My Thoughts About Science


This is America

Some ~ 20 years ago I took a taxi at Chicago airport to go home. The driver was from Africa, he asks me what do you do? I am doing a residency in pathology at the University of Chicago. He says “I was a Doctor in my country.” I say; why don’t you take the USMLE and get a medical license here? He says: I have no time I have to work to eat. I say: bullshit, I did it, you can do it too, if you want to study you can, don’t you wait hours to get a client at O’Hare? As you wait, study. He says: I have no money to buy the books. I say, look, this is America, stop feeling sorry for yourself and get your medical license, I will give you my books, but only a little bit at the time, you show me you pass USMLE1 and I will give you the books for USMLE2 and 3. He says “OK”. I gave him the books. He came every now and then to my home in Hyde Park to exchange books and to talk. Last time I saw him was 7:00 am: he was really happy, he returned the last set of books, he had passed USMLE3 and got into a residency. I do not know what happened to him, he is practicing somewhere. This is America.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on May 29, 2017

New photo Fewer young scientists apply for US grants, WHY?

The American Cancer Society (ACS) sent an email to its members asking why there is a steep drop in grant applications. The ACS funds only investigators in the early stages of their career. So, the number of bright young scientists competing for grants is decreasing. Why? Why wouldn’t? We pay our post docs (i.e., PhDs) ~$47,500, per NIH guidelines. The same PhD can make >100K in a company. That is just the beginning! Then that “crazy” kid who was so in love with science to enter Academia will face a very low grant pay-line –this will likely get worse given the proposed ~20% NIH budget cut. Without a grant he/she has no future in Academia. In this economy good start up packages for young scientists are rare, for a tenure track position you need a grant. When you get a grant, you will be asked to get a second one to cover ~50% of your salary (not easy), or your salary will be reduced. Presently a bright young PhD must love science very much, and needs to be a little bit crazy, to chose Academia. If you do, you better learn quickly how to fund raise and not be dependent exclusively on federal grants that, alone, can no longer support the increasing costs of biomedical research.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on May 24, 2017

New photo How we measure scientists, and how we should measure scientists.

I met someone at a meeting. I ask what do you do? “All you need to know about me is that I published 12 papers in the New England Journal of Medicine”. Wow! Am I supposed to be impressed? How do I know if any of those papers turned out to be of some use? Most papers even in top journals are inconsequential. Was this his own research or he only made some minor contribution and got co-authorship? How do I know that? This is the problem in generating artificial “standards” to try to measure scientists and physician. Take the H-index, the most used metrics to compare us. Sure has some value, but will not distinguish between someone who played a minor role, say author 22 out of 40, versus first or senior authors. All authors get the same credit with the H-index, which is nonsense. Moreover, scientists in a large research field obviously get more references than those working on rare diseases. Yet more and more we are evaluated with these unreliable metrics. Much more reliable is to explain in a few sentences how your work has changed our understanding of biology and medicine and/or improved the human condition, how many lives you have saved, and list 1-10 papers to support that.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on May 7, 2017

New photo Ethical Dilemma in Research

And what if a person shows up in my office and tells me: I am dying and you could have saved my life with a phone call?

In 2011 we discovered a new cancer syndrome caused by inherited germline mutation of the BAP1 gene (click here for a link to the 2011 article in Nature Genetics).  Later, combining genetic, genealogical and molecular studies we connected several families across the world that we found descended from the same couple that immigrated in the US in the early 1700s (Carbone M et al., PLOS Genetics 2015). Using this novel approach we continue to find new branches of these families that are almost certainly obligated mutation carriers. All BAP1 mutation carriers have developed one or more cancers: some are curable ONLY when detected early, i.e., skin and eye melanoma, renal cell carcinoma, etc. So don’t you think we should inform those who are likely mutation carriers, tell them to get tested, so if they do carry BAP1 mutations they can undergo regular medical screening for early detection and curative resection? The IRB, the “ethical committee”, says that it would be intrusion of privacy to call people out of the blue and tell them to get tested. But if we do not call them, they may die and we could have saved them. What are we supposed to do?

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on April 28, 2017

New photo Why become a doctor?

Why do you want to become a physician?

I used to volunteer in a program that organized meetings between physicians and high-school kids who where considering becoming MDs. The kids answer to my question was invariably “to help people who suffer” or close to that.

Yet when you sit at a table with physicians they usually talk about career, money, the nonsense of administrative issues we have to deal with, or if they are in Academia, they talk about prestigious publications. It is very rare, although fortunately does happen, that the discussion revolves around “what are we doing or what can we do to help people who suffer”. If then you switch the discussion to how your work is evaluated by the Hospital or University administration, the question “what have you done to help patients or people from becoming patients” is rarely on the table: it is all, or almost all, about “how much money you bring into our Institution? And what can we do so that you can bring in more money?”

So either we lied when we were in high school, or something happened along our life and our priorities changed, or we are wasting our life prioritizing issues that are not the reason we became doctors in the first place.

I still try to help people and I measure people based on that.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on April 19, 2017

New photo Proposals to restrict H-1B Visas and cut the NIH Fogarty Center will reduce the number of foreign scientists and cause harm to the US and the world. Why wreck a win-win deal?

