There’s a notion that computers get faster and cheaper by making their logic gates smaller, and how you improve a design with physics keeps bumping up against how you make these little units smaller. Well, using biology, the solution seems self-evident—you just line up the pieces of DNA, and if you put the right pieces of DNA in the right places, the resulting parts are so much smaller than the things we can do with physics. You can imagine, even though it’s just a theory now, computers continuing to become many times smaller and cheaper—and be made via environmentally benign manufacturing processes—through biomolecular construction.
Now that’s exciting from one point of view, but from another, it’s not that revolutionary, because you’re just using DNA as a piece of physics. It’s not really biology—it’s merely a biological molecule being used to make better physics.
For a different example, if you think about the way we make things, the way we manufacture plastics, gasoline, energy—we have to do all that using chemistry, and to make that chemistry happen, we have to input a lot of energy—in fact, one of the most costly industries in terms of energy usage is the energy industry. You have to put in so much energy to refine petroleum and things like that. And to make plastics, ceramics—things of that nature—is also very energy intensive, and it’s also where a lot of pollution comes from, because you’re mixing together all these chemicals that really didn’t want to be mixed together. You get what you want, but you get a lot of byproducts, toxins, etc.
Well, people have started to realize that a lot of this work can be redone through the use of biology. You can turn corn into fuel or plastic, and you can make magnetic or electrical storage devices out of biological units (viruses can pattern the crystals, so instead of using mixtures of toxic chemicals, you just pull the viruses with the right properties together). Right on this tabletop, you could make materials that by current manufacturing processes would otherwise cause a great amount of environmental hazard.
As for another exciting development—well, to preface, one of the problematic things about modern agriculture is the necessity of using fertilizers (there are insecticides to be concerned about, too), but fertilizer manufacturing is terrible for the environment. You have to make fertilizer out of ammonia and that’s a horribly polluting and energy-intensive manufacturing process. What you could potentially do, instead, is program into bacteria the genes that take nitrogen out of air, turning it into organic nitrogen then just scatter the bacteria onto the field—and you wouldn’t need to make ammonium using the current very caustic processes.
These are the sorts of things I mean—and we haven’t even touched on medicine, yet. People tend to think about medicinal advances, first, but before you even get to medicine, you can think about energy, manufacturing, materials, and agriculture. In 50 years, we should be able to do things in ways we don’t do them now, that will be cheaper, less toxic, less polluting, more efficient, and so forth.
ER: A lot of people are nervous about the idea of “programming” life. Can you respond to this fear as a Christian?
DL: As a Christian, I would say that God gave humankind dominion over the earth, to do good things—he gave us minds, a passion for understanding how things work, and then he put in this world all these fascinating processes, which, if we figured them out, we could do good things, could feed more people—could feed more people without causing extensive damage to the environment. And cure disease and injury. And the list goes on. I think all that is good, and that God would be pleased that we would be using His creation to live better—I’m not saying more luxuriously, but more happily, contentedly, with each other.
ER: But back to the topic—advances using biology in the next century. You had just mentioned medicine…
DL: So, yes, there’s also medicine. Now, obviously, in thinking about this, the use of stem cells comes to immediately the fore. There are a lot of diseases out there that you really do need to correct using cellular processes. Right now, we try to make these corrections through chemistry. For instance, we give you a pill, and that pill should interfere with something that’s going wrong in your body—and yet it’s really never adequate to just interfere with something that goes wrong in the body, because you don’t really set it right just by getting in the way of it.
The opportunity with stem cells is that you can say, “I’ll replace the cells in the body that are doing something wrong with cells that are actually doing it right again.” If you program cells to be neurons, heart cells, or bone cells, you can regenerate properly functioning physiology. Rather than, say, replacing a hip with a metal part, you could regenerate the bone, itself, or you could regenerate neurons in Alzheimer’s patients. Never in the past has medicine been able to regenerate a proper physiology; it’s only tried to replace it with an inadequate surrogate, or minimize how much damage a disease is doing. With the use of stem cells, you can actually imagine returning the body to its proper physiology.
A different use of stem cells is to generate human tissue in the laboratory for better studies of human physiology and pathology and improved testing of drug effectiveness and toxicity. This will be a major advance over animal models, because of the significant disparities between animal physiology and human physiology.
