Juan Enriquez, director, Life Sciences program, Harvard The GNW Interview:
Juan Enriquez, Director
Life Sciences Program, Harvard University
 

Juan Enriquez's articles in Harvard Business Review --"Gene Research, the Mapping of Life and the Global Economy" in 1999 and "Transforming Life, Transforming Business: The Life-Science Revolution" in 2000 -- are considered required reading by anybody with a stake in the future.

Enriquez is a collector of maps; graphical documents of discovery and knowledge. The completion of the human genome, and those of other animals and plants, is a map unfolding to new worlds we are just beginning to understand.

Gene sequencers are "the new cartographers," Enriquez wrote. "Instead of mapping continents, oceans, peninsulas, rivers and lakes, they are mapping the four base pairs that make up the DNA of living organisms. This is the source code for all forms of life on the planet. Their work will change the way we look at and live with every other person, animal, plant, bacteria, and virus on this planet."

As a fundamental technological change, genomics cuts across almost all types of business, ranging from health care and pharmaceuticals to insurance and law enforcement. Genomics is a powerful force that will profoundly affect our personal lives and the global economy.

These are some of the issues explored by Enriquez in his first mainstream book, As the Future Catches You, subtitled "How genomics and other forces are changing your life, work, health and wealth" (Crown Business, NY; 2001).

Those expecting a volume of impenetrable academic prose might be surprised to find pages reading more like free-form verse. Small bites of information are presented on pages with lots of white space, in a variety of line lengths, paragraph formats and font sizes, as though keyed by a hyper-caffeinated compositor.

BG: You took an unconventional approach to As the Future Catches You. It could have been a thick academic tome, but you've presented it artistically, almost poetical in parts. Why did you choose such a different approach?

Enriquez: The book started out as 800 pages of single-spaced text. When I finished it, I took a look at it realized that there are about 50 people in the world who are going to read it.

The issues that genomics brings up are so widespread, and my interest at this point is to get more people involved in the debate. I want 17-year-olds to be able to read this, for housewives to read and understand it.

If you write it as thick tome, it very quickly eliminates your audience. I'm worried about this slew of genomics books. It's the same group of us reading them. The books are very good, and they're teaching us a lot, but they're almost preaching to the converted.

The impact of genomics is becoming so broad on society, and the debates are coming up so quickly -- the Senate hearings [on human cloning] yesterday, or anthrax, or antibiotic resistence -- there's things in the newspaper every day, and people just don't have a have a context for them. I wanted to get a much broader audience, because otherwise it's very easy to scare people.


The language of genomics is
far more powerful than the
language of machines
of the industrial revolution

BG: You write almost as though speaking very slowly, like explaining things to a child. I found myself often reading a couple of pages, and then pondering the implications for a while. Letting it sink in. You're talking about some huge concepts.

Enriquez: Well, look at the industrial revolution, when you have a language that transmits information so more much more efficiently. Think of what the digital revolution did, how broad the change was.

The language of genomics is far more powerful than the language of machines of the industrial revolution, far more powerful than the language of the digital revolution, because the changes are so fundamental and they are self-reproducing. You can make digital code self-reproduce, I guess, but most of the time it requires that somebody wish to apply that code. Life code is an awful lot more powerful because once you put this stuff out there, it's loose. And the impact on the globe, the consequences of mistakes, are that much larger. The benefits are also that much larger.

It used to take a nation-state or an empire to really affect huge chunks of people, land or nature. One of the interesting things of these systems, for example, as we wire together financial networks we're empowering individuals in extraordinarily ways. A single rogue trader in a copper market in Japan can take down the world copper market, or a couple of guys fooling around with Enron can do some really interesting stuff to the global energy market.

This is now spreading into arenas like warfare, and also arenas like designing life forms. People can generate some pretty extraordinary breakthroughs in medical treatments.

One of the interesting trends out there is that if you look at the pharmaceutical pipeline, a couple years ago they were pretty empty. All of a sudden, with genomes and protein structures coming online, you have an absolutely full preclinical pipeline. Instead of one or two drugs coming through the pipeline each year, you have twenty.

BG: Do you see genomics as fundamental a change as the industrial revolution, as profoundly transforming our society, culture and economy?

Enriquez: It's very hard to find a part of the economy that won't be fundamentally changed.

There are two different debates going on. There's one side that says, "Jeez, not one drug has come out of the pipeline because of genomics yet." Well, it takes twelve years for a drug to get through the pipeline, and the first sequence of an living organism was Hemophilus influenza in 1995. So you're talking about technologies that have come online, as far as humans are concerned, officially on the 12th of February, 2001. And unofficially, in databases, for maybe the last two or three years.

