The Immortal Consenting of Henrietta Lacks

Rebecca Skloot has an essay in today’s New York Times discussing the recent publication of the genome sequence of a widely used human cell line. Skloot, as most of you already know, wrote a book about the history this cell line  – known as HeLa for Henrietta Lacks, the woman from whom they were obtained.

In her book, Skloot describes how the cells were taken from Lacks, who was dying of agressive ovarian cancer, without her knowledge or consent, and how the family was kept in the dark about the cells for decades, even as they researchers showed up to take samples from Lacks’ descendants. Skloot has done a wonderful job of not only gaining the Lacks family’s support for her book, but of engaging them with the legacy of Henrietta’s unwitting contribution to science and medicine.

So it makes sense that Skloot would take umbrage with the release of the complete sequence of HeLa cells, published without the consent of knowledge of the Lacks family. I can understand how this happened – HeLa cells are so ubiquitous in the lab, it’s easy to forget that they come from a real person (although it’s hard to believe the authors of the paper hadn’t read, or at least heard of, Skloot’s book). But it’s really not acceptable, something the authors now realize and are trying to correct.

Unfortunately, Skloot’s NYT essay on this topic was muddled – conflating two distinct issues – one very general, the other specific to HeLa cells – that have to be dealt with separately.

The first issue is one of consent from Henrietta Lacks to sequence and publish the genome of cells derived from her body. As Skloot made very clear in her book, no such consent was obtained. And, since Lacks died a long time ago, it can not be obtained. Lots of people, including Skloot, point out that consent was neither required nor generally obtained in the 1950’s when Lacks was sick. And knowing that Lacks was a poor African-American woman, it’s hard not to see more sinister overtones her treatment.

To me, there really is no moral question here. We should not be using HeLa cells because no consent was obtained to take them. And I am very uncomfortable with the general idea that heirs/descendants should be allowed to retroactively consent for a dead relative. Nothing that can happen now or in the future can make up for the lack of real consent. But whether they should be used or not, these cells are being used all over the planet. Given that this is unlikely to change, there’s really no choice but to de facto give the Lacks family a kind of proxy consenting power to act on Henrietta’s behalf.

However Skloot’s piece glides from the issue of how to retroactively get Henrietta’s permission to experiment with and publish about her cells to the seemingly related  issue of whether publication of the HeLa cell genome is an invasion of the privacy of Lacks’ living relatives. Skloot repeatedly raises the issue of all the things we can learn about an individual and their relatives by sequencing their DNA, and whether family members should have some kind of veto power over the publishing of a relatives genome.

But this is a very different than the question of how to obtain consent from an individual who is not longer alive. To see why, lets stipulate that Henrietta Lacks had consented to all these studies – had, in sound mind, given permission for the doctors to take her cell lines, establish cultures, send them around the world to be used for any purpose and to freely publish the results of any studies on these cells. Would you still require the authors of the paper to consent Lacks’ family?

Skloot clearly thinks the answer is yes – positing that publishing any individual’s genome sequence is intrinsically   an invasion of the privacy of their relatives – whether or not the sequenced individual consented to the process. Hence this quote:

“That is private family information,” said Jeri Lacks-Whye, Lacks’s granddaughter. “It shouldn’t have been published without our consent.”

This has nothing nothing to do with the history of Henrietta Lacks and HeLa cells. It is an active assertion about familial privacy rights that would – if you accept it – be just as true if the paper in question had described the sequencing of anyone else’s genome. Why weren’t the same issues raised when the genome belonged not to Henrietta Lacks, but to Jim Watson or Craig Venter?

I find the way Skloot’s NYT piece moves back and forth between the historical transgressions against Henrietta Lacks and the contemporary threat to her relatives’ privacy incredibly misleading. I doubt this was intentional – rather I think it reflects muddled thinking on her part about these issues. But either way, by juxtaposing the entirely justifiable empowering of the Lacks family to grant individual consent on Henrietta’s behalf with the desire of the same family to protect its genetic privacy, Skloot is implying that these are one and the same – that we should give ANY family the right to veto the publication of a relative’s genome.

But this is a logical fallacy. We probably all agree that the Lacks family should have been consulted about the publication of the HeLa genome because Henrietta herself never gave such permission. And some of you (not me) may think that a family’s right to genetic privacy trumps the right of an individual to publish their genome. But the former does not, in any way, imply the latter, and I think Skloot did the conversation around these issues a huge diservice by conflating them in such a prominent way.