A key point to emphasize is that there are different kinds of stem cells, which involve big differences in potential concerns. For Christians, clearly, stem cells derived from embryos present a tremendous ethical issue. Fortunately, a good proportion of stem cell technologies can be pursued using stem cells from adult tissue. These cells can be stimulated to develop into certain tissue-specific physiological behavior, or can now even be “re-programmed” to become quite similar to the more broadly flexible stem cells derived from embryos but now not requiring the embryonic source. Happily, the days of reliance on embryo-derived stem cells appear to be over for purposes of beneficial technologies.
We also should consider genomic medicine, and what’s attractive about that field is that with the way we do medicine now, which is chemistry-based—say you have a disease, and we might give you a pill to correct it—well, the biggest problem with that is that while I think this pill will help ameliorate your condition, maybe it won’t. Maybe that drug only works in ten percent of the patients and not ninety percent.
For example, consider cancer. You’ve got a particular kind of cancer, and we prescribe a certain treatment… well, hopefully you’re among the lucky ten percent, and you’ll be in much better shape in two or three years. If you’re not, then we’ve wasted your time. In fact, we’ve probably hurt you rather than helped you, because we’re using chemistry to interfere with things, and even though we might be reducing the damage of some things, we’re probably causing toxicity elsewhere in the system, because that same chemistry is also interfering over there.
So the value of genomic medicine is to get enough information about you through sequencing your genome that we can say, “Ah, for you this particular pill is not a good idea; it will actually do more damage than good. But for your brother, it’s likely to work, and the ratio of benefit to harm is much better.” This is the reason genomic medicine is more imminent—it’s what’s closest on the horizon to being realized—because we can use the same drugs we have now, we’ll just be using them more effectively. At the moment, we can sequence genomes, and we do have these treatments that help, and it’s just a matter of matching up these two technologies.
Now, on the other hand, when you think about genome sequencing, you can find out all sorts of things, and you have to decide, “What if I learn something negative?” Let’s say you have your genome sequenced when you’re eight years old, and let’s say you find out that you have this mutation that gives you a 20 percent more chance of having this or that disease. What do we do about that, and what are the downsides, say, with your future employer, if they know you’re at higher risk of a heart attack or something like that? If we can’t do anything about a basic risk, then all we’ve done is make your life worse, because now you’re worried about it, and if inappropriate people get that information, they could use it to your detriment with respect to comprising situations or limiting opportunities. So there is a risk that at least some of this kind of information can potentially do more harm than good.
Yet, even if you protect everything else, sequencing your genome can still affect the decisions you make in profound ways—and maybe some would say, “Well, now you can be more rational about how you live moving forward,” or something like that—but maybe not. Maybe you’re more fearful.
Of course, we can push this even further down the line—say, the fact that we can now do prenatal genome sequencing. Now, what do we do with that information?
For instance, many people argue that if you can know that a fetus has the Down Syndrome mutation, then it’s better off not being born. This is a reality even today—future parents are having to make that kind of decision, and many of them are deciding to terminate a pregnancy for which the outcome is a child with Down Syndrome. To many future parents out there, this is an excruciating thing to have to decide.
Obviously, there are a lot of problematic areas like that. Say, your fetus is not the gender you hoped for. Or, it has the gene mutation that will lead to cystic fibrosis. How do you pass a law that says if you get information about a fetus’s genome, you can only act on it with respect to certain aspects of the information but not in other ways? This is a serious concern.
ER: So this kind of decision-making—decisions based on potentialities indicated in your genome—will be an issue that we deal with every day?
DL: Yes. Right now the main obstacle is cost. Today, if you wanted your genome sequenced, it would cost about ten thousand dollars. Now to a lot of people that’s not big deal—a lot of people can plunk down ten thousand dollars, and some are doing just that. This is along the lines of “concierge medicine:” for the wealthiest, it’s like, “Sure, I’ll decide to get all this information which is just not accessible to the larger part of the population.” That’s changing. There’s little question that by 2020 sequencing your whole genome will cost under a thousand dollars.
Also, by that point, we will have discovered more things, more genes, that are actionable, so the ratio of benefit to risk will be improved, at least. This is the second current issue with human genome sequencing, understanding the meaning of the information gained.
ER: What’s the one thing you wish the average person understood about bioengineering?
