus detection capability will always come in handy.
Now, how you do diagnostics is relatively straightforward. Just look at a company that’s quite fascinating: Mammoth Biosciences. It is one of the new companies that have been built on the CRISPR gene editing technology. CRISPR has essentially two components: an element that scans genetic information for a particular sequence of code with high precision – like a barcode, and another component that can cut the genetic code and either delete or add code to that segment. So, if you take the recognition part of the CRISPR system and you couple it with an enzyme that just produces a caller signal, you essentially have a reporter for any precise sequence of genetic code. If it finds a given sequence of genetic code, say for the Zika virus, then it produces a color signal. It’s so precise that it can identify any virus. Now, you can make a panel of every known virus and do a single test to basically identify all viruses in a sample. That could be built into a very small device – a universal virus detector, as simple as a pregnancy test. That’s an example that I think is really powerful.
Moving forward, I fully expect that we will have an Internet-connected device not much bigger than an inhaler or an EpiPen that will actually contain a miniature pharmaceutical company able to produce for example a vaccine, an anti-virus or even a viral gene therapy. As these agents are literally a few hundred nanometers, manufacturing of these components will be done inside the device on biochips.
Just to follow through your example, you’re not feeling very well, you think you may have a cold, you blow into a device, and it tells you exactly what virus you have and this information is used to produce an anti-virus, all within a few minutes, in your own home. This is not science-fiction, the technologies all exist today. It’s all about being able to make it miniaturized, accessible and consumer-priced points, all the while building a new regulatory architecture that understands and advances this approach.
If it’s technologically possible to make these devices, why don’t we have them yet?
To be able to answer that, you have to look at the history of computing. In the early 1970s, we had electronic computers and computer chips, but did we have the cellphone yet? No, that took until the 1980s. Did we have the smartphone yet? No, we had to wait until the 2000s. It takes time for these technologies to grow because each phase of the technology has to be understood, brought to market, develop consumer acceptance towards it and then, you have to push the boundaries yet again.
Now, I think we’re getting faster and faster at doing this type of evolution. I believe we’re going to see a very different pace of advancement in biotechnologies versus computer and consumer goods in the computer space because essentially we live in a giant living world. Planet Earth is a giant factory that can make incredibly diverse forms of cells and cellular systems including us. And there’s a universal programming language for this machinery, the genetic code, so this is why I think it might get off to a relatively slow start, but then incredibly accelerate as we start to build up a head of steam here.
The only example I have for this is the relative pace of advancement in DNA sequencing technology vs. computer technology, essentially Moore’s Law versus what they call the Carlson curve. It was named after Rob Carlson who mapped the pace of advancement in DNA sequencing and synthesis. So if you look at Moore’s Law, there’s a consistent exponential advancement of computing technology, but it’s ultimately tied to how quickly new factories can be built, or how people will buy new electronic products. Then, if you look at genome sequencing, to read the first human genome required an international consortium of scientists and industry groups working together – and that was 3 billion dollars of investment, many millions of person-hours, time and energy. But the second genome cost about a hundred million dollars. Afterward, it kind of tracked Moore’s Law until about 2007 and then we saw this incredible acceleration in DNA sequencing capability due to a new generation of DNA sequencers.
That acceleration continued until around 2015-2016 when it kind of bottomed out again for a while at about a 1000 dollars a genome – and now we’re seeing that plummet to zero in just the last three years. Now, your whole genome can be free and we’re going to see that trend continue to the point where you get paid for being sequenced, flipping the entire equation, as I mentioned before. So let’s just say we don’t have it yet, the fire is just smoldering right now, but it’s going to turn into a global inferno over the next few years.
You touched upon a very exciting point with this image of the inferno: when we discuss progress in biotechnology, the first comments we get are about doubt and fear similar to how people are afraid of artificial intelligence. Shifting to the point where we don’t understand anymore what’s happening around us. Where do you think this threshold is in biotechnology, what’s the red line that’s being crossed we would lose our humanity?
Well, let’s actually unpack the being human part at first. Why is it that we seem to accept technologies like computing, mechanical or electrical systems quite easily and yet fear biotechnologies? I’m no historian but I believe this is actually a false comparison. In the early days of mechanical systems, there was tremendous resistance to mechanical systems replacing human workers, just think of the Luddites. More recently, in my lifetime, I’ve seen that fear around artificial intelligence, personal computing, and robots in the factory. Will they take our jobs, will they rise up and become our masters, will they ultimately turn on us?
