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Craig Venter

Craig Venter: Equal forces

The environment could be as determining as the genes themselves

You might not like the restless Craig Venter, founder of Celera Genomics, the North American company which published last month its version of the human genome in the magazine Science, while the Public Consortium did the same thing on the pages of Nature, but it is impossible to ignore his influence in the destiny of genome research over the last ten years. In 1992, disillusioned with the bureaucracy of the NIH (National Institute of Health) of the United States, he decided to start a genomic research institute. Created in Rockville, in the State of Maryland, a half-hour drive from the capital, Washington DC, the TIGR (The Institute for Genomic Research) has become a productive center of studies and sequencing.

In 1998, Dr. Venter began to definitely write his name into the history of genomics. In that year he started up the company Celera, also in Rockville, with a clear purpose: to establish the correct order of the 3 billion pairs of bases which make up the human genome within a maximum time scale of three years, a lot less time than that originally proposed by the international Public Consortium which had planned to hit the same goal only in 2005. The entrance of Celera, a company prepared to impose a frantic pace into the research, and thus way make money with its discoveries, caused lots of polemic discussion and incited the debate on ethics, but no doubt about it, made the Public Consortium revise its work chronogram. The promised year of the complete sequencing was advanced from 2005 to 2003.

With the arrival of 2001, one can say that Celera kept its promise, though not quite fully. The company published a version of the human genome which still contains gaps and is not definite, the same thing that happened to the work of the Public Consortium. Two weeks after partially releasing the data on their outline of the genome, – only those who sign up for the data bank of the company have full access to the information of Celera. Dr. Venter was interviewed by phone by the reporter Marcos Pivetta:

The revelation that the human genome has less genes than that was expected, is a good thing or a bad thing?
Well, it is not necessarily one thing or the other, but I would say that it is good news because now we know what is the answer (to the number of genes). It is a good base for the researchers to follow up.

Does it mean that it will be easier or more difficult to understand the genome?
Ironically, the low number of genes shows that biology is more complicated than lots of people would like it to be. Many people thought on the basis of “one gene, one protein, one biological function, one illness”. However, thing don’t work like that. I believe that the sequencing of the genome has helped to demonstrate something that many of us already knew, but weren’t fully aware of the extent of the complications. Biology is still the same as it was before the sequencing of the genome, only that now we have a better understanding of its complexity.

Less genes in the human being means less genes to be patented. How does Celera see this question?
This is irrelevant. To patent genes is not a key factor in what Celera is doing. It has never been. Our goal is to help the rest of the scientific community, pharmacology and pharmaceutics to understand how to use the human genome tin order o develop better diagnostics and therapies. This is our only goal, to develop new treatments for diseases.

Can the genome still be considered the “book of life”? Do you agree with the researchers who say that the information on the genome is a bad blow to the determinism genetics?
I’m one of those people whom you are referring to. I hope I agree with this (laughing). There are many different terms used to describe the genome: book of life, photography of humanity. The genetic code is not a portrait of a human being, nor the dictionary of life. It holds important parts to our history, important instructions for our cells, about how to modify them. However, you cannot go into a chromosome and find the instructions on how to make a heart, a brain. This discussion has to do with the previous question, about the complexity of the human being. The information is on the following levels, in the interplay between the proteins and between the structures of the cells. All of this is not directly codified in our DNA.

From here onwards, will the influence of the environment be re-evaluated regarding the appearance of illnesses?
Our studies show that, in a general form, genes and the environment have probably the same importance. In each illness, in each human condition there is an different mix of the influence of these two factors. The biological molecule proves that the environment is really an essential part of life, of biology. They are not separated. The people who only look at genes or only at the environment, start out missing the point. By definition, it has to be the two of them together.

Do you believe that this idea is acceptable among the majority of researchers?
This is something that I cannot assure you. I hope so, but I suspect that it will still be necessary considerable time to go by before people absorb all of this information. I’ve had the opportunity to think about this much more than most people.

What comes after the genome?
All the rest of biology. There is not a one, single step which will solve everything. We have to integrate all of the information in order to understand biology.

Many people have been talking about proteome as the next step of the genomics.
We have a lot of research being developed about the separation and sequencing of proteins. We are building the largest unit in the world of the sequencing of proteins and we have been carrying out research in the area of proteomics for some time now.

How do you make a comparison of the data of Celera with that of the Public Consortium?
We believe that the Consortium has done a great job. However, the data bank of Celera is substantially more accurate. Our sequencing is in a more correct order, something that the Public Consortium will take another two or three years to complete. One thing is to have the parts of the sequencing, another is to put them in the correct order and to obtain the correct sequencing of the genes. That is the reason that the data bank of Celera is so popular with the scientists. They know we have the better data by far.

How many clients does the Celera data bank have?
Up until yesterday(the 1st of March) , we had 37 clients, including schools of medicine and academic institutions such as the Rockefeller Institute. Scientists throughout the world, such as the Karolinska Institute of Sweden, and the Max Planck Institute, trust our information.

Is this number of clients sufficiently large for you?
Celera has been around for only two and a half years. During this time we sequenced the Drosophila melanogaster (fruit fly), the human genome and now the mouse. All of this in two and a half years. Already we have a substantial number of clients and we are only at the beginning. We are waiting for Brazil to sign on to our service.

Brazilian researchers, the majority being financed by FAPESP, have produced a large quantity of data on the human genome, a million ESTs of the codifying regions of the genes. How do you yourself evaluate the quality of this information?
I don’t have specific knowledge about the human ESTs produced in Brazil. However, I know that other sequences of ESTs, the first that were obtained in your country and that were produced in collaboration with my institute (TIGR, The Institute for Genomic Research), were of high quality. The Brazilian scientists carried out an excellent piece of research in the sequencing of the first plant pathogen (the Xylella fastidiosa ).

In Brazil, the researchers have been talking more about the study of transcriptome rather than the proteome for the next few years, different from what is going on abroad. Why do you think this is happening and what is the importance of transcriptome?
It is a term that nobody recognizes, as far as I know, as a valid term from the scientific point of view. For this reason you don’t often hear it mentioned. I believe that I have never used this word in this context. People are studying RNA all the time. It is an intermediary which could help with some indications on the variations in the proteins, but it cannot say with any great precision what happens to the proteins.

Then do you consider the study of proteome to be much more important that that of transcriptome?
My position is to adopt a holistic view of biology. I try not to make judgments … You would not have a single protein in the body without RNA and no RNA without the genome. Everything is important and needs to be studied and understood. The greater part of biology occurs at the proteins level. People measure RNA to generally attempt to guess how much protein exists. Now we have new techniques for measuring the amount of protein directly, but there is still an academic interest in measuring the RNA in some places. Both techniques are very important.

Do you believe that the software used for the sequencing of the human genome can also be used in the study of proteins?
We are developing new software to handle the proteins but the understanding of it is totally based on an understanding of the genome. When one deals with an integrated system, all the components are necessary. However, we will definitely need new and better software and computers.

Did all that was published in Nature and Science about the human genome make you change some of your more intimate convictions, such as in God, in destiny or in human evolution?
No. Not one of my convictions changed. I am still the same person, though it gave me an even greater reckoning on how complex biology is.