Kevin Davies Ph.D. Executive Vice President, Strategic Development Mary Ann Liebert, Inc.

Gene Therapy Pioneer Plans Next Steps Following Release from Prison

As he attempts to carve out a semblance of a normal life, William French Anderson, M.D., still hopes to contribute to science and gene therapy—the field he helped launch almost 30 years ago. The odds, he acknowledges, are stacked against him: He is 81 years old and has just been released after serving 12 years in prison.

“My legacy is a dark one at the moment—being a convicted child molester felon is a very black mark,” Anderson told GEN in a phone interview this week. “Until I’m exonerated, there’s zero opportunity—except in my wife’s kitchen.”

Together with his colleagues Michael R. Blaese, M.D., and Ken Culver, M.D., Dr. Anderson shepherded the first approved gene therapy trial in 1990 at the National Institutes of Health (NIH). Six months earlier, Dr. Anderson had launched Human Gene Therapy, a major new peer-reviewed journal from Mary Ann Liebert, Inc. (publisher of Genetic Engineering & Biotechnology NewsGEN). The journal, he wrote in his debut editorial, would “evolve with this major new frontier” of gene transfer and “document the progress and the setbacks as we go.”

Those setbacks duly arrived—notably the death of Jesse Gelsinger in a gene therapy trial in 1999—and were followed shortly thereafter by reports of leukemia arising in clinical trial patients in Europe. Dr. Anderson’s own career, if not his life, came to a shuddering halt in July 2004 when he was arrested and later convicted of sexual abuse of the teenage daughter of a former colleague. (Dr. Anderson continues to maintain his innocence.)

Following his prison release in May 2018, Dr. Anderson gave his first press interview to Sharon Begley of STAT. During his incarceration, Begley noted, Dr. Anderson devoured mailed copies of GEN, Human Gene Therapy, and other science journals. “Those are what I lived on for the last 12 years,” he said, speaking from his home in Southern California. “All I had in the prison library was Popular Mechanics.”

The Outsider

Dr. Anderson was eager to give GEN more insight on his future plans and survey the progress that has swept gene therapy during his absence.

“The evening I got out of prison, I called about 50 people to thank them—so many wrote letters supporting me, stayed in contact with [my wife],” Dr. Anderson said. Although some have expressed interest in collaborating with Dr. Anderson, he says he won’t consult for anyone unless and until he is exonerated (a process he estimates will take two years).

“I’m 81 and have been out of things for 14 years. I’m an outsider, but I’m an outsider with insider knowledge. I might be able to think ‘outside the box’ to help solve some problems, simply because I’ve got a long history in gene therapy and genetic research,” he said.

On CRISPR gene editing, Dr. Anderson said, “even though it has an extraordinary future, it was not unexpected.” CRISPR he said “is like so many disruptive technologies: It starts off with people being very excited. Then some problems come along and enthusiasm is sharply curtailed.”

Fresh in his mind are the safety concerns flagged in a recent study published by Allan Bradley, Ph.D., and colleagues, in Nature Biotechnology. “The current unexpected genome damage is just a problem to be solved,” Dr. Anderson said. “We had the same problem with gene therapy.”

Just as the gene therapy field retrenched after the Gelsinger tragedy, Dr. Anderson says researchers in time will determine “how to use CRISPR with whatever Cas [protein] is most appropriate in a safe way… Yes, it’s a problem, but it’s simply a problem to be solved. It might take three years, it might take five years. In gene therapy, it took about ten years.”

Reflecting on advances in gene therapy over the past decade, Dr. Anderson says, “What is most exciting for me is not any individual thing—though Jean Bennet’s [University of Pennsylvania] work [on congenital blindness] to me was the most exciting [and also] the first FDA-approval from Novartis.”

What pleases Dr. Anderson the most is how widespread gene therapy has become, realizing many of the medical applications predicted at the dawn of the field. “Look at almost any major disease: Someone is working on a gene therapy treatment for it,” he said. “There are hundreds of gene therapy trials taking place around the world. It’s wonderful. And if CRISPR is able to correct genetic diseases and cancer and so on more effectively than gene therapy, then wonderful for that.”

Indeed, “CRISPR might very well supplant the idea of introducing genes with a vector. Vector-carrying gene therapy might be passé 10–15 years from now,” he said.

Kitchen Sink Approach

While a consulting role remains a distant hope, there is one experiment Dr. Anderson is “dead serious” about conducting. He wants to follow up an observation he made 52 years ago in the NIH lab of Marshall Nirenberg, Ph.D., who went onto share the Nobel Prize in 1968 for the discovery of the genetic code. Dr. Anderson at the time was tasked with synthesizing various genetic triplets for the final genetic code experiments.

“Nirenberg honored me by being the first person to present the final genetic code [in April 1966] at the FASEB meeting,” Dr. Anderson recalled, two months before Nirenberg gave his own seminal presentation at Cold Spring Harbor Laboratory.

The experiment might shed light on the origins of life on earth. In Dr. Anderson’s view, the key question isn’t where the building blocks of life came from—asteroids containing organic molecules—but rather “how do you build something like an RNA chain or DNA chain from nucleotides? There isn’t any indication of how you can get that first string of amino acids or ribonucleic acids.”

Back in 1966, Dr. Anderson said, “I happened to be heating up some GpC dinucleotides. I got to talking to somebody and I held it over a Bunsen burner longer than I meant to, and I said, ‘Oh my gosh, I hope it doesn’t boil over.’ I looked at it and realized it was solid—it was a gel! I turned the tube upside down and it’s an absolutely solid gel… I cooled it down and it went back to a liquid, heated it up again and it went back to a gel. No one could explain it… I took it to every physical chemist I could find at NIH and Harvard: No one could understand it, no one knew how to study it. I kept it in the back of my head.”

Today, Dr. Anderson says there is ample new technology to study this phenomenon. He believes that chemical bonds were formed in producing this gel-like substance. “Maybe they were random bonds and mean nothing. But the other possibility is that GpC—under the appropriate conditions of concentration, temperature, pressure, etc.—can actually form a helical-type structure, but without bonding.”

That could explain how the original biomolecule chains were built three billion years ago. “And that’s something I can do in my own kitchen, which is what I plan to do!” he said.

Dr. Anderson plans to order some GpC dinucleotides, buffers (“because I don’t remember the exact conditions of what I had 52 years ago”), and test tubes. His gas stove will substitute for a Bunsen burner. And if the results look promising, he’ll find a university researcher to help determine the gel’s structure.

“Most scientific ideas lead to nothing. It probably will not work, but I’m going to do it,” he said. “I’m going to do it at the kitchen sink I’m looking at right now.”

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