These are significant fears that aren’t eradicated today, but I think because we build these technologies, we ultimately become more comfortable with them over time, and we lose our fear. But we should be fearful! Every new robot we build and every new factory that we open to make mechanical, electrical, or computational products first means the destruction and the degradation of our ecosystems and ultimately the pollution of our land, our oceans, and our air. We know it’s unsustainable, yet we don’t stop.
Now, conversely, biotechnologies are sustainable, infinitely recyclable. Biology is created from elemental materials, carbon, hydrogen, oxygen, sulfur, phosphorus, some trace elements. And biology makes an incredible diversity of machinery: plants, animals and people, microbes that make our human machines look like toys, crude rocks, and sticks. Biology is so advanced that people ascribe this technology to Gods. But for hundreds of years we’ve been trying to learn about this technology. Four hundred years ago, we recognized that life is built from cells and, about a hundred and some years ago, we started to understand the microbial nature of life and the presence of viral agents. Since then, biologists have cataloged every living thing that humanity can get its hands on. Darwin discussed mechanisms on how diversity is created. We’ve moved to a molecular understanding of these agents and now we understand most of the cellular processes, DNA, RNA, proteins and so on.
We’ve been reverse engineering this incredibly complex machinery for so long and yet it’s not widely known. Most people don’t pick up biology and understand this because it’s not part of our daily lives and in fact, the only time we really think about these systems is when they’re not working right. And part of the time when they’re not working right we’re sick, hungry or fearful, our crops are dying, our animals and our children are suffering. So, this ignorance gets cross-connected with our deepest fears and our deepest loss. I think this changes as we start to be able to build and manipulate these systems like we’re programming computers, building a machine or a factory.
I’ve started to see that shift in young people who come into the field of synthetic biology. They are quite young, at around the same age as they would start to program computers. They get the concepts early and start writing programs and circuits as early as 8 or 9 years old. By the time they’re 12 or 15, they can be incredibly proficient, and by the time they’re 20 they are experts. We’re starting to see the dynamic in this field – with programmes like the International Genetically Engineered Machine Competition that has now trained some 40.000 young people in how to do this work in a completely open and transparent way.
And as long as we keep it open, transparent and not lock people out, if you look forward 10-20 years, we’ll finally get over this hump that biology is immediately something fearful. We’ll start to see it as the most powerful tool humanity has ever had, being able to sustain humanity here on Earth in far larger numbers than we can probably imagine today. While it also helps sustain us in going off exploring off-world, whether it’s living in lower orbit around the Moon or Mars or further beyond.
That sounds reassuring, but just pushing your boundaries a little, could you describe your dystopian nightmare connected to biotechnologies?
Look, the only fear that I have in moving forward with these technologies are humans. Right now, there is asymmetry between the ability to make a virus and that to defend against a virus. We’re working on closing that gap today. In other words, the technology is accessible and powerful enough today for someone to create a virus nefariously or by accident that could cause spreading infection, but systems aren’t yet in place to catch this early and mitigate it. Now, I don’t think this infection would necessarily be worse than the infections that Mother Nature generates at regular intervals, infections that we’ve learned how to isolate, counter and vaccinate against.
However, I want to be clear. There’s a short-term potential for a human-made virus to do harm because we simply haven’t put together the detectors and regulatory agencies necessary to neutralize new threats. So, hackers have a slight advantage today. But rewind to the late 1980s. Back then, computer hackers had a slight advantage because there was no vaccination of personal computers or networks. That gap got closed very quickly. And I expect to see the same here.
Thus, the only fear I really have is humans. We sometimes fight each other, kill each other’s kids, and hate each other for the stupidest reasons and this should stop. Because these tools are very powerful. And if we decide to use bioweapons in warfare, then fights can get pretty horrific. Somehow we’ve managed to avoid nuclear war as of yet. I definitely do not want to see biological war. We need to solve these issues very quickly. We need to be more cooperative and collaborative, not competitive. We need to be much more empathetic. It’s not okay for someone who has money to get better healthcare than someone who is poor. That’s not okay. In today’s world, a rich and a poor person can both have the same phone. I don’t know why we think that’s okay and yet accept the fact that one can’t get the same medicine. That’s just wrong.
So this is why my company, Humane Genomics is about open sourcing genomics and other advanced tools for all of society. I believe we have to create an entirely new biotech industry that is much more open and much more collaborative just as the Internet is a base that allows everyone small or large to participate.