BG: And the human genome is still being mapped. We're just getting started on the functional parts of it.

Enriquez: Exactly, and that's why I compare it to Columbus's map. The first printed map of America wasn't until 1556. In 1556, you still had maps with the Atlantic and the Pacific on the same scale, you had Japan in the middle of the Pacific Ocean, and you had India sitting up by the Arctic Circle. The fact that those maps were wrong, the fact that people thought there was a river longer than the Amazon, the fact that people had no idea what was in the interior of South America, doesn't mean that the whole balance of power in Europe didn't change. They didn't have a clue as to how quickly things were happening, or why they were happening.

I'll bet you that within ten years, three to five of the world's largest companies are in life sciences. There's a whole pile of genomics firms that are going to go belly up. The firms that are dominant today may not be the firms that are dominant tomorrow.

BG: Do these companies exist today?

Enriquez: Some do and some don't, or they're small start-ups.

BG: Somewhere out there are still some Yahoos, up-and-comers?

Enriquez: I don't call them Yahoos, I call them Microsofts. These are really big entities.

BG: Are there some Ataris out there?

Enriquez: There are some Ataris and there are some Yahoos. Every version of firework you see, from those that actually work to those that fizzle, all of those are being sent up. A lot of them are trading today. I don't know who is going to be dominant, for example, in the biochip market. Today it looks like Affymetrix. But somebody is going to be a very large company once you start heading towards personalized medicine, because biochips are going to be one of the ways in which we'll genotype our reaction to medicines.

BG: In the past few years the computer companies have made substantial investments in life sciences, which seems to be a very high priority for companies like Motorola, IBM, Compaq. Will there be a merging between software, hardware and biology?

Enriquez: It will happen in two distinct stages. The first is that digital code and the nucleotide code are going to become basically one and the same. As, Ts, Gs and Cs can all be coded with ones and zeroes. [Genomics] is one of the largest uses of computer power. You have four really large scale computing problems out there; weather, nuclear weapons simulation, decrypting global communications, and then you've got the code of life.

Once you start getting into protein research and protein interactions, it may turn out that the largest single use of computer power in the world becomes understanding how life works, how the body works, how proteins fold and create instructions, how they vary from individual to individual.

That's what computer companies are seeing, so for large hardware companies -- Sun, IBM, Compaq -- the driving force behind bigger and bigger chips on a commercial scale is proteomics. That's why you see [IBM's supercomputer] Blue Gene, why you see Sun ads with DNA running across the words. You'll see a merger of hardware and digital code and nucleotide code and protein code.

The second stage, which I think you're referring to, is DNA computers. We know that the genome is one of the greatest information processing apparatus anywhere. [DNA computing] is more blue-sky stuff, further out. Some of it will be possible in 15-20 years out as we get better with nanotech, to start thinking about the possibility of biological computers, but that's not going to affect your or my stock portfolio in the short term.

BG: There seems to be a pervasive sense that genomics is over. We've got the code, been there and done that. As you talk with people, are they aware of the implications of genomics as it cuts across industries? People in pharmaceuticals may be aware of genomics, but what about the insurance industry, law enforcement, other fields?

Enriquez: They seem to be two or three technological generations behind. What's really interesting is that some people are paying attention to genomes are already talking about the post-genomic era, when most people are still getting used to the digital era. The whole genomic era came and went so quickly. In a sense, it started in 1995, and it almost ends with the publication of the human genome. You're still working on mice, and the rat, and the zebra fish and all sorts of model organisms, but now it's an issue of interpreting the next steps, which is what is the expression of this particular code. This is where a lot of interesting questions are today.

You've got a very small subset of the world focused on really, really exciting stuff. And then you've got a whole pile of people who are intelligent and literate, like those who run insurance companies and doctors offices, who haven't even gotten to the point where they understand the implications of the Drosophilia sequence, having the ability to sequence a whole human genome for $1 million.

It took about $3 billion to get the human genome sequence, and by the spring [of 2002] there will be companies that will give you a reasonably accurate genome sequence for about $1 million. By the end of the year after that, it's likely you'll have most known human genes on a single chip. As chips start coming down in cost, the era of personalized medicine is not that far off. That has massive effects on the pharmaceutical world.


Within ten years, three to
five of the world's largest
companies are in life sciences

BG: How far off is practical individualized medicine -- five years, ten years?