Posted in bioethics, publishing, race, science | Comments closed

Another paper ready for open review: comparative ChIP-seq and RNA-seq in Drosophila embryos

As I wrote about for our last paper, I hate the way scientific publishing works today, especially the insane delays (average is about 9 months) between when a lab is ready to share its work and when the work is actually available. So, from now on we are going to post all of our papers online when we feel they’re ready to share – before they go to a journal. We’ll then solicit comments from our colleagues and use them to improve the work prior to formal publication.Physicists and mathematicians have been doing this for decades, as have increasing number of biologists. It’s time for this to become standard practice.

Ground rules: I will not filter comments except to remove obvious spam. You are welcome to post comments under your name or under a pseudonym – I will not reveal anyone’s identity – but I urge you to use your real name as I think we should have fully open peer review in science. The original paper and comments will remain available here as a record of the review process.

Paris M et al. (2013). Gene expression in early Drosophila embryos is highly conserved despite extensive divergence of transcription factor binding. Full manuscript. Text only. Figures only.

The paper is now available at arXiv. Please use the arXiv version for formal citations.

This paper is the result of several years of work from Mathilde Paris, a very talented postdoctoral fellow in my lab. Mathilde was interested in looking at the evolution of transcription factor binding in highly diverged Drosophila species and the effect of changes in transcription factor binding on gene expression. So she carried out a series of chromatin immunoprecipitation experiments using antibodies raised against four D. melanogaster proteins involved in early anterior-posterior (head -> tail) patterning. She carried out ChIP-seq experiments in D. melanogaster as well as D. pseudoobscura (diverged ~30mya) and D. virilis (diverged ~40mya). There were a lot of technical challenges in getting these experiments to work to our satisfaction (described in the methods section of the paper), but eventually Mathilde had a dataset in which we had sufficient confidence to analyze in detail.

The most striking observation about the ChIP data is just how different the binding patterns of these factors are in these different species, which, for all intents and purposes, undergo identical early developmental processes. We can identify two clear factors driving this divergence: the gain and loss of binding sites for these two factors (for background on binding site turnover see this 2008 paper from our lab), and the gain and loss of binding sites for the early embryonic master regulator Zelda (see this 2011 paper from our lab for more information about Zelda). However, these two effects did not completely explain the observed divergence, which may also be influenced by environmental factors (the species do not all develop at the same temperatures or same rates) and developmental, biochemical and experimental noise.

In contrast to the divergence of transcription factor binding, gene expression in stage-matched embryos is highly conserved. And one of the central issues discussed in the paper is why there is this discordance between transcription factor binding and gene expression divergence.

As always, we await your comments, and will respond as quickly as we can.

Posted in EisenLab, open access | Comments closed

No celebrations here: why the White House public access policy is bad for open access

I am taking a lot of flak from my friends in the open access community about my sour response to the White House’s statement on public access to papers arising from federally-funded scientific research.

While virtually everyone in the open access movement is calling for “celebration” of this “landmark” event, I see a huge missed opportunity that will ultimately be viewed as a major setback for open access. Since I seem to be the only person with this point of view, I feel I should explain why.

The statement was nominally triggered by a petition posted on the White House’s “We the People” page last May calling for greater access to the results of federally funded research, pointing to the successful NIH public access policy as a model for other agencies.

Under this new White House directive, all federal agencies with R&D budgets in excess of $100,000,000 will have to develop their own public access policies that will “ensure the public can read, download, and analyze in digital form” published works arising from federally-funded research within 12 months of publication.

There is no doubt this is a good thing. Once the new policies are implemented everyone will have access to the full range outputs of federally funded research. That is better than what is available today. So why aren’t I dancing in the streets?

When the NIH announced its public access policy in 2008, this truly was a landmark event. The biggest funder of non-classified scientific research in the world (The NIH research budget is around $30b/year) was acting to ensure public access to the entire body of its funded works. The policy was imperfect – it allowed a 12 months embargo, and had no provisions for reuse of the works. But this was big news – the instantiation of a new right – the right of the public to access the results of taxpayer funded research.

And the NIH policy has been very successful. The research community has accepted the mandate with nary a hitch – over 80% of NIH funded works end up in PubMed Central, the NIH’s open archive of scientific journal articles – and the database is heavily accessed by both researchers and the public.

It should have been a complete no brainer for other federal agencies to follow the NIH’s pioneering actions. But sadly, none did. And given the remarkable progress in open access that has happened in the intervening five years, for the White House to merely extend the NIH policy to other agencies is lame, retrograde action.

And it’s even worse than that. When the NIH policy was announced, people like me who believe that publicly funded works should be immediately freely available looked at the 12 month embargo period as a kind of opening bid – a concession to publishers that was necessary to get the policy off the ground, but which would ultimately disappear.

But now the White House has taken the 12 months embargo period and reified it.Year long delays are no longer an experiment by one agency. They are, in effect, the law of the land.

