The Century of Biology

J. Craig Venter and Daniel Cohen are two of the world’s leading genetic scientists. When Venter, an American, was at the National Institutes for Health, and Cohen, a Frenchman, was at the Center for the Study of Human Polymorphism in Paris, they pioneered the mapping of the human genome, identifying DNA fragments and their function.

Dr. Venter went on to lead the mapping of the human genome. Dr. Cohen is the principal scientist at the Paris-based GENSET, a company focusing on the genetic origins of Alzheimer’s disease and prostate cancer. This was first published in NPQ in 1997.

PARIS—If the 20th century was the century of physics, the 21st century will be the century of biology. While combustion, electricity and nuclear power defined scientific advance in the last century, the new biology of genome research—which will provide the complete genetic blueprint of a species, including the human species—will define the next.

For the first time, we will have a complete description of life at the most fundamental level of the genetic code. This map will describe for us the exact content and structure, not only of each and every gene associated with a species, but also the precoded information, or “chemical spelling,” that controls when a particular gene is turned “on” or “off,” leading to a biological effect. In humans, for example, this means we will know exactly what genetic predisposition makes a person susceptible, say, to prostate cancer or Alzheimer’s disease. We will also know how to manipulate a gene to produce blue eyes or dark skin. The human genome is 1.5 meters long and has three billion letters, all of which are likely to be decoded, along with the genomes of hundreds of other species.

The millions to billions of letters in the genetic code of each species from ourselves to the simplest bacteria contain the recorded history of 4.2 billion years of evolution. With every gene identified and every letter of the chemical spelling deciphered, we will be able to see the exact differences at the genetic level—not just the physical level observed by Darwin and evolutionary scientists to this day—between any two species. How humans are different from other species, and how they are not, will finally be revealed.

In a very real sense, then, man will reach the final frontier of his own fate when, in the Age of the Genome, he possesses the blueprint to redesign his own species. The central issue of the next century, as none other than former United States National Security Advisor Zbigniew Brzezinski has put it, will thus no longer be the boundaries of the nation state, but the boundaries of the person. What is specific to humanity? When science intervenes to alter a genome that took millennia to develop, where is the boundary between culture and nature? What genetic intervention, if any, is off limits?

These are the great ethical questions that the new biology presents to us. History has shown that knowledge provides the power for positive change as well as for new levels of abuse. And abuse of the knowledge of the human genome is something that cannot at all be taken lightly in this era of revived nationalism and ethnic cleansing from the Balkans to Rwanda.

THE BENEFITS | The use of genomic information over the next 10 to 100 years will utterly transform medicine and the medical industry. As elucidation of the human genetic code progresses, we will begin to find associations between minor differences in the spelling of some genes that will determine the susceptibility to disease.

Once we know the exact “misspelling” which causes the susceptibility to disease, we can target that gene with a drug or virus designed for that purpose, or even “graft” a correct spelling onto the targeted gene to cure the disease. At the least we can determine who is “at risk” for Alzheimer’s or Huntington’s or a certain cancer and monitor the person. For example, a person who is at high risk of getting prostate cancer after age 40 can have checkups every six months to be sure there is no activity. If cancer is caught in the early stages, it is curable. If a person is determined not to be at risk, he or she can live with peace of mind.

Prediction and prevention of disease will thus be the earliest consequences of genome research in medicine.

With this knowledge, future drug prescriptions, for example, will be given based on genetic testing and phenotypes. Employees in the chemical industry, to take another case, will be screened ahead of time to ensure they do not have the genetic traits that would make them susceptible to cancer from the chemicals they will work with.

Genetic knowledge will also enable humanity to confront an even larger problem just over the horizon. The overuse of antibiotics during the 20th century has produced strains of micororganisms that are resistant to its cures. As a result, the world could well revert to the pre-antibiotic era when millions could die from infections.

Genomics is already having an impact here. The first organism to have its genetic code completely decoded was a human pathogen. By early in this century, we expect to have deciphered the genomes of 50-100 micro-organisms, including the biggest killers such as TB, cholera and malaria which, together, are responsible for 20 million deaths each year. Each deciphered genome provides one to six potential targets for biotech and pharmaceutical companies to develop new antibiotics.