The best young foreign scientists come to the US to receive advanced training and contribute to technological progress. The US gets some of the best scientists at no cost to us, their education was paid by foreign countries. We select the top 1% of them and offer them permanent residency for “National Interest” –which most take. After 5 years the others go home as required by their Visas, bringing back advanced knowledge gained in the US. They are our ambassadors and help expand local science and create bridges with the US. Foreign scientists help keep the US at the forefront of biomedical research, develop new therapies, and produce patents to keep our economy strong. A post-doc makes ~$46,500/year in Academia: the size of our NIH grants does not allow us to pay more. The same individual makes >$100K if she/he works for the industry. Most US graduates choose Industry. US Academic biomedical research relies on top foreign scientists who are willing to work for less pay: no surprise that they comprise ~25% of the US NAS members.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on April 7, 2017

Dr. Carbone in his lab Fake Data in Medical Research

Why do people publish fake data? First let's distinguish between honest error and deliberate fake. The first is inherent to the human condition. The latter comes in two ways: data that are entirely false, very rare; and data that contain some deliberate manipulation, usually loading controls of protein gels that have been switched, re-used, or Photoshop editing to make the image look better than it is. If one Figure is wrong how can you trust the others? Science self-corrects itself: if others reproduce the data, even if a figure was wrong, the message may be correct. This is usually the case. Then, why would a researcher be so stupid to manipulate an image of an overall correct paper and jeopardize everything? I cannot explain that, but reviewers and editors bear some responsibility when they seem to think that the higher the IF of a journal the more difficult they have to make the life for scientists by demanding “perfect” images rather than focusing on the data’s relevance. This pressure may drive a frustrated student or post-doc, rarely a PI, to use "make up"-very difficult to catch - to improve an image and get the paper published. Perfection is not reality: let us focus on substance.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on March 22, 2017

Dr. Carbone in his lab Science in the Era of Budget Cuts to the National Institutes of Health

Next year’s US budget includes a proposed19% cut to the National Institutes of Health (NIH). Even without this cut it is time to look for new ways to fund medical research. In 2002 my modular R01 grant from the NIH was 250K/year. In 2002 Fetal Bovine Serum (FBS) to grow cells in culture was $90/bottle. Today my R01 is 229K/year: the list price for the same bottle of FBS is $750! The cost of all reagents increased, the salary of lab personnel almost doubled. 15 years ago, we could publish a paper in a top journal with ~4 Figures, each with 4 panels. Today reviewers ask for many more (at times unnecessary) supplementary data that few will ever look at. A paper in a top journal often has over 100 panels: each representing multiple experiments –in order to show standard deviation- at the cost of thousand of dollars per panel. How are we supposed to pay for all that? Collaborations and team work helps spread costs. More is needed. A strength of the US is that when the public sector falls short the private sector kicks in: in the future successful labs will need to win grants and ALSO fund-raise via philanthropy, industry, etc.

The era when competitive research can be done only with Federal grants is probably over.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD on March 16, 2017

Impact factor The Despised Impact Factor (IF)

Researchers can publish anything we want in a so-called peer reviewed journal: every day, a new journal pops out. Some are legitimate, some are businesses that will publish research for a few thousand dollars.  So the fact that a paper was published does not mean it is any good. 

Today, I rejected a manuscript that I reviewed for a top journal. The paper was flawed. When I read the Title and Abstract, I did not realize it was flawed.  Only when I read the Methods and Result did it become obvious: The research design and approach could not prove what the Authors wanted to prove. 

You can bet that paper will end up in a low impact factor (IF) journal.  Well, most of the time, we scientists are tempted to read only the Title and Abstract of a peer-reviewed paper! Only when the paper is relevant do we read the full text--and almost never the Methods and Supplementary information.  There are not enough hours in a day, and there are too many interesting papers!

So we must rely on others to decide if the research is sound: editors and reviewers. The higher the (despised) IF of a journal, the stricter the review process usually is: thus, the IF, a tool invented by librarians to choose what magazines to purchase, has become the tool we use to decide whether we can trust the conclusions of a paper we have no time to read, and to judge people's CVs.

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD, posted March 9, 2017.

With Dr. Baris in Capadoccia Is Scientific Research a Passion or a Business?

Surprisingly to me, thousands of people read my brief LinkedIn post on grants. Yet what I wrote everybody in medical research knows. We are measured by grants. If you want a job, if you want to get promoted, the single most important question is “How well are you funded?” Yet grants should merely be tools to make discoveries and save lives from cancer or other diseases. The risk is that while we should be doing something for passion, to better the world, it becomes a business like many others: get money. Fortunately, Nobel prizes, the Lasker Award, and other important prizes are still awarded based on what you have contributed to science and medicine rather than how much money you got for something (and what if you did not do anything good with that money?). A great friend of mine, Dr. Izzettin Y. Baris did a lot of good to this world, and helped save many lives to cancer. He never got a grant! I wrote about him when he died. You can find the story of Baris on my Website, it would be great if young scientists and physicians would take him as an example

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD, posted March 6, 2017.


Carbone and Yang Team at UH Cancer Center Chasing Grants

Cancer Research is about finding new ways to prevent or treat cancer, I think. However, we spend a tremendous amount of time chasing grants. We need grants to do the experiments, to do field work, and to pay salaries. But the system has become so much grant-oriented that we are often measured by our peers and Institution by the amount of grants we win rather than the impact of the discoveries we made and the lives we saved to cancer in our research career . When we retire what are we going to answer if someone asks us what did you do to fight cancer? I won 100 grants? And so what? I see many researchers chasing grants rather than innovative ideas: that is the opposite I do. I go, after my ideas, and I never worry about doing a certain research to win a grant. Instead I did my research career by going around the world, looking for new things to study and when I found something that interested me, I tried to make new discoveries and fix the problem: then the grants -I hope- will follow. So far, it has worked quite well!

Link to LinkedIn post from Dr. Michele Carbone, MD, PhD, posted March 3, 2017.