And why, after so clearly articulating the importance of public access in the begininning of their policy announcement, did the White House ultimately sell out the public? Here is what they say:

The Administration also recognizes that publishers provide valuable services, including the coordination of peer review, that are essential for ensuring the high quality and integrity of many scholarly publications. It is critical that these services continue to be made available.

The administration fell hook line and sinker for the ridiculous argument put forth by publishers that the only way for researchers and the public to get the servies they provide is to give them monopoly control over the articles for a year – the year when they are of greatest potential use.

Think about how absurd this is. Publishers, whose role should be to disseminate information as widely as possible, are now the only reason why the public will continue to not have access to research results their tax dollars paid for.

The White House chose this path even though there is now ample evidence that this concession is unnecessary. PLoS, BioMed Central and many other open access publishers have proven that publishers can create healthy businesses that provide all the services people value without ever restricting access to the papers they publish.

That the White House chose to ignore the rise of open access publishing and allow 12 month embargoes to persist shows that they care more about industries with well payed lobbyists than they do about the public good. And if you have any doubt that the publishers got what they wanted out of this policy, you only have to read the response of the Association of American Publishers – an industry group that has long opposed any moves towards public access and has backed repeated efforts to repeal the NIH policy:

The Association of American Publishers supports the Policy on Access to Research Outputs, released today by the White House Office of Science and Technology Policy (OSTP), which outlines a reasonable, balanced resolution of issues around public access to research funded by federal agencies.

Clearly the publishers got what they wanted out of the White House. And do you really think it’s going to stop there? They have established their ability to corrupt policy making, and will continue to exploit it. I predict that as these policies are implemented in different agencies, that they will be heavily tilted towards what the publishers want. There will be no central archives – just links out to publishers websites. And there will be pressure to increase – not decrease – embargo periods. The publishers are already laying the groundwork for this in their statement:

The key to the success of the policy, however, depends on how the agencies use their flexibility to avoid negative impacts to the successful system of scholarly communication that advances science, technology and innovation.

It’s sad. Had the White House actually looked at the landscape of scientific publishing with an eye towards maximizing public access, they would have realized that embargoes  are completely unnecessary. They could easily have come out with a policy that said:

From this point onward, the federal government will operate with a simple principle. Whenever the taxpayers of the United States sponsor scientific research, the results of this research will be immediately available to everyone.

Instead, once again, our government let us down, allowing a dying, useless industry to dictate policy that serves to line their pockets at the expense of the public good. And so I ask my friends in the open access movement, and everyone who cares about ensuring that the scientific research is as accessible and useful as it can be, is this really something you want to be celebrating?

Posted in open access, politics, science | Comments closed

Please review our new paper: Sequencing mRNA from cryo-sliced Drosophila embryos to determine genome-wide spatial patterns of gene expression

It’s no secret to people who read this blog that I hate the way scientific publishing works today. Most of my efforts in this domain have focused on removing barriers to the access and reuse of published papers. But there are other things that are broken with the way scientists communicate with each other, and chief amongst them is pre-publication peer review. I’ve written about this before, and won’t rehash the arguments here, save to say that I think we should publish first, and then review. But one could argue that I haven’t really practiced what I preach, as all of my lab’s papers have gone through peer review before they were published.

No more. From now on we are going to post all of our papers online when we feel they’re ready to share – before they go to a journal. We’ll then solicit comments from our colleagues and use them to improve the work prior to formal publication. Physicists and mathematicians have been doing this for decades, as have an increasing number of biologists. It’s time for this to become standard practice.

Some ground rules. I will not filter comments except to remove obvious spam. You are welcome to post comments under your name or under a pseudonym – I will not reveal anyone’s identity – but I urge you to use your real name as I think we should have fully open peer review in science.

OK. Now for the paper, which is posted on arxiv and can be linked to, cited there. We also have a copy here, in case you’re having trouble with figures on arXiv.

Peter A. Combs and Michael B. Eisen (2013). Sequencing mRNA from cryo-sliced Drosophila embryos to determine genome-wide spatial patterns of gene expression. 

Several years ago a postdoc in my lab, Susan Lott (now at UC Davis) developed methods to sequence the RNA’s from single Drosophila embryos. She was interested in looking at expression differences between males and females in early embryogenesis, and published a beautiful paper on that topic.

Although we were initially worried that we wouldn’t be albe to get enough RNA from single embryos to get reliable sequencing results, it turns out we got more than enough. Each embryo yielded around 100ng of total RNA, and we would end up loading only ~10% of the sample onto the sequencer. So it occurred to us that maybe we could work with material from pieces of individual embryos and thereby get spatial expression information on a genomic scale in a single quick experiment – an alternative to highly informative, but slow imaging-based methods.