The impact of this knowledge on the health industry can’t be underestimated. Just 50 diseases are responsible for 90 percent of human illness and death. If these diseases can be predicted and prevented, or treated by newly designed antibiotics, the high cost of hospital care—the most rapidly rising costs in modern economies—will plummet dramatically. Conversely, the pharmaceutical companies that develop drugs that can target genes identified with disease will come to dominate the health industry worldwide.

TOO MANY HEALTHY | As always in science, positive advances can have negative consequences elsewhere. Six billion people will inhabit the world in this century. If we save millions more and their children through genomics, how will the planet cope?

In principle, responsible scientific advances that prolong life must go forward only in tandem with efforts to ensure the biosphere’s compatibility with more population. Already, population growth is outpacing food production, and the oceans are being rapidly depleted.

One answer of genomics is plant engineering, or transgenics, that can increase crop yields. The map of the genetic code of a plant will be completed by early in the 21st century. Already, genes that confer resistance to certain insects have been inserted in the corn genome, resulting in crops with over 20 percent increased yields. This kind of development is critical for a country like China where there is a burgeoning population, but every square inch of arable land is already under cultivation. The positive impact of agricultural transgenics for everyone becomes clear when we realize that, if food production stopped today, there would be only six weeks of food reserves left to feed the entire planet.

POTENTIAL ABUSE | The history of eugenics from early in the century to the Nazis and the more recent rage of “ethnic cleansing” are certainly a warning that humanity may not be ready for the genetic knowledge we are coming to possess. Master-race efforts at “genetic cleansing” may well be imaginable in the distant future and cannot be excluded.

The immediate threat, however, is genetic discrimination. While we are just now beginning to identify the spelling errors in the genetic code associated with colon or breast cancer or Alzheimer’s or Huntington’s, there will be a gap of years if not decades between this discovery and a cure based on the targeted gene. In the meantime, individuals so diagnosed might well be discriminated against by insurance companies who will refuse to take them on, or employers who will refuse to hire them. Clearly, human rights and civil rights law will have to be updated to include this new class of diagnosed person.

At this stage, one can only imagine the future potential of abuse.

Is it possible to have a new human being? Once we know the full lay of the genome map, we can, theoretically, design such a new human being. If enough money and research are put into human and bird genome research, we could no doubt put a bird’s wings on a man. As a joke, some scientists once discussed creating “minimals,” giraffes or elephants the size of household pets. Will some entertainment-funded lab take this seriously?

These are not trivial issues. In a hundred years, all this will be possible. We have to admit it could happen.

Historical experience has shown time and again that when something becomes possible, sooner or later someone does it. That is the risk.

THE REVERSIBILITY PRINCIPLE | So where do we draw the line? Here is the basic principle which responsible scientists must heed: Never do anything that you are certain is irreversible. Everything which may have irreversible consequences for the species must be declared genetically inviolable, a sanctuary from intervention.

For example, if we assume the right to interfere with cleavage cells, to manipulate cells that have just been fertilized, we will be authorizing irreversible genetic modifications that will be passed down to heirs.

The diversifying cells that grow from this initial cleavage will all carry the mutation, causing the individual who has been modified in this way to carry these specific genes from here to eternity.

Even if this principle is borne in mind, there is a host of other issues that must be addressed, ranging from the present concern over genetic discrimination to the more distant worry that human beings could be genetically engineered for the production and profitable sale of organs needed for transplant.

By and large, scientists who increase knowledge are not the ones who apply the knowledge. Einstein and Oppenheimer often made this point with respect to nuclear energy.

A scientist can merely say that, “from this discovery, very good and very bad consequences can be born.” But there is no universal system of ethical criteria that says, “This is good. This is possible, but it is bad, so don’t do it.”

Now that we are at the threshold of the most fundamental knowledge man can attain of his own being, such a universal system is imperative. What we propose is the establishment of a kind of worldwide “upper chamber of parliament” for this purpose.

