Who's Looking to Profit from Human Germline Changes?

Biopolitical Times
Intrexon marketing material. Below its logo and brand is the following statement: "A better world  through better DNA."

The National Academies summit on human germline gene editing has dominated discussion over the last few months, with talk about international agreements and a voluntary moratorium or formal ban. But perhaps those of us concerned about the prospect have been looking in the wrong direction. Consider this scenario:

A multi-billionaire becomes fascinated by synthetic biology. He starts with a fairly small company, and decides to turn it into a big one without using venture capital. His goal is to make it "the Google of the life sciences." Among the acquisitions and partnerships he makes are:

  • a company developing personalized cell and gene therapies using iPS cells
  • an animal cloning company (both the agricultural and pet markets)
  • a biopharmaceutical company focused on cancer immunotherapies
  • a drug development and delivery company
  • a company that makes genetically modified fish (even before selling them was legal)
  • a company that makes sterile mosquitoes in order to effect permanent germline changes
  • a company that makes genetically modified apples
  • a company pushing hard into multiple IVF markets around the world, with
    • products not currently legal in the U.S., and
    • research into human egg precursors with the explicit intention of producing hundreds of eggs and possibly embryos — and the ambition of editing them

In short, lots of private money, deep connections with the pharmaceutical industry, a major focus on synthetic biology, a willingness to jump borders for legal convenience, a deep interest in reproductive technologies, and the clear intention to work on "enhancing" embryos.

That could turn into a nightmare. But it's real, and it's happening now.

The billionaire is Randal Kirk, the main company Intrexon, which cannily snagged the URL dna.com. The iPS company is Fibrocell; the cloning one is Viagen (part of Trans Ova Genetics); the (disappointing so far) biopharmaceutical is Ziopharm; the drug company is Halozyme; the fish are AquAdvantage salmon made by AquaBounty; Oxitec makes the sterile mosquitoes; the Arctic® Apple was developed by Okanagan; and the IVF company is the extremely controversial OvaScience.

The billionaire is Randal Kirk, the main company Intrexon, which cannily snagged the URL dna.com. The iPS company is Fibrocell; the cloning one is Viagen (part of Trans Ova Genetics); the (disappointing so far) biopharmaceutical is Ziopharm; the drug company is Halozyme; the fish are AquAdvantage salmon made by AquaBounty; Oxitec makes the sterile mosquitoes; the Arctic® Apple was developed by Okanagan; and the IVF company is the extremely controversial OvaScience.

Kirk, a lawyer by training, made his first fortune ($65 million) with a medical supplies company; his first big one with New River Pharmaceuticals (he cleared $1.2 billion); his second with Clinical Data (roughly $600 million); and his third when he took Intrexon public in 2013 (his shares have been valued at $1.5 billion). He avoids outside venture capital, and held onto over 60% of Intrexon; the success of its IPO may have been largely because of his existing reputation.

Clearly Kirk bought Intrexon as a way into synthetic biology. Its founder, molecular geneticist Thomas Reed, positioned what was originally called Genomatix as a gene-tools or DNA-parts venture, but Kirk had much broader ambitions (yes, the Google quote was his, though he said it before Google became the Google of the life sciences). In a 2011 profile, Forbes also reported Kirk's prediction that:

in a decade it [Intrexon] could become "the largest, most significant company" in its burgeoning field.

He could be right.

Of course, he also might not. Indeed, Viagen was a spin-off from Genetic Savings and Clone (GSC), a pet cloning company that was set up by the billionaire John Sperling. GSC was finally abandoned, partly for technical and ethical reasons and above all because it was not commercially viable.

Intrexon and OvaScience

Last April, MIT Technology Review noted that OvaScience intended to "correct [harmful genetic] mutations before we generate your child," and Motley Fool pointed out the potential synergies between OvaScience and Intrexon, focused on a joint venture called OvaXon, described on the Intrexon website thus:

The joint venture looks to create new applications for improving human and animal health. Under the joint venture, OvaScience's EggPC platform will be combined with Intrexon's genome engineering capabilities with the goal of offering an innovative approach for the prevention of inherited diseases in humans, such as mitochondrial and other genetic disorders.

The technology behind OvaScience is scientifically controversial, ultimately based on the disputed discovery of "egg precursor cells" that "have the potential to develop into mature eggs, thereby replenishing a woman’s egg supply." Its main product at present is Augment, which "uses the energy-producing mitochondria from your own egg precursor (EggPC℠) cells … to supplement the existing mitochondria in your eggs" and thus supposedly improve fertility.

One of the founders of OvaScience told a stock analyst last spring that using CRISPR in germline engineering was not on the current agenda ("they have enough headaches at this point") but they do admit to being aware of the potential to use it that way.

The FDA will not allow Augment to be sold in the U.S. without clinical trials. However, it is sold in Canada, where the first baby was born after that treatment in May, 2015; and also in Japan, Turkey and Dubai. A British IVF clinic is applying for permission to use the procedure "in a pilot trial involving about 20 women."

Permission may not be granted in the UK — Robin Lovell-Badge, for one, is extremely skeptical — but the attempt illustrates the difficulty of establishing, let alone enforcing, international standards. The company is trying to pressure the FDA by creating consumer demand here with promotional stories from abroad.

Intrexon and its subsidiaries have other experience with transnational evasion techniques: AquaBounty was an American company, founded in Maynard, MA, and incorporated in Delaware, that set up in Canada to create eggs that would be grown in Panama. It nearly went bust until Kirk bought in.

Kirk is arguably "Biotech's Best Investor." He's clearly a technophile and definitely thinks that synthetic biology is the future — he's called his partner Reed "the Henry Ford of DNA" — but he does not seem to be primarily an ideologue; he wants to make another boatload of money.

So what's to stop Kirk and his companies and allies, or people like them, from developing a germline "enhancement" technology that they could introduce in, say, Dubai and promote everywhere else?

[This post was edited on January 30th to include Oxitec, previously omitted by mistake.]

Previously on Biopolitical Times: