About five months ago, researchers at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany published a complete genome sequence for the famous laboratory cell line known as HeLa. The work spurred vociferous shouting that went on for weeks, ultimately spurring the authors to apologize and take the sequence data offline. Today, a team of scientists at the University of Washington in Seattle published another genome sequence for HeLa cells. I predict far less shouting this time, because the second group handled the job properly.
To understand this controversy, we need to put HeLa cells into context. This immortalized cell line, originally derived from a human cervical tumor in 1951, has been a laboratory staple for decades. During my time in the lab, we kept a large “spinner” culture of HeLas growing all the time, and a technician subcultured that batch onto petri dishes several times a week. Anyone who needed plates of HeLas could simply order them a day or two in advance, and the tech would have them waiting in time for the experiment. They were like pipets or bottles of culture media – something we used constantly with barely a second thought. We knew these cells had come from a cancer patient way back when, but that was as far as the story went. The name HeLa was an abbreviation of the patient’s name, which we assumed had been lost to history.
That changed dramatically in 2010, when Rebecca Skloot published The Immortal Life of Henrietta Lacks. Lacks was the source of HeLa cells, and it turned out that her family was largely unaware that their relative’s tumor was still living in labs around the world. I read the book when it came out, and enjoyed the story even if I didn’t agree with the author’s general theme or the ethical revisionism of much of the subsequent commentary. Henrietta’s treatment was completely in line with the ethics of her time; judging the physicians and scientists of 1951 by the standards of 2010 is absurd. That Lacks was black also tinged the discussion with race, a topic that carries immense ethical and cultural baggage of its own in American society and tends to add more heat than light to these types of debates. However, Skloot did manage to touch on many of the complex social questions that modern biological research is raising, and her book became an instant bestseller.
Because HeLas are ubiquitous in lab work, EMBL’s idea of publishing a reference sequence for the cell line made great scientific sense. Unfortunately, perhaps because the German group didn’t quite grasp the implications of the racially charged discussion already underway in the US, they didn’t bother to ask anyone if it made ethical sense.
A genome sequence of an individual’s cells is an indirect genome sequence of an entire family. Lacks’s family, recently schooled in bioethics, might reasonably object to having Helen’s tumor’s sequence posted for the world to see. They did.
The EMBL team’s error was innocent but still inexcusable. They should’ve asked the family and they didn’t. Thanks to Skloot’s bestseller, it’s not just easy to find out who the original HeLa donor was and how her family feels about it, it’s difficult not to find out. A single email or phone call would’ve put the researchers in touch with Lacks’s family. They could’ve explained their case and probably reached an appropriate agreement to publish the data. By skipping this easy and obvious step, they thrust themselves into a fight they couldn’t win, doomed their own work, and jeopardized the prospects for anyone who wanted to follow them. If a group of scientists had subjected my family to such arrogant and thoughtless treatment, I’d be inclined to tell the next group to go shit in their hats.
Fortunately, the Lackses seem to be more forgiving than me. In the wake of the EMBL debacle, officials from the NIH contacted them and did what the EMBL should’ve done: talked, then listened, and then listened some more. The result was an agreement that allows researchers to sequence HeLa cells and make the data available to other scientists, provided they maintain strong safeguards to protect the family’s genetic privacy.
Cynics will argue that this new agreement is a bit of a sham. Thousands of fragments of HeLa sequences are already in public databases. Anyone could download the fragments and the appropriate open-source software and assemble a fairly complete genome without asking for permission. Meanwhile, DNA sequencing is cheap and getting cheaper by the minute. Anyone could simply order a reference sample of HeLas, then send them to a sequencing company and get the genome from scratch for a few thousand dollars, again without any kind of clearance. The “HeLa genome” is also far from monolithic. This is a tumor cell line that’s been growing for thousands of generations in laboratory cultures, accumulating mutations and rearrangements and generally evolving for its artificially maintained lifestyle. Different labs’ HeLas have different genomes, undercutting the argument about genetic privacy; the genome sequences of Lacks’s relatives – or even Lacks herself – would probably bear only a vague resemblance to the sequence of HeLa cells.
Those arguments are as true as they are irrelevant. We are hurtling toward a future in which everyone’s genome will be sequenced and put into a database somewhere. These won’t be sequences of thirdhand cultures of a distant relative’s tumor, but direct sequences of primary samples, linked to specific individual identities. Your doctor will have access to your genome sequence, and you’ll want him to. I’ll wager your health insurance company will also have access, whether you want them to or not. By focusing on getting the Lacks family’s informed consent to sequence HeLa genomes, and by restricting access to those sequences, the NIH has now placed a crucial boundary marker on this issue. We may not know what ethical standards future generations will judge us by, but we must at least honor those of our own time.
The University of Washington team’s sequence is the first publication to follow the new guidelines, and it’s a neat piece of work. Among other things, the new sequence reveals the integration site of human papillomavirus 18 in the HeLa genome, which was probably the event that led to Lacks’s tumor in the first place. That’s the kind of detailed information that points to a bright future for genome sequencing in clinical research and medicine – provided we do it right.