DL: As we talked about, there are more and more things now that are becoming theoretically imaginable in terms of what we can do with biology. The biggest problem is the uncertainty about what’s actually going to happen when we try it. That’s the big difference between biology and physics and chemistry—right now, we can predict very little about interventions in biological systems.
Even though you can think in principle about a lot of things—I can put these genes into a bacteria that will help turn nitrogen into ammonium—well, alright, how predictably designable is that? Is it like creating a computer, a spacecraft, an aircraft, an automobile? No. We’re not at the point yet where we can write down the equations that say, “Yes, if you do X, Y will happen with 90, 95 percent certainty.” Biology today has very, very low predictive capability. On the one hand, these things are in principle imaginable, and all sorts of amazing things can be done, but right now, the biggest chance is that if you tried it, what you wanted to do with it wouldn’t actually happen.
The question is, when will that change? When will biological intervention, biological design be more predictable? The time scale of that depends on the system in question. For bacteria, it’s on the order of a decade, because we really can get pretty close to understanding all the parts of bacteria. Human organisms—certainly not ten years, but maybe fifty—it’ll be after I’m gone from this world, but for people of the next generation, these things will be much more predictably designable. This goal, in fact, is the central mission of our MIT Biological Engineering Department—to make interventions in, and manipulations of, biological systems more predictable so that they can become reliable technologies.
I guess another thing I would emphasize is that this will be a lot like some other things we humans have developed—fire, gunpowder, nuclear power—it seems the amount of harm you can do is just about proportional to the amount of good you can do. The more powerful something is, the more good you can do with it, and probably the more harm you can do with it, too. Biology is on that scale. You put any of these things—stem cell intervention, genome sequencing, bacterial genome synthesis—on a scale, well, if there’s massive potential good, there’s also massive potential harm; and if there’s minimal harm, then there’s also probably only minimal potential good. The scale is, I think, proportional like that. And the worries there are pretty profound.
ER: What kinds of questions should we be asking about the future of genomic medicine?
DL: I think the key question to ask is, “What would, or could, we do with the information if we got it?” You have to know what you could do first, and only then can you decide what you would do. So yes, I would ask, “Ok, if I get this information, what could actually be done with it?” And right now, the answer is probably: not so much. This is related to what we were just speaking about—what it will take to gain better prediction about the operation of biological systems, including human patients, from information we can measure. How do we go from genome sequence to actual pathophysiology? This will require bioengineering methods to gain information at more mechanistic levels of biology, such as the operation of proteins in cells and tissues, and turn them into computational models. Only then can the greater promise of genomic medicine be attained.
ER: In terms of your purpose as a Christian, do you feel like God has guided you to where you are? Does God watch over this kind of work, and is God responsible for some of the “eureka” moments you have had?
DL: My main conviction about my purpose is being in a situation where I interact with students on a day to day basis, and I can encourage them when they are trying to figure out not just their science but how to go about doing it, how to interact with people, what are their priorities, struggles, etc. I can actually be there as an ambassador for Christ.
I am merely a Christian living in a very interesting situation—you know, we’re trying to learn more about God’s world—there’s nothing more noble about that than any other persons’ tasks, it simply happens to be what we’re doing day in, day out. But then how do you live and how do you think about your life? Being a Christian in the midst of this setting—that’s what I think I’m here for. In a lot of ways, the actual science that we do is more the means to an end, and what’s really important to me is living out Christ in this set of people.
Now, having said that, it’s not as if the science itself is irrelevant. It’s a means to an end, but it’s not irrelevant. I do think that God creates us with talents and passions, and that’s my number one advice to all my students that I interact with when they come up to me and say, “Well what should I do—people tell me that focusing my career on this one technology is more important, or that this other one is going nowhere, or that I can get a job here…”
I say exactly this. “You are created with talents and passions—so follow those things. Don’t let anybody else tell you what to be interested in or good at.” In my particular case, my talents ran mostly to mathematical analysis and quantitative thinking, but my passions were learning about biology works, how cells work… Well, 30 years ago, that didn’t make much sense. People weren’t interested in joining the two—yet now, it’s become very popular and important. I’m only in this place because those were the talents and interests God gave me.
As for any particular insight, or result—you know, I hate to single any particular moment or discovery out—I just think God gives us our minds and the people we work with, so whatever ideas came out of those relationships, well, in the end, they’re all God’s “ideas,” hints toward understanding His creation. It doesn’t matter what I did along the way, it’s all from God.
