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Sunday, June 23, 2024

"Cancer Virus Hunters" by Gregory J. Morgan

That seven Nobel Prizes were awarded directly or indirectly for work in tumor virology illustrates the impact of the field on biomedical understanding. (p. 273)

We've entered a new era in the field of molecular biology. Almost all of the emphasis and excitement these days is based on studies of mammals, especially humans. Most of the big bucks are for studying some aspect of medicine so that even if you are interested in basic science you have to slant it toward curing some disease.

It's a new era because modern scientists seem to be unaware of the history of molecular biology and all the work that was done with bacteria and phage to work out the fundamentals of regulation, transcription, translation, and DNA replication. None of that stuff is taught in undergraduate courses any more and this is not a good thing.

In his book Cancer Virus Hunters, Gregory Morgan reminds us that there's another aspect of that history that we've forgotten. An offshoot of the 'phage group concentrated on mammalian viruses in order to understand how the fundamental principles seen in bacteria and 'phage applied to complex eukaryotes. This was a different approach from those who decided to work with simple eukaryote organisms such as yeast, Drosophila, and Caenorhabditis elegans.

Morgan covers the deliberate strategy of moving into mammalian viruses by creating centers devoted to their study, especially the groups at Cold Spring Harbor that were set up by Jim Watson. The administrative decision to invest in certain fields instead of others is an aspect of science history that's often ignored and it's nice to see it described in this book.

Throughout the book he describes the personalities and the background of the scientists who did the work. Unlike some other books, this isn't just "fluff" designed to soften the impact of the hard science that forms the main part of the book. Morgan uses these descriptions to help us understand why these scientists took the direction they did and why they were prepared to recognize new discoveries. I knew some of those scientists and I can confirm that his descriptions are accurate, although he does tend to be a bit lenient on some of them who, in my opinion, deserve harsher treatment. Of the ones I met, most, but not all, were very nice people

One of the more fascinating stories concerns the discovery of introns and splicing. Few people know that this came out of work on gene expression in cells infected with adenovirus. Morgan describes the initial work of Phil Sharp at MIT and the discovery of a mature mRNA that appeared to be processed from a larger transcript by removing internal sequences. He also covers the work done at Cold Spring Harbor Laboratories (CHSL) by groups headed by Richard ("Rich") Roberts, and separate groups headed by Tom Broker and Louise Chow. (Broker and Chow were married.) If you've ever wondered who did the important work and who got credit—not necessarily the same people—then this is the place to find out.

The chapters on the discovery of oncogenes are fascinating. I hadn't realized that there were so many laboratories working on the same problem; namely, the identification of cellular DNA that could transform cells into cancer cells. There were four or five labs that published within months of each other. I also didn't realize that the mutation that converts the normal cellular version of ras into the oncogene was discovered in 1982.

The story about the discovery of human immunodeficiency virus (HIV)—the virus that causes AIDS—is fascinating. Morgan covers the collaboration and the conflict between Robert Gallo's lab in the United States and Luc Montagnier's lab in France. He tells you whose cultures were contaminated, who was right about the identify of the virus, and whether Gallo really was guilty of scientific misconduct. Montagnier got the Nobel Prize in 20081 and Gallo didn't. Was that fair? You'll have to read the book to find out!

... those ignorant of history are not condemned to repeat it; they are merely destined to be confused. Stephen Jay Gould Ontogeny and Phylogeny (1977)The history of HIV has been covered many times but I like the way it's described here in Chapter 14. Morgan is very objective ("just the facts") and he avoids proselytizing. I recommend buying his book for this chapter alone.

There's a chapter on the discovery of human papillomavirus (HPV) that's just as fascinating as all the others. I like the fact that Morgan covers the work of many scientists in different labs and describes both their collaboration and their competition. When it comes to final credit—in this case a Nobel Prize for Harald zur Hausen—the award seems appropriate when Morgan describes it.

The role of patents, vaccines, and getting rich is an unfortunate part of the history of cancer virology and Morgan covers several examples. The patent debates and the lawsuits over the papillomavirus vaccine is just one example in this book. It's not a very flattering account of the behavior of the scientists who did the work but it serves as an illustration of how "pure" science can be easily contaminated when money and drug companies get involved.

The final chapter covers the overall impact of tumor virology on basic science and on the treatment of cancer. Morgan explains how this research impacted science in many ways that aren't all that obvious at first glance. It made me realize that I had not fully appreciated or understood the role of the cancer virus hunters. I do now.

I strongly recommend this book to anyone who's interested in the history of molecular biology. You don't have to know the history of every discovery in your field but if you are going to refer to it in the introduction to your papers then you'd better be sure you get it right.

1. With Françoise Barré-Sinoussi.


Sharon James, Editor said...

Larry is there anything about how the world works that you don't lament? Why pick a fight against prioritizing translational research? Do you really believe the world might overlook the importance of fundamental discoveries that have historically laid the groundwork for translational applications?

Anonymous said...

This is very interesting stuff. Morgan's book is now my list of books to read.

Anonymous said...

*on my list

Larry Moran said...

@Sharon James: Yes, I really believe that some of the money spent on "translational research" should be diverted to basic science and work on other organisms.

My lab was interested in how genes were expressed in yeast and Drosophila. Those were good systems to work with but in order to get enough money to run my lab I had to switch to working with mice genes and make up some story about how it was going to cure cancer.

I was also interested in molecular evolution back in the early 1990s but I couldn't come up with a convincing explanation of how that was going to translate into improving human health.

John Janis said...

Apart from a wealthy patron or an enlightened funding agency it's a game researchers have had to play for I don't know how long. At least you could say it stimulates creativity! Back in the mid-1970s we grad students would devour RFPs from NSERC and the like seeing where we could force-fit work we wanted to do into the mold of what some committee said they wanted. At that time anything to do with aging or life extension was hot. We were quantum chemists so we would emphasize how we could model . Today I suspect we would be tarting up predictive models and peppering proposals with the new holy buzzword "AI". I suspect a lot of pure research gets funded by bootstrapping - charging bits and bobs to other projects over time to get enough data to write a proposal that meets some threshold for actual funding. Of course, there will always be researchers pro-bono contributions. Most are addicted to science.