I recruited a new biophysics student, Peter Combs, to work on slicing embryos with a microtome along the anterior-posterior axis and sequencing each of the sections to identify genes with patterned expression along the A-P axis. In typical PI fashion, I figured this would take a few weeks, but it ended up taking over a year to get right.

The major challenge was that, while a tenth of an embyro contains more than enough RNA to analyze by mRNA-seq, it turned out to be very difficult to shepherd that RNA successfully from a single cryosection to the sequencer. Peter was routinely failing to recover RNA and make libraries from these samples using methods that worked great for whole embryos. While there are various protocols out there claiming to analyze RNA from single cells, we were reluctant to use these amplification-based strategies.

The typical way people deal with loss of small quantities of nucleic acids during experimental manipulation is to add carrier RNA or DNA – something like tRNA or salmon sperm DNA. We didn’t want to do that, since we would just end up with tons of useless sequencing reads. So we came up with a different strategy – adding embryos from distantly related Drosophila species to each slice at an early stage in the process. This brought the total amount of RNA in each sample well amove the threshold where our purification and library preparation worked robustly, and we could easily separate the D. melanogaster RNA we were interested in for this experiment from that of the “carrier” embryo. But we could avoid wasting sequencing reads by turning the carrier RNAs into an experiment of their own – in this case looking at expression variation between species.

With this trick, the method now works great, and the paper is really just a description of the method and a demonstration that accurate expression patterns can be recovered from individual cryosectioned embryos. The resolution here is not that great – we used 6 slices of ~60um each per embryo. But we’ve started to make smaller sections, and a back of the envelope calculation suggests we can, with available sample handling and sequencing techniques, make up to 100 slices per embryo. This would be more than enough to see stripes and other subtle patterns missed in the current dataset.

Our immediate near term goals are to do a developmental time course, compare patterns in male and female embryos, look at other species and examine embryos from strains carrying various patterning defects. For those of you going to the fly meeting in DC in April, Peter’s talk will, I hope, have some of this new data.

Anyway, we would love comments on either the method or the manuscript.

 

Posted in EisenLab, gene regulation, My lab, open access, science | Comments closed

For patents, against open access: The sad state of university leadership

Quick. Name a leader of a major research university who has taken a courageous stand on any important issue in the last decade. I know they’re out there. They must be. But I can’t think of one.

Instead, I’m left dumfounded reading this amicus brief filed in a case – Bowman v. Monsanto – about to be heard by the US Supreme Court.

The case, which pits a farmer who planted soybeans containing Monsanto’s “Roundup Ready” technology without paying their license fees, boils down to a question of how much control patent holders have in their invention after it has been sold.

I am very interested in the issues in this case – I strongly support the development and use of geneticly modified crops, but also believe that our patent laws are completely out of whack. So a line in the NYT article on the case that universities had filed a brief on behalf of Monsanto caught my eye – all the more so because by own University of California had signed on.

The basic arguments put forth by the universities is that ruling in favor of the farmer would “greatly diminish, and add uncertainty to, the value of patents covering artificial, progenetive technologies” and would “devalue the extensive benefits achieved by the Bayh-Dole Act”.

Why are most of the most prominent state universities in the US arguing in front of the Supreme Court in favor of stronger patent laws? Why do they have any interest in who wins the case? The answer is that universities have become major producers and wielders of intellectual property – profiting, in many cases extensively, from patents taken out on inventions made by their faculty.

I have made no secret of my utter disdain for this process. We would all be better off if there were no patents on inventions produced at state universities and/or by publicly funded scientists. Universities don’t support strengthening patent laws because they believe it’s the right thing to do in some abstract sense, they support strengthening patent laws because it makes them money. And thus university administrators – when faced with a choice between the public good and their balance sheet – choose the money.

Meanwhile, as their lawyers were off siding with major corporations against a small-time farmer, universities have chosen to be completely silent on another major issue pitting corporate greed against the public good: providing free access to papers describing the results of publicly funded research.

A bill was introduced in Congress that would require scientists receiving money from the federal government to make copies of their published work available to the public. While many people from universities across the country have spoken up in favor of this bill and its predecessors, the University of California has never voiced its support for this action, and virtually all other universities have been equally silent.

In failing to support this legislation, universities are not just being passive bystanders. They are a major player in this issue, and their silence is widely interpreted as ambivalence or outright opposition, and helped to ensure that previous versions of this bill never made it out of committee.

So we have major public universities in America that see fit to use their resources to defend stronger patent laws, but choose to let legislation that would provide free access to knowledge to the public. There is only one word to describe this: pathetic.

 

 

Posted in GMO, intellectual property, open access, politics | Comments closed

The Association of American Publishers are a bunch of complete and total fu*kheads

It didn’t take long following the introduction of the Fair Access to Science and Technology Research Act of 2013 (FASTR) for Dr. Evil The Association of American Publishers to respond.