We mean a parliament in the sense of a deliberative body of experienced scientists and philosophers—let us say of 60 or so members rotating in two-year terms—to advise decision-makers in business and politics with the weight of their collective authority. This body, perhaps under United Nations’ auspices, would inform the public of what is at stake in a given scientific advance and propose solutions.

A deliberative body is necessary because, aside from the reversibility principle, genetic science is advancing at such a pace that one cannot predict ahead of time what is right or wrong, or even what the questions will be. Science has advanced so far beyond the ancient times when the principles of the main religions were formed that in and of themselves they provide little clear guidance in the coming Age of the Genome.

As it is, the scientist is focused on the task in front of him. He or she does not appreciate the bigger picture. The philosophers, on the other hand, rarely understand the science. Decision-makers are driven by political or stockholder expediency. Given the advancing state of science, this is a recipe for a catastrophe of the human essence.

By the end of this century, the human genome project could be judged as the Manhattan Project of our time and us scientists as tinkering Frankensteins who couldn’t leave well enough alone. Or, mapping the human genome could be judged as the greatest advance in the history of our species since we stood up on two legs.

Everything depends on the prudent application of the accumulated wisdom of human experience to the stunning new scientific discoveries of our age. Cognizant of both the great possibilities and risks knowledge of the human genetic code brings, our hope is that future generations will never have to ask, with T.S. Eliot, “Where is the wisdom we have lost in knowledge?”

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Microbial Manufacturing Is Next Phase of Evolution (2008)

NPQ | During the past few years, your research vessel, Sorcerer II, like Darwin’s Beagle, plied the oceans searching out the secrets of evolution and the range of life. What have been the most important scientific results of your voyage?

J. Craig Venter | We discovered there was vastly more diversity of life than we ever thought. Based on the sequence information of the microbial organisms we scooped up in our filters, six million new genes were discovered, more than double the genes known to science before. This blue planet dominated by the oceans is clearly a planet of bacteria.

We found that every 200 miles across the sea, on the order of 85 percent of genetic sequences were unique to that site. So, instead of the ocean being a homogeneous mixture, as many thought, it is comprised of millions and millions of micro-environments based on local nutrients, temperature and availability of sunlight.

What enabled this diversity, we found, was that most of the bacterial organisms near the ocean’s surface get their energy directly from sunlight—without the photosynthesis that plants use.

It turns out these organisms have photoreceptors very similar to our own visual pigments. But instead of the light being turned into electric signals to the brain, as in our case, in these bacteria the light is turned into electrical signals that provide energy directly for the cells.

Previously, we thought there could not be much diversity in a place like the Sargasso Sea because it was a very low-nutrient environment. It turns out that these organisms can live straight from sunlight.

NPQ | What are the more practical implications of these discoveries? Obviously, in an age of global warming, discovering biological mechanisms that produce energy directly from the sun would seem hugely significant.

Venter | First, because these millions of microbial species are so sensitive to environmental conditions, they can act as the proverbial canaries in a cage, warning us of change before it happens on a much more macro scale. From our discoveries, we now have a baseline from which we can detect change and try to figure out why, for example, coral reefs are dying. A one- to two-degree temperature change can transform the milieu of the bacteria that are there, and that can change whether a reef lives or dies.

Separate, but related, is the issue of energy as a resource. When we look at the environment, the single largest problem is taking non-renewable carbon out of the ground and burning it, releasing carbon dioxide in the atmosphere, having a huge impact on the oceans and climate.

Instead of just monitoring the planet going downhill, it seems the only solution is to come up, sooner rather than later, with substitutes for burning oil and coal. To that end, my research teams have been working on biological sources of energy—in part brought on from our discoveries in the ocean of light-driven biology. Surely there are some answers and alternatives in all these thousands of new forms of metabolism out there on our blue planet.

One thing we are trying to do now is engineer bacteria that transform simple sugars into burnable fuels that are much more efficient than ethanol or butanol.

NPQ | So, instead of breaking down plants into biofuels, you will make energy directly?

