It’s 1975, and at a Soviet research institute in Leningrad, Andrei Kozlov is onto something.
The biomedical scientist has just defended a PhD thesis, impenetrable to the uninitiated. Something about how genes are expressed in tumors and normal tissue.
His professor, the renowned Russian oncologist Iozef Seitz, pipes up. “Andrei, but how do the tumors fit into this picture?”
Kozlov, just 25, shrugs. “I don’t know yet.”
Nearly four decades later, the death of communism and the chaotic 1990s having passed in a time-lapse blur, Kozlov has arrived at a theory that he hopes will provide science with a springboard in the fight against cancer.
In his new book, “Evolution by Tumor Neofunctionalization,” Kozlov makes the eye-opening assertion that tumors play a positive role in evolution.
Andrei Kozlov has posited a theory that goes against the grain of traditional thinking, his peers say
The potentially killer growths, he moots, are a testing ground for genes to fully “express” themselves without the distraction of the regular genetic activity in the tumors’ hosts.
Genes are free to work inside tumors, and through trial and error can eventually prompt useful organs to evolve, given enough time, Kozlov says.
Conclusion one is that people who have tumors are evolution’s chosen guinea pigs, Kozlov posits. Conclusion two, somewhat jarringly, is we should stop seeking to kill off tumors altogether if we want humanity to maximize its evolutionary potential.
Kozlov is not suggesting that people should somehow be prevented from removing tumors if they turn malignant, but rather a way should be found to keep tumors in what he calls a "controlled chronic condition." How that is to be achieved, he freely admits, is unclear.
The theory goes further than recent publications on how evolution may influence tumors, instead considering their active role in shaping it.
The book's publisher claims that the theory is so far-reaching it could prompt new research in oncology, evolutionary biology, molecular biology, molecular evolution, embryology, tumor immunology and pathology.
Kozlov, now 64, expands on his findings in an interview to sk.ru.
“If new genes appear in the genomes of evolving multicellular organisms, they need new space to act because pre-existing cell types are all occupied by the products of activity of evolutionarily older genes,” he says.
“Evolutionarily novel genes need what I call ‘extra cell masses,’ which are not differentiated and not functionally necessary to the organism. Such cell masses are tumors by definition.”
“Tumors can and have played a positive role in evolution because they provide a testing ground for gene expression.”
“To be inherited, evolutionarily novel genes should originate in germ cells, not in tumors. But they are newly expressed in tumors. Such new expression is inherited due to epigenetic mechanisms.”
Epigenetic mechanisms involve the activation or deactivation of certain genes to make a person more predisposed to certain biological processes.
“The book makes up a foundation for a new oncological ‘platform,’ or a new strategy in the war on cancer based on the new attitude to tumors,” says Kozlov.
“If tumors are continuously encountered (chronic) in evolution, then we should try to keep human tumors in the similar chronic condition, instead of trying to kill tumors.”
Kozlov made it a life goal to validate the theory.
“I always understood the importance of the discovery,” Kozlov adds, “but I also understood that it will be very difficult to prove it and to write the book.”
Salvation appeared in the form of a goldfish.
Years of experiments yielded the smoking-gun evidence that Kozlov needed to start writing his book: That the hood of the oranda goldfish is in fact a tumor.
Kozlov says he has proved the hood of the oranda goldfish is a tumor
“We proved that the hoods are benign tumors. This means that tumors were selected by selectionists over several hundred years to form new organs of fish, which strongly supports the concept of the book.”
Six months have passed since the first edition of Kozlov’s book was published by Academic Press/Elsevier, and although “the response will take several years,” already some aspects of the research have been pounced upon by U.S. vaccine producers.
By comparing tumorous and non-tumorous DNA on computers, Kozlov’s team at the Biomedical Center in St. Petersburg singled out the gene protein known as brachyury as one that may provide antitumor immunity.
Kozlov immediately registered a patent in the United States and now two companies – GlobeImmune Inc. and Bavarian Nordic – are running clinical trials for a potential vaccine.
During the Cold War and after, Kozlov developed a solid if unspectacular reputation among a cohort of Western scientists, doing a fellowship in the laboratories of Robert Gallo, a co-discoverer of HIV, and working with Jeffrey Schlom, chief of the Laboratory of Tumor Immunology and Biology at the Center for Cancer Research within the National Cancer Institute, among others.
Schlom is familiar with Kozlov’s new research, though is yet to study it in detail.
“This is very, very intriguing work. It’s very exciting, it’s very provocative. It’s a very unique observation that goes against a lot of the dogma that’s out there,” Schlom told sk.ru.
Schlom, who collaborated with Kozlov in researching brachyury, called Kozlov a “zealot,” but added “I don’t think that’s a bad thing to be for a research scientist.”
While his discoveries in oncology are yet to be widely appraised, Kozlov’s work in the field of AIDS and HIV have earned positive reviews.
He was commended in a 2006 AIDS Journal editorial for helping to reverse Russia’s underreporting of HIV infection statistics, while in 2010 Science magazine called him a “talented investigator” of the virus.
Science magazine also intimated that Kozlov’s bolshie character may have done little to erode barriers in the Russian science community, but otherwise revealed nothing untoward as a researcher.
Sk.ru contacted five prominent scientists who had, at one time or another, worked with Kozlov. Other than Schlom there were two responses – both positive. One stated his “admiration” for Kozlov’s work, but both declined to be identified in this article. A top UK-based scientist said he was "not interested" in commenting and did not respond to a question as to why that was the case.
So the world must wait to discover if Kozlov’s peers agree his research is potentially “sensational.”
In the meantime, he recalls its germination.
“My paper published in 1979 in the Journal of Theoretical Biology contains the sentence that tumors might be the place where evolutionarily novel genes could be first expressed,” he said.
“It was just a statement. … It was very difficult to explain and illustrate such a statement, and to put down the text. I remember how painful it was at some moments. There was a series of papers in 1980-1990 in which the concept was developing. Sometimes I had a feeling that it was not me writing."
Kozlov's book, first published in February
In some ways, Kozlov is the archetypal recluse, living in the forest 40km outside St. Petersburg, enjoying literary classics over a glass of red. In others, he is very much the progressive.
“I like Skolkovo style,” he says, in reference to the Skolkovo ecosystem of innovation, whose goal is to turn ideas into marketable products and reduce Russia’s economic dependence on oil and gas.
“Skolkovo is more in applied science at the present time, but I think with Skoltech development its role in science may increase, and I am ready to participate in the process.”
Skoltech is the Skolkovo Institute of Science and Technology, where Kozlov is to begin giving lectures in the near future.
As for the book, Kozlov is not about to put his feet on the desk and wait for the reviews to roll in.
“I am writing a new chapter: 'Tumor Immunology and Evolution,' and I hope to arrive at important new conclusions,” he says.
“But I don't know the whole story yet.”