As if trying to outdo themselves, this latest anti-open access screed contains more misleading statements and outright lies than their previous efforts to undermine public access legislation.

Here is the text with my comments in red.

AAP STATEMENT ON FASTR ACT

Thursday, 14 February 2013 | Andi Sporkin

“Different Name, Same Boondoggle”

A boondoggle is, according to Wikipedia, a “project that is considered a useless waste of both time and money, yet is often continued due to extraneous policy motivations.” If there is any aspect of science today that should be considered a boondoggle, it is the existence of subscription-based publishers, who steal receive billions of dollars in public money, much of which they pocket as profit, while failing to provide access to the material they publish to the taxpayers who funded the work and to many of scientists, students and teachers worldwide.

Washington, DC; February 14, 2013 — Calling it “different name, same boondoggle,” the Association of American Publishers said today that the Fair Access to Science and Technology Research (FASTR) Act is unnecessary and a waste of federal resources.

The bill revives the majority of the terms set out in the Federal Research Public Access Act (FRPAA), which was introduced without further action in each of the last three Congresses. It would require federal agencies to undertake extensive, open-ended work already being performed successfully by the private sector.

This is a boldface lie. First, the purpose of the bill is explicitly to provide access to federally funded research to all Americans. This is something that publishers are, inarguably, NOT doing today. If the private sector were actually providing this service, then the bill would be superfluous. 

It would add significant, unspecified, ongoing costs to those agencies’ budgets in the midst of ongoing federal deficit reduction efforts.

Again, this is completely laughable. The publishing industry is, by far, the biggest waste of money in  science spending today. If we eliminated them entirely, we could save billions of dollars a year, while providing unlimited free access to the results of research. If publishers want to save taxpayers money, they should go out of business. 

Finally, it would undermine publishers’ efforts to provide access to high-quality peer-review research publications in a sustainable way, while ignoring progress made by agencies collaborating with publishers to improve funding transparency.

The science publishing industry – with skyrocketing costs and ever decreasing services – is the textbook example of an unsustainable business. Ask any library across the country to tell you about the efforts of publishers to create a sustainable publishing model, and they will laugh heartily at this claim. And I have no idea what they’re talking about as far as funding transparency goes. 

“This bill would waste so much taxpayers’ money at a time of budgetary crisis, squander federal employees’ time with busywork and require the creation and maintenance of otherwise-unneeded technology,” said Allan Adler, General Counsel and Vice President, Government Affairs, AAP, “all the while ignoring the fact that its demands are already being performed successfully by the private sector.”

Sorry, Allan Adler, but you are completely full of shit. The publishing industry has had nearly two decades to respond to the opportunity created by the internet and make the scientific literature freely available to the public. They have failed. The waste of taxpayer money is continuing to funnel billions of dollars to these ungrateful and almost completely useless businesses. And, I almost fell out of my chair laughing when I read the thing about “busywork”. Anybody who has spent their time interacting with scientific journals where know why. 

AAP also noted:

The bill ignores crucial distinctions among federal agencies and scientific disciplines and would attempt to shoehorn every group into a one-size-fits-all mandate on publication methods and embargo periods.

It is not a one-size-fits-all mandate. It’s a simple statement. The taxpayers funded it, they get to read it. If the AAP has a better model for how to accomplish this, we’re all ears. But if they don’t, they should just shut up.

FASTR disregards what is being accomplished through public-private partnerships and agency collaborations such as the CrossRef “FundRef” pilot to standardize funding source information for scholarly publications

Huh? What does this do to provide access to anyone? NOTHING. 

The bill would require agencies to undertake extensive new duties and reporting requirements while also requiring them to invest in new taxpayer-funded technology resources and systems. FASTR would demand that federal agencies’ staffs develop and implement processes to collect materials, create and permanently maintain redundant digital repositories — resources that are currently in place — and fulfill new government requirements for studies and analyses.

Adler added, “Such systems and protocols are already in place, functioning effectively. Researchers should not be required to duplicate what’s available to them and taxpayers shouldn’t be stuck footing the bill for it too.”

Again, this is a total misdirect. None of the systems in place from publishers accomplish the clear objective of this legislation – to provide the American public with access to the research they fund. If the AAP wants to devote their resources to doing this – great. But to pretend that they are doing it, and then criticizing government efforts to accomplish what the publishers have failed to do, is disgraceful. 

There are many publishers who are members of the AAP who, I suspect, do not agree with their repulsive stance on FASTR. It is time for these groups to speak up and repudiate the AAP’s stance.

