Today's date:
  Fall 2004

The Century of Biology

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, by the year 2005.

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?"