Venter | Yes. Biofuels has almost become a meaningless term because it is so broad that it includes everything from ethanol to McDonald’s kitchen grease. The chemicals are actually designed in the lab, and we are using biology to produce them. They are biologically produced fuels. It is not hard even to imagine, with the breadth of biology, making gasoline or octane to put in our tanks. Bacteria can make all those fuels.

The question now, of course, is the sheer volume of demand for such fuels. If we had a million bio-refineries, each one would have to produce 17,000 liters every day to replace the oil we consume.

We also have to come up with distribution infrastructure. One obvious solution is decentralization. Each one of these mini-refineries would be the size of a barn silo built where the demand is so it doesn’t have to be distributed. This could help developing countries without energy infrastructure to leapfrog to energy sufficiency without the expensive intermediary steps, just as cell phones have enabled communication without all those fixed telephone lines.

But just because we solve the problem in the lab doesn’t mean we can solve it in society. There is a huge road ahead, not least from political lobbies who want to protect doing things the old way.

NPQ | So, if I were a science-fiction writer looking ahead 100 years, I wouldn’t be off base to imagine that all the energy we will use in that future would be biologically manufactured?

Venter | I’m hoping it wouldn’t take that long. If it takes that long, the planet may not make it. Let’s hope biologically manufactured fuels are dominant 15-20 years from now.

NPQ | What we’ve been talking about is what you call “environmental genomics.” You say this is “the toolkit for the new phase of evolution.” What do you mean by toolkit?

Venter | With synthetic genomics, we are trying to design organisms in the lab that provide solutions for the planet. As we’ve been discussing, over the last several years in our labs we’ve been designing a genetic code based on what information we’ve read into the computer, and then trying to actually manufacture those coded cells which, for example, produce octane that can go right into existing cars.

We’re starting with fuel because it is the biggest problem. But, in general, the chemistry that can be done with bacteria far exceeds what traditional chemists can do in the laboratory. DuPont is already making industrial chemicals using genetically modified bacteria. Food producers in Europe have been producing amino acids and vitamin supplements through genetic engineering. Clearly, bio-manufacturing of this kind will be a major industry in the future.

All these new genes we are discovering are the new toolkit for this shift. In the 1940s and 1950s, we had resistors and capacitors, early transistors and the start of integrated circuits in electronics. Similarly, we now have tens of millions different genes—design components—that give us an unbelievable repertoire of engineering capabilities.

We are shifting to a new phase of evolution where we will be able to design new industrial, fuel, food and medicines by directly engineering and building chromosomes based on digital information from reading the genetic code.

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The Next Step of Evolution (2013)

The following is a conversation with NPQ editor Nathan Gardels in November, 2013.

NPQ | With what you call the “dawn of digital life” and the fusion of the digital world with biology, you say we are entering a new phase of evolution?

What do you mean?

J. Craig Venter | Biological evolution has taken three and a half or four billion years to get us where we are. The adaption of our species to the social environment—social evolution – has been must faster. Now that we can read and write the genetic code, put it in digital form and translate it back into synthesized life, it will be possible to speed up biological evolution to the pace of social evolution.

On a theoretical basis, that gives us control over biological design. We can write DNA software, boot it up to a converter and create unlimited variations on biological life.

In 2010 we created the first synthetic cell and it is a forward extrapolation from there. We’ve been able already to change cells so they produce human insulin and will be able in due course to redesign the genetic code to change how we produce food, fuels and chemicals.

We are now engaged in finding new ways to head off pandemics by being able to read the code of flu strains and very rapidly produce vaccines to stop them. We are doing this with Novartis. We have already done the first round of clinical trials on the new H7N9 vaccine based on the work of Chinese scientists who sequenced isolates from the Avian flu outbreak there in 2013. We received the sequence from them in digital form by email and converted it back into DNA to produce the vaccine in about ten hours. Novartis is already scaling up the vaccine before we’ve had a single outbreak in the US.

That is the opposite of what happened with H1N1 when we didn’t have a vaccine until two months after the pandemic had peaked.

In effect, what we are we doing is “teleporting DNA.” There are two components to this process: the sending unit and the digital biological converter.