Posted in open access, politics | Comments closed

Let’s make 2013 the year of legislative access on open access

Yesterday a bi-partisan group of legislatures – Rep. Doyle (D-PA), Rep. Lofgren (D-CA), Rep. Yoder (R-KS), Sen. Wyden (D-OR) and Sen. Cornyn (R-TX) – introduced legislation that would require federal agencies that fund scientific and medical research to make works they fund available to the public. This bill – known as the Fair Access to Science and Technology Research Act of 2013, or FASTR, is a better version of legislation introduced in previous Congresses.

FASTR shortens the acceptable delay from 12 months to 6 months (still 6 months longer than it should be, but headed in the right direction), and, very importantly, adds a requirement that the works be available for text mining and other forms of reuse. It’s not perfect, but it’s very good, and passage of this bill would be a significant milestone in the push for public access to the results of federally funded research.

Previous versions of this bill have gone nowhere, but this is the time. Supporters of open access in the US should contact their representatives in Washington and urge them to sign on as cosponsors of this bill and push for it to reach the House and Senate floor. And every month we should renew this pressure – I hereby declare the first Friday of every month #FASTRFriday (which we will celebrate today for February). Let’s keep the pressure on Congress and see this one through.

Public access legislation is also being introduced in Illinois, New York and California, and I will post updates when these bills are introduced.

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My father, Aaron Swartz, and assigning blame for suicide

Twenty-six years ago, on February 7th, 1987, my father killed himself, and this day is always a complicated one for me.

Me and my father

It is something I have never talked or written about in public. But I am moved to say something this year because of the suicide of Aaron Swartz. My brother had the same reaction, and wrote eloquently about it (although, being a family that never talks about “things”, we didn’t talk about this with each other).

In the years since my father died, I have had friends, colleagues and mentors kill themselves. But none evoked memories of my father like Swartz, a person I knew only as a public figure. There was just something so hauntingly similar about their deaths. 

My father was a scientist at the National Institutes of Health in Bethesda – one of the “yellow berets” who had joined the Public Health Service to fulfill his national service obligations during the Vietnam War. He worked there for my entire childhood, and always seemed to love his work. In the summer of 1986, the year after my freshman year in college, I worked in an NIH lab, and saw my dad during lunch breaks, and everything seemed fine.

When I came home for Thanksgiving, he was preoccupied – doing a lot of scribbling on yellow legal pads. At one point I asked him what he was doing, and he told me someone in his lab had been committing fraud, and he had finally “caught him”. I was too naive to realize just how big a deal this was, and I didn’t think much more about it. Christmas came and went, and I went back to school.

In the meantime, my father had reported the fraud, and a hearing was held on January 28th at which the scientist in question was supposed to, but did not appear. I don’t know what happened at this meeting, but somehow my father left feeling that he was under suspicion – something everyone involved knew he was not. But whatever happened, it set something off.

On February 3rd, I called home and my father answered, but didn’t seem interested in talking to me (which was very unusual) and handed the phone off to my sister. Then, on the morning of February 7th, I went out for a bike ride on a cold Boston winter day – which for me was the last thing I did as a child. When I got back my uncle was waiting in my dorm room to tell me.

The second I read about what had happened with Aaron Swartz, the parallels made me lurch. They both snapped under accusatory pressure. They both hung themselves when they were left alone. But it was more than that. They just seemed like such similar people to me. It’s hard for me to put my finger on exactly why I felt this way – one person I knew only as a child, the other I did not know at all. But they both seemed to possess a “too good for this world” innocence. Everyone describes Swartz exactly the way I remember my father – as a sweet person who was nice to everyone around him and just seemed to want to do good in the world.

And their deaths are also connected by anger. My father’s death broke me, and it took me a long time to recover. But when I did, I was angry. Angry at what the people at the NIH had done to him. Exactly the same way people are angry now at the prosecutors who hounded Swartz. I felt, for a long time, that the faceless people on that NIH committee had literally killed my father, just like so many people seem to think Carmen Ortiz killed Swartz. 

But, you know, it just isn’t true. My father and Swartz’s were wonderful people. They just turned out to be too fragile. Most people have ways of dealing with adversity – not all are healthy, not all are smooth, but we make it through. And for some reason, these two did not. I will never stop trying to figure out why my father responded to this particular stress in the way he did – and I know I will never actually understand it. But the NIH did not kill him, and the prosecutors did not kill Swartz. They killed themselves.

I don’t say this to let anyone off the hook – precisely the opposite. There was no excuse for the way the NIH treated my father – they treat any hint of fraud like a virus, and assume that anyone who came in contact with the person involved must be contaminated. And the way Swartz was prosecuted was nothing short of malignant.

