When Stephane Castel first met with a group of Maori and other Pacific Islanders in New Zealand to talk about his pharmaceutical company’s plans for genetic research, locals were concerned that he might be seeking to profit from members’ genes of the community without giving them much thought.
On the contrary, explained Dr. Castel and his colleagues, that they aimed to make an unconventional deal: In exchange for entrusting them with their genetic heritage, the participating communities would receive a share of the company’s revenue. Dr. Castel also promised not to patent any genes — as many other companies had done — but rather the drugs his company developed from the collaboration.
“A lot of people told us this was a crazy idea and it wouldn’t work,” Dr. Castel said. But five years after that first conversation during an Indigenous health research conference in March 2019, Dr. Castel’s gambit is starting to pay off for both parties.
On Tuesday, his company, Seattle-based Variant Bio, announced a $50 million partnership with drugmaker Novo Nordisk to develop drugs for metabolic disorders, including diabetes and obesity, using data collected from indigenous populations. Variant Bio will distribute a portion of these funds to the communities it has worked with in nine countries or territories, including Maori, and will seek to make the medicines resulting from its work available to these communities at an affordable price.
Indigenous genetics experts said the deal was a positive step for a field plagued by accusations of exploitation and a distrust gap.
“In the past, researchers have come into indigenous communities with empty promises,” said Krystal Tsosie, a geneticist and bioethicist at Arizona State University who runs a nonprofit genetic repository for indigenous peoples. “Variant Bio is the only company, to my knowledge, that has explicitly talked about benefit sharing as part of its mission.”
The idea for Variant Bio was hatched at a Manhattan bar in August 2018 over drinks between Dr. Castel and Kaja Wasik, who had become friends during their graduate studies in genetics at Cold Spring Harbor Laboratory on Long Island.
Although their laboratory research kept them under the glare of fluorescent lights, they shared an appetite for international travel, which they enjoyed during trips together to Peru and Chile. They dreamed of building a company that could take them to remote places.
At the time, pharmacists were forming partnerships with biological repositories such as the UK Biobank, which contains biological samples and health records from half a million people living in Britain, to look for associations between genes and diseases.
But these databases mostly consist of genes from people of European descent.
“What is the value of sequencing 500,001 Britons?” Dr. Castel said. “There is only so much knowledge one can find by studying the same group of people.”
He and Dr. Wasik were most enthusiastic about recent findings from underrepresented groups, such as the discovery of new gene variants that affect metabolism first identified in Inuit populations in Greenland.
Such variants may be more common, and thus easier to detect, in historically isolated populations because they confer some functional benefit on individuals with a particular diet or lifestyle, or simply because of random events in their history. However, they can also serve as promising drug targets that will help a wider segment of the world’s population.
With $16 million in funding from Lux Capital, a venture capital firm in New York, Dr. Castel and Dr. Wasik quit their jobs and started working full-time on their startup. Dr. Wasik traveled to eight countries in Africa, Asia, Europe and the Pacific in the company’s first year, while Dr. Castel has, for the most part, responsibly built their software platform from its base in the United States.
They consulted ethical consultants to develop a benefit-sharing model and went on a listening tour. They knew from the beginning that they would have to tread carefully.
In 2007, a member of the Karitiana tribe in Brazil told the New York Times that his community had been “deceived, lied to and exploited” by scientists who had collected their blood and DNA, which was later sold for $85 per sample. Tribesmen, who said they had been lured with promises of medicine, received nothing.
Ten years later, there was still no consensus on how best to conduct such work. To protect against so-called biopiracy, many countries have ratified the Nagoya Protocol under the United Nations Convention on Biological Diversity, which requires the “equitable sharing of benefits” derived from genetic resources. But the protocol excluded information about the human genome.
During Dr. Castel and Dr. Wasik’s trip to New Zealand in 2019, researchers and community members were troubled by an earlier attempt by American researchers to patent an obesity risk test based on genetic studies conducted in Samoa. The researchers’ universities did not list their Samoan collaborators in their patent application as co-inventors, nor did they have formal benefit-sharing agreements with local institutions. (That patent application has since been abandoned, and the researchers said they always intended to share the benefits with their collaborators.)
One of Variant’s early advisers was Keolu Fox, an outspoken geneticist at the University of California, San Diego, who had been a harsh critic of Samoa’s research.
“This is an extension of all these other forms of colonialism,” said Dr. Fox, who is a native Hawaiian and joined Dr. Wasik and Drs. Castel on their trip to New Zealand. He believed that Variant could lead by example.
In the company’s benefit-sharing program, up to 10 percent of a project’s budget goes to community programs, usually by funding local organizations.
For example, as part of its New Zealand-based study into the genetic causes of kidney disease and other metabolic disorders in Maori and other people of Pacific descent, the company spent $100,000 to fund several local health organizations together with grants and scientific conferences on Indigenous peoples.
“Before Variant came along, we didn’t do it because we couldn’t afford to do it,” said Tony Merriman, a gout specialist at the University of Alabama at Birmingham who has worked with the company on two projects in the Pacific region. . .
Dr Merriman said he also appreciated the company ensuring its findings were shared with the community. In French Polynesia, the company’s research encouraged increased access to a gout drug after it concluded that the local population did not have an increased risk of a fatal drug reaction that had been seen in some Asian populations.
The new Novo Nordisk agreement begins a second, longer-term phase of the benefit-sharing program. The communities will share a 4 percent share of Variant’s revenue and, if the company is ever sold or goes public, 4 percent of its equity. This rate is comparable to the royalties that universities receive for licensing their patents.