Enriquez: Depending on how serious the disease and the side effects are, this is stuff you're already seeing. If you have AIDS, one of your options is a drug that is highly toxic in certain individuals. Doctors are testing to see whether your genotype will react well or not. They're also doing this with leukemia.

So the era of personalized medicine is already here in a certain sense. It's just going to become more formal and widespread, and come down from really serious diseases to other kinds of diseases. And it's going to happen pretty fast. I think within the next five years we'll be seeing a lot of typing for diseases, particularly diseases where there are toxic side effects of medicine.

Thalidomide is a very interesting example, because here's a medicine that was a poster child for a nasty and stupid compound, which it obviously was for women who were pregnant. That molecule was dead, buried, had a stake put through its heart. And then, lo and behold, it is resuscitated through a small private company, first as a treatment for leprosy. And then it turns out to be quite effective against forms of cancer, and it turns out to work in a whole series of things. So it goes through a bunch of clinical trials, and now you have Geraldine Ferraro advocating the use of thalidomide.

This is going to happen with a bunch of compounds. Now if a compound hurts a few individuals, usually it's taken off the market unless the disease is really deadly. You might get a better sense of what's going to happen as you type which individuals are going to get hurt by this stuff.

The lawyers haven't caught on to this yet, but this is going to be a big legal issue, a big insurance issue. The way in which doctors prescribe and pharmacists dispense is going to have to change pretty quickly, in that we can actually tell what compounds do to individuals instead of classes of people.

BG: One of the points that permeates your book is the effect of this new technology on the economic balance of the world, a new economy, and the differences between the wealthy countries and poor countries. Places like Singapore are making large investments in life sciences. How is genomics going to reshape the world in the future?

Enriquez: In 1960, very parents would tell their kids to make their future in Singapore. Singapore was a backwater, and not even considered a viable nation-state by some. Taiwan was similar.

The shift in [digital] language meant that small, isolated populations could become highly successful. What life sciences is going to do is make that true not just for nation-states, but for individual areas within nation-states.

BG: Regions within countries?

Enriquez: Regions within countries, or even specific research institutions within a state. In Holland, for example, you have one company that is valued at about one-third the GNP of Holland. It's not going to be long before we have individual companies that are almost the size of a nation's economy, because they're not just selling within the nation and not being traded within the nation, they're traded across stock markets and sell across borders.

These technologies are so powerful and so pervasive that governments don't have the power to block them. Government can promote them, but it's hard for a government to control the process because all it really depends on is a small cluster of really bright individuals with a specialization. So you look at the stem cell debate. The United States is already ahead of the rest of the world in stem cells today. There are companies that are very good with stem cell research and have basic patents. But those companies can move overnight. The stem cell research capital of the world could easily be the UK tomorrow, or easily be Sweden tomorrow.

You make a couple of wrong decisions, a couple of labs move, and that's the end of this country being the capital of stem cell research.

BG: Is the environment in the United States conducive to regenerative medicine, stem cell research, therapeutic cloning?

Enriquez: I think it's right on a knife's edge. I understand why Bush made the decisions he did on stem cell research, because the Republican party is split right down the middle on this. He's walking a knife edge between being a friend of business and keeping the constituency that has very fundamental beliefs.

If you pushed a little bit more, the cost of doing regenerative medicine research is going to become high enough inside the United States that you'll see a shift to other countries. You're already seeing some labs from California that are moving to the UK because they have created laws that are much more conducive to this stuff. Sweden, too, wants to get into this game.

BG: It seems that for every step forward there is a step backward, whether it's the gene therapy death at Penn, the Starlink fiasco, or hysteria over human cloning. Will these setbacks create obstacles to the development of applications and wider acceptance of genomics technology?

Enriquez: There are two questions there. The first is, a lot of the Third World is focusing on the costs of GMOs [genetically modified organisms], whether they should or they shouldn't. What's very frustrating, in this country as well as a lot of developing countries, is that it should be focused from a scientific point of view rather than purely ethical or humanitarian point of view. There should be, in every decision made with genomics, an ethical and humanitarian component and hurdle. Is this something that helps humanity? Is this something that helps people? Is this something consumers want? That hurdle should be there, but it shouldn't be the only place where this issue is debated.

In this country, about 27% of the PhDs in math and science are going to Asians and Asian-Americans. About 2% are going to African-Americans, and about 1% are going to Hispanics. If what amounts to 25% of the US population remains functionally illiterate in the technologies that will drive economic growth, it's going to be very hard to see how those groups are not going to get relatively poorer.

It's very important when people discuss the problems and concerns they have with GMOs, that they also discuss the science too. If that doesn't happen in Argentina and Brazil, what ends up happening is that these social scientists and lawyers find it a lot easier to discuss "oh my god, can this corn become a blue monster?" They have to understand the science behind it.

BG: The argument is that there's a risk of permanently altering the genome of a plant, which escapes into the wild, scenarios of uncontrolled dispersion. With groups like Greenpeace, it's all or nothing. There is no middle ground in GMOs, even to the point of objecting to something like Golden Rice.

Enrqiuez: Any time you have a major change in technology, there are going to be groups to oppose it and be scared of it. And there's a good reason for this. At some point, we're going to make a mistake with genetic modification. It's important for industry to recognize that, and think about what it's going to do the day there is a serious mistake with this stuff. Because unless this is the first technology that mankind has ever invented that doesn't have unintended consequences, at some point some lab somewhere is going to make a mistake. Starlink was a reasonably low-cost way of learning that lesson.

Having acknowledged that, the relative safety of this particular technology versus other technologies is quite high. If you compare, say, the costs of introducing cars or electricity or steel, and some of the consequences of that. There have been some really nasty consequences. I think we'd rather live in a world of steel and electricity and cars, despite those consequences.

I think this is also true of a future where we have better genetic control over life forms. There will be people who use this stuff in the wrong way, but I think it is outweighed by the consequences in terms of the average human life span, in new medical treatments, in terms of our ability to feed the world.

We know that the population of the world is going to be 8 billion people. We hope that more of the world's population eats meat. The wheat-to-meat conversion ratio, to get the same amount of calories out of meat as wheat, is about 20 orders of magnitude. One of the first things that people do, as wealth increases from real poverty, is that they start to eat chicken and meats. This hasn't been part of their traditional diet. Take those two trends together, and one of the things that's going to happen is that if we don't increase agricultural output on current farms in really massive fashion, we're going to have to take an area the size of the Amazon and bring it under cultivation to feed people. There's a clear trade-off.

BG: Will these things reach the people who need them, or will developments be first used by the wealthy? Can genomics equalize the differences between the wealthiest and the poor?

Enriquez: Only if you start spending a lot on education. The way a Singapore becomes a Singapore is by getting serious about education. The thing that's different about Singapore and Taiwan and Korea, despite all the problems that they have, is that the students are very good at math and science, far better than US kids. That hasn't always been true historically, but there was a real effort at the grammar school and high school level to get those kids literate in these languages. If African countries and Latin American countries don't do the same thing -- even if you subsidize them, even if you transfer technology -- it won't work as long as those populations remain illiterate in those languages.


Make a couple of wrong decisions,
a couple of labs move, and that's
the end of this country being the
capital of stem cell research


 BG: So what will happen? Will the wealthy get wealthier?

Enriquez: Given current trends, two things will happen. Average life span throughout the world will continue to improve. Average wealth around the world will continue to improve. But the speed with which it improves will be very different in developed countries than in developing. The absolute gap between the rich and the poor will continue to increase at a very substantial rate, unless we become aware of and address these trends.

BG: Is human cloning is inevitable?

Enriquez: Yes. The technology is becoming relatively trivial. As soon as you know you can clone mammals, and particularly higher-order mammals, then it's not a barrier of technology, it's a barrier of whether you want to do it ethically and politically. It will happen somewhere.

Will it happen in the United States? That's something scientific groups and politicians should debate. Is cloning an embryo at the 8-cell stage human cloning or not? It gets into fundamental debates.

BG: But the technology is moving much faster than the debate can possibly keep up. Human cloning may be going on as we speak, and we wouldn't know.

Enriquez: It's likely that it's happening as we speak.

BG: You said that any decision about genomics should have a humanitarian component, whether it benefits mankind. How do things like this genetically modified glowing rabbit in France fit into the scheme of things? Is this an appropriate use of the technology?

Enriquez: Artists are important to a society because they're very good at coming up with ways of looking at the world. Artists question our notion of what is beautiful, notions of what we're doing. Having this Alba bouncing around, it's a way of an artist asking whether this is something we really want to do. I would not restrict artistic freedom.

These are technologies that are so powerful, we should be debating what they are and what we're doing with them. It's healthy for society to have a debate on this stuff. I happen to think [genomics] will end up being largely beneficial. But I don't want to live in a society where nobody questions this stuff. That's a useful part of the process.

 

© Copyright 2001, 2007 Bruce Goldfarb. All rights reserved.