But so many people writing about Swartz’s death imply that the actions of MIT and Carmen Ortiz were bad Swartz killed himself – that somehow they crossed a line defined by the point at which they drive someone to suicide. But this is madness. What the NIH and the prosecutors did was wrong, and we have to learn how to correct these abuses even when their victims can take it. Nothing will ever change if we measure other people’s actions in units of suicides. 

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Restructuring the NIH and its grant programs to ensure stable careers in science

It is an amazing time to do science, but an incredibly difficult time to be a scientist.

There is so much cool stuff going on. Everywhere I go – my lab, seminar visits, meetings, Twitter – there are biologists young and old are bursting with ideas, eager to take advantage of powerful new ways to observe, manipulate and understand the natural world.

But as palpable as the creative energy is, it is accompanied by an equally palpable sense of dread. We are in one of the worst periods of scientific funding I – and my more senior colleagues – can remember. People aren’t just worried about whether their next grant will get funded, they’re worried about whether a career in academic or public science is even viable (see Kate Clancy’s excellent post on the subject).

There seems to be a broad consensus among the leaders of our community, such as they are, that the solution is for Congress to give us (them) more money. I get emails or calls every few days urging me to contact my senators and representatives to urge them to increase the NIH budget. While I am, in the abstract, in favor of more money for research, if I were in Congress and Francis Collins came to me asking for more money, I’d say “I’m happy to bolster our support for scientific research, but we’re not giving you another single dime until you get your s**t together and stop using the taxpayer’s money to patch over bad decisions and bad policies.”

There are so many things wrong with the NIH today, I could write a book. It’s become an immense, bloated bureaucracy that’s lost sight of its central missions. If it were up to me I’d break it up – turning NIH intramural research into a stand alone entity and creating a separate Institute for Basic Biomedical Research charged allocating funds currently under NIH control to support outstanding and innovative research and to ensure that stable training and career paths exists for American scientists.

This latter issue is the one I want to focus on here. Despite all the challenges of the moment, a lot of outstanding work is getting funded. The problem is, outstanding science needs outstanding scientists. And a lot of outstanding scientists, especially young ones, are leaving academia, unwilling to spend their lives chasing – and in all likelihood not getting – grants.

If I were put in charge of this new institute (or the existing one for that matter) I would devote a large fraction of my budget (I think $10b a year would be a good start) to a “career” award program (not to be confused with the NSF’s CAREER awards).

I would put ~$1b into a pool for young investigator awards. These would be somewhat like current K-99s, in that they would primarily awarded to senior postdocs. These would provide modest startup funds and research support of ~$150k/year for six years – allowing researchers to establish their independent research programs without having to worry about grants. There would be a lot of these – on the order of 1,000 per year. These grants – which would be allocated on the basis of a “people not projects” review, and in all likelihood universities would compete to recruit soon to be independent scientists with these awards.

Recipients of these awards would be evaluated after five years in much the same way people go through tenure reviews today. The purpose of the review would be to assess the researchers contributions to the field and potential for further success. Some would fail to advance, others would be placed in to one of five tiers, representing annual support of between $100,000 (tier 1) and $500,000 (tier 5) – most would be in tier 2 or 3. Every three years research in the career system would be evaluated, with the result of an assessment of their work leading to then either staying in the same tier or moving up or down at most one tier. The total number of people in each tier would be fixed.

I will confess this idea was heavily influenced by the way European soccer leagues operate. At the end of every year, the top teams in each league are promoted to the next higher league, the bottom teams are relegated to a lower division. The system provides a clear opportunity for advancement, but buffers declines – people would only lose their funding after a prolonged period of poor performance, rather than precipitously as happens in the current system if grants do not get renewed.

I estimate that this would cost around $7b/year including overhead. The remaining $3b would support a pool of ~4,500 postdoctoral fellowships and ~12,000 graduate fellowships for trainees to work in career scientists labs. These numbers were meant to provide a pool of 1,500 rising faculty candidates and 2,000 new Ph.D.’s every year, my estimate of what it would take to continually replentish the system.

The $2b left would support a robust equipment grant program for career scientists, including core facilities at institutions with appropriate numbers of career researchers. If the powers that be decide we need more (or fewer) scientists, you scale the whole system by adding or subtracting slots in proportion to available funds.

The $10b was specifically meant not to take the entire NIH extramural budget, but to leave room to fund specific projects, especially high-risk/high reward ones from either career or other labs.

The main goals here are to separate the two crucial function of our granting systems: 1) to fund cutting edge science, and 2) to support a robust scientific infrastructure by providing stable careers to our successful scientists. As I’ve said before, (1) requires (2), but one of the most significant pathologies of our current system is that we mix the two together. In order to support their ongoing research operations, scientists are compelled to dream up “innovative” new projects that can sell in study sections, but often don’t make sense in the real world, while at the same time avoiding truly innovative projects for fear they will be penalized. If labs have a separate mechanism to ensure their financial stability, they will both have more bandwidth to dream up and implement new projects, and the freedom to aim for the stars without worrying they will end up on the street.