In November, we completed a teleporting test in the Mojave desert—the closest environment we have to Mars on earth—with NASA. We took a sample of algae that can grow under clear quartz because the light penetrates the rock and the algae is protected from exposure to the heat and elements on the surface. We chipped off a piece of algae, isolated the DNA genome sequence out there in the desert and then sent it up to the Cloud. Back in our labs in La Jolla, we downloaded the sequence and have been reconstructing in the computer the algae genome in automated fashion.

Our hope is that in the future a NASA probe on Mars will take similar samples of microbes—which I strongly suspect will be DNA based—and beam them back to our lab to reconstruct whatever life form is there in our labs. When Mars and Earth are closest to each other, that will take 4.3 minutes by electromagnetic signal. That is life at the speed of light.

NPQ | What you are really talking about is something akin to “horizontal gene transfer” through human intervention—sharing information from one species to another.

Venter | We are really doing more than that. We are actually creating new genes and enzyme functions that don’t exist in nature at all. We’re dealing with the design of organisms based on the functions we want.

This is something that would never occur on its own in nature. And we can speed up the glacial process that would occur in nature by orders of magnitude.

NPQ | The glacial pace of evolution that took place over billions of years was based on natural selection. What didn’t work didn’t survive. This is the accelerated evolution of un-natural selection.

Human purpose, with the necessary limits of our knowledge, is now projecting mutations with unknown effects into an overall biosystem of which we have incomplete knowledge of all the feed-back loops. Even now in your work, in the simplest cell you are unable to determine the function of 50 genes.

Gregory Bateson, the anthropologist and cybernetic systems theorist, warned that “lack of systemic wisdom is always punished.”

Do you worry about the consequences?

Venter | This is the right question. There are lots of ways to deal with it. We are trying to build kill switches into organisms or chemical dependency so they can’t survive outside a lab or a factory—something that natural evolution would not do.

Natural evolution gave us the 1918 flu virus that killed 3 percent of the world’s population. Our evolution can come up with countermeasures to be sure that never happens again.

There are a lot of negative consequences of the 4 billion years of evolution so far toward humans with pathogens and other threatening organisms in the environment. We can change that. We can also consciously evolve toward zero carbon use; our own research building in La Jolla is zero-carbon, the first of its kind in the world.

Genetic design is something we can use to fight the lack of sustainability we humans are forcing on the earth’s environment. That is man-made evolution as well.

We’ll have better ways to produce food and recycle chemicals through genetic design. Instead of envrionmentalits being worried about what we are doing, they should be the first to embrace it and make sure there are the right rules and regulations around it as well.

The Anthropocentic Age—the first age in which humankind is the dominant species on the planet—cuts both ways: it is up to us to destroy or save the planet.

We certainly have the ability. But do we have the wisdom to do that intelligently? It’s a fair question given the history of humanity.

I was born in 1946, just a few years after we dropped the first atomic weapons and there was a massive world war. Over what? Ego and dominance?

We have a long way to go as a species before we can say confidently “yes, that’s a good idea and we will all benefit from it.”

NPQ | Your own decoded genome is being broadcast electromagnetically out across space. What are you hoping to find, or what or who are you hoping to find you?

Venter | I’m not broadcasting it specifically. Its been bouncing around the radio waves and Internet for 15 years now. To think that is contained within our planet alone is silly.

I refer to this often as a joke. But some are now saying we ought to specifically be sending our DNA code out into space and see what comes back. My standard line is: Well, maybe we’ll get a bunch of Craig Venter’s coming back!

It’s tongue and cheek. But with all the millions of earths and super-earths now being discovered in our own galaxy, this crazy religious human-centric view of life and civilization doesn’t hold water. The odds are strongly in favor of finding life elsewhere.

Space X’s Elon Musk wants to colonize Mars with modules where earthlings can live. My teleporting technology is the number one way those individuals will get new information, new treatments of diseases that will occur there and new food sources. We’ll just email them up a new antibiotic, a new vaccine, a new cell that will create building materials out of the CO2 environment. One day it will all come together.