I’m sure there are a lot of things I haven’t thought about here, and countless details that need to be dealt with. And I’m equally sure that a lot of people will hate this proposal. But I wanted to put this on the table and open it up for discussion, because the one thing we can not do is nothing. We are dangerously close to losing a generation – or many generations – of scientists. Let’s figure out how not to let this happen.

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Addenda: Commenter Jonathan below misunderstood the number of people who would be supported under this system. This was not meant to be an exclusive program. I based my numbers of ~1,000 PIs enter the system per year, with a steady state number probably around 15-20,000. This was a back of the envelope calculation taken from the current size of the NIH grantee and trainee pools. The idea was to stably support a pool of scientists roughly the same size as the current NIH grantee pool, with the PIs trading a more stable funding situation in exchange for lower average levels of support.

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How academia betrayed and continues to betray Aaron Swartz

As news spread last week that digital rights activist Aaron Swartz had killed himself ahead of a federal trial on charges that he illegally downloaded a large database of scholarly articles with the intent to freely disseminate its contents, thousands of academics began posting free copies of their work online, coalescing around the Twitter hashtag #pdftribute.

This was a touching tribute: a collective effort to complete the task Swartz had tried – and many people felt died trying – to accomplish himself. But it is a tragic irony that the only reason Swartz had to break the law to fulfill his quest to liberate human knowledge was that the same academic community that rose up to support his cause after he died had routinely betrayed it while he was alive.

The most obvious culprit was MIT, whose computer system Swartz used for his downloads. Their decision to make sharing journal articles a criminal matter is inexcusable. But their real betrayal was allowing these articles to fall into private hands in the first place.

Although most academic research is funded by the public, universities all but force their scholars to publish their results in journals that take ownership of the work and place it behind expensive pay walls.

Centuries ago, when printing and mailing paper journals was the most efficient way to disseminate new knowledge, a symbiotic relationship developed between scholars, who had ideas they wanted to share, and publishers, who had printing presses and the means to convey printed works to a wide audience. Transferring copyright to publishers, which protected their ability to recover costs and profit from their investment, was a reasonable price for authors to pay to further their disseminating mission.

But with the birth of the internet, scholars no longer needed publishers to distribute their work. As NYU’s Clay Shirky has noted, publishing went from being an industry to being a button.

Had the leaders of major research universities reacted to this technological transformation with any kind vision, Swartz’s dream of universal free access to the scholarly literature would now be a reality. But they did not. Rather than seize this opportunity to greatly facilitate research and education, both within and outside the academy, they chose instead to reify the status quo.

Instead of encouraging their faculty to make their work widely available, virtually all universities send the unmistakable message to current and aspiring faculty that success in their career depends on publishing in the most high profile place you can. Since the most prestigious journals are generally old, this edict has the effect of stifling innovation in scientific communication. While countless alternatives to the traditional model have arisen, academics in most fields are reluctant to embrace them, fearing that doing so would harm their career prospects.

It is hard to account for this abdication on a university’s basic mission to produce and disseminate knowledge as anything but institutional laziness, as universities essentially farm out responsibility for screening job and promotion candidates to journals.

Absurdly, as soon as the scholarly output of our universities is in the hands of publishers, they immediately buy it back, spending billions of scarce institutional dollars every year in subscription and licensing fees to provide access to students and faculty, but leaving everybody else out in the cold.

Posting our PDFs is all fine and good, but the real way to honor Aaron Swartz is to combat this pervasive institutional fecklessness and do everything in our power to make sure no papers ever end up behind pay walls again. We have to demand that our universities alter their policies to reward, rather than punish, free scholarly publishing, and that they stop cutting the checks that keep this immoral system afloat.

Above all else we need to enshrine the principle that the knowledge produced in the academy is a public good whose value is greatly diminished by turning it into private property. And maybe the next time someone shows up at a university wanting only to spread knowledge, instead of calling the cops, they’ll say “Great, how can we help?”

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[Update: I modified the title to reflect the ongoing nature of the betrayal]

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My related writing on science publishing:

What the UC “open access” policy should say

20 years of cowardice: the pathetic response of American universities to the crisis in scholarly publishing

The widely held notion that high-impact publications determine who gets academic jobs, grants and tenure is wrong. Stop using it as an excuse.

You are Elsevier: time to overcome our fears and kill subscription journals

Plagiarist or Puppet? US Rep. Carolyn Maloney’s reprehensible defense of Elsevier’s Research Works Act

Research Bought, Then Paid For

Peer review is f***ed up – let’s fix it

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